(4-BENZO[D]OXAZOL-2-YL)-6,7-DIHYDRO-1H-IMIDAZO[4,5-C]PYRIDINE-5(4H)-YL)METHANONE DERIVATIVES AS MUTANT PAH STABILIZERS FOR THE TREATMENT OF PHENYLKETONURIA

TECHNICAL FIELD

This application pertains to compounds that stabilize phenylalanine hydroxylase (PAH) mutations, pharmaceutical compositions comprising those compounds, and methods of using those compounds for treating phenylketonuria.

BACKGROUND

Phenylketonuria (PKU) is an autosomal recessive disorder affecting approximately 1:10,000 people worldwide (approx. 1:15,000-1:20,000 in the U.S.). The number of patients varies globally depending on region. PKU arises in patients who have mutations in the gene encoding the phenylalanine hydroxylase (PAH) enzyme responsible for converting phenylalanine to tyrosine. PAH is a tetrameric enzyme expressed in the liver requiring BH4 cofactor for activity. Reduction or loss of PAH activity results in toxic accumulation of phenylalanine (Phe) in the blood and brain. High levels of Phe damage brain white matter and interfere with neurotransmitter production. If untreated, high levels of Phe can result in mental retardation and decreased IQ in children and neurocognitive and psychiatric issues in adults, such as executive function deficits (for example, difficulty with attention, memory, flexible thinking, and organization/time management), psychological issues (for example, depression, anxiety, and mood swings), psychiatric and/or behavioral issues (for example, attention deficit hyperactivity disorder, self-harm, schizophrenia, agoraphobia, and agitation) and neurological abnormalities (for example, spasticity, tremor, gait disturbances, and seizures).

PKU phenotypes can vary from mild hyperphenylalaninemia (HPA) to more severe phenotypes that result in untreated blood Phe concentrations exceeding 1200 μM. American medical guidelines currently recommend maintaining blood Phe concentration in the range of 120 to 360 μM in both adults and children under the age of 12 years. European medical guidelines currently recommend maintaining blood Phe concentration below 360 μM in children under the age of 12 years and in pregnant women and below 600 μM in non-pregnant patients older than 12 years.

A standard of care for treating PKU is a Phe-restricted diet that severely limits the intake of natural protein. Such diets are very strict diets and challenging to adhere to. Two medications are currently approved for treating PKU, each having its own challenges. Kuvan (sapropterin dihydrochloride) is a synthetic BH4 cofactor approved in 2007 for use in infants to adults. Kuvan is not effective for all PKU patients, and the current guidelines suggest response testing in patients unless the patient is known to have two null mutations. Pegvaliase is an enzyme substitution therapy approved in 2018 for adults with a blood Phe concentration greater than 600 μM, despite prior management with available treatment options. Pegvaliase typically involves injection of a purified PEGylated form of phenylalanine ammonia lyase that reduces Phe by converting it to ammonia and trans-cinnamic acid instead of tyrosine. One of the main complications with enzyme substitution therapy is the attainment and maintenance of therapeutically effective amounts of protein in vivo due to rapid degradation or inactivation of the infused protein. A current approach to overcome this problem is to perform numerous costly high dose injections.

Pharmaceutical agents that enable patients to increase their intake of natural protein are desired.

SUMMARY

In some aspects, the disclosure provides compounds of Formula I:

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- or a pharmaceutically acceptable salt thereof, wherein:
  - m is 0, 1 or 2;
  - R¹is

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- - E is 0;
  - u is 0 to 2;
  - x is 0 to 4;
  - each R^aindependently is halo, C_1-6alkyl, C_3-6cycloalkyl, C_1-6haloalkyl, C_1-6alkoxy or C_1-6haloalkoxy;
  - each R^bis independently optionally substituted aryl, C_1-6alkyl, C_3-6cycloalkyl, or halo;
- R²is C_1-4alkyl, optionally substituted C_3-8cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
- R³is H or C_1-6alkyl;
- R⁴is H or C_1-6alkyl;
- or R³and R⁴, together with the atom to which they are attached, form a C_3-6cycloalkyl;
- R⁵is H or D;
- R^5Ais H or D;
- L is a bond, carbonyl, optionally substituted C_1-6alkylene, optionally substituted C_1-6alkylenecarbonyl, optionally substituted C_2-6alkenylenecarbonyl, optionally substituted C_1-6haloalkylenecarbonyl, or optionally substituted —C(O)NR^c(C_1-6alkylene)-, wherein the carbon atom of the carbonyl group is connected to N in Formula I; and
- R^cis H or C_1-6alkyl.

In other aspects, the disclosure provides compounds of Formula I-A, I-B, I-C, I-D, I-E, I-F, I-G, I-H, I-I, I-J, I-K, I-L, or I-M, or a pharmaceutically acceptable salt thereof:

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Stereoisomers and mixtures of stereoisomers of the compounds of Formula I, I-A, I-B, I-C, I-D, I-E, I-F, I-G, I-H, I-I, I-J, I-K, I-L, and I-M, and the pharmaceutical salts thereof, are also described

In further aspects, the disclosure provides pharmaceutical compositions comprising one or more compound described herein or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

In yet other aspects, the disclosure provides methods for stabilizing a mutant PAH protein, comprising contacting the protein with one or more compound as described herein or a pharmaceutically acceptable salt thereof. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.

In still further aspects, the disclosure provides methods for reducing phenylalanine levels in a subject suffering from phenylketonuria comprising administering a therapeutically effective amount of one or more compound as described herein or a pharmaceutically acceptable salt thereof.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
Definitions

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. The terminology used in the description is for describing particular embodiments only and is not intended to be limiting of the disclosure.

As used in structures herein, “ custom-character ” indicates the point of attachment of the particular depicted structure or substituent group to the appropriate atom(s) in the remainder of the molecule.

The articles “a” and “an” as used herein and in the appended claims are used herein to refer to one or to more than one (e.g., to at least one) of the grammatical object of the article unless the context clearly indicates otherwise. By way of example, “an element” means one element or more than one element.

“Pharmaceutically acceptable” means approved or approvable by a regulatory agency of the Federal or a state government or the corresponding agency in a country other than the United States, or that is listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, e.g., in humans.

“Pharmaceutically acceptable salt” refers to a salt of a compound of the disclosure that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. In particular, such salts are non-toxic and may be inorganic or organic acid addition salts and base addition salts. Specifically, such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine and the like. Salts further include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, and the like; and when the compound contains a basic functionality, salts of non-toxic organic or inorganic acids, such as hydrochloride, hydrobromide, fumarate, tartrate, mesylate, acetate, maleate, oxalate and the like.

A “pharmaceutically acceptable excipient” refers to a substance that is non-toxic, biologically tolerable, and otherwise biologically suitable for administration to a subject, such as an inert substance, added to a pharmacological composition or otherwise used as a vehicle, carrier, or diluent to facilitate administration of an agent and that is compatible therewith.

The term “alkyl,” when used alone or as part of a substituent group, refers to a straight- or branched-chain hydrocarbon group having from 1 to 12 carbon atoms (“C_1-12”), for example 1 to 6 carbons atoms (“C_1-6”), in the group. Examples of alkyl groups include methyl (C₁), ethyl (C₂), propyl (C₃) (e.g., n-propyl, isopropyl), butyl (C₄) (e.g., n-butyl, tert-butyl, sec-butyl, iso-butyl), pentyl (C₅) (e.g., n-pentyl, 3-pentyl, amyl, neopentyl, 3-methyl-2-butanyl, tertiary amyl), hexyl (C₆) (e.g., n-hexyl), heptyl (C₇) (e.g., n-heptyl), octyl (C₈) (e.g., n-octyl), and the like. In some embodiments, the alkyl group is a C_1-6alkyl; in other embodiments, it is a C_1-4alkyl; and in other embodiments, it is a C_1-3alkyl.

The term “alkylene,” when used alone or as part of a substituent group, refers to an alkyl diradical, i.e., a straight- or branched-chain hydrocarbon group that is attached to two other groups. For example, one embodiment of a C₂alkylene is the diradical —CH₂CH₂—. In some embodiments, the alkylene group is C_1-6alkylene; in other embodiments, it is C_1-4alkylene.

When a range of carbon atoms is used herein, for example, C_1-6, all ranges, as well as individual numbers of carbon atoms are encompassed. For example, “C_1-3” includes C_1-3, C_1-2, C_2-3, C₁, C₂, and C₃.

The term “cycloalkyl” when used alone or as part of a substituent group refers to cyclic-containing, non-aromatic hydrocarbon groups having from 3 to 10 carbon atoms (“C_3-10”), for example from 3 to 7 carbon atoms (“C_3-7”). Examples of cycloalkyl groups include cyclopropyl (C₃), cyclobutyl (C₄), cyclopentyl (C₅), cyclohexyl (C₆), cycloheptyl (C₇), and the like. In some embodiments, the cycloalkyl group is a C_3-4cycloalkyl; in other embodiments, it is a C_3-6cycloalkyl; and in other embodiments, it is C_3-8cycloalkyl. The cycloalkyl may be unsubstituted or substituted. In some embodiments, the cycloalkyl is substituted with two substituents. In further embodiments, the cycloalkyl is substituted with one substituent. In yet other embodiments, the cycloalkyl is substituted with three substituents. In still further embodiments, the cycloalkyl is unsubstituted.

The term “aryl” when used alone or as part of a substituent group also refers to a mono- or bicyclic-aromatic hydrocarbon ring structure having 6 or 10 carbon atoms in the ring, wherein one or more of the carbon atoms in the ring is optionally substituted. The term “aryl” also includes a mono- or bicyclic-aromatic hydrocarbon ring structure having 6 or 10 carbon atoms in the ring, wherein two adjacent carbon atoms in the ring are optionally substituted such that said two adjacent carbon atoms and their respective substituents form a cycloalkyl or heterocyclyl ring. Examples of aryl groups include phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, and the like. The aryl may be unsubstituted or substituted. In other embodiments, the optionally substituted phenyl has four substituents. In further embodiments, the optionally substituted phenyl has three substituents. In yet other embodiments, the optionally substituted phenyl has two substituents. In still further embodiments, the optionally substituted phenyl has one substituent. In other embodiments, the optionally substituted phenyl is unsubstituted.

As used herein, the term “alkenyl” refers to a straight- or branched-chain group having from 2 to 12 carbon atoms (“C_2-12”) in the group, wherein the group includes at least one carbon-carbon double bond. Examples of alkenyl groups include vinyl (—CH═CH₂; C₂alkenyl), allyl (—CH₂—CH═CH₂; C₃alkenyl), propenyl (—CH═CHCH₃; C₃alkenyl), isopropenyl (—C(CH₃)=CH₂; C₃alkenyl), butenyl (—CH═CHCH₂CH₃; C₄alkenyl), sec-butenyl (—C(CH₃)=CHCH₃; C₄alkenyl), iso-butenyl (—CH═C(CH₃)₂; C₄alkenyl), 2-butenyl (—CH₂CH═CHCH₃; C₄alkyl), pentenyl (—CH═CHCH₂CH₂CH₃; C₃alkenyl), and the like. In some embodiments, the alkenyl group is a C_2-6alkenyl group; in other embodiments, it is C₂-4alkenyl.

As used herein, the term “alkynyl” refers to a straight- or branched-chain group having from 2 to 12 carbon atoms (“C_2-12”) in the group, and wherein the group includes at least one carbon-carbon triple bond. Examples of alkynyl groups include ethynyl (—C≡CH; C₂alkynyl), propargyl (—CH₂—C≡CH; C₃alkynyl), propynyl (—C≡CCH₃; C₃alkynyl), butynyl (—C≡CCH₂CH₃; C₄alkynyl), pentynyl (—C≡CCH₂CH₂CH₃; C₅alkynyl), and the like. In some embodiments, the alkynyl group is a C_2-6alkynyl group; in other embodiments, it is C_2-4alkynyl.

The term “carbonyl” as used by itself or as part of another group refers to C(O) or C(═O).

The term “alkylcarbonyl” as used by itself or as part of another group refers to an alkyl group as defined above wherein at least one carbon is bonded to an oxo group. For example, one embodiment of an C₃alkylcarbonyl is —CH₂C(O)CH₃. In some embodiments, the alkylcarbonyl group is a C_1-6alkylcarbonyl group.

The term “alkenylenecarbonyl” as used by itself or as part of another group refers to an —C(O)-(alkenylene) group, where alkenylene refers to an alkylene diradical, i.e., a straight- or branched-chain hydrocarbon group containing at least one carbon-carbon double bond that is attached to two other groups. For example, one embodiment of a —C(O)—C₂alkenylene is —C(O)—CH═CH—. In some embodiments, the alkenylene group of the alkenylenecarbonyl is a C_2-6alkenylene group; in other embodiments, the alkenylene group is C_2-4alkenylene.

The term “halo” or “halogen,” as used by itself or as part of another group refers to a fluorine, chlorine, bromine, or iodine atom.

As used herein, the term “haloalkyl” refers to an alkyl group wherein one or more of the hydrogen atoms has been replaced with one or more halogen atoms which may be the same or different. In some embodiments, the alkyl is substituted by at least one halogen. In other embodiments, the alkyl is substituted by one, two, or three F and/or Cl. Examples of haloalkyl groups include fluoromethyl (CH₂F), 1-fluoroethyl (CH(CH₃)F), 2-fluoroethyl, difluoromethyl (CHF₂), trifluoromethyl (CF₃), pentafluoroethyl, 1,1-difluoroethyl (C(CH₃)F₂), 2,2-difluoroethyl (CH₂CHF₂), 2,2,2-trifluoroethyl (CH₂CF₃), 2-fluoropropan-2-yl (C(CH₃)₂F), 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, trichloromethyl and the like. In some embodiments, the haloalkyl group is a C_1-6haloalkyl; in other embodiments, it is a C_1-4haloalkyl; and in other embodiments, it is a C_1-3haloalkyl.

The term “haloalkylenecarbonyl” as used by itself or as part of another group refers to a —C(O)-(haloalkylene) group, where the haloalkylene refers to a haloalkyl diradical. For example, one embodiment of a —C(O)—C₁haloalkylene is —C(O)—CF₂—. In some embodiments, the haloalkylene group is a C_1-6haloalkylene; in other embodiments, it is a C_1-4haloalkylene; and in other embodiments, it is a C_1-3haloalkylene.

The term “cyanoalkyl” as used by itself or as part of another group refers to an alkyl as defined herein that is substituted by one or more CN. In some embodiments, the alkyl is substituted by at least one CN. In other embodiments, the alkyl is substituted by one, two, or three CN. In further embodiments, the cyanoalkyl group is a C_1-6cyanoalkyl. In yet other embodiments, the cyanoalkyl is a C_1-4cyanoalkyl. Examples of cyanoalkyl groups include CH₂CN, CH₂CH₂CN, CH(CN)CH₃, CH₂CH₂CH₂CN, C(CH₃)₂CN, CH₂CH(CN)CH₃, CH(CN)CH₂CH₃, and the like.

The term “hydroxyalkyl” as used by itself or as part of another group refers to an alkyl group as defined herein wherein one or more of the hydrogen atoms has been replaced with one or more hydroxyl (i.e., —OH). In some embodiments, the hydroxyalkyl contains one OH. In other embodiments, the hydroxyalkyl contains two OH. In further embodiments, the hydroxyalkyl contains three OH. Examples of hydroxyalkyl groups include hydroxymethyl, hydroxyethyl (e.g., 1-hydroxyethyl, 2-hydroxyethyl), 1,2-dihydroxyethyl, hydroxypropyl (e.g., 2-hydroxypropyl, 3-hydroxypropyl), hydroxybutyl (e.g., 3-hydroxybutyl, 4-hydroxybutyl), 2-hydroxy-1-methylpropyl, 1,3-dihydroxyprop-2-yl, and the like. In some embodiments, the hydroxyalkyl group is C_1-6hydoxyalkyl; in other embodiments, it is C_1-4hydroxyalkyl; and in other embodiments, it is C_1-3hydroxyalkyl.

The term “cycloalkylsulfonyl” as used by itself or as part of another group refers to a cycloalkyl as defined herein that is bound to a sulfonyl, i.e., —SO₂—, and the sulfonyl group forms the point of attachment to the remainder of the molecule. In some embodiments, the cycloalkylsulfonyl is a C_3-8cycloalkylsulfonyl; in other embodiments, it is a C_3-6cycloalkylsulfonyl. Examples of cycloalkylsulfonyl groups include —SO₂-cyclopropyl, —SO₂-cyclobutyl, —SO₂-cyclopentyl, and the like.

The term “alkylsulfonyl” as used by itself or as part of another group refers to an alkyl as defined herein that is bound to a sulfonyl, i.e., —SO₂—, and the sulfonyl group forms the point of attachment to the remainder of the molecule. In some embodiments, the alkylsulfonyl is C_1-6alkylsulfonyl; in other embodiments, it is a C_1-4alkylsulfonyl. Examples of alkylsulfonyl groups include —SO₂CH₃, —SO₂CH₂CH₃, and the like.

The term “alkylsulfonyl(alkylene)” as used by itself or as part of another group refers to an alkylene group as defined herein that is bound to the sulfonyl of an alkylsulfonyl group as defined herein. Examples of alkylsulfonyl(alkylene) groups include —C(CH₃)₂SO₂CH₃, —CH₂SO₂CH₃, —CH(CH₃)SO₂CH₃, and the like.

The term “alkoxy” as used by itself or as part of another group refers to an oxygen radical attached to an alkyl group by a single bond. Examples of alkoxyl groups include methoxy (OCH₃), ethoxy (OCH₂CH₃), propoxy (e.g., —OⁿPr, —OⁱPr), or butoxy (e.g., —OⁿBu, —OⁱBu, —O^sBu, —O^tBu), and the like. In other embodiments, the alkoxy group is a C_1-6alkoxy. In further embodiments, the alkoxy group is a C_1-4alkoxy.

The term “alkoxy(alkylene)” as used by itself or as part of another group refers to an alkylene group as defined herein that is bound to an alkoxy group as defined herein. Examples of alkoxy(alkylene) groups include —CH₂OCH₃, —CH₂CH₂OCH₃, and the like.

The term “haloalkoxy” as used by itself or as part of another group refers to an oxygen radical attached to a haloalkyl group by a single bond, wherein haloalkyl is defined above. Examples of haloalkoxy groups include fluoromethoxy (OCH₂F), 2-fluoroethoxy, difluoromethoxy (OCHF₂), trifluoromethoxy (OCF₃), pentafluoroethoxy, 1,1-difluoroethoxy (OC(CH₃)F₂), 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy (OCH₂CF₃), 3,3,3-trifluoropropoxy, 4,4,4-trifluorobutoxy, trichloromethoxy groups, and the like. In some embodiments, the haloalkoxy group is a C_1-6haloalkoxy; in other embodiments, it is C_1-4haloalkoxy; and in other embodiments, it is C_1-3haloalkoxy.

The term “haloalkoxy(alkylene)” as used by itself or as part of another group refers to an alkylene group as defined herein that is bound to an haloalkoxy group as defined herein. Examples of haloalkoxy(alkylene) groups include —CH₂OCF₃, and the like.

The term “heteroaryl” when used alone or as part of a substituent group refers to a mono- or bicyclic-aromatic ring structure including carbon atoms as well as up to four heteroatoms that are each independently nitrogen, oxygen, or sulfur. Heteroaryl rings can include a total of 5, 6, 9, or 10 ring atoms. In some embodiments, heteroaryl rings are characterized by the number of ring atoms in the heteroaryl group. For example, a 6-membered heteroaryl group refers to a heteroaryl group having 6 ring atoms in the group. Similarly, a 5-membered heteroaryl group refers to a heteroaryl group having 5 ring atoms in the group. The heteroaryl moiety can be unsubstituted, or one or more of the carbon atoms or nitrogen atoms in the ring can be substituted. Examples of heteroaryl groups include thienyl, benzo[b]thienyl, furanyl, benzofuryl, pyranyl, thiophenyl, isobenzofuranyl, benzoxazinyl, chromenyl, xanthenyl, 2H pyrrolyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl, isoquinolyl, quinolyl, quinoxalyl, phthalazinyl, naphthyridinyl, cinnolinyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, quinazolinyl, pteridinyl, pyrimidinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, furazanyl, pyrazolo[1,5-a]pyridinyl, benzoisothiazolyl, imidazol[1,5-a]pyridinyl, pyrrolo[1,2]pyridazinyl, benzo[d]thiazolyl, benzo[d]imidazolyl, benzo[d]oxazolyl, benzoisoxazolyl, isothiazolyl, tetrahydropyrazolo[1,5-a]pyridinyl and the like. In some embodiments, the heteroaryl is thienyl (e.g., thien-2-yl and thien-3-yl), furyl (e.g., 2-furanyl, 3-furanyl, 4-furanyl), pyrrolyl (e.g., pyrrol-2-yl, pyrrol-3-yl), imidazolyl (e.g., imidazol-2-yl, imidazol-4-yl), pyrazolyl (e.g., pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl), pyridyl (e.g., pyridin-1-yl, pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl), pyrimidinyl (e.g., pyrimidin-2-yl, pyrimidin-4-yl, and pyrimidin-5-yl), thiazolyl (e.g., thiazol-2-yl, thiazol-4-yl, and thiazol-5-yl), isothiazolyl (e.g., isothiazol-3-yl, isothiazol-4-yl, and isothiazol-5-yl), oxazolyl (e.g., oxazol-2-yl, oxazol-4-yl, and oxazol-5-yl), isoxazolyl (e.g., isoxazol-3-yl, isoxazol-4-yl, and isoxazol-5-yl), pyrazinyl (e.g., pyrazin-2-yl, pyrazin-3-yl, pyrazin-5-yl, pyrazin-6-yl), triazolyl (e.g., 1,2,4-triazol-1-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl), thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thidiazolyl, 1,3,4-thiadiazolyl), oxadiazolyl (e.g., 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl), indazolyl (e.g., indazol-3-yl), pyrazolo[1,5-a]pyridinyl (e.g., pyrazolo[1,5-a]pyridin-3-yl), imidazol[1,5-a]pyridinyl (e.g., imidazol[1,5-a]pyridin-1-yl), pyrrolo[1,2]pyridazinyl (e.g., pyrrolo[1,2]pyridazin-5-yl, pyrrolo[1,2]pyridazin-6-yl), benzo[d]thiazolyl (e.g., benzo[d]thiazol-3-yl, benzo[d]thiazol-2-yl), benzo[d]imidazolyl (e.g., benzo[d]imidazol-2-yl), benzo[d]oxazolyl (e.g., benzo[d]oxazol-2-yl), benzo[d]isoxazolyl (e.g., benzo[d]isoxazol-3-yl), benzo[d]isothiazolyl (e.g., benzo[d]isothiazol-3-yl), benzo[c]isoxazolyl (e.g., benzo[c]isoxazol-3-yl), quinolinyl (e.g., quinolin-3-yl), and pyridazinyl (e.g., pyridazin-3-yl, pyridazin-4-yl). The term “heteroaryl” also includes N-oxides. The heteroaryl may be unsubstituted or substituted. In some embodiments, the heteroaryl is substituted with two substituents. In further embodiments, the heteroaryl is substituted with one substituent. In yet other embodiments, the heteroaryl is substituted with three substituents. In still further embodiments, the heteroaryl is unsubstituted. Substitution may occur on any available carbon or heteroatom (e.g., nitrogen), or both, as permitted by substituent valency.

In some embodiments, the heteroaryl is a 5- or 6-membered heteroaryl. In some embodiments, the heteroaryl is a 5-membered heteroaryl, i.e., the heteroaryl is a monocyclic aromatic ring system having 5 ring atoms wherein at least one carbon atom of the ring is replaced with a heteroatom independently selected from nitrogen, oxygen, and sulfur.

Examples of 5-membered heteroaryl groups include thienyl, furyl, pyrrolyl, oxazolyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, and isoxazolyl and the like. In other embodiments, the heteroaryl is a 6-membered heteroaryl, e.g., the heteroaryl is a monocyclic aromatic ring system having 6 ring atoms wherein at least one carbon atom of the ring is replaced with a nitrogen atom. Examples of 6-membered heteroaryl groups include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl and the like.

The term “heterocyclyl” as used by itself or as part of another group refers to non-aromatic, saturated or partially unsaturated, e.g., containing one or two double bonds, cyclic groups containing one, two, or three rings having from three to fourteen ring members, i.e., a 3-14-membered heterocyclyl, wherein at least one carbon atom of one of the rings is replaced with a heteroatom. Each heteroatom is independently selected from oxygen, sulfur, including sulfoxide and sulfone, and/or nitrogen atoms, which can be oxidized or quaternized. The term “heterocyclyl” also includes groups wherein a ring —CH₂— is replaced with a —C(═O)—. The term “heterocyclyl” also includes groups having fused optionally substituted aryl groups, e.g., indolinyl or chroman-4-yl and groups having fused optionally substituted cycloalkyl groups, e.g., 6-azaspiro[2.5]octanyl. In some embodiments, the heterocyclyl group is a C_4-6heterocyclyl, i.e., a 4-, 5- or 6-membered cyclic group, containing one ring and one or two oxygen and/or nitrogen atoms. In other embodiments, the heterocyclyl is a C_4-6heterocyclyl containing one ring and one nitrogen atom. The heterocyclyl can be optionally linked to the rest of the molecule through any available carbon or heteroatom that results in a stable structure. Examples of heterocyclyl groups include azetidinyl, dioxanyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, pyrrolidinyl, indolinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, aziridinyl, dioxolanyl, imidazolidinyl, pyrazolidinyl, thianyl, dithianyl, thiomorpholinyl, oxazepanyl, oxiranyl, tetrahydropyranyl, and the like. In some embodiments, the heterocyclyl group includes azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, and 6-azaspiro[2.5]octanyl. The heterocyclyl may be unsubstituted or substituted. In some embodiments, the heterocyclyl is substituted with two substituents. In further embodiments, the heterocyclyl is substituted with one substituent. In yet other embodiments, the heterocyclyl is substituted with three substituents. In still further embodiments, the heterocyclyl is unsubstituted.

The term “(heterocyclyl)alkylene” as used by itself or part of another group refers to an alkylene group as defined herein that is bound to a heterocyclyl group as defined herein.

The term “optionally substituted,” as used herein to describe a chemical moiety defined herein, means that the moiety may, but is not required to be, substituted with one or more suitable functional groups or other substituents as provided herein. For example, a substituent may be optionally substituted with one or more of: halo, cyano, —NO₂, —N₃, —OH, —SH, C_1-6alkyl, C_3-8cycloalkyl, C_3-8cycloalkenyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_1-6alkylcarbonyl, C_1-6cyanoalkyl, C_1-6hydoxyalkyl, C_1-6alkylenethio, (CR^vR^x)_pNR^yR^z(wherein R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare independently H, C_1-6alkyl, C_3-6cycloalkyl, C_1-6hydroxyalkyl, C_1-6haloalkyl, C_1-6alkoxy(alkylene), or C(O)OC_1-6alkyl, and p is 0, 1, 2, or 3), —C(O)NH₂, —C(O)NHC_1-6alkyl, —C(O)N(C_1-6alkyl)₂, —C(O)NHC_3-6cycloalkyl, —C(O)N(C_3-6cycloalkyl)₂, —COOH, —C_1-6alkyleneCOOH, —C_3-6cycloalkylCOOH, —C_1-6alkyleneCONH₂, C_3-6cycloalkylCONH₂, —C_1-6alkyleneCONHC_1-6alkyl, —C_1-6alkyleneCON(C_1-6alkyl)₂, —C(O)OC_1-6alkyl, —NHCO(C_1-6alkyl), —N(C_1-6alkyl)C(O)(C_1-6alkyl), —S(O)C_1-6alkyl, —S(O)C_3-6cycloalkyl, C_1-6alkylsulfonyl, C_3-8cycloalkylsulfonyl, C_1-6alkylsulfonyl(alkylene), oxo (═O), 3-7-membered heterocyclyl, heterocyclyl(alkylene), aryl, aryl(alkylene), or heteroaryl groups. In some embodiments, the C_1-6alkyl group in any of the substituent groups in this paragraph is a C_1-4alkyl; in other embodiments it is C_1-3alkyl. In some embodiments, the C_1-6alkylene group in any of the substituent groups in this paragraph is a C_1-4alkylene. In some embodiments, the C_1-6haloalkyl substituent is a C_1-4haloalkyl; in other embodiments, it is C_1-3haloalkyl. In some embodiments, the C_3-6cycloalkyl substituent is a C_3-4cycloalkyl substituent. In some embodiments, the C_1-6alkoxy substituent is a C_1-3alkoxy; in other embodiments, it is C_1-4alkoxy. In some embodiments, the C_1-6haloalkoxy substituent is a C_1-3haloalkoxy; in other embodiments, it is C_1-4haloalkoxy.

In some embodiments, a substituent may be optionally substituted with one or more of: C_1-6alkyl, optionally substituted C_2-6alkenyl, halo, CN, C_1-6cyanoalkyl, C_1-6haloalkyl, OH, optionally substituted C_3-8cycloalkyl, optionally substituted C_3-8cycloalkenyl, optionally substituted aryl, optionally substituted aryl(alkylene), optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclyl(alkylene), C_1-6hydroxyalkyl, C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6deuteratedalkoxy(alkylene), C_1-6alkylcarbonyl, C_3-8cycloalkylsulfonyl, C_1-6alkylsulfonyl(alkylene), (CR^vR^x)_pNR^yR^z(wherein R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^z, are independently, H, C_1-6alkyl, C_3-6cycloalkyl, C_1-6hydroxyalkyl, C_1-6haloalkyl, C_1-6alkoxy(alkylene), or C(O)OC_1-6alkyl, and p is 0, 1, 2, or 3), and C(O)NR^y2R^z2(wherein R^y2and R^z2, are independently, H, C_1-6alkyl, or C_3-6cycloalkyl).

The term “nitrogen protecting group” refers to a moiety that is attached to a nitrogen atom to prevent reaction at that nitrogen atom. Nitrogen protecting groups will be known by those skilled in the art and include those described in Wuts, P.G., Greene's Protective Groups in Organic Synthesis. Wiley; 5th edition (Oct. 27, 2014), which is incorporated by reference herein.

Recitation of ranges of values herein are intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein.

The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended to better illustrate the disclosure and is not a limitation on the scope of the disclosure unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the disclosure.

The term “about” when used in combination with a numeric value or range of values means the value or range of values may deviate to an extent deemed reasonable to one of ordinary skill in the art.

Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including supercritical fluid chromatography (SFC), chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E. L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, S. H. Tables of Resolving Agents and Optical Resolutions p. 268 (E. L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972).

Exemplary compounds of the disclosure including a chiral center may be depicted herein as having particular stereochemistries, but for which absolute stereochemistry has not been obtained. Absolute configurations can be obtained using methods known in the art.

As used herein, the term “stereoisomers” refers to compounds which have identical chemical constitution and connectivity, but differ with regard to the arrangement of the atoms or groups in space, e.g., enantiomers or diastereomers.

When the stereochemical configuration at a chiral center in a compound having one or more chiral centers is depicted by its chemical name (e.g., where the configuration is indicated in the chemical name by “R” or “S”) or structure (e.g., the configuration is indicated by dashed or wedge bonds), the enrichment of the indicated configuration relative to the opposite configuration is greater than 50%, 60%, 70%, 80%, 90%, 99% or 99.9%. “Enrichment of the indicated configuration relative to the opposite configuration” is a mole percent and is determined by dividing the number of compounds with the indicated stereochemical configuration at the chiral center(s) by the total number of all of the compounds with the same or opposite stereochemical configuration in a mixture.

When a disclosed compound is named or depicted by structure without indicating stereochemistry, it is understood that the name or the structure encompasses one of the possible stereoisomers or geometric isomers free of the others, or a mixture of the encompassed stereoisomers or geometric isomers.

It will be understood that certain compounds disclosed herein may exist in tautomeric forms. Such forms are included as part of the present disclosure. Thus, when a compound herein is represented by a structural formula or designated by a chemical name herein, all tautomeric forms which may exist for the compound are encompassed by the structural formula.

When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that they include both E and Z geometric isomers.

In some embodiments, the compounds described herein are isotopically enriched compounds, e.g., an isotopologue. The term “isotopically enriched” refers to an atom having an isotopic composition other than the naturally abundant isotopic composition of that atom. “Isotopically enriched” may also refer to a compound containing at least one atom having an isotopic composition other than the natural isotopic composition of that atom. In an isotopologue, “isotopic enrichment” refers to the percentage of incorporation of an amount of a specific isotope of a given atom in a molecule in the place of that atom's natural isotopic composition. For example, deuterium enrichment of 1% at a given position means that 1% of the molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156%, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156%. In one embodiment, one or more hydrogen atoms on a described compound may be replaced by deuterium.

Thus, as used herein, and unless otherwise indicated, the term “isotopic enrichment factor” refers to the ratio between the isotopic composition and the natural isotopic composition of a specified isotope.

With regard to the compounds provided herein, when a particular atom's position is designated as having deuterium or “D” or “²H”, it is understood that the abundance of deuterium at that position is substantially greater than the natural abundance of deuterium, which is about 0.015%. A position designated as having deuterium typically has a minimum isotopic enrichment factor of, in particular embodiments, at least 1000 (15% deuterium incorporation), at least 2000 (30% deuterium incorporation), at least 3000 (45% deuterium incorporation), at least 3500 (52.5% deuterium incorporation), at least 4000 (60% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation) at each designated deuterium atom. The isotopic enrichment and isotopic enrichment factor of the compounds provided herein can be determined using conventional analytical methods known to one of ordinary skill in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy.

The term “patient” or “subject” is used throughout the specification to describe an animal, preferably a human or a domesticated animal, to whom treatment, including prophylactic treatment, with the compounds or compositions according to the present disclosure is provided. For treatment of those conditions or disease states which are specific for a specific animal such as a human patient, the term patient refers to that specific animal, including a domesticated animal such as a dog or cat or a farm animal such as a horse, cow, sheep, etc. In general, in the present disclosure, the term patient refers to a human patient unless otherwise stated or implied from the context of the use of the term.

The terms “therapeutically effective amount” or “effective amount” means an amount or dose of a compound of the disclosure (or a pharmaceutically acceptable salt thereof) sufficient to generally bring about the desired therapeutic benefit in subjects in need of such treatment for the designated disease or disorder. Further, a therapeutically effective amount with respect to a compound of the disclosure means that amount of therapeutic agent alone, or in combination with other therapies, that provides a therapeutic benefit in the treatment or prevention of a disease.

“Treating” or “treatment” of any disease or disorder refers, in one embodiment, to ameliorating the disease or disorder (e.g., arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In another embodiment “treating” or “treatment” refers to ameliorating at least one physical parameter, which may not be discernible by the subject. In yet another embodiment, “treating” or “treatment” refers to modulating the disease or disorder, either physically (e.g., stabilization of a discernible symptom), physiologically (e.g., stabilization of a physical parameter), or both. In yet another embodiment, “treating” or “treatment” refers to delaying the onset of the disease or disorder.

The terms “prevent,” “preventing,” and “prevention” refer to the prevention of the onset, recurrence, or spread of the disease in a subject resulting from the administration of a prophylactic or therapeutic agent.

The Compounds

The present disclosure provides compounds of Formula I or pharmaceutically acceptable salts thereof:

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In Formula I, m is 0, 1, or 2. In other embodiments, m is 1 or 2. In some embodiments, m is 1. In other embodiments, m is 2. In yet other embodiments, m is 0.

In formula I, R¹is

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In some embodiments, R¹is

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In other embodiments, R¹is

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In the structures for R¹, u is 0 to 2. In some embodiments, u is 0. In other embodiments, u is 1. In further embodiments, u is 2.

In the structures for R¹, x is 0 to 4. In some embodiments, x is 0. In other embodiments, x is 1. In further embodiments, x is 2. In yet other embodiments, x is 3. In still further embodiments, x is 4.

In the structures for R¹, E is O.

In the structures for R¹, each R^ais independently halo, C_1-6alkyl, C₃-6cycloalkyl, C_1-6haloalkyl, C_1-6alkoxy or C_1-6haloalkoxy. In some embodiments, R^ais halo such as F, Cl, Br, or I. In other embodiments, R^ais F, Br, or Cl. In still other embodiments, R^ais F. In further embodiments, R^ais Br. In yet other embodiments, R^ais Cl. In still further embodiments, R^ais I. In other embodiments, R^ais C_1-6alkyl such as methyl, ethyl, propyl, butyl, pentyl, or hexyl. In yet other embodiments, R^ais methyl. In further embodiments, R^ais C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In still further embodiments, R^ais cyclopropyl. In yet other embodiments, R^ais C_1-6haloalkyl such as CF₃, CHF₂, CH₂F, CH₂CF₃, C(CH₃)₂F, or C(CH₃)F₂. In still other embodiments, R^ais CF₃or CHF₂. In yet other embodiments, R^ais CF₃. In further embodiments, R^ais C_1-6alkoxy such as methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy. In yet other embodiments, R^ais methoxy or ethoxy. In still further embodiments, R^ais methoxy. In other embodiments, R^ais C_1-6haloalkoxy such as OCF₃or OCH₂CF₃. In yet other embodiments, R^ais OCF₃. In still other embodiments, one R^ais halo such as Br, Cl, or F or C_1-6alkyl such as methyl, and the second R^ais halo such as Br, Cl, or F, C_1-6alkoxy such as methoxy, or C_1-6alkyl such as methyl.

In the structures for R¹, each R^bis independently optionally substituted aryl, C_1-6alkyl, C_3-6cycloalkyl, or halo. In some embodiments, R^bis halo such as F, Cl, Br, or I. In other embodiments, R^bis F, Br, or Cl. In still other embodiments, R^bis F. In yet other embodiments, R^bis Br. In still other embodiments, R^bis Cl. In yet other embodiments, R^bis I. In other embodiments, R^bis C_1-6alkyl such as methyl, ethyl, propyl, butyl, pentyl, or hexyl. In yet other embodiments, R^bis methyl. In further embodiments, R^bis C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In still further embodiments, R^bis cyclopropyl. In further embodiments, R^bis optionally substituted aryl such as phenyl. In some embodiments, R^bis aryl, substituted with one or more of halo, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, or C_3-8cycloalkyl. In other embodiments, R^bis unsubstituted phenyl.

In further embodiments, R¹is

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and x is 0 or 1 such as

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In other embodiments, R¹is

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In still other embodiments, R¹is

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In still other embodiments, R¹is

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In yet other embodiments, R¹is

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In still other embodiments, R¹is

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In further embodiments, R¹is

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and x is 2 such as

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In other embodiments, R¹is

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In yet other embodiments, R¹is

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In still other embodiments, R¹is

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In still other embodiments, R¹is

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In still other embodiments, R¹is

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In yet other embodiments, R¹is

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In further embodiments, R¹is

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wherein R^bis phenyl or halo and u is 1. In some embodiments, R^bis phenyl. In other embodiments, R^bis halo.

In Formula I, R²is C_1-4alkyl, optionally substituted C_3-8cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In further embodiments, R²is optionally substituted C_3-8cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In still further embodiments, R²is unsubstituted C_3-8cycloalkyl, unsubstituted heterocyclyl, unsubstituted aryl, or unsubstituted heteroaryl. In other embodiments, R²is substituted C_3-8cycloalkyl, substituted heterocyclyl, substituted aryl, or substituted heteroaryl. In some embodiments, R²is C_1-4alkyl such as methyl, ethyl, propyl, butyl, or tert-butyl. In other embodiments, R²is optionally substituted C_3-8cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl. In further embodiments, R²is optionally substituted heterocyclyl such as azetidinyl. In still other embodiments, R²is optionally substituted aryl such as phenyl. In yet further embodiments, R²is optionally substituted heteroaryl such as pyridinyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, furanyl, thiophenyl, pyrimidinyl, pyrazinyl, indazolyl, pyrazolo[1,5-a]pyridinyl, imidazol[1,5-a]pyridinyl, pyrrolo[1,2-b]pyridazinyl, benzo[d]thiazolyl, benzo[d]isothiazolyl, benzo[d]imidazolyl, benzo[d]oxazolyl, or benzo[d]isoxazolyl.

In Formula I, R³is H or C_1-6alkyl. In some embodiments, R³is H. In other embodiments, R³is C_1-6alkyl such as methyl, ethyl, propyl, butyl, pentyl, or hexyl. In further embodiments, R³is methyl. In yet other embodiments, R³is ethyl. In still further embodiments, R³is propyl. In other embodiments, R³is butyl. In further embodiments, R³is pentyl. In yet other embodiments, R³is hexyl.

In Formula I, R⁴is H or C_1-6alkyl. In some embodiments, R⁴is H. In other embodiments, R⁴is C_1-6alkyl such as methyl, ethyl, propyl, butyl, pentyl, or hexyl. In further embodiments, R⁴is methyl. In yet other embodiments, R⁴is ethyl. In still further embodiments, R⁴is propyl. In other embodiments, R⁴is butyl. In further embodiments, R⁴is pentyl. In yet other embodiments, R⁴is hexyl.

Alternatively, R³and R⁴, together with the atom to which they are attached, form a C_3-6cycloalkyl. In some embodiments, R³and R⁴together form a cyclopropyl. In other embodiments, R³and R⁴together form a cyclobutyl. In further embodiments, R³and R⁴together form a cyclopentyl. In yet other embodiments, R³and R⁴together form a cyclohexyl.

In some embodiments, both R³and R⁴are H. In other embodiments, R³is methyl and R⁴is H. In still other embodiments, both R³and R⁴are methyl.

In Formula I, R⁵is H or D. In some embodiments, R⁵is H. In further embodiments, R⁵is D.

In Formula I, R^5Ais H or D. In some embodiments, R^5Ais H. In further embodiments, R^5Ais D.

In Formula I, L is a bond, carbonyl, optionally substituted C_1-6alkylene, optionally substituted C_1-6alkylenecarbonyl, optionally substituted C_2-6alkenylenecarbonyl, optionally substituted C_1-6haloalkylenecarbonyl, or optionally substituted —C(O)NR^c(C_1-6alkylene)-, wherein the carbon atom of the carbonyl group is connected to N in Formula I.

In some embodiments, L is a bond. In other embodiments, L is carbonyl (wherein the carbon atom of the carbonyl group is connected to N in Formula I). In further embodiments, L is optionally substituted C_1-6alkylene such as methylene, ethylene, propylene, butylene, pentylene, or hexylene. In other embodiments, L is C₁alkylene. In still other embodiments, L is C₂alkylene. In further embodiments, L is C₃alkylene. In yet other embodiments, L is C₄alkylene. In still further embodiments, L is C₅alkylene. In other embodiments, L is C₆alkylene. In yet other embodiments, L is optionally substituted C_1-6alkylenecarbonyl (wherein the carbon atom of the carbonyl group is connected to N in Formula I). In further embodiments, L is —C₁alkylene-C(O)—. In other embodiments, L is —C₂alkylene-C(O)—. In further embodiments, L is —C₃alkylene-C(O)—. In yet other embodiments, L is —C₄alkylene-C(O)—. In still further embodiments, L is —C₅alkylene-C(O)—. In other embodiments, L is —C₆alkylene-C(O)—. In still further embodiments, L is optionally substituted C_2-6alkenylenecarbonyl (wherein the carbon atom of the carbonyl group is connected to N in Formula I). In other embodiments, L is —C₂alkenylene-C(O)—. In further embodiments, L is —C₃alkenylene-C(O)—. In yet other embodiments, L is —C₄alkenylene-C(O)—. In still further embodiments, L is —C₅alkenylene-C(O)—. In other embodiments, L is —C₆alkenylene-C(O)—. In other embodiments, L is optionally substituted C_1-6haloalkylenecarbonyl (wherein the carbon atom of the carbonyl group is connected to N in Formula I). In yet other embodiments, L is —C₁haloalkylene-C(O)—. In other embodiments, L is —C₂haloalkylene-C(O)—. In further embodiments, L is —C₃haloalkylene-C(O)—. In yet other embodiments, L is —C₄haloalkylene-C(O)—. In still further embodiments, L is —C₅haloalkylene-C(O)—. In other embodiments, L is —C₆haloalkylene-C(O)—. In further embodiments, L is —C(O)NR^c(C_1-6alkylene)- (wherein the carbon atom of the carbonyl group is connected to N in Formula I). In yet other embodiments, L is —C(O)NR^cC₁alkylene-. In other embodiments, L is —C(O)NR^cC₂alkylene-. In further embodiments, L is —C(O)NR^cC₃alkylene-. In yet other embodiments, L is —C(O)NR^cC₄alkylene-. In still further embodiments, L is —C(O)NR^cC₅alkylene-. In other embodiments, L is —C(O)NR^cC₆alkylene-.

In the structures for L, R^cis H or C_1-6alkyl. In some embodiments, R^cis H. In other embodiments, R^cis C_1-6alkyl, such as methyl, ethyl, propyl, butyl, pentyl, or hexyl. In further embodiments, R^cis methyl. In yet other embodiments, R^cis ethyl. In still further embodiments, R^cis propyl. In other embodiments, R^cis butyl. In further embodiments, R^cis pentyl. In yet other embodiments, R^cis hexyl.

In some embodiments, L is a bond, —C(O)—, —C(O)CH₂—, —C(O)CH₂CH₂—, —C(O)CH₂CH₂CH₂—, —C(O)CF₂—, —C(O)CHF—, —C(O)C(CH₃)₂—, —C(O)CH═CH—,

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—C(O)NHCH₂—, —CH₂—, or —CH₂CH₂—. In yet other embodiments, L is a bond, —C(O)—, —C(O)CH₂—, —C(O)CH₂CH₂—, or

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In some embodiments, R²is cyclopentyl, cyclobutyl, cyclopropyl, azetidinyl, phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazolo[1,5-a]pyridinyl, indazolyl, thiadiazolyl, imidazol[1,5-a]pyridinyl, pyrrolo[1,2]pyridazinyl, thiophenyl, isoxazolyl, isothiazolyl, benzo[d]thiazolyl, benzo[d]imidazolyl, benzo[d]oxazolyl, benzo[d]isoxazolyl, benzo[d]isothiazolyl, furanyl, or pyrazinyl, each of which is optionally substituted.

In further embodiments, R²is cyclopentyl, cyclobutyl, cyclopropyl, cyclohexyl, azetidinyl, phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazolo[1,5-a]pyridinyl, indazolyl, thiadiazolyl, imidazol[1,5-a]pyridinyl, pyrrolo[1,2]pyridazinyl, thiophenyl, isoxazolyl, isothiazolyl, benzo[d]thiazolyl, benzo[d]imidazolyl, benzo[d]oxazolyl, benzo[d]isoxazolyl, benzo[c]isoxazolyl, benzo[d]isothiazolyl, furanyl, pyrazinyl or quinolinyl, each of which is optionally substituted.

In other embodiments, R²is cyclopentyl, cyclobutyl, cyclopropyl, azetidinyl, phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazolo[1,5-a]pyridinyl, indazolyl, thiadiazolyl, imidazol[1,5-a]pyridinyl, pyrrolo[1,2]pyridazinyl, thiophenyl, isoxazolyl, isothiazolyl, benzo[d]thiazolyl, benzo[d]imidazolyl, benzo[d]oxazolyl, benzo[d]isoxazolyl, benzo[d]isothiazolyl, furanyl, or pyrazinyl, each of which is unsubstituted.

In yet other embodiments, R²is cyclopentyl, cyclobutyl, cyclopropyl, cyclohexyl, azetidinyl, phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazolo[1,5-a]pyridinyl, indazolyl, thiadiazolyl, imidazol[1,5-a]pyridinyl, pyrrolo[1,2]pyridazinyl, thiophenyl, isoxazolyl, isothiazolyl, benzo[d]thiazolyl, benzo[d]imidazolyl, benzo[d]oxazolyl, benzo[d]isoxazolyl, benzo[c]isoxazolyl, benzo[d]isothiazolyl, furanyl, pyrazinyl or quinolinyl, each of which is unsubstituted.

In further embodiments, R²is optionally substituted cyclopentyl. In further embodiments, R²is optionally substituted cyclobutyl. In still other embodiments, R²is optionally substituted cyclopropyl. In yet other embodiments, R²is optionally substituted cyclohexyl. In yet further embodiments, R²is optionally substituted azetidinyl. In other embodiments, R²is optionally substituted phenyl. In further embodiments, R²is optionally substituted pyrazolyl. In still other embodiments, R²is optionally substituted oxazolyl. In yet further embodiments, R²is optionally substituted thiazolyl. In other embodiments, R²is optionally substituted triazolyl. In further embodiments, R²is optionally substituted oxadiazolyl. In still other embodiments, R²is optionally substituted pyridinyl. In yet further embodiments, R²is optionally substituted pyrimidinyl. In other embodiments, R²is optionally substituted pyrazolo[1,5-a]pyridinyl. In further embodiments, R²is optionally substituted indazolyl. In yet other embodiments, R²is optionally substituted thiadiazolyl. In other embodiments, R²is optionally substituted imidazol[1,5-a]pyridinyl. In further embodiments, R²is optionally substituted pyrrolo[1,2]pyridazinyl. In still other embodiments, R²is optionally substituted thiophenyl. In yet further embodiments, R²is optionally substituted isoxazolyl. In further embodiments, R²is optionally substituted isothiazolyl. In other embodiments, R²is optionally substituted benzo[d]thiazolyl. In further embodiments, R²is optionally substituted benzo[d]imidazolyl. In still other embodiments, R²is optionally substituted benzo[d]oxazolyl. In yet further embodiments, R²is benzo[d]isoxazolyl. In yet other embodiments, R²is optionally substituted benzo[c]isoxazolyl. In still further embodiments, R²is optionally substituted benzo[d]isothiazolyl. In other embodiments, R²is optionally substituted furanyl. In yet other embodiments, R²is optionally substituted pyrazinyl. In still further embodiments, R²is optionally substituted quinolinyl.

In other embodiments, R²is azetidin-1-yl, azetidin-3-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, 1,2,4-triazol-1-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,3-triazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, pyrazolo[1,5-a]pyridin-3-yl, indazol-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, 1,3,4-thiadiazol-2-yl, pyridin-1-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, imidazol[1,5-a]pyridin-1-yl, pyrrolo[1,2]pyridazin-5-yl, pyrrolo[1,2]pyridazin-6-yl, thiophen-2-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, benzo[d]thiazol-2-yl, benzo[d]thiazol-3-yl, benzo[d]imidazol-2-yl, benzo[d]oxazol-2-yl, benzo[d]isoxazol-3-yl, benzo[d]isothiazol-3-yl, furan-3-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, or pyrazin-2-yl, each of which is optionally substituted.

In yet other embodiments, R²is azetidin-1-yl, azetidin-3-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, 1,2,4-triazol-1-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,3-triazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, pyrazolo[1,5-a]pyridin-3-yl, indazol-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, 1,3,4-thiadiazol-2-yl, pyridin-1-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, imidazol[1,5-a]pyridin-1-yl, pyrrolo[1,2]pyridazin-5-yl, pyrrolo[1,2]pyridazin-6-yl, thiophen-2-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, benzo[d]thiazol-2-yl, benzo[d]thiazol-3-yl, benzo[d]imidazol-2-yl, benzo[d]oxazol-2-yl, benzo[d]isoxazol-3-yl, benzo[d]isothiazol-3-yl, furan-3-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazin-2-yl, benzo[c]isoxazole-3-yl, or quinolin-3-yl, each of which is optionally substituted.

In further embodiments, R²is C_3-8cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with one or more of C_1-6alkyl, optionally substituted C_2-6alkenyl, halo, CN, C_1-6cyanoalkyl, C_1-6haloalkyl, OH, optionally substituted C_3-8cycloalkyl, optionally substituted C_3-8cycloalkyl(alkylene), optionally substituted C_3-8cycloalkenyl, optionally substituted aryl, optionally substituted aryl(alkylene), optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclyl(alkylene), C_1-6hydroxyalkyl, C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6deuteratedalkoxy(alkylene), C_1-6alkylcarbonyl, C_3-8cycloalkylsulfonyl, C_1-6alkylsulfonyl, C_1-6alkylsulfonyl(alkylene), (CR^vR^x)_pNR^yR^z(wherein R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^z, are independently, H, C_1-6alkyl, C_3-6cycloalkyl, C_1-6hydroxyalkyl, C_1-6haloalkyl, C_1-6alkoxy(alkylene), or C(O)OC_1-6alkyl and p is 0, 1, 2, or 3), or C(O)NR^y2R^z2(wherein R^y2and R^z2, are independently, H, C_1-6alkyl, or C_3-6cycloalkyl). In other embodiments, R²is optionally substituted with C_1-6alkyl, such as methyl, ethyl, propyl, isopropyl, or tert-butyl. In yet further embodiments, R²is optionally substituted with C_2-6alkenyl such as CH═CH₂, CH═CHC(CH₃)₂OH, or CH═CH-cyclopropyl. In further embodiments, R²is optionally substituted with halo such as Br, Cl, or F. In yet other embodiments, R²is optionally substituted with CN. In still further embodiments, R²is optionally substituted with C_1-6cyanoalkyl such as C(CH₃)₂CN. In other embodiments, R²is optionally substituted with C_1-6haloalkyl, such as CF₃, CHF₂, CH₂F, CH(CH₃)F, CH₂CF₃, C(CH₃)₂F, C(CH₃)F₂, or CH₂CHF₂. In further embodiments, R²is optionally substituted with OH. In still other embodiments, R²is optionally substituted with optionally substituted C_3-8cycloalkyl, such as optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, or optionally substituted cyclohexyl. In further embodiments, R²is optionally substituted with optionally substituted C_3-8cycloalkyl(alkylene) such as optionally substituted cyclopropyl(alkylene) or optionally substituted cyclobutyl(alkylene). In other embodiments, R²is optionally substituted with optionally substituted C_3-8cycloalkenyl, such as optionally substituted cyclohexenyl. In yet further embodiments, R²is optionally substituted with optionally substituted aryl such as optionally substituted phenyl. In further embodiments, R²optionally substituted with optionally substituted aryl(alkylene) such as optionally substituted benzyl. In other embodiments, R²is optionally substituted with optionally substituted heteroaryl, such optionally substituted pyrazolyl, optionally substituted imidazolyl, optionally substituted pyridinyl, optionally substituted pyrimidinyl, or optionally substituted pyrazinyl. In yet other embodiments, R²is optionally substituted with optionally substituted heteroaryl, such optionally substituted pyrazolyl, optionally substituted imidazolyl, optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, or optionally substituted pyridazinyl. In further embodiments, R²is optionally substituted with optionally substituted heterocyclyl such as optionally substituted azetidinyl, optionally substituted piperidinyl, optionally substituted piperazinyl, optionally substituted pyrrolidinyl, optionally substituted morpholinyl, or optionally substituted 6-azaspiro[2.5]octan-6-yl. In yet further embodiments, R²is optionally substituted with optionally substituted morpholinyl(alkylene), optionally substituted piperidinyl(alkylene), optionally substituted piperazinyl(alkylene), or optionally substituted azetidinyl(alkylene). In still other embodiments, R²is optionally substituted with C_1-6hydroxyalkyl such as C(CH₃)₂OH, CH(CH₃)OH, C(CH₃)₂CH₂OH, CH₂C(CH₃)₂OH, or CH(CH₂CH₃)OH. In yet further embodiments, R²is optionally substituted with C_1-6haloalkoxy such as OCF₃, OCH₂CF₃, or OCH₂CH₂CF₃. In still further embodiments, R²is optionally substituted with C_1-6haloalkoxy(alkylene) such as CH₂OCF₃. In other embodiments, R²is optionally substituted with C_1-6alkoxy, such as methoxy or ethoxy. In yet other embodiments, R²is optionally substituted with C_1-6alkoxy(alkylene), such as C(CH₃)₂OCH₃, CH₂OCH₃, or (CH₂)₂OCH₃. In further embodiments, R²is optionally substituted with C_1-6deuteratedalkoxy(alkylene) such as CH₂OCD₃. In further embodiments, R²is optionally substituted with C_1-6alkylcarbonyl, such as C(═O)CH₃or CH₂C(═O)CH₃. In yet other embodiments, R²is optionally substituted with C_3-8cycloalkylsulfonyl such as cyclopropylsulfonyl, cyclobutylsulfonyl, or cyclopentylsulfonyl. In other embodiments, R²is optionally substituted with C_1-6alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, or propylsulfonyl. In yet other embodiments, R²is optionally substituted with C_1-6alkylsulfonyl(alkylene), such as C(CH₃)₂SO₂CH₃. In still further embodiments, R²is optionally substituted with (CR^vR^x)_pNR^yR^z, wherein R^v, R^x, R^y, R^z, and p are defined above, such as NH₂, NHcyclopropyl, NHCH₃, N(CH₃)₂, CH₂N(CH₃)₂, (CH₂)₂N(CH₃)₂, CH₂N(CH₃)(CH₂CH₃), C(CH₃)₂NH(CH₃), C(CH₃)₂N(CH₃)₂, CH₂N(CH₃)cyclobutyl, or CH₂N(CH₃)(C(O)Otert-butyl). In some embodiments, p is 0. In other embodiments, p is 1. In further embodiments, p is 2. In still other embodiments, p is 3. In some embodiments, RV and R^xare, independently, hydrogen or methyl. In other embodiments, R^yand R^zare, independently, hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, C(O)Omethyl, C(O)Oethyl, C(O)Opropyl, or C(O)Otert-butyl. In other embodiments, R²is C(O)NR^y2R^z2, wherein R^y2and R^z2are defined above, such as C(O)N(CH₃)₂or C(O)NHcyclopropyl. In yet other embodiments, R^y2and R^z2are, independently, hydrogen, methyl, or cyclopropyl. In further embodiments, R²is substituted with one or more of methyl, ethyl, propyl, isopropyl, tert-butyl, CH═CH₂, CH═CHC(CH₃)₂OH, CH═CH-cyclopropyl, Br, Cl, F, CN, C(CH₃)₂CN, CF₃, CHF₂, CH₂F, CH(CH₃)F, CH₂CF₃, C(CH₃)₂F, C(CH₃)F₂, CH₂CHF₂, OH, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, optionally substituted cyclohexyl, optionally substituted cyclohexenyl, optionally substituted cyclopropyl(alkylene), optionally substituted cyclobutyl(alkylene), optionally substituted phenyl, optionally substituted benzyl, optionally substituted pyrazolyl, optionally substituted imidazolyl, optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted azetidinyl, optionally substituted piperidinyl, optionally substituted piperazinyl, optionally substituted pyrrolidinyl, optionally substituted morpholinyl, optionally substituted 6-azaspiro[2.5]octan-6-yl, optionally substituted morpholinyl(alkylene), optionally substituted piperidinyl(alkylene), optionally substituted piperazinyl(alkylene), or optionally substituted azetidinyl(alkylene), C(CH₃)₂OH, CH(CH₃)OH, C(CH₃)₂CH₂OH, CH₂C(CH₃)₂OH, CH(CH₂CH₃)OH, OCF₃, OCH₂CF₃, OCH₂CH₂CF₃, CH₂OCF₃, methoxy, ethoxy, C(CH₃)₂OCH₃, CH₂OCH₃, (CH₂)₂OCH₃, CH₂OCD₃, C(═O)CH₃, CH₂C(═O)CH₃, cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, C(CH₃)₂SO₂CH₃, NH₂, NHcyclopropyl, NHCH₃, N(CH₃)₂, CH₂N(CH₃)₂, (CH₂)₂N(CH₃)₂, CH₂N(CH₃)(CH₂CH₃), C(CH₃)₂NH(CH₃), C(CH₃)₂N(CH₃)₂, CH₂N(CH₃)cyclobutyl, CH₂N(CH₃)(C(O)Otert-butyl), C(O)N(CH₃)₂, or C(O)NHcyclopropyl.

In yet further embodiments, R²

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In other embodiments, R²is

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In yet other embodiments, R²is

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In some embodiments, R²is heterocyclyl, optionally substituted with one or more of halo, C_1-6haloalkyl, or optionally substituted heteroaryl. In still other embodiments,

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In yet other embodiments, R²is heterocyclyl, substituted with one or more of halo, C_1-6haloalkyl, or optionally substituted heteroaryl. In further embodiments, R²is

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In still further embodiments, R²is

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In some embodiments, R²is C_3-8cycloalkyl, optionally substituted with one or more of halo, C_1-6alkyl, C_1-6haloalkyl, or OH In yet other embodiments, R²is unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, unsubstituted cyclohexyl

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In further embodiments, R²is C_3-8cycloalkyl, substituted with one or more of halo, C_1-6alkyl, C_1-6haloalkyl, or OH. In still further embodiments, R²is

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In other embodiments, R²is

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In yet other embodiments, R²is unsubstituted cyclopropyl,

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In some embodiments, R²is aryl, optionally substituted with one or more of halo or C_1-6alkoxy. In other embodiments, R²is unsubstituted phenyl,

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In yet other embodiments, R²is aryl, substituted with one or more of halo or C_1-6alkoxy. In further embodiments, R²is

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In other embodiments, R²is

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In some embodiments, R²is optionally substituted pyridinyl, optionally substituted pyrimidinyl, or optionally substituted pyrazinyl. In other embodiments, the pyridinyl, pyrimidinyl, or pyrazinyl group is substituted with one or more of halo, C_1-6haloalkyl, cyano, or NR^yR^z, wherein R^yand R^zare independently H or C_1-6alkyl.

In still further embodiments, R²is heteroaryl, substituted with one or more of C_1-6alkyl, C_1-6cyanoalkyl, C_1-6haloalkyl, or C_1-6hydroxyalkyl. In other embodiments, R²is heteroaryl substituted with one or more of C_1-6alkyl. In yet other embodiments, R²is heteroaryl substituted with one or more of C_1-6cyanoalkyl. In further embodiments, R²is heteroaryl substituted with one or more of C_1-6haloalkyl. In still further embodiments, R²is heteroaryl, substituted with one or more of C_1-6fluoroalkyl. In yet other embodiments, R²is heteroaryl substituted with one or more of C_1-6hydroxyalkyl. In other embodiments, R²is heteroaryl, substituted with one or more of methyl, ethyl, isopropyl, tert-butyl, C(CH₃)₂CN, CH(CH₃)OH, C(CH₃)₂OH, C(CH₃)₂CH₂OH, CH(CH₂CH₃)OH, CH₂C(CH₃)₂OH, CH₂F, CHF₂, CF₃, CH₂CF₃, CH₂CHF₂, CH(CH₃)F, C(CH₃)F₂, or C(CH₃)₂F. In yet other embodiments, R²is heteroaryl, substituted with methyl. In still other embodiments, R²is heteroaryl, substituted with ethyl. In yet other embodiments, R²is heteroaryl, substituted with isopropyl. In other embodiments, R²is heteroaryl, substituted with tert-butyl. In yet other embodiments, R²is heteroaryl, substituted with C(CH₃)₂CN. In still further embodiments, R²is heteroaryl, substituted with CH(CH₃)OH. In other embodiments, R²is heteroaryl, substituted with C(CH₃)₂OH. In yet other embodiments, R²is heteroaryl, substituted with C(CH₃)₂CH₂OH. In still other embodiments, R²is heteroaryl, substituted with CH(CH₂CH₃)OH. In further embodiments, R²is heteroaryl, substituted with CH₂C(CH₃)₂OH. In further embodiments, R²is heteroaryl, substituted with CHF₂. In yet other embodiments, R²is heteroaryl, substituted with CH₂F. In still other embodiments, R²is heteroaryl, substituted with CF₃. In further embodiments, R²is heteroaryl, substituted with CH₂CF₃. In yet other embodiments, R²is heteroaryl, substituted with CH₂CHF₂. In further embodiments, R²is heteroaryl, substituted with C(CH₃)F₂. In still other embodiments, R²is heteroaryl, substituted with CH(CH₃)F. In other embodiments, R²is heteroaryl, substituted with C(CH₃)₂F.

In other embodiments, R²is heteroaryl, substituted with C_3-8cycloalkyl, wherein the C_3-8cycloalkyl itself is optionally substituted with one or more of halo, OH, C_1-6haloalkyl, C_1-6alkyl or C_1-6alkoxy. In yet other embodiments, R²is heteroaryl, substituted with an unsubstituted C_3-8cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In further embodiments, R²is heteroaryl, substituted with cyclopropyl or cyclobutyl. In yet other embodiments, R²is heteroaryl, substituted with C_3-8cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein the C_3-8cycloalkyl itself is substituted with one or more of halo, OH, C_1-6haloalkyl, C_1-6alkyl or C_1-6alkoxy. In some embodiments, the substituted C_3-8cycloalkyl is substituted with OH. In still further embodiments, the substituted C_3-8cycloalkyl is substituted with one or more of halo, such as F, Cl, or Br. In other embodiments, the substituted C_3-8cycloalkyl is substituted with C_1-6alkyl, such as methyl, ethyl, or propyl. In further embodiments, the substituted C_3-8cycloalkyl is substituted with C_1-6haloalkyl, such as CF₃, CH₂CF₃, or CHF₂. In still other embodiments, the substituted C_3-8cycloalkyl is substituted with C_1-6alkoxy, such as methoxy, ethoxy, or propoxy. In further embodiments, the substituted C_3-8cycloalkyl is cyclopropyl or cyclobutyl, each of which is substituted with one or more of F, OH, or methyl. In other embodiments, R²is heteroaryl, substituted with

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In other embodiments, R²is heteroaryl, substituted with aryl, wherein the aryl itself is optionally substituted with one or more of halo, C_1-6haloalkyl, C_1-6alkyl, or C_3-8cycloalkyl. In yet other embodiments, R²is heteroaryl, substituted with an unsubstituted phenyl. In further embodiments, R²is heteroaryl, substituted with aryl, such as phenyl, wherein the aryl itself is substituted with one or more of halo, C_1-6haloalkyl, C_1-6alkyl, or C_3-8cycloalkyl. In some embodiments, the substituted aryl is substituted with one or more of halo, such as F, Cl, or Br. In yet other embodiments, the substituted aryl is substituted with C_1-6haloalkyl, such as CF₃, CH₂CF₃, or CHF₂. In still further embodiments, the substituted aryl is substituted with C_1-6alkyl, such as methyl, ethyl, or propyl. In other embodiments, the substituted aryl is substituted with C_3-8cycloalkyl, such as cyclopropyl, cyclobutyl, or cyclopentyl. In yet other embodiments, the substituted aryl is phenyl that is substituted with one or more of F, methyl, or CF₃. In further embodiments, R²is heteroaryl, substituted with

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In still further embodiments, R²is heteroaryl, substituted with

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In still further embodiments, R²is heteroaryl, substituted with an optionally substituted heteroaryl. In some embodiments, the optionally substituted heteroaryl is optionally substituted pyridinyl, optionally substituted pyrazinyl, optionally substituted pyrazolyl, optionally substituted imidazolyl, or optionally substituted pyrimidinyl. In yet other embodiments, the optional substitution on the heteroaryl is one or more of halo, C_1-6haloalkyl, C_1-6alkyl, C_1-6alkoxy, C_1-6haloalkoxy, C_3-8cycloalkyl or C_3-8cycloalkylsulfonyl. In other embodiments, the optionally substituted heteroaryl is substituted with one or more of halo, such as F, Cl, or Br. In still other embodiments, the optionally substituted heteroaryl is substituted with one or more of C_1-6haloalkyl, such as CF₃, CH₂CF₃, CH₂CHF₂, or CHF₂. In other embodiments, the optionally substituted heteroaryl is substituted with one or more of C_1-6alkyl, such as methyl, ethyl, propyl, or isopropyl. In still other embodiments, the optionally substituted heteroaryl is substituted with one or more of C_1-6alkoxy, such as methoxy, ethoxy, or propoxy. In other embodiments, the optionally substituted heteroaryl is substituted with one or more of C_1-6haloalkoxy, such as OCF₃. In yet other embodiments, the optionally substituted heteroaryl is substituted with one or more of C_3-8cycloalkyl, such as cyclopropyl, cyclobutyl, or cyclopentyl. In other embodiments, the optionally substituted heteroaryl is substituted with one or more of C_3-8cycloalkylsulfonyl, such as cyclopropylsulfonyl, cyclobutylsulfonyl, or cyclopentylsulfonyl. In still other embodiments, the optionally substituted heteroaryl is substituted with one or more of F, CF₃, CH₂CF₃, CH₂CHF₂, CHF₂, methyl, isopropyl, methoxy, OCF₃, cyclopropyl, cyclobutyl, or cyclopropylsulfonyl.

In yet other embodiments, R²is heteroaryl, substituted with pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl, pyrazin-3-yl, pyrazin-4-yl, pyrazin-5-yl, imidazol-4-yl, or imidazol-5-yl, each of which can be optionally substituted. In further embodiments, R²is substituted with pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl, pyrazin-3-yl, pyrazin-4-yl, pyrazin-5-yl, imidazol-4-yl, imidazol-5-yl, pyridazin-3-yl, pyridazin-4-yl, each of which is optionally substituted. In still further embodiments, R²is substituted with optionally substituted pyrazol-1-yl. In other embodiments, R²is substituted with optionally substituted pyrazol-3-yl. In further embodiments, R²is substituted with optionally substituted pyrazol-4-yl. In yet further embodiments, R²is substituted with optionally substituted pyridin-2-yl. In other embodiments, R²is substituted with optionally substituted pyridin-3-yl. In further embodiments, R²is substituted with optionally substituted pyridin-4-yl. In further embodiments, R²is substituted with optionally substituted imidazol-4-yl. In yet other embodiments, R²is substituted with optionally substituted imidazol-5-yl. In further embodiments, R²is substituted with optionally substituted pyrimidin-2-yl. In other embodiments, R²is substituted with optionally substituted pyrimidin-4-yl. In still further embodiments, R²is substituted with optionally substituted pyrimidin-5-yl. In yet other embodiments, R²is substituted with optionally substituted pyrazin-2-yl. In other embodiments, R²is substituted with optionally substituted pyridazin-3-yl. In further embodiments, R²is substituted with optionally substituted pyridazin-4-yl.

In some embodiments, R²is heteroaryl, substituted with

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In still further embodiments, R is heteroaryl, substituted with

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In still further embodiments, R²is heteroaryl, substituted with

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In some embodiments, R²is heteroaryl, substituted with

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In other embodiments, R²is heteroaryl, substituted with

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In still other embodiments, R²is heteroaryl, substituted with

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In other embodiments, R²is heteroaryl, substituted with heterocyclyl or heterocyclyl(alkylene), wherein the heterocyclyl and heterocyclyl(alkylene) groups themselves are each optionally substituted with one or more of halo, OH, C_1-6haloalkyl, C_1-6alkyl, C_1-6hydroxyalkyl, C_1-6alkoxy, C(O)O(C_1-6alkyl), or C_3-8cycloalkyl. In yet other embodiments, R²is heteroaryl, substituted with an unsubstituted heterocyclyl group such as azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or 6-azaspiro[2.5]octan-6-yl or unsubstituted heterocyclyl(alkylene) group, such as azetidinyl(alkylene), pyrrolidinyl(alkylene), piperidinyl(alkylene), piperazinyl(alkylene), or morpholinyl(alkylene). In further embodiments, R²is heteroaryl, substituted with heterocyclyl, such as azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or 6-azaspiro[2.5]octan-6-yl or heterocyclyl(alkylene), such as azetidinyl(alkylene), pyrrolidinyl(alkylene), piperidinyl(alkylene), piperazinyl(alkylene), or morpholinyl(alkylene), wherein the heterocyclyl and heterocyclyl(alkylene) groups themselves are each substituted with one or more of halo, OH, C_1-6haloalkyl, C_1-6alkyl, C_1-6hydroxyalkyl, C_1-6alkoxy, C(O)O(C_1-6alkyl), or C_3-8cycloalkyl. In further embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of halo, such as F, Cl, or Br. In yet further embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of OH. In yet other embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of C_1-6haloalkyl, such as CF₃, CH₂CF₃, or CHF₂. In still further embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of C_1-6alkyl, such as methyl, ethyl, or propyl. In yet further embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of C_1-6hydroxyalkyl such as C(CH₃)₂OH, or CH(CH₃)OH. In other embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of C_1-6alkoxy, such as methoxy, ethoxy, or propoxy. In yet other embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of C(O)O(C_1-6alkyl), such as C(O)Omethyl, C(O)Oethyl, C(O)Opropyl, or C(O)Otert-butyl. In further embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of C_3-8cycloalkyl, such as cyclopropyl, cyclobutyl, or cyclopentyl. In yet other embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more of F, OH, methyl, C(CH₃)₂OH, C(O)Otert-butyl, or cyclopropyl. In yet other embodiments where R²is heteroaryl, the R²is substituted with

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In still further embodiments where R²is heteroaryl, the R²is substituted with

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In further embodiments, R²is

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In yet further embodiments, R²is

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In still further embodiments, R²is,

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In other embodiments, R²is

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In further embodiments, R²is

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In yet further embodiments, R²is

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In still further embodiments, R²is

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In yet other embodiments, R²is

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In other embodiments, R²is

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In further embodiments, R²is

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In yet other embodiments, R²is

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In still further embodiments, R²is

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In other embodiments, R²is

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In further embodiments, R²is

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In still other embodiments, R²is

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In yet further embodiments, R²is

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In other embodiments, R²is

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In further embodiments, R²is

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In yet other embodiments, R²is

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In still further embodiments, R²is

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In other embodiments, R²is

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In other embodiments, R²is

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In further embodiments, R²is

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In yet other embodiments, R²is

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In these structures for R², R⁶and R⁷are each independently, H, CN, C_1-6alkyl, C_1-6haloalkyl, C_1-6cyanoalkyl, C_1-6hydroxyalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_1-6deuteratedalkoxy(alkylene), halo, (CR^vR^x)_pNR^yR^z, C(O)NR^y2R^z2, C_1-6alkylcarbonyl, optionally substituted C_3-8cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C_2-6alkenyl, optionally substituted C_3-8cycloalkenyl, optionally substituted (C_3-8cycloalkyl)alkylene, optionally substituted (aryl)alkylene, optionally substituted (heterocyclyl)alkylene, or C_1-6alkylsulfonyl; R⁵is H, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy(alkylene), C_1-6alkylcarbonyl, C_1-6hydroxyalkyl, (CR^vR^x)_pNR^yR^zoptionally substituted C_3-8cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted (C_3-8cycloalkyl)alkylene; R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare, independently, H, C_1-6alkyl, C_1-6alkoxy(alkylene), or C_3-6cycloalkyl; R^y2and R^z2are, independently, H, C_1-6alkyl, or C_3-6cycloalkyl; and p is 0, 1, 2, or 3. In some embodiments, R⁶, R⁷, and R⁵are H.

In other embodiments, R⁶is C_1-6alkyl, C_1-6haloalkyl, C_1-6cyanoalkyl, or C_1-6hydroxyalkyl. In further embodiments, R⁶is C_1-6alkyl such as methyl, ethyl, isopropyl or tert-butyl. In still further embodiments, R⁶is C_1-6haloalkyl such as CF₃, CHF₂, CH₂F, CH₂CF₃, CH(CH₃)F, C(CH₃)F₂, or C(CH₃)₂F. In further embodiments, R⁶is C_1-6cyanoalkyl such as C(CH₃)₂CN. In other embodiments, R⁶is C_1-6hydroxyalkyl such as C(CH₃)₂OH, CH(CH₃)OH, CH(CH₂CH₃)OH, CH₂C(CH₃)₂OH, or C(CH₃)₂CH₂OH. In further embodiments, R⁶is methyl, ethyl, isopropyl, tert-butyl, CF₃, CHF₂, CH₂F, CH(CH₃)F, C(CH₃)F₂, C(CH₃)₂F, C(CH₃)₂CN, C(CH₃)₂OH, CH(CH₃)OH, CH(CH₂CH₃)OH, CH₂C(CH₃)₂OH, or C(CH₃)₂CH₂OH.

In other embodiments, R⁶is C_3-6cycloalkyl optionally substituted with one or more of halo, OH, C_1-6haloalkyl, C_1-6alkyl, or C_1-6alkoxy. In further embodiments, R⁶is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, optionally substituted with one or more of halo, OH, C_1-6haloalkyl, C_1-6alkyl, or C_1-6alkoxy. In still further embodiments, R⁶is unsubstituted cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In other embodiments, R⁶is C_3-6cycloalkyl substituted with one or more halo such as F, Cl, or Br. In yet other embodiments, R⁶is C_3-6cycloalkyl substituted with one or more OH. In still further embodiments, R⁶is C_3-6cycloalkyl substituted with one or more C_1-6haloalkyl such as CF₃, CH₂CF₃, or CHF₂. In further embodiments, R⁶is C_3-6cycloalkyl substituted with one or more C_1-6alkyl such as methyl, ethyl, or propyl. In still further embodiments, R⁶is C_3-6cycloalkyl substituted with C_1-6alkoxy, such as one or more methoxy, ethoxy, or propoxy. In other embodiments, R⁶is cyclopropyl, cyclobutyl, or cyclohexyl, each of which is optionally substituted with one or more of F, OH, or methyl. In other embodiments, R⁶is

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In further embodiments, R⁶is aryl optionally substituted with one or more of halo, C_1-6haloalkyl, C_1-6alkyl or C_3-6cycloalkyl. In other embodiments, R⁶is phenyl optionally substituted with one or more of halo, C_1-6haloalkyl, C_1-6alkyl or C_3-6cycloalkyl. In still other embodiments, R⁶is aryl optionally substituted with one or more of halo such as F, C₁, or Br. In yet other embodiments, R⁶is aryl optionally substituted with one or more of C_1-6haloalkyl such as CF₃, CH₂CF₃, or CHF₂. In other embodiments, R⁶is aryl optionally substituted with one or more of C_1-6alkyl such as methyl, ethyl, or propyl. In yet other embodiments, R⁶is aryl optionally substituted with one or more of C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, or cyclopentyl. In other embodiments, R⁶is aryl (e.g., phenyl) optionally substituted with F, methyl, or CF₃. In other embodiments, R⁶is

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In yet other embodiments, R⁶is

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In yet other embodiments, R⁶is heteroaryl, optionally substituted with one or more of halo, C_1-6haloalkyl, C_1-6alkyl, C_1-6alkoxy, C_1-6haloalkoxy, C_3-6cycloalkyl, or C_3-6cycloalkylsulfonyl. In still other embodiments, R⁶is pyridinyl, pyrazolyl, pyrazinyl, imidazolyl, or pyrimidinyl, each of which is optionally substituted. In still other embodiments, R⁶is pyridinyl, pyrazolyl, pyrazinyl, pyridazinyl, imidazolyl, or pyrimidinyl, each of which is optionally substituted. In further embodiments, R⁶is optionally substituted pyrazinyl such as pyrazin-2-yl, pyrazin-3-yl, pyrazin-4-yl, or pyrazin-5-yl. In other embodiments, R⁶is optionally substituted pyrazolyl such as pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, or pyrazol-5-yl. In still further embodiments, R⁶is optionally substituted pyridinyl such as pyridin-2-yl, pyridin-3-yl, or pyridin-4-yl. In other embodiments, R⁶is optionally substituted pyridazinyl such as pyridazin-3-yl or pyridazin-4-yl. In yet other embodiments, R⁶is optionally substituted imidazolyl such as imidazol-4-yl or imidazol-5-yl. In further embodiments, R⁶is optionally substituted pyrimidinyl such as pyridimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl. In other embodiments, R⁶is pyrazin-2-yl, pyrazin-3-yl, pyrazin-4-yl, pyrazin-5-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, imidazol-4-yl, imidazol-5-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl, each of which is optionally substituted. In yet other embodiments, R⁶is pyrazin-2-yl, pyrazin-3-yl, pyrazin-4-yl, pyrazin-5-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, imidazol-4-yl, imidazol-5-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl or pyridazin-4-yl, each of which is optionally substituted. In further embodiments, R⁶is unsubstituted pyridin-2-yl, unsubstituted pyridin-3-yl, unsubstituted pyridin-4-yl, unsubstituted pyrimidin-2-yl, unsubstituted pyrimidin-4-yl, unsubstituted pyrimidin-5-yl, or unsubstituted pyrazin-2-yl. In further embodiments, R⁶is unsubstituted pyridin-2-yl, unsubstituted pyridin-3-yl, unsubstituted pyridin-4-yl, unsubstituted pyrimidin-2-yl, unsubstituted pyrimidin-4-yl, unsubstituted pyrimidin-5-yl, unsubstituted pyrazin-2-yl, or unsubstituted pyridazin-3-yl. In other embodiments, R⁶is optionally substituted with one or more halo such as F, Cl, or Br. In yet other embodiments, R⁶is optionally substituted with one or more C_1-6haloalkyl such as CF₃, CH₂CF₃, or CHF₂. In other embodiments, R⁶is optionally substituted with one or more C_1-6alkyl such as methyl, ethyl, propyl, or isopropyl. In still other embodiments, R⁶is optionally substituted with one or more C_1-6alkoxy such as methoxy, ethoxy, or propoxy. In yet further embodiments, R⁶is optionally substituted with one or more C_1-6haloalkoxy such as OCF₃. In further embodiments, R⁶is optionally substituted with one or more C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, or cyclopentyl. In yet further embodiments, R⁶is optionally substituted with one or more C_3-6cycloalkylsulfonyl such as cyclopropylsulfonyl, cyclobutylsulfonyl, or cyclopentylsulfonyl. In yet other embodiments, R⁶is heteroaryl optionally substituted with one or more of F, CF₃, CH₂CF₃, CH₂CHF₂, CHF₂, methyl, isopropyl, methoxy, OCF₃, cyclopropyl, cyclobutyl, or cyclopropylsulfonyl.

In other embodiments, R⁶is a five-membered heteroaryl, optionally substituted with one or more of CF₃, CH₂CF₃, CH₂CHF₂, CHF₂, methyl, isopropyl, cyclopropyl, cyclobutyl, or cyclopropylsulfonyl. In further embodiments, R⁶is

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In still further embodiments, R⁶is

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In other embodiments, R⁶is

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In still further embodiments, R⁶is

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In yet further embodiments, R⁶is

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In further embodiments, R⁶is or

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In yet further embodiments, R⁶is

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In other embodiments, R⁶is a six-membered heteroaryl, optionally substituted with one or more of F, CF₃, methoxy, OCF₃, or methyl. In still other embodiments, R⁶is

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In still further embodiments, R⁶is

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In yet other embodiments, R⁶is

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In yet other embodiments, R⁶is heterocyclyl or heterocyclyl(alkylene), each optionally substituted with one or more of halo, OH, C_1-6haloalkyl, C_1-6alkyl, C_1-6hydroxyalkyl, C_1-6alkoxy, C(O)O(C_1-6alkyl), or C_3-6cycloalkyl. In further embodiments, R⁶is optionally substituted azetidinyl, optionally substituted pyrrolidinyl, optionally substituted piperidinyl, optionally substituted piperazinyl, or optionally substituted morpholinyl. In other embodiments, R⁶is optionally substituted azetidinyl. In yet other embodiments, R⁶is optionally substituted pyrrolidinyl. In further embodiments, R⁶is optionally substituted piperidinyl. In yet other embodiments, R⁶is optionally substituted piperazinyl. In still further embodiments, R⁶is optionally substituted morpholinyl. In other embodiments, R⁶is optionally substituted morpholinyl(alkylene), optionally substituted piperidinyl(alkylene), optionally substituted piperazinyl(alkylene), or optionally substituted azetidinyl(alkylene). In further embodiments, R⁶is unsubstituted azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl. In other embodiments, R⁶is unsubstituted morpholinyl(alkylene), piperidinyl(alkylene), piperazinyl(alkylene), or azetidinyl(alkylene). In yet other embodiments, R⁶is unsubstituted morpholinyl or morpholinyl(alkylene). In other embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more halo such as F, Cl, or Br. In yet other embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more OH. In further embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more C_1-6haloalkyl such as CF₃, CH₂CF₃, or CHF₂. In still further embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more C_1-6alkyl such as methyl, ethyl, or propyl. In further embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more C_1-6hydroxyalkyl such as C(CH₃)₂OH. In yet further embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more C_1-6alkoxy, such as methoxy, ethoxy, or propoxy. In other embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more C(O)O(C_1-6alkyl), such as C(O)Omethyl, C(O)Oethyl, C(O)Opropyl, or C(O)Otert-butyl. In still further embodiments, the heterocyclyl and heterocyclyl(alkylene) groups are optionally substituted with one or more C_3-6cycloalkyl such as one or more cyclopropyl, cyclobutyl, or cyclopentyl. In yet other embodiments, R⁶is heterocyclyl and heterocyclyl(alkylene), each optionally substituted with one or more of F, OH, C(CH₃)₂(OH), methyl, C(O)O(tert-butyl), or cyclopropyl.

In further embodiments, R⁶is

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In yet other embodiments, R⁶is

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In further embodiments, R⁶is

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In still further embodiments, R⁶is

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In yet other embodiments, R⁶is

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In other embodiments, R⁶is

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In yet further embodiments, R⁶is

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In further embodiments, R⁶is H, CN, C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_1-6deuteratedalkoxy(alkylene), halo, (CR^vR^x)_pNR^yR^z, C(O)NR^y2R^z2, C_1-6alkylcarbonyl, optionally substituted C_2-6alkenyl, optionally substituted C_3-6cycloalkenyl, optionally substituted (C_3-6cycloalkyl)alkylene, optionally substituted (aryl)alkylene, or C_1-6alkylsulfonyl. In other embodiments, R⁶is H. In further embodiments, R⁶is CN. In still other embodiments, R⁶is C_1-6alkoxy such as methoxy. In yet other embodiments, R⁶is C_1-6alkoxy(alkylene) such as CH₂OCH₃, C(CH₃)₂OCH₃, or (CH₂)₂OCH₃. In still other embodiments, R⁶is C_1-6haloalkoxy such as OCF₃, OCHF₂, OCH₂F, or O(CH₂)₂CF₃. In other embodiments, R⁶is C_1-6haloalkoxy(alkylene) such as CH₂OCF₃. In yet other embodiments, R⁶is C_1-6deuteratedalkoxy(alkylene) such as CH₂OCD₃. In further embodiments, R⁶is halo such as F, Br, or Cl. In yet further embodiments, R⁶is (CR^vR^x)_pNR^yR^zsuch as NH₂, N(CH₃)₂, NHCH₂CF₃, NHCH₂CH₂OCH₃, NH(cyclopropyl), CH₂N(CH₃)₂, (CH₂)₂N(CH₃)₂, C(CH₃)₂NHCH₃, C(CH₃)₂N(CH₃)₂, CH₂NH(cyclopropyl), or CH₂CH₂NH(cyclopropyl). In other embodiments, R⁶is C(O)NR^y2R^z2such as C(O)N(CH₃)₂or C(O)NH(cyclopropyl). In yet other embodiments, R⁶is C_1-6alkylcarbonyl such as C(O)CH₃. In further embodiments, R⁶is optionally substituted C_2-6alkenyl such as CH═CH₂, CH═CH-cyclopropyl, or CH═CHC(CH₃)₂OH. In yet other embodiments, R⁶is optionally substituted C_3-6cycloalkenyl such as

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In still other embodiments, R⁶is optionally substituted (C_3-6cycloalkyl)alkylene such as CH₂-cyclopropyl, CH₂CH₂-cyclopropyl or C(CH₃)OH-cyclopropyl. In further embodiments, R⁶is optionally substituted (aryl)alkylene such as benzyl. In other embodiments, C_1-6alkylsulfonyl(alkylene) such as C(CH₃)₂SO₂CH₃. In yet other embodiments, R⁶is H, CH₂OCH₃, C(CH₃)₂OCH₃, (CH₂)₂OCH₃, O(CH₂)₂CF₃, CH₂OCF₃, CH₂OCD₃, Br, Cl, NH₂, NH(cyclopropyl), CH₂N(CH₃)₂, (CH₂)₂N(CH₃)₂, C(CH₃)₂NHCH₃, C(CH₃)₂N(CH₃)₂, CH═CHC(CH₃)₂OH, CH═CH-cyclopropyl,

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CH₂-cyclopropyl, CH₂CH₂-cyclopropyl, C(CH₃)OH-cyclopropyl, benzyl, or C(CH₃)₂SO₂CH₃.

In some embodiments, R⁷is H, CN, C_1-6alkyl, C_1-6haloalkyl, halo, C_3-8cycloalkyl, aryl, or heteroaryl. In yet other embodiments, R⁷is H. In still further embodiments, R⁷is CN. In other embodiments, R⁷is C_1-6alkyl, such as methyl, ethyl, or propyl. In further embodiments, R⁷is methyl. In yet other embodiments, R⁷is C_1-6haloalkyl, such as CHF₂, CH₂F, C(CH₃)F₂, CH₂CHF₂, or CF₃. In further embodiments, R⁷is halo, such as F, Br, or Cl. In yet other embodiments, R⁷is Br or Cl. In still further embodiments, R⁷is C_3-6cycloalkyl, such as cyclopropyl, cyclobutyl, or cyclopentyl. In other embodiments, R⁷is cyclopropyl. In further embodiments, R⁷is aryl. In yet other embodiments, R⁷is phenyl. In still further embodiments, R⁷is heteroaryl. In other embodiments, R⁷is pyridinyl. In further embodiments, R⁷is H, CN, methyl, CF₃, CH₂F, CHF₂, CF₂(CH₃), CH₂CHF₂, Br, Cl, cyclopropyl, phenyl, or pyridinyl.

In some embodiments of R², R⁸is H. In other embodiments, R⁸is C_1-6alkyl such as methyl, ethyl, propyl, isopropyl, or tert-butyl. In further embodiments, R⁸is C_1-6haloalkyl such as CF₃, CHF₂, CH₂F, CH₂CF₃, CH₂CHF₂, C(CH₃)₂F, or C(CH₃)F₂. In still further embodiments, R⁸is C_1-6alkoxy(alkylene) such as CH₂CH₂OCH₃. In other embodiments, R⁸is C_1-6alkylcarbonyl such as CH₂C(═O)CH₃. In still other embodiments, R⁸is C_1-6hydroxyalkyl such as CH₂C(CH₃)₂OH. In further embodiments, R⁸is (CR^vR^x)_pNR^yR^zsuch as (CH₂)₂N(CH₃)₂. In yet other embodiments, R⁸is optionally substituted C_3-8cycloalkyl such as optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, or optionally substituted cyclohexyl. In other embodiments, R⁸is optionally substituted aryl such as optionally substituted phenyl. In further embodiments, R⁸is optionally substituted heteroaryl such as optionally substituted pyridinyl. In yet other embodiments, R⁸is optionally substituted (C_3-8cycloalkyl)alkylene such as

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In still further embodiments, R⁸is H, methyl, ethyl, isopropyl, tert-butyl, CHF₂, CH₂CF₃, CH₂CHF₂, CF₃, CH₂C(═O)CH₃, CH₂C(CH₃)₂OH, CH₂CH₂OCH₃, (CH₂)₂N(CH₃)₂, cyclopropyl, phenyl, 4-fluorophenyl,

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CH₂-cyclopropyl or

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In some embodiments, one or both of R^vand R^xare H. In other embodiments, one or both of R^vand R^xare C_1-6alkyl such as methyl, ethyl, propyl, or butyl. In yet other embodiments, one or both of R^vand R^xare methyl. In some embodiments, one or both of R^yand R^zare H. In other embodiments, one or both of R^yand R^zare C_1-6alkyl such as methyl, ethyl, propyl, or butyl. In yet other embodiments, one or both of R^yand R^zare C_1-6alkoxy(alkylene) such as CH₂OCH₃. In further embodiments, one or both of R^yand R^zare C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In some embodiments, one or both of R^y2and R^z2are H. In other embodiments, one or both of R^y2and R^z2are C_1-6alkyl such as methyl, ethyl, propyl, or butyl. In further embodiments, one or both of R^y2and R^z2are C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In further embodiments, p is 0. In other embodiments, p is 1. In still further embodiments, p is 2. In yet other embodiments, p is 3.

In some embodiments, R²is

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wherein: R⁶is H, C_1-6alkyl, C_1-6haloalkyl, C_1-6cyanoalkyl, C_1-6hydroxyalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_1-6deuteratedalkoxy(alkylene), (CR^vR^x)_pNR^yR^z, optionally substituted C_3-6cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted C_2-6alkenyl, optionally substituted (C_3-8cycloalkyl)alkylene, optionally substituted (heterocyclyl)alkylene, or C_1-6alkylsulfonyl(alkylene); R⁷is H, CN, C_1-6alkyl, C_1-6haloalkyl, halo, C_3-6cycloalkyl, aryl, or heteroaryl; R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare, independently, H, C_1-6alkyl, or C₃-6cycloalkyl; and p is 0, 1, 2, or 3. In further embodiments, R⁶is H, C_1-6alkyl, C_1-6haloalkyl, C_1-6cyanoalkyl, C_1-6hydroxyalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_1-6deuteratedalkoxy(alkylene), (CR^vR^x)_pNR^yR^z, optionally substituted C_3-6cycloalkyl, optionally substituted heterocyclyl, or optionally substituted heteroaryl; R⁷is H, C_1-6alkyl, C_1-6haloalkyl, halo, or C_3-6cycloalkyl; R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare, independently, H, C_1-6alkyl, or C_3-6cycloalkyl; and p is 0, 1, 2, or 3. In some embodiments, the optionally substituted heteroaryl is substituted with one or more of C_1-6alkyl such as methyl, C_1-6haloalkyl such as CF₃, halo such as F, or C_1-6alkoxy such as methoxy. In other embodiments, the optionally substituted C_3-6cycloalkyl is substituted with one or more OH. In yet other embodiments, the optionally substituted heterocyclyl is substituted with one or more of halo such as F or C_1-6alkyl such as methyl. In other embodiments, R⁶is H. In further embodiments, R⁶is C_1-6alkyl. In still further embodiments, R⁶is methyl, isopropyl, or tert-butyl. In yet other embodiments, R⁶is C_1-6haloalkyl. In still further embodiments, R⁶is CF₂H, C(CH₃)₂F, CH(CH₃)F, or CF₃. In other embodiments, R⁶is C_1-6cyanoalkyl. In further embodiments, R⁶is C(CH₃)₂CN. In yet other embodiments, R⁶is C_1-6hydroxyalkyl. In still further embodiments, R⁶is C(CH₃)₂OH, CH₂C(CH₃)₂OH, CH(CH₂CH₃)OH, C(CH₃)₂(CH₂OH), or CH(CH₃)OH. In other embodiments, R⁶is C_1-6alkoxy, such as methoxy. In yet other embodiments, R⁶is C_1-6alkoxy(alkylene). In further embodiments, R⁶is CH₂OCH₃, C(CH₃)₂OCH₃, or (CH₂)₂OCH₃. In still other embodiments, R⁶is C_1-6haloalkoxy. In yet other embodiments, R⁶is O(CH₂)₂CF₃. In other embodiments, R⁶is C_1-6haloalkoxy(alkylene) In further embodiments, R⁶is CH₂OCF₃. In yet other embodiments, R⁶is C_1-6deuteratedalkoxy(alkylene). In still other embodiments, R⁶is CH₂OCD₃. In further embodiments, R⁶is (CR^vR^x)_pNR^yR^z. In yet other embodiments, R⁶is NH₂, CH₂N(CH₃)₂, (CH₂)₂N(CH₃)₂, C(CH₃)₂NHCH₃, C(CH₃)₂N(CH₃)₂, or NHcyclopropyl. In still other embodiments, R⁶is optionally substituted C_3-6cycloalkyl. In further embodiments, R⁶is

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In still further embodiments, R⁶is

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In other embodiments, R⁶is optionally substituted aryl. In further embodiments, R⁶is phenyl, 4-fluorophenyl, 3-fluorophenyl, 2-fluorophenyl, or 2,6-difluorophenyl. In other embodiments, R⁶is optionally substituted heterocyclyl. In further embodiments, R⁶is

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In other embodiments, R⁶is optionally substituted heteroaryl. In yet other embodiments, R⁶is optionally substituted pyridinyl, optionally substituted pyrazolyl, optionally substituted pyrazinyl, optionally substituted pyrimidinyl, or optionally substituted imidazolyl. In further embodiments, R⁶is

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In still further embodiments, R⁶is

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In other embodiments, R⁶is optionally substituted C_2-6alkenyl. In further embodiments, R⁶is CH═CH₂, CH═CHC(CH₃)₂OH, or CH═CH-cyclopropyl. In other embodiments, R⁶is optionally substituted (C_3-8cycloalkyl)alkylene. In further embodiments, R⁶is CH₂-cyclopropyl, CH₂CH₂-cyclopropyl or C(CH₃)OH-cyclopropyl. In other embodiments, R⁶is optionally substituted (heterocyclyl)alkylene. In further embodiments, R⁶is

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In other embodiments, C_1-6alkylsulfonyl(alkylene). In further embodiments, R⁶is C(CH₃)₂SO₂CH₃. In other embodiments, R⁶is H, methyl, isopropyl, tert-butyl, C(CH₃)₂F, CH(CH₃)F, CF₃, C(CH₃)₂CN, C(CH₃)₂OH, CH₂C(CH₃)₂OH, CH(CH₂CH₃)OH, C(CH₃)₂(CH₂OH), CH(CH₃)OH, CH₂OCH₃, C(CH₃)₂OCH₃, (CH₂)₂OCH₃, O(CH₂)₂CF₃, CH₂OCF₃, CH₂OCD₃, NH₂, CH₂N(CH₃)₂, (CH₂)₂N(CH₃)₂, C(CH₃)₂NHCH₃, C(CH₃)₂N(CH₃)₂, NHcyclopropyl,

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phenyl,

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CH═CHC(CH₃)₂OH, CH═CH-cyclopropyl, CH₂-cyclopropyl, CH₂CH₂-cyclopropyl, C(CH₃)OH-cyclopropyl,

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or C(CH₃)₂SO₂CH₃. In yet other embodiments, R⁶is H, tert-butyl, C(CH₃)₂F, C(CH₃)₂CN, C(CH₃)₂OH, C(CH₃)₂(CH₂OH), CH(CH₃)OH, CH₂OCH₃, CH₂OCF₃,

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In yet other embodiments, R⁷is H. In still further embodiments, R⁷is CN. In other embodiments, R⁷is C_1-6alkyl. In further embodiments, R⁷is methyl. In yet other embodiments, R⁷is C_1-6haloalkyl. In still further embodiments, R⁷is CHF₂, CH₂F, C(CH₃)F₂, CH₂CHF₂, or CF₃. In further embodiments, R⁷is halo. In yet other embodiments, R⁷is Br or C₁. In still further embodiments, R⁷is C_3-6cycloalkyl. In other embodiments, R⁷is cyclopropyl. In further embodiments, R⁷is aryl. In yet other embodiments, R⁷is phenyl. In still further embodiments, R⁷is heteroaryl. In other embodiments, R⁷is pyridinyl. In yet other embodiments, R⁷is H, CN, methyl, CHF₂, CH₂F, C(CH₃)F₂, CH₂CHF₂, CF₃, Br, Cl, cyclopropyl, phenyl, or pyridinyl. In still other embodiments, R⁷is H, methyl, CHF₂, CH₂F, C(CH₃)F₂, CH₂CHF₂, CF₃, Br, Cl, or cyclopropyl.

In other embodiments, R²is

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wherein: R⁶is H, C_1-6alkyl, C_1-6haloalkyl, C_1-6hydroxyalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), optionally substituted C_3-6cycloalkyl, (CR^vR^x)_pNR^yR^z, optionally substituted aryl, optionally substituted aryl(alkylene), optionally substituted heteroaryl, optionally substituted C_3-8cycloalkenyl, or optionally substituted heterocyclyl; R⁷is H, C_1-6alkyl, C_1-6haloalkyl, halo, or C_3-6cycloalkyl; R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare, independently, H, C_1-6alkyl, or C_3-6cycloalkyl; and p is 0, 1, 2, or 3. In yet other embodiments, R⁶is H, C_1-6alkyl, C_1-6haloalkyl, or optionally substituted heteroaryl; and R⁷is H. In further embodiments, R⁶is H. In further embodiments, R⁶is C_1-6alkyl. In still further embodiments, R⁶is methyl, isopropyl, or tert-butyl. In yet other embodiments, R⁶is C_1-6haloalkyl. In still further embodiments, R⁶is CHF₂, C(CH₃)F₂, C(CH₃)₂F, or CF₃. In yet other embodiments, R⁶is C_1-6hydroxyalkyl. In still further embodiments, R⁶is C(CH₃)₂OH. In other embodiments, R⁶is C_1-6alkoxy. In still other embodiments, R⁶is methoxy. In yet other embodiments, R⁶is C_1-6alkoxy(alkylene). In further embodiments, R⁶is CH₂OCH₃. In other embodiments, R⁶is optionally substituted C_3-6cycloalkyl. In yet further embodiments, R⁶is

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In further embodiments, R⁶is (CR^vR^x)_pNR^yR^z. In yet other embodiments, R⁶is NHcyclopropyl. In other embodiments, R⁶is optionally substituted aryl. In further embodiments, R⁶is phenyl, 3-fluorophenyl, 4-fluorophenyl, or 2,6-difluorophenyl. In other embodiments, R⁶is optionally substituted aryl(alkylene). In further embodiments, R⁶is benzyl. In other embodiments, R⁶is optionally substituted heteroaryl. In yet other embodiments, R⁶is optionally substituted pyridinyl or optionally substituted pyrazolyl. In further embodiments, R⁶is

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In still further embodiments, R⁶is

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In other embodiments, R⁶is optionally substituted C_3-8cycloalkenyl. In further embodiments, R⁶is

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In other embodiments, R⁶is optionally substituted heterocyclyl. In further embodiments, R⁶is

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In other embodiments, R⁶is H, methyl, tert-butyl, CF₃, CHF₂, C(CH₃)₂F, C(CH₃)F₂, C(CH₃)₂OH, CH₂OCH₃,

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NH-cyclopropyl, phenyl,

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benzyl,

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In further embodiments, R⁶is H, tert-butyl, C(CH₃)F₂,

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In yet other embodiments, R⁷is H. In other embodiments, R⁷is C_1-6alkyl. In further embodiments, R⁷is methyl. In yet other embodiments, R⁷is C_1-6haloalkyl. In still further embodiments, R⁷is CF₂H or CF₃. In further embodiments, R⁷is halo. In yet other embodiments, R⁷is Br or Cl. In still further embodiments, R⁷is C_3-6cycloalkyl. In other embodiments, R⁷is cyclopropyl. In still further embodiments, R⁷is H, methyl, CF₂H, CF₃, Br, Cl, or cyclopropyl.

In further embodiments, R²is

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wherein R⁶and R⁷are independently H, C_1-6alkyl, C_1-6haloalkyl, halo, optionally substituted C_3-6cycloalkyl, or optionally substituted aryl. In other embodiments, R⁶and R⁷are each H. In further embodiments, one of R⁶or R⁷is C_1-6alkyl such as methyl. In yet other embodiments, one of R⁶or R⁷is C_1-6haloalkyl such as CF₃. In still other embodiments, one of R⁶or R⁷is halo such as Br or Cl. In yet further embodiments, one of R⁶or R⁷is optionally substituted C_3-6cycloalkyl such as unsubstituted cyclopropyl. In other embodiments, one of R⁶or R⁷is optionally substituted aryl such as unsubstituted phenyl. In yet other embodiments, R⁶is methyl, CF₃, C₁, cyclopropyl, or phenyl and R⁷is H. In still other embodiments, R⁷is methyl, CF₃, C₁, cyclopropyl, or phenyl and R⁶is H. In still further embodiments, R⁷is Cl, and R⁶is H.

In yet further embodiments, R²is

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wherein R⁶is H, C_1-6alkyl, halo, or optionally substituted aryl. In other embodiments, R⁶is H. In further embodiments, R⁶is C_1-6alkyl, such as methyl, ethyl, isopropyl, or tert-butyl. In other embodiments, R⁶is methyl or ethyl. In other embodiments, R⁶is halo, such as F, Br, or Cl. In further embodiments, R⁶is Br. In other embodiments, R⁶is optionally substituted aryl. In further embodiments, R⁶is phenyl. In yet other embodiments, R⁶is H, methyl, ethyl, Br, or phenyl.

In yet other embodiments, R²is

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wherein R⁶is H, C_1-6alkyl, C_1-6haloalkyl, C_1-6hydroxyalkyl, (CR^vR^x)_pNR^yR^z, C_1-6haloalkoxy, optionally substituted C_3-6cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, or optionally substituted heteroaryl; R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare, independently, H, C_1-6alkyl, C_1-6alkoxy(alkylene), or C_3-6cycloalkyl; and p is 0, 1, 2, or 3. In further embodiments, R⁶is H, C_1-6alkyl, C_1-6haloalkyl, C_1-6hydroxyalkyl, optionally substituted C_3-6cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl. In some embodiments, the optionally substituted heteroaryl is substituted with one or more of C_1-6alkyl such as methyl, ethyl, or isopropyl, C_1-6haloalkyl such as CF₃, CH₂CF₃, or CHF₂, halo such as F, C_1-6alkoxy such as methoxy, ethoxy, or propoxy, C_3-6cycloalkyl such as cyclopropyl or cyclobutyl; or C_3-6cycloalkylsulfonyl such as cyclopropylsulfonyl, cyclobutylsulfonyl, or cyclopentylsulfonyl. In other embodiments, the optionally substituted aryl is substituted with one or more of halo such as F, C_1-6alkyl such as methyl, or C_1-6haloalkyl such as CF₃. In some embodiments, R⁶is H. In further embodiments, R⁶is C_1-6alkyl. In other embodiments, R⁶is methyl, ethyl, isopropyl, or tert-butyl. In other embodiments, R⁶is C_1-6haloalkyl. In further embodiments, R⁶is CHF₂, CF₃, or C(CH₃)₂F. In yet other embodiments, R⁶is C_1-6hydroxyalkyl. In still further embodiments, R⁶is C(CH₃)₂OH or CH(CH₃)OH. In other embodiments, R⁶is (CR^vR^x)_pNR^yR^z. In further embodiments, R⁶is NH₂, N(CH₃)₂, NHCH₂CF₃, NHCH₂CH₂OCH₃, NH(cyclopropyl), CH₂N(CH₃)₂, CH₂NH(cyclopropyl), or CH₂CH₂NH(cyclopropyl). In still further embodiments, R⁶is C_1-6haloalkoxy such as OCF₃, OCHF₂, OCH₂F, or OCH₂CH₂CF₃. In yet other embodiments, R⁶is optionally substituted C_3-6cycloalkyl. In further embodiments, R⁶is unsubstituted C_3-6cycloalkyl. In still further embodiments, R⁶is

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In still other embodiments, R⁶is

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In other embodiments, R⁶is optionally substituted aryl. In further embodiments, R⁶is

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In still other embodiments, R⁶is optionally substituted heterocyclyl. In yet further embodiments, R⁶is

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In other embodiments, R⁶is optionally substituted heteroaryl such as optionally substituted pyrazolyl, optionally substituted imidazolyl, optionally substituted pyridinyl, or optionally substituted pyrazinyl.

In yet other embodiments, R⁶is

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In still other embodiments, R⁶is

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In further embodiments, R⁶is methyl, tert-butyl, C(CH₃)₂F, C(CH₃)₂OH, N(CH₃)₂, NH(cyclopropyl), OCH₂CH₂CF₃,

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In still further embodiments, R⁶is tert-butyl, C(CH₃)₂F, CF₃, C(CH₃)₂OH,

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In still further embodiments, R²is

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wherein: R⁶and R⁷are, independently, H, halo, C_1-6alkyl, C_1-6haloalkyl, (CR^vR^x)_pNR^yR^z, or C_3-6cycloalkyl; R⁸is H, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkylcarbonyl, C_1-6hydroxyalkyl, C_1-6alkoxy(alkylene), (CR^vR^x)_pNR^yR^z, C_3-6cycloalkyl, optionally substituted aryl, heteroaryl, or optionally substituted C_3-8cycloalkyl(alkylene); R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare, independently, H, C_1-6alkyl, or C_3-6cycloalkyl; and p is 0, 1, 2, or 3. In other embodiments, R⁶and R⁷are, independently, H, halo, C_1-6alkyl, or C_1-6haloalkyl; R⁸is H, C_1-6alkyl, C_1-6haloalkyl, C_3-6cycloalkyl, or heteroaryl. In some embodiments, one or both of R⁶and R⁷are H. In still other embodiments, one of R⁶or R⁷is halo. In further embodiments, one of R⁶or R⁷is C₁or Br. In yet other embodiments, one of R⁶or R⁷is C_1-6alkyl. In still further embodiments, one of R⁶or R⁷is methyl. In other embodiments, one of R⁶or R⁷is C_1-6haloalkyl. In further embodiments, one of R⁶or R⁷is CHF₂, CH₂CF₃, CH₂F, or CF₃. In yet other embodiments, one of R⁶or R⁷is CHF₂. In other embodiments, one of R⁶or R⁷is (CR^vR^x)_pNR^yR^z. In further embodiments, one of R⁶or R⁷is NH₂. In other embodiments, one of R⁶or R⁷is C_3-6cycloalkyl. In further embodiments, one or both of R⁶or R⁷are cyclopropyl or cyclobutyl. In yet other embodiments, R⁶and R⁷are each independently H, C₁, Br, methyl, CHF₂, CFH₂, CF₃, NH₂, or cyclobutyl. In further embodiments, R⁶and R⁷are each independently H, C₁, methyl, or CHF₂. In some embodiments, R⁸is H. In other embodiments, R⁸is C_1-6alkyl. In further embodiments, R⁸is methyl, ethyl, isopropyl, or tert-butyl. In other embodiments, R⁸is methyl or isopropyl. In still other embodiments, R⁸is C_1-6haloalkyl. In yet further embodiments, R⁸is CHF₂, CH₂CF₃, CF₂H, CH₂CHF₂, or CF₃. In other embodiments, R⁸is C_1-6alkylcarbonyl. In further embodiments, R⁸is C(═O)CH₃or CH₂C(═O)CH₃. In other embodiments, R⁸is C_1-6hydroxyalkyl. In further embodiments, R⁸is CH₂C(CH₃)₂OH. In other embodiments, R⁸is C_1-6alkoxy(alkylene). In further embodiments, R⁸is CH₂CH₂OCH₃. In other embodiments, R⁸is (CR^vR^x)_pNR^yR^z. In further embodiments, R⁸is (CH₂)₂N(CH₃)₂. In other embodiments, R⁸is C_3-6cycloalkyl. In further embodiments, R⁸is cyclopropyl. In yet other embodiments, R⁸is optionally substituted aryl. In still further embodiments, R⁸is phenyl or 4-fluorophenyl. In other embodiments, R⁸is heteroaryl. In further embodiments, R⁸is pyridinyl. In other embodiments, R⁸is substituted C_3-8cycloalkyl(alkylene). In further embodiments, R⁸is CH₂-cyclopropyl or

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In still other embodiments, R⁸is H, methyl, isopropyl, tert-butyl, CHF₂, CH₂CF₃, CH₂CHF₂, CF₃, CH₂C(═O)CH₃, CH₂C(CH₃)₂OH, CH₂CH₂OCH₃, (CH₂)₂N(CH₃)₂, cyclopropyl, phenyl, 4-fluorophenyl,

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CH₂-cyclopropyl or

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In further embodiments, R⁸is methyl, isopropyl, CHF₂, CH₂CF₃, CH₂CHF₂, CF₃, cyclopropyl, or pyridinyl.

In further embodiments, R²is

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wherein R⁶is H, C_1-6alkyl, halo, C_1-6haloalkyl, C_3-6cycloalkyl, or C_1-6cyanoalkyl; and R⁸is H, C_1-6alkyl, C_1-6haloalkyl, or C_3-6cycloalkyl. In other embodiments, R⁶is H, C_1-6alkyl, halo, C_1-6haloalkyl, or C_3-6cycloalkyl; and R⁸is H or C_1-6alkyl. In some embodiments, R⁶is H. In still other embodiments, R⁶is C_1-6alkyl such as methyl. In yet other embodiments, R⁶is halo such as Cl or Br. In other embodiments, R⁶is C_1-6haloalkyl such as CHF₂or CF₃. In yet other embodiments, R⁶is C_3-6cycloalkyl such as cyclopropyl. In other embodiments, R⁶is C_1-6cyanoalkyl such as C(CH₃)₂CN. In still further embodiments, R⁶is H, methyl, C₁, Br, CHF₂, CF₃, cyclopropyl, or C(CH₃)₂CN. In some embodiments, R⁸is H. In other embodiments, R⁸is C_1-6alkyl such as methyl, ethyl, or isopropyl. In yet other embodiments, R⁸is C_1-6haloalkyl, such as CF₃or CHF₂. In other embodiments, R⁸is C_3-6cycloalkyl such as cyclopropyl. In yet other embodiments, R⁸is methyl, ethyl, isopropyl, or cyclopropyl.

In yet other embodiments, R²is

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In these structures, W is S or NR¹⁵; W¹is S, O, or NR¹⁵; R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are each independently H, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6hydroxyalkyl, C_1-6haloalkoxy, C_1-6haloalkoxy(alkylene), C_2-6alkenyl, CN, halo, (CR^vR^x)_pNR^yR^z, C(O)NR^y2R^z2, optionally substituted C_3-8cycloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl(alkylene), optionally substituted aryl, or optionally substituted heteroaryl; R^vand R^xare, independently, H or C_1-6alkyl; R^yand R^zare, independently, H, C_1-6alkyl, C_3-6cycloalkyl, C_1-6hydroxyalkyl, C_1-6haloalkyl, C_1-6alkoxy(alkylene), or C(O)OC_1-6alkyl; R^y2and R^z2, are independently, H, C_1-6alkyl, or C_3-6cycloalkyl; p is 0, 1, 2, or 3; and R¹⁵is H or C_1-6alkyl.

In some embodiments, W is S. In other embodiments, W is NR¹⁵. In some embodiments, W¹is S. In other embodiments, W¹is O. In further embodiments, W¹is NR¹⁵. In some embodiments, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are each H. In some embodiments, R¹⁰, R¹¹, R¹², and R¹³are each H. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkyl. In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6haloalkyl. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkoxy. In still other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkoxy(alkylene). In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6hydroxyalkyl. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6haloalkoxy. In still other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6haloalkoxy(alkylene). In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_2-6alkenyl. In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is CN. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is halo. In still further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is (CR^vR^x)_pNR^yR^z. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C(O)NR^y2R^z2. In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted C_3-8cycloalkyl. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted heterocyclyl. In still other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted heterocyclyl(alkylene). In still further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted aryl. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted heteroaryl. In some embodiments, one or both of R^vand R^xare H. In other embodiments, one or both of R^vand R^xare C_1-6alkyl. In some embodiments, one or both of R^yand R^zare H. In other embodiments, one or both of R^yand R^zare C_1-6alkyl. In further embodiments, one or both of R^yand R^zare C_3-6cycloalkyl. In yet other embodiments, one or both of R^yand R^zare C_1-6hydroxyalkyl. In still further embodiments, one or both of R^yand R^zare C_1-6haloalkyl. In yet other embodiments, one or both of R^yand R^zare C_1-6alkoxy(alkylene). In further embodiments, one or both of R^yand R^zare C(O)OC_1-6alkyl. In some embodiments, one or both of R^y2and R^z2are H. In other embodiments, one or both of R^y2and R^z2are C_1-6alkyl. In further embodiments, one or both of R^y2and R^z2are C_3-6cycloalkyl. In some embodiments, p is 0. In other embodiments, p is 1. In further embodiments, p is 2. In yet other embodiments, p is 3. In some embodiments, R¹⁵is H. In other embodiments, R¹⁵is C_1-6alkyl.

In further embodiments, R²is

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wherein R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are each independently H, C_1-6alkyl, C_1-6haloalkyl, C_3-6cycloalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), C_1-6hydroxyalkyl, CN, halo, C_2-6alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclyl(alkylene), optionally substituted heteroaryl, or (CR^vR^x)_pNR^yR^z. In other embodiments, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are each independently H, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6alkoxy(alkylene), optionally substituted heterocyclyl, optionally substituted heterocyclyl(alkylene), optionally substituted heteroaryl, or (CR^vR^x)_pNR^yR^z. In some embodiments, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are H. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkyl such as methyl or ethyl. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkyl such as methyl. In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6haloalkyl such as CF₃or C(CH₃)₂F. In yet further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_3-6cycloalkyl such as cyclopropyl. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkoxy such as methoxy. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkoxy(alkylene) such as CH₂OCH₃or (CH₂)₂OCH₃. In still further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6hydroxyalkyl such as C(CH₃)₂OH. In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is CN. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is halo such as F, Br, or Cl. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_2-6alkenyl such as CH═CH₂. In still further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted aryl such as unsubstituted phenyl. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹and R¹⁴is optionally substituted heterocyclyl such as

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In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted heterocyclyl(alkylene) such as

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In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is optionally substituted heteroaryl such as optionally substituted pyridinyl, optionally substituted pyrazinyl, optionally substituted pyrimidinyl, or optionally substituted pyrazolyl. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is

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In still other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is unsubstituted pyridinyl or

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In still further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is (CR^vR^x)_pNR^yR^zsuch as NH₂, NH(CH₃), N(CH₃)₂, CH₂N(CH₃)₂, or CH₂CH₂N(CH₃)₂. In further embodiments, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴each are independently H, methyl, ethyl, C(CH₃)₂F, C(CH₃)₂OH, cyclopropyl, methoxy, CH₂OCH₃, (CH₂)₂OCH₃, Br, F, Cl, CN, CH═CH₂, phenyl,

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NH₂, NH(CH₃), N(CH₃)₂, CH₂N(CH₃)₂, or CH₂CH₂N(CH₃)₂. In yet other embodiments, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴each are independently H, methyl, C(CH₃)₂F, CF₃, methoxy, CH₂OCH₃, (CH₂)₂OCH₃, Br, F, Cl,

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pyridinyl,

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NH₂, NH(CH₃), N(CH₃)₂, CH₂N(CH₃)₂, or CH₂CH₂N(CH₃)₂. In other embodiments, R¹⁰, R¹³, and R¹⁴are each hydrogen. In further embodiments, R¹⁰, R¹³, and R¹⁴are each hydrogen; and R¹¹is halo. In yet further embodiments, R¹⁰, R¹¹, R¹³, and R¹⁴are each hydrogen.

In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is substituted heterocyclyl or substituted heterocyclyl(alkylene), substituted with one or more of halo such as F, Cl, or Br; C_1-6haloalkyl such as CF₃, CH₂CF₃, or CHF₂; C_1-6alkyl such as methyl, ethyl, or propyl; OH; C_1-6hydroxyalkyl such as C(CH₃)₂OH, C_1-6alkoxy such as methoxy, ethoxy, or propoxy; or C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, or cyclopentyl. In other embodiments, the substituted heterocyclyl or substituted heterocyclyl(alkylene) is substituted with one or more methyl, OH, F, C(CH₃)₂OH, or cyclopropyl.

In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is substituted heteroaryl, substituted with one or more of halo such as F, Cl, or Br; C_1-6haloalkyl such as CF₃, CH₂CF₃, or CHF₂; C_1-6alkyl such as methyl, ethyl, propyl, or isopropyl; C_1-6alkoxy such as methoxy, ethoxy, or propoxy; C_1-6haloalkoxy such as OCF₃; C_3-6cycloalkyl such as cyclopropyl, cyclobutyl, or cyclopentyl; or C_3-6cycloalkylsulfonyl such as cyclopropylsulfonyl, cyclobutylsulfonyl, or cyclopentylsulfonyl. In still further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is substituted heteroaryl, substituted with one or more C_1-6alkyl such as methyl, ethyl, propyl, or isopropyl. In yet other embodiments, the substituted heteroaryl is substituted with methyl.

In other embodiments, R²is

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wherein R¹⁰, R¹¹, R¹², and R¹³are independently H, C_1-6alkyl, or halo and R¹⁵is H or C_1-6alkyl. In some embodiments, R¹⁰, R¹¹, R¹², and R¹³are each H. In other embodiments, at least one of R¹⁰, R¹¹, R¹², and R¹³is C_1-6alkyl. In further embodiments, at least one of R¹⁰, R¹¹, R¹², and R¹³is halo. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², and R¹³is Br. In some embodiments, R¹⁵is H. In other embodiments, R¹⁵is C_1-6alkyl. In further embodiments, R¹⁵is methyl. In yet other embodiments, R¹⁵is H or methyl.

In further embodiments, R²is

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wherein R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are independently H, halo, or C_1-6alkyl. In some embodiments, R²is

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In other embodiments, R²is

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In some embodiments, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are each H. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is halo. In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³and R¹⁴is C_1-6alkyl.

In yet other embodiments, R²is

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wherein R¹⁰, R¹¹, R¹², R¹³and R¹⁴are independently H, halo, or C_1-6alkyl. In some embodiments, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴are each H. In other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is halo. In further embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is Br. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², R¹³, and R¹⁴is C_1-6alkyl.

In still further embodiments, R²is

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wherein R¹⁰, R¹¹, R¹², and R¹³are independently H, C_1-6alkyl, or halo. In some embodiments, R²is

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In other embodiments, R²is

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In further embodiments, R²is

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In some embodiments, R¹⁰, R¹¹, R¹², and R¹³are each H. In other embodiments, at least one of R¹⁰, R¹¹, R¹², and R¹³is halo. In further embodiments, at least one of R¹⁰, R¹¹, R¹², and R¹³is F. In yet other embodiments, at least one of R¹⁰, R¹¹, R¹², and R¹³is C_1-6alkyl. In still further embodiments, at least one of R¹⁰, R¹¹, R¹², and R¹³is methyl. In yet other embodiments, R¹⁰, R¹¹, R¹², and R¹³are independently H, methyl, or F.

In other embodiments, R²is

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wherein R⁶is defined herein and R⁷is H. In yet other embodiments, R²is

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In further embodiments, R²is

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In further embodiments, R²is

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wherein R is defined herein and R⁷is CH₃. In other embodiments, R²is

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In yet other embodiments, R²is

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In yet other embodiments, R²is

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wherein R⁶is defined herein and R⁷is cyclopropyl. In further embodiments, R²is

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In still further embodiments, R²is

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In still further embodiments, R²is

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wherein R⁶is defined herein and R⁷is CHF₂. In other embodiments, R²is

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In yet other embodiments, R²is

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In other embodiments, R²is

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wherein R⁶is defined herein and R⁷is CF₃. In still other embodiments, R²is

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In yet other embodiments, R²is

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In other embodiments, R²is

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wherein R⁶is defined herein and R⁷is CHF₂, C(CH)₂F, or CH₂CHF₂. In further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is defined herein and R⁷is CN. In still further embodiments, R²is

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In yet other embodiments, R²is

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wherein R⁶is defined herein and R⁷is Br or Cl. In further embodiments, R²is

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In still further embodiments, R²is

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In still further embodiments, R²is

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wherein R⁶is defined herein and R⁷is phenyl or pyridinyl. In other embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is defined herein and R⁷is H. In other embodiments, R²is

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In yet other embodiments, R²is

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In still other embodiments, R²is

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wherein R⁶is defined herein and R⁷is CF₃, cyclopropyl, or CH₃. In yet other embodiments, R²is

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In yet further embodiments, R²is

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wherein R⁶and R⁷are defined herein. In other embodiments, R²is

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In yet other embodiments, R²is

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In other embodiments, R²is

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wherein R⁶—R⁸are defined herein.

In further embodiments, R²is

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In still further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶—R⁸are defined herein. In yet other embodiments, R²is

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In further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is optionally substituted heterocyclyl. In yet other embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is optionally substituted heteroaryl. In yet other embodiments, R²is

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In further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is optionally substituted aryl. In yet other embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is C_1-6alkyl. In yet other embodiments, R²is

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In still further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is C_1-6haloalkyl or C_1-6hydroxyalkyl. In yet other embodiments, R²is

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In still further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is optionally substituted C_3-8cycloalkyl. In yet other embodiments, R²is

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In still further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is (CR^vR^x)_pNR^yR^z, and p, R^v, R^x, R^y, and R^zare defined herein. In yet other embodiments, R²is

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In other embodiments, R²is

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wherein R⁶is H, i.e.,

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In further embodiments, R²is

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wherein R⁶is C_1-6alkyl. In yet other embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is halo. In yet other embodiments, R²is

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In further embodiments, R²is

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wherein R⁶is aryl. In yet other embodiments, R²is

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In further embodiments, R²is

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wherein R⁸is C_1-6alkyl and R⁶is defined herein. In yet other embodiments, R²is

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In still further embodiments, R²is

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In further embodiments, R²is

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wherein R⁶and R⁸are defined herein. In yet other embodiments, R²is

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In further embodiments, R²is

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wherein R¹⁰—R¹⁴are defined herein. In yet other embodiments, R²is

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In still further embodiments,

R²is

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In further embodiments, R²is

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wherein R¹³is H and R¹⁰, R¹¹, R¹², and R¹³are defined herein. In yet other embodiments, R²is

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In further embodiments, R²is

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wherein R¹⁰-R¹³are defined herein. In yet other embodiments, R²is

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In some embodiments, the compound of Formula I is of Formula I-A or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, L, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In other embodiments, the compound of Formula I is of Formula I-B or a pharmaceutically acceptable salt thereof:

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is H

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In further embodiments, the compound of Formula I is of Formula I-C or a pharmaceutically acceptable salt thereof:

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In still other embodiments, the compound of Formula I is of Formula I-D or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In still further embodiments, the compound of Formula I is of Formula I-E or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In further embodiments, the compound of Formula I is of Formula I-F or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In further embodiments, the compound of Formula I is of Formula I-G or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In yet other embodiments, the compound of Formula I is of Formula I-H or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In still further embodiments, the compound of Formula I is of Formula I-I or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In further embodiments, the compound of Formula I is of Formula I-J or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In further embodiments, the compound of Formula I is of Formula I-K or a pharmaceutically acceptable salt thereof:

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such as

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wherein R¹, R², R⁵, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In still other embodiments, the compound of Formula I is of Formula I-L or a pharmaceutically acceptable salt thereof:

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wherein R¹, R², R⁵, L, and m are defined herein. In further embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In yet further embodiments, the compound of Formula I is of Formula I-M or a pharmaceutically acceptable salt thereof:

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wherein R¹, R², R⁵, L, and m are defined herein. In other embodiments, the compound is

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or a pharmaceutically acceptable salt thereof.

In some embodiments, compounds of the disclosure are any one or more of the compounds of Tables 1S, 1R, and 2, and their pharmaceutically acceptable salts and/or isotopologues. Compounds having the Formula I are further disclosed in the Exemplification and are included in the present disclosure. Pharmaceutically acceptable salts thereof as well as the neutral forms are included.

The disclosure further provides R-enantiomers, S-enantiomers, or racemic mixtures of any of the compounds described herein. In some embodiments, the compound is an S-enantiomer. In other embodiments, the compound is the R-enantiomer. In further embodiments, the compound is racemic. In some embodiments, the compound is a single enantiomer, and the R¹moiety is in an alpha (α) configuration. In other embodiments, the compound is a single enantiomer, and the R¹moiety is in an beta (β) configuration.

In another embodiment, the compounds of the disclosure may be enantiomerically enriched, e.g., the enantiomeric excess or “ee” of the compound is greater than about 5% as measured by chiral HPLC. In some embodiments, the ee is greater than about 10%. In other embodiments, the ee is greater than about 20%. In further embodiments, the ee is greater than about 30%. In yet other embodiments, the ee is greater than about 40%. In still further embodiments, the ee is greater than about 50%. In other embodiments, the ee is greater than about 60%. In further embodiments, the ee is greater than about 70%. In still other embodiments, the ee is greater than about 80%. In yet further embodiments, the ee is greater than about 85%. In other embodiments, the ee is greater than about 90%. In further embodiments, the ee is greater than about 91%. In yet other embodiments, the ee is greater than about 92%. In still further embodiments, the ee is greater than about 93%. In other embodiments, the ee is greater than about 94%. In further embodiments, the ee is greater than about 95%. In still other embodiments, the ee is greater than about 96%. In yet further embodiments, the ee is greater than about 97%. In other embodiments, the ee is greater than about 98%. In further embodiments, the ee is greater than about 99%.

The present disclosure encompasses the preparation and use of salts of compounds of the disclosure. Salts of compounds of the disclosure can be prepared during the final isolation and purification of the compounds or separately by reacting the compound with an acid or base as appropriate.

Treatment Methods

Compounds of the disclosure have several uses as described herein. In some embodiments, compounds of the disclosure are useful in methods for stabilizing mutant PAH proteins. These methods comprise contacting the protein with one or more compounds described herein or a pharmaceutically acceptable salt thereof. The compounds of the disclosure can provide for better Phe control for patients whose disease is not well-managed on diet alone and lessen the severity of a patient's phenylketonuria. Thus, patients administered a compound of the disclosure will have a better quality of life, e.g., a more normal lifestyle and/or none or fewer dietary restrictions, as compared with phenylketonuria patients who have not been administered a compound of the disclosure. In some embodiments, patients administered a compound of the disclosure may experience increases in executive function, decreases in anxiety symptoms, and/or decreases in attention deficit hyperactivity disorder symptoms.

The term “mutant PAH gene” as used herein refers to the full DNA sequence of PAH that differs in one or more ways from the canonically accepted sequence (“the basis gene”) that is published in any one of a variety of curated databases. As one example, the sequence described by GenBank Accession number NG_008690.2 describes the basis gene.

The term “mutant PAH protein” as used herein refers to a PAH protein that contains at least one mutation in the amino acid sequence relative to that encoded by the reference. The reference human PAH protein is described by Genbank Accession number NP_000268 and contains 452 amino acids. PAH protein mutations can be identified using methods known in the art. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation. In still other embodiments, the mutant PAH protein contains at least one R408W, R243Q, R408Q, V388M, or L348V mutation. In yet other embodiments, the mutant PAH protein contains at least one R408W mutation. In further embodiments, the mutant PAH protein contains at least two R408W mutations. In further embodiments, the mutant PAH protein contains at least one R261Q mutation. In yet other embodiments, the mutant PAH protein contains at least one R243Q mutation. In yet other embodiments, the mutant PAH protein contains at least one Y414C mutation. In still further embodiments, the mutant PAH protein contains at least one L48S mutation. In other embodiments, the mutant PAH protein contains at least one A403V mutation. In further embodiments, the mutant PAH protein contains at least one I65T mutation. In yet further embodiments, the mutant PAH protein contains at least one R241C mutation. In yet other embodiments, the mutant PAH protein contains at least one L348V mutation. In further embodiments, the mutant PAH protein contains at least one R408Q mutation. In other embodiments, the mutant PAH protein contains at least one V388M mutation. In other embodiments, the mutant PAH protein contains at least one F39L mutation. In still further embodiments, the mutant PAH protein contains at least one A300S mutation. In yet further embodiments, the mutant PAH protein contains at least one L48S mutation.

In other embodiments, the disclosure provides methods for stabilizing the activity of mutant phenylalanine hydroxylase (PAH) proteins as compared to wild type PAH.

Such methods include contacting phenylalanine hydroxylase with one or more compounds described herein, or a pharmaceutically acceptable salt thereof. The term “stabilizing” as used herein refers to modulating the activity or quantity of a PAH enzyme so that it catalyzes hydroxylation of the aromatic side-chain of phenylalanine at a rate that is more similar to the PAH catalysis rate of a control population having wild type PAH, i.e., without a mutant PAH gene mutation, as compared to the baseline PAH catalysis rate. In some aspects, the term “stabilizing” refers to modulating the activity of a subject's PAH so that it catalyzes hydroxylation of the aromatic side-chain of phenylalanine at a flux more similar to the PAH catalytic flux of a control subject population without a mutant PAH gene mutation. In some embodiments, “stabilizing” activity of PAH includes increasing levels of the enzyme PAH as compared to baseline. By increasing the buildup of stabilized active PAH protein, a subject's toxic Phe levels can be reduced as compared to the subject's baseline levels of dietary Phe prior to administration of a compound of the disclosure or a pharmaceutical composition comprising compounds of the disclosure.

In some embodiments, the disclosure provides methods for reducing blood phenylalanine concentrations in a subject suffering from phenylketonuria to a concentration less than or equal to about 600 μM. In other embodiments, the blood Phe concentration is reduced to a concentration less than or equal to about 360 PM. In other embodiments, the disclosure provides methods for reducing blood Phe concentrations as compared to untreated baseline. In some embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by a percentage including but not limited at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90%. In other embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 10%. In further embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 20%. In yet other embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 30%. In still further embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 40%. In other embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 50%. In further embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 60%. In yet other embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 70%. In still further embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 80%. In other embodiments, a subject's blood Phe concentration as compared to untreated baseline is reduced by at least about 90%. A subject's Phe concentration can be determined by blood tests and methods for measuring such levels are known in the art. In some embodiments, the reduction in Phe concentration achieved using compounds of the disclosure is obtained in conjunction with the subject actively managing their dietary Phe intake. In other embodiments, the reduction in Phe concentration is obtained in conjunction with the subject maintaining a Phe-restricted diet.

In some embodiments, a subject is treated with compounds of the disclosure, or a pharmaceutical composition comprising compounds of the disclosure. The compound is administered in an amount sufficient for stabilizing the PAH protein, or for reducing blood phenylalanine concentration in a subject, or combinations thereof in the subject.

In further embodiments, the subject is a human patient, such as is a human adult over 18 years old in need of treatment. In yet further embodiments, the human patient is a human child less than 18 years old. In yet other embodiments, the human patient is a human child less than 12 years old. In still further embodiments, the human patient is a human child between 12 years and 18 years old. In any of the embodiments, the subject has phenylketonuria (PKU), optionally classic PKU or severe PKU. In some embodiments, the subject has a blood Phe concentration greater than about 600 μM prior to administration of a compound of the disclosure or a pharmaceutical composition comprising compounds of the disclosure. In other embodiments, the subject's blood Phe concentration prior to administration is greater than about 700 μM. In further embodiments, the subject's blood Phe concentration prior to administration is greater than about 800 μM. In still further embodiments, the subject's blood Phe concentration prior to administration is greater than about 900 μM. In yet other embodiments, the subject's blood Phe concentration prior to administration is greater than about 1000 μM. In further embodiments, the subject's blood Phe concentration prior to administration is greater than about 1100 PM. In other embodiments, the subject's blood Phe concentration prior to administration is greater than about 1200 μM.

The present methods also encompass administering an additional therapeutic agent to the subject in addition to the compounds of the disclosure. In some embodiments, the additional therapeutic agent is selected from drugs known as useful in a stabilizing mutant PAH protein and/or reducing blood Phe concentrations. The additional therapeutic agent is different from the compounds of the disclosure. In some embodiments, the additional therapeutic agent is sapropterin or sepiapterin, In other embodiments, the additional therapeutic agent is a nutritional supplement. Nutritional supplements that may be used include those that contain amino acids and other nutrients. In further embodiments, the nutritional supplement contains large neutral amino acids such as leucine, tyrosine, tryptophan, methionine, histidine, isoleucine, valine, threonine. In other embodiments, the nutritional supplement contains tyrosine. In further embodiments, the nutritional supplement contains casein glycomacropeptide, i.e., a milk peptide naturally free of Phe in its pure form. In other embodiments, the additional therapeutic agent is an enzyme substrate or enzyme co-factor. In yet other embodiments, the enzyme substrate or co-factor is tetrahydrobiopterin. In other embodiments, the additional therapeutic agent is a biopterin analogue. In further embodiments, the additional therapeutic agent is a biotherapeutic, synthetic biotic, microbiota or probiotic. In yet other embodiments, the biotherapeutic, synthetic biotic, microbiota or probiotic contains a genetically modified phenylalanine ammonia lyase (PAL) gene, such as, for example, E. coli Nissle PAL. Examples of genetically modified E. coli Nissle PAL biotherapetuics include SYNB1934 and SYNB1618, and the like. In still further embodiments, the additional therapeutic agent is an inhibitor of an amino acid transporter. In some embodiments, the amino acid transporter is B⁰AT1 (also referred to as SLC6A19), and the additional therapeutic agent is a SLC6A19 inhibitor. Examples of SLC6A19 inhibitors include nimesulide, benztropine, NSC63912, NSC22789, cinromide, CB3, E62, JNT-517, and the like.

Compounds of the disclosure and the additional therapeutic agents can be administered simultaneously or sequentially to achieve the desired effect. In addition, the compounds of the disclosure and additional therapeutic agent can be administered in a single composition or two separate compositions.

The additional therapeutic agent is administered in an amount to provide its desired therapeutic effect. The effective dosage range for each additional therapeutic agent is known in the art, and the additional therapeutic agent is administered to an individual in need thereof within such established ranges.

Compounds of the disclosure and the additional therapeutic agents can be administered together as a single-unit dose or separately as multi-unit doses, wherein the compounds of the disclosure are administered before the additional therapeutic agent or vice versa. One or more doses of the compounds of the disclosure and/or one or more dose of the additional therapeutic agents can be administered.

The compounds of the disclosure may also be administered sequentially or concurrently with non-pharmacological techniques. In some embodiments, the patient uses non-pharmacological techniques to maintain lower Phe levels. In other embodiments, the non-pharmacological technique is administering a diet that is low in Phe. One skilled in the art would be able to determine what type of diet to maintain appropriate levels of Phe. In some embodiments, a phenylamine diet containing about 200 to about 500 mg/day (patients 10 years or younger) of Phe or less than about 600 mg/day (patients over 10 years of age). In other embodiments, the diet may include restricting or eliminating one or more foods that are high in Phe, such as soybeans, egg whites, shrimp, chicken breast, spirulina, watercress, fish, nuts, crayfish, lobster, tuna, turkey, legumes, and low-fat cottage cheese.

An example of a dose is in the range of from about 0.001 to about 100 mg of compound per kg of subject's body weight per day, in single or divided dosage units (e.g., BID, TID, QID). For a 70-kg human, a suitable dosage amount is from about 0.05 to about 7 g/day.

In some embodiments, the therapeutically effective amount of one or more compounds described herein is an amount that is effective in stabilizing a mutant PAH protein described herein. In other embodiments, the therapeutically effective amount of one or more compounds described herein is an amount that is effective in reducing blood phenylalanine concentrations.

Unless otherwise noted, the amounts of the compounds described herein are set forth on a free base basis. That is, the amounts indicate that amount of the compound administered, exclusive of, for example, solvent or counterions (such as in pharmaceutically acceptable salts).

Pharmaceutical Compositions

The disclosure also provides pharmaceutical compositions comprising compounds of the disclosure and a pharmaceutically acceptable carrier or excipient.

The methods of the present disclosure can be accomplished by administering compounds of the disclosure as the neat compound or as a pharmaceutical composition. Administration of a pharmaceutical composition, or neat compound of the disclosure, can be performed at any time period as determined by the attending physician.

Typically, the pharmaceutical compositions contain no toxic, carcinogenic, or mutagenic compounds that would cause an adverse reaction when administered.

Pharmaceutical compositions include those wherein compounds of the disclosure are administered in an effective amount to achieve its intended purpose. The exact formulation, route of administration, and dosage is determined by an individual physician.

Compounds of the disclosure can be administered by any suitable route, e.g., by oral, buccal, inhalation, sublingual, rectal, vaginal, intracisternal or intrathecal through lumbar puncture, transurethral, nasal, percutaneous, i.e., transdermal, or parenteral (including intravenous, intramuscular, subcutaneous, intracoronary, intradermal, intramammary, intraperitoneal, intraarticular, intrathecal, retrobulbar, intrapulmonary injection and/or surgical implantation at a particular site) administration. Parenteral administration can be accomplished using a needle and syringe or using a high-pressure technique.

The above-mentioned additional therapeutically active agents, one or more of which can be used in combination with compounds of the disclosure, are prepared and administered as described in the art.

Compounds of the disclosure may be administered in admixture with pharmaceutical carriers selected with regard to the intended route of administration and standard pharmaceutical practice. Pharmaceutical compositions for use in accordance with the present disclosure are formulated in a conventional manner using one or more physiologically acceptable carriers comprising excipients and/or auxiliaries that facilitate processing of compounds of the disclosure.

Administration of the compounds or pharmaceutical compositions of the disclosure can be effected by any method that enables delivery of the compounds to the site of action. These methods include oral routes, intraduodenal routes, parenteral injection (including intravenous, intraarterial, subcutaneous, intramuscular, intravascular, intraperitoneal or infusion), topical (e.g. transdermal application), rectal administration, via local delivery by catheter or stent or through inhalation. Compounds can also be administered intraadiposally or intrathecally.

The amount of the compound administered will be dependent on the subject being treated, the severity of the disorder or condition, the rate of administration, the disposition of the compound and the discretion of the prescribing physician. The desired dose can be administered in a single dose, or as multiple doses administered at appropriate intervals, e.g., as one, two, three, four or more subdoses per day. In some embodiments, the compounds disclosed herein are effective over a wide dosage range. For example, in the treatment of adult humans, dosage forms containing from about 0.01 to 2000 mg of a compound disclosed herein per day are examples of dosage forms that may be used. The exact dosage will depend upon the route of administration, the form in which the compound is administered, the subject to be treated, the body weight of the subject to be treated, and the preference and experience of the attending physician. In some instances, dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger doses may be employed without causing any harmful side effect, e.g. by dividing such larger doses into several small doses for administration throughout the day.

In some embodiments, a compound of the disclosure is administered in a single dose.

Typically, such administration will be by a solid oral dosage form such as tablet or capsule. However, other routes may be used as appropriate. A single dose of a compound may also be used for treatment of an acute condition.

In some embodiments, a compound of the disclosure may be administered in multiple doses. Dosing may be about once, twice, three times, four times, five times, six times, or more than six times per day. In another embodiment, a compound described herein and another therapeutic agent are administered together about once per day to about 6 times per day. Administration of the compounds disclosed herein may continue as long as necessary. In some embodiments, a compound is administered chronically on an ongoing basis, e.g., for the treatment of chronic effects.

An effective amount of a compound of the disclosure may be administered in either single or multiple doses by any of the accepted modes of administration of therapeutic agents having similar utilities, including rectal, buccal, intranasal and transdermal routes, by intra-arterial injection, intravenously, intraperitoneally, parenterally, intramuscularly, subcutaneously, orally, topically, or as an inhalant.

The pharmaceutical composition may, for example, be in a form suitable for oral administration as a tablet, capsule, pill, powder, sustained release formulations, solution, suspension, for parenteral injection as a sterile solution, suspension or emulsion, for topical administration as an ointment or cream or for rectal administration as a suppository.

The pharmaceutical composition may be in unit dosage forms suitable for single administration of precise dosages. The pharmaceutical composition will include one or more conventional pharmaceutical carriers or excipients and a compound disclosed herein as an active ingredient. In addition, it may include other medicinal or pharmaceutical agents, carriers, adjuvants, etc.

Exemplary parenteral administration forms include solutions or suspensions of the compound of the disclosure in sterile aqueous solutions, for example, aqueous propylene glycol or dextrose solutions. Such dosage forms can be suitably buffered, if desired.

Pharmaceutical Compositions for Oral Administration

In some embodiments, the disclosure provides a pharmaceutical composition for oral administration containing a compound of the disclosure and pharmaceutical excipients suitable for oral administration.

In some embodiments, the disclosure provides a solid pharmaceutical composition for oral administration containing: (i) an effective amount of a compound of the disclosure; optionally (ii) an effective amount of a second therapeutic agent; and (iii) a pharmaceutical excipient suitable for oral administration. In some embodiments, the composition further contains: (iv) an effective amount of a third therapeutic agent.

In some embodiments, the pharmaceutical composition may be a pharmaceutical composition suitable for oral consumption. Pharmaceutical compositions containing a compound of the disclosure suitable for oral administration can be presented as discrete dosage forms, such as capsules, cachets, or tablets, or liquids or aerosol sprays each containing a predetermined amount of an active ingredient as a powder or in granules, a solution, or a suspension in an aqueous or non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil liquid emulsion. Such dosage forms can be prepared by any of the methods of pharmacy, but all methods include the step of bringing the compound of the disclosure into association with the carrier, which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the compound of the disclosure with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation. For example, a tablet can be prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as powder or granules, optionally mixed with an excipient such as, but not limited to, a binder, a lubricant, an inert diluent, and/or a surface active or dispersing agent.

Molded tablets can be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.

This disclosure further encompasses anhydrous pharmaceutical compositions and dosage forms comprising an active ingredient, since water can facilitate the degradation of some compounds. For example, water may be added (e.g., 5%) in the pharmaceutical arts as a means of simulating long-term storage in order to determine characteristics such as shelf-life or the stability of formulations over time. Anhydrous pharmaceutical compositions and dosage forms containing a compound of the disclosure can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions. Pharmaceutical compositions and dosage forms containing a compound of the disclosure which contain lactose can be made anhydrous if substantial contact with moisture and/or humidity during manufacturing, packaging, and/or storage is expected. An anhydrous pharmaceutical composition may be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions may be packaged using materials known to prevent exposure to water such that they can be included in suitable formulary kits. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, plastic or the like, unit dose containers, blister packs, and strip packs.

The compound of the disclosure can be combined in an intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier can take a wide variety of forms depending on the form of preparation desired for administration. In preparing the compositions for an oral dosage form, any of the usual pharmaceutical media can be employed as carriers, such as, for example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like in the case of oral liquid preparations (such as suspensions, solutions, and elixirs) or aerosols; or carriers such as starches, sugars, micro-crystalline cellulose, diluents, granulating agents, lubricants, binders, and disintegrating agents can be used in the case of oral solid preparations, in some embodiments without employing the use of lactose. For example, suitable carriers include powders, capsules, and tablets, with the solid oral preparations. If desired, tablets can be coated by standard aqueous or nonaqueous techniques.

Binders suitable for use in pharmaceutical compositions and dosage forms include, but are not limited to, corn starch, potato starch, or other starches, gelatin, natural and synthetic gums such as acacia, sodium alginate, alginic acid, other alginates, powdered tragacanth, guar gum, cellulose and its derivatives (e.g., ethyl cellulose, cellulose acetate, carboxymethyl cellulose calcium, sodium carboxymethyl cellulose), polyvinyl pyrrolidone, methyl cellulose, pre-gelatinized starch, hydroxypropyl methyl cellulose, colloidal silicon dioxide, microcrystalline cellulose, and mixtures thereof.

Examples of suitable fillers for use in the pharmaceutical compositions and dosage forms disclosed herein include, but are not limited to, talc, calcium carbonate (e.g., granules or powder), microcrystalline cellulose, powdered cellulose, dextrates, kaolin, mannitol, silicic acid, sorbitol, starch, pre-gelatinized starch, and mixtures thereof.

Disintegrants may be used in the compositions of the disclosure to provide tablets that disintegrate when exposed to an aqueous environment. Too much of a disintegrant may produce tablets which may disintegrate in the bottle. Too little may be insufficient for disintegration to occur and may thus alter the rate and extent of release of the active ingredient(s) from the dosage form. Thus, a sufficient amount of disintegrant that is neither too little nor too much to detrimentally alter the release of the active ingredient(s) may be used to form the dosage forms of the compounds disclosed herein. The amount of disintegrant used may vary based upon the type of formulation and mode of administration, and may be readily discernible to those of ordinary skill in the art. About 0.5 to about 15 weight percent of disintegrant, or about 1 to about 5 weight percent of disintegrant, may be used in the pharmaceutical composition. Disintegrants that can be used to form pharmaceutical compositions and dosage forms of the disclosure include, but are not limited to, agar-agar, alginic acid, calcium carbonate, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, potato or tapioca starch, other starches, pre-gelatinized starch, other starches, clays, other algins, other celluloses, gums or mixtures thereof.

Lubricants which can be used to form pharmaceutical compositions and dosage forms of the disclosure include, but are not limited to, calcium stearate, magnesium stearate, sodium stearyl fumarate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol, other glycols, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oil (e.g., peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil), zinc stearate, ethyl oleate, ethyl laureate, agar, or mixtures thereof. Additional lubricants include, for example, a syloid silica gel, a coagulated aerosol of synthetic silica, or mixtures thereof. A lubricant can optionally be added, in an amount of less than about 2 weight percent of the pharmaceutical composition.

When aqueous suspensions and/or elixirs are desired for oral administration, the active ingredient therein may be combined with various sweetening or flavoring agents, coloring matter or dyes and, if so desired, emulsifying and/or suspending agents, together with such diluents as water, ethanol, propylene glycol, glycerin and various combinations thereof.

The tablets can be uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate can be employed. Formulations for oral use can also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin or olive oil.

Surfactants which can be used to form pharmaceutical compositions and dosage forms of the disclosure include, but are not limited to, hydrophilic surfactants, lipophilic surfactants, and mixtures thereof. That is, a mixture of hydrophilic surfactants may be employed, a mixture of lipophilic surfactants may be employed, or a mixture of at least one hydrophilic surfactant and at least one lipophilic surfactant may be employed.

A suitable hydrophilic surfactant may generally have an HLB value of at least 10, while suitable lipophilic surfactants may generally have an HLB value of or less than about 10. An empirical parameter used to characterize the relative hydrophilicity and hydrophobicity of non-ionic amphiphilic compounds is the hydrophilic-lipophilic balance (“HLB” value). Surfactants with lower HLB values are more lipophilic or hydrophobic, and have greater solubility in oils, while surfactants with higher HLB values are more hydrophilic, and have greater solubility in aqueous solutions.

Hydrophilic surfactants are generally considered to be those compounds having an HLB value greater than about 10, as well as anionic, cationic, or zwitterionic compounds for which the HLB scale is not generally applicable. Similarly, lipophilic (i.e., hydrophobic) surfactants are compounds having an HLB value equal to or less than about 10. However, HLB value of a surfactant is merely a rough guide generally used to enable formulation of industrial, pharmaceutical, and cosmetic emulsions.

Hydrophilic surfactants may be either ionic or non-ionic. Suitable ionic surfactants include, but are not limited to, alkylammonium salts; fusidic acid salts; fatty acid derivatives of amino acids, oligopeptides, and polypeptides; glyceride derivatives of amino acids, oligopeptides, and polypeptides; lecithins and hydrogenated lecithins; lysolecithins and hydrogenated lysolecithins; phospholipids and derivatives thereof; lysophospholipids and derivatives thereof; carnitine fatty acid ester salts; salts of alkylsulfates; fatty acid salts; sodium docusate; acyl lactylates; mono- and di-acetylated tartaric acid esters of mono- and di-glycerides; succinylated mono- and di-glycerides; citric acid esters of mono- and di-glycerides; and mixtures thereof.

Within the aforementioned group, ionic surfactants include, by way of example: lecithins, lysolecithin, phospholipids, lysophospholipids and derivatives thereof; carnitine fatty acid ester salts; salts of alkylsulfates; fatty acid salts; sodium docusate; acylactylates; mono- and di-acetylated tartaric acid esters of mono- and di-glycerides; succinylated mono- and di-glycerides; citric acid esters of mono- and di-glycerides; and mixtures thereof.

Ionic surfactants may be the ionized forms of lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidic acid, lysophosphatidylserine, PEG-phosphatidylethanolamine, PVP-phosphatidylethanolamine, lactylic esters of fatty acids, stearoyl-2-lactylate, stearoyl lactylate, succinylated monoglycerides, mono/diacetylated tartaric acid esters of mono/diglycerides, citric acid esters of mono/diglycerides, cholylsarcosine, caproate, caprylate, caprate, laurate, myristate, palmitate, oleate, ricinoleate, linoleate, linolenate, stearate, lauryl sulfate, teracecyl sulfate, docusate, lauroyl carnitines, palmitoyl carnitines, myristoyl carnitines, and salts and mixtures thereof.

Hydrophilic non-ionic surfactants may include, but are not limited to, alkylglucosides; alkylmaltosides; alkylthioglucosides; lauryl macrogolglycerides; polyoxyalkylene alkyl ethers such as polyethylene glycol alkyl ethers; polyoxyalkylene alkylphenols such as polyethylene glycol alkyl phenols; polyoxyalkylene alkyl phenol fatty acid esters such as polyethylene glycol fatty acids monoesters and polyethylene glycol fatty acids diesters; polyethylene glycol glycerol fatty acid esters; polyglycerol fatty acid esters; polyoxyalkylene sorbitan fatty acid esters such as polyethylene glycol sorbitan fatty acid esters; hydrophilic transesterification products of a polyol with at least one member of the group consisting of glycerides, vegetable oils, hydrogenated vegetable oils, fatty acids, and sterols; polyoxyethylene sterols, derivatives, and analogues thereof; polyoxyethylated vitamins and derivatives thereof; polyoxyethylene-polyoxypropylene block copolymers; and mixtures thereof; polyethylene glycol sorbitan fatty acid esters and hydrophilic transesterification products of a polyol with at least one member of the group consisting of triglycerides, vegetable oils, and hydrogenated vegetable oils. The polyol may be glycerol, ethylene glycol, polyethylene glycol, sorbitol, propylene glycol, pentaerythritol, or a saccharide.

Other hydrophilic-non-ionic surfactants include, without limitation, PEG-10 laurate, PEG-12 laurate, PEG-20 laurate, PEG-32 laurate, PEG-32 dilaurate, PEG-12 oleate, PEG-15 oleate, PEG-20 oleate, PEG-20 dioleate, PEG-32 oleate, PEG-200 oleate, PEG-400 oleate, PEG-15 stearate, PEG-32 distearate, PEG-40 stearate, PEG-100 stearate, PEG-20 dilaurate, PEG-25 glyceryl trioleate, PEG-32 dioleate, PEG-20 glyceryl laurate, PEG-30 glyceryl laurate, PEG-20 glyceryl stearate, PEG-20 glyceryl oleate, PEG-30 glyceryl oleate, PEG-30 glyceryl laurate, PEG-40 glyceryl laurate, PEG-40 palm kernel oil, PEG-50 hydrogenated castor oil, PEG-40 castor oil, PEG-35 castor oil, PEG-60 castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-60 corn oil, PEG-6 caprate/caprylate glycerides, PEG-8 caprate/caprylate glycerides, polyglyceryl-10 laurate, PEG-30 cholesterol, PEG-25 phyto sterol, PEG-30 soya sterol, PEG-20 trioleate, PEG-40 sorbitan oleate, PEG-80 sorbitan laurate, polysorbate 20, polysorbate 80, POE-9 lauryl ether, POE-23 lauryl ether, POE-10 oleyl ether, POE-20 oleyl ether, POE-20 stearyl ether, tocopheryl PEG-1000 succinate, PEG-24 cholesterol, polyglyceryl-10-oleate, Tween 40, Tween 60, sucrose monostearate, sucrose mono laurate, sucrose monopalmitate, PEG 10-100 nonyl phenol series, PEG 15-100 octyl phenol series, and poloxamers.

Suitable lipophilic surfactants include, by way of example only: fatty alcohols; glycerol fatty acid esters; acetylated glycerol fatty acid esters; lower alcohol fatty acids esters; propylene glycol fatty acid esters; sorbitan fatty acid esters; polyethylene glycol sorbitan fatty acid esters; sterols and sterol derivatives; polyoxyethylated sterols and sterol derivatives; polyethylene glycol alkyl ethers; sugar esters; sugar ethers; lactic acid derivatives of mono- and di-glycerides; hydrophobic transesterification products of a polyol with at least one member of the group consisting of glycerides, vegetable oils, hydrogenated vegetable oils, fatty acids and sterols; oil-soluble vitamins/vitamin derivatives; and mixtures thereof. Within this group, preferred lipophilic surfactants include glycerol fatty acid esters, propylene glycol fatty acid esters, and mixtures thereof, or are hydrophobic transesterification products of a polyol with at least one member of the group consisting of vegetable oils, hydrogenated vegetable oils, and triglycerides.

In one embodiment, the composition may include a solubilizer to ensure good solubilization and/or dissolution of the compound of the disclosure and to minimize precipitation of the compound of the disclosure. This can be important for compositions for non-oral use, e.g., compositions for injection. A solubilizer may also be added to increase the solubility of the hydrophilic drug and/or other components, such as surfactants, or to maintain the composition as a stable or homogeneous solution or dispersion.

Examples of suitable solubilizers include, but are not limited to, the following: alcohols and polyols, such as ethanol, isopropanol, butanol, benzyl alcohol, ethylene glycol, propylene glycol, butanediols and isomers thereof, glycerol, pentaerythritol, sorbitol, mannitol, transcutol, dimethyl isosorbide, polyethylene glycol (PEG), polypropylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose and other cellulose derivatives, cyclodextrins and cyclodextrin derivatives; ethers of polyethylene glycols having an average molecular weight of about 200 to about 6000, such as tetrahydrofurfuryl alcohol PEG ether (glycofurol) or methoxy PEG; polyethylene glycol 660 12-hydroxystearate; amides and other nitrogen-containing compounds such as 2-pyrrolidone, 2-piperidone, F-caprolactam, N-alkylpyrrolidone, N-hydroxyalkylpyrrolidone, N-alkylpiperidone, N-alkylcaprolactam, dimethylacetamide and polyvinylpyrrolidone; esters such as ethyl propionate, tributylcitrate, acetyl triethylcitrate, acetyl tributyl citrate, triethylcitrate, ethyl oleate, ethyl caprylate, ethyl butyrate, triacetin, propylene glycol monoacetate, propylene glycol diacetate, F-caprolactone and isomers thereof, δ-valerolactone and isomers thereof, P-butyrolactone and isomers thereof; and other solubilizers known in the art, such as dimethyl acetamide, dimethyl isosorbide, N-methyl pyrrolidones, monooctanoin, diethylene glycol monoethyl ether, and water.

Mixtures of solubilizers may also be used. Examples include, but not limited to, triacetin, triethylcitrate, ethyl oleate, ethyl caprylate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cyclodextrins, ethanol, transcutol, propylene glycol, and dimethyl isosorbide. Particularly preferred solubilizers include sorbitol, glycerol, triacetin, ethyl alcohol, PEG having an average molecular weight of about 100 to about 8000 g/mole, glycofurol and propylene glycol.

The amount of solubilizer that can be included is not particularly limited. The amount of a given solubilizer may be limited to a bioacceptable amount, which may be readily determined by one of skill in the art. In some circumstances, it may be advantageous to include amounts of solubilizers far in excess of bioacceptable amounts, for example to maximize the concentration of the drug, with excess solubilizer removed prior to providing the composition to a subject using conventional techniques, such as distillation or evaporation. Thus, if present, the solubilizer can be in a weight ratio of less than about 10%, less than about 25%, less than about 50%, about 100%, or up to less than about 200% by weight, based on the combined weight of the drug, and other excipients. If desired, very small amounts of solubilizer may also be used, such as less than about 5%, less than about 2%, less than about 1% or even less. Typically, the solubilizer may be present in an amount of less than about 1% to about 100%, more typically less than about 5% to less than about 25% by weight.

The composition can further include one or more pharmaceutically acceptable additives and excipients. Such additives and excipients include, without limitation, detackifiers, anti-foaming agents, buffering agents, polymers, antioxidants, preservatives, chelating agents, viscomodulators, tonicifiers, flavorants, colorants, odorants, opacifiers, suspending agents, binders, fillers, plasticizers, lubricants, and mixtures thereof.

Pharmaceutical Compositions for Injection

In some embodiments, the disclosure provides a pharmaceutical composition for injection containing a compound described herein and pharmaceutical excipients suitable for injection. Components and amounts of agents in the compositions are as described herein.

The forms in which the compositions of the disclosure may be incorporated for administration by injection include aqueous or oil suspensions or emulsions. Such compositions may comprise sesame oil, corn oil, cottonseed oil, peanut oil, elixirs containing mannitol or dextrose, sterile water, and similar pharmaceutical vehicles.

Aqueous solutions in saline are also conventionally used for injection. Ethanol, glycerol, propylene glycol, liquid polyethylene glycol, and the like (and suitable mixtures thereof), cyclodextrin derivatives, and vegetable oils may also be employed. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, for the maintenance of the required particle size in the case of dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like.

Sterile injectable solutions are prepared by incorporating the compound of the disclosure in the required amount in the appropriate solvent with various other ingredients as enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, certain desirable methods of preparation are vacuum-drying and freeze-drying techniques which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

Other Pharmaceutical Compositions

Pharmaceutical compositions may also be prepared from compositions described herein and one or more pharmaceutically acceptable excipients suitable for topical, sublingual, buccal, rectal, intraosseous, intraocular, intranasal, epidural, or intraspinal administration. Preparations for such pharmaceutical compositions are well-known in the art. See, e.g., Anderson, Philip O.; Knoben, James E.; Troutman, William G, eds., Handbook of Clinical Drug Data, Tenth Edition, McGraw-Hill, 2002; Pratt and Taylor, eds., Principles of Drug Action, Third Edition, Churchill Livingston, New York, 1990; Katzung, ed., Basic and Clinical Pharmacology, Ninth Edition, McGraw Hill, 2004; Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw Hill, 2001; Remington's Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins., 2000; Martindale, The Extra Pharmacopoeia, Thirty-Second Edition (The Pharmaceutical Press, London, 1999); all of which are incorporated by reference herein in their entirety.

Synthesis of Compounds of the Disclosure

Compounds of the disclosure can be prepared by methods described in the General Schemes, procedures, and Examples set forth within, and by related methods known in the art. For example, Compounds of Formula I can be prepared by the general methods shown in General Schemes 1, 1A, 2, 2A, and 3-11.

General Scheme 1: Preparation of Compounds of Formula I

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Compounds of Formula I were obtained through the reactions depicted in General Scheme 1. An amine of formulas 1.1 or 1.2 and an aldehyde of formula 1.3 were first reacted under Pictet-Spengler reaction conditions to afford the core amine of formula 1.4. To the extent that an imine by-product is formed during the Pictet-Spengler reaction, the imine by-product can be converted to the core amine of formula 1.4 by reaction with sodium borohydride in an alcoholic solvent (for example, methanol or ethanol). Various L and R²groups were then installed by using either a nucleophilic substitution reaction (Method A1), a Buchwald or other similar cross-coupling reaction (Method A2), a reductive animation reaction (Method B), or amide coupling reactions (Methods C, D, E, and F). Under Method A1, a R²aryl or heteroaryl halide of formula 1.5 (wherein X is Br, Cl, or F) is coupled to the core amine of formula 1.4 using a nucleophilic substitution reaction under basic conditions, such as DIPEA, to afford compounds of formula 1.6. Under Method A2, a R²aryl or heteroaryl halide of formula 1.5 (wherein X is Br, Cl, or I) is coupled to the core amine of formula 1.4 using Buchwald coupling or cross-coupling conditions known in the art, such as using a palladium catalyst (for example, CPhos-Pd-G3, Pd(OAc)₂, Pd(dppf)Cl₂), and a base such as Cs₂CO₃to afford compounds of formula 1.6. Under Method B, a R²aryl or heteroaryl aldehyde of formula 1.7 is coupled to the core amine of formula 1.4 under reductive animation reaction conditions using a hydride such as sodium triacetoxyborohydride to afford compounds of formula 1.8. Under Method C, a R²carboxylic acid of formula 1.9 or a basic salt (i.e., Li, K, or Na) thereof is coupled to core amine of formula 1.4 using acid coupling conditions known in the art, such as using one of the following reagents-HOBt, EDCI, HATU, T3P-along with a base, such as DIPEA (Hunig's base), pyridine, or TEA, to afford compounds of formula 1.11, wherein L²is a bond, optionally substituted C_1-6alkylene, optionally substituted C_2-6alkenylene, or optionally substituted C_1-6haloalkylene. Alternatively, under Method D, a R²acid chloride of formula 1.10 is coupled to the core amine of formula 1.4 under basic conditions to afford compounds of formula 1.11, wherein L²is a bond, optionally C_1-6alkylene, optionally substituted C_2-6alkenylene, or optionally substituted C_1-6haloalkylene. Under Method E, a R²acid chloride of formula 1.12 is coupled to the core amine of formula 1.4 under basic conditions to afford compounds of formula 1.14, wherein L³is a bond or optionally substituted C_1-6alkylene. Under Method F, an R²amine of formula 1.13 is coupled to the core amine of formula 1.4 and carbonyldiimidazole under basic conditions to afford compounds of formula 1.14, wherein L³is a bond or optionally substituted C_1-6alkylene.

General Scheme 1A: Preparation of Compounds of Formula I-A

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Compounds of Formula I-A wherein m is 0 and R³and R⁴are each hydrogen can be obtained through the reactions depicted in General Scheme 1A. Starting with an amine of formula 1.16, prepared as described in General Scheme 2A, various L and R²groups can be installed by using either a nucleophilic substitution reaction (Method A1), a Buchwald or other similar cross-coupling reaction (Method A2), a reductive animation reaction (Method B), or amide coupling reactions (Methods C, D, E, and F). Under Method A1, a R²aryl or heteroaryl halide of formula 1.5 (wherein X is Br, Cl, or F) is coupled to the core amine of formula 1.16 using a nucleophilic substitution reaction under basic conditions, such as DIPEA. Under Method A2, a R²aryl or heteroaryl halide of formula 1.5 (wherein X is Br, Cl, or I) is coupled to the core amine of formula 1.16 using Buchwald coupling or cross-coupling conditions known in the art, such as using a palladium catalyst (for example, CPhos-Pd-G3, Pd(OAc)₂, Pd(dppf)Cl₂)), and a base such as Cs₂CO₃. Under Method B, a R²aryl or heteroaryl aldehyde of formula 1.7 is coupled to the core amine of formula 1.16 under reductive animation reaction conditions using a hydride such as sodium triacetoxyborohydride. Under Method C, a R²carboxylic acid of formula 1.9 or a basic salt (i.e., Li, K, or Na) thereof is coupled to core amine of formula 1.16 using acid coupling conditions known in the art, such as using one of the following reagents-HOBt, EDCI, HATU, T3P—along with a base, such as DIPEA (Hunig's base) or TEA, to afford compounds of formula 1.19 (after any remaining protecting groups are removed), wherein L²is a bond, optionally substituted C_1-6alkylene, optionally substituted C_2-6alkenylene, or optionally substituted C_1-6haloalkylene. Alternatively, under Method D, a R²acid chloride of formula 1.10 is coupled to the core amine of formula 1.16 under basic conditions to afford compounds of formula 1.19 (after any remaining protecting groups are removed), wherein L²is a bond, optionally C_1-6alkylene, optionally substituted C_2-6alkenylene, or optionally substituted C_1-6haloalkylene. Under Method E, a R²acid chloride of formula 1.12 is coupled to the core amine of formula 1.16 under basic conditions to afford compounds of formula 1.20 (after any remaining protecting groups are removed), wherein L³is a bond or optionally substituted C_1-6alkylene. Under Method F, an R²amine of formula 1.13 is coupled to the core amine of formula 1.16 and carbonyldiimidazole under basic conditions to afford compounds of formula 1.20 (after any remaining protecting groups are removed), wherein L³is a bond or optionally substituted C_1-6alkylene. After the coupling reactions in Methods A1, A2, B, C, D, E, or F are completed, any remaining protecting groups (PG) on the imidazole ring or R²group can be removed under suitable conditions to afford the depicted products in General Scheme IA (compounds of formulas 1.17, 1.18, 1.19, and 1.20). For example, the TIPS protecting group can be removed via reaction with tetrabutylammonium fluoride and the amine t-boc protecting group can be removed under acidic conditions.

General Scheme 2: Preparation of Deuterated Core Amine Intermediates of Formula 2.2

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Compounds of Formula I wherein R⁵is D are prepared in accordance with General Scheme 2. An amine of formula 1.1 or 1.2 and an aldehyde of formula 1.3 are reacted under Pictet-Spengler reaction conditions to afford compounds of formula 2.1 or mixtures of compounds of formula 2.1 and the imine by-product of formula 2.1a. Compounds of formula 2.1 or mixtures of compounds of formulas 2.1 and 2.1a are then reacted with sodium borodeuteride in deuterated methanol to afford deuterated core amine of formula 2.2. Deuterated core amine intermediates of formula 2.2 can then be further coupled to various L and R²groups via methods A1, A2, B, C, D, E, and F as described in General Scheme 1 to afford Compounds of Formula I, wherein R⁵is D.

General Scheme 2A: Preparation of Core Amine Intermediates of Formula 1.16

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Intermediates of formula 1.16 were prepared in accordance with General Scheme 2A. Starting with tert-butyl 4,6-dihydro-1H-pyrrolo[3,4-d]imidazole-5-carboxylate (2.3), the imidazole amine was protected with a N,N-dimethylsulfamoyl protecting group or another suitable nitrogen protecting group in the presence of a strong base such as LDA and NaH to afford compound 2.4. The acidic proton on the imidazole ring was then protected with a triisopropylsilyl (TIPS) group or other suitable silyl protecting group in the presence of a strong base such as LDA, t-BuLi, or n-BuLi to afford compound 2.5. A methyl ester (or alternatively a C₂-C₄alkyl ester) was installed by reacting dimethyl carbonate and a strong base such as LDA to afford methyl ester 2.6. Under Route A, the methyl ester in compound 2.6 was then hydrolyzed with a basic hydroxide such as LiOH or NaOH to afford carboxylic acid 2.7. The carboxylic acid in compound 2.7 was then reacted with 2-aminophenol (or alternatively a substituted 2-aminophenol) using acid coupling conditions known in the art, such as using one of the following reagents-HOBt, EDCI, HATU, T3P-along with a base, such as DIPEA (Hunig's base) or TEA, to afford compounds of formula 2.8. A compound of formula 2.8 was cyclized using Mitsunobu reaction conditions known in the art, such as PPh₃and DIAD or DEAD, to form the benzoxazole R¹group in compounds of formula 2.9. The Boc protecting group was then removed in a compound of formula 2.9 under acidic conditions such as HCl or TFA to afford the amine of formula 2.10. Alternatively, under Route B, the TIPS protecting group can be removed from compound 2.6 prior to hydrolysis of the methyl ester. Amine intermediates of formula 2.10 and 2.15 can then be further coupled to various L and R²groups via methods A1, A2, B, C, D, E, and F as described in General Scheme 1A to afford Compounds of Formula IA, wherein m is 0 and R³and R⁴are each hydrogen.

General Scheme 3: Preparation of Oxazolyl R²Acid Intermediates

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Oxazolyl R²carboxylic acid intermediates containing substitutions at the R⁶and/or R⁷positions were prepared in accordance with General Scheme 3. A carboxylic acid of formula 3.1 was reacted with oxalyl chloride and catalytic N,N-dimethylformamide to afford acid chloride of formula 3.2. Acid chloride of formula 3.2 was then reacted with an enamine of formula 3.3 to afford an enamide of formula 3.4. An enamide of formula 3.4 then underwent hypervalent iodine-mediated cyclization after reaction with [bis(trifluoroacetoxy)iodo]benzene and boron trifluoride diethyl etherate to afford oxazole of formula 3.5. Hydrolysis of the ester of the oxazole formula 3.5 with a base such as LiOH, KOH, or NaOH in THF/water afforded compounds of formula 3.6. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formula 3.6 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 4: Preparation of Oxazolyl R²Acid Intermediates

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Oxazolyl R²carboxylic acid intermediates containing substitutions at the R⁶and/or R⁷positions were prepared in accordance with General Scheme 4. A j-keto ester of formula 4.1 was halogenated with a chlorinating agent such as SOCl₂or brominating agent such as NBS to yield compounds of formula 4.2 (wherein X¹is Br or Cl). Compounds of formula 4.2 were reacted with urea to afford amine oxazole compounds of formula 4.3. In addition, compounds of formula 4.2 were reacted with amides of formula 4.5 to afford oxazole compounds of formula 4.6. The amine in compounds of formula 4.3 was subjected to Sandmeyer reaction conditions to afford compounds of formula 4.4 (wherein X is Cl, Br, or F) and compounds of formula 4.10. Alternatively, compounds of formula 4.10 may be obtained by deprotonating a compound of formula 4.8 with a base such as LiHMDS followed by reaction in a nucleophilic substitution reaction with reagents of formula 4.9 (wherein Y is a suitable leaving group such as Br, Cl, mesylate, or tosylate) to afford compounds of formula 4.10. Hydrolysis of the ester of compounds of formulas 4.6 and 4.10 with a base such as LiOH, KOH, or NaOH in THF/water affords compounds of formulas 4.7 and 4.11. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formulas 4.7 and 4.11 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 5: Synthesis of Thiazolyl and Oxazolyl R²Acid Intermediates

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Oxazolyl and thiazolyl R²carboxylic acid intermediates containing substitutions at the R⁶and/or R⁷positions were prepared in accordance with General Scheme 5. Under Method A, a halide of formula 5.1 was reacted with a heteroaryl or aryl of formula 5.2 in either a Suzuki coupling (where Y is a boronic acid or ester) or a Stille coupling (where Y is SnR₃) to afford compounds of formula 5.3. Under Method B, compounds of formula 5.3 were obtained by reaction of a compound of formula 5.4 with a heteroaryl or aryl halide compound of formula 5.5 in a cross-coupling reaction using a metal catalyst such as a Buchwald catalyst or Ullman catalyst. Under Method C, a halide of formula 5.1 may also be reacted with an amine of formula 5.7 or a heterocyclic amine such as piperidine, morpholine, piperazine, azetidine, and pyrrolidine, and a base such as TEA in a displacement reaction to afford compounds of formula 5.8. Hydrolysis of the ester of compounds of formulas 5.3 and 5.8 with a base such as LiOH, KOH, or NaOH in THF/water affords compounds of formulas 5.6 and 5.9. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formulas 5.6 and 5.9 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 6: Synthesis of Thiazolyl and Oxazolyl R²Acid Intermediates

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Oxazolyl and thiazolyl R²carboxylic acid intermediates containing hydroxyalkyl and haloalkyl substitutions were prepared in accordance with General Scheme 6. Under Method A, a halide of formula 6.1 was reacted with tributyl(1-ethoxyvinyl)stannane in a Stille coupling, followed by hydrolysis with acid/water such as TFA to afford compounds of formula 6.3. An alkyl group (“R”) is then added to the ketone in compounds of formula 6.3 using RMgBr or RLi or through reduction of the ketone with NaBR to afford compounds of formula 6.4. Under Method B, compounds of formula 6.4 may also be obtained starting with a compound of formula 6.1 through a Grignard addition reaction with a ketone of formula 6.2 (wherein R is an alkyl) or cyclobutanone and RMgCl such as iPrMgCl. The hydroxyl substituent in compounds of formula 6.4 was converted to a fluorine substituent using a fluorinating agent such as BAST to afford compounds of formula 6.6. Hydrolysis of the ester of compounds of formulas 6.4 and 6.6 with a base such as LiOH, KOH, or NaOH in THF/water affords compounds of formulas 6.5 and 6.7. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formulas 6.5 and 6.7 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 7: Synthesis of Pyrazolo[1,5-a]pyridinyl R²Acid Intermediates

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Substituted pyrazolo[1,5-a]pyridinyl R²carboxylic acid intermediates were prepared in accordance with General Scheme 7. Under Method A, a halide of formula 7.1 (wherein X¹is Br or Cl) was reacted in a C—N cross-coupling reaction using a metal catalyst such as a Buchwald catalyst or Ullman catalyst with an amine of formula 7.2 or a heterocyclic amine such as piperidine, morpholine, piperazine, azetidine, and pyrrolidine to afford compounds of formula 7.3. Under Method B, a halide of formula 7.1 (wherein X¹is Br or Cl) may also be reacted with a heteroaryl or aryl compound of formula 7.5 in either a Suzuki coupling (where Y is a boronic acid or ester) or a Stille coupling (where Y is SnR₃) to afford compounds of formula 7.6. Under Method C, a halide of formula 7.1 (wherein X¹is Br or Cl) was reacted with 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane in a Suzuki coupling to afford compounds of formula 7.8. The olefin in compounds of formula 7.8 then underwent oxidative cleavage to an aldehyde to afford compounds of formula 7.9. Under Method D, the aldehyde in compounds of formula 7.9 was reduced to an alcohol with a hydride such as NaBH₄in an alcoholic solvent such as methanol or ethanol to afford formula 7.13. The alcohol in compounds of formula 7.13 was alkylated with sodium hydride and an alkyl (“R”) halide of formula 7.14 (wherein X is Cl, Br, or F) to afford compounds of formula 7.15. Under Method E, a compound of formula 7.9 was reacted with an amine of formula 7.10 under reductive animation conditions to afford compounds of formula 7.11. Hydrolysis of the ester of compounds of formulas 7.3, 7.6, 7.11, and 7.15 with a base such as LiOH, KOH, or NaOH in THF/water affords compounds of formulas 7.4, 7.7, 7.12, and 7.16. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formulas 7.4, 7.7, 7.12, and 7.16 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 8: Synthesis of Pyrazolo[1,5-a]pyridinyls R²Acid Intermediates

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Di-substituted pyrazolo[1,5-a]pyridinyl R²carboxylic acid intermediates were prepared in accordance with General Scheme 8. Starting reagent 3-bromo-4-chloropyridine was reacted with ethyl (E)-N-((mesitylsulfonyl)oxy)acetimidate to afford the N-aminopyridinium salt 8.1. A cycloaddition reaction of the N-aminopyridinium salt 8.1 with ethyl propiolate and base such as K₂CO₃afforded ethyl 6-bromo-5-chloropyrazolo[1,5-a]pyridine-3-carboxylate 8.2. Compound 8.2 was reacted in a C—N cross-coupling reaction using a metal catalyst such as a Buchwald catalyst or Ullman catalyst with an amine of formula 8.4 or a heterocyclic amine such as piperidine, morpholine, piperazine, azetidine, and pyrrolidine to afford compounds of formula 8.5. Hydrolysis of the ester of compounds of formulas 8.2 and 8.5 with a base such as LiOH, KOH, or NaOH in THF/water affords compounds of formulas 8.3 and 8.6. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formulas 8.3 and 8.6 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 9: Synthesis of 1,3,4-Oxadiazolyl R²Acid Intermediates

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Heteroaryl and aryl-substituted oxadiazolyl R²carboxylic acid intermediates were prepared in accordance with General Scheme 9. Under Method A, heteroaryl and aryl esters of formula 9.1 were reacted with hydrazine hydrate to afford hydrazines of formula 9.2. Compounds of formula 9.2 were then reacted with ethyl-2-chloro-2-oxoacetate to afford compounds of formula 9.3, which subsequently underwent intramolecular cyclization with p-toluenesulfonyl chloride and a base such as TEA to afford the 1,3,4-oxadiazole of formula 9.4. Alternatively, compounds of formula 9.4 can be made using Method B. Under Method B, ethyl 2-hydrazineyl-2-oxoacetate was reacted with 1,1′-thiocarbonyldiimidazole to form the 1,3,4-oxadiazole, which was then alkylated with methyl iodide and base such as TEA to afford ethyl 5-(methylthio)-1,3,4-oxadiazole-2-carboxylate. Ethyl 5-(methylthio)-1,3,4-oxadiazole-2-carboxylate was reacted with a heteroaryl or aryl boronic acid or ester of formula 9.5 in a desulfitative C—C cross coupling reaction (also known as Liebeskind-Srogl cross-coupling) to afford compounds of formula 9.4. Hydrolysis of the ester of compounds of formula 9.4 with a base such as LiOH, KOH, or NaOH in THF/water affords compounds of formula 9.6. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formula 9.6 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 10: Synthesis of 1,3,4-Oxadiazolyl R²Acid Intermediates

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Substituted 1,3,4-oxadiazolyl R²carboxylic acid intermediates were prepared in accordance with General Scheme 10. Starting reagent ethyl 5-amino-1,3,4-oxadiazole-2-carboxylate was subjected to Sandmeyer reaction conditions to afford ethyl 5-bromo-1,3,4-oxadiazole-2-carboxylate (Compound 10.1). The bromo in compound 10.1 was reacted with an amine of formula 10.2 or a heterocyclic amine such as piperidine, morpholine, piperazine, azetidine, and pyrrolidine, and a base such as TEA to afford compounds of formula 10.3. Hydrolysis of the ester of compounds of formula 10.3 with a base such as LiOH, KOH, or NaOH in THF/water afforded compounds of formula 10.4. Alternatively, the basic salt (i.e., Li, K, or Na) of the carboxylic acid of formula 10.4 may be obtained after the hydrolysis reaction by isolating the product at a basic pH. The carboxylic acid or basic salt thereof can then be used without further purification in the coupling reactions described in General Schemes 1 and 1A, Method C.

General Scheme 11: Preparation of Deuterated Core Amine Intermediates of Formulas 11.6 and 11.7

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Compounds of Formula I wherein R^5Ais D are prepared in accordance with General Scheme 11. An amine of formula 2.1, prepared according to General Scheme 2, is protected with a BOC protecting group or other suitable nitrogen protecting group to afford compounds of formula 11.1. The amine in formula 11.1 is then protected with a dimethylsulfamoyl protecting group to afford a mixture of compounds of formula 11.2 and 11.3, which are separated during purification. Deuterium is then incorporated at the RSA position by deprotonating compounds of formula 11.2 with butyllithium and then adding D₂O to afford compounds of formulas 11.4 and 11.5. Deprotection of the nitrogen protecting groups with acid afforded deuterated core amine intermediates of formulas 11.6. Deuterated core amine intermediates of formulas 11.6 can be further coupled to various L and R²groups via methods A1, A2, B, C, D, E, and F as described in General Scheme 1 to afford Compounds of Formula I, wherein R^5Ais D.

The present disclosure will be more fully understood by reference to the following examples. The examples provided herein are illustrative and should not, however, be construed as limiting the scope of the present disclosure.

EXAMPLES

In some embodiments, the disclosure provides specific examples of Formula I, and their pharmaceutically acceptable salts and/or isotopologues, as set forth in Table 1S below.

TABLE 1S

Benzo[d]oxazoles

Ex.

#
Structure
Name

1

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(S)-(5-chlorothiazol-2-yl)(4-(5- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

3

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(S)-1-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)-2- cyclopropylethanone

5

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(pyridin-2- yl)thiazol-5-yl)methanone

7

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(S)-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(2-(pyridin-2- yl)oxazol-5-yl)methanone

9

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(1-methyl-1H- pyrazol-4-yl)thiazol-5-yl)methanone

11

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(pyridin-2- yl)oxazol-5-yl)methanone

13

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(2-fluoropropan-2- yl)oxazol-5-yl)methanone

15

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(S)-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

17

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(S)-(2-(tert-butyl)thiazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

19

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(6- methylpyrazolo[1,5-a]pyridin-3-yl)methanone

21

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(S)-(2-(tert-butyl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

23

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

25

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(S)-(5-(2,6-difluorophenyl)-1,3,4-oxadiazol-2-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

27

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(4-fluorophenyl)- 1,3,4-oxadiazol-2-yl)methanone

29

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- (methoxymethyl)pyrazolo[1,5-a]pyridin-3- yl)methanone

31

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyl-2-(pyridin- 2-yl)oxazol-5-yl)methanone

33

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(5- fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

35

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(S)-(2-(1,1-difluoroethyl)thiazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

37

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(S)-2-cyclopropyl-1-(4-(5-fluorobenzo[d]oxazol-2- yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)ethanone

39

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

41

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(S)-(4-cyclopropyloxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

43

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(S)-(4-cyclopropyl-2-(pyridin-2-yl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

45

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(2-hydroxypropan- 2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

47

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(S)-(6-(2-(dimethylamino)ethyl)pyrazolo[1,5- a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

49

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(pyridin-2-yl)-4- (trifluoromethyl)oxazol-5-yl)methanone

51

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

53

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(S)-(2-cyclopropyl-4-(difluoromethyl)oxazol-5-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

55

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(S)-1-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)-2-(1- hydroxycyclobutyl)ethanone

57

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(S)-(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

59

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(S)-1-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)-2-(3- fluorocyclobutyl)ethanone

61

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((S)-2,2-difluorocyclopropyl)((S)-4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

63

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(S)-(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

65

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4- methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3- yl)methanone

67

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

69

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(S)-(6-bromopyrazolo[1,5-a]pyridin-3-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

71

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(1-methyl-1H- pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

73

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- methoxypyrazolo[1,5-a]pyridin-3-yl)methanone

75

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(S)-(5-(3,4-difluorophenyl)-1,3,4-oxadiazol-2-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

77

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(S)-(5-(4-fluoro-2-methylphenyl)-1,3,4-oxadiazol-2- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

79

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(S)-(5-chloro-6-(2- (dimethylamino)ethyl)pyrazolo[1,5-a]pyridin-3-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

81

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(pyridin-2- yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

84

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(S)-(5-(2,4-difluorophenyl)-1,3,4-oxadiazol-2-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

85

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(S)-(4-(difluoromethyl)-2-(pyridin-2-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

88

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-4- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

90

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(4- (trifluoromethyl)phenyl)-1,3,4-oxadiazol-2- yl)methanone

91

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(S)-(6-(dimethylamino)pyrazolo[1,5-a]pyridin-3- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

93

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

95

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(S)-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

97

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(S)-(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

99

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(S)-(5-(5-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4- (5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

101

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(S)-(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

103

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(S)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2- yl)(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

106

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

107

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

110

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(S)-(4-(difluoromethyl)-2-(methoxymethyl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

111

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(S)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2- yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

113

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

115

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(S)-(4-(difluoromethyl)-2- ((trifluoromethoxy)methyl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

118

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-3- (trifluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2- yl)methanone

119

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(S)-(5-(1,4-dimethyl-1H-pyrazol-5-yl)-1,3,4- oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

122

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[(4S)-4-(5-fluoro-1,3-benzoxazol-2-yl)-1,4,6,7- tetrahydroimidazo[4,5-c]pyridin-5-yl]-[5-[4- (trifluoromethyl)-2-pyridyl]-1,3,4-oxadiazol-2- yl]methanone

124

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(S)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

126

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(5-methylpyridin- 2-yl)-1,3,4-oxadiazol-2-yl)methanone

127

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(S)-(3-chloro-1-methyl-1H-pyrazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

129

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(S)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

131

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-5-yl)-1,3,4-oxadiazol-2-yl)methanone

133

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(S)-(6-(4-cyclopropylpiperazin-1-yl)pyrazolo[1,5- a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

135

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((S)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-((R)-1- hydroxyethyl)-4-methyloxazol-5-yl)methanone

137

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

139

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(3,3,4- trimethylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3- yl)methanone

141

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(S)-(4-(difluoromethyl)-2-(1- hydroxycyclopropyl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

143

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(S)-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

145

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(S)-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

147

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(S)-(4-(5-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

149

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(S)-(4-(5-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

151

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(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

153

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(S)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

155

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(S)-(4-(difluoromethyl)-2-((methoxy- d3)methyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2- yl)-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5- yl)methanone

157

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(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

159

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(S)-2-(4-(difluoromethyl)-5-(4-(5- fluorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-1H- imidazo[4,5-c]pyridine-5-carbonyl)oxazol-2-yl)-2- methylpropanenitrile

161

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(S)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

163

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(6- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

165

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(S)-(6-bromo-5-chloropyrazolo[1,5-a]pyridin-3-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

167

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

169

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(4- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

171

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

173

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

175

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(S)-(5-chloro-6-morpholinopyrazolo[1,5-a]pyridin-3- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

177

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(S)-(6-amino-5-chloropyrazolo[1,5-a]pyridin-3-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

179

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (fluoromethyl)oxazol-5-yl)methanone

181

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(S)-(5-chloro-6-(4-methylpiperazin-1-yl)pyrazolo[1,5- a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

183

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(S)-(5-(difluoromethyl)-1-(2,2,2-trifluoroethyl)-1H- pyrazol-4-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

185

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(S)-2-(5-(4-(5-fluorobenzo[d]oxazol-2-yl)-4,5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-5-carbonyl)-4- methyloxazol-2-yl)-2-methylpropanenitrile

187

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

189

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(6- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

191

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

193

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

195

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

197

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

199

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

201

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(4- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

203

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(S)-(5-chloro-6- ((dimethylamino)methyl)pyrazolo[1,5-a]pyridin-3- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanonee

205

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(S)-(5-chloro-6-(methylamino)pyrazolo[1,5-a]pyridin- 3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

207

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(S)-(5-chloro-6-(dimethylamino)pyrazolo[1,5- a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

210

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((S)-4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-((R)-1- hydroxyethyl)-4-methyloxazol-5-yl)methanone

211

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-(fluoromethyl)-2- (2-hydroxypropan-2-yl)oxazol-5-yl)methanone

214

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(S)-(4-(difluoromethyl)-2-(1- hydroxycyclopropyl)oxazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

215

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(S)-(4-(difluoromethyl)-2-(1- hydroxycyclopropyl)oxazol-5-yl)(4-(4- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

217

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((S)-4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-((R)-1- hydroxyethyl)-4-methyloxazol-5-yl)methanone

219

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(S)-(5-chloro-6-fluoropyrazolo[1,5-a]pyridin-3-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

221

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(S)-(4-(difluoromethyl)-2-(2-(methylamino)propan-2- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

225

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(4-bromo-2-(1-hydroxyethyl)oxazol-5-yl)((S)-4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone Diastereomer #1 (Rt = 4.793 min)

226

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(4-bromo-2-(1-hydroxyethyl)oxazol-5-yl)((S)-4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone Diastereomer #2 (Rt = 5.231 min)

227

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(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

229

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(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

231

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(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

235

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(4-chloro-2-(1-hydroxyethyl)oxazol-5-yl)((S)-4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone Diastereomer #1 (Rt = 4.258 min)

236

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(4-chloro-2-(1-hydroxyethyl)oxazol-5-yl)((S)-4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone Diastereomer #2 (Rt = 4.417 min)

237

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(S)-(4-(difluoromethyl)-2-(1- hydroxycyclopropyl)oxazol-5-yl)(4-(6- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

239

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(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

241

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((S)-4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-((S)-1- hydroxyethyl)-4-methyloxazol-5-yl)methanone

243

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(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

245

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(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5- yl)((S)-4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

247

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((S)-4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-((S)-1- hydroxyethyl)-4-methyloxazol-5-yl)methanone

249

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(S)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

252

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(S)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

253

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(2-hydroxypropan- 2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

255

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(S)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(2-hydroxypropan- 2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

257

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(2-hydroxypropan- 2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

259

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(2-hydroxypropan- 2-yl)-4-methyloxazol-5-yl)methanone

261

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-(trifluoromethyl)- 1H-pyrazol-5-yl)methanone

263

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(S)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

265

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- (methoxymethyl)pyrazolo[1,5-a]pyridin-3- yl)methanone

268

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(2-hydroxypropan- 2-yl)-4-methyloxazol-5-yl)methanone

269

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(S)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

272

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(S)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

274

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(S)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

275

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- (methoxymethyl)pyrazolo[1,5-a]pyridin-3- yl)methanone

277

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(S)-(3-chloro-1-methyl-1H-1,2,4-triazol-5-yl)(4-(4- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

279

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-methyl-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)methanone

281

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(oxazol-5- yl)methanone

283

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(S)-(3-chloro-1-methyl-1H-1,2,4-triazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

285

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(S)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

287

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(S)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-(trifluoromethyl)- 1H-pyrazol-5-yl)methanone

289

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-(trifluoromethyl)- 1H-pyrazol-5-yl)methanone

291

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(S)-(4-(difluoromethyl)-2-(2-(dimethylamino)propan- 2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

293

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-(trifluoromethyl)- 1H-pyrazol-5-yl)methanone

295

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(S)-(4-(5,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

297

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(S)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

299

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(S)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

301

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(S)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

303

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(S)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

305

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(S)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

307

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

309

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

311

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

313

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(5- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

315

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(6-methylbenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

317

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(6- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

319

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(S)-(2-(2-hydroxypropan-2-yl)-4-methyloxazol-5- yl)(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

321

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(S)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

323

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- methylpyrazolo[1,5-a]pyridin-3-yl)methanone

325

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- methoxypyrazolo[1,5-a]pyridin-3-yl)methanone

327

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5-(trifluoromethyl)benzo[d]oxazol- 2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

329

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5- (trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

331

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(S)-(2-(2-hydroxypropan-2-yl)-4-methyloxazol-5- yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

333

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

335

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

337

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

339

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5-methoxybenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

341

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

343

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(S)-(3-chloro-1-methyl-1H-1,2,4-triazol-5-yl)(4-(6- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

345

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

347

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(S)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

350

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(S)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

351

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5- (trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

354

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5- (trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

355

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(S)-(5-(1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(5- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

357

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(S)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2- yl)(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

359

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(S)-(5-(1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(6- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

361

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

363

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4- methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3- yl)methanone

365

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- morpholinopyrazolo[1,5-a]pyridin-3-yl)methanone

368

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4-(2- hydroxypropan-2-yl)piperidin-1-yl)pyrazolo[1,5- a]pyridin-3-yl)methanone

369

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4-fluoropiperidin- 1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

371

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4- hydroxypiperidin-1-yl)pyrazolo[1,5-a]pyridin-3- yl)methanone

373

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

375

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(S)-(4-(5-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

378

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(S)-(4-(5-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

379

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-1,4,6,7- tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)(5-(1- methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2- yl)methanone

382

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(4- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

383

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(1-methyl-1H- pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

385

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1-[(4S)-4-(7-fluoro-1,3-benzoxazol-2-yl)-1,4,6,7- tetrahydroimidazo[4,5-c]pyridin-5-yl]-3-thiazol-2-yl- propan-1-one

387

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(S)-1-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)-3-(oxazol-2- yl)propan-1-one

389

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(S)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2- yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

392

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

393

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

395

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(S)-(6-(6-azaspiro[2.5]octan-6-yl)pyrazolo[1,5- a]pyridin-3-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

397

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(S)-1-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)-3-(thiazol-2- yl)propan-1-one

399

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-3-yl)- 1,3,4-oxadiazol-2-yl)methanone

401

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(S)-(4-(difluoromethyl)-2-(4-fluoropiperidin-1- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

403

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(S)-(4-(difluoromethyl)-2-(4-methylpiperazin-1- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

406

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(S)-(4-(difluoromethyl)-2-(pyrimidin-5-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

407

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(S)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

409

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(S)-1-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)-3-(thiazol-5- yl)propan-1-one

411

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-3- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

413

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(S)-(4-(difluoromethyl)-2-morpholinooxazol-5-yl)(4- (5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

415

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[(4S)-4-(5-bromo-1,3-benzoxazol-2-yl)-1,4,6,7- tetrahydroimidazo[4,5-c]pyridin-5-yl]-[4- (difluoromethyl)-2-(1-hydroxy-1-methyl- ethyl)oxazol-5-yl]methanone

418

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(S)-(4-(difluoromethyl)-2-(5-fluoropyridin-2- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

420

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(S)-(4-(difluoromethyl)-2-(pyridin-3-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

421

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(S)-(4-(difluoromethyl)-2-(pyridin-4-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

423

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(S)-(4-(7-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

425

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(S)-(4-(7-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

427

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(4-methoxybenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

429

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(4- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

431

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(S)-(4-(4-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

433

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(S)-(4-(4-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

435

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[(4S)-4-(4-chloro-1,3-benzoxazol-2-yl)-1,4,6,7- tetrahydroimidazo[4,5-c]pyridin-5-yl]-[4- (difluoromethyl)-2-(1-hydroxy-1-methyl- ethyl)oxazol-5-yl]methanone

437

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[(4S)-4-(4-chloro-1,3-benzoxazol-2-yl)-1,4,6,7- tetrahydroimidazo[4,5-c]pyridin-5-yl]-[4- (difluoromethyl)oxazol-5-yl]methanone

439

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(S)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5- yl)(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

442

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(5- methoxypyridin-2-yl)-1,3,4-oxadiazol-2- yl)methanone

444

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(S)-(4-(difluoromethyl)-2-(5-(trifluoromethyl)pyridin- 2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

445

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(S)-(4-(difluoromethyl)-2-(5-methoxypyridin-2- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

447

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(S)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

449

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(4- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

451

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(pyridin-2- yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

453

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(7-(trifluoromethyl)benzo[d]oxazol- 2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

455

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(7-methoxybenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

457

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

460

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(S)-(4-(7-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

461

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(S)-(4-(7-bromobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

463

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(4-(trifluoromethyl)benzo[d]oxazol- 2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

465

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(4- (trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

467

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

470

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-(difluoromethyl)- 2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

471

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(S)-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)(4-(4- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

473

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(S)-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

475

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4- methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3- yl)methanone

477

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4-fluoropiperidin- 1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

480

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(S)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2- yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

482

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(S)-(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

483

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(oxazol-5- yl)methanone

486

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(3- (difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)methanone

487

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1- (difluoromethyl)-1H-pyrazol-5-yl)methanone

489

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(S)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1- (difluoromethyl)-1H-pyrazol-5-yl)methanone

491

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(S)-(5-(1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(5- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

493

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7- (trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

495

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(S)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

497

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(S)-(3-cyclopropyl-1-methyl-1H-1,2,4-triazol-5-yl)(4- (7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

499

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(7-fluoro-5-methylbenzo[d]oxazol- 2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

501

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-fluoro-5- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

504

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- morpholinopyrazolo[1,5-a]pyridin-3-yl)methanone

505

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(S)-(6-(6-azaspiro[2.5]octan-6-yl)pyrazolo[1,5- a]pyridin-3-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

507

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4-(2- hydroxypropan-2-yl)piperidin-1-yl)pyrazolo[1,5- a]pyridin-3-yl)methanone

509

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(S)-(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(oxazol-5- yl)methanone

511

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(S)-(2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

513

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(S)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1- (difluoromethyl)-1H-pyrazol-5-yl)methanone

515

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(S)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

518

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

520

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

522

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(S)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

523

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(S)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

526

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(S)-(4-(difluoromethyl)-2-(pyrimidin-4-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

527

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(S)-(4-(difluoromethyl)-2-(pyrazin-2-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

529

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(7- (trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

532

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7- (trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

533

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(4- (trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

536

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(4- (trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

537

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- methylpyrazolo[1,5-a]pyridin-3-yl)methanone

539

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6- methoxypyrazolo[1,5-a]pyridin-3-yl)methanone

541

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(1-methyl-1H- pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

543

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(6-(pyridin-2- yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

546

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(S)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

547

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(oxazol-5- yl)methanone

549

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(S)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)(4-(5-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

551

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(5- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

553

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(S)-(4-(5-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

555

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(S)-(4-(5-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

557

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(S)-(4-cyclopropyl-2-(2-hydroxypropan-2-yl)oxazol- 5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

560

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(S)-(4-(difluoromethyl)-2-(pyridin-4-yl)oxazol-5- yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

561

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(3-(difluoromethyl)- 1-methyl-1H-1,2,4-triazol-5-yl)methanone

563

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-(difluoromethyl)- 1H-pyrazol-5-yl)methanone

565

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(S)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2- yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

567

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(S)-(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

569

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyloxazol-5- yl)methanone

571

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(S)-(4-(5-bromo-7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

573

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(S)-(4-(5-bromo-7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

575

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(oxazol-5- yl)methanone

577

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(3- (difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)methanone

580

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

581

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

583

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

585

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(2-(1- hydroxycyclobutyl)-4-(trifluoromethyl)oxazol-5- yl)methanone

587

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(S)-(4-(difluoromethyl)-2-(pyridin-2-yl)oxazol-5- yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

590

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(S)-(4-(difluoromethyl)-2-(pyridin-3-yl)oxazol-5- yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

591

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-3- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

594

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyl-2-(pyridin- 2-yl)oxazol-5-yl)methanone

596

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyl-2-(1- methyl-1H-pyrazol-4-yl)oxazol-5-yl)methanone

597

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(S)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyloxazol-5- yl)methanone

599

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyloxazol-5- yl)methanone

601

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(S)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

603

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(4- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

605

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(S)-(4-(5-chloro-7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5- yl)methanone

608

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(S)-(4-(5-chloro-7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)oxazol-5-yl)methanone

609

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

611

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(S)-(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(oxazol-5- yl)methanone

613

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(S)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

616

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(S)-(4-(difluoromethyl)-2-(5-methoxypyridin-2- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

617

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(S)-(4-(difluoromethyl)-2-(4-methylpiperazin-1- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

620

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(S)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

621

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(S)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(oxazol-5- yl)methanone

624

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(S)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

626

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(S)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

628

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyrazin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

629

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(S)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(pyridin-2-yl)- 1,3,4-oxadiazol-2-yl)methanone

632

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(S)-(4-(difluoromethyl)-2-(5-fluoropyridin-2- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

633

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(S)-(4-(difluoromethyl)-2-(5-(trifluoromethyl)pyridin- 2-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

636

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-4- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

638

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(2-(pyridin-2- yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

639

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(S)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

641

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-4- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

643

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(7-fluoro-5- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

645

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(S)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

648

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(S)-(4-(difluoromethyl)-2-morpholinooxazol-5-yl)(4- (7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

649

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(S)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(6- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

651

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(S)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(4- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

653

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(S)-(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4- (5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

655

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5-fluoro-7-methylbenzo[d]oxazol- 2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

657

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-fluoro-7- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

659

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(4,7-dimethylbenzo[d]oxazol-2- yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

661

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(S)-(4-(difluoromethyl)-2-(pyrimidin-2-yl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

663

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-fluoro-5- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

665

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)(5-(1-methyl-1H- pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

667

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(S)-(4-(difluoromethyl)-2-(pyrimidin-2-yl)oxazol- 5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

669

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(2-(1-methyl- 1H-pyrazol-4-yl)-4-(trifluoromethyl)oxazol-5- yl)methanone

671

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(5- (trifluoromethoxy)pyridin-2-yl)-1,3,4-oxadiazol-2- yl)methanone

673

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

676

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(S)-(4-(difluoromethyl)-2-(4-fluoropiperidin-1- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

677

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(S)-(5-(5-methoxypyridin-2-yl)-1,3,4-oxadiazol-2- yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

679

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(S)-(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl) (4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

681

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)(4-(6-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

683

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-methyl-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)methanone

685

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(S)-(1-methyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

687

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-5- yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

689

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(S)-(4-(difluoromethyl)-2-(1- hydroxycyclobutyl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

692

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-5- yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

693

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(S)-(4-(difluoromethyl)-2-(pyrazin-2-yl)oxazol-5- yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

695

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

697

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(S)-(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-methyl-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)methanone

699

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(S)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(6-(4- hydroxypiperidin-1-yl)pyrazolo[1,5-a]pyridin-3- yl)methanone

701

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(S)-(6-(4-hydroxypiperidin-1-yl)pyrazolo[1,5- a]pyridin-3-yl)(4-(4-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

703

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)(4-(6-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

705

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-isopropyl-1H- 1,2,4-triazol-5-yl)methanone

707

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-isopropyl- 1H-1,2,4-triazol-5-yl)methanone

710

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(S)-(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1- (trifluoromethyl)-1H-pyrazol-5-yl)methanone

711

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1-methyl-1H- pyrazol-5-yl)methanone

713

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)(2-(2-hydroxypropan- 2-yl)oxazol-5-yl)methanone

715

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5-fluoro-7- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

718

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-fluoro- 7-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

719

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(5-fluoro-4- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)- yl)methanone

722

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-fluoro- 4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

723

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(S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-(4-fluoro-7- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)- yl)methanone

725

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1- cyclopropyl-1H-pyrazol-5-yl)methanone

727

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(S)-(1-cyclopropyl-1H-pyrazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

729

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)(1-(pyridin-2-yl)-1H- pyrazol-5-yl)methanone

731

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)- yl)(3-(difluoromethyl)- 1-methyl-1H-pyrazol-5-yl)methanone

733

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(S)-(3-(difluoromethyl)-1-methyl- 1H-pyrazol-5-yl)(4-(7-fluorobenzo[d] oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

735

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(S)-(3-(difluoromethyl)-1-methyl- 1H-pyrazol-5-yl)(4-(7-fluorobenzo[d] oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

737

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(S)-(4-(difluoromethyl)-2-(pyridin- 2-yl)oxazol-5-yl)(4-(5-methylbenzo[d] oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

740

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c] pyridin-5(4H)-yl)(4-(difluoromethyl)- 2-(pyridin-2-yl)oxazol-5-yl)methanone

742

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(S)-(4-(difluoromethyl)-2- (pyrimidin-5-yl)oxazol-5- yl)(4-(7-fluorobenzo[d]oxazol- 2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)- yl)methanone

743

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4- (4-fluoro-7-methylbenzo[d] oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

745

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(S)-(1-methyl-1H-1,2,4-triazol-5- yl)(4-(5-methylbenzo[d]oxazol- 2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)- yl)methanone

747

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(S)-(1-methyl-1H-pyrazol-5-yl)(4-(7- methylbenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

749

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(S)-(4-(7-methoxybenzo[d] oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin- 5(4H)-yl)(1-methyl-1H- pyrazol-5-yl)methanone

752

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)(1-isopropyl-1H- pyrazol-5-yl)methanone

753

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(S)-(2-(tert-butyl)-4-(difluoromethyl)oxazol-5- yl)(4-(5-fluorobenzo[d]oxazol-2- yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

755

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol- 3-yl)oxazol-5-yl)(4-(5-methylbenzo[d] oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)- yl)methanone

758

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol- 5-yl)oxazol-5-yl)(4-(5-methylbenzo[d]oxazol- 2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

760

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(1-methyl-1H- pyrazol-4-yl)oxazol-5-yl)methanone

761

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(1-methyl-1H-pyrazol-3-yl) oxazol-5-yl)methanone

764

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (difluoromethyl)-2-(1-methyl-1H-imidazol- 5-yl)oxazol-5-yl)methanone

765

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(S)-(1-isopropyl-1H-pyrazol-5-yl)(4-(7- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

767

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(S)-(1-cyclopropyl-1H-pyrazol-5-yl)(4-(7- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

769

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(S)-(1,3-dimethyl-1H-pyrazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

771

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-4- yl)oxazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

773

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(S)-(4-(difluoromethyl)-2-(pyrimidin-4-yl)oxazol- 5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

775

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(S)-(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1- methyl-1H-1,2,4-triazol-5-yl)methanone

777

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(S)-(3-(difluoromethyl)-1-methyl-1H-pyrazol-5- yl)(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

779

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(1,3-dimethyl-1H- pyrazol-5-yl)methanone

781

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(S)-(1,3-dimethyl-1H-pyrazol-5-yl)(4-(7- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

784

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol- 4-yl)oxazol-5-yl)(4-(5-methylbenzo[d]oxazol-2- yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

786

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-(difluoromethyl)- 2-(1-methyl-1H-imidazol-4-yl)oxazol-5- yl)methanone

787

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(2-(1-methyl- 1H-pyrazol-3-yl)-4-(trifluoromethyl)oxazol-5- yl)methanone

790

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(2-(1-methyl- 1H-imidazol-4-yl)-4-(trifluoromethyl)oxazol-5- yl)methanone

791

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(2-(1-methyl- 1H-imidazol-5-yl)-4-(trifluoromethyl)oxazol-5- yl)methanone

793

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyloxazol- 5-yl)methanone

795

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

797

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(4- (trifluoromethyl)oxazol-5-yl)methanone

800

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5- (3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2- yl)methanone

801

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1- (difluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol- 2-yl)methanone

803

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(4-(difluoromethyl)oxazol-5-yl)((4S)-4-(7- fluorobenzo[d]oxazol-2-yl)-7-methyl-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone Diastereomer #1 (Rt = 0.949 min)

804

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(4-(difluoromethyl)oxazol-5-yl)((4S)-4-(7- fluorobenzo[d]oxazol-2-yl)-7-methyl-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone Diastereomer #1 (Rt = 1.175 min)

807

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyloxazol- 5-yl)methanone

811

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(S)-(5-(1-cyclobutyl-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)(4-(4,7-difluorobenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

813

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(S)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5- yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

817

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- imidazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

819

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(S)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(4- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

821

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(S)-(1,3-dimethyl-1H-pyrazol-5-yl)(4-(7- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

824

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(S)-(4-(difluoromethyl)-2-(1-hydroxy-2- methylpropan-2-yl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

825

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-methyl-2- (1-methyl-1H-pyrazol-3-yl)oxazol-5-yl) methanone

827

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(S)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(4- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

830

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(S)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)(4-(7-(trifluoromethyl) benzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

832

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(S)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)(4-(7-(trifluoromethyl) benzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

833

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(3- fluoropyridin-2- yl)-1,3,4-oxadiazol-2-yl)methanone

835

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)- yl)(1-(2,2-difluoroethyl)-1H- pyrazol-5-yl)methanone

838

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(S)-(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl) (4-(7-(trifluoromethyl)benzo[d]oxazol- 2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

840

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(S)-(5-(3-fluoropyridin-2-yl)-1,3,4- oxadiazol-2-yl)(4-(7-(trifluoromethyl) benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

841

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1- (difluoromethyl)-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)methanone

843

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-methyl-1H- pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

846

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1- (difluoromethyl)-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)methanone

847

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(S)-(1-(2,2-difluoroethyl)-1H-pyrazol-5-yl)(4- (7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

850

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(S)-(1-(2,2-difluoroethyl)-1H-pyrazol-5-yl)(4- (4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

852

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(S)-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)(4-(4,7- difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

854

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)- 1,3,4-oxadiazol-2-yl)(4-(7- (trifluoromethyl)benzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

855

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(S)-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)(4-(4,7- difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

858

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(S)-(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol- 2-yl)(4-(7-methylbenzo[d]oxazol-2- yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

860

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)(4-(7-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

862

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

863

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(S)-(4-(2,2-difluoroethyl)oxazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

865

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(S)-(4-(2,2-difluoroethyl)oxazol-5-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

868

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(S)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol- 2-yl)methanone

869

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(S)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4- oxadiazol-2-yl)(4-(7-methylbenzo[d] oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5- c]pyridin-5(4H)-yl)methanone

872

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)- 1,3,4-oxadiazol-2-yl)(4-(7-methylbenzo[d] oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5- c]pyridin-5(4H)-yl)methanone

873

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(S)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-(2,2- difluoroethyl)oxazol-5-yl)methanone

875

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(S)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)- 1,3,4-oxadiazol-2-yl)(4-(7-fluorobenzo[d] oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5- c]pyridin-5(4H)-yl)methanone

877

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(S)-(6-(methoxymethyl)pyrazolo[1,5-a]pyridin- 3-yl)(4-(5-methylbenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

879

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)(1-(pyridin-2-yl)-1H- pyrazol-4-yl)methanone

881

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(S)-(5-(1,3-dimethyl-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-2- yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)methanone

884

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(6- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

885

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(S)-(4-ethyl-4H-1,2,4-triazol-3-yl)(4-(5- fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

887

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(S)-1-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)- 3-(oxazol-2-yl)propan-1-one

890

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(4,7- dimethylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

892

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(S)-(4-(difluoromethyl)-2-(1-methyl-1H- imidazol-4-yl)oxazol-5-yl)(4-(7- fluorobenzo[d]oxazol-2-yl)- 1,4,6,7-tetrahydro-5H-imidazo [4,5-c]pyridin-5-yl)methanone

893

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(S)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)(2-(2-hydroxypropan- 2-yl)oxazol-5-yl)methanone

895

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(S)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)- 6,7-dihydro-1H-imidazo[4,5-c]pyridin- 5(4H)-yl)(6-(4-hydroxypiperidin-1- yl)pyrazolo[1,5-a]pyridin-3- yl)methanone

898

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-(7- fluoro-4-methylbenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)methanone

899

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4-deuterium- 4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

901

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(S)-(1-methyl-1H-1,2,4-triazol-5-yl)(4-(4- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

903

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(S)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7- dihydro-1H-imidazo[4,5-c]pyridin-5(4H)- yl)(1-methyl-1H-1,2,4-triazol-5-yl)methanone

905

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(S)-(4-(deuterium)-2-(2-hydroxypropan-2- yl)oxazol-5-yl)(4-fluoro-4-(5-fluorobenzo[d] oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c] pyridin-5(4H)-yl)methanone

907

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(S)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(7- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

909

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(S)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(7- methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

911

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(S)-(4-(difluoromethyl)oxazol-5-yl)(4′-(7- fluorobenzo[d]oxazol-2-yl)spiro[cyclopropane- 1,7′-imidazo[4,5-c]pyridin]-5′(1′H,4′H,6′H)-yl) methanone

913

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(S)-1-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)-3-(thiazol-2- yl)propan-1-one

915

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(2- (trifluoromethyl)pyrazolo[1,5-a]pyridin-3- yl)methanone

917

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(S)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro- 1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-(oxazol-5- yl)cyclopropyl)methanone

919

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(S)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(7- methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H- imidazo[4,5-c]pyridin-5(4H)-yl)methanone

In some embodiments, the disclosure provides specific examples of Formula I, and their pharmaceutically acceptable salts and/or isotopologues, as set forth in Table 1R below.

TABLE 1R

Benzo[d]oxazoles

Ex.

#
Name

2
(R)-(5-chlorothiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-

imidazo[4,5-c]pyridin-5(4H)-yl)methanone

4
(R)-1-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)-2-cyclopropylethanone

6
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(pyridin-2-yl)thiazol-5-yl)methanone

8
(R)-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(pyridin-2-yl)oxazol-5-yl)methanone

10
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(1-methyl-1H-pyrazol-4-yl)thiazol-5-yl)methanone

12
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(pyridin-2-yl)oxazol-5-yl)methanone

14
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-fluoropropan-2-yl)oxazol-5-yl)methanone

16
(R)-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

18
(R)-(2-(tert-butyl)thiazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-

imidazo[4,5-c]pyridin-5(4H)-yl)methanone

20
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-methylpyrazolo[1,5-a]pyridin-3-yl)methanone

22
(R)-(2-(tert-butyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-

imidazo[4,5-c]pyridin-5(4H)-yl)methanone

24
((R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

26
(R)-(5-(2,6-difluorophenyl)-1,3,4-oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

28
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)methanone

30
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(methoxymethyl)pyrazolo[1,5-a]pyridin-3-yl)methanone

32
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-methyl-2-(pyridin-2-yl)oxazol-5-yl)methanone

34
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(5-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

36
(R)-(2-(1,1-difluoroethyl)thiazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

38
(R)-2-cyclopropyl-1-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-

c]pyridin-5(4H)-yl)ethanone

40
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

42
(R)-(4-cyclopropyloxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-

imidazo[4,5-c]pyridin-5(4H)-yl)methanone

44
(R)-(4-cyclopropyl-2-(pyridin-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

46
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

48
(R)-(6-(2-(dimethylamino)ethyl)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

50
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(pyridin-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

52
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

54
(R)-(2-cyclopropyl-4-(difluoromethyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

56
(R)-1-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)-2-(1-hydroxycyclobutyl)ethanone

58
(R)-(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

60
(R)-1-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)-2-(3-fluorocyclobutyl)ethanone

62
((S)-2,2-difluorocyclopropyl)((R)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-

imidazo[4,5-c]pyridin-5(4H)-yl)methanone

64
(R)-(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

66
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

68
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

70
(R)-(6-bromopyrazolo[1,5-a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

72
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

74
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-methoxypyrazolo[1,5-a]pyridin-3-yl)methanone

76
(R)-(5-(3,4-difluorophenyl)-1,3,4-oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

78
(R)-(5-(4-fluoro-2-methylphenyl)-1,3,4-oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

80
(R)-(5-chloro-6-(2-(dimethylamino)ethyl)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

82
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(pyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

83
(R)-(5-(2,4-difluorophenyl)-1,3,4-oxadiazol-2-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

86
(R)-(4-(difluoromethyl)-2-(pyridin-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

87
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-4-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

89
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)methanone

92
(R)-(6-(dimethylamino)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

94
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

96
(R)-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

98
(R)-(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

100
(R)-(5-(5-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

102
(R)-(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

104
(R)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(6-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

105
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

108
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

109
(R)-(4-(difluoromethyl)-2-(methoxymethyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

112
(R)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

114
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

116
(R)-(4-(difluoromethyl)-2-((trifluoromethoxy)methyl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

117
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-

yl)methanone

120
(R)-(5-(1,4-dimethyl-1H-pyrazol-5-yl)-1,3,4-oxadiazol-2-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

121
[(4R)-4-(5-fluoro-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-

yl]-[5-[4-(trifluoromethyl)-2-pyridyl]-1,3,4-oxadiazol-2-yl]methanone

123
(R)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

125
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(5-methylpyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

128
(R)-(3-chloro-1-methyl-1H-pyrazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

130
(R)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

132
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-1H-pyrazol-5-yl)-1,3,4-oxadiazol-2-yl)methanone

134
(R)-(6-(4-cyclopropylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

136
((R)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-((R)-1-hydroxyethyl)-4-methyloxazol-5-yl)methanone

138
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

140
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(3,3,4-trimethylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

142
(R)-(4-(difluoromethyl)-2-(1-hydroxycyclopropyl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

144
(R)-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

146
(R)-(4-(6-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)oxazol-5-yl)methanone

148
(R)-(4-(5-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

150
(R)-(4-(5-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)oxazol-5-yl)methanone

152
(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

154
(R)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

156
(R)-(4-(difluoromethyl)-2-((methoxy-d3)methyl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-

yl)methanone

158
(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

160
(R)-2-(4-(difluoromethyl)-5-(4-(5-fluorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-

1H-imidazo[4,5-c]pyridine-5-carbonyl)oxazol-2-yl)-2-methylpropanenitrile

162
(R)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

164
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

166
(R)-(6-bromo-5-chloropyrazolo[1,5-a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

168
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

170
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

172
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

174
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

176
(R)-(5-chloro-6-morpholinopyrazolo[1,5-a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

178
(R)-(6-amino-5-chloropyrazolo[1,5-a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

180
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(fluoromethyl)oxazol-5-yl)methanone

182
(R)-(5-chloro-6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

184
(R)-(5-(difluoromethyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

186
(R)-2-(5-(4-(5-fluorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-

c]pyridine-5-carbonyl)-4-methyloxazol-2-yl)-2-methylpropanenitrile

188
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(6-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

190
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

192
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

194
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

196
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

198
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

200
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

202
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

204
(R)-(5-chloro-6-((dimethylamino)methyl)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanonee

206
(R)-(5-chloro-6-(methylamino)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

208
(R)-(5-chloro-6-(dimethylamino)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

209
((R)-4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-((R)-1-hydroxyethyl)-4-methyloxazol-5-yl)methanone

212
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(fluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

213
(R)-(4-(difluoromethyl)-2-(1-hydroxycyclopropyl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

216
(R)-(4-(difluoromethyl)-2-(1-hydroxycyclopropyl)oxazol-5-yl)(4-(4-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

218
((R)-4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-((R)-1-hydroxyethyl)-4-methyloxazol-5-yl)methanone

220
(R)-(5-chloro-6-fluoropyrazolo[1,5-a]pyridin-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

222
(R)-(4-(difluoromethyl)-2-(2-(methylamino)propan-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

223
(4-bromo-2-(1-hydroxyethyl)oxazol-5-yl)((R)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

Diastereomer #1 (Rt = 5.902 min)

224
(4-bromo-2-(1-hydroxyethyl)oxazol-5-yl)((R)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

Diastereomer #2 (Rt = 6.092 min)

228
(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(4-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

230
(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(4-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

232
(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(6-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

233
(4-chloro-2-(1-hydroxyethyl)oxazol-5-yl)((R)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

Diastereomer #1 (Rt-5.433 min)

234
(4-chloro-2-(1-hydroxyethyl)oxazol-5-yl)((R)-4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

Diastereomer #2 (Rt-5.625 min)

238
(R)-(4-(difluoromethyl)-2-(1-hydroxycyclopropyl)oxazol-5-yl)(4-(6-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

240
(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(6-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

242
((R)-4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-((S)-1-hydroxyethyl)-4-methyloxazol-5-yl)methanone

244
(4-(difluoromethyl)-2-((S)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

246
(4-(difluoromethyl)-2-((R)-1-hydroxyethyl)oxazol-5-yl)((R)-4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

248
((R)-4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-((S)-1-hydroxyethyl)-4-methyloxazol-5-yl)methanone

250
(R)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(6-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

251
(R)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

254
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

256
(R)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

258
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

260
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)-4-methyloxazol-5-yl)methanone

262
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-(trifluoromethyl)-1H-pyrazol-5-yl)methanone

264
(R)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

266
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(methoxymethyl)pyrazolo[1,5-a]pyridin-3-yl)methanone

267
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)-4-methyloxazol-5-yl)methanone

270
(R)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(6-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

271
(R)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

273
(R)-(4-chloro-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

276
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(methoxymethyl)pyrazolo[1,5-a]pyridin-3-yl)methanone

278
(R)-(3-chloro-1-methyl-1H-1,2,4-triazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

280
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-methyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)methanone

282
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(oxazol-5-yl)methanone

284
(R)-(3-chloro-1-methyl-1H-1,2,4-triazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

286
(R)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)(4-(7-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

288
(R)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-(trifluoromethyl)-1H-pyrazol-5-yl)methanone

290
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-(trifluoromethyl)-1H-pyrazol-5-yl)methanone

292
(R)-(4-(difluoromethyl)-2-(2-(dimethylamino)propan-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

294
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-(trifluoromethyl)-1H-pyrazol-5-yl)methanone

296
(R)-(4-(5,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

298
(R)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

300
(R)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

302
(R)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

304
(R)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

306
(R)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

308
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

310
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

312
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

314
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

316
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(6-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

318
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

320
(R)-(2-(2-hydroxypropan-2-yl)-4-methyloxazol-5-yl)(4-(6-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

322
(R)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

324
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-methylpyrazolo[1,5-a]pyridin-3-yl)methanone

326
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-methoxypyrazolo[1,5-a]pyridin-3-yl)methanone

328
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-

(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

330
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

332
(R)-(2-(2-hydroxypropan-2-yl)-4-methyloxazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

334
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

336
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

338
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

340
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

342
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

344
(R)-(3-chloro-1-methyl-1H-1,2,4-triazol-5-yl)(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

346
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

348
(R)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

349
(R)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

352
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-

(trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

353
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-(trifluoromethoxy)benzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

356
(R)-(5-(1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

358
(R)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(6-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

360
(R)-(5-(1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(6-methylbenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

362
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

364
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

366
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-morpholinopyrazolo[1,5-a]pyridin-3-yl)methanone

367
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)pyrazolo[1,5-a]pyridin-3-

yl)methanone

370
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-fluoropiperidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

372
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-hydroxypiperidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

374
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

376
(R)-(4-(5-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

377
(R)-(4-(5-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)oxazol-5-yl)methanone

380
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-

5-yl)(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

381
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

384
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

386
1-[(4R)-4-(7-fluoro-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-

yl]-3-thiazol-2-yl-propan-1-one

388
(R)-1-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)-3-(oxazol-2-yl)propan-1-one

390
(R)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

391
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

394
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

396
(R)-(6-(6-azaspiro[2.5]octan-6-yl)pyrazolo[1,5-a]pyridin-3-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

398
(R)-1-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)-3-(thiazol-2-yl)propan-1-one

400
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(pyridin-3-yl)-1,3,4-oxadiazol-2-yl)methanone

402
(R)-(4-(difluoromethyl)-2-(4-fluoropiperidin-1-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

404
(R)-(4-(difluoromethyl)-2-(4-methylpiperazin-1-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

405
(R)-(4-(difluoromethyl)-2-(pyrimidin-5-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

408
(R)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

410
(R)-1-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)-3-(thiazol-5-yl)propan-1-one

412
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-3-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

414
(R)-(4-(difluoromethyl)-2-morpholinooxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

416
[(4R)-4-(5-bromo-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-

yl]-[4-(difluoromethyl)-2-(1-hydroxy-1-methyl-ethyl)oxazol-5-yl]methanone

417
(R)-(4-(difluoromethyl)-2-(5-fluoropyridin-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

419
(R)-(4-(difluoromethyl)-2-(pyridin-3-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

422
(R)-(4-(difluoromethyl)-2-(pyridin-4-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

424
(R)-(4-(7-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

426
(R)-(4-(7-chlorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)oxazol-5-yl)methanone

428
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

430
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

432
(R)-(4-(4-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

434
(R)-(4-(4-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)oxazol-5-yl)methanone

436
[(4R)-4-(4-chloro-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-

yl]-[4-(difluoromethyl)-2-(1-hydroxy-1-methyl-ethyl)oxazol-5-yl]methanone

438
[(4R)-4-(4-chloro-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-

yl]-[4-(difluoromethyl)oxazol-5-yl]methanone

440
(R)-(4-bromo-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(6-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

441
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(5-methoxypyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

443
(R)-(4-(difluoromethyl)-2-(5-(trifluoromethyl)pyridin-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

446
(R)-(4-(difluoromethyl)-2-(5-methoxypyridin-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

448
(R)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)(4-(4-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

450
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

452
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(pyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

454
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-

(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

456
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

458
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

459
(R)-(4-(7-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

462
(R)-(4-(7-bromobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-(difluoromethyl)oxazol-5-yl)methanone

464
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-

(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

466
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(4-(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

468
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(difluoromethyl)oxazol-5-yl)methanone

469
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

472
(R)-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

474
(R)-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

476
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

478
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-fluoropiperidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

479
(R)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(4-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

481
(R)-(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

484
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(oxazol-5-yl)methanone

485
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)methanone

488
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-(difluoromethyl)-1H-pyrazol-5-yl)methanone

490
(R)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-(difluoromethyl)-1H-pyrazol-5-yl)methanone

492
(R)-(5-(1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

494
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

496
(R)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

498
(R)-(3-cyclopropyl-1-methyl-1H-1,2,4-triazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

500
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-fluoro-5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

502
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-fluoro-5-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

503
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-morpholinopyrazolo[1,5-a]pyridin-3-yl)methanone

506
(R)-(6-(6-azaspiro[2.5]octan-6-yl)pyrazolo[1,5-a]pyridin-3-yl)(4-(4-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

508
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)pyrazolo[1,5-a]pyridin-3-

yl)methanone

510
(R)-(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(oxazol-5-yl)methanone

512
(R)-(2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

514
(R)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-(difluoromethyl)-1H-pyrazol-5-yl)methanone

516
(R)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

517
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

519
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

521
(R)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

524
(R)-(4-(4,6-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

525
(R)-(4-(difluoromethyl)-2-(pyrimidin-4-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

528
(R)-(4-(difluoromethyl)-2-(pyrazin-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

530
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-

(trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

531
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-(trifluoromethoxy)benzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

534
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-

(trifluoromethoxy)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

535
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(4-(trifluoromethoxy)benzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

538
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-methylpyrazolo[1,5-a]pyridin-3-yl)methanone

540
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-methoxypyrazolo[1,5-a]pyridin-3-yl)methanone

542
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

544
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(6-(pyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

545
(R)-(4-(6,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

548
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(oxazol-5-yl)methanone

550
(R)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)(4-(5-

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

552
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(5-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

554
(R)-(4-(5-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

556
(R)-(4-(5-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

558
(R)-(4-cyclopropyl-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

559
(R)-(4-(difluoromethyl)-2-(pyridin-4-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

562
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(3-

(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)methanone

564
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-

(difluoromethyl)-1H-pyrazol-5-yl)methanone

566
(R)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

568
(R)-(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

570
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-methyloxazol-5-yl)methanone

572
(R)-(4-(5-bromo-7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-

c]pyridin-5(4H)-yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-

yl)methanone

574
(R)-(4-(5-bromo-7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-

c]pyridin-5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

576
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(oxazol-5-yl)methanone

578
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)methanone

579
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

582
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-

methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

584
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-

(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

586
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(1-hydroxycyclobutyl)-4-(trifluoromethyl)oxazol-5-yl)methanone

588
(R)-(4-(difluoromethyl)-2-(pyridin-2-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

589
(R)-(4-(difluoromethyl)-2-(pyridin-3-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

592
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-3-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

593
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-methyl-2-(pyridin-2-yl)oxazol-5-yl)methanone

595
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-methyl-2-(1-methyl-1H-pyrazol-4-yl)oxazol-5-yl)methanone

598
(R)-(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-methyloxazol-5-yl)methanone

600
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-methyloxazol-5-yl)methanone

602
(R)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)(4-(4-

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

604
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

606
(R)-(4-(5-chloro-7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-

c]pyridin-5(4H)-yl)(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-

yl)methanone

607
(R)-(4-(5-chloro-7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-

c]pyridin-5(4H)-yl)(4-(difluoromethyl)oxazol-5-yl)methanone

610
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

612
(R)-(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(oxazol-5-yl)methanone

614
(R)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)(4-(7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

615
(R)-(4-(difluoromethyl)-2-(5-methoxypyridin-2-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

618
(R)-(4-(difluoromethyl)-2-(4-methylpiperazin-1-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

619
(R)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

622
(R)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(oxazol-5-yl)methanone

623
(R)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

625
(R)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

627
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

630
(R)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

631
(R)-(4-(difluoromethyl)-2-(5-fluoropyridin-2-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

634
(R)-(4-(difluoromethyl)-2-(5-(trifluoromethyl)pyridin-2-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

635
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-4-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

637
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(pyridin-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

640
(R)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

642
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-4-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

644
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(7-fluoro-5-

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

646
(R)-(4-(4,5-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

647
(R)-(4-(difluoromethyl)-2-morpholinooxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

650
(R)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(6-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

652
(R)-(4-(1,1-difluoroethyl)oxazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

654
(R)-(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

656
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-fluoro-7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

658
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-fluoro-7-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

660
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4,7-

dimethylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

662
(R)-(4-(difluoromethyl)-2-(pyrimidin-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

664
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-fluoro-5-methoxybenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

666
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

668
(R)-(4-(difluoromethyl)-2-(pyrimidin-2-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

670
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(1-methyl-1H-pyrazol-4-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

672
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(5-(trifluoromethoxy)pyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

674
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

675
(R)-(4-(difluoromethyl)-2-(4-fluoropiperidin-1-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

678
(R)-(5-(5-methoxypyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4-(5-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

680
(R)-(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4-(6-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

682
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(6-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

684
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-

methyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)methanone

686
(R)-(1-methyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)(4-(7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

688
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-5-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

690
(R)-(4-(difluoromethyl)-2-(1-hydroxycyclobutyl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

691
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-5-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

694
(R)-(4-(difluoromethyl)-2-(pyrazin-2-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

696
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

698
(R)-(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-methyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)methanone

700
(R)-(4-(5,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(6-(4-hydroxypiperidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

702
(R)-(6-(4-hydroxypiperidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)(4-(4-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

704
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(6-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

706
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-

isopropyl-1H-1,2,4-triazol-5-yl)methanone

708
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-isopropyl-1H-1,2,4-triazol-5-yl)methanone

709
(R)-(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-(trifluoromethyl)-1H-pyrazol-5-yl)methanone

712
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-

methyl-1H-pyrazol-5-yl)methanone

714
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

716
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-fluoro-7-

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

717
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-fluoro-7-methoxybenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

720
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-fluoro-4-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

72
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(5-fluoro-4-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

724
(R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(4-fluoro-7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

726
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-

cyclopropyl-1H-pyrazol-5-yl)methanone

728
(R)-(1-cyclopropyl-1H-pyrazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

730
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-(pyridin-2-yl)-1H-pyrazol-5-yl)methanone

732
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(3-

(difluoromethyl)-1-methyl-1H-pyrazol-5-yl)methanone

734
(R)-(3-(difluoromethyl)-1-methyl-1H-pyrazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

736
(R)-(3-(difluoromethyl)-1-methyl-1H-pyrazol-5-yl)(4-(7-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

738
(R)-(4-(difluoromethyl)-2-(pyridin-2-yl)oxazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

739
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(difluoromethyl)-2-(pyridin-2-yl)oxazol-5-yl)methanone

741
(R)-(4-(difluoromethyl)-2-(pyrimidin-5-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

744
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(4-fluoro-7-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

746
(R)-(1-methyl-1H-1,2,4-triazol-5-yl)(4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

748
(R)-(1-methyl-1H-pyrazol-5-yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-

imidazo[4,5-c]pyridin-5(4H)-yl)methanone

750
(R)-(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-methyl-1H-pyrazol-5-yl)methanone

751
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-

isopropyl-1H-pyrazol-5-yl)methanone

754
(R)-(2-(tert-butyl)-4-(difluoromethyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

756
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-3-yl)oxazol-5-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

757
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-5-yl)oxazol-5-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

759
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(difluoromethyl)-2-(1-methyl-1H-pyrazol-4-yl)oxazol-5-yl)methanone

762
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(difluoromethyl)-2-(1-methyl-1H-pyrazol-3-yl)oxazol-5-yl)methanone

763
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(difluoromethyl)-2-(1-methyl-1H-imidazol-5-yl)oxazol-5-yl)methanone

766
(R)-(1-isopropyl-1H-pyrazol-5-yl)(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

768
(R)-(1-cyclopropyl-1H-pyrazol-5-yl)(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

770
(R)-(1,3-dimethyl-1H-pyrazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

772
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-pyrazol-4-yl)oxazol-5-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

774
(R)-(4-(difluoromethyl)-2-(pyrimidin-4-yl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

776
(R)-(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-methyl-1H-1,2,4-triazol-5-yl)methanone

778
(R)-(3-(difluoromethyl)-1-methyl-1H-pyrazol-5-yl)(4-(7-methoxybenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

780
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1,3-

dimethyl-1H-pyrazol-5-yl)methanone

782
(R)-(1,3-dimethyl-1H-pyrazol-5-yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

783
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-4-yl)oxazol-5-yl)(4-(5-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

785
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(difluoromethyl)-2-(1-methyl-1H-imidazol-4-yl)oxazol-5-yl)methanone

788
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(1-methyl-1H-pyrazol-3-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

789
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(1-methyl-1H-imidazol-4-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

792
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(1-methyl-1H-imidazol-5-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

794
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

methyloxazol-5-yl)methanone

796
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-(trifluoromethyl)oxazol-5-yl)methanone

798
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(trifluoromethyl)oxazol-5-yl)methanone

799
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

802
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

805
(4-(difluoromethyl)oxazol-5-yl)((4R)-4-(7-fluorobenzo[d]oxazol-2-yl)-7-methyl-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

Diastereomer #2 (Rt = 1.335 min)

806
(4-(difluoromethyl)oxazol-5-yl)((4R)-4-(7-fluorobenzo[d]oxazol-2-yl)-7-methyl-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

Diastereomer #2 (Rt = 1.213 min)

808
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(4-methyloxazol-5-yl)methanone

809
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(2-fluoropropan-2-yl)-1,3,4-oxadiazol-2-yl)methanone

810
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(2-fluoropropan-2-yl)-1,3,4-oxadiazol-2-yl)methanone

812
(R)-(5-(1-cyclobutyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(4,7-

difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

814
(R)-(3-(difluoromethyl)-1-methyl-1H-1,2,4-triazol-5-yl)(4-(4-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

815
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

816
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

818
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(5-(1-methyl-1H-imidazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

820
(R)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

822
(R)-(1,3-dimethyl-1H-pyrazol-5-yl)(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

823
(R)-(4-(difluoromethyl)-2-(1-hydroxy-2-methylpropan-2-yl)oxazol-5-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

826
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(4-methyl-2-(1-methyl-1H-pyrazol-3-yl)oxazol-5-yl)methanone

828
(R)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

829
(R)-(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

831
(R)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

834
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(3-

fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

836
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(1-

(2,2-difluoroethyl)-1H-pyrazol-5-yl)methanone

837
(R)-(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4-(7-(trifluoromethyl)benzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

839
(R)-(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

842
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-

(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)methanone

844
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-

methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

845
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(5-(1-

(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)methanone

848
(R)-(1-(2,2-difluoroethyl)-1H-pyrazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

849
(R)-(1-(2,2-difluoroethyl)-1H-pyrazol-5-yl)(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

851
(R)-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

853
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

(trifluoromethyl)benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)methanone

856
(R)-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

857
(R)-(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)(4-(7-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

859
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

861
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

864
(R)-(4-(2,2-difluoroethyl)oxazol-5-yl)(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

866
(R)-(4-(2,2-difluoroethyl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

867
(R)-(4-(7-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazol-2-yl)methanone

870
(R)-(5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

871
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

874
(R)-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)(4-

(2,2-difluoroethyl)oxazol-5-yl)methanone

876
(R)-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

878
(R)-(6-(methoxymethyl)pyrazolo[1,5-a]pyridin-3-yl)(4-(5-methylbenzo[d]oxazol-2-

yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

880
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-(pyridin-2-yl)-1H-pyrazol-4-yl)methanone

882
(R)-(5-(1,3-dimethyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)(4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

883
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

886
(R)-(4-ethyl-4H-1,2,4-triazol-3-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

888
(R)-1-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)-3-(oxazol-2-yl)propan-1-one

889
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(4,7-dimethylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

891
(R)-(4-(difluoromethyl)-2-(1-methyl-1H-imidazol-4-yl)oxazol-5-yl)(4-(7-

fluorobenzo[d]oxazol-2-yl)-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-

yl)methanone

894
(R)-(4-(4-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(2-hydroxypropan-2-yl)oxazol-5-yl)methanone

896
(R)-(4-(4,7-difluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(6-(4-hydroxypiperidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)methanone

897
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-(7-fluoro-4-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

900
(R)-(4-(difluoromethyl)oxazol-5-yl)(4-deuterium-4-(7-fluorobenzo[d]oxazol-2-yl)-

6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

902
(R)-(1-methyl-1H-1,2,4-triazol-5-yl)(4-(4-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-

1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

904
(R)-(4-(4-methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-

5(4H)-yl)(1-methyl-1H-1,2,4-triazol-5-yl)methanone

906
(R)-(4-(deuterium)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-fluoro-4-(5-

fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

908
(R)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

910
(R)-(1,3-dimethyl-1H-1,2,4-triazol-5-yl)(4-(7-methoxybenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

912
(R)-(4-(difluoromethyl)oxazol-5-yl)(4′-(7-fluorobenzo[d]oxazol-2-

yl)spiro[cyclopropane-1,7′-imidazo[4,5-c]pyridin]-5′(1′H,4′H,6′H)-yl)methanone

914
(R)-1-(4-(benzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)-3-

(thiazol-2-yl)propan-1-one

916
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl)methanone

918
(R)-(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)(1-(oxazol-5-yl)cyclopropyl)methanone

920
(R)-(1-(difluoromethyl)-1H-pyrazol-5-yl)(4-(7-methylbenzo[d]oxazol-2-yl)-6,7-

dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

In some embodiments, the disclosure provides specific examples of Formula I, and their pharmaceutically acceptable salts and/or isotopologues, as set forth in Table 2 below.

TABLE 2

Ex. #
Structure
Name

921

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-(difluoromethyl)oxazol-5- yl)methanone

922

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-(difluoromethyl)oxazol-5- yl)methanone

923

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-methyl-1H-pyrazol-5-yl)methanone

924

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-methyl-1H-pyrazol-5-yl)methanone

925

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(oxazol-5-yl)methanone

926

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(oxazol-5-yl)methanone

927

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(pyridin-3-yl)methanone

928

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(pyridin-3-yl)methanone

929

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(pyrazolo[1,5-a]pyridin-3-yl)methanone

930

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(pyrazolo[1,5-a]pyridin-3-yl)methanone

931

embedded image

(S)-2,2′-(4,6-dihydropyrrolo[3,4-d]imidazole-4,5(1H)- diyl)bis(benzo[d]oxazole)

932

embedded image

(R)-2,2′-(4,6-dihydropyrrolo[3,4-d]imidazole-4,5(1H)- diyl)bis(benzo[d]oxazole)

933

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(pyridin-4-yl)methanone

934

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(pyridin-4-yl)methanone

935

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)methanone

936

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(5-(1-methyl-1H-pyrazol-4-yl)-1,3,4- oxadiazol-2-yl)methanone

937

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2- yl)methanone

938

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(5-(pyridin-2-yl)-1,3,4-oxadiazol-2- yl)methanone

939

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-methyl-1H-1,2,4-triazol-5- yl)methanone

940

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-methyl-1H-1,2,4-triazol-5- yl)methanone

941

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-methyloxazol-5-yl)methanone

942

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-methyloxazol-5-yl)methanone

943

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-(trifluoromethyl)oxazol-5- yl)methanone

944

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-(trifluoromethyl)oxazol-5- yl)methanone

945

embedded image

(R)-2-(5-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)-1,4,5,6- tetrahydropyrrolo[3,4-d]imidazol-4-yl)benzo[d]oxazole

946

embedded image

(S)-2-(5-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)-1,4,5,6- tetrahydropyrrolo[3,4-d]imidazol-4-yl)benzo[d]oxazole

947

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-(difluoromethyl)-2-(2- hydroxypropan-2-yl)oxazol-5-yl)methanone

948

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(4-(difluoromethyl)-2-(2- hydroxypropan-2-yl)oxazol-5-yl)methanone

949

embedded image

(S)-2-(5-(5-(trifluoromethyl)pyrimidin-2-yl)-1,4,5,6- tetrahydropyrrolo[3,4-d]imidazol-4-yl)benzo[d]oxazole

950

embedded image

(R)-2-(5-(5-(trifluoromethyl)pyrimidin-2-yl)-1,4,5,6- tetrahydropyrrolo[3,4-d]imidazol-4-yl)benzo[d]oxazole

951

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-(difluoromethyl)-1H-pyrazol-5- yl)methanone

952

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-(difluoromethyl)-1H-pyrazol-5- yl)methanone

953

embedded image

(S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-(trifluoromethyl)-1H-pyrazol-5- yl)methanone

954

embedded image

(R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4- d]imidazol-5(1H)-yl)(1-(trifluoromethyl)-1H-pyrazol-5- yl)methanone

In further embodiments, the compound of Formula I is one or more of the compounds in Table 2 that is the S-enantiomer, or a pharmaceutically acceptable salt thereof.

In still further embodiments, the compound of Formula I is one or more of Examples 5, 23, 29, 33, 39, 47, 51, 67, 93, 107, 124, 141, 157, 161, 163, 167, 169, 171, 173, 187, 191, 193, 195, 197, 199, 201, 217, 227, 229, 231, 239, 243, 245, 247, 252, 259, 263, 269, 272, 277, 281, 283, 285, 301, 305, 309, 373, 467, 483, 486, 487, 518, 561, 563, 569, 599, and 683, or a pharmaceutically acceptable salt thereof. In yet other embodiments, the compound of Formula I is one or more of Examples 5, 23, 29, 39, 51, 67, 93, 107, 124, 141, 157, 161, 163, 167, 169, 171, 173, 187, 191, 193, 195, 197, 199, 201, 217, 227, 229, 243, 245, 247, 252, 259, 263, 269, 272, 277, 281, 283, 285, 301, 305, 309, 373, 467, 483, 486, 487, 518, 561, 563, 569, 599, and 683, or a pharmaceutically acceptable salt thereof.

In other embodiments, the compound of Formula I is a racemate of one or more of the compounds in Table 1S, or a pharmaceutically acceptable salt thereof.

Abbreviations and Terms List

aq
aqueous

min
minute(s)

hrs
hours

mL
milliliter

μL
microliter

mmol
millimole(s)

μmol
micromole(s)

mol
mole(s)

M
molar

eq
equivalents

LCMS
Liquid chromatography mass spectrometry

NMR
nuclear magnetic resonance

TLC
thin layer chromatography

HPLC
high-performance liquid chromatography

SFC
supercritical fluid chromatography

sat
saturated

° C.
degrees Celsius

rt
room temperature

N₂
nitrogen gas

Hz
Hertz

δ
chemical shift

s
singlet

d
doublet

t
triplet

q
quartet

m
multiplet

br
broad

dd
doublet of doublets

ddd
doublet of doublet or doublets

td
triplet of doublets

dt
doublet of triplets

CDCl₃
chloroform-d

CD₃OD
methanol-d₄

DMSO-d₆
dimethyl sulfoxide-d₆

Solvents and Reagents

DCE
1,2-dichloroethane

DCM
dichloromethane

DMAc
dimethylacetamide

DME
dimethoxyethane

DMF
dimethylformamide

EtOH
ethyl alcohol

EtOAc
ethyl acetate

i-PrOH or IPA
isopropanol

MeOH
methyl alcohol

MeCN or ACN
acetonitrile

NMP
1-methyl-2-pyrrolidone

PE
petroleum ether

TBME
tert-butyl methyl ether

H₂O
water

THF
tetrahydrofuran

HOAc
acetic acid

HCl
hydrochloric acid

H₂SO₄
sulfuric acid

FA
formic acid

TFA
trifluoroacetic acid

TsOH
p-toluenesulfonic acid

TosCl or TsCl
p-toluenesulfonyl chloride

NH₄Cl
ammonium chloride

KOH
Potassium hydroxide

LiOH
lithium hydroxide

K₂CO₃
potassium carbonate

Na₂CO₃
sodium carbonate

Cs₂CO₃
cesium carbonate

Na₂SO₄
sodium sulfate

NaHCO₃
sodium bicarbonate

Na₂S₂O₃
sodium thiosulfate

Et₃N or TEA
triethylamine

DIPEA
N,N-diisopropylethylamine

Py
pyridine

KOAc
potassium acetate

KF
potassium fluoride

CsF
cesium fluoride

TBAF
tetrabutylammonium fluoride

NH₃
ammonia

LDA
lithium diisopropylamine

t-BuLi
tert-butyllithium

n-BuLi
n-butyllithium

LiHMDS
lithium bis(trimethylsilyl)amide

MeMgBr
methylmagnesium bromide

iPrMgCl•LiCl
isopropylmagnesium chloride lithium

chloride complex

PFIB
perfluoroisobutene

BuOK
potassium t-butoxide

CAN
cerium ammonium nitrate

DIBAL-H
diisobutylaluminium hydride

NaOMe
sodium methoxide

NaH
sodium hydride

DMP
Dess-Martin periodinane

MnO₂
manganese(IV) oxide

IBX
2-iodoxybenzoic acid

t-BuONO
tert-butyl nitrite

PIDA
(diacetoxyiodo)benzene

NFSI
N-fluorodi(benzenesulfonyl)amine

NBS
N-bromosuccinimide

NCS
N-chlorosuccinimide

MeI
methyl iodide

LiBH₄
lithium borohydride

NaBH₄
sodium borohydride

NaBH(OAc)₃
Sodium triacetoxyborohydride

EDCI
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

HOBt
1-hydroxybenzotriazole

HATU
1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-

b]pyridinium 3-oxid hexafluorophosphate

T3P
Propanephosphonic acid anhydride

CDI
carbonyldiimidazole

Thio-CDI
1,1′-Thiocarbonyldiimidazole

DPPA
diphenylphosphoryl azide

BCl₃
boron trichloride

Boc₂O
di-tert-butyl dicarbonate

DHP
Dihydropyran

Pd/C
palladium on carbon

Pd(PPh₃)₂Cl₂
bis(triphenylphosphine)palladium(II) dichloride

Pd₂(dba)₃
tris(dibenzylideneacetone)dipalladium

Pd(dppf)Cl₂
(1,1′-Bis(diphenylphosphino)ferrocene)palladium(II)

dichloride

Pd(OAc)₂
palladium(II) acetate

Xantphos
4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene

t-BuXPhos-
[(2-Di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-

Pd-G3
biphenyl)-2-(2′-amino-1,1′-biphenyl)] palladium(II)

methanesulfonate

CPhos-Pd-G3
[(2-Dicyclohexylphosphine-2′,6′-bis(N,N-

dimethylamino)-1,1′-biphenyl)-2-(2′-amino-1,1′-

biphenyl)] palladium(II) methanesulfonate

PPh₃
triphenylphosphine

DEAD
diethyl azodicarboxylate

DIAD
diisopropyl azodicarboxylate

Pin₂B₂
bis(pinacolato)diborane

CuI
copper iodide

CuBr₂
copper (II) bromide

Zn(CN)₂
zinc cyanide

H₂
hydrogen gas

SiO₂
silica

TFAA
Trifluoroacetic anhydride

K₂OsO₄•2H₂O
potassium osmate(VI) dihydrate

NaIO₄
sodium periodate

General Experimental

In the following examples, the reagents and solvents were purchased from commercial sources (such as Alfa, Acros, AstaTech, CombiBlocks, Enamine, Sigma Aldrich, TCI, PharmaBock, Bide Pharmatech Ltd., Accela ChemBio, Aladdin, Shanghai Haohong Pharmaceutical Co., Ltd, Amkchem, Beijing Ouhe Technology Co., Ltd, Haoyuan Chemexpress Co., Ltd, Hualun, Coolpharm, Scochem, Titan and WuXi LabNetwork, and used without further purification unless otherwise specified. Flash chromatography was performed on a CombiFlashRf 150 (ISCO) via column with silica gel particles of 200-300 mesh. HPLC was performed on an Agilent 1100 Liquid Chromatography (Agilent, USA) and a Shimadzu LC 20/20A (Shimadzu, Japan). Supercritical fluid chromatography was performed on a Waters Prep SFC 150 AP/80Q/200/350 system (Waters, USA). Analytical and preparative thin layer chromatography plates (TLC) were HSGF 254 (0.15-0.2 mm thickness, Shanghai Anbang Company, China). Nuclear magnetic resonance (NMR) spectra were obtained on a Brucker AV-400 NMR (Bruker, Switzerland). Chemical shifts were reported in parts per million (ppm, 6) downfield from tetramethylsilane. Mass spectra were given with electrospray ionization (ESI) from a Waters LCT TOF Mass Spectrometer (Waters, USA). LC-MS was performed on an Agilent Prime-6125B/Agilent LC1260-MS6150/Agilent LC1260-MS6125B/Agilent LC1200-MS6110 (Agilent, USA) and a Shimadzu LC20-MS2020. Microwave reactions were run on an Initiator 2.5 Microwave Synthesizer (Biotage, Sweden).

Intermediate (1-(1H-imidazol-5-yl)cyclopropyl)methanamine hydrochloride

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Step 1: Preparation of 2-(3-tritylimidazol-4-yl)acetonitrile (B2)

B2 was prepared starting with 2-(1H-imidazol-5-yl)acetonitrile (B1) in accordance with literature procedures. See, e.g., WO2008/003766 (page 19).

Step 2: Preparation of 1-(3-tritylimidazol-4-yl)cyclopropanecarbonitrile (B3)

To a solution of 2-(3-tritylimidazol-4-yl)acetonitrile (B2) (10 g, 28.6 mmol) in THF (200 mL) was added LDA (2 M, 42.9 mL, 3 eq) dropwise at −78° C. After addition was complete, the reaction mixture was stirred at −20° C. to −10° C. for 1 hr. The reaction mixture was then cooled to −78° C., and 1,2-dibromoethane (10.75 g, 57.2 mmol, 4.32 mL, 2 eq) was added dropwise at −78° C. After the addition was complete, the reaction mixture was warmed to rt slowly and stirred for another 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). The reaction mixture was quenched with sat. NH₄Cl solution (200 mL) and stirred at rt for 0.5 hr. The aqueous portion was extracted with EtOAc (100 mL×3), and the combined organic layers were dried over Na₂SO₄, filtered, and concentrated to dryness. The residue (combined with two other reactions performed using 10 g of B2) was purified by flash silica gel chromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, eluent of 0-40% EtOAc/PE, gradient @40 mL/min) to give B3 (23.4 g, 72% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.30-7.52 (m, 10H), 7.09 (dd, 6H), 6.84 (d, 1H), 1.51-1.66 (m, 2H), 1.29-1.46 (m, 2H).

Step 3: Preparation of 1-(3-tritylimidazol-4-yl)cyclopropyl]methanamine (B4)

A mixture of 1-(3-tritylimidazol-4-yl)cyclopropanecarbonitrile (B3) (19 g, 50.6 mmol), Raney-Ni (4.60 g, 53.7 mmol, 1.06 eq), NH₃·H₂O (591 mg, 5.06 mmol, 650 μL, 30% purity, 0.1 eq) in MeOH (200 mL) was degassed and purged with H₂3 times, and then the reaction mixture was stirred at 45° C. for 16 hrs under H₂(45 psi) atmosphere. Reaction progress was tracked using TLC (DCM:MeOH=10:1). The reaction mixture was filtered, and additional Raney-Ni (4.60 g, 53.7 mmol, 1.06 eq) was added. The reaction mixture was stirred at 45° C. under H₂(45 psi) atmosphere for another 24 hrs. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated to dryness to give B4 (18 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 7.33-7.44 (m, 9H), 7.18-7.25 (m, 1H), 7.04-7.13 (m, 6H), 6.64-6.71 (m, 1H), 3.17 (br s, 2H), 2.58-2.74 (m, 2H), 0.60-0.82 (m, 4H).

Step 4: Preparation of [1-(1H-imidazol-5-yl)cyclopropyl]methanamine hydrochloride (B5)

To a solution of [1-(3-tritylimidazol-4-yl)cyclopropyl]methanamine (B4) (18 g, 47.4 mmol) in MeOH (100 mL) was added HCl/MeOH (4 M, 100 mL, 8.4 eq). The reaction mixture was stirred at 60° C. for 16 hrs. Reaction progress was tracked using LC-MS.

The reaction mixture was concentrated to dryness, and the residue was triturated with EtOAc (40 mL) and stirred for 15 min. The precipitate was collected by filtration and then dried in vacuo to give B5 (8.5 g, 2HCl salt). ¹H NMR (400 MHz, DMSO-d₆) δ 14.73 (br s, 1H), 9.04 (s, 1H), 8.27 (br s, 2H), 7.51 (s, 1H), 2.98-3.22 (m, 2H), 0.90-1.23 (m, 4H).

Intermediate 2-(1H-imidazol-5-yl)-2-methylpropan-1-amine hydrochloride

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Step 1: Preparation of (2-methyl-2-(3-tritylimidazol-4-yl)propanenitrile (B6)

To a solution of 2-(3-tritylimidazol-4-yl)acetonitrile (B2) (12 g, 34.3 mmol) in THF (400 mL) was drop-wise added LiHMDS (1 M, 96.2 mL, 2.8 eq) at −78° C. The reaction mixture was stirred at −78° C. for 15 min, and then Mel was added (14.62 g, 103 mmol, 6.41 mL, 3 eq). The reaction mixture was stirred at −78° C. for 1 hr, and then warmed to rt for 18 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). The reaction mixture was cooled to 0° C., quenched by the addition of sat. NH₄Cl solution (15 mL) and then H₂O (60 mL) was added. The aqueous portion was extracted with EtOAc (60 mL×3). The combined organic layers were washed with brine (60 mL), dried over Na₂SO₄, and concentrated to dryness. The residue (combined with the residue from another reaction performed using 2 g of B2) was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, eluent of 0-80% EtOAc/PE, gradient @60 mL/min) to give B6 (14 g, 92% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, 1H), 7.32-7.39 (m, 9H), 7.08-7.16 (m, 6H), 6.81 (d, 1H), 1.69 (s, 6H).

Step 2: Preparation of (2-methyl-2-(3-tritylimidazol-4-yl)propan-1-amine (B7)

To a solution of 2-methyl-2-(3-tritylimidazol-4-yl)propanenitrile (B6) (14 g, 37.1 mmol) in MeOH (350 mL) was added Raney-Ni (2 g, 23.3 mmol, 0.63 eq) under N₂. The reaction mixture was degassed under vacuum and purged with H₂several times. The reaction mixture was stirred under H₂(50 psi) at 40° C. for 36 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). The reaction mixture was filtered through of pad of celite, and the filtrate was concentrated to dryness to afford B7 (12 g, 85% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.38 (s, 1H), 7.29-7.36 (m, 9H), 7.10-7.18 (m, 6H), 6.55 (s, 1H), 3.49 (br s, 1H), 2.74 (s, 2H), 1.20 (s, 6H); LCMS: m/z 382.2 μM+H]⁺.

Step 3: Preparation of (2-(1H-imidazol-5-yl)-2-methyl-propan-1-amine (B8)

To a solution of 2-methyl-2-(3-tritylimidazol-4-yl)propan-1-amine (B7) (14 g, 36.7 mmol) in MeOH (150 mL) was added HCl/MeOH (4 M, 150 mL, 16.4 eq), and the reaction mixture was stirred at 50° C. for 18 hrs. Reaction progress was tracked using TLC (EtOAc). The reaction mixture was concentrated to dryness, and 200 mL of EtOAc was added. The mixture was stirred at 60° C. for 1 hr. The precipitate was collected by filtration and rinsed with EtOAc, and then dried in vacuo to give B8 (7.0 g, 90% yield, 2HCl salt). ¹H NMR (400 MHz, CD₃OD) δ 8.96 (s, 1H), 7.52 (s, 1H), 3.20-3.27 (m, 2H), 1.49 (s, 6H).

Intermediate 2-(1H-imidazol-5-yl)propan-1-amine hydrochloride

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Step 1: Preparation of 2-(3-tritylimidazol-4-yl)propanenitrile (B9)

To a solution of 2-(3-tritylimidazol-4-yl)acetonitrile (B2) (15 g, 42.9 mmol) in THF (120 mL) was added LiHMDS (1 M, 51.5 mL, 1.2 eq) dropwise at −78° C. After addition, the reaction mixture was stirred for 0.5 hr, and then Mel (10.97 g, 77.3 mmol, 4.81 mL, 1.8 eq) was added dropwise at −78° C. The reaction mixture was stirred at −78° C. for 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=2:1). The reaction mixture was quenched by the addition of sat. NH₄Cl solution (120 mL) and stirred for 15 min. The aqueous portion was extracted with EtOAc (400 mL), and the organic layer washed by water (100 mL) and brine (60 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue (combined with the residue from another reaction performed using 15 g of B2) was purified by column chromatography on silica gel (PE:EtOAc=20:1 to 2:1) to give B9 (33.5 g, 75% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.38-7.45 (m, 10H), 7.06-7.13 (m, 6H), 6.82-6.92 (m, 1H), 4.12-4.23 (m, 1H), 1.48 (d, 3H).

Step 2: Preparation of 2-(3-tritylimidazol-4-yl)propan-1-amine (B10)

A mixture of 2-(3-tritylimidazol-4-yl)propanenitrile (B9) (16.5 g, 45.4 mmol), Raney-Ni (4.08 g, 47.7 mmol, 1.05 eq), NH₃·H₂O (910 mg, 7.79 mmol, 1 mL, 30% purity) in MeOH (300 mL) was degassed under vacuum and purged with H₂3 times. The reaction mixture was stirred at 45° C. for 16 hrs under H₂(45 psi) atmosphere. Reaction progress was tracked using TLC (PE:EtOAc=2:1). The reaction mixture was filtered through a pad of Celite and the filtrate was concentrated to dryness to afford B10 (33 g), which was used without further purification. ¹H NMR (400 MHz, CD₃OD) δ 7.36-7.44 (m, 10H), 7.13-7.20 (m, 6H), 6.72 (br s, 1H), 2.57-2.92 (m, 3H), 1.21 (br d, 3H).

Step 3: Preparation of 2-(1H-imidazol-5-yl)propan-1-amine (B11)

To a solution of 2-(3-tritylimidazol-4-yl)propan-1-amine (B10) (23 g, 62.6 mmol) in MeOH (100 mL) was added HCl/MeOH (4 M, 100 mL). The mixture was stirred at rt for 12 hrs. Reaction progress was tracked using TLC (EtOAc). The reaction mixture (combined with the reaction mixture from another reaction performed using 23 g of B10) was concentrated to dryness. H₂O (40 mL) was added to the residue, and the aqueous layer washed with EtOAc (50 mL). The aqueous layer was lyophilized to give B11 (21 g, 2HCl). ¹H NMR (400 MHz, CD₃OD) δ 8.96 (d, 1H), 7.56 (s, 1H), 3.43-3.51 (m, 1H), 3.17-3.32 (m, 2H), 1.29-1.53 (m, 3H).

Intermediate 2-[(2R)-2-(1H-imidazol-5-yl)propyl]isoindoline-1,3-dione and 2-[(2S)-2-(1H-imidazol-5-yl)propyl]isoindoline-1,3-dione

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Step 1: Preparation of 2-[2-(1H-imidazol-5-yl)propyl]isoindoline-1,3-dione (B13)

To a solution of 2-(1H-imidazol-5-yl)propan-1-amine (B11) (10 g, 50.5 mmol, 2HCl) and phthalic anhydride (7.85 g, 53.0 mmol, 1.05 eq) in i-PrOH (400 mL) was added Et₃N (15.32 g, 151 mmol, 21.1 mL, 3 eq). The reaction mixture was stirred at 100° C. for 18 hrs under N₂atmosphere. After cooling, the reaction mixture was concentrated to dryness. Water (200 mL) was then added, and the mixture was stirred at rt for 10 mins. The precipitate was collected by filtration, rinsed with water (100 mL), and dried in vacuo to afford B13 (13 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d6) δ 7.71-7.89 (m, 4H), 7.49 (s, 1H), 6.79 (s, 1H), 3.70-3.76 (m, 1H), 3.60-3.65 (m, 1H), 3.15-3.23 (m, 1H), 1.16 (d, 3H).

Step 2: SFC Separation

Compound 2-[2-(1H-imidazol-5-yl)propyl]isoindoline-1,3-dione (13 g) was separated by SFC separation (column: DAICEL CHIRALPAK AD (250 mm*50 mm, 10 um); mobile phase: [0.1% NH₃H₂O ETOH]; B %: 40%-40%, min) to afford Enantiomer 1 (4.8 g, 37% yield, Rt=3.953 min) and Enantiomer 2 (5.2 g, 40% yield, Rt=4.652 min).

Enantiomer 1: 2-[(2R)-2-(1H-imidazol-5-yl)propyl]isoindoline-1,3-dione (B13A). ¹H NMR (400 MHz, CD₃OD) δ 7.73-7.89 (m, 4H), 7.56 (d, 1H), 6.82 (s, 1H), 3.84-3.93 (m, 1H), 3.70-3.82 (m, 1H), 3.36-3.39 (m, 1H), 1.31 (d, 3H); SFC: 98.4% ee.

Enantiomer 2: 2-[(2S)-2-(1H-imidazol-5-yl)propyl]isoindoline-1,3-dione (B13B). ¹H NMR (400 MHz, CD₃OD) δ 7.77-7.88 (m, 4H), 7.55 (d, 1H), 6.82 (s, 1H), 3.84-3.97 (m, 1H), 3.72-3.82 (m, 1H), 3.36-3.42 (m, 1H), 1.31 (d, 3H); SFC: 99.1% ee.

Preparation of Intermediate 6-(1,3-benzoxazol-2-yl)-N,N-dimethyl-2-triisopropylsilyl-5,6-dihydro-4H-pyrrolo[3,4-d]imidazole-3-sulfonamide

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Step 1: Preparation of tert-butyl 3-(dimethylsulfamoyl)-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B15)

To a solution of tert-butyl 4,6-dihydro-1H-pyrrolo[3,4-d]imidazole-5-carboxylate (B14) (4.5 g, 21.5 mmol) in DMF (60 mL) was added NaH (1.72 g, 43.0 mmol, 60% dispersion in mineral oil, 2 eq) at 0° C. The reaction mixture was stirred at 0° C. for 30 min, then N,N-dimethylsulfamoyl chloride (4.63 g, 32.3 mmol, 3.46 mL) was added to the reaction mixture at 0° C., and the reaction mixture was stirred at rt for 1 hr. Reaction progress was tracked using TLC (DCM:EtOAc=1:1). Sat. aq. NH₄Cl (80 mL) was added to the reaction mixture, and the aqueous portion extracted with DCM (100 mL). The organic layer was washed by water (80 mL) and brine (80 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, DCM/EtOAc=1/0 to 1/1) to give B15 (5.6 g, 82.3% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.70 (s, 1H), 4.46-4.64 (m, 2H), 4.36 (dt, 2H), 2.83 (d, 6H), 1.44 (s, 9H).

Step 2: Preparation of tert-butyl 3-(dimethylsulfamoyl)-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B16)

To a solution of tert-butyl 3-(dimethylsulfamoyl)-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B15) (9.2 g, 29.1 mmol) in THF (120 mL) was added t-BuLi (1.3 M in pentane, 26.8 mL) at −78° C., and the reaction mixture was stirred at −78° C. for 1 hr. Then 2-[diisopropyl(trifluoromethoxysulfonyl)silyl]propane (10.69 g, 34.9 mmol, 40.6 uL) in THF (10 mL) was added to the reaction mixture dropwise at −78° C., and the mixture was stirred at −78° C. for 1 hr. Reaction progress was tracked using TLC (PE:EtOAc=2:1). Sat. aq. NH₄Cl solution (300 mL) was added, and the aqueous portion extracted with DCM (200 mL). The organic layer was washed by water (100 mL) and brine (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 5/1) to give B16 (7.4 g, 53.8% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.39-4.66 (m, 4H), 2.89-3.04 (m, 6H), 1.66 (quin, 3H), 1.52 (s, 9H), 1.17 (d, 18H)

Step 3: Preparation of 5-(tert-butyl) 4-methyl 3-(N,N-dimethylsulfamoyl)-2-(triisopropylsilyl)-4,6-dihydropyrrolo[3,4-d]imidazole-4,5(3H)-dicarboxylate (B17)

To a solution of dimethyl carbonate (610 mg, 6.77 mmol, 570 uL) and tert-butyl 3-(dimethylsulfamoyl)-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B16) (2 g, 4.23 mmol) in THF (40 mL) was added LDA (2 M, 3.60 mL) at −78° C., and the reaction mixture was stirred at −78° C. for 1 hr. Reaction progress was tracked using LCMS. Sat. aq. NH₄Cl solution (100 mL) was added, and the aqueous portion extracted with EtOAc (200 mL). The organic layer was washed by sat. aq. Na₂CO₃(150 mL) and brine (150 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified prep. HPLC (column: Xtimate C18 150*40 mm*10 um; mobile phase: [water(NH3H₂O+NH₄HCO₃)-ACN]; B %: 85%-100%, 7 min) to give B17 (1 g, 44.1% yield). ¹H NMR (400 MHz, CDCl₃) δ 5.20-5.36 (m, 1H), 4.56-4.66 (m, 1H), 4.41-4.54 (m, 1H), 3.78 (d, 3H), 2.91 (d, 6H), 1.63-1.75 (m, 3H), 1.41-1.55 (m, 9H), 1.16 (d, 18H).

Step 4: Preparation of 5-tert-butoxycarbonyl-3-(dimethylsulfamoyl)-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-6-carboxylic acid (B18)

To a solution of 5-(tert-butyl) 4-methyl 3-(N,N-dimethylsulfamoyl)-2-(triisopropylsilyl)-4,6-dihydropyrrolo[3,4-d]imidazole-4,5(3H)-dicarboxylate (B17) (420 mg, 791 μmol) in THF (4 mL), MeOH (3 mL) and H₂O (2 mL) was added NaOH (47.5 mg, 1.19 mmol), and the reaction mixture was stirred at rt for 24 hrs. The reaction mixture was concentrated in vacuum to remove the organic solvents, and H₂O (10 mL) was added. Reaction progress was tracked using LCMS. The aqueous layer was adjusted to pH ˜7 by the addition of 0.5 μM HCl. The reaction mixture was concentrated to dryness to give B18 (400 mg, 95.2% yield). ¹H NMR (400 MHz, CDCl₃) δ 5.14-5.58 (m, 1H), 4.49 (br s, 2H), 2.83-2.99 (m, 6H), 1.58-1.71 (m, 3H), 1.46-1.56 (m, 9H), 1.16 (d, 18H).

Step 5: Preparation of tert-butyl 3-(dimethylsulfamoyl)-6-[(2-hydroxyphenyl)carbamoyl]-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B19)

To a solution of 2-aminophenol (50.7 mg, 464 μmol) in DMF (3 mL) was added EDCI (96.5 mg, 503 μmol), HOBt (68.0 mg, 503 μmol) and 5-tert-butoxycarbonyl-3-(dimethylsulfamoyl)-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-6-carboxylic acid (B18) (200 mg, 387 μmol), and the reaction mixture was stirred at rt for 1 hr. Reaction progress was tracked using LCMS. EtOAc was added to the reaction mixture (30 mL), and the organic layer was washed by water (10 mL) and brine (10 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 1/1) to give B19 (110 mg, 46.8% yield). ¹H NMR (400 MHz, CDCl₃) δ 9.15 (s, 1H), 8.61 (s, 1H), 6.73-7.14 (m, 4H), 5.29-5.65 (m, 1H), 4.41-4.64 (m, 2H), 2.74-2.90 (m, 6H), 1.54-1.59 (m, 3H), 1.46 (s, 9H), 1.05-1.09 (m, 18H).

Step 6: Preparation of tert-butyl 6-(1,3-benzoxazol-2-yl)-3-(dimethylsulfamoyl)-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B20)

To a solution of tert-butyl 3-(dimethylsulfamoyl)-6-[(2-hydroxyphenyl)carbamoyl]-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B19) (100 mg, 165 μmol) in THF (1 mL) was added PPh₃(86.3 mg, 329 μmol), DEAD (57.3 mg, 329 μmol, 59.8 μL) at 0° C., and the reaction mixture was stirred at rt for 12 hrs. Reaction progress was tracked using LCMS. DCM was added (30 mL), and the organic layer washed by water (10 mL) and brine (10 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by prep. HPLC (column: Phenomenex C18 75*30 mm*3 um; mobile phase: [water (NH₃H₂O+NH₄HCO₃)-ACN]; B %: 70%-100%, 7 min) to give B20 (90 mg, 92.8% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.68-7.79 (m, 1H), 7.48-7.60 (m, 1H), 7.32-7.43 (m, 2H), 6.07-6.38 (m, 1H), 4.52-4.87 (m, 2H), 2.39-2.74 (m, 6H), 1.61-1.67 (m, 3H), 1.25-1.52 (m, 9H), 1.17 (dd, 18H).

Step 7: Preparation of 6-(1,3-benzoxazol-2-yl)-N,N-dimethyl-2-triisopropylsilyl-5,6-dihydro-4H-pyrrolo[3,4-d]imidazole-3-sulfonamide (B21)

To a solution of tert-butyl 6-(1,3-benzoxazol-2-yl)-3-(dimethylsulfamoyl)-2-triisopropylsilyl-4,6-dihydropyrrolo[3,4-d]imidazole-5-carboxylate (B20) (50 mg, 84.8 μmol) in DCM (2 mL) was added TFA (308 mg, 2.70 mmol, 0.2 mL), and the reaction mixture was stirred at rt for 1 hr. Reaction progress was tracked using LCMS. Water (10 mL) was added, and the aqueous layer was adjusted to pH ˜8 by the addition of sat. aq. NaHCO₃solution. The suspension was extracted with DCM/MeOH (50/5 mL) 3 times. The combined organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness to afford B21 (41 mg, 100% yield). LC-MS: m/z 490.2 μM+H]⁺.

Intermediate 1,3-benzoxazole-2-carbaldehyde

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To a solution of 1,3-benzoxazol-2-ylmethanol (5.5 g, 36.9 mmol) in MeCN (170 mL) was added IBX (13.42 g, 47.9 mmol, 1.3 eq) in portions at rt. The mixture was stirred at 80° C. for 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). The reaction mixture was filtered, and the filtrate was concentrated to dryness to afford 1,3-benzoxazole-2-carbaldehyde (5.7 g), which was used without further purification. ¹H NMR (400 MHz, CDCl₃) δ 10.03 (s, 1H), 7.98 (d, 1H), 7.72 (d, 1H), 7.62 (td, 1H), 7.50-7.56 (m, 1H).

Intermediate 5-methyl-1,3-benzoxazole-2-carbaldehyde

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Step 1: Preparation of ethyl 5-methyl-1,3-benzoxazole-2-carboxylate (C2)

To a solution of 2-amino-4-methyl-phenol (5 g, 40.6 mmol) in dioxane (120 mL) was added ethyl 2-oxoacetate (16.58 g, 81.2 mmol, 2 eq) in two portion per hour. The reaction mixture was heated at 50° C. for 2 hrs, CAN (24.48 g, 44.7 mmol, 22.3 mL, 1.1 eq) was then added, and the reaction mixture was stirred at 120° C. for 6 hrs. Reaction progress was tracked using TLC (PE:EtOAc=5:1). The reaction mixture was filtered, and the filtrate was concentrated to dryness. The residue was purified by column chromatography on silica gel (PE:EtOAc=20:1 to 5:1) to give C2 (1.6 g, 19% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.65-7.77 (m, 2H), 7.39 (dd, 1H), 4.39 (q, 2H), 2.43 (s, 3H), 1.29-1.37 (m, 3H).

Step 2: Preparation of (5-methyl-1,3-benzoxazol-2-yl)methanol (C3)

To a solution of ethyl 5-methyl-1,3-benzoxazole-2-carboxylate (C2) (2.5 g, 12.2 mmol) and THF (40 mL) and EtOH (4 mL) was added NaBH₄(2.30 g, 60.9 mmol, 5 eq) in portions at 0° C. The reaction mixture was stirred at rt for 4 hrs. Reaction progress was checked using TLC (PE:EtOAc=1:1). The reaction mixture was quenched with sat. NH₄Cl solution (20 mL), and the aqueous portion was extracted with EtOAc (100 mL). The organic layer was washed with water (30 mL) and brine (30 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography on silica gel (PE:EtOAc=20:1 to 1:1) to give C3 (600 mg, 24% yield). LCMS: m/z 164.2 μM+H]⁺.

Step 3: Preparation of 5-methyl-1,3-benzoxazole-2-carbaldehyde (C4)

To a solution of (5-methyl-1,3-benzoxazol-2-yl)methanol (C3) (400 mg, 2.45 mmol) in DCM (15 mL) was added DMP (2.08 g, 4.90 mmol, 1.5 mL, 2 eq). The mixture was stirred at rt for 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). DCM (60 mL) was added, and the organic layer washed with sat. NaHCO₃solution (20 mL) and brine (20 mL), dried over Na₂SO₄, filtered, and concentrated to dryness to afford C₄(300 mg), which was used without further purification.

Intermediate 5-fluorobenzo[d]oxazole-2-carbaldehyde

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Step 1: Preparation of ethyl 5-fluorobenzo[d]oxazole-2-carboxylate (C5)

To a solution of 2-amino-4-fluorophenol (120 g, 944 mmol) in THF (360 mL) was added Et₃N (191 g, 1.89 mol, 2 eq) and ethyl 2-chloro-2-oxoacetate (142 g, 1.04 mol, 1.1 eq). The reaction mixture was stirred at rt for 1 hr. PPh₃(384 g, 1.46 mol, 1.55 eq) in THF (360 mL) and DEAD (247 g, 1.42 mol, 1.5 eq) was added to the reaction mixture dropwise at 0° C. The reaction mixture was stirred at rt for 1 hr. Reaction progress was tracked using TLC (PE/EtOAc=1:1). The reaction mixture was filtered, and MTBE (700 mL) was added to the filtrate. The organic layer was washed with H₂O (700 mL) and brine (400 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=100/1 to 3/1) to give C₅(145 g, 73% yield). ¹H NMR (400 MHz DMSO-d₆) δ 7.91-7.95 (m, 1H), 7.79-7.82 (m, 1H), 7.47-7.79 (m, 1H), 4.41-4.46 (m, 2H), 1.31-1.38 (m, 3H).

Step 2: Preparation of 5-fluorobenzo[d]oxazol-2-yl)methanol (C6)

To a solution of ethyl 5-fluorobenzo[d]oxazole-2-carboxylate (C5) (145 g, 693 mmol) in THF (430 mL) and EtOH (430 mL) was added NaBH₄(78.7 g, 2.08 mol, 3 eq) in portions at 0° C. The mixture was stirred at rt for 2 hrs. Reaction progress was tracked using TLC (PE/EtOAc=1/1). DCM (600 mL) was added, and the organic layer washed with H₂O (500 mL) and brine (300 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=30/1 to 1/1) to compound C₆(75.5 g, 65% yield). ¹H NMR (400 MHz DMSO-d₆) δ 7.75-7.78 (m, 1H), 7.60-7.63 (m, 1H), 7.24-7.30 (m, 1H), 5.89-5.92 (t, 1H), 4.69-4.71 (d, 2H).

Step 3: Preparation of 5-fluorobenzo[d]oxazole-2-carbaldehyde (C7)

To a solution of 5-fluorobenzo[d]oxazol-2-yl)methanol (C6) (75.5 g, 452 mmol) in ACN (450 mL) was added IBX (164 g, 587 mmol, 1.3 eq) at rt. The reaction mixture was stirred at 80° C. for 2 hrs. Reaction progress was tracked using TLC (PE/EtOAc=1/1). The reaction mixture was filtered, and the filter cake was washed with DCM (200 mL×2). The filtrate was concentrated to dryness, then triturated with PE (200 mL) at rt for 30 min, and filtered to give a filter cake. The filter cake was dissolved in DCM (200 mL) and the organic layer washed with 1 μM K₂CO₃solution (150 mL), dried over Na₂SO₄, filtered, and concentrated to dryness to give C7 (52.0 g, 70% yield). ¹H NMR (400 MHz DMSO-d₆) δ 9.91 (s, 1H), 7.92-8.00 (m, 2H), 7.53-7.55 (m, 1H).

Intermediates 2-amino-3-(trifluoromethoxy)phenol and 4-(trifluoromethoxy)benzo[d]oxazole-2-carbaldehyde

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Step 1: Preparation of tert-butyl N-[2-methoxy-6-(trifluoromethoxy)phenyl]carbamate (C8)

To a solution of 2-methoxy-6-(trifluoromethoxy)benzoic acid (1 g, 4.23 mmol) in t-BuOH (3 mL) was added DPPA (1.52 g, 5.51 mmol, 1.2 mL, 1.3 eq), Boc₂O (2.77 g, 12.7 mmol, 2.9 mL, 3 eq) and TEA (643 mg, 6.35 mmol, 884 μL, 1.5 eq), the mixture was stirred at 85° C. for 3 hrs. EtOAc (220 mL) was added, and the organic layer washed with water (200 mL) and brine (150 mL), dried over Na₂SO₄, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 10/1) to give C₈(470 mg, 36% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.20 (t, 1H), 6.92 (dt, 1H), 6.85 (dd, 1H), 5.92 (br s, 1H), 3.73-3.96 (m, 3H), 1.50 (s, 9H).

Step 2: Preparation of 2-amino-3-(trifluoromethoxy)phenol (C9)

To a solution of tert-butyl N-[2-methoxy-6-(trifluoromethoxy)phenyl]carbamate (C8) (1 g, 3.25 mmol) in DCM (10 mL) was added BCl₃(1 M, 9.8 mL, 3 eq), the reaction mixture was stirred at rt for 12 hrs. The reaction mixture was adjusted to pH ˜9 by the addition of sat. NaHCO₃solution, and the aqueous portion extracted with DCM (30 mL×3). The combined organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 5/1) to give C₉(400 mg, 64% yield). ¹H NMR (400 MHz, DMSO-d6) δ 9.66 (s, 1H), 6.56-6.74 (m, 2H), 6.37-6.51 (m, 1H), 4.64 (br s, 2H).

C₉was then used to prepare 4-(trifluoromethoxy)benzo[d]oxazole-2-carbaldehyde following the procedure described above for C7.

Intermediate 4-fluoro-7-methyl-1,3-benzoxazole-2-carbaldehyde

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Step 1: Preparation of 2-amino-3-fluoro-6-methyl-phenol (C10)

To a solution of 3-fluoro-6-methyl-2-nitro-phenol (1 g, 5.84 mmol, 1 eq) in MeOH (100 mL) was added Pd/C (250 mg, 584 μmol, 20% purity, 0.1 eq), the mixture was degassed in vacuum and purged with H₂for 3 times, and then the reaction mixture was stirred at rt for 2 hrs under H₂(15 psi). Reaction progress was tracked using TLC (PE:EtOAc=10:1) and LCMS. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated to give C10 (880 mg), which was used without further purification. ¹H NMR (400 MHz, CDCl₃) δ 6.45-6.64 (m, 2H), 3.83 (br s, 2H), 2.20 (s, 3H); LCMS: m/z 142.1 μM+H]⁺.

Step 2: Preparation of (4-fluoro-7-methyl-1,3-benzoxazol-2-yl)methyl acetate (C11)

To a solution of 2-amino-3-fluoro-6-methyl-phenol (C10) (880 mg, 6.23 mmol) in THF (15 mL) was added (2-chloro-2-oxo-ethyl) acetate (970 mg, 7.11 mmol, 764 μL, 1.1 eq) dropwise at 0° C. The reaction mixture was stirred at rt for 1 hr. Reaction progress was tracked using TLC (PE:EtOAc=5:1). Water (100 mL) was added, and the aqueous portion extracted with EtOAc (100 mL×3). The combined organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness. The residue (1.7 g) was dissolved in THF (20 mL), PPh₃(2.77 g, 10.6 mmol, 1.5 eq) was added, and then DEAD (1.84 g, 10.6 mmol, 1.9 mL, 1.5 eq) was added dropwise at 0° C. The reaction mixture was stirred at rt for 14 hrs. Reaction progress was tracked using LCMS. Water (60 mL) was added, and the aqueous portion extracted with EtOAc (60 mL×3). The combined organic phase was concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0-20% EtOAc/PE gradient @35 mL/min) to give C₁₁(1.1 g, 68% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.11 (dd, 1H), 6.92-7.04 (m, 1H), 5.35 (s, 2H), 2.49 (s, 3H), 2.22 (s, 3H); LCMS: m/z 224.1 μM+H]⁺.

Step 3: Preparation of (4-fluoro-7-methyl-1,3-benzoxazol-2-yl)methanol (C12)

To a solution of (4-fluoro-7-methyl-1,3-benzoxazol-2-yl)methyl acetate (C11) (1.1 g, 4.93 mmol) in THF (10 mL) and H₂O (3 mL) was added LiOH·H₂O (248 mg, 5.91 mmol, 1.2 eq), and the reaction mixture was stirred at rt for 1 hr. Reaction progress was tracked using LCMS. EtOAc (60 mL) was added, and the organic layer washed with water (20 mL) and brine (20 mL), dried over Na₂SO₄, filtered, and concentrated to dryness to afford C12 (1.2 g), which was used without further purification. LCMS: m/z 182.1 μM+H]⁺.

Step 4: Preparation of 4-fluoro-7-methyl-1,3-benzoxazole-2-carbaldehyde (C13)

To a solution of (4-fluoro-7-methyl-1,3-benzoxazol-2-yl)methanol (C12) (580 mg, 3.20 mmol) in CH₃CN (30 mL) was added IBX (1.17 g, 4.16 mmol, 1.3 eq) at rt. The reaction mixture was stirred at 80° C. for 3 hrs. Reaction progress was tracked using LCMS. The reaction mixture was filtered, and filtrate was concentrated to dryness to afford C13 (650 mg, 90% yield), which was used without further purification. ¹HNMR (400 MHz, CDCl₃) δ 9.99 (s, 1H), 7.31 (dd, 1H), 7.10 (t, 1H), 2.55 (s, 3H); LCMS: m/z 180.1 μM+H]⁺.

Intermediate 5-(trifluoromethyl)benzo[d]oxazole-2-carbaldehyde

Intermediate 5-(trifluoromethyl)benzo[d]oxazole-2-carbaldehyde was prepared starting from 2-amino-4-(trimethyl)phenol following the procedure for steps 2, 3, and 4 above for C₁₃. In the hydrolysis step 3, K₂CO₃and MeOH was used as the base and solvent instead of LiOH and THF/H₂O.

Intermediate 5-fluoro-7-methoxy-1,3-benzoxazole-2-carbaldehyde

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Step 1: Preparation of [2-(3-bromo-5-fluoro-2-hydroxy-anilino)-2-oxo-ethyl]acetate (C14)

To a solution of 2-amino-6-bromo-4-fluoro-phenol (3.56 g, 17.3 mmol) in THF (70 mL) was added (2-chloro-2-oxo-ethyl) acetate (2.71 g, 19.9 mmol, 2.1 mL, 1.15 eq) dropwise at 0° C. The reaction mixture was stirred at rt for 1 hr. Reaction progress was tracked using LCMS. H₂O (200 mL) was added, and the aqueous portion extracted with EtOAc (100 mL×3). The organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness to afford C14 (5.29 g), which was used without further purification. LCMS: m/z 306.0 μM+H]⁺.

Step 2: Preparation of (7-bromo-5-fluoro-1,3-benzoxazol-2-yl) methyl acetate (C15)

To a solution of [2-(3-bromo-5-fluoro-2-hydroxy-anilino)-2-oxo-ethyl]acetate (C14) (5.29 g, 17.3 mmol) and PPh₃(6.80 g, 25.9 mmol, 1.5 eq) in THF (70 mL) was added DEAD (4.51 g, 25.9 mmol, 4.7 mL, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at rt for 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=2:1). Water (200 mL) was added, and the aqueous portion extracted with EtOAc (100 mL×3). The combined organic phase was concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0-100% EtOAc/PE gradient @35 mL/min) to give C15 (2.42 g, 49% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.30-7.42 (m, 2H), 5.35 (s, 2H), 2.23 (s, 3H).

Step 3: Preparation of [5-fluoro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-yl]methyl acetate (C16)

To a solution of (7-bromo-5-fluoro-1,3-benzoxazol-2-yl)methyl acetate (C15) (2.42 g, 8.40 mmol) in dioxane (100 mL) was added Pin₂B₂(2.56 g, 10.1 mmol, 1.2 eq) KOAc (1.65 g, 16.8 mmol, 2 eq) and Pd(dppf)Cl₂(615 mg, 840 μmol, 0.1 eq). The mixture was stirred at 80° C. for 16 hrs under N₂. Reaction progress was tracked using LCMS. Water (200 mL) was added, and the aqueous portion extracted with EtOAc (100 mL×3). The combined organic phase was concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, Eluent of 0-100% EtOAc/PE gradient @35 mL/min) to give C₁₆(2.46 g, 87% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.46-7.53 (m, 2H), 5.38 (s, 2H), 2.23 (s, 3H), 1.40 (s, 12H); LCMS: m/z 336.2 μM+H]⁺.

Step 4: Preparation of (5-fluoro-7-hydroxy-1,3-benzoxazol-2-yl)methyl acetate (C17)

To a solution of [5-fluoro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-yl]methyl acetate (C16) (2.46 g, 7.34 mmol) in THF (40 mL) was added H₂O₂(1.25 g, 11.0 mmol, 1.1 mL, 30% purity, 1.5 eq) and NaOH (1 M, 7.7 mL, 1.05 eq) at 0° C. The mixture was stirred at rt for 3 hrs. Reaction progress was tracked using LCMS. Water (100 mL) was added, and the aqueous portion extracted with EtOAc (50 mL×3). The combined organic phase was concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0-100% EtOAc/PE gradient @35 mL/min) to give C17 (1.65 g, 100% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.38-8.11 (m, 1H), 6.99 (dd, 1H), 6.69 (dd, 1H), 5.32 (s, 2H), 2.19 (s, 3H); LCMS: m/z 226.1 μM+H]⁺.

Step 5: Preparation of (5-fluoro-7-methoxy-1,3-benzoxazol-2-yl) methyl acetate (C18)

To a solution of (5-fluoro-7-hydroxy-1,3-benzoxazol-2-yl)methyl acetate (C₁₇) (1.65 g, 7.34 mmol) in MeCN (30 mL) was added K₂CO₃(2.13 g, 15.4 mmol, 2.1 eq) and Mel (1.15 g, 8.07 mmol, 503 μL, 1.1 eq) at 0° C. The reaction mixture was stirred at rt for 16 hrs. Reaction progress was tracked using LCMS. Water (50 mL) was added, and the aqueous portion extracted with EtOAc (30 mL×3). The combined organic phase was concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0-100% EtOAc/PE gradient @35 mL/min) to give C18 (1.14 g, 65% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.03 (dd, 1H), 6.66 (dd, 1H), 5.31 (s, 2H), 4.01 (s, 3H), 2.20 (s, 3H); LCMS: m/z 240.1 μM+H]⁺.

Step 6: Preparation of (5-fluoro-7-methoxy-1,3-benzoxazol-2-yl)methanol (C19)

To a solution of (5-fluoro-7-methoxy-1,3-benzoxazol-2-yl)methyl acetate (C18) (1.14 g, 4.77 mmol) in MeOH (20 mL) was added K₂CO₃(725 mg, 5.24 mmol, 1.1 eq) at 0° C. The mixture was stirred at rt for 2 hrs. Reaction progress was tracked using LCMS.

The reaction mixture was concentrated to dryness. Water (15 mL) was added, and the aqueous portion extracted with EtOAc (10 mL×3). The combined organic phase was dried over Na₂SO₄, filtered, and concentrated to dryness to give C19 (910 mg), which was used without further purification. ¹H NMR (400 MHz, CDCl₃) δ 7.02 (dd, 1H), 6.65 (dd, 1H), 4.92 (s, 2H), 4.01 (s, 3H); LCMS: m/z 198.1 μM+H]⁺.

Step 7: Preparation of 5-fluoro-7-methoxy-1,3-benzoxazole-2-carbaldehyde (C20)

To a solution of (5-fluoro-7-methoxy-1,3-benzoxazol-2-yl)methanol (C19) (910 mg, 4.62 mmol) in MeCN (20 mL) was added IBX (1.68 g, 6.00 mmol, 1.3 eq), and then the mixture was stirred at 80° C. for 2 hr. Reaction progress was tracked using LCMS. The reaction mixture was filtered, and the filtrate was concentrated to dryness to afford C20 (960 mg), which was used without further purification. ¹H NMR (400 MHz, CDCl₃) δ 9.98 (s, 1H), 7.20 (dd, 1H), 6.83 (dd, 1H), 4.06 (s, 3H); LCMS: m/z 196.1 μM+H]⁺.

Intermediate 7-fluoro-5-methoxy-1,3-benzoxazole-2-carbaldehyde

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Step 1: Preparation of [2-(5-bromo-3-fluoro-2-hydroxy-anilino)-2-oxo-ethyl]acetate (C21)

To a solution of 2-amino-4-bromo-6-fluoro-phenol (6.4 g, 31.1 mmol) in THF (80 mL) was added (2-chloro-2-oxo-ethyl) acetate (4.84 g, 35.4 mmol, 3.8 mL, 1.14 eq) dropwise at 0° C. The reaction mixture was stirred at rt for 1 hr. Reaction progress was checked using TLC (PE:EtOAc=3:1). The reaction mixture was concentrated to dryness. Water (100 mL) was added, and the aqueous portion extracted with EtOAc (150 mL×2). The combined organic layers were washed with brine (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness to afford C21 (9.4 g), which was used without purification.

Step 2: Preparation of (5-bromo-7-fluoro-1,3-benzoxazol-2-yl)methyl acetate (C22)

To a solution of [2-(5-bromo-3-fluoro-2-hydroxy-anilino)-2-oxo-ethyl]acetate (C21) (9.4 g, 30.7 mmol) and PPh₃(12.08 g, 46.1 mmol, 1.5 eq) in THF (100 mL) was added DEAD (8.02 g, 46.1 mmol, 8.4 mL, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at rt for 12 hrs. Reaction progress was checked using TLC (PE:EtOAc=2:1). The reaction mixture was concentrated to dryness. Water (300 mL) was added, and the aqueous portion extracted with EtOAc (300 mL×2). The combined organic layers were washed with brine (300 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by silica gel chromatography (eluent PE:EtOAc 20:1 to 10:1) to afford C₂₂(7.5 g, 85% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.94 (d, 1H), 7.75 (dd, 1H), 5.41 (s, 2H), 2.16 (s, 3H).

Step 3: Preparation of [7-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-yl]methyl acetate (C23)

A mixture of (5-bromo-7-fluoro-1,3-benzoxazol-2-yl)methyl acetate (1 g, 3.47 mmol) (C22), Pin₂B₂(970 mg, 3.82 mmol, 1.1 eq), Pd(dppf)Cl₂(127 mg, 174 μmol, 0.05 eq) and KOAc (681 mg, 6.94 mmol, 2 eq) in dioxane (10 mL) was degassed and purged with N₂for 3 times. The reaction mixture was stirred at 80° C. for 24 hrs under N₂atmosphere. Reaction progress was checked using TLC (PE:EtOAc=3:1). The reaction mixture was filtered and concentrated to dryness. The residue was purified by silica gel chromatography (eluent PE:EtOAc from 50:1 to 10:1) to afford C23 (1 g, 86% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.82 (s, 1H), 7.50 (d, 1H), 5.41 (s, 2H), 2.16 (s, 3H), 1.32 (s, 12H).

Step 4: Preparation of (7-fluoro-5-hydroxy-1,3-benzoxazol-2-yl)methyl acetate (C24)

To a solution of [7-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-yl]methyl acetate (C23) (1 g, 2.98 mmol) in THF (20 mL) was added H₂02 (507 mg, 4.48 mmol, 430 μL, 30% purity, 1.5 eq) and NaOH (1 M, 3.1 mL, 1.05 eq). The reaction mixture was stirred at rt for 3 hrs. Reaction progress was checked using TLC (PE:EtOAc=3:1). EtOAc (60 mL) was added, and the organic portion washed with sat. Na₂S203 solution (20 mL) and brine (20 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 24 g SepaFlash® Silica Flash Column, Eluent of 0-20% EtOAc/PE gradient @35 mL/min) to give C24 (0.78 g). ¹H NMR (400 MHz, DMSO-d₆) δ 9.98 (s, 1H), 6.90 (br s, 1H), 6.77 (br d, 1H), 5.33 (s, 2H), 2.14 (s, 3H); LCMS: m/z 225.9 μM+H]⁺.

Step 5: Preparation of (7-fluoro-5-methoxy-1,3-benzoxazol-2-yl)methyl acetate (C25)

To a solution of (7-fluoro-5-hydroxy-1,3-benzoxazol-2-yl)methyl acetate (C₂₄) (2.3 g, 10.2 mmol) and K₂CO₃(2.96 g, 21.5 mmol, 2.1 eq) in DMF (2 mL) was added CH₃I (1.59 g, 11.2 mmol, 699 μL, 1.1 eq). The mixture was stirred at rt for 6 hrs. Reaction progress was tracked using TLC (PE:EtOAc=2:1). The reaction mixture was concentrated to dryness. Water (10 mL) was added, and the aqueous portion extracted with EtOAc (30 mL). The organic layer was washed with brine (10 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 24 g SepaFlash® Silica Flash Column, Eluent of 0-20% EtOAc/PE gradient @35 mL/min) to give C₂₅(1.3 g, 53% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.20 (d, 1H), 7.04 (dd, 1H), 5.36 (s, 2H), 3.82 (s, 3H), 2.15 (s, 3H).

Step 6: Preparation of (7-fluoro-5-methoxy-1,3-benzoxazol-2-yl)methanol (C26)

To a solution of (7-fluoro-5-methoxy-1,3-benzoxazol-2-yl)methyl acetate (C25) (1.4 g, 5.85 mmol) in MeOH (15 mL) was added K₂CO₃(971 mg, 7.02 mmol, 1.2 eq).

The mixture was stirred at rt for 3 hrs. Reaction progress was tracked using TLC (PE:EtOAc=2:1). The reaction mixture was concentrated to dryness. Water (20 mL) was added, and the aqueous portion extracted with EtOAc (30 mL×2). The combined organic layers were washed with brine (30 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 24 g SepaFlash® Silica Flash Column, Eluent of 0-20% EtOAc/PE gradient @35 mL/min) to give C26 (1.1 g, 95% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.15 (d, 1H), 6.99 (dd, 1H), 5.94 (t, 1H), 4.70 (d, 2H), 3.81 (s, 3H).

Step 7: Preparation of 7-fluoro-5-methoxy-1,3-benzoxazole-2-carbaldehyde (C27)

To a solution of (7-fluoro-5-methoxy-1,3-benzoxazol-2-yl)methanol (C27) (1.1 g, 5.58 mmol) in MeCN (20 mL) was added IBX (2.07 g, 7.25 mmol, 98% purity, 1.3 eq) at rt. The mixture was stirred at 80° C. for 3 hrs. Reaction progress was tracked using TLC (PE:EtOAc=3:1). The reaction mixture was filtered, and the filtrate was concentrated to dryness to afford C27 (1 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 9.89 (s, 1H), 7.41 (d, 1H), 7.28 (dd, 1H), 3.87 (s, 3H).

Intermediate 4-(difluoromethyl)oxazole-5-carboxylic acid according to General Scheme 4

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Step 1: Preparation of ethyl 2-bromo-4,4-difluoro-3-oxo-butanoate (E1)

To a solution of ethyl 4,4-difluoro-3-oxo-butanoate (20 g, 120 mmol) in DCM (240 mL) was added TsOH (4.15 g, 24.1 mmol, 0.2 eq) and NBS (22.50 g, 126 mmol, 1.05 eq) in portions at 0° C. After addition was complete, the reaction mixture was stirred at rt for 1 hr. The reaction progress was checked using TLC (PE:EtOAc=5:1). DCM was added (100 mL), and the organic portion was washed with sat. Na₂CO₃solution (100 mL) and brine (150 mL), dried over Na₂SO₄, filtered, and concentrated to dryness to afford E1 (34 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 5.81-6.16 (m, 1H), 4.34-4.41 (m, 1H), 4.12-4.20 (m, 2H), 1.17-1.23 (m, 3H).

Step 2: Preparation of ethyl 2-amino-4-(difluoromethyl) oxazole-5-carboxylate (E2)

A mixture of E1 (37 g, 151 mmol) and urea (45.34 g, 755 mmol, 40.5 mL, 5 eq) in DMF (30 mL) was stirred at 120° C. for 12 hrs. The reaction progress was checked using LC-MS. The reaction mixture was cooled to rt and poured into 100 mL of water. The reaction mixture was stirred for 15 min at 0° C., and the precipitate was collected by filtration, rinsed with water (50 mL), dried in vacuo to give E2 (15.5 g, 63% yield for steps 1 and 2). LC-MS: m/z 207.2 (M+H)⁺; ¹H NMR (400 MHz, DMSO-d₆) δ 7.86 (s, 2H), 6.84-7.44 (m, 1H), 4.27 (q, 2H), 1.28 (t, 3H).

Step 3: Preparation of ethyl 4-(difluoromethyl)oxazole-5-carboxylate (E3)

To a solution of ethyl 2-amino-4-(difluoromethyl)oxazole-5-carboxylate (20 g, 97.0 mmol) in THF (300 mL) was added t-BuONO (30.01 g, 291 mmol, 34.6 mL, 3 eq) dropwise at 0° C., the reaction mixture was stirred at rt for 12 hrs. DCM (300 mL) was added, and the organic portion was washed with water (200 mL) and brine (200 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 10/1) to give E3 (12.7 g, 69% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.05 (s, 1H), 6.93-7.27 (m, 1H), 4.44 (q, 2H), 1.40 (t, 3H).

Step 5: Preparation of 4-(difluoromethyl)oxazole-5-carboxylic acid (E4)

To a solution of ethyl 4-(difluoromethyl)oxazole-5-carboxylate (12.7 g, 66.5 mmol) in THF (100 mL) and H₂O (20 mL) was added LiOH·H₂O (3.07 g, 73.1 mmol, 1.1 eq). The reaction mixture was stirred at rt for 1 hr and then concentrated in vacuo to remove THF. Water (80 mL) was added, and the aqueous portion extracted with TBME (50 mL). The aqueous layer was then adjusted to pH˜6 by the addition of 0.5 μM HCl. The aqueous layer was concentrated to dryness to give E4 (11 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 8.30 (s, 1H), 7.34-7.76 (m, 1H).

Intermediate ethyl 2-bromo-4-(difluoromethyl)oxazole-5-carboxylate according to General Scheme 4

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Preparation of ethyl 2-bromo-4-(difluoromethyl)oxazole-5-carboxylate (E5)

To a solution of ethyl 2-amino-4-(difluoromethyl)oxazole-5-carboxylate (E2) (25 g, 121 mmol) in MeCN (200 mL) was added CuBr₂(40.63 g, 182 mmol, 8.5 mL, 1.5 eq) at 0° C. The mixture turned dark green and further stirred for 15 min at rt. t-BuONO (18.76 g, 182 mmol, 21.6 mL, 1.5 eq) was added at 0° C. The reaction was stirred at rt for 2 hrs, and then was heated to 50° C. and stirred for 12 hrs. Reaction progress was tracked using TLC (EtOAc:PE=5:1). The reaction mixture was filtered. DCM (200 mL) was added to the filtrate, and the organic layer was washed by water (100 mL) and brine (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, Eluent of 0-20% EtOAc/PE gradient @100 mL/min) to afford E5 (19 g, 58% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.02 (t, 1H), 4.39 (q, 2H), 1.35 (t, 3H).

Intermediate 4-(difluoromethyl)-2-(1-hydroxy-1-methyl-ethyl)oxazole-5-carboxylic acid according to General Scheme 6, Method A

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Step 1: Preparation of ethyl 2-acetyl-4-(difluoromethyl)oxazole-5-carboxylate (E6)

To a solution of ethyl 2-bromo-4-(difluoromethyl)oxazole-5-carboxylate (E5) (10 g, 37.0 mmol) in toluene (150 mL) was added Pd(PPh₃)₂Cl₂(2.60 g, 3.70 mmol, 0.1 eq) and tributyl(1-ethoxyvinyl)stannane (17.39 g, 48.1 mmol, 16.3 mL, 1.3 eq). The mixture was stirred at 85° C. for 12 hrs under N₂atmosphere. The reaction progress was checked using TLC (PE:EtOAc). EtOAc (100 mL) was added to the reaction mixture, and the organic portion washed with sat. KF solution (150 mL) and brine (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was dissolved in THF (60 mL) and treated with HCl (4 M, 60 mL), and then was stirred at 40° C. for 12 hrs. The reaction progress was checked by TLC (Petroleum ether:EtOAc=10:1). EtOAc (100 mL) was added to the reaction mixture, and the organic portion washed with water (50 mL) and brine (50 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, eluent of 0-20% EtOAc/PE gradient @40 mL/min) to give E6 (7.1 g, 82% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.00-7.36 (m, 1H), 4.48 (q, 2H), 2.66-2.86 (m, 3H), 1.43 (t, 3H).

Step 2: Preparation of ethyl 4-(difluoromethyl)-2-(1-hydroxy-1-methyl-ethyl)oxazole-5-carboxylate (E7)

To a solution of E6 (2.5 g, 10.7 mmol) in THF (120 mL) was added MeMgBr (3 M, 7.15 mL, 2 eq) at −78° C. The mixture was stirred at −78° C. for 1 hr. The reaction progress was checked by TLC (PE:EtOAc=2:1). The reaction mixture was quenched by addition of sat. NH₄Cl solution (50 mL) and then water (100 mL) was added. The aqueous portion was extracted with EtOAc (100 mL×3). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, eluent of 0-12% EtOAc/PE gradient @40 mL/min) to give E7 (3.2 g, 60% yield). ¹H NMR (400 MHz, CDCl₃) δ 6.94-7.29 (m, 1H), 4.46 (q, 2H), 2.86 (s, 1H), 1.72 (s, 6H), 1.44 (t, 3H). The starting material E6 (300 mg) was also recovered.

Step 3: Preparation of 4-(difluoromethyl)-2-(1-hydroxy-1-methyl-ethyl)oxazole-5-carboxylic acid (E8)

To a solution of E7 (3.9 g, 15.7 mmol) in THF (40 mL) and H₂O (40 mL) was added LiOH·H₂O (690 mg, 16.4 mmol, 1.05 eq). The mixture was stirred at rt for 1 hr. The reaction progress was checked using TLC (PE:EtOAc=5:1). The reaction mixture was concentrated to remove THF. The aqueous mixture was then adjusted to pH˜3 by the addition of 1M HCl, and then lyophilized in vacuo to give E8 (4 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 7.35-7.71 (m, 1H), 5.68 (br s, 1H), 1.50 (s, 6H).

Intermediate 2-(1-hydroxycyclobutyl)-4-(trifluoromethyl)oxazole-5-carboxylic acid

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Step 1: Preparation of ethyl 4-(trifluoromethyl)oxazole-5-carboxylate (E10)

To a solution of ethyl 2-amino-4-(trifluoromethyl)oxazole-5-carboxylate (2.00 g, 8.92 mmol) in THF (60 mL) was added t-BuONO (1.84 g, 17.9 mmol, 2.12 mL, 2 eq). The reaction mixture was stirred at 55° C. for 24 hrs. EtOAc (120 mL) was added to the reaction mixture, and the organic portion washed with water (100 mL) and brine (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 8/1) to give E10 (1.2 g, 64% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 4.39 (q, 2H), 1.34 (t, 3H).

Step 2: Preparation of ethyl 2-(1-hydroxycyclobutyl)-4-(trifluoromethyl)oxazole-5-carboxylate (E11)

To a solution of ethyl 4-(trifluoromethyl)oxazole-5-carboxylate (1.2 g, 5.74 mmol) in THF (30 mL) was added LiHMDS (1 M, 8.61 mL, 1.5 eq) at −78° C., and the reaction mixture was stirred at −78° C. for 0.5 hr. Cyclobutanone (1.21 g, 17.2 mmol, 1.29 mL, 3 eq) in THF (5 mL) was added to the reaction mixture, and the mixture was stirred at −78° C. for 2 hrs under N₂atmosphere. The reaction mixture was quenched by the addition of sat. NH₄Cl solution (30 mL), and the aqueous portion extracted with EtOAc (100 mL). The organic layer washed by water (70 mL) and brine (70 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 10/1) to give E11 (600 mg, 37% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.29 (q, 2H), 2.78-2.94 (m, 1H), 2.52-2.65 (m, 2H), 2.24-2.38 (m, 2H), 1.78-1.98 (m, 3H), 1.26 (t, 3H).

Step 3: Preparation of 2-(1-hydroxycyclobutyl)-4-(trifluoromethyl)oxazole-5-carboxylic acid (E12)

To a solution of ethyl 2-(1-hydroxycyclobutyl)-4-(trifluoromethyl)oxazole-5-carboxylate (600 mg, 2.15 mmol) in H₂O (2 mL) and THF (10 mL) was added LiOH·H₂O (99.2 mg, 2.36 mmol, 1.1 eq) at 0° C. The reaction mixture was stirred at rt for 2 hrs and concentrated in vacuo to remove THF. Water (10 mL) was added, and the aqueous portion extracted with TBME (30 mL). The aqueous layer was then adjusted to pH˜6 by the addition of 0.5 μM HCl and concentrated to dryness to give E12 (540 mg), which was used without further purification. ¹H NMR (400 MHz, CD₃OD) δ 2.54-2.67 (m, 2H), 2.19-2.34 (m, 2H), 1.81-1.95 (m, 1H), 1.66-1.80 (m, 1H).

Intermediate ethyl 4-bromo-2-(2-hydroxypropan-2-yl)oxazole-5-carboxylate according to General Scheme 6

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Step 1: Preparation of Ethyl 4-bromooxazole-5-carboxylate (E14)

Ethyl oxazole-5-carboxylate (E13) (500 mg, 3.54 mmol) was added in THF (2.50 mL) and DMF (2.50 mL) at approximately 10° C. The reaction mixture was cooled to −80° C. and LiHMDS (1 M, 4.61 mL, 1.30 eq) was added dropwise at approximately −80° C. The reaction mixture was stirred at approximately −80° C. for 0.5 hr. Br₂(736 mg, 4.61 mmol, 1.3 eq) was then added dropwise at approximately −80° C. The reaction mixture was stirred at approximately −80° C. for 0.5 hr. The reaction progress was checked using LC-MS. The reaction mixture was combined with 19 other reactions performed using 500 mg of E13. The combined reaction mixture was poured into sat. citric acid at approximately −10° C. The aqueous portion was extracted with EtOAc (50 mL×3). The combined organic layer was washed with brine (50 mL), dried with Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 0/1) to give E14 (3.00 g, 19% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 8.70 (s, 1H), 4.29-4.34 (m, 2H), 1.29 (t, 3H); LC-MS: m/z 219.9 & 221.9 (M+H)+.

Step 2: Preparation of Ethyl 4-bromo-2-iodooxazole-5-carboxylate (E15)

Ethyl 4-bromooxazole-5-carboxylate (E14) (3.15 g, 14.3 mmol, 1.00 eq) was added in THF (15.0 mL) at rt. LiHMDS (1 M, 17.2 mL, 1.20 eq) was added dropwise at approximately −80° C. 12 (5.45 g, 21.5 mmol, 1.50 eq) in THF (15.0 mL) was then added dropwise at approximately −80° C. The reaction mixture was stirred at approximately −80° C. for 1 hr. The reaction progress was checked using TLC (PE/EtOAc). The reaction mixture was poured into saturated citric acid (30 mL) at approximately −10° C. The aqueous phase was extracted with ethyl acetate (30 mL×3). The combined organic layer was washed with brine (30 mL), dried with Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 0/1) to afford E15 (1.10 g, 22% yield). ¹H NMR (400 MHz, DMSO-d₆) δ: 4.29-4.35 (m, 2H), 1.30 (t, 3H). LC-MS: m/z 345.8 & 347.9 (M+H)+.

Step 3: Preparation of Ethyl 4-bromo-2-(2-hydroxypropan-2-yl)oxazole-5-carboxylate (E16)

Ethyl 4-bromo-2-iodooxazole-5-carboxylate (E15) (1.10 g, 3.18 mmol) was added in THF (10 mL) at approximately 10° C. under N₂. The reaction mixture was degassed under vacuum and purged with N₂three times. The mixture was cooled to −80° C., and iPr-MgCl·LiCl (1.3 M, 2.45 mL, 1 eq) was added dropwise at approximately −80° C. The reaction mixture was stirred at approximately −80° C. for 0.5 hr, and then acetone (222 mg, 3.82 mmol, 1.20 eq) was added dropwise at approximately −80° C. The mixture was stirred at approximately −80° C. for 0.5 hr. The reaction progress was checked using TLC (PE/EtOAc=5/1). The reaction mixture was poured into sat. citric acid solution (5 mL) at approximately −10° C. The aqueous portion was extracted with ethyl acetate (5 mL×3). The combined organic layer was washed with brine (5 mL), dried with Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 0/1) and further purified by prep-HPLC (column: Phenomenex luna C18 80×40 mm×3 um; mobile phase: [water (0.04% HCl)-ACN]; B %: 18%-45%, 7 min) to afford E16 (140 mg, 16% yield). ¹H NMR (400 MHz, DMSO-d₆) δ: 5.93 (s, 1H), 4.30-4.37 (m, 2H), 1.50 (s, 6H), 1.32 (t, 3H). LC-MS: m/z 277.9 & 279.9 (M+H)+.

Intermediate ethyl 4-chloro-2-(2-hydroxypropan-2-yl)oxazole-5-carboxylate according to General Scheme 6

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Step 1: Preparation of Ethyl 4-chlorooxazole-5-carboxylate (E17)

Ethyl oxazole-5-carboxylate (E13) (10.0 g, 70.9 mmol) was added in DMF (50 mL) at approximately 10° C. The reaction mixture was cooled to −80° C., and LiHMDS (1 M, 92.1 mL, 1.3 eq) was added dropwise at approximately −80° C. The reaction mixture was stirred at approximately −80° C. for 0.5 hr, and NCS (12.3 g, 92.1 mmol, 1.3 eq) in THF (50 mL) was then added dropwise at approximately −80° C. The mixture was stirred at approximately −80° C. for 0.5 hr. The reaction progress was checked using TLC (PE/EtOAc=5/1). The reaction mixture was combined for workup with seven other reactions each performed using 10 g of E13. The combined reaction mixture was poured into sa citric acid solution (100 mL) at approximately −10° C. The aqueous portion was extracted with ethyl acetate (100 mL×3). The combined organic layer was washed with brine (50 mL), dried with Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 0/1) to afford E17 (18.0 g, 18% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.94 (s, 1H), 4.44 (q, 2H), 1.42 (t, 3H); LC-MS: m/z 176.0 (M+H)⁺.

Step 2: Preparation of Ethyl 4-chloro-2-iodooxazole-5-carboxylate (E18)

Three reactions were carried out in parallel. Ethyl 4-chlorooxazole-5-carboxylate (E17) (6.00 g, 34.2 mmol) was dissolved in THF (30 mL) at rt. LiHMDS (1 M, 41.0 mL, 1.2 eq) was added dropwise at approximately −80° C., followed by the dropwise addition of 12 (13.0 g, 51.3 mmol, 1.5 eq) in THF (30 mL) at approximately −80° C. The reaction mixture was stirred at approximately −80° C. for 1 hr. The reaction progress was checked using TLC (PE/EtOAc=5/1). The three parallel reactions were combined together for workup. The combined reaction mixture was poured into sat. citric acid solution (100 mL) at approximately −5° C. The aqueous portion was extracted with ethyl acetate (100 mL×3). The combined organic layer was washed with brine (50 mL), dried with Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 0/1) to afford E18 (10.0 g, 32% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 4.20-4.27 (m, 2H), 1.21 (t, 3H); LC-MS: m/z 301.9 (M+H)⁺.

Step 3: Preparation of Ethyl 4-chloro-2-(2-hydroxypropan-2-yl)oxazole-5-carboxylate (E19)

Two reactions were carried out in parallel. Compound E18 (5.00 g, 16.6 mmol) was added in THF (50 mL) at approximately 10° C. under N₂. The suspension was degassed under vacuum and purged with N₂three times. The mixture was cooled to −80° C., and iPr-MgCl·LiCl (1.3 M, 12.8 mL, 1 eq) was added dropwise at approximately −80° C. The mixture was stirred at approximately −80° C. for 0.5 hr, and acetone (1.16 g, 19.9 mmol, 1.2 eq) was then added dropwise at approximately −80° C. The mixture was stirred at approximately −80° C. for 0.5 hr. The reaction progress was checked using TLC (PE/EtOAc=5/1). The two parallel reactions were combined together for workup. The combined reaction mixture was poured into sat. citric acid solution (50 mL) at approximately −10° C. The aqueous portion was extracted with ethyl acetate (50 mL×3). The combined organic layer was washed with brine (50 mL), dried with Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=I/O to 0/1) and further purified by prep-HPLC (column: Phenomenex luna C18 (250×70 mm, 15 um); mobile phase: [water (0.05% HCl)-ACN]; B %: 20%-50%, 23 min) to afford E19 (1.80 g, 23% yield). ¹H NMR (400 MHz, DMSO-d₆) δ: 5.92 (s, 1H), 4.32-4.37 (m, 2H), 1.51 (s, 6H), 1.31 (t, 3H); LC-MS: m/z 234.0 (M+H)⁺.

Intermediate 4-(difluoromethyl)-2-(2-cyanopropan-2-yl)oxazole-5-carboxylic acid

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Step 1: Preparation of 2-cyano-2-methyl-propanoyl chloride (E20)

To a solution of 2-cyano-2-methyl-propanoic acid (2 g, 17.7 mmol) and DMF (129 mg, 1.77 mmol, 136 μL, 0.1 eq) in DCM (20 mL) was added oxalyl chloride (2.69 g, 21.2 mmol, 1.86 mL, 1.2 eq) dropwise at 0° C., and then the reaction mixture was stirred at rt for 1 hr. The reaction mixture was concentrated to dryness to afford E20 (2.5 g), which was used without further purification.

Step 2: Preparation of ethyl (Z)-3-[(2-cyano-2-methyl-propanoyl)amino]-4,4-difluoro-but-2-enoate (E21)

To a solution of ethyl (Z)-3-amino-4,4-difluoro-but-2-enoate (2 g, 12.1 mmol) in dioxane (20 mL) was added a solution of 2-cyano-2-methyl-propanoyl chloride (E20) (2.39 g, 18.2 mmol, 1.5 eq) in dioxane (20 mL) at rt. The reaction mixture was stirred at 110° C. for 12 hrs. The reaction progress was checked using TLC (PE/Ethyl acetate=5/1). The reaction mixture was concentrated to dryness, and the residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, eluent of 0-7% EtOAc/PE gradient @40 mL/min) to give E21 (2.4 g, 76% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 10.90 (s, 1H), 6.95-7.27 (m, 1H), 5.81 (s, 1H), 4.12-4.29 (m, 2H), 1.51-1.69 (m, 6H), 1.20 (t, 3H); LCMS: m/z 259.1 μM+H]⁺.

Step 3: Preparation of ethyl 2-(1-cyano-1-methyl-ethyl)-4-(difluoromethyl)oxazole-5-carboxylate (E22)

To a solution of ethyl (Z)-3-[(2-cyano-2-methyl-propanoyl)amino]-4,4-difluoro-but-2-enoate (E21) (2.4 g, 9.22 mmol) in DCE (20 mL) was added BF₃·Et₂O (2.62 g, 18.4 mmol, 2.28 mL, 2 eq) and PIDA (4.16 g, 12.9 mmol, 1.4 eq) at rt. The mixture was stirred at 90° C. for 18 hrs. The reaction progress was checked by TLC (PE/EtOAc). The reaction mixture was concentrated to dryness. DCM (100 mL) was added to the residue, and the organic layer washed with sat. Na₂CO₃solution (10 mL) and brine (50 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, eluent of 0-7% EtOAc/PE gradient @30 mL/min) to give E22 (0.25 g, 11% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.03-7.55 (m, 1H), 4.35 (q, 2H), 1.77 (s, 6H), 1.29 (t, 3H).

Step 4: Preparation of 2-(1-cyano-1-methyl-ethyl)-4-(difluoromethyl)oxazole-5-carboxylic acid (E23)

To a solution of ethyl 2-(1-cyano-1-methyl-ethyl)-4-(difluoromethyl)oxazole-5-carboxylate (E22) (0.25 g, 968 μmol) in THF (3 mL) and H₂O (1 mL) was added LiOH·H₂O (48.8 mg, 1.16 mmol, 1.2 eq). The mixture was stirred at rt for 18 hrs. Reaction completeness was checked using TLC (PE:EtOAc=5:1). The reaction mixture was concentrated under reduced pressure to remove THF. The aqueous portion was adjusted with 2 μM HCl to pH ˜7, and then lyophilized under vacuo to give E23 (0.22 g, 99% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.23-7.74 (m, 1H), 1.73 (s, 6H).

Intermediate 4-(difluoromethyl)-2-(pyrimidin-2-yl)oxazole-5-carboxylic acid according to General Scheme 5, Method B

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Step 1: Preparation of ethyl 4-(difluoromethyl)-2-pyrimidin-2-yl-oxazole-5-carboxylate (E24)

To a solution of ethyl 4-(difluoromethyl)oxazole-5-carboxylate (E4) (1 g, 5.23 mmol), Pd₂(dba)₃(240 mg, 262 μmol, 0.05 eq), (5-diphenylphosphanyl-9,9-dimethyl-xanthen-4-yl)-diphenyl-phosphane (151 mg, 262 μmol, 0.05 eq) and Cs₂CO₃(3.41 g, 10.5 mmol, 2 eq) in 1,2-dimethoxyethane (3 mL) was added 2-chloropyrimidine (599 mg, 5.23 mmol) under N₂atmosphere. The reaction mixture was stirred at 90° C. for 12 hrs. DCM (50 mL) was added to the reaction mixture, and the organic portion washed by water (40 mL) and brine (40 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 1/1) to give E24 (400 mg, 25% yield). ¹H NMR (400 MHz, CDCl₃) δ 9.02 (br d, 2H), 7.52 (t, 1H), 7.38 (s, 1H), 7.24 (s, 1H), 7.11 (s, 1H), 4.54 (q, 2H), 1.48 (t, 3H).

Step 2: Preparation of 4-(difluoromethyl)-2-pyrimidin-2-yl-oxazole-5-carboxylic acid (E25)

To a solution of ethyl 4-(difluoromethyl)-2-pyrimidin-2-yl-oxazole-5-carboxylate (E24) (450 mg, 1.67 mmol) in THF (2 mL) and H₂O (2 mL) was added LiOH·H₂O (77.2 mg, 1.84 mmol, 1.1 eq). The reaction mixture was stirred at rt for 1 hr. The reaction mixture was concentrated to remove THF, and H₂O (10 mL) was added. The aqueous layer was extracted with TBME (30 mL). The aqueous layer was then adjusted to pH˜6 with 0.5 μM HCl and extracted with DCM/MeOH (30/3 mL) 3 times. The combined DCM/MeOH organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness to afford E25 (350 mg), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 9.06 (d, 2H), 7.75 (t, 1H), 7.20-7.57 (m, 1H).

Intermediate 2-(1-hydroxy-1-methyl-ethyl)-4-methyl-oxazole-5-carboxylic acid according to General Scheme 4 and General Scheme 6, Method A

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Step 1: Preparation of ethyl 2-amino-4-methyl-oxazole-5-carboxylate (E26)

A mixture of ethyl 2-chloro-3-oxo-butanoate (55 g, 334 mmol, 46.2 mL) and urea (100.34 g, 1.67 mol, 89.6 mL, 5 eq) in DMF (100 mL) was stirred at 120° C. for 12 hours. Reaction progress was checked using TLC (PE:EtOAc=5:1). The reaction mixture was cooled to rt, poured into H₂O (400 ml), and stirred at 0° C. for 30 min. The solid was collected by filtration, rinsed with water (30 mL), and then dried in vacuo to give E26 (22.2 g, 39% yield). ¹H NMR (400 MHz, CD₃OD) δ 4.29 (q, 2H), 2.32 (s, 3H), 1.35 (t, 3H).

Step 2: Preparation of ethyl 2-bromo-4-methyl-oxazole-5-carboxylate (E27)

To a solution of E26 (11.1 g, 65.2 mmol) in MeCN (120 mL) was added CuBr₂(21.85 g, 97.9 mmol, 4.58 mL, 1.5 eq) at 0° C. The mixture turned dark green and was further stirred for 15 min at rt. t-BuONO (10.09 g, 97.9 mmol, 11.6 mL, 1.5 eq) was added. The reaction was stirred at rt for 2 hrs and then heated at 50° C. for 4 hrs. Reaction progress was checked using TLC (Petroleum ether:EtOAc=3:1). The reaction mixture was concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, eluent of 0-5% EtOAc/PE gradient @100 mL/min) to give E27 (8.5 g, 56% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.25-4.35 (m, 2H), 2.45 (s, 3H), 1.32 (t, 3H).

Step 3: Preparation of ethyl 2-acetyl-4-methyloxazole-5-carboxylate (E28)

A mixture of E27 (9.5 g, 40.6 mmol), tributyl(1-ethoxyvinyl) stannane (17.59 g, 48.7 mmol, 16.4 mL, 1.2 eq) and Pd(PPh₃)₂Cl₂(2.85 g, 4.06 mmol, 0.1 eq) in toluene (200 mL) was stirred at 90° C. for 12 hrs under N₂atmosphere. Reaction progress was checked using TLC (Petroleum ether:EtOAc=5:1). EtOAc (300 ml) was added, followed by sat. KF solution (500 ml). The resulting mixture was stirred at rt for 40 min, the mixture filtered, and the filtrate separated. The organic layer was washed with brine (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was dissolved in THF (300 ml), and 4 N HCl (300 ml) was added. The mixture was stirred at rt for 12 hrs. LCMS indicated the desired mass was detected. The reaction mixture was extracted with DCM (100 mL×3). The combined organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 24 g SepaFlash® Silica Flash Column, eluent of 0-10% EtOAc/PE gradient @35 mL/min) to give E28 (6.8 g, 85% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.35 (q, 2H), 2.62 (s, 3H), 2.48 (s, 3H), 1.34 (t, 3H); LCMS: m/z 198.1 (M+H)⁺.

Step 4: Preparation of ethyl 2-(2-hydroxypropan-2-yl)-4-methyloxazole-5-carboxylate (E29)

To a solution of E28 (2.5 g, 12.7 mmol) in THF (25 mL) was added MeMgBr (3 M, 12.7 mL, 3 eq) dropwise under N₂at −78° C. The reaction was stirred at −78° C. for 1.5 hr. Reaction progress was checked using TLC (Petroleum ether:EtOAc=5:1, by UV). The reaction was quenched by the addition of sat. NH₄Cl solution (30 mL) slowly and then the organic portion extracted with EtOAc (30 mL×3). The combined organic phase was washed with brine (30 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, Petroleum ether/EtOAc=1/0 to 1/1) to give E29 (1.7 g, 63% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.39 (q, 2H), 2.47 (s, 3H), 1.67 (s, 6H), 1.40 (t, 3H).

Alternatively, E29 can be prepared by reacting 2-hydroxy-2-methylpropanamide with ethyl 2-chloro-3-oxo-butanoate in a neat reaction at 150° C. for 6 hrs.

Step 5: Preparation of ethyl 2-(2-hydroxypropan-2-yl)-4-methyloxazole-5-carboxylic acid (E30)

To a solution of E29 (3.4 g, 16.0 mmol) in THF (30 mL) and H₂O (15 mL) was added LiOH·H₂O (803 mg, 19.1 mmol, 1.2 eq). The reaction was stirred at rt for 1.5 hr. Reaction progress was tracked using LCMS. The reaction mixture was adjusted to pH 7 with HCl (1 M) and concentrated to dryness to afford E30 (4 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 5.67 (s, 1H), 2.30 (s, 2H), 1.44 (s, 6H); LCMS: m/z 186.1 (M+H)⁺.

Intermediate 4-cyclopropyl-2-(2-hydroxypropan-2-yl)oxazole-5-carboxylic acid according to General Scheme 4

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Step 1: Preparation of ethyl 2-bromo-3-cyclopropyl-3-oxo-propanoate (E31)

To a solution of ethyl 3-cyclopropyl-3-oxo-propanoate (8 g, 51.2 mmol) in DCM (100 mL) was added NBS (9.12 g, 51.2 mmol) and TsOH·H₂O (1.95 g, 10.2 mmol, 0.2 eq). The reaction mixture was stirred at rt for 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=10:1). The reaction mixture was concentrated to dryness. EtOAc (120 mL) was added to the residue, and the mixture filtered. The filtrate was washed with sat. NaHCO₃solution (2×100 mL) and water (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1:0 to 10:1) to give E31 (12 g, 100% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 5.71 (s, 1H), 4.18 (q, 2H), 2.14-2.28 (m, 1H), 1.18 (t, 3H), 1.01-1.08 (m, 2H), 0.89-0.96 (m, 2H); LCMS: m/z 235.0 μM+H]⁺.

Step 2: Preparation of ethyl 4-cyclopropyl-2-(1-hydroxy-1-methyl-ethyl)oxazole-5-carboxylate (E32)

To a solution of ethyl 2-bromo-3-cyclopropyl-3-oxo-propanoate (E31) (1 g, 4.25 mmol) in DMF (2 mL) was added 2-hydroxy-2-methyl-propanamide (2.19 g, 21.3 mmol, 5 eq). The mixture was stirred at 110° C. for 40 hrs. Reaction progress was tracked using LC-MS. The reaction mixture was adjusted to pH˜8 by addition of sat. aq. NaHCO₃at 0° C. H₂O (50 mL) was added, and the aqueous portion extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1:0 to 2:1) to give E32 (0.15 g, 14% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 5.70 (s, 1H), 4.29 (q, 2H), 2.40-2.45 (m, 1H), 1.43 (s, 6H), 1.27 (t, 3H), 0.94-1.04 (m, 2H), 0.79-0.92 (m, 2H); LCMS: m/z 240.0 μM+H]⁺.

Step 3: Preparation of 4-cyclopropyl-2-(1-hydroxy-1-methyl-ethyl)oxazole-5-carboxylic acid (E33)

To a solution of ethyl 4-cyclopropyl-2-(1-hydroxy-1-methyl-ethyl)oxazole-5-carboxylate (E32) (590 mg, 2.47 mmol) in THF (4 mL) and H₂O (4 mL) was added LiOH·H₂O (114 mg, 2.71 mmol, 1.1 eq). The reaction mixture was stirred at rt for 16 hrs. Reaction progress was tracked using LC-MS. The reaction mixture was concentrated to remove THF. The aqueous portion was adjusted to pH˜7 by the addition of HCl (1 M) and then lyophilized to give E33 (550 mg, 90% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 2.70-2.84 (m, 1H), 1.39 (s, 6H), 0.62-0.81 (m, 4H); LCMS: m/z 212.0 μM+H]⁺.

Intermediate 4-cyanooxazole-5-carboxylic acid

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Step 1: Preparation of ethyl 4-cyanooxazole-5-carboxylate (E34)

To a solution of ethyl 4-bromooxazole-5-carboxylate (E14) (10 g, 45.5 mmol) in THF (30 mL) and H₂O (150 mL) was added Zn(CN)₂(3.74 g, 31.8 mmol, 2.02 mL, 0.7 eq) and t-BuXPhos-Pd-G3 (1.81 g, 2.27 mmol, 0.05 eq). The reaction mixture was degassed under vacuum and purged with N₂3 times, and then the mixture was stirred at 40° C. for 16 hrs under N₂. Reaction progress was tracked using TLC (PE:EtOAc=5:1). EtOAc (300 mL) was added to the reaction mixture, and the organic layer washed with H₂O (50 mL) and brine (50 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=100/1 to 10/1) to give E34 (7.5 g, 99% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 8.89 (s, 1H), 4.37 (q, 2H), 1.30 (t, 3H).

Step 2: Preparation of (4-cyanooxazole-5-carbonyl)oxylithium (E35)

To a solution of E34 (5 g, 30.1 mmol) in THF (40 mL) and H₂O (80 mL) was added LiOH·H₂O (1.33 g, 31.6 mmol, 1.05 eq). The mixture was stirred at rt for 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=5:1). The reaction mixture was concentrated in vacuo to remove most of the THF and then lyophilized in vacuo to give E35 (4.5 g), which was used without further purification. H NMR (400 MHz, DMSO-d₆) δ 8.47 (s, 1H).

Intermediate [5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-1,3,4-oxadiazole-2-carbonyl]oxylithium according to General Scheme 9

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Step 1: Preparation of ethyl 5-methylsulfanyl-1,3,4-oxadiazole-2-carboxylate (E36)

A mixture of ethyl 2-hydrazino-2-oxo-acetate (16 g, 121 mmol) and di(1H-imidazol-1-yl)methanethione (25.90 g, 145 mmol, 1.2 eq) in THF (300 mL) was stirred at rt for 12 hrs, and then heated to 75° C. for 4 hrs. After cooling to rt, K₂CO₃(50.21 g, 363 mmol, 3 eq) and CH₃I (85.95 g, 606 mmol, 37.7 mL, 5 eq) were added. The resulting mixture was stirred at rt for 2 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). The reaction mixture was combined with another reaction performed with 8.5 g of ethyl 2-hydrazino-2-oxo-acetate and quenched by the addition of H₂O (100 mL). DCM (500 mL) was added, and the organic layer was separated and washed with brine (2×100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (Eluent of 0-25% PE:EtOAc @40 mL/min) to give E36 (25 g). ¹H NMR (400 MHz, CDCl₃) δ 4.43 (q, 2H), 2.72 (s, 3H), 1.38 (t, 3H).

Step 2: Preparation of ethyl 5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-1,3,4-oxadiazole-2-carboxylate (E37)

A mixture of E36 (233 mg, 1.24 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole (410 mg, 1.49 mmol, 1.2 eq), Na₂CO₃(394 mg, 3.71 mmol, 3 eq), thiophene-2-carbonyloxycopper (472 mg, 2.48 mmol, 2 eq) and Pd(dppf)Cl₂(181 mg, 248 μmol, 0.2 eq) in dioxane (9 mL) was degassed and purged with N₂3 times, and then the reaction mixture was stirred at 75° C. for 16 hrs under N₂. Reaction progress was tracked using TLC (PE:EtOAc=2:1). EtOAc (100 mL) was added to the reaction mixture, and the organic layer washed with water (30 mL) and brine (30 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 2/1) to give E37 (140 mg, 39% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.61 (s, 1H), 8.22 (s, 1H), 5.12 (q, 2H), 4.51 (q, 2H), 1.44 (t, 3H); LCMS: m/z 291.1 (M+H)⁺.

Step 3: Preparation of [5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-1,3,4-oxadiazole-2-carbonyl]oxylithium (E38)

To a solution of E37 (140 mg, 482 μmol) in THF (1.5 mL) was added LiOH·H₂O (22.3 mg, 531 μmol, 1.1 eq) in H₂O (3 mL). The reaction mixture was stirred at rt for 2 hrs. Reaction progress was tracked using TLC (DCM:MeOH). The reaction mixture was concentrated in vacuo to remove most of the THF and then lyophilized in vacuo to give E38 (115 mg), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 8.58 (s, 1H), 8.14 (s, 1H), 5.27 (q, 2H).

Alternatively, ethyl 5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-1,3,4-oxadiazole-2-carboxylate (E37) can be prepared accordingly to the following scheme

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Step A: Preparation of ethyl 1-(2,2,2-trifluoroethyl)pyrazole-4-carboxylate (E39)

To a solution of ethyl 1H-pyrazole-4-carboxylate (10 g, 71.4 mmol) and K₂CO₃(19.72 g, 142 mmol, 2 eq) in DMF (45 mL) was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (21.53 g, 92.8 mmol, 1.3 eq) dropwise, and then the resulting mixture was stirred at 50° C. for 6 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). EtOAc (300 mL) was added to the reaction mixture, and the organic layer washed with H₂O (100 mL) and brine (2×100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, eluent of 0-12% PE/EtOAc @60 mL/min) to give E39 (16 g). ¹H NMR (400 MHz, CDCl₃) δ 8.01 (d, 2H), 4.73 (q, 2H), 4.32 (q, 2H), 1.36 (t, 3H).

Step B: Preparation of 1-(2,2,2-trifluoroethyl)pyrazole-4-carbohydrazide (E40)

To a solution of E39 (16 g, 72.0 mmol) in THF (100 mL) was added NH₂NH₂·H₂O (7.73 g, 151 mmol, 7.5 mL, 98% purity, 2.1 eq), and then the reaction mixture was stirred at 80° C. for 15 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). The reaction mixture was concentrated to dryness. The residue was triturated with TBME (50 mL) and stirred for 15 min. The precipitate was collected by filtration, and then dried in vacuo to give E40 (13 g). ¹H NMR (400 MHz, CD₃OD) δ 8.19 (s, 1H), 7.93 (s, 1H), 4.98 (q, 2H).

Step C: Preparation of ethyl N-[[1-(2,2,2-trifluoroethyl)pyrazole-4-carbonyl]amino]carbamate (E41)

To a solution of E40 (3 g, 14.4 mmol) in THF (70 mL) was added ethyl 2-chloro-2-oxo-acetate (2.36 g, 17.3 mmol, 1.9 mL, 1.2 eq) dropwise at 0° C., and then the reaction mixture was stirred at rt for 3 hrs. The precipitate was collected by filtration and rinsed with TBME (30 mL), and then dried in vacuo to give E41 (1.5 g, 37% yield). ¹H NMR (400 MHz, CDCl₃) δ 9.75 (br s, 1H), 9.06 (br s, 1H), 8.25 (s, 1H), 7.99 (s, 1H), 4.76 (q, 2H), 4.42 (q, 2H), 1.42 (t, 3H).

Step D: Preparation of ethyl 5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-1,3,4-oxadiazole-2-carboxylate (E37)

To a solution of E41 (1.5 g, 5.35 mmol) and Et₃N (271 mg, 2.68 mmol, 373 μL, 0.5 eq) in DCM (30 mL) was added TsCl (491 mg, 6.96 mmol, 1.3 eq) in portions at 0° C., and then the resulting mixture was stirred at rt for 18 hrs. Reaction progress was tracked using TLC (PE:EtOAc=1:1). DCM (100 mL) was added to the reaction mixture, and the organic layer washed with sat. Na₂CO₃solution (60 mL) and brine (60 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, Eluent of 0-16% PE/EtOAc @40 mL/min) to give E37 (0.65 g, 42% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.16-8.29 (m, 2H), 4.80 (q, 2H), 4.53 (q, 2H), 1.47 (t, 3H).

Intermediate lithium 5-morpholino-1,3,4-oxadiazole-2-carboxylate according to General Scheme 10

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Step 1: Preparation of ethyl 5-bromo-1, 3, 4-oxadiazole-2-carboxylate (E42)

To a solution of ethyl 5-amino-1,3,4-oxadiazole-2-carboxylate (5 g, 31.8 mmol) in MeCN (60 mL) was added CuBr₂(10.66 g, 47.7 mmol, 2.2 mL, 1.5 eq) at 0° C. The reaction mixture turned dark green and was stirred for 15 min at rt. t-BuONO (4.92 g, 47.7 mmol, 5.7 mL, 1.5 eq) was added at 0° C., and the reaction mixture was stirred at rt for 2 hrs, then heated at 50° C. for another 12 hrs. The reaction progress was checked using TLC (PE/EtOAc=1/1). The reaction mixture was filtered and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, eluent of 0-50% EtOAc/PE gradient @40 mL/min) to give E42 (4.5 g, 64% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.52 (q, 2H), 1.45 (t, 3H).

Step 2: Preparation of ethyl 5-morpholino-1,3,4-oxadiazole-2-carboxylate (E43)

To a solution of ethyl 5-bromo-1,3,4-oxadiazole-2-carboxylate (E42) (1 g, 4.52 mmol) and morpholine (473 mg, 5.43 mmol, 478 μL, 1.2 eq) in THF (40 mL) was added DIPEA (1.17 g, 9.05 mmol, 1.6 mL, 2 eq) at 0° C. The mixture was stirred at rt for 1 hr. The reaction progress was checked using TLC (PE/EtOAc=1/1). EtOAc (100 mL) was added to the reaction mixture, and the organic portion washed with water (30 mL) and brine (30 mL×2), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0-30% EtOAc/PE gradient @35 mL/min) to give E43 (800 mg, 78% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 4.37 (q, 2H), 3.68-3.74 (m, 4H), 3.48-3.52 (m, 4H), 1.31 (t, 3H).

Step 3: Preparation of (5-morpholino-1, 3, 4-oxadiazole-2-carbonyl) oxylithium (E44)

To a solution of ethyl 5-morpholino-1, 3, 4-oxadiazole-2-carboxylate (E43) (800 mg, 3.52 mmol) in THF (8 mL) and H₂O (12 mL) was added LiOH·H₂O (162 mg, 3.87 mmol, 1.1 eq). The reaction mixture was stirred at rt for 12 hrs. The reaction progress was checked using TLC (PE/EtOAc=1/1). The reaction mixture was concentrated to dryness to afford E44 (600 mg), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 3.62-3.74 (m, 4H), 3.36 (br d, 4H).

Intermediate [5-(5-fluoro-2-pyridyl)-1,3,4-oxadiazole-2-carbonyl]oxylithium according to General Scheme 9, Method A

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Step 1: Preparation of methyl 5-fluoropyridine-2-carboxylate (E45)

A solution of 5-fluoropyridine-2-carbonitrile (15 g, 123 mmol) in HCl/MeOH (4 M, 180 mL, 5.9 eq) was stirred at 60° C. for 12 hrs. The reaction mixture was concentrated in vacuo, and the residue was dissolved in EtOAc (150 mL), washed with sat. NaHCO₃solution (50 mL) and brine (20 mL). The organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0-25% EtOAc/PE gradient @60 mL/min) to give E45 (15.24 g, 80% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, 1H), 8.20 (dd, 1H), 7.53 (ddd, 1H), 4.00 (s, 3H).

Step 2: Preparation of 5-fluoropyridine-2-carbohydrazide (E46)

A mixture of methyl 5-fluoropyridine-2-carboxylate (E45) (16 g, 103 mmol), NH₂NH₂·H₂O (11.06 g, 217 mmol, 10.7 mL, 98% purity, 2.1 eq) in EtOH (70 mL) was degassed and purged with N₂for 3 times, and then the reaction mixture was stirred at rt for 3 hrs under N₂atmosphere. The reaction mixture was concentrated to dryness to give E46 (15 g, 94% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 9.89 (br s, 1H), 8.61 (d, 1H), 8.07 (dd, 1H), 7.88 (td, 1H), 4.57 (br s, 2H).

Step 3: Preparation of ethyl 2-[2-(5-fluoropyridine-2-carbonyl)hydrazino]-2-oxo-acetate (E47)

To a mixture of 5-fluoropyridine-2-carbohydrazide (E46) (13.5 g, 87.0 mmol) and TEA (17.61 g, 174 mmol, 24.2 mL, 2 eq) in DCM (500 mL) was added ethyl 2-chloro-2-oxo-acetate (15.45 g, 113 mmol, 12.7 mL, 1.3 eq) over a period of 10 min at 0° C. The reaction mixture was stirred for 2 hrs at rt. H₂O (100 mL) was added to the reaction mixture, and the aqueous portion extracted with DCM (300 mL×3). The combined organic layer was washed with brine (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0-2.5% EtOAc/PE gradient @60 mL/min) to give E47 (16 g, 53% yield). ¹H NMR (400 MHz, CDCl₃) δ 10.03-10.15 (m, 1H), 9.65 (br d, 1H), 8.35-8.42 (m, 1H), 8.11-8.18 (m, 1H), 7.51 (td, 2H), 4.35 (q, 1H), 1.34 (t, 3H); LCMS: m/z 256.2 μM+H]⁺.

Step 4: Preparation of ethyl 5-(5-fluoro-2-pyridyl)-1,3,4-oxadiazole-2-carboxylate (E48)

To a solution of ethyl 2-[2-(5-fluoropyridine-2-carbonyl)hydrazino]-2-oxo-acetate (E47) (16 g, 62.7 mmol) in DCM (350 mL) was added TEA (8.25 g, 81.5 mmol, 11.3 mL, 1.3 eq) and TosCl (5.98 g, 31.4 mmol, 0.5 eq) in 3 portions at 0° C. The mixture was stirred at rt for 3 hrs. Sat. NaHCO₃solution (200 mL) was added, and the aqueous portion extracted with DCM (400 mL×3). The combined organic layer was washed with brine (200 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, Eluent of 0˜2.5% MeOH/DCM@85 mL/min) to give E48 (8.2 g, 49% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.71 (d, 1H), 8.39 (dd, 1H), 7.66 (ddd, 1H), 4.59 (q, 2H), 1.51 (t, 3H); LCMS: m/z 238.2 μM+H]⁺.

Step 5: Preparation of [5-(5-fluoro-2-pyridyl)-1,3,4-oxadiazole-2-carbonyl]oxylithium (E49)

To a solution of ethyl 5-(5-fluoro-2-pyridyl)-1,3,4-oxadiazole-2-carboxylate (E48) (12 g, 50.6 mmol) in THF (140 mL) and H₂O (180 mL) was added LiOH·H₂O (2.23 g, 53.1 mmol, 1.05 eq). The mixture was stirred at rt for 2 hrs. The reaction mixture was concentrated in vacuo to remove most of THF, and the aqueous portion was lyophilized in vacuo to give E49 (11.5 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 8.79 (d, 1H), 8.24 (dd, 1H), 7.99 (td, 1H).

Intermediate 5-(difluoromethyl)-1-(2,2,2-trifluoroethyl)pyrazole-4-carboxylic acid

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Step 1: Preparation of ethyl 5-(difluoromethyl)-1-(2,2,2-trifluoroethyl)pyrazole-4-carboxylate (E50)

To a solution of (Z)-ethyl 2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate (1 g, 4.52 mmol) in THF (8 mL) was added 2,2,2-trifluoroethylhydrazine (670 mg, 5.88 mmol, 1.3 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 1 hr, and then stirred at rt for 16 hrs. Reaction progress was checked using LCMS. The reaction mixture was concentrated to dryness, and the residue was purified by flash silica gel chromatography (Eluent: 0-5% EtOAc/PE gradient) to give E50 (850 mg, 69% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.02 (s, 1H), 7.38-7.75 (m, 1H), 4.95 (q, 2H), 4.37 (q, 2H), 1.40 (t, 3H); LCMS: m/z 273.1 μM+H]⁺.

Step 2: Preparation of 5-(difluoromethyl)-1-(2,2,2-trifluoroethyl)pyrazole-4-carboxylic acid (E51)

To a solution of ethyl 5-(difluoromethyl)-1-(2,2,2-trifluoroethyl)pyrazole-4-carboxylate (E50) (910 mg, 3.34 mmol) in THF (5 mL) and H₂O (5 mL) was added LiOH·H₂O (224 mg, 5.35 mmol, 1.6 eq). The mixture was stirred at rt for 2 hrs. The reaction progress was checked using TLC (PE:EtOAc=2:1). The reaction mixture was concentrated to remove THF. The aqueous portion was adjusted to pH˜6 by the addition of HCl (1 M). The resulting precipitate was collected by filtration and then dried in vacuo to give E51 (816 mg, 100% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 8.08 (s, 1H), 7.45-7.78 (m, 1H), 5.30 (q, 2H).

Intermediate ethyl 2-(2-pyridyl)pyrazole-3-carboxylate

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Step 1: Preparation of ethyl (E)-4-(dimethylamino)-2-oxo-but-3-enoate (E52)

Ethyl 2-oxopropanoate (2 g, 17.2 mmol, 1.9 mL) and 1,1-dimethoxy-N,N-dimethyl-methanamine (2.09 g, 17.6 mmol, 2.3 mL, 1.02 eq) were stirred at rt for 12 hrs. The reaction progress was checked using TLC (PE:EtOAc=10:1). The reaction mixture was concentrated to dryness to give E52 (2.4 g), which was used without further purification.

Step 2: Preparation of ethyl 2-(2-pyridyl)pyrazole-3-carboxylate (E53)

A mixture of ethyl (E)-4-(dimethylamino)-2-oxo-but-3-enoate (E52) (2.4 g, 14.0 mmol) and 2-pyridylhydrazine (1.53 g, 14.0 mmol) in HOAc (100 mL) was stirred at 110° C. for 12 hrs. The reaction progress was checked using TLC (PE:EtOAc=10:1). The reaction mixture was adjusted to pH ˜9 by the addition of sat. Na₂CO₃solution. The aqueous portion was extracted with EtOAc (300 mL). The organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=100/1 to 50/1) to give E53 (1.03 g, 34% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 8.48 (dt, 1H), 8.05 (td, 1H), 7.83-7.96 (m, 1H), 7.76 (d, 1H), 7.49 (ddd, 1H), 6.96-7.05 (m, 1H), 4.21 (q, 2H), 1.05-1.23 (m, 3H); LCMS: m/z 218.1 μM+H]⁺.

Ethyl 1-(2-pyridyl)pyrazole-3-carboxylate (E53a) was also obtained (190 mg, 6% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 8.70-8.81 (m, 1H), 8.54 (dd, 1H), 7.92-8.13 (m, 2H), 7.47 (ddd, 1H), 7.02 (d, 1H), 4.35 (q, 2H), 1.34 (t, 3H). The regiochemistry of E53 and E53a were confirmed by HSQC and HMBC NMR analysis.

Step 3: Preparation of 2-(2-pyridyl)pyrazole-3-carboxylic acid (E54)

To a solution of ethyl 2-(2-pyridyl)pyrazole-3-carboxylate (E53) (1 g, 4.60 mmol) in THF (10 mL) and H₂O (10 mL) was added LiOH·H₂O (386 mg, 9.21 mmol, 2 eq), and the reaction mixture was stirred at rt for 12 hrs. The reaction progress was checked using TLC (PE/EtOAc=1/1). The reaction mixture was concentrated under reduced pressure to remove THF. The aqueous portion was adjusted to pH˜7 by the addition of 2 μM HCl and lyophilized in vacuo to give (E54) (1.2 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 8.36-8.44 (m, 1H), 7.88 (td, 1H), 7.44-7.53 (m, 2H), 7.35 (ddd, 1H), 6.44 (d, 1H).

Intermediate [5-(difluoromethyl)-2-methyl-1,2,4-triazole-3-carbonyl]oxylithium

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Step 1: Preparation of tert-butyl (Z)-2-(1-amino-2-ethoxy-2-oxoethylidene)hydrazine-1-carboxylate (E55)

Tert-butyl (Z)-2-(1-amino-2-ethoxy-2-oxoethylidene)hydrazine-1-carboxylate was prepared from ethyl 2-amino-2-thioxoacetate following the procedure in Bioorg. Med. Chem., 26 (2016) 3223-3225. The reaction was heated to reflux.

Step 2: Preparation of ethyl 3-(difluoromethyl)-1H-1,2,4-triazole-5-carboxylate (E56)

Reagent 2,2-difluoroacetyl chloride was prepared by adding oxalyl dichloride (18.90 g, 149 mmol, 13.0 mL, 1.1 eq) dropwise at 0° C. to a solution of 2,2-difluoroacetic acid (13 g, 135 mmol, 8.5 mL) and DMF (989 mg, 13.5 mmol, 1.0 mL, 0.1 eq) in DCM (80 mL). The reaction mixture was stirred at rt for 1 hr, and the solution was used without further purification.

To a solution of tert-butyl (Z)-2-(1-amino-2-ethoxy-2-oxoethylidene)hydrazine-1-carboxylate (E55) (13 g, 56.2 mmol) in pyridine (90 mL) was added 2,2-difluoroacetyl chloride (15.47 g, 135 mmol, 2.4 eq). The reaction mixture was heated to 120° C. and stirred for 12 hrs. Reaction progress was checked using LCMS. The reaction mixture was concentrated to dryness. DCM (200 mL) was added to the residue, and the organic portion washed with 1 μM HCl (30 mL) and brine (60 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography on silica gel (PE:EtOAc=20:1 to 2:1) to give E56 (8.87 g, 83% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.01-7.32 (m, 1H), 4.36 (q, 2H), 1.30 (t, 3H); LCMS: m/z 192.0 μM+H]⁺.

Step 3: Preparation of ethyl 5-(difluoromethyl)-2-methyl-1,2,4-triazole-3-carboxylate (E57)

To a solution of ethyl 3-(difluoromethyl)-1H-1,2,4-triazole-5-carboxylate (E56) (10 g, 52.3 mmol) in DMF (80 mL) was added Mel (22.28 g, 157 mmol, 9.8 mL, 3 eq) and K₂CO₃(21.69 g, 157 mmol, 3 eq). The mixture was stirred at rt for 12 hrs. Reaction progress was checked using TLC (PE:EtOAc=1:1). The reaction mixture was filtered, and the precipitate was rinsed with EtOAc (150 mL). The filtrate was washed with water (30 mL) and brine (30 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography on silica gel (PE:EtOAc=20:1 to 1:1) to give E57 (4.46 g, 42% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 6.99-7.34 (m, 1H), 4.39 (q, 2H), 4.11-4.22 (m, 3H), 1.35 (t, 3H).

Step 4: Preparation of [5-(difluoromethyl)-2-methyl-1,2,4-triazole-3-carbonyl]oxylithium (E58)

To a solution of ethyl 5-(difluoromethyl)-2-methyl-1,2,4-triazole-3-carboxylate (E57) (2.35 g, 11.5 mmol) in THF (40 mL) and H₂O (10 mL) was added LiOH·H₂O (505 mg, 12.0 mmol, 1.05 eq). The reaction mixture was stirred at rt for 1 hr. Reaction progress was checked using TLC (PE:EtOAc=2:1). The reaction mixture was concentrated in vacuo to remove THF. H₂O (20 mL) was added, and the aqueous portion extracted with TBME (20 mL), and then lyophilized in vacuo to give E58 (2.15 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 6.75-7.21 (m, 1H), 4.09 (s, 3H).

Intermediate ethyl 3-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazole-5-carboxylate

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Step 1: Preparation of N′,2-dihydroxy-2-methyl-propanamidine (E59)

To a solution of 2-hydroxy-2-methyl-propanenitrile (2.14 g, 25.2 mmol, 2.3 mL) in EtOH (20 mL) was added hydroxylamino hydrochloride (3.49 g, 50.3 mmol, 2 eq) and Na₂CO₃(5.33 g, 50.3 mmol, 2 eq), and then the reaction was stirred at 70° C. for 16 hrs. The reaction mixture was concentrated to dryness. EtOAc (200 mL) was added to the residue, and the organic portion washed twice with water (50 mL) and brine (50 mL), dried over Na₂SO₄, filtered, and concentrated to dryness to afford E59 (1 g), which was used without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 10.11 (s, 1H), 8.86 (s, 1H), 5.03 (br s, 1H), 1.70 (s, 3H), 1.66 (s, 3H).

Step 2: Preparation of ethyl 3-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazole-5-carboxylate (E60)

To a solution of N′,2-dihydroxy-2-methyl-propanamidine (E59) (520 mg, 4.40 mmol) and pyridine (696 mg, 8.80 mmol, 711 μL, 2 eq) in toluene (15 mL) was added ethyl 2-chloro-2-oxo-acetate (601 mg, 4.40 mmol, 493 μL) at 0° C. The reaction mixture was stirred at rt for 1 hr, and then stirred at 100° C. for 15 hrs. Reaction progress was checked using LCMS. The reaction mixture was concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 2/1) and further purified by prep-HPLC (column: Boston Uni C18 40*150*5 um; mobile phase: [water (0.225% FA)-ACN]; B %: 16%-46%, 7.7 min) to give E60 (250 mg, 28% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.52 (q, 2H), 2.65 (br s, 1H), 1.67 (s, 6H), 1.45 (t, 3H); LCMS: m/z 201.1 μM+H]⁺.

Step 3: Preparation of ethyl 3-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazole-5-carboxylate (E61)

To a solution of ethyl 3-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazole-5-carboxylate (E60) (200 mg, 999 μmol) in THF (5 mL) and H₂O (5 mL) was added LiOH·H₂O (41.9 mg, 999 μmol), and then the reaction mixture was stirred at rt for 1 hr. The solvent was removed in vacuo, and the aqueous portion was lyophilized in vacuo to give E61 (170 mg), which was used without further purification.

Intermediates E62, E63, E64, E65, E66, and E67

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Step A: Preparation of methyl 6-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (E62) and methyl 6-bromo-7-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (E63)

To a solution of methyl 6-bromopyrazolo[1,5-a]pyridine-3-carboxylate (1 g, 3.92 mmol) in THF (10 mL) was added i-PrMgCl—LiCl (1.3 M, 6.03 mL, 2 eq) at −78° C. The reaction mixture was stirred at −78° C. for 15 min, then acetone (1.37 g, 23.5 mmol, 1.7 mL, 6 eq) was added dropwise to the reaction mixture. The reaction mixture was stirred at −78° C. for 1 hr. Reaction progress was checked using LCMS. The reaction mixture was dropwise added to 10 mL of aq. NH₄Cl solution. Water (30 mL) was added, and the aqueous portion extracted with EtOAc (25 mL×2). The combined organic layers were washed with brine (20 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 20:1) to give E62 (320 mg, 34% yield) and E63 (300 mg, 23% yield).

E62: ¹H NMR (400 MHz, CD₃OD) δ 8.40-8.54 (m, 1H), 8.14 (dd, 1H), 7.57 (dd, 1H), 7.27 (dd, 1H), 3.88-4.03 (m, 3H), 1.77-1.92 (m, 6H); LCMS: m/z 235.2 μM+H]⁺.

E63: ¹H NMR (400 MHz, CD₃OD) δ 8.46 (s, 1H), 8.02 (d, 1H), 7.76 (d, 1H), 3.93 (s, 3H), 1.95 (s, 6H); LCMS: m/z 313.0 μM+H]⁺.

Step B: Preparation of 6-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (E64)

To a solution of methyl 6-(1-hydroxy-1-methyl-ethyl)pyrazolo[1,5-a]pyridine-3-carboxylate (E62) (500 mg, 2.13 mmol) in MeOH (3 mL) and H₂O (1 mL) was added LiOH·H₂O (116 mg, 2.77 mmol, 1.3 eq). The reaction mixture was stirred at 40° C. for 12 hrs. Reaction progress was checked using LCMS. The reaction mixture was concentrated in vacuo to remove MeOH, and water (50 mL) was added. The aqueous portion was extracted with TBME (30 mL), and the aqueous layer was then adjusted to pH ˜6 by the addition of 0.5 μM HCl. The resulting white suspension was extracted with DCM/MeOH (100/10 mL) 3 times. The combined DCM/MeOH organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness to afford E64 (420 mg, 89% yield). LCMS: m/z 221.1 μM+H]⁺.

Step C: Preparation of 6-bromo-7-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (E65)

To a solution of methyl 6-bromo-7-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (E63) (120 mg, 383 μmol) in MeOH (2 mL) and H₂O (1 mL) was added LiOH·H₂O (17.69 mg, 422 μmol, 1.1 eq), the mixture was stirred at 40° C. for 12 hr.

Reaction progress was checked using LCMS. The reaction mixture was concentrated in vacuo to remove MeOH, and water (10 mL) was added. The aqueous portion was extracted with TBME (30 mL) and was then adjusted to pH ˜6 by the addition of 0.5 μM HCl. The resulting white suspension was extracted with DCM/MeOH (30/3 mL) 3 times. The combined DCM/MeOH organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness to afford E65 (100 mg, 87% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.44 (s, 1H), 8.07 (d, 1H), 7.74 (d, 1H), 1.96 (s, 6H); LCMS: m/z 301.1 μM+H]⁺.

Step D: Preparation of methyl 7-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (E66)

To a solution of methyl 6-bromo-7-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (E63) (450 mg, 1.44 mmol) in MeOH (10 mL) was added Pd/C (100 mg, 10% purity) under N₂. The resulting mixture was degassed under vacuum and purged with H₂3 times, and then the mixture was stirred at rt for 1 hr under H₂(15 psi). Reaction progress was checked using LCMS. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated in vacuo to afford E66 (350 mg), which was used without further purification. LCMS: m/z 234.9 μM+H]⁺.

Step E: Preparation of 7-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (E67)

To a solution of methyl 7-(2-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (E66) (350 mg, 1.49 mmol) in MeOH (5 mL) and H₂O (1 mL) was added NaOH (89.64 mg, 2.24 mmol, 1.5 eq), the mixture was stirred at 40° C. for 12 hrs. Reaction progress was checked using LCMS. The reaction mixture was concentrated in vacuo to remove MeOH, and water (10 mL) was added. The aqueous portion was extracted with TBME (30 mL), and then adjusted to pH ˜6 by the addition of 0.5 μM HCl. The resulting white suspension was extracted with DCM/MeOH (30/3 mL) 3 times. The combined DCM/MeOH organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness to afford E67 (320 mg), which was used without further purification. LCMS: m/z 220.9 μM+H]⁺.

Intermediate E72 according to General Scheme 7, Methods C and D

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Step A: Preparation of methyl 6-vinylpyrazolo[1,5-a]pyridine-3-carboxylate (E68)

A mixture of 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (8.15 g, 52.9 mmol, 8.98 mL), methyl 6-bromopyrazolo[1,5-a]pyridine-3-carboxylate (9 g, 35.3 mmol), K₃PO₄(22.47 g, 106 mmol) and Pd(dppf)Cl₂(1.29 g, 1.76 mmol) in dioxane (80 mL) and H₂O (40 mL) was stirred at 80° C. for 12 hrs under N₂. Reaction progress was checked using LCMS. The reaction mixture was combined with another 1 g batch reaction, and DCM (200 mL) was added. The organic layer was washed with brine (2×80 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 4/1) to give E68 (6.4 g, 80.2% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.37 (s, 1H), 8.30 (s, 1H), 8.03 (d, 1H), 7.52 (dd, 1H), 6.61 (dd, 1H), 5.76 (d, 1H), 5.34 (d, 1H), 3.84 (s, 3H); LCMS: m/z 203.1 μM+H]⁺.

Step B: Preparation of methyl 6-formylpyrazolo[1,5-a]pyridine-3-carboxylate (E69)

To a solution of methyl 6-vinylpyrazolo[1,5-a]pyridine-3-carboxylate (E68) (6.4 g, 31.7 mmol) in THF (80 mL) and H₂O (80 mL) was added K₂OsO₄·2H₂O (583 mg, 1.58 mmol) and NaIO4 (16.92 g, 79.1 mmol, 4.38 mL) at 0° C., and then the reaction mixture was stirred at rt for 12 hrs. Reaction progress was checked using LCMS. DCM (200 mL) was added to the reaction mixture, and the organic layer was washed with brine (2×80 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, DCM/EtOAc=1/0 to 6/1) to give E69 (5.9 g, 91.3% yield). ¹H NMR (400 MHz, CDCl₃) δ 9.94 (s, 1H), 8.90-8.98 (m, 1H), 8.48 (s, 1H), 8.18 (d, 1H), 7.80 (dd, 1H), 3.88 (s, 3H); LCMS: m/z 204.9 μM+H]⁺.

Step C: Preparation of methyl 6-(hydroxymethyl)pyrazolo[1,5-a]pyridine-3-carboxylate (E70)

To a solution of methyl 6-formylpyrazolo[1,5-a]pyridine-3-carboxylate (E69) (2.4 g, 11.8 mmol) in THF (30 mL) and MeOH (30 mL) was added NaBH₄(1.78 g, 47.0 mmol) at 0° C., and then the reaction mixture was stirred at rt for 1 hr. Reaction progress was checked using LCMS. The reaction mixture was quenched by the addition of sat. aq.

NH₄Cl (50 mL), and the aqueous portion extracted with EtOAc (100 mL). The organic layer was washed with water (50 mL) and brine (40 mL), dried over Na₂SO₄, filtered, and concentrated to dryness to give E70 (2.3 g, 94.9% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.54 (s, 1H), 8.38 (s, 1H), 8.11 (d, 1H), 7.41 (dd, 1H), 4.78 (s, 2H), 3.93 (s, 3H); LCMS: m/z 207.0 μM+H]⁺.

Step D: Preparation of methyl 6-(methoxymethyl)pyrazolo[1,5-a]pyridine-3-carboxylate (E71)

To a solution of methyl 6-(hydroxymethyl)pyrazolo[1,5-a]pyridine-3-carboxylate (E70) (2.2 g, 10.7 mmol) in THF (50 mL) was added NaH (512 mg, 12.8 mmol, 60% purity) at 0° C. The reaction mixture was stirred at 0° C. for 15 min, and then Mel (1.82 g, 12.8 mmol, 797 μL) was added to the reaction mixture. The reaction mixture was stirred at rt for 1 hr, and reaction progress was checked using LCMS. The reaction mixture was quenched by the addition of sat. aq. NH₄Cl (40 mL), and the aqueous portion extracted with DCM (2×60 mL). The combined organic layer was washed by water (30 mL) and brine (30 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 5/1) to give E71 (1.8 g, 76.6% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.52 (s, 1H), 8.41 (s, 1H), 8.16 (d, 1H), 7.42 (dd, 1H), 4.53 (s, 2H), 3.94 (s, 3H), 3.46 (s, 3H); LCMS: m/z 221.1 μM+H]⁺.

Step E: Preparation of 6-(methoxymethyl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (E72)

To a solution of methyl 6-(methoxymethyl)pyrazolo[1,5-a]pyridine-3-carboxylate (E71) (1.8 g, 8.17 mmol) in MeOH (40 mL) and H₂O (40 mL) was added NaOH (719 mg, 18.0 mmol), and the reaction mixture was stirred at 40° C. for 12 hrs. Reaction progress was checked using LCMS. The reaction mixture was concentrated to remove MeOH, and then H₂O (10 mL) was added. The pH of the aqueous mixture was adjusted to ˜6 by the addition of 0.5 μM HCl, and the aqueous mixture was filtered. The precipitate was dried in vacuo to give E72 (1.6 g, 94.9% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.57 (s, 1H), 8.45-8.51 (m, 1H), 8.21 (d, 1H), 7.48 (dd, 1H), 4.55 (s, 2H), 3.48 (s, 3H); LCMS: m/z 206.7 μM+H]⁺.

Intermediate E78 according to General Scheme 9, Method A

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Step A: Preparation of 2,6-difluorobenzohydrazide (E73)

To a solution of methyl 2,6-difluorobenzoate (25 g, 145 mmol) in MeOH (250 mL) was added NH₂NH₂·H₂O (18.18 g, 363 mmol, 17.7 mL), and the reaction mixture was stirred at 60° C. for 12 hrs. Reaction progress was checked using TLC. Additional NH₂NH₂·H₂O (7.27 g, 145 mmol, 7.05 mL) was added, and the reaction mixture was stirred at 60° C. for another 3 hrs. The reaction mixture was concentrated in vacuo to give E73 (25 g), which was used without further purification. ¹H NMR (400 MHz, CDCl₃) δ 7.37 (s, 1H), 6.93 (t, 2H), 3.45-3.89 (m, 2H).

Step B: Preparation of methyl 2-[2-(2,6-difluorobenzoyl)hydrazino]-2-oxo-acetate (E74)

To a solution of 2,6-difluorobenzohydrazide (E73) (25 g, 145 mmol) in THF (250 mL) was added methyl 2-chloro-2-oxo-acetate (19.57 g, 160 mmol, 14.7 mL) at 0° C., and the reaction mixture was stirred at 0° C. for 1 hr. Reaction progress was checked using TLC. The reaction mixture was filtered. The precipitate was washed with MTBE (800 mL), and then dried in vacuo to give E74 (37 g). ¹H NMR (400 MHz, DMSO-d₆) δ 7.59 (ddd, 2H), 7.21 (t, 1H), 3.83 (s, 2H).

Step C: Preparation of methyl 5-(2,6-difluorophenyl)-1,3,4-oxadiazole-2-carboxylate (E75)

To a solution of methyl 2-[2-(2,6-difluorobenzoyl)hydrazino]-2-oxo-acetate (E74) (15 g, 58.1 mmol) in DCM (250 mL) was added Et₃N (23.52 g, 232 mmol, 32.4 mL) and TosCl (14.40 g, 75.5 mmol) in portions at 0° C. The reaction mixture was allowed to warm to rt and stirred at rt for 12 hrs. Reaction progress was checked using TLC. DCM (100 mL) was added to the reaction mixture, and the organic layer was washed with sat. aq. NaHCO₃(100 mL) and water (100 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 1/1) to give E75 (4.3 g, 30.8% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.61 (tt, 1H), 7.14 (t, 2H), 4.10 (s, 3H).

Step D: Preparation of 5-(2,6-difluorophenyl)-1,3,4-oxadiazole-2-carboxylic acid (E76)

To a solution of methyl 5-(2,6-difluorophenyl)-1,3,4-oxadiazole-2-carboxylate (E75) (300 mg, 1.25 mmol) in H₂O (2 mL) and THF (4 mL) was added LiOH·H₂O (52.4 mg, 1.25 mmol). The reaction mixture was stirred at rt for 1 hr. Reaction progress was checked using LCMS. The reaction mixture was concentrated in vacuo to give E76 (300 mg), which was used without further purification. LCMS: m/z 226.8 μM+H]+

Step E: Preparation of 2-(2,6-difluorophenyl)-1,3,4-oxadiazole (E77)

To a solution of 5-(2,6-difluorophenyl)-1,3,4-oxadiazole-2-carboxylic acid (E76) (4 g, 17.7 mmol) in H₂O (20 mL) was added HCl (1 M, 35.4 mL), and the reaction mixture was stirred at rt for 1 hr. Reaction progress was checked using LCMS and TLC. DCM (60 mL) was added to the reaction mixture, and the organic layer washed by water (20 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 1/1) to give E77 (1.5 g, 46.6% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.63 (s, 1H), 7.57 (tt, 1H), 7.12 (t, 2H); LCMS: m/z 182.8 μM+H]⁺.

Step F: Preparation of 2-bromo-5-(2,6-difluorophenyl)-1,3,4-oxadiazole (E78)

To a solution of 2-(2,6-difluorophenyl)-1,3,4-oxadiazole (E77) (1.5 g, 8.24 mmol) in THF (50 mL) was added LiHMDS (1 M, 16.5 mL) dropwise at −78° C. The reaction mixture was stirred at −78° C. for 30 min, then Br₂(2.63 g, 16.5 mmol, 849 μL) was added to the reaction mixture at −78° C. dropwise. The reaction mixture was stirred at −78° C. for 2 hrs. Reaction progress was checked using TLC. Sat. aq. NH₄Cl (100 mL) was added to the reaction mixture, and the aqueous portion extracted with DCM (3×50 mL). The combined organic layer was washed with brine (40 mL), dried over Na₂SO₄, filtered and concentrated to dryness. The residue was purified by column chromatography (SiO₂, PE/EtOAc=1/0 to 3/1) to give E78 (1.6 g, 54.2% yield). ¹H NMR (400 MHz, DMSO-d₆) δ 7.79 (tt, 1H), 7.41 (t, 2H); LCMS: m/z 341.2 μM+H]⁺.

Preparation of Examples 107 and 108 according to General Scheme 1, Method C

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Step 1: Preparation of [4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl]-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl]methanone

To a solution of 5-fluoro-2-(4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-4-yl)-1,3-benzoxazole (4.00 g, 15.5 mmol) and 4-(difluoromethyl)-2-(1-hydroxy-1-methyl-ethyl) oxazole-5-carboxylic acid (E8) (3.77 g, 17.0 mmol, 1.1 eq) in DMF (80 mL) was added HOBt (2.72 g, 20.1 mmol, 1.3 eq) and EDCI (3.86 g, 20.1 mmol, 1.3 eq). The reaction mixture was stirred at rt for 16 hrs. Reaction progress was tracked using LCMS. DCM (300 mL) was added, and the organic portion washed with sat. NaHCO₃solution (50 mL) and brine (50 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0-5% DCM:MeOH @35 mL/min) to give compound [4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl]-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl]methanone (4.4 g, 60% yield). LCMS: m/z 462.1 μM+H]⁺.

Step 2: SFC Separation

[4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl]-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl]methanone (4.4 g) underwent SFC separation (column: DAICEL CHIRALPAK IC (250 mm*50 mm, 10 um); mobile phase: [Neu-IPA]; B %: 40%-40%, min) to afford Enantiomer 1 (1.75 g, 39.6%, Rt=3.174 min) and Enantiomer 2 (1.79 g, 39% yield, Rt=3.769 min).

Enantiomer 1 (Example 107): (S)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone. ¹H NMR (400 MHz, CD₃OD) δ 7.57-7.78 (m, 2H), 7.35-7.53 (m, 1H), 6.88-7.31 (m, 2H), 6.47-6.82 (m, 1H), 4.59 (br d, 1H), 4.44-4.64 (m, 1H), 3.96 (br s, 0.7H), 3.63 (br s, 0.3H), 2.77-3.27 (m, 2H), 1.47-1.73 (m, 6H); LCMS: m/z 462.1 μM+H]⁺; SFC: 98.1% ee.

Enantiomer 2 (Example 108): (R)-(4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)oxazol-5-yl)(4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone. ¹H NMR (400 MHz, CD₃OD) δ 7.57-7.85 (m, 2H), 7.35-7.54 (m, 1H), 6.91-7.31 (m, 2H), 6.59-6.87 (m, 1H), 4.57 (br s, 1H), 3.96 (br s, 0.7H), 3.59 (br s, 0.3H), 2.74-3.19 (m, 2H), 1.42-1.72 (m, 6H); LCMS: m/z 462.1 μM+H]⁺; SFC: 93.9% ee.

Preparation of Examples 925 and 926 according to General Scheme 1A, Method C

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Step A: Preparation of 6-(benzo[d]oxazol-2-yl)-N,N-dimethyl-5-(oxazole-5-carbonyl)-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide

Oxazole-5-carboxylicacid (39.6 mg, 350 μmol) was dissolved in DMF (1.5 mL), and then HATU (145 mg, 382 μmol) and Diisopropylethylamine (82.3 mg, 110 μL, 637 μmol) were added. 6-(benzo[d]oxazol-2-yl)-N,N-dimethyl-2-(triisopropylsilyl)-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide (156 mg, 319 μmol) was then added. The reaction mixture was stirred at rt overnight. DCM (30 mL) was added, and the organic layer was washed by water (10 mL) and brine (10 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, Heptane/EtOAc=1/0 to 0/1) to give 6-(benzo[d]oxazol-2-yl)-N,N-dimethyl-5-(oxazole-5-carbonyl)-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide (110 mg, 59.1% yield). LC-MS: m/z 585.1 μM+H]⁺.

Step B: Preparation of 6-(benzo[d]oxazol-2-yl)-N,N-dimethyl-5-(oxazole-5-carbonyl)-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide

6-(benzo[d]oxazol-2-yl)-N,N-dimethyl-5-(oxazole-5-carbonyl)-2-(triisopropylsilyl)-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide (110 mg, 188 μmol) was dissolved in THF (2.6 mL) and cooled to 0° C. Tetrabutylammonium fluoride (98.4 mg, 376 μL, 1M in THF, 376 μmol) was then added, and the reaction mixture was stirred at 0° C. for 1 hr. DCM was added (30 mL), and the organic layer washed by water (10 mL) and brine (10 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by prep. HPLC (column: XSelect CSH C18 5 μm, 19×100 mm; mobile phase: 30-36% MeCN in H₂O [with 0.1% formic acid]) to give 6-(benzo[d]oxazol-2-yl)-N,N-dimethyl-5-(oxazole-5-carbonyl)-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide (20 mg, 25% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.03 (s, 1H), 7.87 (s, 1H), 7.79 (s, 1H), 7.67-7.65 (d, 1H), 7.56-7.54 (d, 1H), 7.37-7.29 (m, 2H), 6.68 (s, 1H), 5.32-5.28 (dd, 1H), 5.09-5.06 (d, 1H), 2.66 (s, 6H); LC-MS: m/z 429.1 μM+H]⁺.

Step C: Preparation of (6-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(oxazol-5-yl)methanone

6-(benzo[d]oxazol-2-yl)-N,N-dimethyl-5-(oxazole-5-carbonyl)-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide (19 mg, 44 μmol) was dissolved in 1,4-dioxane (0.49 mL) and then hydrogen chloride (49 mg, 0.33 mL, 4M in dioxane, 1.3 mmol) was added. The reaction mixture was stirred at rt for 3 hrs, and then sat. aq. Na₂CO₃was added until the pH of the aqueous layer was −8. The aqueous layer was extracted with DCM (-10 mL) three times. The combined organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by HPLC (column: XSelect CSH C18 5 um, 19×100 mm, gradient: 13-17% MeCN in H₂O [with 0.1% formic acid]) to give (6-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(oxazol-5-yl)methanone (9 mg, 60% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.45 (s, 1H), 7.91 (s, 1H), 7.72 (s, 1H), 7.66-7.59 (m, 2H), 7.41-7.35 (m, 2H), 6.46 (s, 1H), 5.36 (s, 1H), 5.23 (s, 1H); LC-MS: m/z 322.0 μM+H]⁺.

Step D: SFC Separation

(6-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(oxazol-5-yl)methanone (11 mg, 34 μmol) was separated into its enantiomers by SFC (column: ColumnTek Enantiocel A2S-5 250 (L)×20 (ID) mm; mobile phase: 25% EtOH with CO₂) to give Enantiomer 1 (5 mg, Rt=4.617 min) and Enantiomer 2 (5 mg, Rt=6.066 min).

Enantiomer 1 (Example 925): (S)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(oxazol-5-yl)methanone. ¹H NMR (400 MHz, CD₃OD) δ 8.45 (s, 1H), 7.91 (s, 1H), 7.72 (s, 1H), 7.65-7.59 (m, 2H), 7.42-7.35 (m, 2H), 6.47 (s, 1H), 5.38-5.35 (d, 1H), 5.23-5.20 (d, 1H); LC-MS: 332.1 (M+H)⁺; SFC: 99.5% ee.

Enantiomer 2 (Example 926): (R)-(4-(benzo[d]oxazol-2-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(oxazol-5-yl)methanone. ¹H NMR (400 MHz, CD₃OD) δ 8.44 (s, 1H), 7.91 (s, 1H), 7.72 (s, 1H), 7.65-7.59 (m, 2H), 7.41-7.34 (m, 2H), 6.47 (s, 1H), 5.37-5.34 (d, 1H), 5.23-5.20 (d, 1H); LC-MS: 332.1 (M+H)⁺; SFC: 96.8% ee.

Preparation of Examples 931 and 932 According to General Scheme 1A, Method B

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Step A: Preparation of 5,6-bis(benzo[d]oxazol-2-yl)-N,N-dimethyl-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide

6-(1,3-benzoxazol-2-yl)-N,N-dimethyl-2-triisopropylsilyl-5,6-dihydro-4H-pyrrolo[3,4-d]imidazole-3-sulfonamide (66 mg, 0.13 mmol) was dissolved in NMP (1.3 mL), and then 2-chlorobenzo[d]oxazole (25 mg, 18 μL, 0.16 mmol) and diisopropylethylamine (26 mg, 35 μL, 0.20 mmol) were added. The reaction mixture was stirred overnight at 60° C. The reaction was allowed to cool and DCM (30 mL) was added. The organic layer was washed by water (10 mL) and brine (10 mL), dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by column chromatography (SiO₂, Heptane/EtOAc=I/O to 0/1) to give 5,6-bis(benzo[d]oxazol-2-yl)-N,N-dimethyl-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide (44 mg, 72% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.89 (s, 1H), 7.73-7.71 (m, 1H), 7.54-7.52 (m, 1H), 7.40-7.38 (m, 1H), 7.36-7.32 (m, 2H), 7.31-7.28 (m, 1H), 7.17-7.13 (td, 1H), 7.05-7.01 (td, 1H), 6.61-6.59 (m, 1H), 5.09-5.05 (dd, 1H), 4.96-4.92 (dd, 1H), 2.70 (s, 6H); LC-MS: m/z 451.0 μM+H]⁺.

Step B: Preparation of 2,2′-(4,6-dihydropyrrolo[3,4-d]imidazole-4,5(1H)-diyl)bis(benzo[d]oxazole)

5,6-bis(benzo[d]oxazol-2-yl)-N,N-dimethyl-5,6-dihydropyrrolo[3,4-d]imidazole-1(4H)-sulfonamide (44 mg, 98 μmol) was dissolved in dioxane (0.98 mL), and then hydrogen chloride (0.11 g, 0.73 mL, 4M in dioxane, 2.9 mmol) was added. The reaction mixture was stirred at rt for 3 hrs. Sat. aq. Na₂CO₃was added until the pH was −8. The aqueous layer was extracted with DCM (-10 mL) three times. The combined organic layer was dried over Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by HPLC (column: XSelect CSH C18 5 μm, 30×100 mm, gradient: 28-32% MeCN in H₂O [with 0.1% formic acid]) to give 2,2′-(4,6-dihydropyrrolo[3,4-d]imidazole-4,5(1H)-diyl)bis(benzo[d]oxazole) (15 mg, 45% yield). ¹H NMR (400 MHz, CD₃OD) δ 7.72 (s, 1H), 7.68-7.66 (m, 1H), 7.62-7.60 (m, 1H), 7.42-7.36 (m, 2H), 7.32-7.29 (m, 2H), 7.18-7.14 (td, 1H), 7.07-7.03 (td, 1H), 6.45 (s, 1H), 5.11-5.07 (dd, 1H), 5.01-4.98 (d, 1H); LC-MS: m/z 344.0 μM+H]⁺.

Step C: SFC Separation

2,2′-(4,6-dihydropyrrolo[3,4-d]imidazole-4,5(1H)-diyl)bis(benzo[d]oxazole) (19 mg, 55 umol) was separated into its enantiomers by SFC (column: ColumnTek Enantiocel C₄-5, 250 (L)×30 (ID) mm; mobile phase: 40% EtOH (0.1% DEA) with C₀₂to give Enantiomer 1 (8.5 mg, Rt=7.070 min) and Enantiomer 2 (8.6 mg, Rt=9.800 min).

Enantiomer 1 (Example 931): (S)-2,2′-(4,6-dihydropyrrolo[3,4-d]imidazole-4,5(1H)-diyl)bis(benzo[d]oxazole). ¹H NMR (400 MHz, CD₃OD) δ 7.72 (s, 1H), 7.67-7.65 (m, 1H), 7.62-7.59 (dd, 1H), 7.41-7.36 (m, 2H), 7.34-7.29 (m, 2H), 7.18-7.14 (td, 1H), 7.07-7.03 (td, 1H), 6.45 (s, 1H), 5.11-5.07 (dd, 1H), 5.01-4.98 (d, 1H); LC-MS: 344.1 (M+H)⁺; SFC: >99% ee.

Enantiomer 2 (Example 932): (R)-2,2′-(4,6-dihydropyrrolo[3,4-d]imidazole-4,5(1H)-diyl)bis(benzo[d]oxazole). ¹H NMR (400 MHz, CD₃OD) δ 7.72 (s, 1H), 7.67-7.65 (m, 1H), 7.61-7.59 (m, 1H), 7.41-7.35 (m, 2H), 7.34-7.29 (m, 2H), 7.18-7.14 (td, 1H), 7.07-7.02 (td, 1H), 6.45-6.44 (d, 1H), 5.10-5.06 (dd, 1H), 5.00-4.97 (dd, 1H). LC-MS: 344.1 (M+H)⁺; SFC: >99% ee.

The compounds of Tables 1S, 1R, and 2 were characterized using proton NMR and LCMS and the enantiomeric excess determined. See, Table 3.

TABLE 3

Ex.

LCMS

#

¹H NMR (400 MHz)
m/z
% ee

1
(CD₃OD) δ 8.12 (br s, 0.5 H), 7.75-7.91 (m, 1 H), 7.66 (s, 1
399.9
83.9%

H), 7.32-7.53 (m, 2 H), 7.10-7.28 (m, 1 H), 6.77 (br s, 0.5 H),
[M + H]⁺

5.78 (br dd, 0.5 H), 4.98 (br d, 0.5 H), 3.81 (br s, 0.5 H), 3.46

(br s, 0.5 H), 2.85-3.18 (m, 1 H), 2.79 (br d, 1 H), 2.43 (br s, 3

H)

2
(CD₃OD) δ 8.12 (br s, 0.5 H), 7.76-7.92 (m, 1 H), 7.66 (s, 1
399.9
89.1%

H), 7.35-7.51 (m, 2 H), 7.22 (br d, 1 H), 6.78 (br s, 0.5 H),
[M + H]⁺

5.61-5.88 (m, 0.5 H), 4.98 (br s, 0.5 H), 3.80 (br s, 0.5 H),

3.46 (br s, 0.5 H), 2.85-3.17 (m, 1 H), 2.79 (br d, 1 H), 2.43

(br s, 3 H)

3
(CD₃OD) δ 7.88 (d, 1 H), 7.51-7.71 (m, 3 H), 6.81 (br s, 0.7
403.0
93.2%

H), 6.35 (br s, 0.3 H), 4.95-5.03 (m, 0.4 H), 4.33 (dd, 0.6 H),
[M + H]⁺

3.80 (br s, 1 H), 2.95 (br s, 1 H), 2.71-2.86 (m, 1 H), 2.42-2.66

(m, 2 H), 1.08 (br d, 1 H), 0.50-0.61 (m, 2 H), 0.24 (br d, 2 H)

4
(CD₃OD) δ 7.88 (d, 1 H), 7.50-7.72 (m, 3 H), 6.82 (br s, 0.7
402.9
96.8%

H), 6.36 (br s, 0.3 H), 4.95-5.04 (m, 0.3 H), 4.33 (dd, 0.7 H),
[M + H]⁺

3.80 (br s, 1 H), 2.95 (br s, 1 H), 2.68-2.86 (m, 1 H), 2.41-2.66

(m, 2 H), 1.08 (br d, 1 H), 0.49-0.65 (m, 2 H), 0.24 (br d, 2 H)

5
(CD₃OD) δ 8.63 (d, 1 H), 8.35 (br s, 1 H), 8.25 (d, 1 H), 7.97
447.1
95.9%

(td, 1 H), 7.62-7.79 (m, 2 H), 7.39-7.57 (m, 2 H), 7.23 (td, 1
[M + H]⁺

H), 6.74 (br s, 1 H), 4.63 (s, 1 H), 3.96 (s, 1 H), 3.14 (br d, 1

H), 2.87 (br d, 1 H)

6
(CD₃OD) δ 8.63 (d, 1 H), 8.35 (br s, 1 H), 8.24 (d, 1 H), 7.97
447.0
94.6%

(td, 1 H), 7.59-7.80 (m, 2 H), 7.38-7.56 (m, 2 H), 7.22 (td, 1
[M + H]⁺

H), 6.77 (br s, 1 H), 4.63 (br s, 1 H), 3.96 (br s, 1 H), 3.11 (br

d, 1 H), 2.77-2.96 (m, 1 H)

7
(DMSO-d₆) δ 12.23 (br s, 1 H), 8.76 (br s, 1 H), 8.12-8.26 (m,
491.0
99.2%

2 H), 7.95-8.11 (m, 2 H), 7.73 (br d, 1 H), 7.55-7.65 (m, 3 H),
[M + H]⁺

6.62 (br s, 1 H), 4.66 (br s, 1 H), 3.94 (br s, 1 H), 3.11 (br s, 1

H), 2.83 (br d, 1 H)

8
(DMSO-d₆) δ 12.22 (br s, 1 H), 8.76 (br s, 1 H), 8.13-8.25 (m,
491.0
99.0%

2 H), 7.97-8.12 (m, 2 H), 7.73 (br d, 1 H), 7.56-7.64 (m, 3 H),
[M + H]⁺

6.60 (br s, 1 H), 4.66 (br s, 1 H), 3.95 (br s, 1 H), 3.11 (br s, 1

H), 2.83 (br d, 1 H)

9
(CD₃OD) δ 8.26 (s, 1 H), 8.22 (br s, 1 H), 8.01 (s, 1 H), 7.73
450.1
97.3%

(s, 1 H), 7.68 (dd, 1 H), 7.46 (dd, 1 H), 7.23 (td, 1 H), 6.73 (br
[M + H]⁺

s, 1 H), 4.68 (br s, 1 H), 3.98 (s, 4 H), 3.03-3.20 (m, 1 H),

2.80-2.92 (m, 1 H)

10
(CD₃OD) δ 8.26 (s, 1 H), 8.22 (br s, 1 H), 8.01 (s, 1 H), 7.73
450.2
94.3%

(s, 1 H), 7.68 (dd, 1 H), 7.40-7.50 (m, 1 H), 7.23 (td, 1 H),
[M + H]⁺

6.73 (br s, 1 H), 4.67 (br s, 1 H), 3.98 (s, 4 H), 3.07-3.17 (m, 1

H), 2.87 (br dd, 1 H)

11
(CD₃OD) δ 8.69 (br s, 1 H), 8.23 (br s, 1 H), 7.99 (br s, 2 H),
431.2
97.2%

7.70 (s, 1 H), 7.64 (dd, 1 H), 7.56 (br s, 1 H), 7.42 (br s, 1 H),
[M + H]⁺

7.19 (br t, 1 H), 6.80 (s, 1 H), 4.74-4.85 (m, 1 H), 3.98 (br s, 1

H), 3.20 (br s, 1 H), 2.88 (br d, 1 H)

12
(CD₃OD) δ 8.54-8.79 (m, 1 H), 8.22 (br s, 1 H), 7.98 (br s, 2
431.2
88.1%

H), 7.69 (s, 1 H), 7.64 (br dd, 1 H), 7.56 (br s, 1 H), 7.42 (br s,
[M + H]⁺

1 H), 7.19 (br t, 1 H), 6.80 (s, 1 H), 4.75-4.86 (m, 1 H), 3.99

(br s, 1 H), 3.20 (br s, 1 H), 2.88 (br d, 1 H)

13
(CD₃OD) δ 7.83 (br s, 1 H), 7.60-7.76 (m, 2 H), 7.44 (br d, 1
414.2
91.5%

H), 7.21 (td, 1 H), 6.74 (br s, 1 H), 4.54-4.82 (m, 1 H), 3.98
[M + H]⁺

(br s, 1 H), 2.71-3.23 (m, 2 H), 1.84 (br d, 6 H)

14
(CD₃OD) δ 7.83 (br s, 1 H), 7.61-7.75 (m, 2 H), 7.44 (br d, 1
414.2
95.5%

H), 7.21 (td, 1 H), 6.73 (br s, 1 H), 4.67 (br s, 1 H), 3.99 (br s,
[M + H]⁺

1 H), 2.72-3.24 (m, 2 H), 1.65-1.98 (m, 6 H)

15
(CD₃OD) δ 7.67 (s, 1 H), 7.58-7.65 (m, 1 H), 7.36-7.41 (m, 1
395.1
96.3%

H), 7.12-7.25 (m, 1 H), 6.78 (br s, 1 H), 5.21 (dd, 0.7 H), 5.04
[M + H]⁺

(dd, 0.3 H), 3.91 (br s, 0.7 H), 3.58 (br s, 0.3 H), 3.11 (br s,

0.8 H), 2.92-3.02 (m, 0.2 H), 2.84 (br d, 1 H), 2.18-2.39 (m, 1

H), 1.15-1.28 (m, 4 H)

16
(CD₃OD) δ 7.67 (s, 1 H), 7.57-7.65 (m, 1 H), 7.39 (br dd, 1
395.1
86.1%

H), 7.12-7.22 (m, 1 H), 6.80 (br s, 1 H), 5.21 (dd, 0.7 H), 5.04
[M + H]⁺

(dd, 0.3 H), 3.89 (br s, 0.6 H), 3.58 (br s, 0.4 H), 3.06-3.20 (m,

0.8 H), 2.94 (br s, 0.2 H), 2.84 (br d, 1 H), 2.18-2.36 (m, 1 H),

1.15-1.30 (m, 4 H)

17
(CD₃OD) δ 8.15 (br s, 1 H), 7.66-7.74 (m, 2 H), 7.45 (br d, 1
426.0
98.4%

H), 7.22 (td, 1 H), 6.70 (br s, 1 H), 4.63 (s, 1 H), 3.95 (br s, 1
[M + H]⁺

H), 3.00-3.19 (m, 1 H), 2.85 (br d, 1 H), 1.49 (s, 9 H)

18
(CD₃OD) δ 8.15 (br s, 1 H), 7.66-7.74 (m, 2 H), 7.45 (br d, 1
426.1
97.2%

H), 7.23 (t, 1 H), 6.68 (br s, 1 H), 4.64 (s, 1 H), 3.93 (s, 1 H),
[M + H]⁺

3.03-3.20 (m, 1 H), 2.87 (br s, 1 H), 1.49 (s, 9 H)

19
(CD₃OD) δ 8.45 (s, 1 H), 8.34 (s, 1 H), 7.84 (d, 1 H), 7.59-
417.1
99.3%

7.70 (m, 2 H), 7.37-7.47 (m, 1 H), 7.32 (d, 1 H), 7.12-7.22 (m,
[M + H]⁺

1 H), 6.73 (s, 1 H), 4.62-4.77 (m, 1 H), 3.88 (br s, 1 H), 3.02-

3.15 (m, 1 H), 2.76-2.88 (m, 1 H), 2.37 (s, 3 H)

20
(CD₃OD) δ 8.45 (s, 1 H), 8.34 (s, 1 H), 7.84 (d, 1 H), 7.57-
417.1
98.7%

7.69 (m, 2 H), 7.38-7.45 (m, 1 H), 7.32 (d, 1 H), 7.17 (td, 1
[M + H]

H), 6.73 (br s, 1 H), 4.63-4.76 (m, 1 H), 3.87 (br s, 1 H), 3.01-

3.15 (m, 1 H), 2.75-2.87 (m, 1 H), 2.37 (s, 3 H)

21
(CD₃OD) δ 7.63-7.80 (m, 3 H), 7.44 (br d, 1 H), 7.16-7.28
410.0
96.8%

(m, 1 H), 6.71 (br s, 1 H), 4.65-4.80 (m, 1 H), 3.57-4.11 (m, 1
[M + H]⁺

H), 3.00-3.14 (m, 1 H), 2.90 (br s, 1 H), 1.44 (br s, 9 H)

22
(CD₃OD) δ 7.62-7.79 (m, 3 H), 7.44 (br d, 1 H), 7.22 (td, 1
410.1
97.2%

H), 6.73 (br s, 1 H), 4.70 (br s, 1 H), 3.56-4.10 (m, 1 H), 3.11
[M + H]⁺

(br s, 1 H), 2.90 (br s, 1 H), 1.44 (br s, 9 H)

23
(CD₃OD) δ 8.40-8.51 (m, 1 H), 7.55-7.73 (m, 2 H), 7.40 (dd,
422.1
91.0%

1 H), 7.19 (td, 1 H), 6.79 (br s, 0.8 H), 6.03-6.20 (m, 0.2 H),
[M + H]⁺

3.81-4.12 (m, 1.8 H), 3.57 (br s, 0.2 H), 2.73-3.03 (m, 2 H)

24
(CD₃OD) δ 8.37-8.52 (m, 1 H), 7.54-7.72 (m, 2 H), 7.40 (dd,
422.1
92.3%

1 H), 7.18 (td, 1 H), 6.79 (br s, 0.8 H), 6.10 (br s, 0.2 H), 3.84-
[M + H]⁺

4.11 (m, 1.7 H), 3.58 (br d, 0.3 H), 2.70-3.06 (m, 2 H)

25
(CD₃OD) δ 7.64-7.78 (m, 3 H), 7.40-7.54 (m, 1 H), 7.17-7.34
467.0
90.6%

(m, 3 H), 6.89 (br s, 1 H), 5.25 (dd, 0.7 H), 5.14 (dd, 0.3 H),
[M + H]⁺

4.00 (br s, 0.7 H), 3.60-3.78 (m, 0.3 H), 3.20-3.31 (m, 0.7 H),

2.97-3.10 (m, 0.3 H), 2.92 (br d, 1 H)

26
(CD₃OD) δ 7.61-7.81 (m, 3 H), 7.41-7.57 (m, 1 H), 7.16-7.35
467.0
83.6%

(m, 3 H), 6.89 (br s, 1 H), 5.25 (dd, 0.7 H), 5.14 (dd, 0.3H),
[M + H]⁺

4.00 (br s, 0.7H), 3.56-3.76 (m, 0.3 H), 3.19-3.30 (m, 0.7 H),

2.98-3.10 (m, 0.3 H), 2.92 (br d, 1 H)

27
(CD₃OD) δ 8.08-8.24 (m, 2 H), 7.68-7.72 (m, 1 H), 7.59-7.67
449.0
96.8%

(m, 1 H), 7.56 (s, 0.3 H), 7.30-7.43 (m, 3 H), 7.15-7.22 (m, 1
[M + H]⁺

H), 6.87 (s, 0.7 H), 5.32 (dd, 0.7 H), 5.10 (dd, 0.3 H), 3.88-

4.02 (m, 0.7 H), 3.64 (br s, 0.3 H), 3.13-3.24 (m, 0.6 H), 2.97

(br d, 0.4 H), 2.79-2.93 (m, 1 H)

28
(CD₃OD) δ 8.06-8.24 (m, 2 H), 7.67-7.71 (m, 1 H), 7.67-7.71
449.0
99.4%

(m, 1 H), 7.59-7.67 (m, 0.3 H), 7.25-7.44 (m, 3 H), 7.14-7.22
[M + H]⁺

(m, 1 H), 6.87 (s, 0.7 H), 5.31 (dd, 0.7 H), 5.10 (br dd, 0.3 H),

3.90-4.00 (m, 0.7 H), 3.58-3.68 (m, 0.3 H), 2.79-3.25 (m, 2 H)

29
(CD₃OD) δ 8.58 (s, 1 H), 8.41 (br s, 1 H), 7.92 (d, 1 H), 7.63-
474.1
100%

7.73 (m, 2 H), 7.38-7.48 (m, 2 H), 7.21 (td, 1 H), 6.77 (br s, 1
[M + H]⁺

H), 4.67-4.80 (m, 1 H), 3.90 (br d, 1 H), 3.05-3.20 (m, 1 H),

2.80-2.95 (m, 3 H), 2.63-2.76 (m, 2 H), 2.38 (s, 6 H)

30
(CD₃OD) δ 8.61 (s, 1 H), 8.42 (br s, 1 H), 7.93 (d, 1 H), 7.61-
474.1
88.4%

7.75 (m, 2 H), 7.44 (td, 2 H), 7.21 (td, 1 H), 6.77 (br s, 1 H),
[M + H]⁺

4.74 (br d, 1 H), 3.91 (br s, 1 H), 3.05-3.21 (m, 1 H), 2.78-

3.04 (m, 5 H), 2.51 (s, 6 H)

31
(CD₃OD) δ 8.71 (br s, 1 H), 8.20 (br s, 0.7 H), 8.00 (br s, 1.3
445.0
89.8%

H), 7.67 (dt, 2 H), 7.56 (br s, 1 H), 7.43 (br d, 1 H), 7.21 (td, 1
[M + H]⁺

H), 6.75 (br s, 1 H), 4.64-4.87 (m, 1 H), 3.57-4.09 (m, 1 H),

3.26 (br s, 1 H), 2.87 (br d, 1 H), 2.48 (s, 3 H)

32
(CD₃OD) δ 8.67 (br s, 1 H), 8.17 (br s, 0.4 H), 7.97 (br s, 1.6
445.0
90.4%

H), 7.60-7.71 (m, 2 H), 7.53 (br s, 1 H), 7.40 (br d, 1 H), 7.14-
[M + H]⁺

7.22 (m, 1 H), 6.72 (br s, 1 H), 4.62-4.78 (m, 1 H), 3.96 (br s,

1 H), 3.22 (br s, 1 H), 2.85 (br d, 1 H), 2.46 (s, 3 H)

33
(CD₃OD) δ 8.64-8.73 (m, 1 H), 8.30-8.42 (m, 1 H), 7.82-7.95
449.9
100%

(m, 1 H), 7.62-7.76 (m, 2 H), 7.55 (s, 0.3 H), 7.36-7.46 (m, 1
[M + H]⁺

H), 7.12-7.27 (m, 1 H), 6.90 (s, 0.7 H), 5.28 (dd, 0.7 H), 5.07-

5.18 (m, 0.3 H), 3.93-4.09 (m, 0.7 H), 3.61-3.73 (m, 0.3 H),

3.17-3.28 (m, 0.7 H), 3.02 (td, 0.3 H), 2.84-2.95 (m, 1 H)

34
(CD₃OD) δ 8.66-8.75 (m, 1 H), 8.31-8.42 (m, 1 H), 7.83-7.94
449.9
97.6%

(m, 1 H), 7.62-7.78 (m, 2 H), 7.55 (s, 0.3 H), 7.38-7.45 (m, 1
[M + H]⁺

H), 7.15-7.27 (m, 1 H), 6.91 (s, 0.7 H), 5.28 (dd, 0.7 H), 5.13

(br dd, 0.3 H), 3.92-4.06 (m, 0.7 H), 3.62-3.72 (m, 0.3 H),

3.18-3.28 (m, 0.7 H), 2.98-3.06 (m, 0.3 H), 2.84-2.95 (m, 1 H)

35
(CD₃OD) δ 8.28 (br s, 1 H), 7.59-7.71 (m, 2 H), 7.41 (br d, 1
434.1
85.8%

H), 7.19 (td, 1 H), 6.73 (br s, 1 H), 4.47 (br s, 1 H), 3.98 (br s,
[M + H]⁺

1 H), 3.07 (br s, 1 H), 2.81 (br d, 1 H), 2.11 (t, 3 H)

36
(CD₃OD) δ 8.28 (br s, 1 H), 7.58-7.71 (m, 2 H), 7.42 (br d, 1
434.1
88.1%

H), 7.19 (td, 1 H), 6.72 (br s, 1 H), 4.47 (br s, 1 H), 3.97 (br s,
[M + H]⁺

1 H), 3.07 (br s, 1 H), 2.81 (br d, 1 H), 2.11 (t, 3 H)

37
(CD₃OD) δ 7.41-7.55 (m, 2 H), 7.15-7.32 (m, 1 H), 6.94-7.07
341.1
95.9%

(m, 1 H), 6.65 (s, 0.8 H), 6.19 (s, 0.2 H), 4.82 (br d, 0.3 H),
[M + H]⁺

4.14 (br dd, 0.7 H), 3.51-3.70 (m, 0.8 H), 3.02-3.11 (m, 0.2

H), 2.53-2.84 (m, 2 H), 2.29-2.46 (m, 2 H), 0.84-0.98 (m, 1

H), 0.32-0.45 (m, 2 H), 0.04-0.13 (m, 2 H)

38
(CD₃OD) δ 7.60-7.69 (m, 2 H), 7.34-7.47 (m, 1 H), 7.18 (td, 1
341.0
92.0%

H), 6.82 (s, 0.8 H), 6.35 (s, 0.2 H), 4.31 (br dd, 1 H), 3.66-
[M + H]⁺

3.88 (m, 1 H), 2.72-2.98 (m, 2 H), 2.40-2.65 (m, 2 H), 1.07 (br

d, 1 H), 0.49-0.62 (m, 2 H), 0.23 (br d, 2 H)

39
(CD₃OD) δ 8.69-8.78 (m, 1 H), 8.22-8.32 (m, 1 H), 8.00-8.10
432.1
97.1%

(m, 1 H), 7.66-7.73 (m, 1 H), 7.58-7.66 (m, 2 H), 7.52 (br s,
[M + H]⁺

0.3 H), 7.32-7.44 (m, 1 H), 7.09-7.24 (m, 1 H), 6.87 (s, 0.7 H),

5.04-5.32 (m, 1 H), 3.54-4.05 (m, 1 H), 2.94-3.26 (m, 1 H),

2.81-2.94 (m, 1 H)

40
(CD₃OD) δ 8.69-8.77 (m, 1 H), 8.21-8.31 (m, 1 H), 8.00-8.09
432.1
98.4%

(m, 1 H), 7.67-7.73 (m, 1 H), 7.58-7.66 (m, 2 H), 7.52 (br s,
[M + H]⁺

0.3 H), 7.34-7.43 (m, 1 H), 7.10-7.22 (m, 1 H), 6.87 (s, 0.7 H),

5.05-5.32 (m, 1 H), 3.55-4.03 (m, 1 H), 2.93-3.25 (m, 1 H),

2.79-2.92 (m, 1 H)

41
(CD₃OD) δ 8.12 (s, 1 H), 7.59-7.68 (m, 2 H), 7.39 (dd, 1 H),
394.0
95.4%

7.17 (td, 1 H), 6.64 (br s, 1 H), 4.76-4.83 (m, 1 H), 3.89 (br s,
[M + H]⁺

1 H), 3.06 (br s, 1 H), 2.82 (br d, 1 H), 2.38 (br d, 1 H), 0.93-

0.98 (m, 4 H)

42
(CD₃OD) δ 8.13 (s, 1 H), 7.60-7.69 (m, 2 H), 7.39 (dd, 1 H),
394.0
98.3%

7.17 (td, 1 H), 6.67 (br s, 1 H), 4.79-4.84 (m, 1 H), 3.87 (br s,
[M + H]⁺

1 H), 3.05 (br s, 1 H), 2.82 (br d, 1 H), 2.37 (quin, 1 H), 0.93-

0.98 (m, 4 H)

43
(CD₃OD) δ 8.67 (br s, 1 H), 8.17 (br s, 1 H), 7.99 (br s, 1 H),
471.1
92.7%

7.65-7.75 (m, 2 H), 7.56 (br s, 1 H), 7.45 (dd, 1 H), 7.23 (td, 1
[M + H]⁺

H), 6.78 (br s, 1 H), 4.71-4.87 (m, 1 H), 3.73-4.16 (m, 1 H),

3.22 (br s, 1 H), 2.90 (br d, 1 H), 2.38-2.55 (m, 1 H), 1.01-

1.16 (m, 4 H)

44
(CD₃OD) δ 8.67 (br s, 1 H), 7.87-8.27 (m, 2 H), 7.66-7.74 (m,
471.2
91.5%

2 H), 7.56 (br s, 1 H), 7.45 (dd, 1 H), 7.23 (td, 1 H), 6.78 (br s,
[M + H]⁺

1 H), 4.63-4.65 (m, 1 H), 3.99 (s, 1 H), 3.23 (br s, 1 H), 2.90

(br d, 1 H), 2.38-2.59 (m, 1 H), 1.00-1.15 (m, 4 H)

45
(CD₃OD) δ 7.53-7.73 (m, 2 H), 7.40 (dd, 1 H), 7.18 (td, 1 H),
480.0
85.3%

5.87-6.84 (m, 1 H), 3.53-4.07 (m, 2 H), 2.67-3.16 (m, 2 H),
[M + H]⁺

1.50-1.69 (m, 6 H)

46
(CD₃OD) δ 7.57-7.69 (m, 2 H), 7.40 (dd, 1 H), 7.18 (td, 1 H),
480.0
85.7%

6.01-6.87 (m, 1 H), 3.49-4.07 (m, 2 H), 2.72-3.13 (m, 2 H),
[M + H]⁺

1.51-1.71 (m, 6 H)

47
(CD₃OD) δ 8.55 (s, 1 H), 8.37 (br s, 1 H), 7.89 (d, 1 H), 7.61-
474.2
83.9%

7.67 (m, 2 H), 7.36-7.44 (m, 2 H), 7.18 (td, 1 H), 6.72 (br s, 1
[M + H]⁺

H), 4.70 (br d, 1 H), 3.72-4.09 (m, 1 H), 3.10 (br s, 1 H), 2.78-

2.93 (m, 3 H), 2.62-2.72 (m, 2 H), 2.34 (s, 6 H)

48
(CD₃OD) δ 8.54 (s, 1 H), 8.37 (br s, 1 H), 7.88 (d, 1 H), 7.61-
474.2
95.7%

7.68 (m, 2 H), 7.35-7.44 (m, 2 H), 7.18 (td, 1 H), 6.73 (br s, 1
[M + H]⁺

H), 4.70 (br d, 1 H), 3.76-4.02 (m, 1 H), 3.04-3.16 (m, 1 H),

2.77-2.91 (m, 3 H), 2.60-2.69 (m, 2 H), 2.31 (s, 6 H)

49
(CD₃OD) δ 8.71 (br d, 0.7 H), 8.46 (br s, 0.3 H), 8.28 (d, 0.7
499.0
97.2%

H), 8.00-8.12 (m, 1 H), 7.92 (br s, 0.3 H), 7.48-7.78 (m, 3 H),
[M + H]⁺

7.35-7.47 (m, 1 H), 7.20 (td, 1 H), 6.20-6.92 (m, 1 H), 4.92-

5.08 (m, 0.3 H), 4.22 (br dd, 0.7 H), 3.60-4.07 (m, 1 H), 2.95-

3.16 (m, 1 H), 2.82 (br d, 1 H)

50
(CD₃OD) δ 8.71 (br d, 0.8 H), 8.46 (br s, 0.2 H), 8.28 (d, 0.7
499.0
77.6%

H), 8.04 (br t, 1 H), 7.93 (br s, 0.3 H), 7.48-7.78 (m, 3.3 H),
[M + H]⁺

7.42 (br d, 1.2 H), 7.20 (td, 1 H), 6.24-6.92 (m, 0.5 H), 4.94-

5.10 (m, 0.3 H), 4.22 (br dd, 0.7 H), 3.59-4.07 (m, 1 H), 2.93-

3.17 (m, 1 H), 2.84 (br s, 1 H)

51
(CD₃OD) δ 8.47 (br s, 1 H), 7.63-7.73 (m, 2 H), 7.43 (dd, 1
403.9
90.8%

H), 6.99-7.29 (m, 2 H), 6.60-6.89 (m, 1 H), 4.45-4.66 (m, 1
[M + H]⁺

H), 3.49-4.05 (m, 1 H), 2.96-3.20 (m, 1 H), 2.86 (br d, 1 H)

52
(CD₃OD) δ 8.47 (br s, 1 H), 7.63-7.73 (m, 2 H), 7.38-7.63 (m,
404.0
82.8%

1 H), 6.96-7.30 (m, 2 H), 6.77 (br s, 1 H), 4.56 (br d, 1 H),
[M + H]⁺

3.46-4.04 (m, 1 H), 3.11 (br s, 1 H), 2.86 (br d, 1 H)

53
(CD₃OD) δ 7.64-7.75 (m, 2 H), 7.44 (br d, 1 H), 6.93-7.28 (m,
444.2
95.0%

2 H), 6.71 (br s, 1 H), 4.53-4.61 (m, 1 H), 3.54-4.04 (m, 1 H),
[M + H]⁺

3.07 (br s, 1 H), 2.88 (br s, 1 H), 2.26 (br s, 1 H), 1.21 (br s, 4

H)

54
(CD₃OD) δ 7.52-7.61 (m, 2 H), 7.32 (br d, 1 H), 6.81-7.16 (m,
444.1
70.9%

2 H), 6.60 (br s, 1 H), 4.37-4.48 (m, 1 H), 3.46-3.92 (m, 1 H),
[M + H]⁺

2.94 (br s, 1 H), 2.75 (br d, 1 H), 2.14 (br s, 1 H), 1.09 (br s, 4

H)

55
(CD₃OD) δ 7.60-7.70 (m, 2 H), 7.34-7.48 (m, 1 H), 7.16-7.24
371.2
98.6%

(m, 1 H), 6.61-6.92 (m, 1 H), 4.99 (br dd, 0.3 H), 4.47 (dd, 0.7
[M + H]⁺

H), 3.42-3.88 (m, 1 H), 2.68-3.21 (m, 4 H), 2.03-2.34 (m, 4

H), 1.57-1.86 (m, 2 H)

56
(CD₃OD) δ 7.62-7.68 (m, 2 H), 7.38-7.47 (m, 1 H), 7.16-7.24
371.2
92.4%

(m, 1 H), 6.58-6.94 (m, 1 H), 4.99 (br dd, 0.3 H), 4.47 (dd, 0.7
[M + H]⁺

H), 3.73-3.83 (m, 1 H), 2.64-3.17 (m, 4 H), 2.03-2.30 (m, 4

H), 1.61-1.85 (m, 2 H)

57
(CD₃OD) δ 8.44-8.51 (m, 1 H), 7.69 (br s, 1 H), 7.55 (d, 1 H),
418.1
93.1%

7.38-7.48 (m, 1 H), 7.22 (d, 1 H), 6.81 (br d, 0.6 H), 6.06 (br
[M + H]⁺

s, 0.2 H), 4.93 (br d, 0.7 H), 3.80-4.06 (m, 1 H), 3.43-3.68 (m,

0.4 H), 2.95 (br dd, 1 H), 2.72-2.89 (m, 1 H), 2.49 (s, 3 H)

58
(CD₃OD) δ 8.43-8.51 (m, 1 H), 7.69 (s, 1 H), 7.54 (d, 1 H),
418.2
92.5%

7.38-7.47 (m, 1 H), 7.22 (d, 1 H), 6.82 (br s, 1 H), 6.07 (br s,
[M + H]⁺

0.4 H), 4.89-5.05 (m, 0.1 H), 3.86-3.97 (m, 0.8 H), 3.85-4.03

(m, 1 H), 3.45-3.62 (m, 0.3 H), 2.91-3.03 (m, 1 H), 2.76-2.90

(m, 1 H), 2.49 (s, 3 H)

59
(CD₃OD) δ 7.48-7.60 (m, 2 H), 7.24-7.36 (m, 1 H), 7.02-7.14
373.2
96.5%

(m, 1 H), 6.67 (s, 0.8 H), 6.28 (s, 0.2 H), 5.05-5.15 (m, 0.5 H),
[M + H]⁺

4.90-5.01 (m, 0.5 H), 4.63-4.72 (m, 0.3 H), 4.21 (dd, 0.7 H),

3.59-3.71 (m, 0.8 H), 3.01-3.15 (m, 0.2 H), 2.56-2.90 (m, 5

H), 1.97-2.50 (m, 4 H)

60
(CD₃OD) δ 7.55-7.69 (m, 2 H), 7.28-7.47 (m, 1 H), 7.06-7.23
373.2
99.0%

(m, 1 H), 6.75 (br s, 0.7 H), 6.35 (br s, 0.3 H), 5.18 (br t, 0.5
[M + H]⁺

H), 4.96-5.10 (m, 0.5 H), 4.29 (br dd, 1 H), 3.74 (br s, 1 H),

2.65-3.00 (m, 5 H), 2.00-2.48 (m, 4 H)

61
(CD₃OD) δ 7.56-7.73 (m, 2 H), 7.31-7.49 (m, 1 H), 7.11-7.26
363.0
99.4%

(m, 1 H), 6.87 (s, 0.8 H), 6.67 (s, 0.2 H), 4.96 (br dd, 0.3 H),
[M + H]⁺

4.44-4.54 (m, 0.7 H), 3.80-3.94 (m, 0.7 H), 3.36-3.45 (m, 0.3

H), 3.10-3.25 (m, 1 H), 2.73-2.99 (m, 2 H), 1.97-2.20 (m, 1

H), 1.69-1.94 (m, 1 H)

62
(CD₃OD) δ 7.56-7.75 (m, 2 H), 7.35-7.51 (m, 1 H), 7.12-7.25
363.0
99.2%

(m, 1 H), 6.71 (s, 0.7 H), 6.45 (s, 0.3 H), 4.91-4.97 (m, 0.3 H),
[M + H]⁺

4.50 (dd, 0.7 H), 3.82-4.04 (m, 0.7 H), 3.11-3.29 (m, 1.3 H),

2.93-3.10 (m, 0.7 H), 2.68-2.91 (m, 1.3 H), 2.01-2.30 (m, 1

H), 1.73-1.99 (m, 1 H)

63
(CD₃OD) δ 8.35-8.60 (m, 1 H), 7.70 (s, 1 H), 7.35-7.57 (m, 2
418.0
100%

H), 7.25 (d, 1 H), 6.83 (s, 0.8 H), 6.09 (br s, 0.2 H), 4.95 (br d,
[M + H]⁺

0.2 H), 3.84-4.11 (m, 1.6 H), 3.58 (br d, 0.2 H), 2.76-3.06 (m,

2 H), 2.46 (s, 3 H)

64
(CD₃OD) δ 8.39-8.57 (m, 1 H), 7.71 (s, 1 H), 7.40-7.58 (m, 2
418.0
98.8%

H), 7.25 (d, 1 H), 6.83 (s, 0.8 H), 6.09 (br s, 0.2 H), 4.93-5.00
[M + H]⁺

(m, 0.3 H), 3.97-4.05 (m, 0.7 H), 3.84-3.95 (m, 0.8 H), 3.57

(br s, 0.2 H), 2.77-3.02 (m, 2 H), 2.46 (s, 3 H)

65
(CD₃OD) δ 8.32 (br s, 1 H), 8.12 (d, 1 H), 7.85 (d, 1 H), 7.63-
501.1
86.6%

7.71 (m, 2 H), 7.39-7.49 (m, 2 H), 7.20 (td, 1 H), 6.77 (br s, 1
[M + H]⁺

H), 4.75 (br dd, 1 H), 3.92 (br s, 1 H), 3.18-3.26 (m, 4 H),

3.06-3.17 (m, 1 H), 2.85 (br dd, 3.0 Hz, 1 H), 2.61-2.73 (m, 4

H), 2.39 (s, 3 H)

66
(CD₃OD) δ 8.33 (br s, 1 H), 8.13 (d, 1 H), 7.86 (d, 1 H), 7.61-
501.1
85.6%

7.73 (m, 2 H), 7.39-7.49 (m, 2 H), 7.21 (td, 1 H), 6.77 (br s, 1
[M + H]⁺

H), 4.75 (br dd, 1 H), 3.92 (br s, 1 H), 3.19-3.27 (m, 4 H),

3.06-3.17 (m, 1 H), 2.85 (br dd, 1 H), 2.66-2.75 (m, 4 H), 2.42

(s, 3 H)

67
(CD₃OD) δ 8.30-8.42 (m, 1 H), 7.99-8.14 (m, 1 H), 7.49-7.73
435.0
100%

(m, 2.3 H), 7.32-7.45 (m, 1 H), 7.10-7.27 (m, 1 H), 6.85 (br s,
[M + H]⁺

0.7 H), 5.30 (br dd, 0.8 H), 5.08 (br dd, 0.2 H), 3.83-4.06 (m,

4 H), 3.61 (br s, 0.4 H), 3.10-3.23 (m, 0.6 H), 2.76-3.03 (m, 1

H)

68
(CD₃OD) δ 8.28-8.43 (m, 1 H), 7.97-8.14 (m, 1 H), 7.51-7.72
435.0
82.8%

(m, 2.3 H), 7.31-7.46 (m, 1 H), 7.11-7.28 (m, 1 H), 6.85 (br s,
[M + H]⁺

0.7 H), 5.30 (br dd, 0.7 H), 5.08 (br dd, 0.3 H), 3.85-4.03 (m,

4 H), 3.59 (br d, 0.3 H), 3.10-3.22 (m, 0.7 H), 2.78-3.01 (m, 1

H)

69
(CD₃OD) δ 8.82 (dd, 1 H), 8.32 (br s, 1 H), 7.79 (d, 1 H),
482.9
96.7%

7.52-7.59 (m, 2 H), 7.39-7.52 (m, 1 H), 7.26-7.39 (m, 1 H),
[M + H]⁺

7.09 (td, 1 H), 6.65 (br s, 1 H), 4.60 (br d, 1 H), 3.80 (br s, 1

H), 2.92-3.10 (m, 1 H), 2.73 (dd, 1 H)

70
(CD₃OD) δ 8.78-8.82 (m, 1 H), 8.31 (br s, 1 H), 7.78 (d, 1 H),
482.9
94.1%

7.52-7.59 (m, 2 H), 7.42 (d, 1 H), 7.26-7.38 (m, 1 H), 7.08 (td,
[M + H]⁺

1 H), 6.65 (br s, 1 H), 4.59 (br d, 1 H), 3.81 (br s, 1 H), 2.93-

3.08 (m, 1 H), 2.73 (dd, 1 H)

71
(CD₃OD) δ 8.78 (s, 1 H), 8.31 (br s, 1 H), 7.99 (s, 1 H), 7.79-
483.0
94.5%

7.89 (m, 2 H), 7.51-7.63 (m, 3 H), 7.34 (dd, 1 H), 7.10 (td, 1
[M + H]⁺

H), 6.67 (br s, 1 H), 4.64 (br d, 1 H), 3.85 (s, 4 H), 2.93-3.09

(m, 1 H), 2.74 (br dd, 1 H)

72
(CD₃OD) δ 8.77 (s, 1 H), 8.30 (br s, 1 H), 7.99 (s, 1 H), 7.77-
483.0
91.1%

7.91 (m, 2 H), 7.51-7.63 (m, 3 H), 7.34 (dd, 1 H), 7.10 (td, 1
[M + H]⁺

H), 6.67 (br s, 1 H), 4.64 (br d, 1 H), 3.85 (s, 4 H), 2.95-3.10

(m, 1 H), 2.74 (br dd, 1 H)

73
(CD₃OD) δ 8.15-8.28 (m, 2 H), 7.75 (d, 1 H), 7.52-7.59 (m, 2
433.0
92.5%

H), 7.32 (dd, 1 H), 7.06-7.15 (m, 2 H), 6.65 (br s, 1 H), 4.63
[M + H]⁺

(br dd, 1 H), 3.78 (s, 4 H), 2.94-3.07 (m, 1 H), 2.73 (br dd, 1

H)

74
(CD₃OD) δ 8.16-8.27 (m, 2 H), 7.75 (d, 1 H), 7.52-7.59 (m, 2
433.0
86.6%

H), 7.32 (dd, 1 H), 7.00-7.16 (m, 2 H), 6.65 (br s, 1 H), 4.63
[M + H]⁺

(br dd, 1 H), 3.78 (s, 4 H), 2.96-3.06 (m, 1 H), 2.73 (br dd, 1

H)

75
(CD₃OD) δ 7.94-8.19 (m, 2 H), 7.63-7.76 (m, 2 H), 7.50-7.61
467.1
100%

(m, 1.4 H), 7.38-7.48 (m, 1 H), 7.15-7.29 (m, 1 H), 6.90 (br s,
[M + H]⁺

0.6 H), 5.35 (dd, 0.7 H), 5.14 (dd, 0.3 H), 4.00 (br s, 0.7 H),

3.68 (br s, 0.3 H), 3.18-3.28 (m, 0.7 H), 3.01 (br d, 0.3 H),

2.92 (br d, 1 H)

76
(CD₃OD) δ 8.11 (br s, 2 H), 7.72-7.82 (m, 1 H), 7.64-7.71 (m,
467.1
83.2%

1 H), 7.51-7.63 (m, 1.3 H), 7.40-7.49 (m, 1 H), 7.17-7.29 (m,
[M + H]⁺

1 H), 6.92 (s, 0.7 H), 5.36 (dd, 0.7 H), 5.15 (dd, 0.3 H), 4.01

(br t, 0.7 H), 3.62-3.77 (m, 0.3 H), 3.14-3.31 (m, 0.7 H), 2.98-

3.12 (m, 0.3 H), 2.81-2.98 (m, 1 H)

77
(DMSO-d₆) δ 12.25 (br s, 1 H), 7.89-8.05 (m, 1 H), 7.83 (dd,
463.1
65.4%

1 H), 7.58-7.71 (m, 2 H), 7.23-7.43 (m, 3 H), 6.61-7.20 (m, 1
[M + H]⁺

H), 4.82-5.17 (m, 1 H), 3.59-4.07 (m, 1 H), 2.79-3.12 (m, 2

H), 2.60-2.69 (m, 3 H)

78
(DMSO-d₆) δ 12.18-12.29 (m, 1 H), 7.91-8.04 (m, 1 H), 7.83
463.1
76.6%

(dd, 1 H), 7.60-7.71 (m, 2 H), 7.25-7.43 (m, 3 H), 6.63-7.19
[M + H]⁺

(m, 1 H), 4.86-5.16 (m, 1 H), 3.65-4.05 (m, 1 H), 2.82-3.11

(m, 2 H), 2.59-2.70 (m, 3 H)

79
(CD₃OD) δ 8.69 (s, 1 H), 8.43 (br s, 1 H), 8.05 (s, 1 H), 7.58-
508.1
95.7%

7.76 (m, 2 H), 7.32-7.53 (m, 1 H), 7.20 (td, 1 H), 6.61-6.85
[M + H]⁺

(m, 1 H), 4.54-4.79 (m, 1 H), 3.89 (br s, 1 H), 3.06-3.20 (m, 1

H), 2.96-3.03 (m, 2 H), 2.84 (br dd, 1 H), 2.72 (dd, 2 H), 2.41

(s, 6 H)

80
(CD₃OD) δ 8.70 (s, 1 H), 8.44 (br s, 1 H), 8.05 (s, 1 H), 7.61-
508.0
97.8%

7.77 (m, 2 H), 7.43 (dd, 1 H), 7.20 (td, 1 H), 6.74 (br s, 1 H),
[M + H]⁺

4.72 (br d, 1 H), 3.90 (br s, 1 H), 3.06-3.20 (m, 1 H), 2.96-

3.06 (m, 2 H), 2.84 (br dd, 1 H), 2.73 (dd, 2 H), 2.42 (s, 6 H))

81
(CD₃OD) δ 9.34 (s, 1 H), 8.69 (d, 1 H), 8.52 (s, 1 H), 8.06-
480.4
96.0%

8.17 (m, 2 H), 7.91-8.05 (m, 3 H), 7.69 (dd, 1 H), 7.38-7.52
[M + H]⁺

(m, 2 H), 7.23 (td, 1 H), 6.90 (s, 1 H), 4.78 (br dd, 1 H), 3.91

(br s, 1 H), 3.10-3.24 (m, 1 H), 2.90 (br dd, 1 H)

82
(CD₃OD) δ 9.35 (s, 1 H), 8.70 (d, 1 H), 8.53 (s, 1 H), 8.06-
480.4
98.7%

8.28 (m, 3 H), 7.91-8.04 (m, 2 H), 7.70 (dd, 1 H), 7.36-7.55
[M + H]⁺

(m, 2 H), 7.24 (td, 1 H), 6.93 (s, 1 H), 4.79 (br dd, 1 H), 3.90

(br s, 1 H), 3.12-3.26 (m, 1 H), 2.83-2.98 (m, 1 H)

83
(CD₃OD) δ 8.03-8.26 (m, 1 H), 7.57-7.78 (m, 2 H), 7.49 (br s,
467.0
98.4%

0.2 H), 7.35-7.43 (m, 1 H), 7.13-7.32 (m, 3 H), 6.86 (br s, 0.7
[M + H]⁺

H), 5.25 (br dd, 0.7 H), 5.10 (br dd, 0.4 H), 3.87-4.05 (m, 0.8

H), 3.63 (br s, 0.4 H), 2.79-3.27 (m, 2 H)

84
(CD₃OD) δ 8.06-8.33 (m, 1 H), 7.57-7.73 (m, 2 H), 7.50 (br s,
467.0
100%

0.3 H), 7.35-7.44 (m, 1 H), 7.13-7.33 (m, 3 H), 6.87 (br s, 0.7
[M + H]⁺

H), 5.26 (br dd, 0.7 H), 5.10 (br dd, 0.4 H), 3.95 (br t, 0.8 H),

3.62 (br d, 0.4 H), 2.78-3.27 (m, 2 H)

85
(CD₃OD) δ 8.42-8.82 (m, 1 H), 7.86-8.39 (m, 2 H), 7.65-7.77
481.0
98.9%

(m, 2 H), 7.40-7.64 (m, 2 H), 7.05-7.38 (m, 2 H), 6.82 (s, 1
[M + H]⁺

H), 5.00 (br s, 0.3 H), 4.76 (br d, 0.7 H), 3.57-4.09 (m, 1 H),

2.97-3.30 (m, 1 H), 2.91 (br d, 1 H)

86
(CD₃OD) δ 8.43-8.81 (m, 1 H), 7.87-8.38 (m, 2 H), 7.65-7.77
481.0
96.9%

(m, 2 H), 7.40-7.65 (m, 2 H), 7.02-7.38 (m, 2 H), 6.82 (br s, 1
[M + H]⁺

H), 5.01 (br s, 0.3 H), 4.76 (br d, 0.7 H), 3.56-4.10 (m, 1 H),

2.97-3.29 (m, 1 H), 2.91 (br d, 1 H)

87
(CD₃OD) δ 7.84-8.47 (m, 2 H), 7.58-7.77 (m, 2 H), 6.95-7.53
484.1
99.2%

(m, 3 H), 6.77 (s, 1 H), 4.71 (br s, 1 H), 3.98 (br s, 4 H), 2.63-
[M + H]⁺

3.23 (m, 2 H)

88
(CD₃OD) δ 7.86-8.60 (m, 2 H), 7.60-7.85 (m, 2 H), 6.95-7.58
484.1
98.8%

(m, 3 H), 6.77 (s, 1 H), 4.52-4.80 (m, 1 H), 3.98 (br s, 4 H),
[M + H]⁺

2.76-3.26 (m, 2 H)

89
(CD₃OD) δ 8.16-8.37 (m, 2 H), 7.66-7.95 (m, 2 H), 7.43-7.65
498.9
99.1%

(m, 2.4 H), 7.22-7.37 (m, 1 H), 6.91-7.20 (m, 1 H), 6.80 (s, 0.6
[M + H]⁺

H), 4.98-5.33 (m, 1 H), 3.47-3.95 (m, 1 H), 2.70-3.14 (m, 2 H)

90
(CD₃OD) δ 8.21-8.42 (m, 2 H), 7.81-7.98 (m, 2 H), 7.50-7.75
499.0
99.1%

(m, 2.4 H), 7.34-7.48 (m, 1 H), 7.09-7.24 (m, 1 H), 6.88 (s, 0.6
[M + H]⁺

H), 5.06-5.37 (m, 1 H), 3.57-4.02 (m, 1 H), 2.69-3.23 (m, 2 H)

91
(CD₃OD) δ 8.26 (br s, 1 H), 7.94 (d, 1 H), 7.83 (d, 1 H), 7.63-
446.2
90.1%

7.69 (m, 2 H), 7.41 (ddd, 2 H), 7.20 (td, 1 H), 6.76 (br s, 1 H),
[M + H]⁺

4.75 (br dd, 1 H), 3.89 (br s, 1 H), 3.07-3.16 (m, 1 H), 2.96 (s,

6 H), 2.83 (br dd, 1 H)

92
(CD₃OD) δ 8.26 (br s, 1 H), 7.93 (s, 1 H), 7.82 (d, 1 H), 7.63-
446.2
91.6%

7.68 (m, 2 H), 7.36-7.44 (m, 2 H), 7.19 (td, 1 H), 6.75 (s, 1 H),
[M + H]⁺

4.74 (br dd, 1 H), 3.89 (br s, 1 H), 3.06-3.16 (m, 1 H), 2.95 (s,

6 H), 2.79-2.87 (m, 1 H)

93
(CD₃OD) δ 7.58-7.88 (m, 4 H), 7.39-7.51 (m, 1 H), 7.20 (td, 1
403.0
98.6%

H), 6.23-6.92 (m, 2 H), 4.28 (br d, 1 H), 3.93 (br s, 1 H), 2.94-
[M + H]⁺

3.11 (m, 1 H), 2.80 (br d, 1 H)

94
(CD₃OD) δ 7.56-7.88 (m, 4 H), 7.39-7.53 (m, 1 H), 7.21 (td, 1
403.0
97.7%

H), 6.25-6.95 (m, 2 H), 4.17-4.38 (m, 1 H), 3.93 (br s, 1 H),
[M + H]⁺

2.95-3.09 (m, 1 H), 2.80 (br d, 1 H)

95
(CD₃OD) δ 8.06 (br s, 1 H), 7.55-7.73 (m, 2 H), 7.42 (br d, 1
417.1
97.1%

H), 7.19 (td, 1 H), 6.64-7.05 (m, 2 H), 4.12-4.39 (m, 1 H),
[M + H]⁺

3.98 (s, 3 H), 3.63-3.91 (m, 1 H), 2.88-3.07 (m, 1 H), 2.76 (br

dd, 1 H)

96
(CD₃OD) δ 7.90-8.05 (m, 2 H), 7.71 (s, 1 H), 7.36-7.58 (m, 2
417.1
96.2%

H), 6.69-7.12 (m, 2 H), 4.16 (br d, 1 H), 3.97 (s, 3 H), 3.45-
[M + H]⁺

3.81 (m, 1 H), 2.87-3.05 (m, 1 H), 2.74 (br dd, 1 H)

97
(CD₃OD) δ 8.75-8.81 (m, 1 H), 8.27-8.35 (m, 1 H), 8.05-8.13
428.2
100%

(m, 1 H), 7.63-7.76 (m, 2 H), 7.45-7.59 (m, 2 H), 7.20-7.32
[M + H]⁺

(m, 1 H), 6.92 (s, 1 H), 5.27 (dd, 0.7 H), 5.12 (dd, 0.3 H),

3.93-4.03 (m, 0.7 H), 3.57-3.72 (m, 0.3 H), 2.81-3.29 (m, 2

H), 2.44-2.49 (m, 3 H)

98
(CD₃OD) δ 8.69-8.80 (m, 1 H), 8.27-8.34 (m, 1 H), 8.02-8.12
428.2
98.3%

(m, 1 H), 7.63-7.76 (m, 2 H), 7.45-7.59 (m, 2 H), 7.20-7.30
[M + H]⁺

(m, 1 H), 6.92 (s, 1 H), 5.27 (dd, 0.7 H), 5.12 (dd, 0.3 H),

3.92-4.03 (m, 0.7 H), 3.64 (td, 0.3 H), 2.85-3.29 (m, 2 H),

2.41-2.49 (m, 3 H)

99
(CD₃OD) δ 8.67-8.73 (m, 1 H), 8.33-8.41 (m, 1 H), 7.85-7.93
446.2
100%

(m, 1 H), 7.70-7.75 (m, 1 H), 7.45-7.58 (m, 2 H), 7.21-7.30
[M + H]⁺

(m, 1 H), 6.91 (s, 1 H), 5.28 (dd, 0.7 H), 5.12 (dd, 0.3 H),

3.86-4.05 (m, 0.7 H), 3.56-3.71 (m, 0.3 H), 2.83-3.29 (m, 2

H), 2.41-2.50 (m, 3 H)

100
(CD₃OD) δ 8.56-8.76 (m, 1 H), 8.21-8.45 (m, 1 H), 7.80-7.96
446.2
98.5%

(m, 1 H), 7.73 (br s, 1 H), 7.36-7.60 (m, 2 H), 7.19-7.31 (m, 1
[M + H]⁺

H), 6.91 (br s, 1 H), 5.20-5.33 (m, 0.7 H), 5.12 (br d, 0.3 H),

3.97 (br t, 0.7 H), 3.58-3.73 (m, 0.3 H), 2.83-3.28 (m, 2 H),

2.43-2.55 (m, 3 H)

101
(CD₃OD) δ 8.70-8.78 (m, 1 H), 8.22-8.30 (m, 1 H), 8.01-8.09
428.1
97.2%

(m, 1 H), 7.39-7.73 (m, 4 H), 7.14-7.22 (m, 1 H), 6.89 (s, 1
[M + H]⁺

H), 5.24 (dd, 0.7 H), 5.09 (br dd, 0.3 H), 3.95 (ddd, 0.7 H),

3.55-3.66 (m, 0.3 H), 3.15-3.26 (m, 0.7 H), 2.95-3.06 (m, 0.3

H), 2.80-2.93 (m, 1 H), 2.43-2.49 (m, 3 H)

102
(CD₃OD) δ 8.72-8.78 (m, 1 H), 8.24-8.31 (m, 1 H), 8.02-8.10
428.1
97.0%

(m, 1 H), 7.40-7.73 (m, 4 H), 7.16-7.23 (m, 1 H), 6.90 (s, 1
[M + H]⁺

H), 5.25 (dd, 0.7 H), 5.09 (br dd, 0.3 H), 3.95 (ddd, 0.7 H),

3.56-3.66 (m, 0.3 H), 3.16-3.27 (m, 0.7 H), 2.96-3.07 (m, 0.3

H), 2.82-2.93 (m, 1 H), 2.43-2.50 (m, 3 H)

103
(CD₃OD) δ 8.30-8.51 (m, 1 H), 8.04-8.19 (m, 1 H), 7.72 (s, 1
431.1
100%

H), 7.43-7.65 (m, 2.4 H), 7.18-7.29 (m, 1 H), 6.89 (br s, 0.6
[M + H]⁺

H), 5.32 (dd, 0.7 H), 5.10 (dd, 0.3 H), 3.91-4.08 (m, 3.8 H),

3.61 (br s, 0.2 H), 3.15-3.25 (m, 0.6 H), 2.86-3.07 (m, 1.4 H),

2.47-2.54 (m, 3 H)

104
(CD₃OD) δ 8.35-8.47 (m, 1 H), 8.06-8.16 (m, 1 H), 7.72 (s, 1
431.1
99.3%

H), 7.44-7.64 (m, 2.4 H), 7.20-7.27 (m, 1 H), 6.89 (br s, 0.6
[M + H]⁺

H), 5.32 (dd, 0.7 H), 5.10 (dd, 0.3 H), 3.90-4.04 (m, 3.8 H),

3.61 (br s, 0.3 H), 3.16-3.25 (m, 0.6 H), 2.84-3.06 (m, 1.4 H),

2.46-2.54 (m, 3 H)

105
(CD₃OD) δ 7.79-7.89 (m, 1 H), 7.50-7.78 (m, 2.3 H), 7.36-
435.1
96.4%

7.49 (m, 1 H), 7.10-7.28 (m, 1 H), 6.79-7.06 (m, 1.7 H), 5.31
[M + H]⁺

(dd, 0.7 H), 5.13 (dd, 0.3 H), 3.84-4.12 (m, 3.7 H), 3.49-3.75

(m, 0.3 H), 2.81-3.26 (m, 2 H)

106
(CD₃OD) δ 7.78-7.90 (m, 1 H), 7.48-7.77 (m, 2.3 H), 7.36-
435.2
97.4%

7.46 (m, 1 H), 7.11-7.26 (m, 1 H), 6.76-7.06 (m, 1.7 H), 5.31
[M + H]⁺

(dd, 0.7 H), 5.13 (dd, 0.3 H), 3.89-4.11 (m, 3.7 H), 3.65 (br s,

0.3 H), 2.71-3.26 (m, 2 H)

107
Data provided above

108
Data provided above

109
(CD₃OD) δ 7.54-7.76 (m, 2 H), 7.42 (dd, 1 H), 7.17-7.28 (m,
448.1
97.8%

1.3 H), 6.56-7.16 (m, 1.7 H), 4.67 (br s, 2 H), 4.55 (br s, 1 H),
[M + H]⁺

3.94 (br s, 1 H), 3.34-3.69 (m, 3 H), 3.12 (br d, 1 H), 2.85 (br

d, 1 H)

110
(CD₃OD) δ 7.58-7.75 (m, 2 H), 7.41 (dd, 1 H), 7.16-7.26 (m,
448.1
96.2%

1.3 H), 6.57-7.15 (m, 1.7 H), 4.67 (br s, 2 H), 4.56 (br d, 1 H),
[M + H]⁺

3.94 (br s, 1 H), 3.49 (br s, 3 H), 3.12 (br d, 1 H), 2.76-2.92

(m, 1 H)

111
(CD₃OD) δ 8.27-8.42 (m, 1 H), 8.01-8.11 (m, 1 H), 7.68 (s, 1
431.1
100%

H), 7.39-7.59 (m, 2.3 H), 7.12-7.32 (m, 1 H), 6.85 (s, 0.7 H),
[M + H]⁺

5.29 (br dd, 0.7 H), 5.06 (br dd, 0.3 H), 3.86-4.01 (m, 3.8 H),

3.53-3.62 (m, 0.2 H), 2.75-3.21 (m, 2 H), 2.37-2.50 (m, 3 H)

112
(CD₃OD) δ 8.31-8.41 (m, 1 H), 8.02-8.13 (m, 1 H), 7.68 (s, 1
431.1
99.3%

H), 7.37-7.60 (m, 2.3 H), 7.12-7.27 (m, 1 H), 6.85 (br s, 0.7
[M + H]⁺

H), 5.29 (br dd, 0.7 H), 5.06 (br dd, 0.3 H), 3.87-4.00 (m, 3.8

H), 3.58 (br d, 0.2 H), 2.78-3.23 (m, 2 H), 2.36-2.48 (m, 3 H)

113
(CD₃OD) δ 8.31-8.37 (m, 1 H), 7.62-7.86 (m, 3 H), 7.38-7.57
471.2
91.0%

(m, 1.5 H), 7.15-7.27 (m, 2 H), 6.90 (br s, 0.5 H), 5.30 (dd, 0.7
[M + H]⁺

H), 5.05-5.19 (m, 0.3 H), 3.99 (br t, 0.7 H), 3.66 (br s, 0.3 H),

2.97-3.28 (m, 1 H), 2.81-2.96 (m, 1 H)

114
(CD₃OD) δ 8.29-8.39 (m, 1 H), 7.61-7.87 (m, 3 H), 7.38-7.59
471.2
92.7%

(m, 1.5 H), 7.14-7.28 (m, 2 H), 6.90 (br s, 0.5 H), 5.30 (dd, 0.7
[M + H]⁺

H), 5.13 (dd, 0.3 H), 3.99 (br t, 0.7 H), 3.66 (br s, 0.3 H), 2.97-

3.28 (m, 1 H), 2.74-2.96 (m, 1 H)

115
(CD₃OD) δ 7.62-7.75 (m, 2 H), 7.43 (br d, 1 H), 7.09-7.36 (m,
502.2
87.8%

2 H), 6.94-7.04 (m, 0.3 H), 6.53-6.85 (m, 0.7 H), 5.15-5.47
[M + H]⁺

(m, 2 H), 4.96-5.12 (m, 0.3 H), 4.47-4.61 (m, 0.7 H), 3.97 (br

s, 0.7 H), 3.44-3.81 (m, 0.3 H), 3.11 (br s, 1 H), 2.87 (br d, 1

H)

116
(CD₃OD) δ 7.60-7.78 (m, 2 H), 7.40-7.47 (m, 1 H), 7.06-7.31
502.1
87.4%

(m, 2 H), 6.93-7.02 (m, 0.3 H), 6.51-6.87 (m, 0.7 H), 5.14-
[M + H]⁺

5.49 (m, 2 H), 4.94-5.12 (m, 0.3 H), 4.53 (br d, 0.7 H), 3.98

(br s, 0.7 H), 3.47-3.81 (m, 0.3 H), 3.13 (br d, 1 H), 2.87 (br d,

1 H)

117
(CD₃OD) δ 8.48-8.68 (m, 1 H), 7.61-7.81 (m, 2 H), 7.37-7.59
503.2
99.7%

(m, 1.3 H), 7.16-7.30 (m, 1 H), 6.89 (s, 0.7 H), 5.05-5.33 (m, 1
[M + H]⁺

H), 4.04-4.11 (m, 3 H), 3.98 (br t, 0.7 H), 3.57-3.75 (m, 0.3

H), 2.77-3.26 (m, 2 H)

118
(CD₃OD) δ 8.54-8.63 (m, 1 H), 7.63-7.81 (m, 2 H), 7.37-7.60
503.2
99.1%

(m, 1.3 H), 7.13-7.32 (m, 1 H), 6.69-7.07 (m, 0.7 H), 5.27 (dd,
[M + H]⁺

0.7 H), 5.11 (br d, 0.3 H), 4.05-4.11 (m, 3 H), 3.98 (br s, 0.7

H), 3.65 (s, 0.3 H), 3.14-3.26 (m, 1 H), 2.91 (br d, 1 H)

119
(CD₃OD) δ 7.61-7.76 (m, 2 H), 7.37-7.56 (m, 2.3 H), 7.13-
449.1
100%

7.28 (m, 1 H), 6.88 (br s, 0.7 H), 5.32 (dd, 0.7 H), 5.02-5.17
[M + H]⁺

(m, 0.3 H), 4.14-4.29 (m, 3 H), 3.88-4.09 (m, 0.7 H), 3.65 (br

s, 0.3 H), 2.82-3.26 (m, 2 H), 2.22-2.53 (m, 3 H)

120
(CD₃OD) δ 7.59-7.83 (m, 2 H), 7.35-7.55 (m, 2 H), 7.14-7.26
449.1
89.7%

(m, 1 H), 6.88 (s, 1 H), 5.32 (br dd, 0.7 H), 5.12 (br dd, 0.3 H),
[M + H]⁺

4.11-4.29 (m, 3 H), 3.78-4.08 (m, 0.7 H), 3.57-3.72 (m, 0.3

H), 2.80-3.27 (m, 2 H), 2.25-2.45 (m, 3 H)

121
(CD₃OD) δ 8.98-9.08 (m, 1 H), 8.48-8.60 (m, 1 H), 7.90-8.04
500.1
85.6%

(m, 1 H), 7.61-7.77 (m, 2 H), 7.54 (s, 0.3 H), 7.36-7.48 (m, 1
[M + H]⁺

H), 7.13-7.27 (m, 1 H), 6.91 (s, 0.7 H), 5.24-5.38 (m, 0.7 H),

5.13 (dd, 0.3 H), 4.00 (ddd, 0.7 H), 3.58-3.77 (m, 0.3 H), 3.18-

3.26 (m, 0.7 H), 2.97-3.08 (m, 0.3 H), 2.82-2.95 (m, 1 H)

122
(CD₃OD) δ 8.99-9.06 (m, 1 H), 8.50-8.59 (m, 1 H), 7.92-8.00
500.0
86.4%

(m, 1 H), 7.62-7.77 (m, 2 H), 7.54 (s, 0.3 H), 7.38-7.45 (m, 1
[M + H]⁺

H), 7.15-7.25 (m, 1 H), 6.91 (s, 0.6 H), 5.29 (dd, 0.7 H), 5.13

(dd, 0.3 H), 3.93-4.06 (m, 0.7 H), 3.67 (td, 0.3 H), 3.18-3.27

(m, 0.7 H), 2.98-3.07 (m, 0.3 H), 2.84-2.95 (m, 1 H)

123
(CD₃OD) δ 7.62-7.75 (m, 2 H), 7.43 (dd, 1 H), 7.21 (td, 1 H),
490.1
97.4%

6.39-6.84 (m, 1 H), 4.39 (br s, 1 H), 3.58-4.09 (m, 1 H), 3.18
[M + H]⁺

(br s, 1 H), 2.87 (br d, 1 H), 1.48-1.73 (m, 6 H)

124
(CD₃OD) δ 7.63-7.74 (m, 2 H), 7.44 (dd, 1 H), 7.22 (td, 1 H),
492.2
94.5%

6.33-6.84 (m, 1 H), 4.39 (br s, 1 H), 3.62-4.11 (m, 1 H), 3.15
[M + H]⁺

(br s, 1 H), 2.87 (br d, 1 H), 1.66 (br s, 6 H)

125
(CD₃OD) δ 8.58-8.66 (m, 1 H), 8.13-8.29 (m, 1 H), 7.92 (br d,
446.1
98.3%

1 H), 7.63-7.79 (m, 2 H), 7.39-7.60 (m, 1.3 H), 7.14-7.28 (m,
[M + H]⁺

1 H), 6.91 (br s, 0.7 H), 5.07-5.34 (m, 1 H), 4.00 (br s, 0.7 H),

3.67 (br s, 0.3 H), 3.24 (br t, 0.7 H), 3.02 (br d, 0.3 H), 2.91

(br d, 1 H), 2.49 (br s, 3 H)

126
(CD₃OD) δ 8.58-8.66 (m, 1 H), 8.13-8.29 (m, 1 H), 7.92 (br d,
446.1
91.3%

1 H), 7.63-7.79 (m, 2 H), 7.39-7.60 (m, 1.3 H), 7.14-7.28 (m,
[M + H]⁺

1 H), 6.91 (br s, 0.7 H), 5.07-5.34 (m, 1 H), 4.00 (br s, 0.7 H),

3.67 (br s, 0.3 H), 3.24 (br t, 0.7 H), 3.02 (br d, 0.3 H), 2.91 (br

d, 1 H), 2.49 (br s, 3 H)

127
(CD₃OD) δ 7.58-7.76 (m, 2 H), 7.42 (br d, 1 H), 7.20 (td, 1
401.0
96.7%

H), 6.79 (br s, 0.7 H), 6.63 (s, 1.3 H), 4.30 (br d, 1 H), 3.88 (br
[M + H]⁺

s, 4 H), 2.94-3.09 (m, 1 H), 2.80 (br d, 1 H)

128
(CD₃OD) δ 7.58-7.75 (m, 2 H), 7.42 (br d, 1 H), 7.20 (td, 1
401.0
93.7%

H), 6.79 (br s, 0.7 H), 6.63 (s, 1.3 H), 4.30 (br d, 1 H), 3.88 (br
[M + H]⁺

s, 4 H), 2.94-3.10 (m, 1 H), 2.79 (br d, 1 H)

129
(CD₃OD) δ 7.64-7.73 (m, 2 H), 7.43 (dd, 1 H), 7.21 (td, 1 H),
446.2
91.4%

6.43-6.81 (m, 1 H), 4.33-4.55 (m, 1 H), 3.54-4.14 (m, 1 H),
[M + H]⁺

3.16 (br s, 1 H), 2.88 (br d, 1 H), 1.47-1.73 (m, 6 H)

130
(CD₃OD) δ 7.64-7.73 (m, 2 H), 7.43 (dd, 1 H), 7.21 (td, 1 H),
446.2
88.1%

6.38-6.83 (m, 1 H), 4.43 (br s, 1 H), 3.49-4.11 (m, 1 H), 2.96-
[M + H]⁺

3.26 (m, 1 H), 2.88 (br d, 1 H), 1.44-1.75 (m, 6 H)

131
(CD₃OD) δ 7.62-7.79 (m, 3.2 H), 7.37-7.62 (m, 1.3 H), 7.14-
435.30
99.1%

7.37 (m, 1 H), 7.01-7.13 (m, 1 H), 6.90 (br s, 0.5 H), 5.33 (dd,
[M + H]⁺

0.8 H), 5.12 (br d, 0.2 H), 4.27-4.38 (m, 3 H), 4.00 (br s, 0.7

H), 3.68 (br s, 0.3 H), 2.79-3.25 (m, 2 H)

132
(CD₃OD) δ 7.63-7.84 (m, 3.3 H), 7.35-7.62 (m, 1.2 H), 7.15-
435.30
98.3%

7.30 (m, 1 H), 7.02-7.14 (m, 1 H), 6.90 (br s, 0.5 H), 5.33 (dd,
[M + H]⁺

0.7 H), 5.14 (br dd, 0.3 H), 4.25-4.36 (m, 3 H), 4.00 (br s, 0.7

H), 3.69 (br s, 0.3 H), 3.10-3.29 (m, 1 H), 2.86-3.01 (m, 1 H)

133
(CD₃OD) δ 8.30 (br s, 1 H), 8.08 (d, 1 H), 7.83 (d, 1 H), 7.63-
527.3
100%

7.68 (m, 2 H), 7.43 (ddd, 2 H), 7.19 (td, 1 H), 6.75 (br s, 1 H),
[M + H]⁺

4.73 (br dd, 1 H), 3.90 (br s, 1 H), 3.09-3.18 (m, 5 H), 2.81-

2.86 (m, 5 H), 1.72-1.78 (m, 1 H), 0.51-0.56 (m, 2 H), 0.44-

0.49 (m, 2 H)

134
(CD₃OD) δ 8.30 (br s, 1 H), 8.08 (d, 1 H), 7.83 (d, 1 H), 7.62-
527.3
99.5%

7.68 (m, 2 H), 7.41-7.46 (m, 2 H), 7.19 (td, 1 H), 6.75 (br s, 1
[M + H]⁺

H), 4.73 (br dd, 1 H), 3.80-3.99 (m, 1 H), 3.90 (br s, 1 H),

3.07-3.17 (m, 5 H), 2.80-2.86 (m, 5 H), 1.72-1.78 (m, 1 H),

0.51-0.57 (m, 2 H), 0.44-0.49 (m, 2 H)

135
(CD₃OD) δ 7.61-7.76 (m, 2 H), 7.43 (dd, 1 H), 7.21 (td, 1 H),
412.3
88.4%

6.70 (br s, 1 H), 4.79-4.87 (m, 1 H), 4.63 (s, 1 H), 3.92 (br s, 1
[M + H]⁺

H), 2.75-3.22 (m, 1 H), 2.75-3.22 (m, 1 H), 2.23-2.50 (m, 3

H), 1.31-1.75 (m, 3 H)

136
(CD₃OD) δ 7.60-7.75 (m, 2 H), 7.43 (dd, 1 H), 7.21 (td, 1 H),
412.3
91.4%

6.71 (br s, 1 H), 4.81-4.87 (m, 1 H), 4.63 (s, 1 H), 3.91 (br s, 1
[M + H]⁺

H), 2.73-3.23 (m, 2 H), 2.39 (s, 3 H), 1.58 (br s, 3 H)

137
(CD₃OD) δ 8.48 (br s, 1 H), 8.16 (br s, 1 H), 7.43-7.62 (m, 2
400.3
96.8%

H), 7.23-7.37 (m, 1.4 H), 6.70-7.21 (m, 1.6 H), 4.59 (br s, 1
[M + H]⁺

H), 3.87 (br s, 1 H), 3.15 (br s, 1 H), 2.91 (br d, 1 H), 2.48 (s,

3 H)

138
(CD₃OD) δ 8.47 (br s, 1 H), 8.08 (br s, 1 H), 7.45-7.62 (m, 2
400.30
96.0%

H), 7.24-7.36 (m, 1.4 H), 6.67-7.21 (m, 1.6 H), 4.58 (br s, 1
[M + H]⁺

H), 3.87 (br s, 1 H), 3.15 (br s, 1 H), 2.90 (br d, 1 H), 2.47 (s,

3 H)

139
(CD₃OD) δ 8.28 (br s, 1 H), 8.06 (d, 1 H), 7.81 (d, 1 H), 7.59-
265.2
98.7%

7.67 (m, 2 H), 7.37-7.44 (m, 2 H), 7.17 (td, 1 H), 6.71 (br s, 1
[½M + H]⁺

H), 4.71 (br d, 1 H), 3.88 (br s, 1 H), 3.12-3.19 (m, 2 H), 3.09

(br s, 1 H), 2.91 (s, 2 H), 2.81 (br d, 1 H), 2.71-2.78 (m, 2 H),

2.29 (s, 3 H), 1.16 (s, 6 H)

140
(CD₃OD) δ 8.28 (br s, 1 H), 8.06 (d, 1 H), 7.81 (d, 1 H), 7.61-
265.3
98.4%

7.67 (m, 2 H), 7.37-7.43 (m, 2 H), 7.17 (td, 1 H), 6.71 (br s, 1
[½M + H]⁺

H), 4.67-4.76 (m, 1 H), 3.88 (br s, 1 H), 3.13-3.19 (m, 2 H),

3.09 (br s, 1 H), 2.91 (s, 2 H), 2.81 (br d, 1 H), 2.71-2.78 (m, 2

H), 2.29 (s, 3 H), 1.16 (s, 6 H)

141
(CD₃OD) δ 7.77 (s, 1 H), 7.67 (dd, 1 H), 7.43 (dd, 1 H), 7.22
460.20
96.1%

(td, 1 H), 6.90-7.17 (m, 1 H), 6.76 (br s, 1 H), 4.64 (br s, 1 H),
[M + H]⁺

3.94 (br s, 1 H), 3.07-3.21 (m, 1 H), 2.83-2.95 (m, 1 H), 1.29-

1.50 (m, 4 H)

142
(CD₃OD) δ 7.73 (s, 1 H), 7.67 (dd, 1 H), 7.43 (dd, 1 H), 7.22
460.20
96.1%

(td, 1 H), 6.95-7.15 (m, 1 H), 6.75 (br s, 1 H), 4.61 (br s, 1 H),
[M + H]⁺

3.94 (br s, 1 H), 3.06-3.23 (m, 1 H), 2.87 (br d, 1 H), 1.30-

1.53 (m, 4 H)

143
(CD₃OD) δ 8.43-8.58 (m, 1 H), 7.82-7.98 (m, 1 H), 7.73 (s, 1
482.1
98.5%

H), 7.52-7.67 (m, 2 H), 6.83 (s, 0.7 H), 6.14 (br s, 0.3 H),
[M + H]⁺

3.86-4.13 (m, 1.7 H), 3.60 (br d, 0.3 H), 2.79-3.07 (m, 2 H)

144
(CD₃OD) δ 8.40-8.56 (m, 1 H), 7.83-7.96 (m, 1 H), 7.72 (s, 1
484.2
96.7%

H), 7.50-7.65 (m, 2 H), 6.83 (s, 0.8 H), 6.14 (br s, 0.2 H),
[M + H]⁺

3.85-4.13 (m, 1.7 H), 3.61 (br s, 0.3 H), 2.77-3.06 (m, 2 H)

145
(CD₃OD) δ 8.47 (br s, 1 H), 7.91 (d, 1 H), 7.71 (s, 1 H), 7.53-
466.1
97.8%

7.67 (m, 2 H), 7.27 (s, 0.4 H), 7.14 (s, 0.6 H), 7.01 (s, 0.2 H),
[M + H]⁺

6.76 (br s, 0.8 H), 4.55 (br s, 1 H), 3.95 (br s, 1 H), 3.12 (br s,

1 H), 2.87 (br d, 1 H)

146
(CD₃OD) δ 8.47 (br s, 1 H), 7.91 (d, 1 H), 7.71 (s, 1 H), 7.52-
466.1
95.3%

7.65 (m, 2 H), 6.97-7.32 (m, 1 H), 6.76 (br s, 1 H), 4.56 (br d,
[M + H]⁺

1 H), 3.95 (br s, 1 H), 3.13 (br d, 1 H), 2.86 (br d, 1 H)

147
(CD₃OD) δ 8.40-8.54 (m, 1 H), 7.86 (s, 1 H), 7.49-7.74 (m, 3
482.2
96.4%

H), 6.82 (br s, 0.8 H), 6.13 (br s, 0.2 H), 4.95 (br s, 0.3 H),
[M + H]⁺

3.87-4.08 (m, 1.5 H), 3.58 (br s, 0.2 H), 2.74-3.05 (m, 2 H)

148
(CD₃OD) δ 8.39-8.55 (m, 1 H), 7.86 (s, 1 H), 7.49-7.75 (m, 3
482.2
95.4%

H), 6.82 (br s, 0.8 H), 6.13 (br s, 0.2 H), 4.96 (br d, 0.3 H),
[M + H]⁺

3.88-4.06 (m, 1.5 H), 3.58 (br s, 0.2 H), 2.75-3.05 (m, 2 H)

149
(CD₃OD) δ 8.45 (br s, 1 H), 7.85 (s, 1 H), 7.50-7.74 (m, 3 H),
464.1
91.3%

6.93-7.32 (m, 1 H), 6.74 (br s, 1 H), 4.46-4.58 (m, 1 H), 3.50-
[M + H]⁺

4.06 (m, 1 H), 2.75-3.19 (m, 2 H)

150
(CD₃OD) δ 8.45 (br s, 1 H), 7.85 (s, 1 H), 7.48-7.74 (m, 3 H),
466.1
76.2%

6.90-7.32 (m, 1 H), 6.75 (br s, 1 H), 4.54 (br d, 1 H), 3.50-
[M + H]⁺

4.02 (m, 1 H), 2.71-3.19 (m, 2 H)

151
(CD₃OD) δ 7.54-7.79 (m, 2 H), 7.39 (br dd, 1 H), 7.18 (td, 1
448.2
97.1%

H), 6.57-7.11 (m, 2 H), 4.96 (br s, 1 H), 4.55 (br d, 1 H), 3.49-
[M + H]⁺

4.05 (m, 1 H), 2.72-3.22 (m, 2 H), 1.39-1.71 (m, 3 H)

152
(CD₃OD) δ 7.52-7.74 (m, 2 H), 7.39 (dd, 1 H), 7.15-7.26 (m,
448.3
100%

1 H), 6.57-7.11 (m, 2 H), 4.97 (br s, 1 H), 4.57 (br d, 1 H),
[M + H]⁺

3.45-4.11 (m, 1 H), 2.76-3.18 (m, 2 H), 1.35-1.77 (m, 3 H)

153
(CD₃OD) δ 8.40 (s, 1 H), 7.59-7.81 (m, 2 H), 7.44 (dd, 1 H),
418.2
92.5%

7.22 (td, 1 H), 6.84 (br s, 0.8 H), 6.06 (br s, 0.2 H), 4.98 (br s,
[M + H]⁺

0.4 H), 3.87-4.04 (m, 1.5 H), 3.62 (br s, 0.1 H), 2.97 (br d, 1

H), 2.74-2.92 (m, 1 H), 1.99 (t, 3 H)

154
(CD₃OD) δ 8.32-8.47 (m, 1 H), 7.59-7.76 (m, 2 H), 7.44 (dd,
418.2
96.6%

1 H), 7.22 (td, 1 H), 6.84 (br s, 0.8 H), 6.05 (br s, 0.2 H), 4.97-
[M + H]⁺

5.04 (m, 0.4 H), 3.88-4.03 (m, 1.5 H), 3.62 (br s, 0.1 H), 2.92-

3.05 (m, 1 H), 2.74-2.91 (m, 1 H), 1.99 (t, 3 H)

155
(CD₃OD) δ 7.62-7.73 (m, 2 H), 7.43 (dd, 1 H), 6.97-7.28 (m,
451.2
98.5%

2 H), 6.76 (br s, 1 H), 4.51-4.77 (m, 3 H), 3.59-4.06 (m, 1 H),
[M + H]⁺

2.97-3.19 (m, 1 H), 2.79-2.92 (m, 1 H)

156
(CD₃OD) δ 7.51-7.62 (m, 2 H), 7.31 (dd, 1 H), 6.86-7.17 (m, 2
451.3
98.6%

H), 6.65 (br s, 1 H), 4.38-4.60 (m, 3 H), 3.44-3.92 (m, 1 H),
[M + H]⁺

3.00 (br s, 1 H), 2.75 (br d, 1 H)

157
(CD₃OD) δ 7.58-7.71 (m, 2 H), 7.39 (dd, 1 H), 6.89-7.27 (m,
448.2
98.4%

2 H), 6.71 (br s, 1 H), 4.93-4.99 (m, 1 H), 4.51-4.57 (m, 1 H),
[M + H]⁺

3.92 (br s, 1 H), 2.71-3.19 (m, 2 H), 1.39-1.70 (m, 3 H)

158
(CD₃OD) δ 7.55-7.72 (m, 2 H), 7.39 (dd, 1 H), 6.90-7.25 (m,
448.2
100%

2 H), 6.71 (br s, 1 H), 4.96 (br s, 1 H), 4.46-4.58 (m, 1 H),
[M + H]⁺

3.91 (br s, 1 H), 2.77-3.18 (m, 2 H), 1.38-1.74 (m, 3 H)

159
(CD₃OD) δ 7.66 (dt, 2 H), 7.42 (br d, 1 H), 7.15-7.27 (m, 1
471.3
95.7%

H), 6.95-7.15 (m, 1 H), 6.54-6.78 (m, 1 H), 4.54 (br d, 1 H),
[M + H]⁺

3.56-4.08 (m, 1 H), 2.76-3.24 (m, 2 H), 1.71-1.95 (m, 6 H)

160
(CD₃OD) δ 7.66 (dt, 2 H), 7.42 (br d, 1 H), 6.95-7.28 (m, 2
471.2
96.0%

H), 6.54-6.79 (m, 1 H), 4.54 (br d, 1 H), 3.56-4.07 (m, 1 H),
[M + H]⁺

2.76-3.25 (m, 2 H), 1.71-1.94 (m, 6 H)

161
(CD₃OD) δ 8.31-8.44 (m, 1 H), 7.54-7.67 (m, 2 H), 7.29-7.46
422.0
100%

(m, 1 H), 7.08 (ddd, 1 H), 6.72 (s, 0.8 H), 6.01 (br s, 0.2 H),
[M + H]⁺

3.74-4.02 (m, 1.8 H), 3.42-3.59 (m, 0.2 H), 2.83-2.93 (m, 1

H), 2.64-2.78 (m, 1 H)

162
(CD₃OD) δ 8.32-8.42 (m, 1 H), 7.54-7.68 (m, 2 H), 7.28-7.41
422.0
99.2%

(m, 1 H), 7.03-7.17 (m, 1 H), 6.72 (s, 0.8 H), 6.01 (br s, 0.2
[M + H]⁺

H), 3.74-4.00 (m, 1.8 H), 3.48 (br t, 0.2 H), 2.84-2.96 (m, 1

H), 2.66-2.81 (m, 1 H)

163
(CD₃OD) δ 8.32 (s, 0.8 H), 7.52-7.63 (m, 2 H), 7.36 (br d, 1
404.0
98.5%

H), 6.98-7.18 (m, 2 H), 6.87 (s, 0.2 H), 6.65 (br s, 1 H), 4.43-
[M + H]⁺

4.52 (m, 1 H), 3.82 (br s, 0.8 H), 3.50 (br s, 0.2 H), 2.86-3.07

(m, 1 H), 2.74 (br d, 1 H)

164
(CD₃OD) δ 8.33 (s, 0.8 H), 7.53-7.62 (m, 2 H), 7.36 (dd, 1 H),
404.0
96.4%

6.98-7.21 (m, 2 H), 6.88 (s, 1 H), 6.65 (br s, 0.2 H), 4.43 (br s,
[M + H]⁺

1 H), 3.82 (br s, 1 H), 3.00 (br d, 1 H), 2.67-2.80 (m, 1 H)

165
(DMSO-d₆) δ 12.14 (br s, 1 H), 9.44 (s, 1 H), 8.53 (br s, 1 H),
517.1
98.0%

8.00-8.14 (m, 1 H), 7.77 (br dd, 1 H), 7.51-7.65 (m, 2 H), 7.25
[M + H]⁺

(br t, 1 H), 6.45 (br s, 1 H), 4.52 (br s, 1 H), 3.90 (br s, 1 H),

2.92-3.17 (m, 1 H), 2.75 (br d, 1 H)

166
(DMSO-d₆) δ 12.14 (br s, 1 H), 9.45 (s, 1 H), 8.51-8.57 (m, 1
517.1
99.5%

H), 8.08 (s, 1 H), 7.72-7.81 (m, 1 H), 7.50-7.65 (m, 2 H), 7.25
[M + H]⁺

(td, 1 H), 6.45 (s, 1 H), 4.37-4.65 (m, 1 H), 3.91 (br s, 1 H),

2.98-3.16 (m, 1 H), 2.75 (br d, 1 H)

167
(CD₃OD) δ 8.29-8.53 (m, 1 H), 7.60 (s, 1 H), 7.25-7.45 (m, 2
422.2
98.7%

H), 6.93-7.13 (m, 1 H), 6.73 (s, 0.8 H), 6.04 (br s, 0.2 H),
[M + H]⁺

3.73-4.01 (m, 2 H), 2.59-2.99 (m, 2 H)

168
(CD₃OD) δ 8.25-8.47 (m, 1 H), 7.50-7.68 (m, 1 H), 7.22-7.45
422.2
99.1%

(m, 2 H), 6.96-7.10 (m, 1 H), 6.73 (s, 0.8 H), 6.04 (br s, 0.2H),
[M + H]⁺

3.77-4.06 (m, 2 H), 2.54-3.00 (m, 2 H)

169
(CD₃OD) δ 8.46 (br s, 1 H), 7.71 (s, 1 H), 7.49-7.54 (m, 1 H),
404.0
97.7%

7.43 (td, 1 H), 7.28 (s, 0.2 H), 7.10-7.21 (m, 1.6 H), 7.01 (s,
[M + H]⁺

0.2 H), 6.78 (br s, 1 H), 4.47-4.58 (m, 1 H), 3.97 (br d, 1 H),

2.79-3.24 (m, 2 H)

170
(CD₃OD) δ 8.46 (br s, 1 H), 7.76 (s, 1 H), 7.49-7.54 (m, 1 H),
404.0
96.7%

7.43 (td, 1 H), 7.28 (s, 0.2 H), 7.12-7.19 (m, 1.6 H), 7.01 (s,
[M + H]⁺

0.2 H), 6.80 (br s, 1 H), 4.56 (br s, 1 H), 3.96 (br s, 1 H), 2.87-

3.20 (m, 2 H)

171
(CD₃OD) δ 8.43-8.53 (m, 1 H), 7.70 (s, 1 H), 7.52 (d, 1 H),
422.0
98.0%

7.37 (td, 1 H), 7.23 (ddd, 1 H), 6.85 (br s, 0.7 H), 6.17 (br s,
[M + H]⁺

0.2 H), 4.97 (br d, 0.1 H), 3.88-4.08 (m, 1.6 H), 3.55-3.68 (m,

0.3 H), 2.93-3.05 (m, 1 H), 2.77-2.92 (m, 1 H)

172
(CD₃OD) δ 8.43-8.53 (m, 1 H), 7.70 (s, 1 H), 7.51 (d, 1 H),
422.0
94.8%

7.37 (td, 1 H), 7.18-7.27 (m, 1 H), 6.85 (br s, 0.7 H), 6.18 (br
[M + H]⁺

s, 0.3 H), 4.95-5.02 (m, 0.3 H), 3.86-4.12 (m, 1.6 H), 3.55-

3.66 (m, 0.2 H), 2.77-3.04 (m, 2 H)

173
(CD₃OD) δ 8.45 (br s, 1 H), 7.69 (s, 1 H), 7.51 (d, 1 H), 7.37
404.0
94.3%

(td, 1 H), 7.20-7.26 (m, 1 H), 6.98-7.15 (m, 1 H), 6.61-6.88
[M + H]⁺

(m, 1 H), 4.56 (br d, 1 H), 3.97 (br s, 1 H), 3.10 (br s, 1 H),

2.86 (br d, 1 H)

174
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.53 (d, 1 H), 7.39
404.0
90.8%

(td, 1 H), 7.22-7.29 (m, 1 H), 6.99-7.17 (m, 1 H), 6.66-6.91
[M + H]⁺

(m, 1 H), 4.58 (br d, 1 H), 3.99 (br s, 1 H), 3.13 (br s, 1 H),

2.88 (br d, 1 H)

175
(CD₃OD) δ 8.34-8.41 (m, 2 H), 8.02 (s, 1 H), 7.60-7.68 (m, 2
522.30
95.6%

H), 7.41 (dd, 1 H), 7.17 (td, 1 H), 6.72 (br s, 1 H), 4.70 (br d, 1
[M + H]⁺

H), 3.79-3.89 (m, 5 H), 3.01-3.11 (m, 5 H), 2.82 (br d, 1 H)

176
(CD₃OD) δ 8.38 (s, 2 H), 8.01 (s, 1 H), 7.60-7.67 (m, 2 H),
522.20
96.0%

7.41 (dd, 1 H), 7.17 (td, 1 H), 6.72 (br s, 1 H), 4.70 (br d, 1 H),
[M + H]⁺

3.79-3.88 (m, 5 H), 2.97-3.10 (m, 5 H), 2.82 (br d, 1 H)

177
(CD₃OD) δ 8.24 (br s, 1 H), 8.15 (s, 1 H), 7.94 (s, 1 H), 7.56-
452.2
99.2%

7.71 (m, 2 H), 7.40 (dd, 1 H), 7.17 (td, 1 H), 6.72 (br s, 1 H),
[M + H]⁺

4.72 (br dd, 1 H), 3.85 (br s, 1 H), 3.01-3.17 (m, 1 H), 2.81 (br

dd, 1 H)

178
(CD₃OD) δ 8.09-8.32 (m, 2 H), 7.95 (s, 1 H), 7.57-7.70 (m, 2
452.3
99.3%

H), 7.41 (dd, 1 H), 7.17 (td, 1 H), 6.72 (br s, 1 H), 4.72 (br dd,
[M + H]⁺

1 H), 3.85 (br s, 1 H), 3.03-3.15 (m, 1 H), 2.73-2.92 (m, 1 H)

179
(CD₃OD) δ 8.39 (br s, 1 H), 7.60-7.72 (m, 2 H), 7.41 (dd, 1
386.0
98.9%

H), 7.20 (td, 1 H), 6.54-6.82 (m, 1 H), 5.36-5.64 (m, 2 H),
[M + H]⁺

4.54 (br s, 1 H), 3.94 (br s, 1 H), 3.09 (br s, 1 H), 2.84 (br d, 1

H)

180
(CD₃OD) δ 8.39 (br s, 1 H), 7.59-7.74 (m, 2 H), 7.41 (dd, 1
386.0
96.4%

H), 7.20 (td, 1 H), 6.73 (br s, 1 H), 5.38-5.65 (m, 2 H), 4.39-
[M + H]⁺

4.58 (m, 1 H), 3.94 (br s, 1 H), 3.11 (br d, 1 H), 2.84 (br d, 1

H)

181
(CD₃OD) δ 8.37-8.48 (m, 2 H), 8.06 (s, 1 H), 7.65-7.72 (m, 2
535.4
95.3%

H), 7.45 (dd, 1 H), 7.22 (td, 1 H), 6.76 (br s, 1 H), 4.75 (br d, 1
[M + H]⁺

H), 3.91 (br s, 1 H), 3.06-3.23 (m, 5 H), 2.63-2.89 (m, 5 H),

2.41 (s, 3 H)

182
(CD₃OD) δ 8.37-8.48 (m, 2 H), 8.06 (s, 1 H), 7.61-7.74 (m, 2
535.3
97.4%

H), 7.45 (dd, 1 H), 7.22 (td, 1 H), 6.76 (br s, 1 H), 4.76 (br d, 1
[M + H]⁺

H), 3.91 (br s, 1 H), 3.15 (br s, 5 H), 2.64-2.93 (m, 5 H), 2.40

(s, 3 H)

183
(CD₃OD) δ 7.97 (br s, 1 H), 7.54-7.76 (m, 2 H), 7.26-7.52 (m,
485.0
96.7%

1.3 H), 6.66-7.25 (m, 2.5 H), 6.26 (br s, 0.2 H), 5.13 (q, 2 H),
[M + H]⁺

4.25 (br s, 1 H), 3.92 (br s, 1 H), 2.95-3.08 (m, 1 H), 2.79 (dd,

1 H)

184
(CD₃OD) δ 7.97 (br s, 1 H), 7.55-7.77 (m, 2 H), 7.30-7.50 (m,
485.0
95.1%

1.2 H), 6.63-7.24 (m, 2.5 H), 6.24 (br s, 0.3 H), 5.05-5.23 (m,
[M + H]⁺

2 H), 4.26 (br s, 1 H), 3.92 (br s, 1 H), 2.92-3.08 (m, 1 H),

2.79 (br dd, 1 H)

185
(CD₃OD) δ 7.60-7.73 (m, 2 H), 7.41 (dd, 1 H), 7.19 (td, 1 H),
435.0
98.0%

6.67 (br s, 1 H), 4.51 (br s, 1 H), 3.93 (br s, 1 H), 2.73-3.22
[M + H]⁺

(m, 2 H), 2.25-2.58 (m, 3 H), 1.83 (br s, 6 H)

186
(CD₃OD) δ 7.67 (br s, 2 H), 7.41 (br s, 1 H), 7.19 (br s, 1 H),
435.0
99.2%

6.66 (br s, 1 H), 4.51 (br s, 1 H), 3.46-4.13 (m, 1 H), 2.68-3.23
[M + H]⁺

(m, 2 H), 2.38 (br s, 3 H), 1.83 (br s, 6 H)

187
(CD₃OD) δ 7.64-7.77 (m, 2 H), 7.50 (dd, 1 H), 6.94-7.33 (m,
462.2
98.9%

2 H), 6.77 (br s, 1 H), 4.56 (br s, 1 H), 3.54-4.06 (m, 1 H),
[M + H]⁺

2.73-3.26 (m, 2 H), 1.54-1.80 (m, 6 H)

188
(CD₃OD) δ 7.63-7.74 (m, 2 H), 7.50 (dd, 1 H), 6.92-7.32 (m,
462.2
97.7%

2 H), 6.77 (br s, 1 H), 4.50-4.61 (m, 1 H), 3.54-4.07 (m, 1 H),
[M + H]⁺

2.83-3.24 (m, 2 H), 1.52-1.75 (m, 6 H)

189
(CD₃OD) δ 7.61-7.90 (m, 3.8 H), 7.50 (br d, 1.2 H), 7.20 (td,
403.2
99.1%

1 H), 6.71-7.03 (m, 1.8 H), 6.32 (br s, 0.2 H), 4.29 (br d, 1 H),
[M + H]⁺

3.93 (br s, 0.8 H), 3.50 (br s, 0.2 H), 2.97-3.09 (m, 1 H), 2.82

(br d, 1 H)

190
(CD₃OD) δ 7.61-7.89 (m, 3.8 H), 7.50 (br d, 1.2 H), 7.20 (td,
403.2
97.3%

1 H), 6.74-7.02 (m, 1.7 H), 6.32 (br s, 0.3 H), 4.29 (br d, 1 H),
[M + H]⁺

3.92 (br s, 0.7 H), 3.50 (br s, 0.3 H), 2.98-3.10 (m, 1 H), 2.82

(br d, 1 H)

191
(CD₃OD) δ 8.37-8.43 (m, 1 H), 8.07-8.14 (m, 1 H), 7.73 (br s,
435.30
98.0%

1 H), 7.60 (s, 0.3 H), 7.49-7.55 (m, 1 H), 7.33-7.41 (m, 1 H),
[M + H]⁺

7.19-7.27 (m, 1 H), 6.92 (s, 0.7 H), 5.06-5.40 (m, 1 H), 4.00-

4.04 (m, 3 H), 3.95 (br d, 0.6 H), 3.67 (td, 0.3 H), 2.97-3.29

(m, 1 H), 2.81-2.96 (m, 1 H)

192
(CD₃OD) δ 8.37-8.43 (m, 1 H), 8.07-8.14 (m, 1 H), 7.73 (br s,
435.30
95.6%

1 H), 7.60 (s, 0.3 H), 7.49-7.55 (m, 1 H), 7.33-7.41 (m, 1 H),
[M + H]⁺

7.19-7.27 (m, 1 H), 6.92 (s, 0.7 H), 5.06-5.40 (m, 1 H), 4.00-

4.04 (m, 3 H), 3.95 (br d, 0.7 H), 3.67 (td, 0.3 H), 2.97-3.29

(m, 1 H), 2.81-2.96 (m, 1 H)

193
(CD₃OD) δ 7.71 (s, 1 H), 7.53 (d, 1 H), 7.38 (td, 1 H), 6.94-
462.30
97.4%

7.31 (m, 2 H), 6.79 (br s, 1 H), 4.48-4.62 (m, 1 H), 3.99 (br s,
[M + H]⁺

0.7 H), 3.67 (br s, 0.3 H), 2.74-3.22 (m, 2 H), 1.48-1.77 (m, 6

H)

194
(CD₃OD) δ 7.70 (s, 1 H), 7.53 (d, 1 H), 7.39 (td, 1 H), 6.92-
462.20
98.0%

7.32 (m, 2 H), 6.59-6.88 (m, 1 H), 4.61 (br s, 1 H), 3.99 (br s,
[M + H]⁺

0.7 H), 3.67 (br s, 0.3 H), 2.75-3.26 (m, 2 H), 1.48-1.80 (m, 6

H)

195
(CD₃OD) δ 7.59-7.89 (m, 3 H), 7.46-7.57 (m, 1 H), 7.37 (td, 1
403.2
97.7%

H), 7.18-7.27 (m, 1 H), 6.86 (br s, 2 H), 4.28 (br d, 1 H), 3.94
[M + H]⁺

(br s, 0.7 H), 3.50 (br d, 0.3 H), 2.97-3.10 (m, 1 H), 2.74-2.88

(m, 1 H)

196
(CD₃OD) δ 7.60-7.86 (m, 3 H), 7.45-7.57 (m, 1 H), 7.37 (td, 1
403.2
97.4%

H), 7.18-7.26 (m, 1 H), 6.26-6.95 (m, 2 H), 4.28 (br d, 1 H),
[M + H]⁺

3.94 (br s, 0.7 H), 3.42-3.61 (m, 0.3 H), 2.95-3.10 (m, 1 H),

2.82 (br dd, 1 H)

197
(CD₃OD) δ 8.27-8.48 (m, 1 H), 8.00-8.19 (m, 1 H), 7.66-7.78
435.2
100%

(m, 1 H), 7.34-7.63 (m, 2.3 H), 7.03-7.26 (m, 1 H), 6.87 (br s,
[M + H]⁺

0.7 H), 5.05-5.41 (m, 1 H), 3.59-4.06 (m, 4 H), 2.83-3.26 (m,

2 H)

198
(CD₃OD) δ 8.18-8.46 (m, 1 H), 7.87-8.10 (m, 1 H), 7.55-7.75
435.2
99.3%

(m, 1 H), 7.23-7.52 (m, 2.3 H), 6.95-7.15 (m, 1 H), 6.77 (s, 0.7
[M + H]⁺

H), 4.92-5.28 (m, 1 H), 3.49-4.01 (m, 4 H), 2.68-3.16 (m, 2 H)

199
(CD₃OD) δ 7.69 (s, 1 H), 7.35-7.55 (m, 2 H), 6.90-7.32 (m, 2
462.1
99.7%

H), 6.51-6.84 (m, 1 H), 4.57 (br d, 1 H), 3.51-4.07 (m, 1 H),
[M + H]⁺

2.80-3.25 (m, 2 H), 1.49-1.76 (m, 6 H)

200
(CD₃OD) δ 7.72 (s, 1 H), 7.36-7.54 (m, 2 H), 6.92-7.28 (m, 2
462.1
98.0%

H), 6.59-6.84 (m, 1 H), 4.46-4.67 (m, 1 H), 3.50-4.07 (m, 1
[M + H]⁺

H), 2.81-3.23 (m, 2 H), 1.48-1.75 (m, 6 H)

201
(CD₃OD) δ 7.60-7.90 (m, 2.7 H), 7.35-7.57 (m, 2.3 H), 7.14
403.2
97.3%

(t, 1 H), 6.19-6.99 (m, 2 H), 4.20-4.39 (m, 1 H), 3.42-4.05 (m,
[M + H]⁺

1 H), 2.95-3.11 (m, 1 H), 2.81 (br d, 1 H)

202
(CD₃OD) δ 7.58-7.88 (m, 2.7 H), 7.36-7.56 (m, 2.3 H), 7.14
403.2
98.2%

(t, 1 H), 6.21-6.99 (m, 2 H), 4.30 (br d, 1 H), 3.42-4.02 (m, 1
[M + H]⁺

H), 2.96-3.09 (m, 1 H), 2.71-2.90 (m, 1 H)

203
(CD₃OD) δ 8.73 (s, 1 H), 8.47 (br s, 1 H), 8.07 (s, 1 H), 7.61-
494.3
99.5%

7.86 (m, 2 H), 7.16-7.57 (m, 2 H), 6.77 (br s, 1 H), 4.73 (br d,
[M + H]⁺

1 H), 3.80-4.02 (m, 1 H), 3.65 (s, 2 H), 2.78-3.22 (m, 2 H),

2.37 (s, 6 H)

204
(CD₃OD) δ 8.72 (s, 1 H), 8.47 (br s, 1 H), 8.07 (s, 1 H), 7.61-
494.2
99.7%

7.86 (m, 2 H), 7.45 (dd, 1 H), 7.21 (td, 1 H), 6.76 (br s, 1 H),
[M + H]⁺

4.73 (br d, 1 H), 3.92 (br s, 1 H), 3.65 (s, 2 H), 2.79-3.23 (m, 2

H), 2.37 (s, 6 H)

205
(CD₃OD) δ 8.22 (br s, 1 H), 7.91 (s, 1 H), 7.80 (s, 1 H), 7.60-
466.3
98.3%

7.66 (m, 2 H), 7.39 (br d, 1 H), 7.11-7.20 (m, 1 H), 6.72 (s, 1
[M + H]⁺

H), 4.69-4.75 (m, 1 H), 3.85 (br s, 1 H), 3.04-3.14 (m, 1 H),

2.82 (s, 4 H)

206
(CD₃OD) δ 8.23 (br s, 1 H), 7.93 (s, 1 H), 7.82 (s, 1 H), 7.61-
466.2
98.2%

7.66 (m, 2 H), 7.40 (dd, 1 H), 7.17 (td, 1 H), 6.72 (s, 1 H),
[M + H]⁺

4.73 (br dd, 1 H), 3.86 (br s, 1 H), 3.04-3.14 (m, 1 H), 2.78-

2.87 (m, 4 H)

207
(CD₃OD) δ 8.24-8.38 (m, 2 H), 7.95 (s, 1 H), 7.56-7.67 (m, 2
480.3
99.8%

H), 7.38 (dd, 1 H), 7.14 (td, 1 H), 6.72 (br s, 1 H), 4.69 (br dd,
[M + H]⁺

1 H), 3.86 (br s, 1 H), 3.03-3.14 (m, 1 H), 2.76-2.84 (m, 7 H)

208
(CD₃OD) δ 8.32 (s, 2 H), 7.97 (s, 1 H), 7.60-7.66 (m, 2 H),
480.2
99.6%

7.40 (dd, 1 H), 7.16 (td, 1 H), 6.72 (br s, 1 H), 4.70 (br dd, 1
[M + H]⁺

H), 3.85 (br s, 1 H), 3.03-3.14 (m, 1 H), 2.80-2.82 (m, 7 H)

209
(CD₃OD) δ 7.68 (s, 1 H), 7.29-7.54 (m, 2 H), 7.14 (dd, 1 H),
412.2
99.0%

6.69 (br s, 1 H), 4.61 (s, 2 H), 3.59-4.09 (m, 1 H), 2.75-3.21
[M + H]⁺

(m, 2 H), 2.38 (s, 3 H), 1.28-1.73 (m, 3 H)

210
(CD₃OD) δ 7.70 (s, 1 H), 7.34-7.57 (m, 2 H), 7.16 (dd, 1 H),
412.2
96.9%

6.71 (br s, 1 H), 4.62 (s, 2 H), 3.54-4.12 (m, 1 H), 2.75-3.23
[M + H]⁺

(m, 2 H), 2.29-2.55 (m, 3 H), 1.30-1.74 (m, 3 H)

211
(CD₃OD) δ 7.60-7.71 (m, 2 H), 7.42 (dd, 1 H), 7.20 (td, 1 H),
444.0
98.4%

6.72 (br s, 1 H), 5.34-5.60 (m, 2 H), 4.55 (br s, 1 H), 3.94 (br
[M + H]⁺

s, 0.7 H), 3.64 (br s, 0.3 H), 3.13 (br s, 1 H), 2.85 (br d, 1 H),

1.42-1.75 (m, 6 H)

212
(CD₃OD) δ 7.61-7.71 (m, 2 H), 7.42 (br d, 1 H), 7.20 (td, 1
444.0
99.7%

H), 6.70 (br s, 1 H), 5.36-5.61 (m, 2 H), 4.55 (br s, 1 H), 3.67-
[M + H]⁺

4.05 (m, 1 H), 3.14 (br s, 1 H), 2.85 (br d, 1 H), 1.48-1.75 (m,

6 H)

213
(CD₃OD) δ 7.68 (s, 1 H), 7.51 (d, 1 H), 7.37 (td, 1 H), 7.18-
460.1
96.3%

7.26 (m, 1 H), 6.94-7.13 (m, 1 H), 6.76 (br s, 1 H), 4.89-4.97
[M + H]⁺

(m, 1 H), 4.70 (br d, 1 H), 3.96 (br s, 0.7 H), 3.64 (br s, 0.3 H),

3.13 (br s, 1 H), 2.74-2.94 (m, 1 H), 1.27-1.50 (m, 4 H)

214
(CD₃OD) δ 7.68 (s, 1 H), 7.51 (d, 1 H), 7.37 (td, 1 H), 7.20-
460.2
97.9%

7.26 (m, 1 H), 7.10 (br s, 1 H), 6.97 (br s, 1 H), 6.75 (br s, 1
[M + H]⁺

H), 4.89-4.91 (m, 1 H), 4.60 (s, 1 H), 3.55-4.04 (m, 1 H),

3.00-3.21 (m, 1 H), 2.87 (br d, 1 H), 1.26-1.49 (m, 4 H)

215
(CD₃OD) δ 7.58 (s, 1 H), 7.27-7.48 (m, 2 H), 6.79-7.23 (m, 2
460.2
96.0%

H), 6.62 (br s, 1 H), 4.52-4.63 (m, 1 H), 3.37-4.03 (m, 1 H),
[M + H]⁺

2.51-3.15 (m, 2 H), 0.97-1.56 (m, 4 H)

216
(CD₃OD) δ 7.58 (s, 1 H), 7.27-7.46 (m, 2 H), 6.82-7.24 (m, 2
460.2
85.3%

H), 6.62 (br s, 1 H), 4.50-4.65 (m, 1 H), 3.41-4.07 (m, 1 H),
[M + H]⁺

2.51-3.15 (m, 2 H), 1.04-1.55 (m, 4 H)

217
(CD₃OD) δ 7.68 (s, 1 H), 7.49 (d, 1 H), 7.34 (td, 1 H), 7.15-
412.1
99.0%

7.25 (m, 1 H), 6.71 (br s, 1 H), 4.78-4.87 (m, 1 H), 4.59 (br s,
[M + H]⁺

1 H), 3.92 (br dd, 1 H), 3.10 (br s, 1 H), 2.79-2.89 (m, 1 H),

2.37 (s, 3 H), 1.56 (br s, 3 H)

218
(CD₃OD) δ 7.68 (s, 1 H), 7.50 (d, 1 H), 7.35 (td, 1 H), 7.15-
412.1
97.9%

7.24 (m, 1 H), 6.72 (br s, 1 H), 4.95-5.01 (m, 1 H), 4.60 (br s,
[M + H]⁺

1 H), 3.73-4.02 (m, 1 H), 3.11 (br s, 1 H), 2.85 (br d, 1 H),

2.38 (s, 3 H), 1.56 (br s, 3 H)

219
(CD₃OD) δ 8.97 (d, 1 H), 8.49 (br s, 1 H), 8.16 (d, 1 H), 7.64-
455.2
83.2%

7.73 (m, 2 H), 7.45 (dd, 1 H), 7.21 (td, 1 H), 6.76 (br s, 1 H),
[M + H]⁺

4.73 (br d, 1 H), 3.91 (br s, 1 H), 3.08-3.19 (m, 1 H), 2.86 (br

dd, 1 H)

220
(CD₃OD) δ 8.97 (d, 1 H), 8.49 (br s, 1 H), 8.17 (d, 1 H), 7.65-
455.2
87.5%

7.72 (m, 2 H), 7.45 (dd, 1 H), 7.21 (td, 1 H), 6.76 (br s, 1 H),
[M + H]⁺

4.73 (br d, 1 H), 3.91 (br s, 1 H), 3.05-3.24 (m, 1 H), 2.86 (br

dd, 1 H)

221
(CD₃OD) δ 7.56 (dt, 2 H), 7.33 (br s, 1 H), 7.11 (td, 1 H),
475.30
97.4%

6.50-7.06 (m, 2 H), 4.45 (br s, 1 H), 3.46-3.95 (m, 1 H), 2.68-
[M + H]⁺

3.12 (m, 2 H), 1.96-2.25 (m, 3 H), 1.30-1.65 (m, 6 H)

222
(CD₃OD) δ 7.56 (dt, 2 H), 7.33 (br s, 1 H), 7.11 (td, 1 H),
475.30
97.4%

6.47-7.06 (m, 2 H), 4.46 (br s, 1 H), 3.46-3.97 (m, 1 H), 2.64-
[M + H]⁺

3.11 (m, 2 H), 1.98-2.24 (m, 3 H), 1.29-1.57 (m, 6 H)

223
(CD₃OD) δ 7.50-7.64 (m, 2 H), 7.31 (dd, 1 H), 7.10 (td, 1 H),
478.1
91.4%

6.28-6.82 (m, 1 H), 4.78-4.91 (m, 1 H), 4.26 (br s, 1 H), 3.86
[M + H]⁺

(br s, 1 H), 3.01-3.10 (m, 1 H), 2.75 (br d, 1 H), 1.32-1.59 (m,

3 H)

224
(CD₃OD) δ 7.49-7.64 (m, 2 H), 7.31 (dd, 1 H), 7.09 (td, 1 H),
476.1
94.4%

6.18-6.77 (m, 1 H), 4.81-4.91 (m, 1 H), 4.28 (br s, 1 H), 3.86
[M + H]⁺

(br s, 1 H), 3.03 (br s, 1 H), 2.75 (br d, 1 H), 1.47 (br s, 3 H)

225
(CD₃OD) δ 7.51-7.62 (m, 2 H), 7.31 (dd, 1 H), 7.09 (td, 1 H),
476.1
90.1%

6.24-6.67 (m, 1 H), 4.86-5.02 (m, 1 H), 4.29 (br s, 1 H), 3.87
[M + H]⁺

(br s, 1 H), 3.03 (br s, 1 H), 2.71-2.81 (m, 1 H), 1.48 (br s, 3

H)

226
(CD₃OD) δ 7.51-7.67 (m, 2 H), 7.31 (dd, 1 H), 7.09 (td, 1 H),
476.1
92.0%

6.28-6.71 (m, 1 H), 4.87-5.04 (m, 1 H), 4.27 (br s, 1 H), 3.86
[M + H]⁺

(br s, 1 H), 3.03 (br s, 1 H), 2.71-2.79 (m, 1 H), 1.32-1.58 (m,

3 H)

227
(CD₃OD) δ 7.73 (s, 1 H), 7.49-7.56 (m, 1 H), 7.43 (td, 1 H),
448.20
98.4%

6.98-7.31 (m, 2 H), 6.78 (br s, 1 H), 5.01 (br s, 1.4 H), 4.61 (br
[M + H]⁺

d, 0.6 H), 3.78-4.07 (m, 1 H), 2.81-3.25 (m, 2 H), 1.44-1.74

(m, 3 H)

228
(CD₃OD) δ 7.74 (s, 1 H), 7.48-7.55 (m, 1 H), 7.43 (td, 1 H),
448.20
99.5%

6.97-7.31 (m, 2 H), 6.78 (br s, 1 H), 5.00 (br s, 1.4 H), 4.61 (br
[M + H]⁺

d, 0.6 H), 3.86-4.07 (m, 1 H), 2.84-3.26 (m, 2 H), 1.43-1.76

(m, 3 H)

229
(CD₃OD) δ 7.71 (s, 1 H), 7.37-7.56 (m, 2 H), 6.97-7.29 (m, 2
448.1
95.6%

H), 6.77 (br s, 1 H), 5.00 (br s, 1 H), 4.60 (br d, 1 H), 3.63-
[M + H]⁺

4.07 (m, 1 H), 3.15 (br s, 1 H), 2.88 (br d, 1 H), 1.44-1.69 (m,

3 H)

230
(CD₃OD) δ 7.71 (s, 1 H), 7.39-7.54 (m, 2 H), 6.95-7.29 (m, 2
448.1
92.1%

H), 6.77 (br s, 1 H), 5.01 (br s, 1 H), 4.61 (br d, 1 H), 3.54-
[M + H]⁺

4.04 (m, 1 H), 3.00-3.24 (m, 1 H), 2.88 (br d, 1 H), 1.43-1.71

(m, 3 H)

231
(CD₃OD) δ 7.65-7.74 (m, 2 H), 7.48 (dd, 1 H), 6.94-7.32 (m, 2
448.1
98.5%

H), 6.77 (br s, 1 H), 5.01 (br s, 1 H), 4.60 (br s, 1 H), 3.47-
[M + H]⁺

4.01 (m, 1 H), 2.96-3.22 (m, 1 H), 2.87 (br d, 1 H), 1.38-1.73

(m, 3 H)

232
(CD₃OD) δ 7.65-7.74 (m, 2 H), 7.46-7.51 (m, 1 H), 6.95-7.29
448.1
95.6%

(m, 2 H), 6.77 (br s, 1 H), 5.00 (br s, 1 H), 4.60 (br s, 1 H),
[M + H]⁺

3.51-4.09 (m, 1 H), 2.95-3.27 (m, 1 H), 2.87 (br d, 1 H), 1.40-

1.72 (m, 3 H)

233
(CD₃OD) δ 7.61-7.73 (m, 2 H), 7.41 (dd, 1 H), 7.19 (td, 1 H),
432.1
91.3%

6.41-6.77 (m, 1 H), 4.68-4.74 (m, 1 H), 4.44 (br s, 1 H), 3.86-
[M + H]⁺

4.03 (m, 0.7 H), 3.62 (br s, 0.3 H), 3.13 (br s, 1 H), 2.86 (br d,

1 H), 1.57 (br s, 3 H)

234
(CD₃OD) δ 7.74 (s, 1 H), 7.65 (dd, 1 H), 7.41 (dd, 1 H), 7.20
432.1
92.4%

(td, 1 H), 6.45-6.80 (m, 1 H), 4.55-4.66 (m, 1 H), 4.44 (br s, 1
[M + H]⁺

H), 3.86-4.04 (m, 0.7 H), 3.61 (br d, 0.3 H), 2.97-3.23 (m, 1

H), 2.86 (br d, 1 H), 1.37-1.66 (m, 3 H)

235
(CD₃OD) δ 7.60-7.71 (m, 2 H), 7.41 (br d, 1 H), 7.19 (td, 1
432.2
92.2%

H), 6.70 (br s, 1 H), 4.59 (br s, 1 H), 4.27-4.52 (m, 1 H), 3.97
[M + H]⁺

(br s, 1 H), 3.13 (br s, 1 H), 2.85 (br d, 1 H), 1.57 (br s, 3 H)

236
(CD₃OD) δ 7.61-7.72 (m, 2 H), 7.41 (dd, 1 H), 7.19 (td, 1 H),
432.1
92.3%

6.45-6.77 (m, 1 H), 4.59 (br s, 1 H), 4.44 (br s, 1 H), 3.97 (br
[M + H]⁺

s, 0.7 H), 3.63 (br s, 0.3 H), 3.13 (br s, 1 H), 2.85 (br d, 1 H),

1.58 (br s, 3 H)

237
(CD₃OD) δ 7.60-7.78 (m, 2 H), 7.48 (dd, 1 H), 6.87-7.30 (m,
460.2
97.5%

2 H), 6.70 (br s, 1 H), 4.96-5.18 (m, 1 H), 3.51-4.03 (m, 1 H),
[M + H]⁺

2.73-3.22 (m, 2 H), 1.15-1.52 (m, 4 H)

238
(CD₃OD) δ 7.58-7.77 (m, 2 H), 7.48 (dd, 1 H), 6.90-7.29 (m,
460.2
93.9%

2 H), 6.71 (br s, 1 H), 4.94-5.01 (m, 1 H), 3.44-4.04 (m, 1 H),
[M + H]⁺

2.72-3.20 (m, 2 H), 1.12-1.49 (m, 4 H)

239
(CD₃OD) δ 7.56-7.81 (m, 2 H), 7.47 (dd, 1 H), 6.90-7.32 (m,
448.3
93.9%

2 H), 6.74 (br s, 1 H), 4.98 (br s, 1.6 H), 4.52-4.57 (m, 0.4 H),
[M + H]⁺

3.52-4.06 (m, 1 H), 2.77-3.23 (m, 2 H), 1.38-1.78 (m, 3 H)

240
(CD₃OD) δ 7.60-7.77 (m, 2 H), 7.47 (dd, 1 H), 6.87-7.32 (m,
448.2
91.7%

2 H), 6.74 (br s, 1 H), 4.98 (br s, 1.6 H), 4.43-4.56 (m, 0.4 H),
[M + H]⁺

3.51-4.04 (m, 1 H), 2.75-3.21 (m, 2 H), 1.40-1.74 (m, 3 H)

241
(CD₃OD) δ 7.58-7.76 (m, 2 H), 7.47 (dd, 1 H), 7.17 (td, 1 H),
412.2
99.1%

6.69 (br s, 1 H), 4.87-4.98 (m, 2 H), 3.86 (br s, 1 H), 3.09 (br
[M + H]⁺

s, 1 H), 2.75-2.93 (m, 1 H), 2.37 (s, 3 H), 1.55 (br s, 3 H)

242
(CD₃OD) δ 7.57-7.76 (m, 2 H), 7.47 (dd, 1 H), 7.17 (td, 1 H),
412.2
98.3%

6.69 (br s, 1 H), 4.88-5.10 (m, 2 H), 3.56-4.04 (m, 1 H), 3.09
[M + H]⁺

(br s, 1 H), 2.74-2.90 (m, 1 H), 2.28-2.47 (m, 3 H), 1.35-1.65

(m, 3 H)

243
(CD₃OD) δ 7.69 (s, 1 H), 7.51 (d, 1 H), 7.37 (td, 1 H), 6.95-
448.2
86.5%

7.27 (m, 2 H), 6.76 (br s, 1 H), 4.99 (br s, 1 H), 4.52-4.60 (m,
[M + H]⁺

1 H), 3.51-4.07 (m, 1 H), 2.82-3.20 (m, 2 H), 1.47-1.69 (m, 3

H)

244
(CD₃OD) δ 7.69 (s, 1 H), 7.52 (d, 1 H), 7.37 (td, 1 H), 7.19-
448.2
93.0%

7.27 (m, 1 H), 6.73-7.14 (m, 1 H), 4.98 (br s, 1 H), 4.57 (br s,
[M + H]⁺

1 H), 3.60-4.02 (m, 1 H), 2.81-3.23 (m, 2 H), 1.46-1.67 (m, 3

H)

245
(CD₃OD) δ 7.69 (s, 1 H), 7.52 (d, 1 H), 7.37 (td, 1 H), 7.23
448.2
89.2%

(dd, 1 H), 6.94-7.13 (m, 1 H), 6.76 (br s, 1 H), 4.96-4.98 (m, 1
[M + H]⁺

H), 4.60-4.65 (m, 1 H), 3.93 (br dd, 1 H), 3.13 (br s, 1 H), 2.87

(br d, 1 H), 1.44-1.69 (m, 3 H)

246
(CD₃OD) δ 7.69 (s, 1 H), 7.51 (d, 1 H), 7.37 (td, 1 H), 7.19-
448.2
94.6%

7.26 (m, 1 H), 6.94-7.15 (m, 1 H), 6.77 (br s, 1 H), 4.99 (br s,
[M + H]⁺

1 H), 4.53-4.60 (m, 1 H), 3.54-4.08 (m, 1 H), 2.81-3.24 (m, 2

H), 1.46-1.70 (m, 3 H)

247
(CD₃OD) δ 7.68 (s, 1 H), 7.51 (d, 1 H), 7.36 (td, 1 H), 7.22
412.2
99.7%

(dd, 1 H), 6.72 (br s, 1 H), 4.92-4.95 (m, 1 H), 4.60-4.62 (m, 1
[M + H]⁺

H), 3.91 (br s, 1 H), 3.11 (br s, 1 H), 2.85 (br d, 1 H), 2.37 (s,

3 H), 1.55 (br s, 3 H)

248
(CD₃OD) δ 7.67 (s, 1 H), 7.51 (d, 1 H), 7.36 (td, 1 H), 7.22
412.2
99.2%

(dd, 1 H), 6.71 (br s, 1 H), 4.94-5.01 (m, 1 H), 4.60-4.69 (m, 1
[M + H]⁺

H), 3.91 (br s, 1 H), 3.10 (br s, 1 H), 2.85 (br d, 1 H), 2.37 (s,

3 H), 1.56 (br s, 3 H)

249
(CD₃OD) δ 7.66-7.75 (m, 2 H), 7.46-7.54 (m, 1 H), 7.20 (td, 1
492.2
96.4%

H), 6.32-6.82 (m, 1 H), 4.39 (br s, 1 H), 3.48-4.09 (m, 1 H),
[M + H]⁺

2.98-3.27 (m, 1 H), 2.87 (br d, 1 H), 1.65 (br s, 6 H)

250
(CD₃OD) δ 7.66-7.74 (m, 2 H), 7.49 (dd, 1 H), 7.20 (td, 1 H),
490.2
97.2%

6.05-6.88 (m, 1 H), 4.38 (br s, 1 H), 3.53-4.08 (m, 1 H), 2.96-
[M + H]⁺

3.23 (m, 1 H), 2.87 (br d, 1 H), 1.49-1.74 (m, 6 H)

251
(CD₃OD) δ 7.70 (s, 1 H), 7.33-7.56 (m, 2 H), 6.99-7.24 (m, 1
490.20
96.7%

H), 6.33-6.80 (m, 1 H), 4.27-4.58 (m, 1 H), 3.54-4.15 (m, 1
[M + H]⁺

H), 2.69-3.28 (m, 2 H), 1.66 (br s, 6 H)

252
(CD₃OD) δ 7.70 (s, 1 H), 7.30-7.57 (m, 2 H), 7.06-7.26 (m, 1
490.20
96.9%

H), 6.20-6.84 (m, 1 H), 4.28-4.53 (m, 1 H), 3.55-4.14 (m, 1
[M + H]⁺

H), 2.59-3.29 (m, 2 H), 1.42-1.83 (m, 6 H)

253
(CD₃OD) δ 7.67-7.73 (m, 1 H), 7.52 (dd, 1 H), 7.38 (td, 1 H),
480.2
99.6%

7.20-7.27 (m, 1 H), 6.84 (s, 0.7 H), 6.22 (br s, 0.3 H), 3.89-
[M + H]⁺

4.12 (m, 2 H), 2.93-3.11 (m, 1 H), 2.80-2.91 (m, 1 H), 1.52-

1.71 (m, 6 H)

254
(CD₃OD) δ 7.67-7.74 (m, 1 H), 7.52 (dd, 1 H), 7.38 (td, 1 H),
480.2
98.3%

7.24 (dd, 1 H), 6.84 (s, 0.7 H), 6.22 (br s, 0.3 H), 4.02-4.12
[M + H]⁺

(m, 1 H), 3.89-4.00 (m, 0.7 H), 3.57-3.73 (m, 0.3 H), 2.92-

3.11 (m, 1 H), 2.79-2.91 (m, 1 H), 1.52-1.71 (m, 6 H)

255
(CD₃OD) δ 7.60-7.83 (m, 2 H), 7.40-7.55 (m, 1 H), 7.21 (td, 1
480.2
100%

H), 6.80 (br s, 0.7 H), 6.14 (br s, 0.3 H), 4.99 (br s, 0.4 H),
[M + H]⁺

4.02-4.15 (m, 0.6 H), 3.99 (br s, 0.7 H), 3.66 (br s, 0.3 H),

3.05 (br s, 1 H), 2.87 (br s, 1 H), 1.54-1.71 (m, 6 H)

256
(CD₃OD) δ 7.63-7.81 (m, 2 H), 7.42-7.56 (m, 1 H), 7.21 (td, 1
480.2
98.7%

H), 6.82 (br s, 0.7 H), 6.16 (br s, 0.3 H), 4.95 (br s, 0.4 H),
[M + H]⁺

4.01-4.12 (m, 0.6 H), 3.95 (br s, 0.7 H), 3.64 (br s, 0.3 H),

3.03 (br d, 1 H), 2.85 (br d, 1 H), 1.54-1.71 (m, 6 H)

257
(CD₃OD) δ 7.55-7.64 (m, 1 H), 7.27-7.47 (m, 2 H), 7.05 (t, 1
480.2
96.9%

H), 6.05-6.80 (m, 1 H), 4.88 (br s, 0.2 H), 3.82-4.01 (m, 1.5
[M + H]⁺

H), 3.48-3.65 (m, 0.3 H), 2.70-3.01 (m, 2 H), 1.40-1.61 (m, 6

H)

258
(CD₃OD) δ 7.55-7.64 (m, 1 H), 7.29-7.45 (m, 2 H), 7.01-7.13
480.2
97.5%

(m, 1 H), 6.00-6.80 (m, 1 H), 4.86 (br d, 0.2 H), 3.81-4.01 (m,
[M + H]⁺

1.5 H), 3.56 (br s, 0.3 H), 2.86-2.99 (m, 1 H), 2.70-2.81 (m, 1

H), 1.41-1.61 (m, 6 H)

259
(CD₃OD) δ 7.70 (s, 1 H), 7.49-7.55 (m, 1 H), 7.43 (td, 1 H),
426.2
99.3%

7.08-7.24 (m, 1 H), 6.71 (br s, 1 H), 4.61 (br s, 1 H), 3.95 (br
[M + H]⁺

s, 1 H), 3.15 (br s, 1 H), 2.87 (br d, 1 H), 2.40 (s, 3 H), 1.64

(br s, 6 H)

260
(CD₃OD) δ 7.69 (s, 1 H), 7.49-7.54 (m, 1 H), 7.43 (td, 1 H),
426.2
98.9%

7.12-7.20 (m, 1 H), 6.71 (br s, 1 H), 4.61 (s, 1 H), 3.94 (br s, 1
[M + H]⁺

H), 3.15 (br s, 1 H), 2.84-2.94 (m, 1 H), 2.40 (s, 3 H), 1.64 (br

s, 6 H)

261
(CD₃OD) δ 7.80-7.96 (m, 1 H), 7.50-7.76 (m, 2 H), 7.41 (dd,
421.0
100%

1 H), 7.19 (td, 1 H), 6.73-6.93 (m, 1.7 H), 6.07 (s, 0.3 H),
[M + H]⁺

3.78-4.08 (m, 1.6 H), 3.42-3.58 (m, 0.4 H), 2.41-3.08 (m, 2 H)

262
(CD₃OD) δ 7.79-7.99 (m, 1 H), 7.54-7.76 (m, 2 H), 7.41 (dd,
421.0
100%

1 H), 7.19 (td, 1 H), 6.75-6.93 (m, 1.8 H), 6.07 (s, 0.2 H),
[M + H]⁺

3.79-4.06 (m, 1.7 H), 3.41-3.58 (m, 0.3 H), 2.64-2.99 (m, 2 H)

263
(CD₃OD) δ 7.66 (s, 1 H), 7.50 (d, 1 H), 7.35 (td, 1 H), 7.16-
490.0
97.3%

7.26 (m, 1 H), 6.38-6.91 (m, 1 H), 4.37 (br s, 1 H), 3.98 (br s,
[M + H]⁺

0.7 H), 3.62 (br s, 0.3 H), 3.15 (br s, 1 H), 2.85 (br d, 1 H),

1.62 (br s, 6 H)

264
(CD₃OD) δ 7.67 (s, 1 H), 7.50 (d, 1 H), 7.35 (td, 1 H), 7.13-
490.0
91.8%

7.26 (m, 1 H), 6.34-6.83 (m, 1 H), 4.23-4.52 (m, 1 H), 3.51-
[M + H]⁺

4.13 (m, 1 H), 2.79-3.21 (m, 2 H), 1.62 (br s, 6 H)

265
(CD₃OD) δ 8.62 (s, 1 H), 8.42 (br s, 1 H), 7.93 (br d, 1 H),
447.20
94.5%

7.68 (s, 1 H), 7.53 (br d, 1 H), 7.32-7.48 (m, 2 H), 7.18-7.29
[M + H]⁺

(m, 1 H), 6.80 (br s, 1 H), 4.73 (br d, 1.3 H), 4.53 (s, 2 H),

3.94 (br s, 0.7 H), 3.43 (s, 3 H), 3.06-3.21 (m, 1 H), 2.86 (br d,

1 H)

266
(CD₃OD) δ 8.62 (s, 1 H), 8.42 (br s, 1 H), 7.94 (d, 1 H), 7.69
447.20
97.1%

(br s, 1 H), 7.52 (br d, 1 H), 7.32-7.46 (m, 2 H), 7.22 (dd, 1
[M + H]⁺

H), 6.79 (br s, 1 H), 4.72 (br d, 1 H), 4.53 (s, 2 H), 3.92 (br s,

1 H), 3.43 (s, 3 H), 3.05-3.21 (m, 1 H), 2.86 (br d, 1 H)

267
(CD₃OD) δ 7.69 (s, 1 H), 7.53 (d, 1 H), 7.38 (td, 1 H), 7.20-
426.2
100%

7.29 (m, 1 H), 6.73 (br s, 1 H), 4.48-4.64 (m, 1 H), 3.94 (dt, 1
[M + H]⁺

H), 2.79-3.24 (m, 2 H), 2.40 (s, 3 H), 1.64 (br s, 6 H)

268
(CD₃OD) δ 7.70 (s, 1 H), 7.53 (d, 1 H), 7.38 (td, 1 H), 7.20-
426.2
100%

7.29 (m, 1 H), 6.73 (br s, 1 H), 4.55-4.64 (m, 1 H), 3.44-4.07
[M + H]⁺

(m, 1 H), 2.79-3.26 (m, 2 H), 2.39 (s, 3 H), 1.40-1.80 (m, 6 H)

269
(CD₃OD) δ 7.62-7.81 (m, 2 H), 7.49 (dd, 1 H), 7.20 (td, 1 H),
446.2
100%

6.38-6.88 (m, 1 H), 4.43 (br s, 0.6 H), 3.97 (br s, 1 H), 3.66 (br
[M + H]⁺

s, 0.4 H), 3.15 (br s, 1 H), 2.87 (br d, 1 H), 1.65 (br s, 6 H)

270
(CD₃OD) δ 7.62-7.90 (m, 2 H), 7.49 (dd, 1 H), 7.20 (td, 1 H),
446.2
100%

6.41-6.88 (m, 1 H), 4.45 (br s, 0.5 H), 3.97 (br s, 1 H), 3.66 (br
[M + H]⁺

s, 0.5 H), 3.15 (br s, 1 H), 2.87 (br d, 1 H), 1.65 (br s, 6 H)

271
(CD₃OD) δ 7.70 (s, 1 H), 7.53 (br d, 1 H), 7.39 (td, 1 H),
446.2
99.3%

7.17-7.29 (m, 1 H), 6.74 (br s, 1 H), 4.26-4.52 (m, 0.4 H), 4.00
[M + H]⁺

(br s, 1 H), 3.66 (br s, 0.6 H), 3.16 (br s, 1 H), 2.79-2.97 (m, 1

H), 1.64 (br s, 6 H)

272
(CD₃OD) δ 7.70 (br s, 1 H), 7.53 (br d, 1 H), 7.39 (br s, 1 H),
446.2
99.1%

7.18-7.34 (m, 1 H), 6.76 (br s, 1 H), 4.47 (br s, 0.9 H), 4.01 (br
[M + H]⁺

s, 1 H), 3.46-3.82 (m, 0.1 H), 3.17 (br s, 1 H), 2.91 (br s, 1 H),

1.65 (br s, 6 H)

273
(CD₃OD) δ 7.70 (s, 1 H), 7.49-7.59 (m, 1 H), 7.43 (td, 1 H),
446.2
99.7%

7.16 (t, 1 H), 6.73 (br s, 1 H), 4.47 (br s, 0.5 H), 4.02 (br s, 1
[M + H]⁺

H), 3.68 (br s, 0.5 H), 3.15 (br s, 1 H), 2.89 (br d, 1 H), 1.45-

1.83 (m, 6 H)

274
(CD₃OD) δ 7.70 (s, 1 H), 7.49-7.60 (m, 1 H), 7.43 (td, 1 H),
446.2
99.7%

7.08-7.24 (m, 1 H), 6.73 (br s, 1 H), 4.47 (br s, 0.5 H), 4.02 (br
[M + H]⁺

s, 1 H), 3.68 (br s, 0.5 H), 3.15 (br s, 1 H), 2.89 (br d, 1 H),

1.65 (br s, 6 H)

275
(CD₃OD) δ 8.53 (s, 1 H), 8.32 (s, 1 H), 7.85 (d, 1 H), 7.62 (s,
447.30
99.2%

1 H), 7.38-7.44 (m, 1 H), 7.28-7.36 (m, 2 H), 7.01-7.09 (m, 1
[M + H]⁺

H), 6.70 (s, 1 H), 4.62 (br dd, 1 H), 4.43 (s, 2 H), 3.84 (br s, 1

H), 3.33 (s, 3 H), 2.69-3.10 (m, 2 H)

276
(CD₃OD) δ 8.52 (s, 1 H), 8.32 (s, 1 H), 7.85 (d, 1 H), 7.57 (s,
447.20
99.3%

1 H), 7.38-7.43 (m, 1 H), 7.27-7.35 (m, 2 H), 6.99-7.09 (m, 1
[M + H]⁺

H), 6.68 (br s, 1 H), 4.62 (br dd, 1 H), 4.43 (s, 2 H), 3.85 (br s,

1 H), 3.33 (s, 3 H), 2.69-3.10 (m, 2 H)

277
(CD₃OD) δ 7.71 (s, 1 H), 7.36-7.58 (m, 2 H), 7.08-7.23 (m,
402.10
100%

1.3 H), 6.84 (s, 0.7 H), 5.08 (dd, 0.3 H), 4.77 (dd, 0.7 H),
[M + H]⁺

4.02-4.11 (m, 3 H), 3.80-3.96 (m, 0.7 H), 3.45-3.59 (m, 0.3

H), 2.79-3.26 (m, 2 H)

278
(CD₃OD) δ 7.59 (s, 1 H), 7.24-7.44 (m, 2 H), 6.96-7.10 (m,
402.20
98.4%

1.3 H), 6.71 (br s, 0.7 H), 4.96 (dd, 0.3 H), 4.65 (br dd, 0.7 H),
[M + H]⁺

3.91-3.99 (m, 3 H), 3.76 (br d, 0.7 H), 3.40 (br d, 0.3 H), 2.64-

3.15 (m, 2 H)

279
(CD₃OD) δ 7.67-7.76 (m, 1 H), 7.48-7.58 (m, 1 H), 7.33-7.44
436.20
99.6%

(m, 1 H), 7.25 (t, 1 H), 6.81-7.12 (m, 1 H), 5.12 (dd, 0.3 H),
[M + H]⁺

4.77 (dd, 0.7 H), 4.14-4.20 (m, 3 H), 3.55-3.99 (m, 1 H), 2.96-

3.28 (m, 1 H), 2.79-2.94 (m, 1 H)

280
(CD₃OD) δ 7.65-7.77 (m, 1 H), 7.46-7.59 (m, 1 H), 7.32-7.43
436.2
99.0%

(m, 1 H), 7.18-7.30 (m, 1 H), 6.91 (s, 1 H), 5.11 (dd, 0.3 H),
[M + H]⁺

4.77 (dd, 0.7 H), 4.06-4.21 (m, 3 H), 3.56-3.97 (m, 1 H), 2.96-

3.27 (m, 1 H), 2.80-2.94 (m, 1 H)

281
(CD₃OD) δ 8.39 (s, 1 H), 7.83 (br s, 1 H), 7.66 (s, 1 H), 7.49
354.2
98.6%

(br d, 1 H), 7.34 (td, 1 H), 7.11-7.25 (m, 1 H), 6.76-6.89 (m,
[M + H]⁺

1 H), 4.69 (br s, 1 H), 3.96 (br s, 1 H), 3.08 (br s, 1 H), 2.85

(br d, 1 H)

282
(CD₃OD) δ 8.39 (s, 1 H), 7.83 (br s, 1 H), 7.66 (s, 1 H), 7.49
354.2
99.1%

(br d, 1 H), 7.34 (td, 1 H), 7.16-7.25 (m, 1 H), 6.76 (br s, 1 H),
[M + H]⁺

4.68 (br s, 1 H), 3.94 (br s, 1 H), 3.07 (br s, 1 H), 2.85 (br d, 1

H)

283
(CD₃OD) δ 7.71 (s, 1 H), 7.49-7.60 (m, 1 H), 7.33-7.46 (m, 1
402.1
100%

H), 6.79-7.29 (m, 2 H), 5.08 (dd, 0.3 H), 4.78 (dd, 0.7 H),
[M + H]⁺

4.03-4.09 (m, 3 H), 3.83-3.97 (m, 0.7 H), 3.46-3.60 (m, 0.3

H), 2.93-3.27 (m, 1 H), 2.78-2.90 (m, 1 H)

284
(CD₃OD) δ 7.71 (s, 1 H), 7.49-7.56 (m, 1 H), 7.32-7.44 (m, 1
402.1
99.6%

H), 6.74-7.31 (m, 2 H), 5.08 (dd, 0.3 H), 4.78 (dd, 0.7 H),
[M + H]⁺

4.02-4.08 (m, 3 H), 3.89 (br t, 0.7 H), 3.45-3.63 (m, 0.3 H),

2.94-3.26 (m, 1 H), 2.77-2.92 (m, 1 H)

285
(CD₃OD) δ 7.60 (s, 1 H), 7.35-7.45 (m, 1 H), 7.21-7.31 (m, 1
418.3
97.8%

H), 7.09-7.16 (m, 1 H), 6.77-7.08 (m, 1 H), 6.47-6.76 (m, 1
[M + H]⁺

H), 4.99 (dd, 0.3 H), 4.66 (dd, 0.7 H), 3.97-4.05 (m, 3 H),

3.36-3.83 (m, 1 H), 2.83-3.16 (m, 1 H), 2.62-2.80 (m, 1 H)

286
(CD₃OD) δ 7.57-7.62 (m, 1 H), 7.36-7.43 (m, 1 H), 7.20-7.30
418.4
93.6%

(m, 1 H), 7.08-7.16 (m, 1 H), 6.77-7.08 (m, 1 H), 6.47-6.77
[M + H]⁺

(m, 1 H), 4.99 (dd, 0.3 H), 4.66 (dd, 0.7 H), 3.96-4.05 (m, 3

H), 3.34-3.83 (m, 1 H), 2.82-3.17 (m, 1 H), 2.65-2.80 (m, 1 H)

287
(CD₃OD) δ 7.90 (s, 1 H), 7.64-7.75 (m, 2 H), 7.40-7.53 (m, 1
421.0
99.1%

H), 7.19 (td, 1 H), 6.79-6.94 (m, 1.8 H), 6.07 (s, 0.2 H), 4.93-
[M + H]⁺

4.99 (m, 0.4 H), 3.84-4.00 (m, 1.4 H), 3.45-3.58 (m, 0.2 H),

2.71-3.02 (m, 2 H)

288
(CD₃OD) δ 7.90 (s, 1 H), 7.64-7.76 (m, 2 H), 7.38-7.57 (m, 1
421.0
98.5%

H), 7.10-7.31 (m, 1 H), 6.73-6.98 (m, 1.8 H), 6.07 (br s, 0.2
[M + H]⁺

H), 4.96 (br d, 0.4 H), 3.87-4.02 (m, 1.4 H), 3.45-3.57 (m, 0.2

H), 2.70-3.04 (m, 2 H)

289
(CD₃OD) δ 7.90 (s, 1 H), 7.63-7.78 (m, 1 H), 7.53 (br d, 1 H),
421.0
99.3%

7.38 (td, 1 H), 7.11-7.31 (m, 1 H), 6.77-6.98 (m, 1.8 H), 6.04-
[M + H]

6.25 (m, 0.2 H), 4.97 (br d, 0.5 H), 3.97-4.03 (m, 0.5 H), 3.86-

3.96 (m, 0.7 H), 3.43-3.62 (m, 0.3 H), 2.72-3.07 (m, 2 H)

290
(CD₃OD) δ 7.90 (s, 1 H), 7.64-7.79 (m, 1 H), 7.53 (br d, 1 H),
421.0
97.7%

7.38 (td, 1 H), 7.18-7.31 (m, 1 H), 6.75-6.99 (m, 1.8 H), 6.13
[M + H]

(s, 0.2 H), 4.97 (br s, 0.3 H), 3.97-4.04 (m, 0.7 H), 3.85-3.96

(m, 0.7 H), 3.47-3.58 (m, 0.3 H), 2.73-3.02 (m, 2 H)

291
(CD₃OD) δ 7.63-7.76 (m, 2 H), 7.44 (dd, 1 H), 6.59-7.31 (m,
489.10
100%

3 H), 4.98 (br s, 0.4 H), 4.57 (br s, 0.6 H), 3.52-4.09 (m, 1 H),
[M + H]⁺

2.76-3.24 (m, 2 H), 2.03-2.42 (m, 6 H), 1.39-1.76 (m, 6 H)

292
(CD₃OD) δ 7.51-7.64 (m, 2 H), 7.31 (br d, 1 H), 6.41-7.22 (m,
489.20
98.0%

3 H), 4.83-4.90 (m, 0.4 H), 4.46 (br s, 0.6 H), 3.40-3.96 (m, 1
[M + H]⁺

H), 2.66-3.14 (m, 2 H), 1.92-2.31 (m, 6 H), 1.27-1.67 (m, 6 H)

293
(CD₃OD) δ 7.90 (s, 1 H), 7.61-7.78 (m, 1 H), 7.36-7.59 (m, 2
421.0
99.1%

H), 7.16 (t, 1 H), 6.73-6.98 (m, 1.8 H), 6.10 (br s, 0.2 H), 4.98
[M + H]⁺

(br d, 0.2 H), 3.87-4.06 (m, 1.5 H), 3.45-3.63 (m, 0.3 H), 2.72-

3.03 (m, 2 H)

294
(CD₃OD) δ 7.90 (s, 1 H), 7.63-7.78 (m, 1 H), 7.35-7.59 (m, 2
421.1
99.2%

H), 7.15 (t, 1 H), 6.87 (br d, 1.8 H), 6.10 (br s, 0.2 H), 4.99 (br
[M + H]⁺

dd, 0.2 H), 3.87-4.07 (m, 1.5 H), 3.45-3.63 (m, 0.3 H), 2.73-

3.04 (m, 2 H)

295
(CD₃OD) δ 8.47 (br s, 1 H), 7.55-7.87 (m, 3 H), 6.91-7.32 (m,
422.0
93.5%

1 H), 6.76 (br s, 1 H), 4.54 (br s, 1 H), 3.68-4.02 (m, 1 H),
[M + H]⁺

2.78-3.12 (m, 2 H)

296
(CD₃OD) δ 8.47 (br s, 1 H), 7.58-7.74 (m, 3 H), 6.95-7.33 (m,
422.0
94.0%

1 H), 6.76 (br s, 1 H), 4.57 (br s, 1 H), 3.66-4.07 (m, 1 H),
[M + H]⁺

3.13 (br d, 1 H), 2.86 (br d, 1 H)

297
(CD₃OD) δ 7.69 (s, 1 H), 7.49 (br dd, 1 H), 7.29-7.42 (m, 1
480.1
88.4%

H), 6.93-7.27 (m, 1 H), 6.76 (br s, 1 H), 4.50-4.59 (m, 1 H),
[M + H]

3.54-4.06 (m, 1 H), 2.76-3.26 (m, 2 H), 1.49-1.76 (m, 6 H)

298
(CD₃OD) δ 7.69 (s, 1 H), 7.49 (br dd, 1 H), 7.34 (ddd, 1 H),
480.1
94.8%

6.91-7.28 (m, 1 H), 6.76 (br s, 1 H), 4.46-4.58 (m, 1 H), 3.53-
[M + H]

4.06 (m, 1 H), 2.76-3.24 (m, 2 H), 1.51-1.78 (m, 6 H)

299
(CD₃OD) δ 7.69 (s, 1 H), 7.38 (br d, 1 H), 7.24 (br s, 0.2 H),
480.1
97.7%

7.03-7.14 (m, 1.6 H), 6.97 (br s, 0.2 H), 6.73 (br s, 1 H), 4.55
[M + H]⁺

(br s, 1 H), 3.95 (br s, 0.7 H), 3.64 (br s, 0.3 H), 2.94-3.24 (m,

1 H), 2.87 (br d, 1 H), 1.51-1.74 (m, 6 H)

300
(CD₃OD) δ 7.69 (s, 1 H), 7.38 (br d, 1 H), 7.24 (br s, 0.2 H),
480.1
98.5%

7.03-7.13 (m, 1.6 H), 6.97 (br s, 0.2 H), 6.73 (br s, 1 H), 4.48-
[M + H]⁺

4.58 (m, 1 H), 3.95 (br s, 0.7 H), 3.64 (br s, 0.3 H), 2.93-3.23

(m, 1 H), 2.87 (br d, 1 H), 1.50-1.76 (m, 6 H)

301
(CD₃OD) δ 8.46 (br s, 1 H), 7.69 (s, 1 H), 7.38 (br d, 1 H),
422.0
100%

7.26 (s, 0.2 H), 6.96-7.15 (m, 1.8 H), 6.75 (br s, 1 H), 4.56 (br
[M + H]⁺

d, 1 H), 3.93 (br d, 1 H), 3.11 (br s, 1 H), 2.86 (br d, 1 H)

302
(CD₃OD) δ 8.46 (br s, 1 H), 7.69 (s, 1 H), 7.38 (br d, 1 H),
422.0
99.1%

7.26 (s, 0.2 H), 6.97-7.15 (m, 1.9 H), 6.74 (br s, 1 H), 4.55 (br
[M + H]⁺

d, 1 H), 3.94 (br s, 1 H), 3.11 (br s, 1 H), 2.85 (br d, 1 H)

303
(CD₃OD) δ 8.76-8.81 (m, 1 H), 8.28-8.35 (m, 1 H), 8.06-8.13
432.1
100%

(m, 1 H), 7.65-7.75 (m, 3 H), 7.43-7.58 (m, 1 H), 7.12-7.29
[M + H]⁺

(m, 1 H), 6.93 (s, 1 H), 5.10-5.34 (m, 1 H), 3.89-4.07 (m, 0.7

H), 3.61-3.74 (m, 0.3 H), 3.00-3.29 (m, 1 H), 2.83-2.97 (m, 1

H)

304
(CD₃OD) δ 8.76-8.81 (m, 1 H), 8.28-8.35 (m, 1 H), 8.06-8.13
432.1
97.7%

(m, 1 H), 7.65-7.75 (m, 3 H), 7.47-7.59 (m, 1 H), 7.16-7.24
[M + H]⁺

(m, 1 H), 6.92 (br s, 1 H), 5.10-5.40 (m, 1 H), 3.99 (br t, 0.7

H), 3.66 (br s, 0.3 H), 3.00-3.30 (m, 1 H), 2.81-2.97 (m, 1 H)

305
(CD₃OD) δ 8.45 (s, 1 H), 7.69 (s, 1 H), 7.49 (ddd, 1 H), 7.33
422.1
99.5%

(ddd, 1 H), 6.91-7.28 (m, 1 H), 6.77 (br s, 1 H), 4.56 (br d, 1
[M + H]⁺

H), 3.56-4.02 (m, 1 H), 2.82-3.16 (m, 2 H)

306
(CD₃OD) δ 8.45 (s, 1 H), 7.69 (s, 1 H), 7.49 (ddd, 1 H), 7.33
422.0
99.2%

(ddd, 1 H), 6.94-7.27 (m, 1 H), 6.77 (br s, 1 H), 4.44-4.56 (m,
[M + H]⁺

1 H), 3.52-4.03 (m, 1 H), 2.80-3.18 (m, 2 H)

307
(CD₃OD) δ 7.70 (s, 1 H), 7.33 (br d, 1 H), 6.95-7.29 (m, 2 H),
480.1
94.0%

6.76 (br s, 1 H), 4.96-5.00 (m, 0.5 H), 4.50-4.61 (m, 0.5 H),
[M + H]⁺

3.53-4.12 (m, 1 H), 3.15 (br s, 1 H), 2.91 (br s, 1 H), 1.47-1.83

(m, 6 H)

308
(CD₃OD) δ 7.70 (s, 1 H), 7.33 (br d, 1 H), 6.96-7.30 (m, 2 H),
480.1
97.6%

6.75 (br s, 1 H), 4.96-5.03 (m, 0.6 H), 4.52-4.61 (m, 0.4 H),
[M + H]⁺

3.54-4.14 (m, 0.8 H), 2.95-3.24 (m, 1.2 H), 2.92 (br s, 1 H),

1.53-1.79 (m, 6 H)

309
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.33 (br d, 1 H),
422.1
98.0%

6.97-7.29 (m, 2 H), 6.78 (br s, 1 H), 4.95-5.04 (m, 0.5 H),
[M + H]⁺

4.50-4.60 (m, 0.5 H), 3.51-4.11 (m, 1 H), 3.12 (br s, 1 H), 2.88

(br d, 1 H)

310
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.33 (br d, 1 H),
422.1
98.8%

6.95-7.29 (m, 2 H), 6.78 (br s, 1 H), 4.96-5.07 (m, 0.4 H),
[M + H]⁺

4.48-4.60 (m, 0.6 H), 3.53-4.11 (m, 1 H), 3.12 (br s, 1 H), 2.88

(br d, 1 H)

311
(CD₃OD) δ 7.69 (br s, 1 H), 7.42-7.57 (m, 2 H), 7.25 (d, 1 H),
458.1
98.0%

6.94-7.17 (m, 1 H), 6.75 (br s, 1 H), 4.47-4.66 (m, 1 H), 3.92
[M + H]⁺

(br s, 1 H), 2.74-3.15 (m, 2 H), 2.46 (s, 3 H), 1.49-1.72 (m, 6

H)

312
(CD₃OD) δ 7.69 (s, 1 H), 7.44-7.56 (m, 2 H), 7.25 (d, 1.2 H),
458.1
89.9%

7.11 (br s, 0.4 H), 6.98 (br s, 0.2 H), 6.55-6.84 (m, 0.8 H),
[M + H]⁺

4.40-4.67 (m, 1 H), 3.93 (br s, 1 H), 2.65-3.15 (m, 2 H), 2.46

(s, 3 H), 1.41-1.77 (m, 6 H)

313
(CD₃OD) δ 7.77-7.85 (m, 1 H), 7.61-7.73 (m, 2 H), 7.46-7.54
399.1
96.8%

(m, 1 H), 7.25 (d, 1 H), 6.73-6.95 (m, 2 H), 5.98-6.46 (m, 1
[M + H]⁺

H), 4.28 (br d, 1 H), 3.90 (br s, 1 H), 2.93-3.12 (m, 1 H), 2.80

(br d, 1 H), 2.46 (s, 3 H)

314
(CD₃OD) δ 7.78-7.88 (m, 1 H), 7.61-7.72 (m, 2 H), 7.46-7.57
399.1
92.5%

(m, 2 H), 7.26 (d, 1 H), 6.87 (br s, 2 H), 4.27 (br s, 1 H), 3.91
[M + H]⁺

(br s, 1 H), 3.02 (br d, 1 H), 2.81 (br d, 1 H), 2.47 (s, 3 H)

315
(CD₃OD) δ 7.68 (s, 1 H), 7.54 (d, 1 H), 7.46 (s, 1 H), 6.95-
458.1
99.6%

7.27 (m, 2 H), 6.54-6.86 (m, 1 H), 4.55 (br d, 1 H), 3.54-3.97
[M + H]

(m, 1 H), 2.78-3.22 (m, 2 H), 2.48 (s, 3 H), 1.51-1.73 (m, 6 H)

316
(CD₃OD) δ 7.68 (s, 1 H), 7.53 (d, 1 H), 7.45 (s, 1 H), 6.94-
458.1
98.8%

7.30 (m, 2 H), 6.57-6.82 (m, 1 H), 4.54 (br d, 1 H), 3.52-4.00
[M + H]

(m, 1 H), 2.79-3.22 (m, 2 H), 2.48 (s, 3 H), 1.51-1.72 (m, 6 H)

317
(CD₃OD) δ 7.75-7.88 (m, 1.2 H), 7.61-7.74 (m, 1.5 H), 7.40-
399.1
99.7%

7.61 (m, 2.3 H), 7.23 (d, 1 H), 6.84 (br d, 1.7 H), 6.28 (br s,
[M + H]

0.3 H), 4.27 (br d, 1 H), 3.90 (br s, 1 H), 2.96-3.09 (m, 1 H),

2.74-2.88 (m, 1 H), 2.49 (s, 3 H)

318
(CD₃OD) δ 7.75-7.88 (m, 1.2 H), 7.61-7.74 (m, 1.5 H), 7.39-
399.1
99.2%

7.59 (m, 2.3 H), 7.22 (d, 1 H), 6.84 (br d, 1.7 H), 6.28 (br s,
[M + H]

0.3 H), 4.27 (br d, 1 H), 3.42-3.97 (m, 1 H), 2.95-3.08 (m, 1

H), 2.74-2.85 (m, 1 H), 2.49 (s, 3 H)

319
(CD₃OD) δ 7.67 (s, 1 H), 7.53 (d, 1 H), 7.45 (s, 1 H), 7.21 (d,
422.1
98.9%

1 H), 6.70 (br s, 1 H), 4.44-4.59 (m, 1 H), 3.52-3.99 (m, 1 H),
[M + H]

2.75-3.19 (m, 2 H), 2.48 (s, 3 H), 2.37 (s, 3 H), 1.62 (br s, 6

H)

320
(CD₃OD) δ 7.67 (s, 1 H), 7.54 (d, 1 H), 7.45 (s, 1 H), 7.21 (d,
422.1
91.4%

1 H), 6.70 (br s, 1 H), 4.34-4.57 (m, 1 H), 3.52-3.99 (m, 1 H),
[M + H]

3.13 (br s, 1 H), 2.83 (br d, 1 H), 2.48 (s, 3 H), 2.37 (s, 3 H),

1.61 (br s, 6 H)

321
(CD₃OD) δ 7.66-7.75 (m, 1 H), 7.53-7.64 (m, 2 H), 7.46 (br s,
435.1
99.6%

0.3 H), 7.30-7.41 (m, 1 H), 7.03-7.12 (m, 1 H), 6.84-6.95 (m,
[M + H]⁺

1 H), 6.79 (br s, 0.7 H), 4.95-5.22 (m, 1 H), 3.79-3.98 (m, 3.7

H), 3.44-3.58 (m, 0.3 H), 2.85-3.17 (m, 1 H), 2.65-2.83 (m, 1

H)

322
(CD₃OD) δ 7.65-7.76 (m, 1 H), 7.53-7.63 (m, 2 H), 7.46 (br s,
435.1
98.2%

0.3 H), 7.33-7.40 (m, 1 H), 7.01-7.13 (m, 1 H), 6.84-6.91 (m,
[M + H]⁺

1 H), 6.78 (br s, 0.7 H), 4.95-5.21 (m, 1 H), 3.78-3.95 (m, 3.7

H), 3.44-3.58 (m, 0.3 H), 2.85-3.16 (m, 1 H), 2.70-2.84 (m, 1

H)

323
(CD₃OD) δ 8.34-8.51 (m, 2 H), 7.87 (d, 1 H), 7.67 (s, 1 H),
417.1
99.8%

7.53 (d, 1 H), 7.32-7.41 (m, 2 H), 7.18-7.28 (m, 1 H), 6.79 (br
[M + H]⁺

s, 1 H), 4.72 (br s, 1 H), 3.93 (br s, 1 H), 3.03-3.21 (m, 1 H),

2.86 (br d, 1 H), 2.40 (s, 3 H)

324
(CD₃OD) δ 8.33-8.51 (m, 2 H), 7.87 (d, 1 H), 7.67 (s, 1 H),
417.1
96.5%

7.54 (d, 1 H), 7.31-7.44 (m, 2 H), 7.16-7.28 (m, 1 H), 6.79 (br
[M + H]⁺

s, 1 H), 4.72 (br s, 1 H), 3.94 (br s, 1 H), 3.05-3.20 (m, 1 H),

2.86 (br d, 1 H), 2.40 (s, 3 H)

325
(CD₃OD) δ 8.27-8.38 (m, 2 H), 7.86 (d, 1 H), 7.67 (s, 1 H),
433.1
99.5%

7.53 (d, 1 H), 7.37 (td, 1 H), 7.17-7.27 (m, 2 H), 6.79 (s, 1 H),
[M + H]⁺

4.74 (br dd, 1 H), 3.89 (s, 4 H), 3.05-3.18 (m, 1 H), 2.85 (br

dd, 1 H)

326
(CD₃OD) δ 8.27-8.39 (m, 2 H), 7.86 (d, 1 H), 7.67 (s, 1 H),
433.1
99.3%

7.53 (d, 1 H), 7.37 (td, 1 H), 7.17-7.26 (m, 2 H), 6.79 (s, 1 H),
[M + H]⁺

4.74 (br dd, 1 H), 3.89 (s, 4 H), 3.05-3.18 (m, 1 H), 2.85 (dd, 1

H)

327
(CD₃OD) δ 8.02 (br s, 1 H), 7.86 (br d, 1 H), 7.64-7.80 (m, 2
512.1
97.4%

H), 6.92-7.32 (m, 1 H), 6.77 (br s, 1 H), 4.48 (s, 1 H), 3.97 (br
[M + H]⁺

s, 1 H), 3.17 (br s, 1 H), 2.86 (br s, 1 H), 1.39-1.75 (m, 6 H)

328
(CD₃OD) δ 8.02 (br s, 1 H), 7.86 (d, 1 H), 7.65-7.78 (m, 2 H),
512.1
97.1%

6.91-7.30 (m, 1 H), 6.77 (br s, 1 H), 4.92-5.03 (m, 0.6 H), 4.57
[M + H]⁺

(br s, 0.4 H), 3.53-4.08 (m, 1 H), 2.95-3.25 (m, 1 H), 2.88 (br

d, 1 H), 1.40-1.80 (m, 6 H)

329
(CD₃OD) δ 8.46 (br s, 1 H), 8.02 (s, 1 H), 7.85 (d, 1 H), 7.63-
454.0
96.5%

7.78 (m, 2 H), 6.94-7.29 (m, 1 H), 6.79 (br s, 1 H), 4.57 (br d,
[M + H]⁺

1 H), 3.96 (br s, 0.8 H), 3.60 (br s, 0.2 H), 3.11 (br s, 1 H),

2.86 (br d, 1 H)

330
(CD₃OD) δ 8.46 (br s, 1 H), 8.02 (s, 1 H), 7.86 (d, 1 H), 7.65-
454.0
97.1%

7.78 (m, 2 H), 6.95-7.29 (m, 1 H), 6.80 (br s, 1 H), 4.59 (br s,
[M + H]⁺

1 H), 3.96 (br s, 0.8 H), 3.62 (br d, 0.2 H), 3.11 (br s, 1 H),

2.86 (br d, 1 H)

331
(CD₃OD) δ 7.67 (s, 1 H), 7.44-7.56 (m, 2 H), 7.24 (d, 1 H),
422.1
96.9%

6.70 (br s, 1 H), 4.41-4.73 (m, 1 H), 3.42-4.02 (m, 1 H), 2.77-
[M + H]⁺

3.21 (m, 2 H), 2.45 (s, 3 H), 2.37 (s, 3 H), 1.62 (br s, 6 H)

332
(CD₃OD) δ 7.69 (s, 1 H), 7.46-7.58 (m, 2 H), 7.26 (d, 1 H),
422.1
92.2%

6.72 (br s, 1 H), 4.48-4.69 (m, 1 H), 3.92 (br s, 1 H), 2.77-3.21
[M + H]⁺

(m, 2 H), 2.47 (s, 3 H), 2.39 (s, 3 H), 1.37-1.77 (m, 6 H)

333
(CD₃OD) δ 8.73-8.84 (m, 1 H), 8.26-8.38 (m, 1 H), 8.00-8.17
432.0
95.1%

(m, 1 H), 7.63-7.79 (m, 2 H), 7.38-7.59 (m, 2.3 H), 7.08-7.22
[M + H]⁺

(m, 1 H), 6.93 (br s, 0.7 H), 5.12-5.42 (m, 1 H), 3.62-4.13 (m,

1 H), 2.79-3.27 (m, 2 H)

334
(CD₃OD) δ 8.59-8.77 (m, 1 H), 8.12-8.29 (m, 1 H), 7.90-8.04
432.1
94.1%

(m, 1 H), 7.52-7.67 (m, 2 H), 7.24-7.47 (m, 2.3 H), 6.95-7.14
[M + H]⁺

(m, 1 H), 6.81 (br s, 0.7 H), 5.01-5.28 (m, 1 H), 3.51-4.02 (m,

1 H), 2.74-3.17 (m, 2 H)

335
(CD₃OD) δ 8.71-8.80 (m, 1 H), 8.25-8.35 (m, 1 H), 8.03-8.12
432.1
97.5%

(m, 1 H), 7.62-7.75 (m, 2 H), 7.47-7.58 (m, 1 H), 7.32-7.41
[M + H]⁺

(m, 1 H), 7.17-7.27 (m, 1 H), 6.93 (br s, 1 H), 5.28 (dd, 0.7

H), 5.14 (dd, 0.3 H), 4.01 (br s, 0.7H), 3.62-3.79 (m, 0.3 H),

2.85-3.27 (m, 2 H)

336
(CD₃OD) δ 8.72-8.80 (m, 1 H), 8.26-8.34 (m, 1 H), 8.03-8.12
432.1
88.4%

(m, 1 H), 7.62-7.74 (m, 2 H), 7.46-7.58 (m, 1 H), 7.33-7.41
[M + H]⁺

(m, 1 H), 7.18-7.27 (m, 1 H), 6.93 (br s, 1 H), 5.28 (dd, 0.7

H), 5.14 (dd, 0.3 H), 4.01 (br s, 0.7 H), 3.70 (br s, 0.3 H),

2.87-3.26 (m, 2 H)

337
(CD₃OD) δ 7.78-7.83 (m, 1 H), 7.67-7.73 (m, 1 H), 7.49-7.54
435.1
95.2%

(m, 1 H), 7.32-7.41 (m, 1 H), 7.18-7.27 (m, 1 H), 6.85-7.03
[M + H]⁺

(m, 2 H), 5.30 (dd, 0.7 H), 5.12 (br dd, 0.3 H), 4.00-4.03 (m, 3

H), 3.93-3.99 (m, 0.4 H), 3.67 (br s, 0.3 H), 2.83-3.27 (m, 2.3

H)

338
(CD₃OD) δ 7.63-7.84 (m, 2 H), 7.52 (br d, 1 H), 7.33-7.41 (m,
435.1
98.9%

1 H), 7.18-7.27 (m, 1 H), 6.87-7.02 (m, 2 H), 5.30 (br dd, 0.7
[M + H]⁺

H), 5.12 (br d, 0.3 H), 4.00-4.03 (m, 3 H), 3.97 (s, 0.3 H),

3.57-3.86 (m, 0.7 H), 2.88-3.24 (m, 2 H)

339
(CD₃OD) δ 7.71 (s, 1 H), 7.54 (d, 1 H), 7.10-7.32 (m, 2 H),
474.1
100%

6.93-7.06 (m, 1 H), 6.46-6.84 (m, 1 H), 4.57 (br d, 0.7 H),
[M + H]⁺

3.85 (s, 4 H), 3.53-3.70 (m, 0.3 H), 2.96-3.24 (m, 1 H), 2.88

(br d, 1 H), 1.47-1.75 (m, 6 H)

340
(CD₃OD) δ 7.70 (s, 1 H), 7.54 (d, 1 H), 7.09-7.33 (m, 2 H),
474.1
98.1%

6.92-7.05 (m, 1 H), 6.49-6.85 (m, 1 H), 4.57 (br d, 0.7 H),
[M + H]⁺

3.78-4.06 (m, 4 H), 3.51-3.72 (m, 0.3 H), 2.96-3.24 (m, 1 H),

2.88 (br d, 1 H), 1.49-1.74 (m, 6 H)

341
(CD₃OD) δ 8.46 (br s, 1 H), 7.71 (s, 1 H), 7.54 (d, 1 H), 7.10-
416.0
98.5%

7.37 (m, 2 H), 7.02 (dd, 1 H), 6.77 (br s, 1 H), 4.55 (br d, 0.7
[M + H]⁺

H), 3.79-4.08 (m, 4 H), 3.54-3.69 (m, 0.3 H), 3.11 (br s, 1 H),

2.86 (br d, 1 H)

342
(CD₃OD) δ 8.34 (br s, 1 H), 7.58 (s, 1 H), 7.41 (d, 1 H), 6.98-
416.0
96.6%

7.18 (m, 2 H), 6.90 (dd, 1 H), 6.42-6.76 (m, 1 H), 4.43 (br d,
[M + H]⁺

0.7 H), 3.68-3.88 (m, 4 H), 3.34-3.60 (m, 0.3 H), 3.00 (br d, 1

H), 2.65-2.80 (m, 1 H)

343
(CD₃OD) δ 7.49-7.66 (m, 2 H), 7.31-7.41 (m, 1 H), 6.94-7.17
402.1
100%

(m, 1.3 H), 6.70 (br s, 0.7 H), 4.95 (br dd, 0.3 H), 4.64 (dd, 0.7
[M + H]⁺

H), 3.87-3.99 (m, 3 H), 3.74 (br s, 0.7 H), 3.38 (br d, 0.3 H),

2.56-3.14 (m, 2 H)

344
(CD₃OD) δ 7.70 (br s, 1 H), 7.23-7.27 (m, 1 H), 7.00-7.18 (m,
480.3
96.1%

2 H), 6.75 (br s, 1 H), 5.02 (br s, 0.4 H), 4.60 (br s, 0.6 H),
[M + H]⁺

3.62-4.19 (m, 1 H), 2.75-3.25 (m, 2 H), 1.48-1.88 (m, 6 H)

345
(CD₃OD) δ 7.70 (br s, 1 H), 7.23-7.27 (m, 1 H), 7.00-7.18 (m,
480.3
96.1%

2 H), 6.75 (br s, 1 H), 5.02 (br s, 0.4 H), 4.60 (br s, 0.6 H),
[M + H]⁺

3.62-4.19 (m, 1 H), 2.75-3.25 (m, 2 H), 1.48-1.88 (m, 6 H)

346
(CD₃OD) δ 7.58 (br s, 1 H), 7.11-7.15 (m, 1 H), 6.87-7.04 (m,
480.2
96.3%

2 H), 6.75 (br s, 1 H), 4.81-4.95 (m, 0.4 H), 4.39-4.50 (m, 0.6
[M + H]⁺

H), 3.48-4.04 (m, 1 H), 2.72-3.15 (m, 2 H), 1.41-1.69 (m, 6 H)

347
(CD₃OD) δ 7.71 (s, 1 H), 7.50 (dd, 1 H), 7.32-7.46 (m, 1 H),
480.2
99.2%

6.93-7.32 (m, 1 H), 6.73 (br s, 1 H), 4.95-5.01 (m, 0.5 H), 4.58
[M + H]⁺

(br s, 0.5 H), 3.58-4.09 (m, 1 H), 3.17 (br s, 1 H), 2.89 (br d, 1

H), 1.51-1.79 (m, 6 H)

348
(CD₃OD) δ 7.71 (s, 1 H), 7.51 (br d, 1 H), 7.34-7.46 (m, 1 H),
480.2
98.5%

6.94-7.33 (m, 1 H), 6.74 (br s, 1 H), 4.96-5.01 (m, 0.5 H), 4.59
[M + H]⁺

(br s, 0.5 H), 3.56-4.13 (m, 1 H), 3.16 (br d, 1 H), 2.90 (br d, 1

H), 1.49-1.74 (m, 6 H)

349
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.50 (br d, 1 H),
422.1
96.5%

7.33-7.45 (m, 1 H), 6.94-7.32 (m, 1 H), 6.76 (br s, 1 H), 4.58
[M + H]⁺

(br d, 1 H), 3.54-4.14 (m, 1 H), 3.12 (br s, 1 H), 2.88 (br d, 1

H)

350
(CD₃OD) δ 8.47 (br s, 1 H), 7.72 (s, 1 H), 7.50 (br d, 1 H),
422.2
97.4%

7.32-7.44 (m, 1 H), 6.98-7.32 (m, 1 H), 6.76 (br s, 1 H), 4.59
[M + H]⁺

(br d, 1 H), 3.53-4.11 (m, 1 H), 3.13 (br s, 1 H), 2.88 (br d, 1

H)

351
(CD₃OD) δ 7.75 (d, 1 H), 7.61-7.71 (m, 2 H), 7.37 (dd, 1 H),
528.2
98.3%

6.95-7.27 (m, 1 H), 6.76 (br s, 1 H), 4.59 (br s, 1 H), 3.53-4.07
[M + H]⁺

(m, 1 H), 2.78-3.22 (m, 2 H), 1.51-1.72 (m, 6 H)

352
(CD₃OD) δ 7.75 (d, 1 H), 7.59-7.72 (m, 2 H), 7.37 (br d, 1 H),
528.1
97.6%

6.92-7.27 (m, 1 H), 6.73 (br s, 1 H), 4.48-4.59 (m, 1 H), 3.59-
[M + H]⁺

4.04 (m, 1 H), 2.74-3.24 (m, 2 H), 1.49-1.75 (m, 6 H)

353
(CD₃OD) δ 8.45 (br s, 1 H), 7.75 (d, 1 H), 7.59-7.71 (m, 2 H),
470.1
97.7%

7.37 (br d, 1 H), 6.96-7.28 (m, 1 H), 6.75 (br s, 1 H), 4.42-
[M + H]⁺

4.58 (m, 1 H), 3.96 (br s, 1 H), 2.83-3.17 (m, 2 H)

354
(CD₃OD) δ 8.45 (br s, 1 H), 7.75 (d, 1 H), 7.60-7.71 (m, 2 H),
470.2
95.7%

7.37 (dd, 1 H), 6.96-7.29 (m, 1 H), 6.74 (br s, 1 H), 4.46-4.59
[M + H]⁺

(m, 1 H), 3.56-4.05 (m, 1 H), 2.79-3.18 (m, 2 H)

355
(CD₃OD) δ 7.88-7.93 (m, 1 H), 7.72 (s, 1 H), 7.46-7.56 (m, 2
417.2
90.7%

H), 7.21-7.30 (m, 1 H), 7.01-7.09 (m, 1 H), 6.91 (br s, 1 H),
[M + H]⁺

5.06-5.34 (m, 1 H), 3.90-4.05 (m, 0.7 H), 3.62 (br s, 0.3 H),

2.85-3.27 (m, 2 H), 2.42-2.53 (m, 3 H)

356
(CD₃OD) δ 7.88-7.94 (m, 1 H), 7.73 (s, 1 H), 7.47-7.55 (m, 2
417.2
98.7%

H), 7.22-7.29 (m, 1 H), 7.01-7.09 (m, 1 H), 6.91 (br s, 1 H),
[M + H]⁺

5.08-5.31 (m, 1 H), 3.96 (br t, 0.7 H), 3.63 (br d, 0.3 H), 2.86-

3.28 (m, 2 H), 2.42-2.54 (m, 3 H)

357
(CD₃OD) δ 7.77-7.85 (m, 1 H), 7.70 (s, 1 H), 7.40-7.61 (m,
431.3
94.7%

2.4 H), 7.13-7.28 (m, 1 H), 6.82-7.05 (m, 1.6 H), 5.04-5.32
[M + H]⁺

(m, 1 H), 4.00-4.07 (m, 3 H), 3.52-3.99 (m, 1 H), 2.81-3.26

(m, 2 H), 2.44-2.52 (m, 3 H)

358
(CD₃OD) δ 7.77-7.87 (m, 1 H), 7.70 (s, 1 H), 7.40-7.63 (m,
431.3
97.8%

2.3 H), 7.14-7.28 (m, 1 H), 6.80-7.08 (m, 1.7 H), 5.05-5.31
[M + H]⁺

(m, 1 H), 3.99-4.05 (m, 3 H), 3.53-3.98 (m, 1 H), 2.82-3.25

(m, 2 H), 2.40-2.53 (m, 3 H)

359
(CD₃OD) δ 7.91 (br s, 1 H), 7.72 (s, 1 H), 7.44-7.59 (m, 2 H),
417.4
100%

7.18-7.29 (m, 1 H), 7.00-7.10 (m, 1 H), 6.91 (br s, 1 H), 5.07-
[M + H]⁺

5.31 (m, 1 H), 3.54-4.00 (m, 1 H), 2.82-3.25 (m, 2 H), 2.46-

2.54 (m, 3 H)

360
(CD₃OD) δ 7.91 (br d, 1 H), 7.74 (s, 1 H), 7.45-7.61 (m, 2 H),
417.4
100%

7.18-7.29 (m, 1 H), 7.02-7.10 (m, 1 H), 6.92 (s, 1 H), 5.05-
[M + H]⁺

5.35 (m, 1 H), 3.55-4.02 (m, 1 H), 2.85-3.27 (m, 2 H), 2.46-

2.53 (m, 3 H)

361
(CD₃OD) δ 7.70 (br s, 1 H), 7.45 (br d, 1 H), 6.96-7.38 (m, 3
458.3
100%

H), 6.53-6.91 (m, 1 H), 4.59 (br d, 1 H), 3.59-4.17 (m, 1 H),
[M + H]⁺

2.95-3.23 (m, 1 H), 2.91 (br s, 1 H), 2.58 (s, 3 H), 1.55-1.75

(m, 6 H)

362
(CD₃OD) δ 7.70 (br s, 1 H), 7.45 (br d, 1 H), 6.96-7.38 (m, 3
458.2
100%

H), 6.79 (br s, 1 H), 4.57 (br s, 1 H), 3.57-4.17 (m, 1 H), 2.95-
[M + H]⁺

3.28 (m, 1 H), 2.91 (br s, 1 H), 2.57 (s, 3 H), 1.50-1.73 (m, 6

H)

363
(CD₃OD) δ 8.33 (br s, 1 H), 8.12 (d, 1 H), 7.85 (d, 1 H), 7.69
501.4
97.2%

(s, 1 H), 7.54 (d, 1 H), 7.45 (dd, 1 H), 7.38 (td, 1 H), 7.19-7.28
[M + H]⁺

(m, 1 H), 6.80 (br s, 1 H), 4.76 (br dd, 1 H), 3.92 (br d, 1 H),

3.07-3.25 (m, 5 H), 2.87 (br d, 1 H), 2.63-2.71 (m, 4 H), 2.38

(s, 3 H)

364
(CD₃OD) δ 8.33 (br s, 1 H), 8.13 (d, 1 H), 7.86 (d, 1 H), 7.69
501.4
98.5%

(s, 1 H), 7.55 (d, 1 H), 7.46 (dd, 1 H), 7.39 (td, 1 H), 7.24 (dd,
[M + H]⁺

1 H), 6.80 (br s, 1 H), 4.76 (br dd, 1 H), 3.74-4.04 (m, 1 H),

3.08-3.24 (m, 5 H), 2.80-2.93 (m, 1 H), 2.64-2.70 (m, 4 H),

2.39 (s, 3 H)

365
(CDCl₃) δ 8.31 (br s, 1 H), 8.09 (s, 1 H), 7.83 (br d, 1 H), 7.66
488.3
100%

(br s, 1 H), 7.31-7.55 (m, 3 H), 7.16-7.29 (m, 1 H), 6.77 (br s,
[M + H]⁺

1 H), 4.70-4.80 (m, 1 H), 3.85 (br d, 5 H), 3.13 (br d, 5 H),

2.84 (br d, 1 H)

366
(CD₃OD) δ 8.34 (br s, 1 H), 8.12 (s, 1 H), 7.87 (d, 1 H), 7.69
488.3
99.1%

(s, 1 H), 7.55 (d, 1 H), 7.35-7.49 (m, 2 H), 7.20-7.28 (m, 1 H),
[M + H]⁺

6.79 (br s, 1 H), 4.76 (br dd, 1 H), 3.79-4.02 (m, 5 H), 3.13-

3.22 (m, 5 H), 2.87 (br d, 1 H)

367
(CD₃OD) δ 8.32 (br s, 1 H), 8.10 (s, 1 H), 7.84 (d, 1 H), 7.69
544.3
100%

(s, 1 H), 7.55 (d, 1 H), 7.46 (dd, 1 H), 7.39 (td, 1 H), 7.20-7.31
[M + H]⁺

(m, 1 H), 6.79 (br s, 1 H), 4.76 (br dd, 1 H), 3.94 (br s, 1 H),

3.74 (br d, 2 H), 3.13 (br d, 1 H), 2.87 (br d, 1 H), 2.66 (br t, 2

H), 1.94 (br d, 2 H), 1.39-1.62 (m, 3 H), 1.21 (s, 6 H)

368
(CD₃OD) δ 8.32 (br s, 1 H), 8.10 (s, 1 H), 7.84 (d, 1 H), 7.69
544.3
99.4%

(s, 1 H), 7.55 (d, 1 H), 7.46 (dd, 1 H), 7.39 (td, 1 H), 7.18-7.31
[M + H]⁺

(m, 1 H), 6.80 (br s, 1 H), 4.76 (br dd, 1 H), 3.95 (br s, 1 H),

3.74 (br d, 2 H), 3.03-3.22 (m, 1 H), 2.87 (br d, 1 H), 2.65 (br

t, 2 H), 1.94 (br d, 2 H), 1.41-1.64 (m, 3 H), 1.21 (s, 6 H)

369
(CD₃OD) δ 8.33 (br s, 1 H), 8.14-8.16 (m, 1 H), 7.85 (d, 1 H),
504.3
98.1%

7.69 (s, 1 H), 7.55 (d, 1 H), 7.36-7.49 (m, 2 H), 7.24 (t, 1 H),
[M + H]⁺

6.79 (br s, 1 H), 4.68-4.82 (m, 1.5 H), 3.65-4.16 (m, 1 H),

3.34-3.38 (m, 1 H), 3.27-3.31 (m, 1 H), 3.06-3.23 (m, 3 H),

2.87 (br d, 1 H), 1.91-2.20 (m, 4.5 H)

370
(CD₃OD) δ 8.33 (br s, 1 H), 8.15 (s, 1 H), 7.85 (d, 1 H), 7.69
504.3
92.7%

(s, 1 H), 7.55 (d, 1 H), 7.36-7.49 (m, 2 H), 7.25 (t, 1 H), 6.78
[M + H]⁺

(br s, 1 H), 4.76 (br d, 1 H), 3.80-4.08 (m, 1 H), 3.35-3.39 (m,

1 H), 3.27-3.31 (m, 1 H), 3.08-3.23 (m, 4 H), 2.87 (br d, 1 H),

1.87-2.21 (m, 5 H))

371
(CD₃OD) δ 8.32 (br s, 1 H), 8.12 (s, 1 H), 7.84 (d, 1 H), 7.69
502.2
98.6%

(s, 1 H), 7.55 (d, 1 H), 7.46 (br d, 1 H), 7.39 (td, 1 H), 7.17-
[M + H]⁺

7.30 (m, 1 H), 6.78 (br s, 1 H), 4.76 (br dd, 1 H), 3.95 (br d, 1

H), 3.70-3.86 (m, 1 H), 3.45-3.58 (m, 2 H), 3.12 (br d, 1 H),

2.80-2.97 (m, 3 H), 2.03 (br dd, 2 H), 1.61-1.82 (m, 2 H)

372
(CD₃OD) δ 8.32 (br s, 1 H), 8.12 (s, 1 H), 7.84 (d, 1 H), 7.69
502.2
96.5%

(s, 1 H), 7.55 (d, 1 H), 7.46 (br d, 1 H), 7.39 (td, 1 H), 7.16-
[M + H]⁺

7.31 (m, 1 H), 6.78 (br s, 1 H), 4.76 (br dd, 1 H), 3.96 (br s, 1

H), 3.75-3.85 (m, 1 H), 3.46-3.62 (m, 2 H), 3.12 (br d, 1 H),

2.78-3.00 (m, 3 H), 2.03 (br d, 2 H), 1.62-1.82 (m, 2 H)

373
(CD₃OD) δ 8.45 (br s, 1 H), 7.69 (s, 1 H), 7.23 (td, 1.3 H),
422.1
99.4%

7.08-7.17 (m, 1.7 H), 6.72-7.00 (m, 1 H), 4.45-4.65 (m, 1 H),
[M + H]⁺

3.60-4.08 (m, 1 H), 2.82-3.18 (m, 2 H)

374
(CD₃OD) δ 8.45 (br s, 1 H), 7.69 (s, 1 H), 7.09-7.28 (m, 3 H),
422.2
97.6%

6.74-7.01 (m, 1 H), 4.58 (br d, 1 H), 3.59-4.10 (m, 1 H), 2.81-
[M + H]⁺

3.18 (m, 2 H)

375
(CD₃OD) δ 7.62-7.82 (m, 3 H), 7.45 (dd, 1 H), 6.93-7.33 (m,
478.3
92.9%

1 H), 6.76 (br s, 1 H), 4.59 (br d, 1 H), 3.96 (br s, 0.7 H), 3.62
[M + H]⁺

(br s, 0.3 H), 2.96-3.26 (m, 1 H), 2.88 (br d, 1 H), 1.50-1.75

(m, 6 H)

376
(CD₃OD) δ 7.61-7.78 (m, 3 H), 7.45 (dd, 1 H), 6.95-7.35 (m,
478.3
85.5%

1 H), 6.77 (br s, 1 H), 4.59 (br d, 1 H), 3.96 (br s, 0.7 H), 3.53-
[M + H]⁺

3.72 (m, 0.3 H), 2.94-3.24 (m, 1 H), 2.88 (br d, 1 H), 1.50-

1.74 (m, 6 H)

377
(CD₃OD) δ 8.47 (br s, 1 H), 7.69-7.79 (m, 2 H), 7.66 (d, 1 H),
420.3
97.8%

7.44 (dd, 1 H), 6.96-7.35 (m, 1 H), 6.77 (br s, 1 H), 4.57 (br d,
[M + H]⁺

1 H), 3.52-4.07 (m, 1 H), 3.12 (br s, 1 H), 2.86 (br d, 1 H)

378
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 2 H), 7.66 (d, 1 H), 7.39-
420.3
98.2%

7.49 (m, 1 H), 6.95-7.31 (m, 1 H), 6.78 (br s, 1 H), 4.57 (br d,
[M + H]⁺

1 H), 3.52-4.10 (m, 1 H), 3.12 (br s, 1 H), 2.87 (br d, 1 H)

379
(CD₃OD) δ 7.78-7.83 (m, 1 H), 7.68-7.73 (m, 1 H), 7.35-7.57
435.30
94.5%

(m, 2.4 H), 7.10-7.19 (m, 1 H), 6.95-7.01 (m, 1 H), 6.88 (br s,
[M + H]⁺

0.6 H), 5.30 (dd, 0.7 H), 5.12 (dd, 0.3 H), 4.00-4.04 (m, 3 H),

3.93-3.99 (m, 0.7 H), 3.68 (br s, 0.3 H), 2.83-3.27 (m, 2 H)

380
(CD₃OD) δ 7.77-7.84 (m, 1 H), 7.71 (br s, 1 H), 7.37-7.56 (m,
435.20
97.5%

2.4 H), 7.09-7.19 (m, 1 H), 6.94-7.02 (m, 1 H), 6.88 (br s, 0.6
[M + H]⁺

H), 5.29 (dd, 0.7 H), 5.12 (dd, 0.3 H), 3.99-4.05 (m, 3 H),

3.90-3.98 (m, 0.7 H), 3.68 (br s, 0.3 H), 2.85-3.27 (m, 2 H)

381
(CD₃OD) δ 8.47 (br s, 1 H), 7.70 (s, 1 H), 7.44 (br d, 1 H),
400.2
100%

6.99-7.36 (m, 3 H), 6.80 (br s, 1 H), 4.56 (br d, 1 H), 3.53-
[M + H]⁺

4.16 (m, 1 H), 3.12 (br s, 1 H), 2.88 (br d, 1 H), 2.57 (s, 3 H)

382
(CD₃OD) δ 8.47 (br s, 1 H), 7.70 (s, 1 H), 7.45 (br d, 1 H),
400.3
99.8%

6.99-7.39 (m, 3 H), 6.81 (br s, 1 H), 4.55 (br s, 1 H), 3.53-4.18
[M + H]⁺

(m, 1 H), 3.12 (br s, 1 H), 2.88 (br d, 1 H), 2.57 (s, 3 H)

383
(CD₃OD) δ 8.91 (s, 1 H), 8.44 (br s, 1 H), 8.12 (s, 1 H), 7.94-
483.4
98.4%

8.02 (m, 2 H), 7.67-7.79 (m, 2 H), 7.56 (br d, 1 H), 7.35-7.45
[M + H]⁺

(m, 1 H), 7.19-7.31 (m, 1 H), 6.83 (br s, 1 H), 4.77 (br d, 1 H),

3.97 (s, 4 H), 3.15 (br s, 1 H), 2.89 (br d, 1 H)

384
(CD₃OD) δ 8.91 (s, 1 H), 8.45 (br s, 1 H), 8.18 (br s, 1 H),
483.3
85.1%

8.12 (s, 1 H), 8.00 (d, 1 H), 7.95 (s, 1 H), 7.72 (d, 1 H), 7.56
[M + H]⁺

(br d, 1 H), 7.36-7.46 (m, 1 H), 7.23-7.33 (m, 1 H), 6.97 (br s,

1 H), 4.72-4.83 (m, 1 H), 3.97 (s, 4 H), 3.17 (br d, 1 H), 2.92

(br d, 1 H)

385
(CD₃OD) δ 7.48-7.68 (m, 3 H), 7.33-7.43 (m, 2 H), 7.19-7.27
398.20
100%

(m, 1 H), 6.45-6.93 (m, 1 H), 4.33-4.64 (m, 1 H), 3.67-3.89
[M + H]⁺

(m, 1 H), 3.39-3.44 (m, 2 H), 3.12-3.23 (m, 2 H), 2.91-3.05

(m, 1 H), 2.80 (br d, 1 H)

386
(CD₃OD) δ 7.48-7.68 (m, 3 H), 7.34-7.42 (m, 2 H), 7.19-7.27
398.20
99.5%

(m, 1 H), 6.45-6.90 (m, 1 H), 4.33-4.65 (m, 1 H), 3.80 (br s, 1
[M + H]⁺

H), 3.39-3.44 (m, 2 H), 3.11-3.23 (m, 2 H), 2.76-3.01 (m, 2 H)

387
(CD₃OD) δ 7.77 (s, 1 H), 7.64-7.71 (m, 1 H), 7.45-7.56 (m, 1
382.3
100%

H), 7.29-7.40 (m, 1 H), 7.16-7.26 (m, 1 H), 7.03 (s, 1 H),
[M + H]⁺

6.49-6.96 (m, 1 H), 4.94 (br dd, 0.6 H), 4.37 (dd, 0.7 H), 3.81

(br t, 0.7 H), 3.07-3.29 (m, 4 H), 2.70-3.06 (m, 2 H)

388
(CD₃OD) δ 7.77 (s, 1 H), 7.63-7.72 (m, 1 H), 7.45-7.56 (m, 1
382.2
100%

H), 7.31-7.40 (m, 1 H), 7.15-7.27 (m, 1 H), 6.94-7.07 (m, 1
[M + H]⁺

H), 6.41-6.88 (m, 1 H), 4.90-4.99 (m, 0.6 H), 4.37 (dd, 0.7 H),

3.81 (br t, 0.7 H), 3.09-3.29 (m, 4 H), 2.70-3.06 (m, 2 H)

389
(CD₃OD) δ 7.77-7.85 (m, 1 H), 7.70 (s, 1 H), 7.42-7.59 (m, 2
431.1
99.7%

H), 7.15-7.29 (m, 1 H), 6.81-7.02 (m, 2 H), 5.27 (dd, 0.7 H),
[M + H]⁺

5.09 (br dd, 0.3 H), 3.99-4.06 (m, 3 H), 3.94 (br t, 0.8 H), 3.59

(br t, 0.2 H), 3.11-3.26 (m, 0.8 H), 2.95-3.05 (m, 0.2 H), 2.79-

2.93 (m, 1 H), 2.37-2.50 (m, 3 H)

390
(CD₃OD) δ 7.77-7.84 (m, 1 H), 7.70 (s, 1 H), 7.41-7.61 (m, 2
431.1
92.6%

H), 7.17-7.27 (m, 1 H), 6.83-7.01 (m, 2 H), 5.27 (dd, 0.7 H),
[M + H]⁺

5.09 (dd, 0.3 H), 4.00-4.05 (m, 3 H), 3.84-3.98 (m, 0.7 H),

3.60 (br s, 0.3 H), 3.11-3.26 (m, 0.7 H), 2.94-3.06 (m, 0.3 H),

2.88 (br d, 1 H), 2.35-2.52 (m, 3 H)

391
(CD₃OD) δ 7.69 (s, 1 H), 7.48 (d, 1 H), 7.18-7.32 (m, 2 H),
458.1
99.1%

6.92-7.16 (m, 1 H), 6.76 (br s, 1 H), 4.92-5.01 (m, 0.2 H),
[M + H]⁺

4.42-4.66 (m, 0.8 H), 3.94 (br d, 0.7 H), 3.62 (br s, 0.3 H),

2.94-3.23 (m, 1 H), 2.87 (br d, 1 H), 2.55 (s, 3 H), 1.41-1.77

(m, 6 H)

392
(CD₃OD) δ 7.69 (s, 1 H), 7.48 (d, 1 H), 7.19-7.32 (m, 2 H),
458.1
99.5%

6.91-7.16 (m, 1 H), 6.74 (br s, 1 H), 4.92-5.01 (m, 0.3 H),
[M + H]⁺

4.49-4.62 (m, 0.7 H), 3.97 (br s, 0.6 H), 3.53-3.72 (m, 0.3 H),

2.94-3.23 (m, 1 H), 2.88 (br s, 1 H), 2.55 (s, 3 H), 1.40-1.79

(m, 6 H)

393
(CD₃OD) δ 8.45 (s, 1 H), 7.69 (s, 1 H), 7.48 (d, 1 H), 7.16-
400.2
99.2%

7.33 (m, 2 H), 6.94-7.14 (m, 1 H), 6.78 (br s, 1 H), 4.54 (br d,
[M + H]⁺

1 H), 3.95 (br s, 0.8 H), 3.45-3.69 (m, 0.2 H), 3.10 (br s, 1 H),

2.76-2.92 (m, 1 H), 2.54 (s, 3 H)

394
(CD₃OD) δ 8.45 (s, 1 H), 7.69 (s, 1 H), 7.48 (d, 1 H), 7.16-
400.2
99.3%

7.33 (m, 2 H), 6.93-7.15 (m, 1 H), 6.78 (br s, 1 H), 4.52 (br s,
[M + H]⁺

1 H), 3.95 (br s, 0.7 H), 3.48-3.67 (m, 0.3 H), 3.10 (br s, 1 H),

2.86 (br d, 1 H), 2.55 (s, 3 H)

395
(CD₃OD) δ 8.33 (br s, 1 H), 8.12 (s, 1 H), 7.84 (d, 1 H), 7.69
512.3
100%

(s, 1 H), 7.35-7.60 (m, 3 H), 7.20-7.31 (m, 1 H), 6.81 (br s, 1
[M + H]⁺

H), 4.76 (br dd, 1 H), 3.95 (br s, 1 H), 3.20-3.27 (m, 4 H),

3.07-3.19 (m, 1 H), 2.80-2.95 (m, 1 H), 1.57-1.63 (m, 4 H),

0.41 (s, 4 H)

396
(CD₃OD) δ 8.33 (br s, 1 H), 8.12 (d, 1 H), 7.84 (d, 1 H), 7.70
512.2
97.4%

(d, 1 H), 7.35-7.58 (m, 3 H), 7.20-7.29 (m, 1 H), 6.81 (s, 1 H),
[M + H]⁺

4.77 (br dd, 1 H), 3.94 (br s, 1 H), 3.20-3.25 (m, 4 H), 3.09-

3.19 (m, 1 H), 2.87 (dd, 1 H), 1.56-1.65 (m, 4 H), 0.41 (s, 4 H)

397
(CD₃OD) δ 7.64-7.70 (m, 2 H), 7.47-7.50 (m, 1 H), 7.37-7.44
398.20
100%

(m, 2 H), 7.11-7.19 (m, 1 H), 6.83 (s, 0.8 H), 6.48 (br s, 0.2
[M + H]⁺

H), 4.37 (br dd, 1 H), 3.81 (br t, 1 H), 3.39-3.45 (m, 2 H),

3.13-3.20 (m, 2 H), 2.91-3.01 (m, 1 H), 2.80 (br dd, 1 H)

398
(CD₃OD) δ 7.46-7.70 (m, 1 H), 7.46-7.70 (m, 2 H), 7.35-7.45
398.20
99.8%

(m, 2 H), 7.11-7.19 (m, 1 H), 6.42-6.88 (m, 1 H), 4.34-4.64
[M + H]

(m, 1 H), 3.82 (br s, 1 H), 3.40-3.45 (m, 2 H), 3.12-3.24 (m, 2

H), 2.89-3.04 (m, 1 H), 2.80 (br d, 1 H)

399
(CD₃OD) δ 9.29-9.38 (m, 1 H), 8.80-8.89 (m, 1 H), 8.52-8.63
432.2
100%

(m, 1 H), 7.53-7.81 (m, 3.5 H), 7.44 (br d, 1 H), 7.13-7.30 (m,
[M + H]⁺

1 H), 6.90 (br s, 0.5 H), 5.11-5.44 (m, 1 H), 3.59-4.14 (m, 1

H), 3.00-3.29 (m, 1 H), 2.93 (br d, 1 H)

400
(CD₃OD) δ 9.27-9.37 (m, 1 H), 8.79-8.84 (m, 1 H), 8.41-8.65
432.3
99.3%

(m, 1 H), 7.50-7.77 (m, 3.5 H), 7.40-7.47 (m, 1 H), 7.17-7.26
[M + H]⁺

(m, 1 H), 6.90 (br s, 0.5 H), 5.10-5.41 (m, 1 H), 3.62-4.10 (m,

1 H), 2.99-3.29 (m, 1 H), 2.93 (br d, 1 H)

401
(CD₃OD) δ 7.61-7.74 (m, 2 H), 7.44 (br d, 1 H), 6.97-7.30 (m,
505.3
96.8%

2 H), 6.67 (br s, 1 H), 4.81 (br s, 1.3 H), 3.65 (br s, 5.7 H),
[M + H]⁺

3.04 (br s, 1 H), 2.85 (br d, 1 H), 1.89 (br s, 4 H)

402
(CD₃OD) δ 7.65-7.72 (m, 2 H), 7.44 (br d, 1 H), 6.96-7.28 (m,
505.3
95.5%

2 H), 6.67 (br s, 1 H), 4.82 (br s, 1.3 H), 3.66 (br s, 5.7 H),
[M + H]⁺

3.05 (br s, 1 H), 2.85 (br d, 1 H), 1.89 (br s, 4 H)

403
(CD₃OD) δ 7.64-7.71 (m, 2 H), 7.45 (br d, 1 H), 6.94-7.28 (m,
502.3
97.4%

2 H), 6.69 (br s, 1 H), 4.77 (br s, 1 H), 3.53-3.88 (m, 5 H),
[M + H]⁺

3.05 (br s, 1 H), 2.85 (br d, 1 H), 2.53 (br s, 4 H), 2.36 (s, 3 H)

404
(CD₃OD) δ 7.65-7.74 (m, 2 H), 7.45 (br d, 1 H), 6.96-7.29 (m,
502.3
96.1%

2 H), 6.68 (br s, 1 H), 4.78 (br s, 1 H), 3.51-3.90 (m, 5 H),
[M + H]⁺

3.04 (br s, 1 H), 2.85 (br d, 1 H), 2.53 (br s, 4 H), 2.35 (s, 3 H)

405
(CD₃OD) δ 9.31-9.54 (m, 3 H), 7.70 (br d, 2 H), 7.32-7.60 (m,
482.2
88.0%

1 H), 7.01-7.30 (m, 2 H), 6.81 (br s, 1 H), 4.96-5.03 (m, 0.4
[M + H]⁺

H), 4.73 (br d, 0.6 H), 3.72-4.07 (m, 1 H), 3.01-3.30 (m, 1 H),

2.95 (br d, 1 H)

406
(CD₃OD) δ 9.30-9.56 (m, 3 H), 7.70 (br d, 2 H), 7.33-7.60 (m,
482.3
98.0%

1 H), 6.99-7.29 (m, 2 H), 6.81 (br s, 1 H), 4.95-5.06 (m, 0.4
[M + H]⁺

H), 4.74 (br d, 0.6 H), 3.73-4.10 (m, 1 H), 3.01-3.29 (m, 1 H),

2.95 (br d, 1 H)

407
(CD₃OD) δ 7.69 (s, 1 H), 7.42-7.56 (m, 2 H), 7.24 (d, 1 H),
486.2
99.3%

6.34-6.80 (m, 1 H), 4.36 (br s, 1 H), 3.51-4.03 (m, 1 H), 2.92-
[M + H]⁺

3.22 (m, 1 H), 2.85 (br d, 1 H), 2.45 (s, 3 H), 1.63 (br s, 6 H)

408
(CD₃OD) δ 7.68 (s, 1 H), 7.40-7.56 (m, 2 H), 7.24 (br d, 1 H),
486.1
97.8%

6.29-6.80 (m, 1 H), 4.36 (br s, 1 H), 3.52-4.06 (m, 1 H), 3.13
[M + H]⁺

(br s, 1 H), 2.85 (br d, 1 H), 2.45 (s, 3 H), 1.63 (br s, 6 H)

409
(CD₃OD) δ 8.59-8.71 (m, 1 H), 7.50-7.62 (m, 2 H), 7.35-7.47
398.1
100%

(m, 1 H), 7.20-7.29 (m, 1 H), 7.05-7.16 (m, 1 H), 6.23-6.82
[M + H]⁺

(m, 1 H), 4.87 (br dd, 0.2 H), 4.22 (dd, 0.8 H), 3.66 (br t, 0.8

H), 3.17 (br t, 2.2 H), 2.62-3.04 (m, 4 H)

410
(CD₃OD) δ 8.60-8.72 (m, 1 H), 7.51-7.61 (m, 2 H), 7.34-7.46
398.1
92.3%

(m, 1 H), 7.20-7.29 (m, 1 H), 7.04-7.19 (m, 1 H), 6.21-6.93
[M + H]⁺

(m, 1 H), 4.87 (br dd, 0.2 H), 4.22 (br dd, 0.8 H), 3.66 (br t,

0.8 H), 3.17 (br t, 2.2 H), 2.61-3.09 (m, 4 H)

411
(CD₃OD) δ 7.64-7.88 (m, 3 H), 7.44 (br d, 1 H), 6.72-7.37 (m,
484.2
97.5%

4 H), 4.93-5.07 (m, 0.4 H), 4.74 (br s, 0.6 H), 3.75-4.13 (m, 4
[M + H]⁺

H), 3.10-3.28 (m, 1 H), 2.90 (br d, 1 H)

412
(CD₃OD) δ 7.63-7.88 (m, 3 H), 7.44 (br d, 1 H), 6.74-7.35 (m,
484.2
97.2%

4 H), 4.91-5.09 (m, 0.4 H), 4.75 (br s, 0.6 H), 3.57-4.11 (m, 4
[M + H]⁺

H), 3.08-3.30 (m, 1 H), 2.90 (br d, 1 H)

413
(CD₃OD) δ 7.64-7.70 (m, 2 H), 7.44 (dd, 1 H), 6.97-7.29 (m,
489.1
95.9%

2 H), 6.68 (br s, 1 H), 4.77 (br s, 1 H), 3.46-3.87 (m, 9 H),
[M + H]⁺

3.05 (br s, 1 H), 2.85 (br d, 1 H)

414
(CD₃OD) δ 7.63-7.72 (m, 2 H), 7.44 (dd, 1 H), 6.97-7.29 (m,
489.1
98.3%

2 H), 6.70 (br s, 1 H), 4.78 (br s, 1 H), 3.48-3.88 (m, 9 H),
[M + H]⁺

3.05 (br s, 1 H), 2.84 (br d, 1 H)

415
(CD₃OD) δ 7.88 (s, 1 H), 7.70 (br s, 1 H), 7.56-7.64 (m, 2 H),
522.10
94.5%

6.97-7.28 (m, 1 H), 6.74 (br s, 1 H), 4.59 (br d, 1 H), 3.58-
[M + H]⁺

4.05 (m, 1 H), 2.81-3.22 (m, 2 H), 1.52-1.73 (m, 6 H)

416
(CD₃OD) δ 7.87 (s, 1 H), 7.70 (br s, 1 H), 7.56-7.64 (m, 2 H),
524.20
79.2%

6.95-7.30 (m, 1 H), 6.74 (br s, 1 H), 4.59 (br d, 1 H), 3.57-
[M + H]

4.05 (m, 1 H), 2.78-3.25 (m, 2 H), 1.51-1.74 (m, 6 H)

417
(CD₃OD) δ 8.18-8.74 (m, 2 H), 7.64-7.96 (m, 3 H), 7.05-7.52
499.2
98.7%

(m, 3 H), 6.81 (br s, 1 H), 5.02 (br s, 0.3 H), 4.75 (br d, 0.7 H),
[M + H]⁺

3.62-4.10 (m, 1 H), 3.15 (br s, 1 H), 2.91 (br d, 1 H)

418
(CD₃OD) δ 8.05-8.64 (m, 2 H), 7.50-7.82 (m, 3 H), 6.93-7.39
499.2
96.8%

(m, 3 H), 6.69 (s, 1 H), 4.86-4.95 (m, 0.3 H), 4.64 (br d, 0.7
[M + H]⁺

H), 3.51-4.04 (m, 1 H), 2.89-3.16 (m, 1 H), 2.79 (br d, 1 H)

419
(CD₃OD) δ 9.30 (br s, 1 H), 8.76 (br s, 1 H), 8.38-8.58 (m, 1
481.3
96.7%

H), 7.40-7.78 (m, 4 H), 7.04-7.38 (m, 2 H), 6.79 (br s, 1 H),
[M + H]⁺

4.74 (br s, 1 H), 3.63-4.16 (m, 1 H), 3.14 (br s, 1 H), 2.92 (br

s, 1 H)

420
(CD₃OD) δ 9.18 (s, 1 H), 8.65 (br s, 1 H), 8.15-8.49 (m, 1 H),
481.3
96.9%

7.27-7.69 (m, 4 H), 6.91-7.26 (m, 2 H), 6.70 (br s, 1 H), 4.64
[M + H]⁺

(br s, 1 H), 3.57-4.00 (m, 1 H), 2.89-3.17 (m, 1 H), 2.83 (br d,

1 H)

421
(CD₃OD) δ 8.61-8.90 (m, 2 H), 7.88-8.22 (m, 2 H), 7.70 (br s,
481.3
100%

2 H), 7.32-7.58 (m, 1 H), 7.01-7.30 (m, 2 H), 6.80 (br s, 1 H),
[M + H]⁺

4.96-5.08 (m, 0.5 H), 4.72 (br d, 0.5 H), 3.56-4.20 (m, 1 H),

3.25 (br s, 1 H), 2.94 (br s, 1 H)

422
(CD₃OD) δ 8.59-8.89 (m, 2 H), 7.86-8.20 (m, 2 H), 7.71 (br d,
481.3
99.0%

2 H), 7.31-7.58 (m, 1 H), 6.98-7.30 (m, 2 H), 6.81 (br s, 1 H),
[M + H]⁺

4.99 (br s, 0.5 H), 4.72 (br d, 0.5 H), 3.67-4.15 (m, 1 H), 3.24

(br s, 1 H), 2.95 (br d, 1 H)

423
(CD₃OD) δ 7.59-7.73 (m, 2 H), 7.42-7.50 (m, 1 H), 7.32-7.41
478.2
96.9%

(m, 1 H), 6.93-7.28 (m, 1 H), 6.76 (br s, 1 H), 4.47-4.61 (m, 1
[M + H]⁺

H), 3.56-4.12 (m, 1 H), 3.13 (br s, 1 H), 2.87 (br s, 1 H), 1.46-

1.78 (m, 6 H)

424
(CD₃OD) δ 7.57-7.75 (m, 2 H), 7.42-7.49 (m, 1 H), 7.33-7.41
478.2
100%

(m, 1 H), 6.92-7.28 (m, 1 H), 6.76 (br s, 1 H), 4.56 (br s, 1 H),
[M + H]⁺

3.54-4.12 (m, 1 H), 2.95-3.24 (m, 1 H), 2.87 (br s, 1 H), 1.50-

1.74 (m, 6 H)

425
(CD₃OD) δ 8.45 (s, 1 H), 7.58-7.74 (m, 2 H), 7.31-7.49 (m, 2
420.2
98.8%

H), 6.94-7.29 (m, 1 H), 6.80 (br s, 1 H), 4.54 (br s, 1 H), 3.52-
[M + H]⁺

4.10 (m, 1 H), 3.10 (br s, 1 H), 2.87 (br d, 1 H)

426
(CD₃OD) δ 8.45 (s, 1 H), 7.58-7.76 (m, 2 H), 7.43-7.50 (m, 1
420.2
98.5%

H), 7.33-7.42 (m, 1 H), 6.95-7.29 (m, 1 H), 6.79 (br s, 1 H),
[M + H]⁺

4.54 (br s, 1 H), 3.51-4.09 (m, 1 H), 3.12 (br d, 1 H), 2.87 (br

d, 1 H)

427
(CD₃OD) δ 7.70 (s, 1 H), 7.32-7.44 (m, 1 H), 6.98-7.31 (m, 2
474.3
99.2%

H), 6.94 (d, 1 H), 6.55-6.85 (m, 1 H), 4.56 (br d, 1 H), 4.00 (s,
[M + H]⁺

3.8 H), 3.65 (br s, 0.2 H), 2.95-3.24 (m, 1 H), 2.87 (br d, 1 H),

1.51-1.76 (m, 6 H)

428
(CD₃OD) δ 7.70 (br s, 1 H), 7.33-7.43 (m, 1 H), 6.99-7.31 (m,
474.3
98.9%

2 H), 6.94 (d, 1 H), 6.75 (br s, 1 H), 4.57 (br d, 1 H), 4.01 (s,
[M + H]⁺

3.8 H), 3.65 (br s, 0.2 H), 2.94-3.25 (m, 1 H), 2.88 (br d, 1 H),

1.49-1.73 (m, 6 H)

429
(CD₃OD) δ 8.46 (br s, 1 H), 7.70 (s, 1 H), 7.33-7.42 (m, 1 H),
416.3
99.7%

7.00-7.32 (m, 2 H), 6.94 (d, 1 H), 6.76 (br s, 1 H), 4.55 (br d,
[M + H]⁺

1 H), 4.00 (s, 3.9 H), 3.61 (br s, 0.1 H), 3.12 (br s, 1 H), 2.86

(br d, 1 H)

430
(CD₃OD) δ 8.46 (br s, 1 H), 7.70 (s, 1 H), 7.34-7.45 (m, 1 H),
416.3
99.3%

7.00-7.32 (m, 2 H), 6.94 (d, 1 H), 6.76 (br s, 1 H), 4.55 (br d,
[M + H]⁺

1 H), 4.00 (s, 3.9 H), 3.62 (br s, 0.1 H), 3.12 (br s, 1 H), 2.86

(br d, 1 H)

431
(CD₃OD) δ 7.62-7.72 (m, 2 H), 7.57 (d, 1 H), 7.30-7.39 (m, 1
524.2
98.7%

H), 6.95-7.29 (m, 1 H), 6.72 (br s, 1 H), 4.52-4.60 (m, 1 H),
[M + H]⁺

3.63-4.13 (m, 1 H), 2.81-3.24 (m, 2 H), 1.52-1.71 (m, 6 H)

432
(CD₃OD) δ 7.61-7.76 (m, 2 H), 7.57 (d, 1 H), 7.30-7.39 (m, 1
522.2
98.8%

H), 6.94-7.29 (m, 1 H), 6.74 (br s, 1 H), 4.60 (s, 1 H), 3.62-
[M + H]⁺

4.12 (m, 1 H), 2.82-3.21 (m, 2 H), 1.51-1.72 (m, 6 H)

433
(CD₃OD) δ 8.45 (br s, 1 H), 7.61-7.72 (m, 2 H), 7.57 (d, 1 H),
466.1
99.3%

7.30-7.38 (m, 1 H), 6.97-7.29 (m, 1 H), 6.76 (br s, 1 H), 4.51-
[M + H]⁺

4.60 (m, 1 H), 3.54-4.15 (m, 1 H), 2.82-3.18 (m, 2 H)

434
(CD₃OD) δ 8.45 (br s, 1 H), 7.62-7.72 (m, 2 H), 7.56 (d, 1 H),
466.1
99.1%

7.29-7.38 (m, 1 H), 6.94-7.28 (m, 1 H), 6.76 (br s, 1 H), 4.60
[M + H]⁺

(s, 1 H), 3.57-4.10 (m, 1 H), 2.81-3.19 (m, 2 H)

435
(CD₃OD) δ 7.71 (s, 1 H), 7.63 (br d, 1 H), 7.39-7.45 (m, 2 H),
478.30
98.9%

7.00-7.29 (m, 1 H), 6.60-6.83 (m, 1 H), 4.53-4.68 (m, 1 H),
[M + H]

3.65-4.08 (m, 1 H), 3.17 (br d, 1 H), 2.90 (br d, 1 H), 1.54-

1.73 (m, 6 H)

436
(CD₃OD) δ 7.71 (s, 1 H), 7.63 (br d, 1 H), 7.40-7.44 (m, 2 H),
478.30
98.5%

7.01-7.28 (m, 1 H), 6.65-6.80 (m, 1 H), 4.57-4.64 (m, 1 H),
[M + H]

3.68-4.06 (m, 1 H), 3.17 (br d, 1 H), 2.90 (br d, 1 H), 1.55-

1.72 (m, 6 H)

437
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.63 (dd, 1 H),
420.20
99.6%

7.39-7.45 (m, 2 H), 7.02-7.30 (m, 1 H), 6.79 (br s, 1 H), 4.51-
[M + H]⁺

4.66 (m, 1 H), 4.02 (br s, 1 H), 3.13 (br s, 1 H), 2.88 (br d, 1

H)

438
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.63 (dd, 1 H),
420.20
99.6%

7.40-7.44 (m, 2 H), 7.02-7.30 (m, 1 H), 6.79 (br s, 1 H), 4.54-
[M + H]

4.67 (m, 1 H), 4.01 (br s, 1 H), 3.13 (br s, 1 H), 2.89 (br d, 1

H)

439
(CD₃OD) δ 7.68 (s, 1 H), 7.54 (d, 1 H), 7.45 (s, 1 H), 7.21 (d,
486.2
99.5%

1 H), 6.34-6.84 (m, 1 H), 4.35 (br s, 1 H), 3.50-4.05 (m, 1 H),
[M + H]⁺

2.79-3.25 (m, 2 H), 2.48 (s, 3 H), 1.48-1.71 (m, 6 H)

440
(CD₃OD) δ 7.68 (s, 1 H), 7.54 (d, 1 H), 7.46 (s, 1 H), 7.22 (d,
486.2
99.2%

1 H), 6.34-6.83 (m, 1 H), 4.35 (br s, 1 H), 3.52-4.03 (m, 1 H),
[M + H]⁺

2.78-3.25 (m, 2 H), 2.48 (s, 3 H), 1.64 (br s, 6 H)

441
(CD₃OD) δ 8.35-8.54 (m, 1 H), 8.15-8.33 (m, 1 H), 7.51-7.82
462.3
100%

(m, 3.4 H), 7.34-7.48 (m, 1 H), 7.14-7.28 (m, 1 H), 6.76-7.04
[M + H]⁺

(m, 0.6 H), 5.30 (br dd, 0.8 H), 5.14 (br dd, 0.2 H), 3.90-4.11

(m, 3.8 H), 3.66 (br s, 0.2 H), 2.77-3.27 (m, 2 H)

442
(CD₃OD) δ 8.37-8.54 (m, 1 H), 8.15-8.33 (m, 1 H), 7.51-7.80
462.3
98.4%

(m, 3.3 H), 7.33-7.48 (m, 1 H), 7.12-7.33 (m, 1 H), 6.89 (br s,
[M + H]⁺

0.7 H), 5.10-5.36 (m, 1 H), 3.87-4.14 (m, 3.7 H), 3.66 (br s,

0.3 H), 2.74-3.27 (m, 2 H)

443
(CD₃OD) δ 8.65-9.19 (m, 1 H), 8.25-8.58 (m, 2 H), 7.65-7.78
549.3
100%

(m, 2 H), 6.68-7.56 (m, 4 H), 5.02 (br s, 0.2 H), 4.76 (br d, 0.8
[M + H]⁺

H), 3.68-4.13 (m, 1 H), 3.01-3.30 (m, 1 H), 2.92 (br d, 1 H)

444
(CD₃OD) δ 8.52-9.02 (m, 1 H), 8.14-8.42 (m, 2 H), 7.54-7.63
549.3
99.3%

(m, 2 H), 6.66-7.40 (m, 4 H), 4.89 (br s, 0.2 H), 4.64 (br d, 0.8
[M + H]⁺

H), 3.51-3.97 (m, 1 H), 2.89-3.18 (m, 1 H), 2.80 (br d, 1 H)

445
(CD₃OD) δ 8.01-8.55 (m, 2 H), 7.00-7.96 (m, 6 H), 6.79 (br s,
511.1
97.4%

1 H), 4.78 (br s, 1 H), 3.99 (br s, 4 H), 2.64-3.27 (m, 2 H)
[M + H]⁺

446
(CD₃OD) δ 7.95-8.59 (m, 2 H), 7.15-7.91 (m, 5.6 H), 6.40-
511.3
96.6%

7.11 (m, 1.4 H), 4.78 (br s, 1 H), 3.99 (br s, 4 H), 2.69-3.27
[M + H]⁺

(m, 2 H)

447
(CD₃OD) δ 7.67-7.75 (m, 1 H), 7.36-7.48 (m, 1 H), 7.24-7.33
414.1
100%

(m, 1 H), 7.12-7.22 (m, 1 H), 6.88-7.03 (m, 1 H), 6.64-6.88
[M + H]⁺

(m, 1 H), 5.09 (dd, 0.3 H), 4.74 (dd, 0.7 H), 4.12 (s, 3 H),

3.87-4.00 (m, 0.7 H), 3.46-3.58 (m, 0.3 H), 2.95-3.29 (m, 1

H), 2.77-2.92 (m, 1 H), 2.49-2.60 (m, 3 H)

448
(CD₃OD) δ 7.67-7.73 (m, 1 H), 7.37-7.48 (m, 1 H), 7.24-7.33
414.1
99.2%

(m, 1 H), 7.19 (d, 1 H), 6.89-7.16 (m, 1 H), 6.65-6.88 (m, 1
[M + H]⁺

H), 5.09 (dd, 0.3 H), 4.74 (dd, 0.7 H), 4.12 (s, 3 H), 3.94 (br t,

0.7 H), 3.46-3.58 (m, 0.3 H), 2.95-3.28 (m, 1 H), 2.78-2.92

(m, 1 H), 2.52-2.59 (m, 3 H)

449
(CD₃OD) δ 7.85 (br s, 1 H), 7.50-7.76 (m, 2 H), 7.40-7.50 (m,
399.1
97.9%

1 H), 7.31 (t, 1 H), 7.20 (d, 1 H), 6.72-7.06 (m, 1.8 H), 6.33
[M + H]⁺

(br s, 0.2 H), 4.94-5.04 (m, 0.3 H), 4.27 (br d, 0.7 H), 3.43-

4.10 (m, 1 H), 2.94-3.12 (m, 1 H), 2.73-2.88 (m, 1 H), 2.58 (s,

3 H)

450
(CD₃OD) δ 7.85 (br s, 1 H), 7.50-7.75 (m, 2 H), 7.45 (br d, 1
399.1
98.9%

H), 7.30 (t, 1 H), 7.20 (d, 1 H), 6.75-7.04 (m, 1.8 H), 6.21-
[M + H]⁺

6.47 (m, 0.2 H), 4.93 (br s, 0.3 H), 4.27 (br d, 0.7 H), 3.45-

4.07 (m, 1 H), 2.93-3.10 (m, 1 H), 2.82 (br d, 1 H), 2.58 (s, 3

H)

451
(CD₃OD) δ 9.35 (s, 1 H), 8.70 (d, 1 H), 8.53 (br s, 1 H), 8.05-
480.1
95.5%

8.21 (m, 2 H), 7.89-8.04 (m, 2 H), 7.71 (s, 1 H), 7.57 (d, 1 H),
[M + H]⁺

7.36-7.51 (m, 2 H), 7.19-7.33 (m, 1 H), 6.84 (br s, 1 H), 4.77

(br d, 1 H), 3.80-4.19 (m, 1 H), 3.16 (br d, 1 H), 2.90 (br d, 1

H)

452
(CD₃OD) δ 9.35 (s, 1 H), 8.70 (d, 1 H), 8.53 (br s, 1 H), 8.06-
480.2
95.3%

8.20 (m, 2 H), 7.91-8.05 (m, 2 H), 7.71 (s, 1 H), 7.57 (d, 1 H),
[M + H]⁺

7.33-7.50 (m, 2 H), 7.19-7.31 (m, 1 H), 6.84 (br s, 1 H), 4.78

(br d, 1 H), 3.98 (br s, 1 H), 3.11-3.25 (m, 1 H), 2.90 (br d, 1

H)

453
(CD₃OD) δ 7.97 (d, 1 H), 7.66-7.77 (m, 2 H), 7.52-7.60 (m, 1
512.3
96.0%

H), 6.91-7.28 (m, 1 H), 6.81 (br s, 1 H), 4.55 (br s, 1 H), 3.54-
[M + H]⁺

4.07 (m, 1 H), 2.85-3.25 (m, 2 H), 1.48-1.71 (m, 6 H)

454
(CD₃OD) δ 7.97 (d, 1 H), 7.65-7.75 (m, 2 H), 7.52-7.60 (m, 1
512.3
95.6%

H), 6.91-7.26 (m, 1 H), 6.79 (br s, 1 H), 4.47-4.67 (m, 1 H),
[M + H]⁺

3.55-4.11 (m, 1 H), 2.83-3.25 (m, 2 H), 1.49-1.72 (m, 6 H)

455
(CD₃OD) δ 7.70 (s, 1 H), 6.96-7.39 (m, 4 H), 6.62-6.84 (m, 1
474.1
97.4%

H), 4.77-4.86 (m, 0.3 H), 4.57 (br d, 0.7 H), 4.02 (s, 3.7 H),
[M + H]⁺

3.62 (br s, 0.3 H), 2.99-3.23 (m, 1 H), 2.89 (br d, 1 H), 1.53-

1.78 (m, 6 H)

456
(CD₃OD) δ 7.70 (s, 1 H), 6.98-7.37 (m, 4 H), 6.62-6.84 (m, 1
474.1
95.4%

H), 4.81-4.86 (m, 0.3 H), 4.57 (br d, 0.7 H), 4.02 (s, 3.7 H),
[M + H]⁺

3.62 (br s, 0.3 H), 3.00-3.22 (m, 1 H), 2.89 (br d, 1 H), 1.53-

1.76 (m, 6 H)

457
(CD₃OD) δ 8.46 (s, 1 H), 7.70 (s, 1 H), 6.97-7.36 (m, 4 H),
416.1
99.6%

6.81 (br s, 1 H), 4.55 (br d, 1 H), 4.02 (s, 3.8 H), 3.59 (br s,
[M + H]⁺

0.2 H), 3.12 (br s, 1 H), 2.87 (br d, 1 H)

458
(CD₃OD) δ 8.46 (s, 1 H), 7.70 (s, 1 H), 6.98-7.35 (m, 4 H),
416.1
99.4%

6.81 (br s, 1 H), 4.55 (br d, 1 H), 4.02 (s, 3.8 H), 3.61 (br s,
[M + H]⁺

0.2 H), 3.11 (br s, 1 H), 2.87 (br d, 1 H)

459
(CD₃OD) δ 7.66-7.76 (m, 2 H), 7.61 (d, 1 H), 7.23-7.40 (m, 1
522.0
98.2%

H), 6.92-7.21 (m, 1 H), 6.78 (br s, 1 H), 4.63 (s, 1 H), 3.60-
[M + H]⁺

4.12 (m, 1 H), 2.81-3.27 (m, 2 H), 1.50-1.79 (m, 6 H)

460
(CD₃OD) δ 7.63-7.79 (m, 2 H), 7.59 (d, 1 H), 7.32 (t, 1 H),
522.0
97.1%

6.93-7.26 (m, 1 H), 6.76 (br s, 1 H), 4.58 (br d, 1 H), 3.54-
[M + H]⁺

4.13 (m, 1 H), 2.90 (br s, 2 H), 1.68 (br s, 6 H)

461
(CD₃OD) δ 8.45 (s, 1 H), 7.49-7.72 (m, 3 H), 7.31 (t, 1 H),
466.2
96.3%

6.95-7.27 (m, 1 H), 6.80 (br s, 1 H), 4.39-4.73 (m, 1 H), 3.48-
[M + H]⁺

4.10 (m, 1 H), 2.67-3.20 (m, 2 H)

462
(CD₃OD) δ 8.45 (s, 1 H), 7.52-7.74 (m, 3 H), 7.31 (t, 1 H),
464.1
93.5%

6.92-7.26 (m, 1 H), 6.80 (br s, 1 H), 3.84-4.66 (m, 1 H), 3.43-
[M + H]⁺

4.69 (m, 1 H), 2.80-3.17 (m, 2 H)

463
(CD₃OD) δ 7.93 (d, 1 H), 7.63-7.74 (m, 2 H), 7.52-7.62 (m, 1
512.1
98.0%

H), 6.93-7.28 (m, 1 H), 6.75 (br s, 1 H), 4.91-5.04 (m, 1 H),
[M + H]⁺

3.58-4.23 (m, 1 H), 3.14 (br s, 1 H), 2.90 (br s, 1 H), 1.43-1.78

(m, 6 H)

464
(CD₃OD) δ 7.94 (d, 1 H), 7.64-7.74 (m, 2 H), 7.52-7.62 (m, 1
512.4
100%

H), 6.92-7.29 (m, 1 H), 6.78 (br s, 1 H), 4.58 (br s, 1 H), 3.60-
[M + H]⁺

4.20 (m, 1 H), 2.97-3.23 (m, 1 H), 2.89 (br d, 1 H), 1.50-1.78

(m, 6 H)

465
(CD₃OD) δ 8.45 (br s, 1 H), 7.93 (br d, 1 H), 7.64-7.75 (m, 2
454.2
99.9%

H), 7.50-7.63 (m, 1 H), 6.93-7.28 (m, 1 H), 6.80 (br s, 1 H),
[M + H]⁺

4.61 (br s, 1 H), 4.05 (br s, 1 H), 3.10 (br s, 1 H), 2.87 (br d, 1

H)

466
(CD₃OD) δ 8.45 (br s, 1 H), 7.93 (d, 1 H), 7.63-7.72 (m, 2 H),
454.1
97.7%

7.50-7.61 (m, 1 H), 6.93-7.28 (m, 1 H), 6.77 (br s, 1 H), 4.42-
[M + H]⁺

4.59 (m, 1 H), 3.59-4.20 (m, 1 H), 3.09 (br s, 1 H), 2.87 (br d,

1 H)

467
(CD₃OD) δ 8.45 (br s, 1 H), 7.62-7.71 (m, 3 H), 7.35-7.45 (m,
386.2
98.2%

2 H), 6.93-7.30 (m, 1 H), 6.78 (br s, 1 H), 4.54 (br d, 1 H),
[M + H]⁺

3.51-4.02 (m, 1 H), 2.81-3.16 (m, 2 H)

468
(CD₃OD) δ 8.45 (br s, 1 H), 7.62-7.71 (m, 3 H), 7.35-7.45 (m,
386.2
98.4%

2 H), 6.92-7.32 (m, 1 H), 6.78 (br s, 1 H), 4.44-4.64 (m, 1 H),
[M + H]⁺

3.53-4.04 (m, 1 H), 2.82-3.15 (m, 2 H)

469
(CD₃OD) δ 7.57-7.76 (m, 3 H), 7.41 (qd, 2 H), 6.93-7.30 (m,
444.3
99.4%

1 H), 6.75 (br s, 1 H), 4.56 (br d, 1 H), 3.52-4.04 (m, 1 H),
[M + H]⁺

2.76-3.19 (m, 2 H), 1.48-1.74 (m, 6 H)

470
(CD₃OD) δ 7.58-7.78 (m, 3 H), 7.33-7.49 (m, 2 H), 6.92-7.31
444.3
98.0%

(m, 1 H), 6.75 (br s, 1 H), 4.56 (br d, 1 H), 3.53-4.04 (m, 1 H),
[M + H]⁺

2.79-3.20 (m, 2 H), 1.46-1.73 (m, 6 H)

471
(CD₃OD) δ 7.70 (s, 1 H), 7.34-7.56 (m, 2 H), 7.08-7.19 (m, 1
446.0
96.6%

H), 6.81 (br s, 1 H), 5.06 (br dd, 0.3 H), 4.74 (dd, 0.7 H), 4.00-
[M + H]⁺

4.15 (m, 3 H), 3.88 (br s, 0.6 H), 3.50 (br d, 0.4 H), 3.10-3.25

(m, 0.7 H), 2.89-3.04 (m, 0.3 H), 2.73-2.89 (m, 1 H)

472
(CD₃OD) δ 7.70 (s, 1 H), 7.34-7.56 (m, 2 H), 7.02-7.28 (m, 1
446.0
94.1%

H), 6.81 (br s, 1 H), 5.06 (br dd, 0.3 H), 4.74 (dd, 0.7 H), 3.99-
[M + H]⁺

4.17 (m, 3 H), 3.88 (br s, 0.6 H), 3.50 (br d, 0.4 H), 3.11-3.26

(m, 0.7 H), 2.91-3.04 (m, 0.3 H), 2.74-2.89 (m, 1 H)

473
(CD₃OD) δ 7.69 (s, 1 H), 7.45-7.58 (m, 1 H), 7.29-7.42 (m, 1
448.1
99.2%

H), 7.18-7.27 (m, 1 H), 6.78-7.16 (m, 1 H), 5.06 (br dd, 0.3
[M + H]⁺

H), 4.75 (dd, 0.7H), 3.99-4.13 (m, 3 H), 3.87 (br t, 0.7 H),

3.43-3.57 (m, 0.3 H), 3.10-3.24 (m, 0.7 H), 2.92-3.04 (m, 0.3

H), 2.74-2.90 (m, 1 H)

474
(CD₃OD) δ 7.69 (s, 1 H), 7.45-7.58 (m, 1 H), 7.30-7.42 (m, 1
446.1
99.3%

H), 7.17-7.28 (m, 1 H), 6.77-7.16 (m, 1 H), 5.06 (br dd, 0.3
[M + H]⁺

H), 4.75 (dd, 0.7 H), 3.99-4.10 (m, 3 H), 3.40-3.95 (m, 1 H),

2.69-3.24 (m, 2 H)

475
(CD₃OD) δ 8.33 (br s, 1 H), 8.12 (s, 1 H), 7.86 (d, 1 H), 7.69
501.50
95.4%

(s, 1 H), 7.50-7.55 (m, 1 H), 7.38-7.48 (m, 2 H), 7.11-7.20 (m,
[M + H]⁺

1 H), 6.79 (br s, 1 H), 4.76 (br dd, 1 H), 3.95 (br s, 1 H), 3.07-

3.27 (m, 5 H), 2.86 (br d, 1 H), 2.59-2.73 (m, 4 H), 2.39 (s, 3

H)

476
(CD₃OD) δ 8.32 (br s, 1 H), 8.11 (s, 1 H), 7.86 (d, 1 H), 7.69
501.50
99.5%

(s, 1 H), 7.49-7.54 (m, 1 H), 7.36-7.48 (m, 2 H), 7.16 (t, 1 H),
[M + H]⁺

6.79 (br s, 1 H), 4.75 (br dd, 1 H), 3.96 (br s, 1 H), 3.07-3.25

(m, 5 H), 2.80-2.93 (m, 1 H), 2.59-2.73 (m, 4 H), 2.38 (s, 3 H)

477
(CD₃OD) δ 8.28 (br s, 1 H), 8.09 (d, 1 H), 7.80 (d, 1 H), 7.65
504.40
100%

(s, 1 H), 7.44-7.53 (m, 1 H), 7.30-7.42 (m, 2 H), 7.07-7.18 (m,
[M + H]⁺

1 H), 6.75 (br s, 1 H), 4.81-4.85 (m, 0.5 H), 4.72 (dt, 1.5 H),

3.91 (br s, 1 H), 3.25 (br s, 1 H), 3.03-3.18 (m, 3.5 H), 2.82 (br

dd, 1 H), 1.81-2.17 (m, 4.5 H)

478
(CD₃OD) δ 8.28 (br s, 1 H), 8.09 (d, 1 H), 7.81 (d, 1 H), 7.65
504.30
99.6%

(s, 1 H), 7.45-7.50 (m, 1 H), 7.35-7.43 (m, 2 H), 7.08-7.16 (m,
[M + H]⁺

1 H), 6.75 (br s, 1 H), 4.81-4.86 (m, 0.4 H), 4.72 (dt, 1.6 H),

3.92 (br s, 1 H), 3.26 (br s, 1 H), 3.03-3.18 (m, 3.4 H), 2.82 (br

dd, 1 H), 1.88-2.13 (m, 4.6 H)

479
(CD₃OD) δ 8.30-8.52 (m, 1 H), 8.02-8.20 (m, 1 H), 7.72 (s, 1
431.1
100%

H), 7.60 (s, 0.3 H), 7.39-7.51 (m, 1 H), 7.24-7.37 (m, 1 H),
[M + H]⁺

7.11-7.24 (m, 1 H), 6.91 (s, 0.7 H), 5.33 (dd, 0.7 H), 5.11 (br

dd, 0.3 H), 3.97-4.06 (m, 3.7 H), 3.63-3.74 (m, 0.3 H), 3.16-

3.27 (m, 0.7 H), 2.97-3.08 (m, 0.3 H), 2.84-2.96 (m, 1 H),

2.49-2.68 (m, 3 H)

480
(CD₃OD) δ 8.18-8.42 (m, 1 H), 7.89-8.11 (m, 1 H), 7.60 (s, 1
431.1
100%

H), 7.48 (br s, 0.3 H), 7.25-7.39 (m, 1 H), 7.12-7.24 (m, 1 H),
[M + H]⁺

7.01-7.11 (m, 1 H), 6.79 (s, 0.7 H), 5.21 (dd, 0.7 H), 4.99 (br

dd, 0.3 H), 3.82-3.99 (m, 3.7 H), 3.50-3.65 (m, 0.3 H), 3.02-

3.16 (m, 0.7 H), 2.85-2.95 (m, 0.3 H), 2.71-2.84 (m, 1 H),

2.37-2.49 (m, 3 H)

481
(CD₃OD) δ 8.56-8.95 (m, 1 H), 8.23-8.45 (m, 1 H), 8.01-8.19
428.1
99.8%

(m, 1 H), 7.62-7.82 (m, 2 H), 7.56 (br s, 0.3 H), 7.39-7.49 (m,
[M + H]⁺

1 H), 7.24-7.36 (m, 1 H), 7.12-7.24 (m, 1 H), 6.94 (s, 0.7 H),

5.28 (dd, 0.7 H), 5.14 (br dd, 0.3 H), 3.99-4.14 (m, 0.7 H),

3.64-3.77 (m, 0.3 H), 3.20-3.31 (m, 0.7 H), 2.99-3.11 (m, 0.3

H), 2.83-2.98 (m, 1 H), 2.49-2.67 (m, 3 H)

482
(CD₃OD) δ 8.58-8.75 (m, 1 H), 8.11-8.29 (m, 1 H), 7.87-8.05
428.1
99.3%

(m, 1 H), 7.52-7.65 (m, 2 H), 7.44 (br s, 0.3 H), 7.27-7.39 (m,
[M + H]⁺

1 H), 7.12-7.24 (m, 1 H), 7.00-7.12 (m, 1 H), 6.82 (s, 0.7 H),

5.16 (dd, 0.7 H), 5.01 (dd, 0.3 H), 3.86-4.03 (m, 0.7 H), 3.50-

3.70 (m, 0.3 H), 3.07-3.18 (m, 0.7 H), 2.87-2.98 (m, 0.3 H),

2.72-2.86 (m, 1 H), 2.36-2.51 (m, 3 H)

483
(CD₃OD) δ 8.41 (s, 1 H), 7.86 (br s, 1 H), 7.69 (s, 1 H), 7.19-
372.0
99.8%

7.27 (m, 1 H), 7.13 (td, 1 H), 6.77 (br s, 1 H), 4.71 (br s, 1 H),
[M + H]⁺

3.58-4.13 (m, 1 H), 2.81-3.19 (m, 2 H)

484
(CD₃OD) δ 8.41 (s, 1 H), 7.86 (br s, 1 H), 7.69 (s, 1 H), 7.19-
372.0
98.0%

7.26 (m, 1 H), 7.13 (td, 1 H), 6.77 (br s, 1 H), 4.72 (br s, 1 H),
[M + H]⁺

3.99 (br s, 1 H), 3.10 (br s, 1 H), 2.88 (br d, 1 H)

485
(CD₃OD) δ 7.66-7.73 (m, 1 H), 7.08-7.28 (m, 2.3 H), 6.60-
436.1
100%

7.00 (m, 1.7 H), 5.10 (dd, 0.3 H), 4.77 (dd, 0.7 H), 4.09-4.15
[M + H]⁺

(m, 3 H), 3.90 (br t, 0.7 H), 3.51-3.62 (m, 0.3 H), 2.79-3.26

(m, 2 H)

486
(CD₃OD) δ 7.67-7.73 (m, 1 H), 7.06-7.30 (m, 2.3 H), 6.60-
436.1
98.5%

7.00 (m, 1.7 H), 5.10 (dd, 0.3 H), 4.77 (dd, 0.7 H), 4.10-4.15
[M + H]⁺

(m, 3 H), 3.81-3.98 (m, 0.7 H), 3.52-3.65 (m, 0.3 H), 2.79-

3.27 (m, 2 H)

487
(CD₃OD) δ 7.47-7.86 (m, 3 H), 7.08-7.30 (m, 2 H), 6.26-6.99
421.3
98.3%

(m, 2 H), 4.30 (br d, 1 H), 3.97 (br s, 1 H), 2.95-3.10 (m, 1 H),
[M + H]⁺

2.82 (br dd, 1 H)

488
(CD₃OD) δ 7.48-7.86 (m, 3 H), 7.06-7.30 (m, 2 H), 6.26-6.97
421.3
98.2%

(m, 2 H), 4.30 (br d, 1 H), 3.46-4.08 (m, 1 H), 2.95-3.11 (m, 1
[M + H]⁺

H), 2.82 (br dd, 1 H)

489
(CD₃OD) δ 7.75-7.87 (m, 1 H), 7.47-7.74 (m, 2 H), 7.38 (br d,
421.2
99.3%

1 H), 7.09 (br t, 1 H), 6.70-6.97 (m, 2 H), 4.29 (br d, 1 H),
[M + H]⁺

3.93 (br s, 1 H), 2.92-3.13 (m, 1 H), 2.81 (br d, 1 H)

490
(CD₃OD) δ 7.76-7.88 (m, 1 H), 7.46-7.74 (m, 2 H), 7.39 (br d,
421.2
98.9%

1 H), 7.09 (br t, 1 H), 6.70-6.99 (m, 2 H), 4.28 (br d, 1 H),
[M + H]⁺

3.93 (br s, 1 H), 2.94-3.12 (m, 1 H), 2.81 (br d, 1 H)

491
(CD₃OD) δ 8.45 (br s, 1 H), 8.18 (br s, 1 H), 7.56-7.73 (m, 1
417.3
100%

H), 7.43-7.54 (m, 2 H), 7.16-7.27 (m, 1 H), 6.88 (s, 1 H), 5.31
[M + H]⁺

(dd, 0.7 H), 5.08 (br dd, 0.3 H), 3.84-4.03 (m, 0.7 H), 3.60 (td,

4.2 Hz, 0.3H), 3.11-3.26 (m, 0.7 H), 2.95-3.07 (m, 0.3 H),

2.76-2.93 (m, 1 H), 2.38-2.49 (m, 3 H)

492
(CD₃OD) δ 8.34-8.53 (m, 1 H), 8.07-8.26 (m, 1 H), 7.57-7.72
417.3
99.2%

(m, 1 H), 7.42-7.54 (m, 2 H), 7.19-7.28 (m, 1 H), 6.89 (s, 1
[M + H]⁺

H), 5.31 (br dd, 0.7 H), 5.09 (br dd, 0.3 H), 3.88-3.99 (m, 0.7

H), 3.54-3.65 (m, 0.3 H), 3.13-3.25 (m, 0.7 H), 2.95-3.05 (m,

0.3 H), 2.80-2.93 (m, 1 H), 2.38-2.49 (m, 3 H)

493
(CD₃OD) δ 8.45 (s, 1 H), 7.97 (d, 1 H), 7.64-7.76 (m, 2 H),
454.20
91.7%

7.50-7.62 (m, 1 H), 6.93-7.26 (m, 1 H), 6.80 (br s, 1 H), 4.40-
[M + H]⁺

4.64 (m, 1 H), 3.45-4.13 (m, 1 H), 2.77-3.21 (m, 2 H)

494
(CD₃OD) δ 8.45 (s, 1 H), 7.97 (d, 1 H), 7.65-7.75 (m, 2 H),
454.20
87.4%

7.52-7.59 (m, 1 H), 6.94-7.26 (m, 1 H), 6.81 (br s, 1 H), 4.53
[M + H]⁺

(br s, 1 H), 3.52-4.08 (m, 1 H), 2.75-3.20 (m, 2 H)

495
(CD₃OD) δ 7.71 (s, 1 H), 7.48-7.58 (m, 1 H), 7.33-7.45 (m, 1
382.3
100%

H), 6.88-7.31 (m, 2 H), 5.08 (dd, 0.3 H), 4.70 (dd, 0.7 H),
[M + H]⁺

3.95-4.05 (m, 3 H), 3.83-3.94 (m, 0.7 H), 3.48 (td, 0.3 H),

2.94-3.25 (m, 1 H), 2.76-2.91 (m, 1 H), 2.29-2.44 (m, 3 H)

496
(CD₃OD) δ 7.71 (s, 1 H), 7.48-7.61 (m, 1 H), 7.32-7.45 (m, 1
382.2
99.5%

H), 6.81-7.30 (m, 2 H), 5.08 (br dd, 0.3 H), 4.70 (dd, 0.7 H),
[M + H]⁺

3.95-4.05 (m, 3 H), 3.81-3.95 (m, 0.7 H), 3.42-3.56 (m, 0.3

H), 2.93-3.25 (m, 1 H), 2.75-2.91 (m, 1 H), 2.29-2.45 (m, 3 H)

497
(CD₃OD) δ 7.70 (d, 1 H), 7.52 (t, 1 H), 7.32-7.42 (m, 1 H),
408.3
100%

7.18-7.31 (m, 1 H), 6.81-7.12 (m, 1 H), 5.09 (br dd, 0.4 H),
[M + H]⁺

4.67 (br dd, 0.6 H), 3.94-4.04 (m, 3 H), 3.55-3.91 (m, 1 H),

2.92-3.23 (m, 1 H), 2.75-2.90 (m, 1 H), 1.90-2.13 (m, 1 H),

0.50-1.09 (m, 4 H)

498
(CD₃OD) δ 7.70 (d, 1 H), 7.52 (t, 1 H), 7.34-7.42 (m, 1 H),
408.3
98.9%

7.19-7.29 (m, 1 H), 6.86-7.06 (m, 1 H), 5.09 (br dd, 0.4 H),
[M + H]⁺

4.67 (br dd, 0.6 H), 3.94-4.04 (m, 3 H), 3.56-3.92 (m, 1 H),

2.93-3.22 (m, 1 H), 2.73-2.91 (m, 1 H), 1.91-2.10 (m, 1 H),

0.55-1.09 (m, 4 H)

499
(CD₃OD) δ 7.70 (s, 1 H), 6.95-7.39 (m, 3 H), 6.61-6.82 (m, 1
476.3
98.2%

H), 4.59 (br d, 1 H), 3.61-4.05 (m, 1 H), 2.97-3.23 (m, 1 H),
[M + H]⁺

2.89 (br d, 1 H), 2.47 (s, 3 H), 1.54-1.75 (m, 6 H)

500
(CD₃OD) δ 7.70 (s, 1 H), 6.94-7.39 (m, 3 H), 6.77 (br s, 1 H),
476.3
97.8%

4.59 (br d, 1 H), 3.62-4.07 (m, 1 H), 3.00-3.26 (m, 1 H), 2.89
[M + H]⁺

(br d, 1 H), 2.47 (s, 3 H), 1.50-1.76 (m, 6 H)

501
(CD₃OD) δ 8.46 (br s, 1 H), 7.70 (s, 1 H), 6.97-7.36 (m, 3 H),
418.2
99.1%

6.78 (br s, 1 H), 4.55 (br s, 1 H), 3.58-4.11 (m, 1 H), 3.11 (br
[M + H]⁺

s, 1 H), 2.87 (br d, 1 H), 2.46 (s, 3 H)

502
(CD₃OD) δ 8.46 (br s, 1 H), 7.70 (s, 1 H), 6.98-7.36 (m, 3 H),
418.2
98.5%

6.78 (br s, 1 H), 4.56 (br d, 1 H), 3.57-4.05 (m, 1 H), 3.11 (br
[M + H]⁺

s, 1 H), 2.87 (br d, 1 H), 2.46 (s, 3 H)

503
(DMSO-d₆) δ 12.19 (s, 1 H), 8.36 (s, 1 H), 8.23 (s, 1 H), 7.80
488.4
100%

(d, 1 H), 7.41-7.69 (m, 4 H), 7.24-7.33 (m, 1 H), 6.51 (s, 1 H),
[M + H]⁺

4.61 (br d, 1 H), 3.94 (br s, 1 H), 3.73-3.78 (m, 4 H), 3.12 (br

d, 5 H), 2.81 (br d, 1 H)

504
(DMSO-d₆) δ 12.19 (s, 1 H), 8.36 (s, 1 H), 8.23 (s, 1 H), 7.80
488.4
100%

(d, 1 H), 7.40-7.71 (m, 4 H), 7.24-7.32 (m, 1 H), 6.51 (s, 1 H),
[M + H]⁺

4.61 (br d, 1 H), 3.94 (br s, 1 H), 3.72-3.80 (m, 4 H), 3.08-

3.15 (m, 5 H), 2.81 (br d, 1 H)

505
(CD₃OD) δ 8.33 (br s, 1 H), 8.12 (d, 1 H), 7.85 (d, 1 H), 7.70
512.3
98.8%

(s, 1 H), 7.39-7.55 (m, 3 H), 7.13-7.20 (m, 1 H), 6.80 (s, 1 H),
[M + H]⁺

4.76 (br dd, 1 H), 3.95 (br s, 1 H), 3.08-3.26 (m, 5 H), 2.87 (br

dd, 1 H), 1.57-1.63 (m, 4 H), 0.41 (s, 4 H)

506
(CD₃OD) δ 8.32 (br s, 1 H), 8.12 (d, 1 H), 7.85 (d, 1 H), 7.70
512.3
99.3%

(s, 1 H), 7.39-7.55 (m, 3 H), 7.12-7.23 (m, 1 H), 6.80 (s, 1 H),
[M + H]⁺

4.76 (br dd, 1 H), 3.95 (br s, 1 H), 3.07-3.27 (m, 5 H), 2.87 (br

dd, 1 H), 1.57-1.65 (m, 4 H), 0.41 (s, 4 H)

507
(CD₃OD) δ 8.32 (br s, 1 H), 8.09 (s, 1 H), 7.84 (d, 1 H), 7.76
544.4
99.3%

(s, 1 H), 7.49-7.58 (m, 1 H), 7.39-7.48 (m, 2 H), 7.16 (t, 1 H),
[M + H]⁺

6.81 (s, 1 H), 4.76 (br dd, 1 H), 3.93 (br s, 1 H), 3.73 (br d, 2

H), 3.05-3.20 (m, 1 H), 2.80-2.96 (m, 1 H), 2.65 (br t, 2 H),

1.94 (br d, 2 H), 1.42-1.61 (m, 3 H), 1.21 (s, 6 H)

508
(CD₃OD) δ 8.32 (br s, 1 H), 8.10 (s, 1 H), 7.85 (d, 1 H), 7.71
544.4
98.6%

(s, 1 H), 7.50-7.59 (m, 1 H), 7.38-7.49 (m, 2 H), 7.12-7.21 (m,
[M + H]⁺

1 H), 6.80 (s, 1 H), 4.76 (br dd, 1 H), 3.86-4.05 (m, 1 H), 3.74

(br d, 2 H), 3.13 (br s, 1 H), 2.81-2.90 (m, 1 H), 2.59-2.71 (m,

2 H), 1.94 (br d, 2 H), 1.39-1.62 (m, 3 H), 1.21 (s, 6 H)

509
(CD₃OD) δ 8.40 (s, 1 H), 7.76-7.99 (m, 1 H), 7.67 (s, 1 H),
350.3
99.6%

7.42 (d, 1 H), 7.27 (t, 1 H), 7.16 (br d, 1 H), 6.77 (br s, 1 H),
[M + H]⁺

4.57-4.77 (m, 1 H), 3.52-4.20 (m, 1 H), 3.09 (br s, 1 H), 2.86

(br d, 1 H), 2.55 (s, 3 H)

510
(CD₃OD) δ 8.42 (s, 1 H), 7.75-8.13 (m, 1 H), 7.70 (s, 1 H),
350.2
99.7%

7.44 (d, 1 H), 7.29 (t, 1 H), 7.18 (br d, 1 H), 6.79 (br s, 1 H),
[M + H]⁺

4.71 (br s, 1 H), 3.52-4.25 (m, 1 H), 3.11 (br s, 1 H), 2.88 (br

d, 1 H), 2.57 (s, 3 H)

511
(CD₃OD) δ 7.75 (br s, 1 H), 7.67 (s, 1 H), 7.42 (d, 1 H), 7.28
408.3
98.5%

(t, 1 H), 7.17 (br d, 1 H), 6.76 (br s, 1 H), 4.62 (s, 1 H), 3.53-
[M + H]⁺

4.08 (m, 1 H), 3.13 (br s, 1 H), 2.87 (br d, 1 H), 2.56 (s, 3 H),

1.64 (br s, 6 H)

512
(CD₃OD) δ 7.61-7.91 (m, 2 H), 7.42 (d, 1 H), 7.28 (t, 1 H),
408.3
85.5%

7.17 (br d, 1 H), 6.76 (br s, 1 H), 4.72 (br s, 1 H), 3.55-4.15
[M + H]⁺

(m, 1 H), 3.13 (br s, 1 H), 2.87 (br d, 1 H), 2.56 (s, 3 H), 1.64

(br s, 6 H)

513
(CD₃OD) δ 7.46-7.87 (m, 4 H), 7.28-7.42 (m, 1 H), 6.85 (br d,
421.2
99.1%

1.8 H), 6.33 (br s, 0.2 H), 4.29 (br d, 1 H), 3.43-4.07 (m, 1 H),
[M + H]⁺

2.91-3.14 (m, 1 H), 2.81 (br dd, 1 H)

514
(CD₃OD) δ 7.45-7.89 (m, 4 H), 7.34 (dt, 1 H), 6.85 (br d, 1.8
421.2
99.1%

H), 6.33 (br s, 0.2 H), 4.29 (br d, 1 H), 3.43-4.04 (m, 1 H),
[M + H]⁺

2.97-3.10 (m, 1 H), 2.81 (br dd, 1 H)

515
(CD₃OD) δ 8.32-8.47 (m, 1 H), 7.95-8.17 (m, 1 H), 7.71 (s, 1
453.3
96.5%

H), 7.25-7.64 (m, 2.4 H), 6.88 (br s, 0.6 H), 5.34 (dd, 0.7 H),
[M + H]⁺

5.11 (br dd, 0.3 H), 3.93-4.09 (m, 3.7 H), 3.66 (br s, 0.3 H),

2.80-3.24 (m, 2 H)

516
(CD₃OD) δ 8.32-8.45 (m, 1 H), 7.99-8.19 (m, 1 H), 7.66-7.75
453.3
97.8%

(m, 1 H), 7.19-7.63 (m, 2.4 H), 6.89 (br s, 0.6 H), 5.34 (dd, 0.7
[M + H]⁺

H), 5.11 (br dd, 0.3 H), 3.91-4.05 (m, 3.8 H), 3.66 (br s, 0.2

H), 2.83-3.22 (m, 2 H)

517
(CD₃OD) δ 8.36-8.42 (m, 1 H), 8.05-8.12 (m, 1 H), 7.44-7.80
453.30
93.8%

(m, 1.4 H), 7.08-7.28 (m, 2 H), 6.88 (br s, 0.6 H), 5.09-5.38
[M + H]⁺

(m, 1 H), 3.69-4.03 (m, 4 H), 2.88-3.24 (m, 2 H)

518
(CD₃OD) δ 8.36-8.43 (m, 1 H), 8.05-8.13 (m, 1 H), 7.45-7.76
453.40
96.3%

(m, 1.3 H), 7.07-7.29 (m, 2 H), 6.90 (br s, 0.7 H), 5.09-5.39
[M + H]⁺

(m, 1 H), 3.69-4.03 (m, 4 H), 2.87-3.24 (m, 2 H)

519
(CD₃OD) δ 8.70-8.81 (m, 1 H), 8.26-8.35 (m, 1 H), 8.03-8.13
450.20
97.0%

(m, 1 H), 7.49-7.75 (m, 2.3 H), 7.08-7.28 (m, 2 H), 6.93 (br s,
[M + H]⁺

0.7 H), 5.11-5.35 (m, 1 H), 3.69-4.10 (m, 1 H), 2.89-3.25 (m,

2 H)

520
(CD₃OD) δ 8.72-8.80 (m, 1 H), 8.26-8.34 (m, 1 H), 8.03-8.12
450.30
96.5%

(m, 1 H), 7.51-7.73 (m, 2.3 H), 7.09-7.28 (m, 2 H), 6.93 (s, 0.7
[M + H]⁺

H), 5.11-5.35 (m, 1 H), 3.70-4.08 (m, 1 H), 3.12-3.28 (m, 1

H), 2.85-2.97 (m, 1 H)

521
(CD₃OD) δ 8.34-8.42 (m, 1 H), 8.03-8.12 (m, 1 H), 7.67-7.75
453.2
98.3%

(m, 1 H), 7.57 (s, 0.3 H), 7.31-7.42 (m, 1 H), 7.00-7.11 (m, 1
[M + H]⁺

H), 6.86 (s, 0.7 H), 5.33 (dd, 0.7 H), 5.10 (br dd, 0.3 H), 3.98-

4.04 (m, 3 H), 3.86-3.97 (m, 0.6 H), 3.56-3.72 (m, 0.4 H),

3.10-3.26 (m, 0.8 H), 2.94-3.04 (m, 0.2 H), 2.81-2.93 (m, 1 H)

522
(CD₃OD) δ 8.35-8.42 (m, 1 H), 8.03-8.12 (m, 1 H), 7.66-7.74
453.3
99.1%

(m, 1 H), 7.57 (s, 0.3 H), 7.31-7.44 (m, 1 H), 6.98-7.12 (m, 1
[M + H]⁺

H), 6.86 (s, 0.7 H), 5.33 (dd, 0.7 H), 5.10 (dd, 0.3 H), 3.91-

4.02 (m, 3.8 H), 3.61-3.70 (m, 0.2 H), 3.13-3.25 (m, 0.7 H),

2.94-3.05 (m, 0.3 H), 2.80-2.93 (m, 1 H)

523
(CD₃OD) δ 8.72-8.81 (m, 1 H), 8.25-8.34 (m, 1 H), 8.01-8.13
450.2
100%

(m, 1 H), 7.60-7.75 (m, 2 H), 7.53 (br s, 0.3 H), 7.33-7.45 (m,
[M + H]⁺

1 H), 6.99-7.12 (m, 1 H), 6.89 (s, 0.7 H), 5.28 (dd, 0.7 H),

5.13 (br dd, 0.3 H), 3.99 (br t, 0.7 H), 3.58-3.76 (m, 0.3 H),

3.16-3.28 (m, 0.7 H), 2.97-3.07 (m, 0.3 H), 2.82-2.95 (m, 1 H)

524
(CD₃OD) δ 8.70-8.81 (m, 1 H), 8.25-8.34 (m, 1 H), 8.02-8.13
450.2
97.6%

(m, 1 H), 7.61-7.75 (m, 2 H), 7.52 (br s, 0.3 H), 7.33-7.44 (m,
[M + H]⁺

1 H), 7.01-7.13 (m, 1 H), 6.89 (br s, 0.7 H), 5.28 (br dd, 0.7

H), 5.13 (br dd, 0.3 H), 3.99 (br t, 0.7 H), 3.69 (br s, 0.3 H),

3.17-3.27 (m, 0.7 H), 2.97-3.07 (m, 0.3 H), 2.81-2.95 (m, 1 H)

525
(CD₃OD) δ 9.38 (br s, 0.7 H), 9.07 (br d, 1.3 H), 8.10-8.40
482.2
99.2%

(m, 1 H), 7.71 (br d, 2 H), 7.45 (br d, 1 H), 7.05-7.40 (m, 2 H),
[M + H]⁺

6.82 (br s, 1 H), 5.03 (br s, 0.3 H), 4.73 (br d, 0.7 H), 4.02 (br

s, 0.7 H), 3.72 (br s, 0.3 H), 3.21-3.31 (m, 0.7 H), 3.04 (br s,

0.3 H), 2.92 (br d, 1 H)

526
(CD₃OD) δ 9.39 (br s, 0.7 H), 9.07 (br s, 1.3 H), 8.08-8.46 (m,
482.2
98.1%

1 H), 7.72 (br d, 2 H), 7.45 (br d, 1 H), 7.04-7.41 (m, 2 H),
[M + H]⁺

6.82 (br s, 1 H), 5.03 (br s, 0.3 H), 4.73 (br d, 0.7 H), 3.88-

4.12 (m, 0.7 H), 3.72 (br s, 0.3 H), 3.20-3.30 (m, 0.6 H), 2.99-

3.12 (m, 0.4 H), 2.81-2.99 (m, 1 H)

527
(CD₃OD) δ 9.29-9.54 (m, 1 H), 8.45-8.89 (m, 2 H), 7.59-7.79
482.3
99.5%

(m, 2 H), 7.07-7.51 (m, 3 H), 6.81 (br s, 1 H), 5.01 (br s, 0.3
[M + H]⁺

H), 4.75 (br d, 0.7 H), 3.67-4.11 (m, 1 H), 2.98-3.29 (m, 1 H),

2.92 (br d, 1 H)

528
(CD₃OD) δ 9.31-9.51 (m, 1 H), 8.41-8.89 (m, 2 H), 7.58-7.77
482.2
90.2%

(m, 2 H), 7.05-7.52 (m, 3 H), 6.81 (s, 1 H), 5.00 (br s, 0.4 H),
[M + H]⁺

4.75 (br d, 0.6 H), 3.65-4.11 (m, 1 H), 2.99-3.30 (m, 1 H),

2.92 (br d, 1 H)

529
(CD₃OD) δ 7.67-7.79 (m, 2 H), 7.38-7.53 (m, 2 H), 6.93-7.31
528.3
98.7%

(m, 1 H), 6.81 (br s, 1 H), 4.93-5.05 (m, 0.4 H), 4.57 (br s, 0.6
[M + H]⁺

H), 3.52-4.10 (m, 1 H), 2.97-3.26 (m, 1 H), 2.90 (br d, 1 H),

1.50-1.82 (m, 6 H)

530
(CD₃OD) δ 7.68-7.79 (m, 2 H), 7.39-7.55 (m, 2 H), 6.93-7.31
528.3
97.8%

(m, 1 H), 6.82 (br s, 1 H), 4.94-5.07 (m, 0.3 H), 4.59 (br d,
[M + H]⁺

0.7 H), 3.54-4.07 (m, 1 H), 2.98-3.24 (m, 1 H), 2.90 (br d, 1

H), 1.43-1.77 (m, 6 H)

531
(CD₃OD) δ 8.36-8.54 (m, 1 H), 7.69-7.76 (m, 2 H), 7.38-7.55
470.3
81.4%

(m, 2 H), 6.97-7.29 (m, 1 H), 6.83 (br s, 1 H), 4.59 (br d, 1 H),
[M + H]⁺

3.53-4.07 (m, 1 H), 3.15 (br s, 1 H), 2.88 (br d, 1 H)

532
(CD₃OD) δ 8.47 (br s, 1 H), 7.68-7.76 (m, 2 H), 7.39-7.52 (m,
470.3
85.3%

2 H), 6.97-7.33 (m, 1 H), 6.82 (br s, 1 H), 4.55 (br s, 1 H),
[M + H]⁺

3.51-4.11 (m, 1 H), 3.12 (br s, 1 H), 2.89 (br d, 1 H)

533
(CD₃OD) δ 7.63-7.84 (m, 2 H), 7.51 (t, 1 H), 7.36 (br d, 1 H),
528.2
98.0%

6.95-7.31 (m, 1 H), 6.79 (br s, 1 H), 4.94-5.09 (m, 0.4 H), 4.62
[M + H]⁺

(br s, 0.6 H), 3.54-4.14 (m, 1 H), 2.97-3.26 (m, 1 H), 2.90 (br

d, 1 H), 1.48-1.79 (m, 6 H)

534
(CD₃OD) δ 7.63-7.82 (m, 2 H), 7.52 (t, 1 H), 7.36 (d, 1 H),
528.2
98.3%

6.97-7.31 (m, 1 H), 6.78 (br s, 1 H), 4.94-5.06 (m, 0.4 H), 4.60
[M + H]⁺

(br d, 0.6 H), 3.57-4.13 (m, 1 H), 2.98-3.30 (m, 1 H), 2.90 (br

d, 1 H), 1.49-1.75 (m, 6 H)

535
(CD₃OD) δ 8.47 (br s, 1 H), 7.66-7.79 (m, 2 H), 7.51 (t, 1 H),
470.1
97.3%

7.35 (d, 1 H), 6.97-7.30 (m, 1 H), 6.80 (br s, 1 H), 4.95-5.10
[M + H]⁺

(m, 0.2 H), 4.57 (br s, 0.8 H), 3.54-4.14 (m, 1 H), 3.12 (br s, 1

H), 2.88 (br d, 1 H)

536
(CD₃OD) δ 8.47 (br s, 1 H), 7.66-7.81 (m, 2 H), 7.51 (t, 1 H),
470.2
92.2%

7.36 (br d, 1 H), 6.97-7.31 (m, 1 H), 6.80 (br s, 1 H), 4.94-
[M + H]⁺

5.13 (m, 0.2 H), 4.58 (br d, 0.8 H), 3.54-4.15 (m, 1 H), 3.12

(br s, 1 H), 2.88 (br d, 1 H)

537
(CD₃OD) δ 8.32-8.49 (m, 2 H), 7.87 (d, 1 H), 7.67 (s, 1 H),
417.40
99.5%

7.48-7.53 (m, 1 H), 7.41 (td, 1 H), 7.33 (d, 1 H), 7.11-7.18 (m,
[M + H]⁺

1 H), 6.77 (br s, 1 H), 4.72 (br dd, 1 H), 3.94 (br s, 1 H), 3.05-

3.18 (m, 1 H), 2.84 (br dd, 1 H), 2.39 (s, 3 H)

538
(CD₃OD) δ 8.32-8.49 (m, 2 H), 7.87 (d, 1 H), 7.67 (s, 1 H),
417.40
98.3%

7.47-7.53 (m, 1 H), 7.41 (td, 1 H), 7.33 (d, 1 H), 7.14 (t, 1 H),
[M + H]⁺

6.77 (br s, 1 H), 4.72 (br dd, 1 H), 3.94 (br s, 1 H), 3.04-3.18

(m, 1 H), 2.84 (br d, 1 H), 2.39 (s, 3 H)

539
(CD₃OD) δ 8.28-8.36 (m, 2 H), 7.86 (d, 1 H), 7.67 (s, 1 H),
433.30
97.9%

7.47-7.52 (m, 1 H), 7.41 (td, 1 H), 7.23 (dd, 1 H), 7.10-7.18
[M + H]⁺

(m, 1 H), 6.77 (br s, 1 H), 4.74 (br dd, 1 H), 3.89 (s, 4 H),

3.06-3.17 (m, 1 H), 2.84 (br dd, 1 H)

540
(CD₃OD) δ 8.27-8.37 (m, 2 H), 7.86 (d, 1 H), 7.67 (s, 1 H),
433.30
97.2%

7.47-7.52 (m, 1 H), 7.40 (td, 1 H), 7.22 (dd, 1 H), 7.10-7.17
[M + H]⁺

(m, 1 H), 6.77 (s, 1 H), 4.73 (br dd, 1 H), 3.88 (s, 4 H), 3.06-

3.17 (m, 1 H), 2.84 (br dd, 1 H)

541
(CD₃OD) δ 8.88 (s, 1 H), 8.42 (br s, 1 H), 8.10 (s, 1 H), 7.90-
483.4
100%

8.03 (m, 2 H), 7.63-7.77 (m, 2 H), 7.50-7.57 (m, 1 H), 7.43
[M + H]⁺

(td, 1 H), 7.10-7.22 (m, 1 H), 6.81 (s, 1 H), 4.69-4.80 (m, 1

H), 3.97 (s, 4 H), 3.07-3.20 (m, 1 H), 2.87 (br dd, 1 H)

542
(CD₃OD) δ 8.89 (s, 1 H), 8.43 (br s, 1 H), 8.11 (s, 1 H), 7.92-
483.5
99.8%

8.04 (m, 2 H), 7.64-7.77 (m, 2 H), 7.50-7.56 (m, 1 H), 7.43
[M + H]⁺

(td, 1 H), 7.09-7.23 (m, 1 H), 6.81 (br s, 1 H), 4.76 (br d, 1 H),

3.97 (s, 4 H), 3.07-3.22 (m, 1 H), 2.80-2.94 (m, 1 H)

543
(CD₃OD) δ 9.35 (s, 1 H), 8.70 (br d, 1 H), 8.53 (br s, 1 H),
480.3
100%

8.05-8.21 (m, 2 H), 7.91-8.04 (m, 2 H), 7.72 (s, 1 H), 7.54 (d,
[M + H]⁺

1 H), 7.39-7.49 (m, 2 H), 7.12-7.27 (m, 1 H), 6.83 (br s, 1 H),

4.72-4.83 (m, 1 H), 3.79-4.19 (m, 1 H), 3.06-3.23 (m, 1 H),

2.89 (br d, 1 H)

544
(CD₃OD) δ 9.35 (s, 1 H), 8.70 (br d, 1 H), 8.53 (br s, 1 H),
480.3
100%

8.07-8.21 (m, 2 H), 7.91-8.06 (m, 2 H), 7.75 (s, 1 H), 7.52-
[M + H]⁺

7.63 (m, 1 H), 7.38-7.50 (m, 2 H), 7.18 (t, 1 H), 6.84 (br s, 1

H), 4.78 (br d, 1 H), 4.02 (s, 1 H), 3.16 (br s, 1 H), 2.89 (br d,

1 H)

545
(CD₃OD) δ 8.71-8.81 (m, 1 H), 8.24-8.35 (m, 1 H), 8.02-8.13
450.3
100%

(m, 1 H), 7.69-7.76 (m, 1 H), 7.61-7.69 (m, 1 H), 7.43-7.58
[M + H]⁺

(m, 1.4 H), 7.25-7.39 (m, 1 H), 6.92 (s, 0.6 H), 5.28 (dd, 0.7

H), 5.13 (dd, 0.3 H), 3.93-4.05 (m, 0.7 H), 3.69 (td, 0.3 H),

2.87-3.25 (m, 2 H)

546
(CD₃OD) δ 8.72-8.81 (m, 1 H), 8.24-8.36 (m, 1 H), 8.03-8.14
450.2
98.5%

(m, 1 H), 7.69-7.75 (m, 1 H), 7.61-7.68 (m, 1 H), 7.43-7.57
[M + H]⁺

(m, 1.3 H), 7.27-7.41 (m, 1 H), 6.92 (s, 0.7 H), 5.28 (dd, 0.7

H), 5.13 (dd, 0.3 H), 3.95-4.05 (m, 0.7 H), 3.64-3.75 (m, 0.3

H), 2.84-3.25 (m, 2 H)

547
(CD₃OD) δ 8.31 (s, 1 H), 7.75 (br s, 1 H), 7.53-7.60 (m, 3 H),
336.2
99.3%

7.26-7.34 (m, 2 H), 6.68 (br s, 1 H), 4.59 (br s, 1 H), 3.83 (br
[M + H]⁺

s, 1 H), 2.99 (br s, 1 H), 2.76 (br d, 1 H)

548
(CD₃OD) δ 8.43 (s, 1 H), 7.87 (br s, 1 H), 7.65-7.72 (m, 3 H),
336.2
99.1%

7.39-7.45 (m, 2 H), 6.80 (br s, 1 H), 4.71 (br s, 1 H), 3.96 (br
[M + H]⁺

s, 1 H), 3.13 (br d, 1 H), 2.88 (br d, 1 H)

549
(CD₃OD) δ 7.69 (s, 1 H), 7.45-7.56 (m, 1 H), 7.14-7.24 (m,
430.2
100%

1.3 H), 6.62-7.08 (m, 2.7 H), 5.07 (dd, 0.3 H), 4.73 (dd, 0.7
[M + H]⁺

H), 4.07-4.14 (m, 3 H), 3.80-3.90 (m, 3.7 H), 3.47 (td, 0.3 H),

2.92-3.28 (m, 1 H), 2.76-2.89 (m, 1 H)

550
(CD₃OD) δ 7.69 (s, 1 H), 7.42-7.58 (m, 1 H), 7.12-7.24 (m,
430.2
99.1%

1.3 H), 6.62-7.06 (m, 2.7 H), 5.07 (dd, 0.3 H), 4.73 (dd, 0.7
[M + H]⁺

H), 4.06-4.16 (m, 3 H), 3.80-3.92 (m, 3.7 H), 3.47 (td, 0.3 H),

3.14-3.26 (m, 0.7 H), 2.76-3.05 (m, 1.3 H)

551
(CD₃OD) δ 7.43-7.95 (m, 4 H), 7.19 (br s, 1 H), 7.01 (dd, 1
415.2
97.1%

H), 6.20-6.91 (m, 2 H), 4.92-4.99 (m, 0.3 H), 4.28 (br d, 0.7
[M + H]⁺

H), 3.46-3.99 (m, 4 H), 2.95-3.11 (m, 1 H), 2.74-2.87 (m, 1 H)

552
(CD₃OD) δ 7.60-7.92 (m, 4 H), 7.21 (br s, 1 H), 6.11-7.09 (m,
415.3
96.1%

3 H), 4.94-5.07 (m, 0.3 H), 4.30 (br d, 0.7 H), 3.47-4.04 (m, 4
[M + H]⁺

H), 2.99-3.11 (m, 1 H), 2.82 (br d, 1 H)

553
(CD₃OD) δ 8.32-8.45 (m, 1 H), 8.02-8.17 (m, 1 H), 7.72 (s, 1
447.3
100%

H), 7.45-7.64 (m, 1 H), 7.14-7.23 (m, 1 H), 6.95-7.08 (m, 1
[M + H]⁺

H), 6.88 (s, 1 H), 5.04-5.36 (m, 1 H), 3.90-4.04 (m, 3.8 H),

3.81-3.87 (m, 3 H), 3.56-3.67 (m, 0.2 H), 2.96-3.25 (m, 1 H),

2.80-2.94 (m, 1 H)

554
(CD₃OD) δ 8.27-8.47 (m, 1 H), 8.01-8.18 (m, 1 H), 7.72 (s, 1
447.3
99.5%

H), 7.42-7.63 (m, 1 H), 7.13-7.24 (m, 1 H), 6.96-7.05 (m, 1
[M + H]⁺

H), 6.88 (s, 1 H), 5.04-5.38 (m, 1 H), 3.89-4.04 (m, 3.8 H),

3.76-3.88 (m, 3 H), 3.51-3.66 (m, 0.2 H), 2.95-3.26 (m, 1 H),

2.79-2.93 (m, 1 H)

555
(CD₃OD) δ 8.74-8.81 (m, 1 H), 8.27-8.35 (m, 1 H), 8.05-8.13
444.2
100%

(m, 1 H), 7.64-7.75 (m, 2 H), 7.42-7.59 (m, 1 H), 7.13-7.25
[M + H]⁺

(m, 1 H), 6.96-7.06 (m, 1 H), 6.91 (s, 1 H), 5.04-5.34 (m, 1

H), 3.92-4.04 (m, 0.7 H), 3.77-3.90 (m, 3 H), 3.57-3.69 (m,

0.3 H), 2.97-3.29 (m, 1 H), 2.82-2.96 (m, 1 H)

556
(CD₃OD) δ 8.73-8.82 (m, 1 H), 8.25-8.35 (m, 1 H), 7.99-8.19
444.2
94.9%

(m, 1 H), 7.63-7.78 (m, 2 H), 7.43-7.59 (m, 1 H), 7.11-7.24
[M + H]⁺

(m, 1 H), 6.96-7.06 (m, 1 H), 6.91 (s, 1 H), 5.06-5.34 (m, 1

H), 3.93-4.05 (m, 0.7 H), 3.76-3.89 (m, 3 H), 3.64 (td, 0.3 H),

2.99-3.28 (m, 1 H), 2.85-2.95 (m, 1 H)

557
(CD₃OD) δ 7.59-7.77 (m, 2 H), 7.43 (dd, 1 H), 7.21 (td, 1 H),
452.3
98.4%

6.69 (br s, 1 H), 4.62 (br s, 1 H), 3.53-4.09 (m, 1 H), 3.12 (br
[M + H]⁺

s, 1 H), 2.85 (br d, 1 H), 2.31-2.47 (m, 1 H), 1.39-1.73 (m, 6

H), 0.92-1.04 (m, 4 H)

558
(CD₃OD) δ 7.64-7.72 (m, 2 H), 7.43 (dd, 1 H), 7.21 (td, 1 H),
452.4
96.6%

6.69 (br s, 1 H), 4.65 (br s, 1 H), 3.94 (br d, 1 H), 3.12 (br s, 1
[M + H]⁺

H), 2.85 (br d, 1 H), 2.31-2.51 (m, 1 H), 1.58 (br s, 6 H), 0.92-

1.04 (m, 4 H)

559
(CD₃OD) δ 8.63-8.91 (m, 2 H), 8.11 (br s, 2 H), 7.51-7.82 (m,
481.3
96.5%

2 H), 7.02-7.48 (m, 3 H), 6.86 (s, 1 H), 4.97 (br s, 0.5 H), 4.73
[M + H]⁺

(br d, 0.5 H), 3.74-4.13 (m, 1 H), 3.03-3.30 (m, 1 H), 2.80-

3.01 (m, 1 H)

560
(CD₃OD) δ 8.67-8.85 (m, 2 H), 8.11 (br s, 2 H), 7.51-7.78 (m,
481.4
98.1%

2 H), 7.03-7.48 (m, 3 H), 6.85 (s, 1 H), 4.97 (br s, 0.4 H), 4.73
[M + H]⁺

(br d, 0.6 H), 3.72-4.15 (m, 1 H), 3.03-3.30 (m, 1 H), 2.97 (br

d, 1 H)

561
(CD₃OD) δ 7.58-7.74 (m, 3 H), 7.33-7.46 (m, 2 H), 6.60-7.22
400.3
98.5%

(m, 2 H), 5.08 (dd, 0.3 H), 4.75 (dd, 0.7 H), 4.07-4.15 (m, 3
[M + H]⁺

H), 3.81-3.92 (m, 0.7 H), 3.49 (td, 0.3 H), 3.15-3.26 (m, 0.7

H), 2.94-3.04 (m, 0.3 H), 2.76-2.90 (m, 1 H)

562
(CD₃OD) δ 7.57-7.84 (m, 3 H), 7.30-7.52 (m, 2 H), 6.60-7.25
400.3
95.3%

(m, 2 H), 5.10 (br dd, 0.3 H), 4.76 (dd, 0.7 H), 4.07-4.19 (m, 3
[M + H]⁺

H), 3.79-3.95 (m, 0.7 H), 3.44-3.56 (m, 0.3 H), 3.05-3.28 (m,

1 H), 2.74-2.95 (m, 1 H)

563
(CD₃OD) δ 7.60-7.86 (m, 5 H), 7.34-7.54 (m, 2 H), 6.86 (br s,
385.3
96.0%

2 H), 3.82-4.62 (m, 1.5 H), 3.48 (br s, 0.2 H), 2.93-3.10 (m, 1
[M + H]⁺

H), 2.81 (br d, 1 H)

564
(CD₃OD) δ 7.49-7.86 (m, 5 H), 7.41 (quin, 2 H), 6.86 (br s, 2
385.3
98.5%

H), 4.91-5.01 (m, 0.5 H), 3.47-4.64 (m, 1.7 H), 2.97-3.09 (m,
[M + H]⁺

1 H), 2.81 (br d, 1 H)

565
(CD₃OD) δ 8.33-8.44 (m, 1 H), 8.02-8.13 (m, 1 H), 7.71 (s, 1
431.1
99.4%

H), 7.58 (br s, 0.3 H), 7.41-7.52 (m, 1 H), 7.15-7.32 (m, 2 H),
[M + H]⁺

6.90 (s, 0.7 H), 5.32 (dd, 0.7 H), 5.10 (br dd, 0.3 H), 3.92-4.04

(m, 3.8 H), 3.62 (br t, 0.2 H), 3.10-3.26 (m, 0.8 H), 2.96-3.06

(m, 0.3 H), 2.53 (br s, 1 H), 2.45-2.60 (m, 3 H)

566
(CD₃OD) δ 8.32-8.43 (m, 1 H), 8.03-8.13 (m, 1 H), 7.71 (s, 1
431.1
98.4%

H), 7.57 (br s, 0.3 H), 7.43-7.52 (m, 1 H), 7.15-7.31 (m, 2 H),
[M + H]⁺

6.90 (s, 0.7 H), 5.32 (dd, 0.7 H), 5.10 (br dd, 0.3 H), 3.93-4.02

(m, 3.8H), 3.61 (br d, 0.3 H), 3.11-3.26 (m, 0.8 H), 2.99 (br d,

0.2 H), 2.90 (br d, 1 H), 2.48-2.59 (m, 3 H)

567
(CD₃OD) δ 8.67-8.86 (m, 1 H), 8.22-8.36 (m, 1 H), 8.01-8.14
428.4
100%

(m, 1 H), 7.60-7.77 (m, 2 H), 7.41-7.56 (m, 1 H), 7.15-7.32
[M + H]⁺

(m, 2 H), 6.93 (s, 1 H), 5.26 (dd, 0.7 H), 5.12 (dd, 0.3 H),

3.93-4.06 (m, 0.7 H), 3.58-3.75 (m, 0.3 H), 3.17-3.29 (m, 0.7

H), 2.97-3.08 (m, 0.3 H), 2.81-2.95 (m, 1 H), 2.47-2.59 (m, 3

H)

568
(CD₃OD) δ 8.70-8.81 (m, 1 H), 8.19-8.35 (m, 1 H), 8.00-8.14
428.4
100%

(m, 1 H), 7.60-7.75 (m, 2 H), 7.41-7.57 (m, 1 H), 7.14-7.32
[M + H]⁺

(m, 2 H), 6.86-6.97 (m, 1 H), 5.26 (dd, 0.7 H), 5.04-5.16 (m,

0.3 H), 3.90-4.08 (m, 0.7 H), 3.57-3.74 (m, 0.3 H), 2.99-3.27

(m, 1 H), 2.82-2.97 (m, 1 H), 2.43-2.59 (m, 3 H)

569
(CD₃OD) δ 8.26 (s, 1 H), 7.68 (s, 1 H), 7.51 (d, 1 H), 7.36 (td,
367.9
100%

1 H), 7.22 (dd, 1 H), 6.73 (br s, 1 H), 4.61 (br s, 1 H), 3.93 (br
[M + H]⁺

s, 1 H), 3.08 (br s, 1 H), 2.74-2.92 (m, 1 H), 2.39 (s, 3 H)

570
(CD₃OD) δ 8.26 (s, 1 H), 7.68 (s, 1 H), 7.51 (d, 1 H), 7.36 (td,
368.1
99.2%

1 H), 7.22 (dd, 1 H), 6.73 (br s, 1 H), 4.57 (br s, 1 H), 3.74-
[M + H]⁺

4.08 (m, 1 H), 3.08 (br s, 1 H), 2.84 (br dd, 1 H), 2.36-2.42

(m, 3 H)

571
(CD₃OD) δ 7.70 (br d, 2 H), 7.48 (d, 1 H), 6.94-7.28 (m, 1 H),
540.1
95.0%

6.73 (br s, 1 H), 4.91-5.02 (m, 0.3 H), 4.57 (br d, 0.7 H), 3.55-
[M + H]⁺

4.05 (m, 1 H), 2.81-3.21 (m, 2 H), 1.50-1.71 (m, 6 H)

572
(CD₃OD) δ 7.70 (br d, 2 H), 7.48 (d, 1 H), 6.93-7.28 (m, 1 H),
540.0
96.2%

6.73 (br s, 1 H), 4.90-5.05 (m, 0.3 H), 4.45-4.67 (m, 0.7 H),
[M + H]⁺

3.55-4.09 (m, 1 H), 2.77-3.23 (m, 2 H), 1.50-1.72 (m, 6 H)

573
(CD₃OD) δ 8.45 (br s, 1 H), 7.70 (br d, 2 H), 7.48 (d, 1 H),
482.0
92.1%

6.96-7.27 (m, 1 H), 6.74 (br s, 1 H), 4.39-4.69 (m, 1 H), 3.52-
[M + H]⁺

4.09 (m, 1 H), 3.10 (br s, 1 H), 2.86 (br d, 1 H)

574
(CD₃OD) δ 8.45 (br s, 1 H), 7.70 (br d, 2 H), 7.48 (d, 1 H),
484.0
93.6%

6.96-7.27 (m, 1 H), 6.74 (br s, 1 H), 4.56 (br d, 1 H), 3.56-
[M + H]⁺

4.05 (m, 1 H), 3.10 (br s, 1 H), 2.86 (br d, 1 H)

575
(CD₃OD) δ 8.41 (s, 1 H), 7.85 (br s, 1 H), 7.68 (s, 1 H), 7.31
372.1
98.8%

(br d, 1 H), 7.15 (td, 1 H), 6.76 (br s, 1 H), 4.59-4.82 (m, 1 H),
[M + H]⁺

3.97 (br s, 1 H), 2.99-3.25 (m, 1 H), 2.87 (br d, 1 H)

576
(CD₃OD) δ 8.41 (s, 1 H), 7.85 (br s, 1 H), 7.69 (s, 1 H), 7.31
372.2
98.5%

(br d, 1 H), 7.15 (td, 1 H), 6.76 (br s, 1 H), 4.58-4.80 (m, 1 H),
[M + H]⁺

3.68-4.12 (m, 1 H), 3.10 (br s, 1 H), 2.87 (br d, 1 H)

577
(CD₃OD) δ 7.67-7.75 (m, 1 H), 7.28-7.37 (m, 1 H), 7.08-7.22
436.0
100%

(m, 1.3 H), 6.61-7.03 (m, 1.7 H), 5.06-5.16 (m, 0.3 H), 4.79
[M + H]⁺

(dd, 0.7 H), 4.10-4.16 (m, 3 H), 3.91 (s, 0.7 H), 3.58 (br s, 0.3

H), 2.95-3.27 (m, 1 H), 2.78-2.92 (m, 1 H)

578
(CD₃OD) δ 7.71 (br s, 1 H), 7.27-7.40 (m, 1 H), 7.07-7.24 (m,
436.0
99.3%

1.3 H), 6.58-7.04 (m, 1.7 H), 5.11 (br dd, 0.3 H), 4.79 (br dd,
[M + H]⁺

0.7 H), 4.05-4.21 (m, 3 H), 3.91 (br s, 0.7 H), 3.58 (br s, 0.3

H), 2.95-3.27 (m, 1 H), 2.77-2.94 (m, 1 H)

579
(CD₃OD) δ 8.71-8.84 (m, 1 H), 8.21-8.37 (m, 1 H), 7.99-8.15
450.1
100%

(m, 1 H), 7.61-7.80 (m, 2 H), 7.54 (s, 0.3 H), 7.27-7.38 (m, 1
[M + H]⁺

H), 7.10-7.24 (m, 1 H), 6.93 (s, 0.7 H), 5.08-5.36 (m, 1 H),

3.63-4.10 (m, 1 H), 2.98-3.29 (m, 1 H), 2.84-2.97 (m, 1 H)

580
(CD₃OD) δ 8.73-8.81 (m, 1 H), 8.26-8.35 (m, 1 H), 8.05-8.13
449.9
99.2%

(m, 1 H), 7.60-7.82 (m, 2 H), 7.54 (s, 0.3 H), 7.26-7.38 (m, 1
[M + H]⁺

H), 7.06-7.24 (m, 1 H), 6.92 (s, 0.7 H), 5.08-5.36 (m, 1 H),

3.61-4.09 (m, 1 H), 2.99-3.29 (m, 1 H), 2.84-2.97 (m, 1 H)

581
(CD₃OD) δ 8.37-8.45 (m, 1 H), 8.07-8.14 (m, 1 H), 7.65-7.74
417.0
100%

(m, 3 H), 7.62-7.64 (m, 0.3 H), 7.38-7.47 (m, 2 H), 6.92 (br s,
[M + H]⁺

0.7 H), 5.08-5.38 (m, 1 H), 4.00-4.03 (m, 3 H), 3.92-3.99 (m,

0.6 H), 3.46-3.72 (m, 0.4 H), 3.13-3.28 (m, 1 H), 2.85-2.96

(m, 1 H)

582
(CD₃OD) δ 8.35-8.44 (m, 1 H), 8.07-8.15 (m, 1 H), 7.65-7.74
416.9
99.0%

(m, 3 H), 7.62-7.64 (m, 0.3 H), 7.36-7.48 (m, 2 H), 6.92 (s, 0.7
[M + H]⁺

H), 5.07-5.39 (m, 1 H), 4.00-4.04 (m, 3 H), 3.91-3.98 (m, 0.6

H), 3.43-3.72 (m, 0.4 H), 3.13-3.28 (m, 1 H), 2.84-2.95 (m, 1

H)

583
(CD₃OD) δ 8.62-8.71 (m, 1 H), 8.14-8.24 (m, 1 H), 7.92-8.02
414.1
100%

(m, 1 H), 7.60-7.62 (m, 1 H), 7.49-7.59 (m, 3 H), 7.47 (s, 0.3
[M + H]⁺

H), 7.26-7.36 (m, 2 H), 6.83 (s, 0.7 H), 4.98-5.19 (m, 1 H),

3.50-3.92 (m, 1 H), 3.07-3.18 (m, 1 H), 2.73-2.85 (m, 1 H)

584
(CD₃OD) δ 8.74-8.83 (m, 1 H), 8.27-8.35 (m, 1 H), 8.05-8.14
414.2
99.3%

(m, 1 H), 7.73 (br d, 1 H), 7.62-7.71 (m, 3 H), 7.59 (br s, 0.3
[M + H]⁺

H), 7.36-7.49 (m, 2 H), 6.95 (s, 0.7 H), 5.10-5.33 (m, 1 H),

3.60-4.07 (m, 1 H), 3.19-3.31 (m, 1 H), 2.92 (br d, 1 H)

585
(CD₃OD) δ 7.59-7.80 (m, 2 H), 7.44 (dd, 1 H), 7.22 (td, 1 H),
492.2
99.0%

6.82 (s, 0.7 H), 6.20 (br s, 0.3 H), 4.98 (br d, 0.4 H), 4.04-4.16
[M + H]⁺

(m, 0.6 H), 3.88-4.02 (m, 0.7 H), 3.65 (br s, 0.3 H), 2.94-3.10

(m, 1 H), 2.56-2.93 (m, 3 H), 2.24-2.52 (m, 2 H), 1.64-2.12

(m, 2 H)

586
(CD₃OD) δ 7.53-7.93 (m, 2 H), 7.44 (br d, 1 H), 7.13-7.33 (m,
492.1
95.5%

1 H), 6.82 (br s, 0.7 H), 6.20 (br s, 0.3 H), 4.97 (br s, 0.4 H),
[M + H]⁺

4.03-4.21 (m, 0.6 H), 3.88-4.03 (m, 0.7 H), 3.65 (br s, 0.3 H),

3.02 (br d, 1 H), 2.57-2.94 (m, 3 H), 2.21-2.54 (m, 2 H), 1.66-

2.15 (m, 2 H)

587
(CD₃OD) δ 8.47-8.81 (m, 1 H), 8.16-8.39 (m, 1 H), 7.91-8.13
481.2
92.7%

(m, 1 H), 7.52-7.77 (m, 3 H), 7.04-7.45 (m, 3 H), 6.86 (br s, 1
[M + H]⁺

H), 5.02 (br s, 0.3 H), 4.77 (br d, 0.7 H), 3.70-4.09 (m, 1 H),

3.02-3.30 (m, 1 H), 2.93 (br d, 1 H)

588
(CD₃OD) δ 8.43-8.82 (m, 1 H), 8.18-8.38 (m, 1 H), 7.89-8.17
481.1
93.3%

(m, 1 H), 7.50-7.77 (m, 3 H), 7.05-7.44 (m, 3 H), 6.86 (br s, 1
[M + H]⁺

H), 5.01 (br s, 0.3 H), 4.76 (br d, 0.7 H), 3.69-4.16 (m, 1 H),

3.04-3.29 (m, 1 H), 2.93 (br d, 1 H)

589
(CD₃OD) δ 9.20 (br s, 1 H), 8.65 (br s, 1 H), 8.43 (br d, 1 H),
481.2
99.7%

7.36-7.68 (m, 3 H), 7.05-7.35 (m, 3 H), 6.63-7.02 (m, 1 H),
[M + H]⁺

4.82-4.93 (m, 0.5 H), 4.64 (br d, 0.5 H), 3.58-4.02 (m, 1 H),

2.90-3.17 (m, 1 H), 2.85 (br d, 1 H)

590
(CD₃OD) δ 9.20 (br s, 1 H), 8.65 (br s, 1 H), 8.43 (br d, 1 H),
481.2
99.2%

7.36-7.67 (m, 3 H), 7.03-7.35 (m, 3 H), 6.63-7.02 (m, 1 H),
[M + H]⁺

4.82-4.96 (m, 0.5 H), 4.64 (br d, 0.5 H), 3.51-4.03 (m, 1 H),

2.90-3.18 (m, 1 H), 2.85 (br d, 1 H)

591
(CD₃OD) δ 7.61-7.95 (m, 2 H), 7.54 (d, 1 H), 7.39 (td, 1 H),
484.1
97.7%

7.04-7.36 (m, 2 H), 6.77-7.03 (m, 2 H), 4.94-5.11 (m, 0.4 H),
[M + H]⁺

4.75 (br s, 0.6 H), 3.63-4.18 (m, 4 H), 3.24 (br s, 0.7 H), 3.02

(br s, 0.3 H), 2.92 (br d, 1 H)

592
(CD₃OD) δ 7.65-7.89 (m, 2 H), 7.54 (d, 1 H), 7.39 (td, 1 H),
484.2
94.8%

7.04-7.35 (m, 2 H), 6.77-7.04 (m, 2 H), 4.95-5.10 (m, 0.3 H),
[M + H]⁺

4.76 (br s, 0.7 H), 3.65-4.20 (m, 4 H), 3.00-3.29 (m, 1 H),

2.79-2.99 (m, 1 H)

593
(CD₃OD) δ 8.69 (br s, 1 H), 7.89-8.23 (m, 2 H), 7.68 (s, 1 H),
445.3
99.2%

7.52 (br d, 2 H), 7.37 (td, 1 H), 7.18-7.28 (m, 1 H), 6.77 (br s,
[M + H]⁺

1 H), 4.74 (br s, 1 H), 3.98 (br s, 1 H), 3.03-3.29 (m, 1 H),

2.88 (br d, 1 H), 2.48 (s, 3 H)

594
(CD₃OD) δ 8.69 (br s, 1 H), 7.88-8.26 (m, 2 H), 7.68 (br s, 1
445.1
99.2%

H), 7.52 (br d, 2 H), 7.32-7.43 (m, 1 H), 7.14-7.29 (m, 1 H),
[M + H]⁺

6.78 (br s, 1 H), 4.56-4.86 (m, 1 H), 3.69-4.15 (m, 1 H), 3.09-

3.28 (m, 1 H), 2.89 (br d, 1 H), 2.48 (s, 3 H)

595
(CD₃OD) δ 8.22 (br s, 1 H), 7.97 (br s, 1 H), 7.67 (s, 1 H),
448.0
99.1%

7.54 (br d, 1 H), 7.33-7.43 (m, 1 H), 7.19-7.30 (m, 1 H), 6.74
[M + H]⁺

(br s, 1 H), 4.75 (br s, 1 H), 3.97 (s, 4 H), 3.11 (br s, 1 H), 2.88

(br d, 1 H), 2.42 (s, 3 H)

596
(CD₃OD) δ 8.22 (br s, 1 H), 7.97 (br s, 1 H), 7.67 (s, 1 H),
448.1
99.3%

7.54 (br d, 1 H), 7.35-7.41 (m, 1 H), 7.24 (br t, 1 H), 6.74 (br
[M + H]⁺

s, 1 H), 4.76 (br s, 1 H), 3.96 (s, 4 H), 3.12 (br d, 1 H), 2.88

(br d, 1 H), 2.42 (s, 3 H)

597
(CD₃OD) δ 8.25 (s, 1 H), 7.62-7.70 (m, 2 H), 7.47 (dd, 1 H),
368.1
100%

7.17 (td, 1 H), 6.70 (br s, 1 H), 4.54 (br s, 1 H), 3.88 (br s, 1
[M + H]⁺

H), 3.06 (br s, 1 H), 2.83 (br d, 1 H), 2.39 (s, 3 H)

598
(CD₃OD) δ 8.25 (s, 1 H), 7.61-7.72 (m, 2 H), 7.47 (dd, 1 H),
368.2
99.8%

7.17 (td, 1 H), 6.70 (br s, 1 H), 4.55 (br s, 1 H), 3.87 (br s, 1
[M + H]⁺

H), 3.07 (br s, 1 H), 2.83 (br d, 1 H), 2.39 (s, 3 H)

599
(CD₃OD) δ 8.25 (s, 1 H), 7.68 (s, 1 H), 7.46-7.53 (m, 1 H),
368.2
100%

7.41 (td, 1 H), 7.09-7.18 (m, 1 H), 6.71 (br s, 1 H), 4.57 (br s,
[M + H]⁺

1 H), 3.92 (br s, 1 H), 3.08 (br s, 1 H), 2.84 (br d, 1 H), 2.39

(s, 3 H)

600
(CD₃OD) δ 8.25 (s, 1 H), 7.68 (s, 1 H), 7.46-7.52 (m, 1 H),
368.2
99.8%

7.40 (td, 1 H), 7.06-7.18 (m, 1 H), 6.70 (br s, 1 H), 4.57 (br s,
[M + H]⁺

1 H), 3.92 (br s, 1 H), 3.07 (br s, 1 H), 2.74-2.92 (m, 1 H),

2.39 (s, 3 H)

601
(CD₃OD) δ 7.71 (s, 1 H), 7.30-7.44 (m, 1 H), 7.12-7.29 (m,
430.1
99.5%

1.3 H), 6.62-7.04 (m, 2.7 H), 5.08 (dd, 0.3 H), 4.74 (dd, 0.7
[M + H]⁺

H), 4.09-4.19 (m, 3 H), 3.96-4.06 (m, 3 H), 3.83-3.94 (m, 0.7

H), 3.42-3.55 (m, 0.3 H), 3.17-3.28 (m, 0.7 H), 2.94-3.06 (m,

0.3 H), 2.76-2.92 (m, 1 H)

602
(CD₃OD) δ 7.70 (s, 1 H), 7.30-7.42 (m, 1 H), 7.12-7.30 (m,
430.2
97.7%

1.3 H), 6.63-7.05 (m, 2.7 H), 5.08 (dd, 0.2 H), 4.74 (dd, 0.8
[M + H]⁺

H), 4.09-4.21 (m, 3 H), 3.97-4.07 (m, 3 H), 3.82-3.95 (m, 0.7

H), 3.49 (td, 0.3 H), 3.18-3.28 (m, 0.7 H), 2.93-3.07 (m, 0.3

H), 2.72-2.92 (m, 1 H)

603
(CD₃OD) δ 7.49-8.06 (m, 3 H), 7.32-7.43 (m, 1 H), 7.25 (br d,
415.1
100%

1 H), 6.74-7.01 (m, 2.8 H), 6.31 (br s, 0.2 H), 4.91-5.07 (m,
[M + H]⁺

0.3 H), 4.31 (br d, 0.7 H), 4.02 (s, 3.8 H), 3.50 (br s, 0.2 H),

2.97-3.12 (m, 1 H), 2.82 (br d, 1 H)

604
(CD₃OD) δ 7.49-8.07 (m, 3 H), 7.33-7.44 (m, 1 H), 7.25 (br d,
415.1
100%

1 H), 6.75-7.05 (m, 2.8 H), 6.31 (br s, 0.2 H), 4.92-5.03 (m,
[M + H]⁺

0.3 H), 4.31 (br d, 0.7 H), 4.02 (s, 3.8 H), 3.50 (br s, 0.2 H),

2.97-3.12 (m, 1 H), 2.81 (br d, 1 H)

605
(CD₃OD) δ 7.69 (s, 1 H), 7.58 (s, 1 H), 7.36 (dd, 1 H), 6.92-
496.0
99.0%

7.27 (m, 1 H), 6.75 (br s, 1 H), 4.50-4.70 (m, 1 H), 3.97 (br s,
[M + H]⁺

0.7 H), 3.64 (br s, 0.3 H), 3.15 (br d, 1 H), 2.88 (br d, 1 H),

1.50-1.71 (m, 6 H)

606
(CD₃OD) δ 7.69 (s, 1 H), 7.58 (s, 1 H), 7.36 (dd, 1 H), 6.91-
496.0
96.5%

7.27 (m, 1 H), 6.75 (br s, 1 H), 4.50-4.69 (m, 1 H), 3.97 (br s,
[M + H]⁺

0.7 H), 3.65 (br s, 0.3 H), 3.15 (br d, 1 H), 2.88 (br d, 1 H),

1.51-1.71 (m, 6 H)

607
(CD₃OD) δ 8.48 (br s, 1 H), 7.72 (s, 1 H), 7.59 (s, 1 H), 7.37
437.9
98.0%

(br d, 1 H), 6.97-7.31 (m, 1 H), 6.79 (br s, 1 H), 4.58 (br d, 1
[M + H]⁺

H), 3.98 (br s, 1 H), 2.98-3.22 (m, 1 H), 2.88 (br d, 1 H)

608
(CD₃OD) δ 8.47 (br s, 1 H), 7.70 (br d, 1 H), 7.59 (br d, 1 H),
437.9
96.4%

7.37 (br t, 1 H), 6.94-7.30 (m, 1 H), 6.77 (br s, 1 H), 4.48-4.69
[M + H]⁺

(m, 1 H), 3.96 (br s, 1 H), 3.12 (br s, 1 H), 2.87 (br s, 1 H)

609
(CD₃OD) δ 7.61-7.88 (m, 2.7H), 7.29-7.54 (m, 1.3 H), 7.18
421.0
99.2%

(br t, 1 H), 6.79-6.99 (m, 2 H), 4.30 (br d, 1 H), 3.96 (br s, 1
[M + H]⁺

H), 2.98-3.12 (m, 1 H), 2.84 (br d, 1 H)

610
(CD₃OD) δ 7.62-7.89 (m, 3 H), 7.28-7.53 (m, 1 H), 7.18 (br t,
420.9
98.7%

1 H), 6.78-6.97 (m, 2 H), 4.31 (br d, 1 H), 3.96 (br s, 1 H),
[M + H]⁺

2.98-3.11 (m, 1 H), 2.84 (br d, 1 H)

611
(CD₃OD) δ 8.43 (s, 1 H), 7.87 (br s, 1 H), 7.71 (s, 1 H), 7.50
350.1
98.9%

(br d, 1 H), 7.22-7.31 (m, 2 H), 6.80 (br s, 1 H), 4.57-4.77 (m,
[M + H]⁺

1 H), 3.61-4.03 (m, 1 H), 3.13 (br d, 1 H), 2.88 (br d, 1 H),

2.57 (s, 3 H)

612
(CD₃OD) δ 8.43 (s, 1 H), 7.87 (br s, 1 H), 7.71 (s, 1 H), 7.50
350.2
98.3%

(br d, 1 H), 7.22-7.31 (m, 2 H), 6.80 (br s, 1 H), 4.56-4.79 (m,
[M + H]⁺

1 H), 3.99 (br s, 1 H), 3.12 (br s, 1 H), 2.88 (br d, 1 H), 2.57

(s, 3 H)

613
(CD₃OD) δ 7.69-7.75 (m, 1 H), 7.46-7.52 (m, 1 H), 7.20-7.31
414.0
100%

(m, 2.4 H), 7.01 (s, 0.2 H), 6.87-6.93 (m, 1 H), 6.65-6.80 (m,
[M + H]⁺

0.4 H), 5.10 (dd, 0.3 H), 4.76 (dd, 0.7 H), 4.12 (s, 3 H), 3.84-

3.95 (m, 0.7 H), 3.50-3.62 (m, 0.3 H), 3.17-3.28 (m, 0.7 H),

2.96-3.06 (m, 0.3 H), 2.79-2.92 (m, 1 H), 2.50-2.59 (m, 3 H)

614
(CD₃OD) δ 7.69-7.74 (m, 1 H), 7.45-7.53 (m, 1 H), 7.19-7.32
414.0
99.5%

(m, 2.4 H), 7.01 (s, 0.2 H), 6.89 (d, 1 H), 6.65-6.81 (m, 0.4 H),
[M + H]⁺

5.10 (dd, 0.3 H), 4.76 (dd, 0.7 H), 4.12 (s, 3 H), 3.86-3.94 (m,

0.7 H), 3.55 (td, 0.3 H), 3.18-3.28 (m, 0.7 H), 2.96-3.07 (m,

0.3 H), 2.79-2.92 (m, 1 H), 2.49-2.59 (m, 3 H)

615
(CD₃OD) δ 8.09-8.46 (m, 2 H), 7.72 (br s, 1 H), 7.45-7.63 (m,
510.9
99.8%

2 H), 7.05-7.43 (m, 3 H), 6.85 (s, 1 H), 4.97-5.07 (m, 0.4 H),
[M + H]⁺

4.79 (br s, 0.6 H), 3.98 (br s, 4 H), 3.01-3.30 (m, 1 H), 2.92 (br

d, 1 H)

616
(CD₃OD) δ 8.07-8.47 (m, 2 H), 7.72 (br s, 1 H), 7.45-7.62 (m,
511.0
99.4%

2 H), 7.05-7.42 (m, 3 H), 6.84 (s, 1 H), 4.95-5.07 (m, 0.3 H),
[M + H]⁺

4.78 (br d, 0.7 H), 3.98 (br s, 4 H), 2.99-3.29 (m, 1 H), 2.92

(br d, 1 H)

617
(CD₃OD) δ 7.67 (s, 1 H), 7.53 (d, 1 H), 7.38 (td, 1 H), 7.20-
502.2
98.7%

7.29 (m, 1 H), 6.91-7.12 (m, 1 H), 6.71 (s, 1 H), 4.57-4.84 (m,
[M + H]⁺

1 H), 3.63 (br s, 5 H), 2.95-3.19 (m, 1 H), 2.84 (br d, 1 H),

2.53 (br s, 4 H), 2.35 (s, 3 H)

618
(CD₃OD) δ 7.67 (s, 1 H), 7.53 (d, 1 H), 7.33-7.43 (m, 1 H),
502.2
98.2%

7.20-7.28 (m, 1 H), 6.68-7.11 (m, 2 H), 4.56-4.81 (m, 1 H),
[M + H]⁺

3.63 (br s, 5 H), 2.99-3.18 (m, 1 H), 2.84 (br d, 1 H), 2.54 (br

s, 4 H), 2.35 (s, 3 H)

619
(CD₃OD) δ 8.39 (s, 1 H), 7.65-7.80 (m, 1 H), 7.54 (d, 1 H),
418.0
98.0%

7.39 (td, 1 H), 7.21-7.31 (m, 1 H), 6.88 (s, 0.8 H), 6.11 (br s,
[M + H]⁺

0.2 H), 5.02 (br d, 0.2 H), 3.87-4.09 (m, 1.6 H), 3.63 (br s, 0.2

H), 2.94-3.05 (m, 1 H), 2.75-2.92 (m, 1 H), 1.99 (t, 3 H)

620
(CD₃OD) δ 8.39 (s, 1 H), 7.67-7.78 (m, 1 H), 7.54 (d, 1 H),
417.9
95.8%

7.39 (td, 1 H), 7.17-7.31 (m, 1 H), 6.88 (s, 0.8 H), 6.11 (br s,
[M + H]⁺

0.2 H), 5.01 (br d, 0.2 H), 3.87-4.07 (m, 1.6 H), 3.63 (br s, 0.2

H), 2.94-3.08 (m, 1 H), 2.75-2.93 (m, 1 H), 1.99 (t, 3 H)

621
(CD₃OD) δ 8.42 (s, 1 H), 7.87 (br s, 1 H), 7.75 (s, 1 H), 7.33-
366.0
98.7%

7.41 (m, 1 H), 7.24 (d, 1 H), 6.94 (d, 1 H), 6.78 (br s, 1 H),
[M + H]⁺

4.70 (br s, 1 H), 4.01 (s, 4 H), 3.00-3.18 (m, 1 H), 2.81-2.92

(m, 1 H)

622
(CD₃OD) δ 8.42 (s, 1 H), 7.87 (br s, 1 H), 7.72 (s, 1 H), 7.32-
366.0
98.3%

7.41 (m, 1 H), 7.24 (d, 1 H), 6.94 (d, 1 H), 6.77 (br s, 1 H),
[M + H]⁺

4.70 (br s, 1 H), 4.00 (s, 4 H), 3.13 (br d, 1 H), 2.87 (br d, 1 H)

623
(CD₃OD) δ 8.67-8.91 (m, 1 H), 8.26-8.37 (m, 1 H), 8.01-8.18
444.0
95.4%

(m, 1 H), 7.70-7.78 (m, 1 H), 7.63-7.70 (m, 1 H), 7.50-7.61
[M + H]⁺

(m, 0.3 H), 7.30-7.43 (m, 1 H), 7.19-7.29 (m, 1 H), 6.85-6.99

(m, 1.7 H), 5.06-5.33 (m, 1 H), 3.89-4.06 (m, 3.8 H), 3.60-

3.75 (m, 0.2 H), 3.18-3.30 (m, 0.8 H), 2.97-3.09 (m, 0.2 H),

2.83-2.96 (m, 1 H)

624
(CD₃OD) δ 8.55-8.81 (m, 1 H), 8.12-8.29 (m, 1 H), 7.90-8.05
444.0
94.2%

(m, 1 H), 7.58-7.64 (m, 1 H), 7.50-7.58 (m, 1 H), 7.44 (br s,
[M + H]⁺

0.3 H), 7.17-7.30 (m, 1 H), 7.04-7.17 (m, 1 H), 6.67-6.90 (m,

1.7 H), 4.94-5.22 (m, 1 H), 3.78-3.99 (m, 3.7 H), 3.46-3.64

(m, 0.3 H), 3.06-3.18 (m, 0.7 H), 2.86-2.99 (m, 0.3 H), 2.71-

2.85 (m, 1 H)

625
(CD₃OD) δ 8.26-8.57 (m, 1 H), 8.06-8.18 (m, 1 H), 7.72 (s, 1
447.0
99.6%

H), 7.57 (br s, 0.3 H), 7.31-7.42 (m, 1 H), 7.18-7.30 (m, 1 H),
[M + H]⁺

6.81-7.01 (m, 1.7 H), 5.03-5.42 (m, 1 H), 3.89-4.09 (m, 6.8

H), 3.65 (br s, 0.2 H), 3.12-3.27 (m, 0.7 H), 2.96-3.07 (m, 0.3

H), 2.90 (br d, 1 H)

626
(CD₃OD) δ 8.17-8.43 (m, 1 H), 7.90-8.07 (m, 1 H), 7.54-7.67
447.0
98.7%

(m, 1 H), 7.46 (s, 0.3 H), 7.18-7.31 (m, 1 H), 7.02-7.17 (m, 1
[M + H]⁺

H), 6.66-6.91 (m, 1.7 H), 4.93-5.27 (m, 1 H), 3.78-3.96 (m,

6.8 H), 3.45-3.61 (m, 0.2 H), 3.01-3.15 (m, 0.7 H), 2.83-2.95

(m, 0.3 H), 2.68-2.82 (m, 1 H)

627
(CD₃OD) δ 9.40-9.53 (m, 1 H), 8.78-8.92 (m, 2 H), 7.60-7.79
433.0
99.1%

(m, 2 H), 7.40-7.58 (m, 1.3 H), 7.15-7.29 (m, 1 H), 6.92 (br s,
[M + H]⁺

0.7 H), 5.29 (dd, 0.7 H), 5.15 (dd, 0.3 H), 4.02 (br t, 0.7 H),

3.69 (br s, 0.3 H), 3.14-3.30 (m, 1 H), 2.86-3.10 (m, 1 H)

628
(CD₃OD) δ 9.40-9.52 (m, 1 H), 8.80-8.90 (m, 2 H), 7.64-7.77
432.9
97.5%

(m, 2 H), 7.38-7.56 (m, 1.3 H), 7.16-7.27 (m, 1 H), 6.92 (br s,
[M + H]⁺

0.7 H), 5.29 (dd, 0.7 H), 5.15 (dd, 0.3 H), 4.01 (br t, 0.7 H),

3.62-3.75 (m, 0.3 H), 3.14-3.30 (m, 1 H), 2.86-3.09 (m, 1 H)

629
(CD₃OD) δ 8.74-8.85 (m, 1 H), 8.27-8.38 (m, 1 H), 8.05-8.16
450.1
98.9%

(m, 1 H), 7.60-7.77 (m, 2 H), 7.32-7.55 (m, 2.4 H), 6.91 (s, 0.6
[M + H]⁺

H), 5.10-5.37 (m, 1 H), 3.66-4.11 (m, 1 H), 3.21-3.27 (m, 0.5

H), 2.86-3.11 (m, 1.5 H)

630
(CD₃OD) δ 8.75-8.83 (m, 1 H), 8.26-8.38 (m, 1 H), 8.04-8.16
450.1
96.6%

(m, 1 H), 7.62-7.81 (m, 2 H), 7.33-7.56 (m, 2.4 H), 6.91 (s, 0.6
[M + H]⁺

H), 5.11-5.37 (m, 1 H), 3.67-4.11 (m, 1 H), 3.20-3.29 (m, 0.6

H), 2.87-3.10 (m, 1.4 H)

631
(CD₃OD) δ 8.23-8.75 (m, 2 H), 7.52-7.95 (m, 3 H), 7.02-7.46
499.1
99.4%

(m, 3 H), 6.85 (br s, 1 H), 5.01 (br s, 0.4 H), 4.77 (br d, 0.6 H),
[M + H]⁺

3.70-4.14 (m, 1 H), 3.00-3.31 (m, 1 H), 2.93 (br d, 1 H)

632
(CD₃OD) δ 8.08-8.66 (m, 2 H), 7.39-7.85 (m, 3 H), 6.91-7.33
499.1
98.8%

(m, 3 H), 6.72 (br s, 1 H), 4.86-4.96 (m, 0.4 H), 4.65 (br d, 0.6
[M + H]⁺

H), 3.55-4.00 (m, 1 H), 2.87-3.18 (m, 1 H), 2.80 (br d, 1 H)

633
(CD₃OD) δ 8.62-9.17 (m, 1 H), 8.25-8.56 (m, 2 H), 7.73 (br s,
549.1
99.0%

1 H), 7.55 (br d, 1 H), 7.07-7.46 (m, 3 H), 6.86 (br s, 1 H),
[M + H]⁺

5.02 (br s, 0.4 H), 4.77 (br d, 0.6 H), 3.76-4.09 (m, 1 H), 3.02-

3.30 (m, 1 H), 2.94 (br d, 1 H)

634
(CD₃OD) δ 8.65-9.18 (m, 1 H), 8.26-8.55 (m, 2 H), 7.73 (br s,
549.1
99.0%

1 H), 7.54 (br d, 1 H), 7.06-7.45 (m, 3 H), 6.86 (br s, 1 H),
[M + H]⁺

5.02 (br s, 0.4 H), 4.77 (br d, 0.6 H), 3.77-4.13 (m, 1 H), 3.01-

3.31 (m, 1 H), 2.94 (br d, 1 H)

635
(CD₃OD) δ 8.35 (br s, 1 H), 7.87-8.18 (m, 1 H), 7.70 (br s, 1
484.2
99.1%

H), 7.54 (br s, 1 H), 7.38 (br s, 1 H), 7.00-7.33 (m, 2 H), 6.81
[M + H]⁺

(br s, 1 H), 4.73 (br s, 1 H), 3.69-4.07 (m, 4 H), 2.82-3.26 (m,

2 H)

636
(CD₃OD) δ 8.35 (br s, 1 H), 8.08 (br s, 1 H), 7.69 (br s, 1 H),
484.1
98.9%

7.54 (br s, 1 H), 7.38 (br s, 1 H), 6.97-7.34 (m, 2 H), 6.81 (br
[M + H]⁺

s, 1 H), 4.57-4.84 (m, 1 H), 3.47-4.07 (m, 4 H), 2.83-3.27 (m,

2 H)

637
(CD₃OD) δ 8.45-8.78 (m, 1 H), 7.90-8.34 (m, 2 H), 7.52-7.78
499.0
98.7%

(m, 3 H), 7.41 (td, 1 H), 7.22-7.31 (m, 1 H), 6.91 (s, 1 H),
[M + H]⁺

4.99-5.09 (m, 0.2 H), 4.28 (br dd, 0.8 H), 3.95-4.07 (m, 0.7

H), 3.68-3.80 (m, 0.3 H), 2.83-3.19 (m, 2 H)

638
(CD₃OD) δ 8.34-8.66 (m, 1 H), 7.82-8.24 (m, 2 H), 7.41-7.64
499.0
97.0%

(m, 3 H), 7.29 (td, 1 H), 7.10-7.19 (m, 1 H), 6.25-6.85 (m, 1
[M + H]⁺

H), 4.88-4.98 (m, 0.2 H), 4.16 (br dd, 0.8 H), 3.83-3.96 (m,

0.7 H), 3.56-3.71 (m, 0.3 H), 2.72-3.06 (m, 2 H)

639
(CD₃OD) δ 7.78-7.86 (m, 1 H), 7.72 (s, 1 H), 7.58 (br s, 0.5
447.0
100%

H), 7.30-7.42 (m, 1 H), 7.18-7.28 (m, 1 H), 6.85-7.03 (m, 2.5
[M + H]⁺

H), 5.29 (br dd, 0.7 H), 5.10 (br d, 0.3 H), 3.91-4.10 (m, 6.7

H), 3.54-3.76 (m, 0.3 H), 3.14-3.28 (m, 1 H), 2.84-3.06 (m, 1

H)

640
(CD₃OD) δ 7.83 (br s, 1 H), 7.72 (s, 1 H), 7.58 (br s, 0.3 H),
447.0
100%

7.30-7.41 (m, 1 H), 7.17-7.29 (m, 1 H), 6.83-7.05 (m, 2.7 H),
[M + H]⁺

5.29 (dd, 0.7 H), 5.05-5.15 (m, 0.3 H), 3.93-4.07 (m, 6.9 H),

3.64 (br s, 0.1 H), 3.13-3.28 (m, 1 H), 2.83-3.07 (m, 1 H)

641
(CD₃OD) δ 7.61-7.82 (m, 2 H), 7.38-7.52 (m, 2 H), 7.02-7.37
484.1
86.5%

(m, 3 H), 6.81 (br s, 1 H), 4.77 (br d, 1 H), 4.19 (br s, 3 H),
[M + H]⁺

3.99 (br s, 1 H), 3.17-3.30 (m, 1 H), 2.89 (br d, 1 H)

642
(CD₃OD) δ 7.46-7.67 (m, 2 H), 7.27-7.40 (m, 2 H), 6.91-7.25
484.1
96.6%

(m, 3 H), 6.69 (br s, 1 H), 4.65 (br d, 1 H), 3.95-4.16 (m, 3 H),
[M + H]⁺

3.87 (br s, 1 H), 3.06-3.18 (m, 1 H), 2.77 (br d, 1 H)

643
(CD₃OD) δ 7.68 (s, 1 H), 6.95-7.29 (m, 2 H), 6.85 (dd, 1 H),
492.2
99.0%

6.59-6.81 (m, 1 H), 4.57 (br d, 1 H), 3.88-4.06 (m, 1 H), 3.83
[M + H]⁺

(s, 3 H), 2.98-3.26 (m, 1 H), 2.87 (br d, 1 H), 1.48-1.77 (m, 6

H)

644
(CD₃OD) δ 7.69 (s, 1 H), 6.95-7.35 (m, 2 H), 6.86 (dd, 1 H),
492.2
98.4%

6.74 (br s, 1 H), 4.57 (br d, 1 H), 3.89-4.08 (m, 1 H), 3.83 (s, 3
[M + H]⁺

H), 2.94-3.24 (m, 1 H), 2.87 (br d, 1 H), 1.50-1.74 (m, 6 H)

645
(CD₃OD) δ 8.31-8.49 (m, 1 H), 7.99-8.21 (m, 1 H), 7.67-7.79
453.1
100%

(m, 1 H), 6.79-7.60 (m, 3 H), 5.08-5.43 (m, 1 H), 3.63-4.17
[M + H]⁺

(m, 4 H), 3.02-3.31 (m, 1 H), 2.92 (br d, 1 H)

646
(CD₃OD) δ 8.39-8.49 (m, 1 H), 8.01-8.19 (m, 1 H), 7.70-7.80
453.1
98.8%

(m, 1 H), 6.80-7.62 (m, 3 H), 5.10-5.46 (m, 1 H), 3.67-4.05
[M + H]⁺

(m, 4 H), 3.05-3.28 (m, 1 H), 2.86-3.00 (m, 1 H)

647
(CD₃OD) δ 7.69 (s, 1 H), 7.54 (d, 1 H), 7.40 (td, 1 H), 7.22-
489.1
94.6%

7.30 (m, 1 H), 6.97-7.14 (m, 1 H), 6.73 (s, 1 H), 4.76 (br s, 1
[M + H]⁺

H), 3.78 (br s, 5 H), 3.61 (br s, 4 H), 2.99-3.17 (m, 1 H), 2.86

(br d, 1 H)

648
(CD₃OD) δ 7.74 (s, 1 H), 7.54 (d, 1 H), 7.40 (td, 1 H), 7.21-
489.2
97.7%

7.33 (m, 1 H), 6.96-7.15 (m, 1 H), 6.75 (s, 1 H), 4.80 (br s, 1
[M + H]⁺

H), 3.78 (br s, 5 H), 3.61 (br s, 4 H), 2.96-3.19 (m, 1 H), 2.86

(br d, 1 H)

649
(CD₃OD) δ 8.32-8.49 (m, 1 H), 7.63-7.77 (m, 2 H), 7.40-7.55
418.1
99.0%

(m, 1 H), 7.21 (td, 1 H), 6.85 (s, 0.8 H), 6.06 (br s, 0.2 H),
[M + H]⁺

5.00 (br dd, 0.2 H), 3.84-4.07 (m, 1.6 H), 3.55-3.69 (m, 0.2

H), 2.91-3.06 (m, 1 H), 2.74-2.90 (m, 1 H), 1.99 (t, 3 H)

650
(CD₃OD) δ 8.26-8.50 (m, 1 H), 7.60-7.80 (m, 2 H), 7.41-7.56
418.1
99.0%

(m, 1 H), 7.21 (td, 1 H), 6.85 (s, 0.8 H), 6.06 (br s, 0.2 H),
[M + H]⁺

4.97-5.03 (m, 0.2 H), 3.98 (br d, 1.6 H), 3.60 (br s, 0.2 H),

2.92-3.06 (m, 1 H), 2.71-2.91 (m, 1 H), 1.99 (t, 3 H)

651
(CD₃OD) δ 8.23-8.35 (m, 1 H), 7.54-7.67 (m, 1 H), 7.23-7.46
418.1
97.4%

(m, 2 H), 7.05 (t, 1 H), 6.74 (s, 0.8 H), 5.96 (br s, 0.2 H), 4.89
[M + H]⁺

(br dd, 0.2 H), 3.87 (br d, 1.6 H), 3.44-3.59 (m, 0.2 H), 2.80-

2.93 (m, 1 H), 2.62-2.80 (m, 1 H), 1.87 (t, 3 H)

652
(CD₃OD) δ 8.30-8.46 (m, 1 H), 7.63-7.80 (m, 1 H), 7.35-7.57
418.1
98.8%

(m, 2 H), 7.17 (t, 1 H), 6.86 (br s, 0.8 H), 6.08 (br s, 0.2 H),
[M + H]⁺

4.99-5.07 (m, 0.2 H), 3.84-4.11 (m, 1.6 H), 3.55-3.72 (m, 0.2

H), 2.98 (br dd, 1 H), 2.73-2.92 (m, 1 H), 1.91-2.09 (m, 3 H)

653
(CD₃OD) δ 8.54-8.73 (m, 1 H), 7.87-8.04 (m, 1 H), 7.66-7.84
446.1
99.3%

(m, 2 H), 7.42-7.57 (m, 2 H), 7.17-7.32 (m, 1 H), 6.89 (br s, 1
[M + H]⁺

H), 5.06-5.29 (m, 1 H), 3.57-4.12 (m, 1 H), 3.23 (br s, 1 H),

2.90 (br d, 1 H), 2.38-2.49 (m, 3 H)

654
(CD₃OD) δ 8.45-8.77 (m, 1 H), 7.86-8.02 (m, 1 H), 7.65-7.81
446.1
93.9%

(m, 2 H), 7.39-7.58 (m, 2 H), 7.14-7.30 (m, 1 H), 6.91 (s, 1
[M + H]⁺

H), 5.05-5.28 (m, 1 H), 3.51-4.04 (m, 1 H), 2.83-3.28 (m, 2

H), 2.38-2.49 (m, 3 H)

655
(CD₃OD) δ 7.69 (s, 1 H), 6.95-7.25 (m, 3 H), 6.70 (br s, 1 H),
476.2
98.6%

4.92-5.02 (m, 0.5 H), 4.57 (br s, 0.5 H), 3.55-4.06 (m, 1 H),
[M + H]⁺

2.81-3.22 (m, 2 H), 2.55 (s, 3 H), 1.50-1.72 (m, 6 H)

656
(CD₃OD) δ 7.69 (s, 1 H), 6.94-7.25 (m, 3 H), 6.72 (br s, 1 H),
476.2
98.2%

4.94-5.03 (m, 0.5 H), 4.56 (br d, 0.5 H), 3.55-4.07 (m, 1 H),
[M + H]⁺

2.80-3.19 (m, 2 H), 2.55 (s, 3 H), 1.50-1.71 (m, 6 H)

657
(CD₃OD) δ 8.45 (s, 1 H), 7.69 (s, 1 H), 6.98-7.25 (m, 3 H),
418.1
98.0%

6.75 (br s, 1 H), 4.53 (br s, 1 H), 3.50-4.02 (m, 1 H), 2.82-3.13
[M + H]⁺

(m, 2 H), 2.55 (s, 3 H)

658
(CD₃OD) δ 8.45 (s, 1 H), 7.70 (s, 1 H), 6.98-7.26 (m, 3 H),
418.1
99.1%

6.75 (br s, 1 H), 4.47-4.63 (m, 1 H), 3.50-4.04 (m, 1 H), 2.82-
[M + H]⁺

3.15 (m, 2 H), 2.55 (s, 3 H)

659
(CD₃OD) δ 7.68 (s, 1 H), 6.62-7.28 (m, 4 H), 4.49-4.66 (m, 1
472.2
99.8%

H), 4.04 (br s, 1 H), 2.80-3.19 (m, 2 H), 2.45-2.55 (m, 6 H),
[M + H]⁺

1.51-1.73 (m, 6 H)

660
(CD₃OD) δ 7.68 (br s, 1 H), 6.68-7.27 (m, 4 H), 4.49-4.64 (m,
472.2
99.3%

1 H), 3.62-4.15 (m, 1 H), 2.76-3.22 (m, 2 H), 2.46-2.53 (m, 6
[M + H]⁺

H), 1.53-1.70 (m, 6 H)

661
(CD₃OD) δ 8.62-9.14 (m, 2 H), 7.50-7.84 (m, 3 H), 7.44 (dd,
482.1
90.7%

1 H), 7.06-7.40 (m, 2 H), 6.81 (br s, 1 H), 5.05 (br s, 0.3 H),
[M + H]⁺

4.76 (br d, 0.7 H), 4.01 (br s, 0.7 H), 3.69 (br s, 0.3 H), 3.21-

3.32 (m, 0.7 H), 3.02 (br s, 0.3 H), 2.91 (br d, 1 H)

662
(CD₃OD) δ 8.61-9.19 (m, 2 H), 7.51-7.83 (m, 3 H), 7.44 (dd,
482.2
88.8%

1 H), 7.06-7.41 (m, 2 H), 6.82 (br s, 1 H), 5.05 (br s, 0.3 H),
[M + H]⁺

4.76 (br d, 0.7 H), 3.56-4.14 (m, 1 H), 3.22-3.32 (m, 0.7 H),

3.00 (br s, 0.3 H), 2.80-2.97 (m, 1 H)

663
(CD₃OD) δ 8.45 (br s, 1 H), 7.68 (s, 1 H), 6.96-7.32 (m, 2 H),
434.1
99.2%

6.61-6.89 (m, 2 H), 4.53 (br s, 1 H), 3.82-4.04 (m, 4 H), 2.73-
[M + H]⁺

3.18 (m, 2 H)

664
(CD₃OD) δ 8.45 (br s, 1 H), 7.68 (s, 1 H), 6.98-7.27 (m, 2 H),
434.1
96.5%

6.69-6.89 (m, 2 H), 4.49-4.61 (m, 1 H), 3.83 (s, 4 H), 2.79-
[M + H]⁺

3.16 (m, 2 H)

665
(CD₃OD) δ 8.34-8.47 (m, 1 H), 8.05-8.16 (m, 1 H), 7.67-7.77
453.1
100%

(m, 1 H), 7.56 (br s, 0.4 H), 7.27-7.39 (m, 1 H), 7.11-7.23 (m,
[M + H]⁺

1 H), 6.89 (br s, 0.6 H), 5.36 (dd, 0.7 H), 5.13 (dd, 0.3 H),

3.90-4.11 (m, 3.7 H), 3.69 (br s, 0.3 H), 3.13-3.27 (m, 1 H),

2.84-3.07 (m, 1 H)

666
(CD₃OD) δ 8.35-8.47 (m, 1 H), 8.05-8.16 (m, 1 H), 7.72 (s, 1
453.1
98.2%

H), 7.56 (br s, 0.3 H), 7.33 (br d, 1 H), 7.10-7.24 (m, 1 H),
[M + H]⁺

6.89 (br s, 0.7 H), 5.36 (dd, 0.7 H), 5.13 (dd, 0.3 H), 3.90-4.10

(m, 3.7 H), 3.70 (br s, 0.3 H), 3.13-3.26 (m, 1 H), 2.84-3.07

(m, 1 H)

667
(CD₃OD) δ 8.57-9.21 (m, 2 H), 7.50-7.83 (m, 3 H), 7.06-7.44
482.1
97.3%

(m, 3 H), 6.86 (br s, 1 H), 5.06 (br s, 0.4 H), 4.77 (br d, 0.6 H),
[M + H]⁺

3.66-4.19 (m, 1 H), 3.21-3.32 (m, 0.7 H), 3.03 (br s, 0.3 H),

2.93 (br d, 1 H)

668
(CD₃OD) δ 8.58-9.27 (m, 2 H), 7.49-7.84 (m, 3 H), 7.05-7.46
482.1
88.6%

(m, 3 H), 6.85 (br s, 1 H), 5.05 (br s, 0.3 H), 4.77 (br d, 0.7 H),
[M + H]⁺

3.64-4.21 (m, 1 H), 3.19-3.32 (m, 0.7 H), 3.00-3.11 (m, 0.3

H), 2.93 (br d, 1 H)

669
(CD₃OD) δ 8.37 (s, 0.7 H), 8.16 (br s, 0.3 H), 8.09 (s, 0.6 H),
502.2
100%

7.91 (br s, 0.4 H), 7.67-7.74 (m, 1 H), 7.55 (br d, 1 H), 7.40
[M + H]⁺

(br d, 1 H), 7.22-7.31 (m, 1 H), 6.87 (br s, 0.7 H), 6.40 (br s,

0.3 H), 4.92-5.04 (m, 1 H), 4.24 (br d, 0.7 H), 3.96-4.01 (m, 3

H), 3.74 (br s, 0.3 H), 3.00-3.15 (m, 1 H), 2.85-2.94 (m, 1 H)

670
(CD₃OD) δ 8.37 (s, 0.7 H), 8.16 (br s, 0.3 H), 8.09 (s, 0.6 H),
502.2
100%

7.91 (br s, 0.4 H), 7.73 (br s, 1 H), 7.55 (br d, 1 H), 7.40 (br d,
[M + H]⁺

1 H), 7.22-7.32 (m, 1 H), 6.87 (br s, 0.7 H), 6.40 (br s, 0.3 H),

4.91-5.04 (m, 1 H), 4.24 (br d, 0.7 H), 3.96-4.01 (m, 3 H),

3.73 (br s, 0.3 H), 3.00-3.15 (m, 1 H), 2.83-2.96 (m, 1 H)

671
(CD₃OD) δ 8.70-8.90 (m, 1 H), 8.31-8.55 (m, 1 H), 8.02-8.17
516.2
100%

(m, 1 H), 7.71-7.82 (m, 1 H), 7.63-7.71 (m, 1 H), 7.55 (s, 0.3
[M + H]⁺

H), 7.37-7.50 (m, 1 H), 7.14-7.30 (m, 1 H), 6.92 (s, 0.7 H),

5.09-5.36 (m, 1 H), 3.92-4.10 (m, 0.7 H), 3.68 (br dd, 0.3 H),

3.18-3.29 (m, 0.8 H), 2.98-3.09 (m, 0.2 H), 2.82-2.97 (m, 1 H)

672
(CD₃OD) δ 8.58-8.75 (m, 1 H), 8.19-8.46 (m, 1 H), 7.88-8.06
516.2
99.0%

(m, 1 H), 7.59-7.66 (m, 1 H), 7.51-7.59 (m, 1 H), 7.43 (s, 0.3
[M + H]⁺

H), 7.28-7.38 (m, 1 H), 7.04-7.14 (m, 1 H), 6.80 (s, 0.7 H),

4.97-5.24 (m, 1 H), 3.81-3.96 (m, 0.7 H), 3.56 (td, 0.3 H),

3.05-3.17 (m, 0.8 H), 2.86-2.98 (m, 0.2 H), 2.73-2.86 (m, 1 H)

673
(CD₃OD) δ 8.75-9.06 (m, 1 H), 8.09-8.59 (m, 1 H), 7.56-7.82
467.1
100%

(m, 2 H), 7.40-7.54 (m, 2 H), 7.17-7.31 (m, 1 H), 6.89 (s, 1
[M + H]⁺

H), 5.03-5.39 (m, 1 H), 3.54-4.04 (m, 1 H), 2.81-2.94 (m, 2

H), 2.39-2.57 (m, 3 H)

674
(CD₃OD) δ 8.80-9.00 (m, 1 H), 8.20-8.42 (m, 1 H), 7.56-7.84
467.1
98.8%

(m, 2 H), 7.44-7.54 (m, 2 H), 7.14-7.37 (m, 1 H), 6.88 (br s, 1
[M + H]⁺

H), 5.03-5.41 (m, 1 H), 3.53-4.11 (m, 1 H), 2.79-3.27 (m, 2

H), 2.42-2.48 (m, 3 H)

675
(CD₃OD) δ 7.69 (s, 1 H), 7.55 (d, 1 H), 7.40 (td, 1 H), 7.23-
505.2
91.4%

7.31 (m, 1 H), 6.94-7.14 (m, 1 H), 6.72 (br s, 1 H), 4.91-4.99
[M + H]⁺

(m, 1 H), 4.82 (br s, 1 H), 3.62-3.94 (m, 5 H), 2.80-3.13 (m, 2

H), 1.90 (br s, 4 H)

676
(CD₃OD) δ 7.69 (s, 1 H), 7.55 (d, 1 H), 7.40 (td, 1 H), 7.22-
505.2
86.6%

7.30 (m, 1 H), 6.96-7.14 (m, 1 H), 6.73 (br s, 1 H), 4.93 (br s,
[M + H]⁺

1 H), 4.82 (br s, 1 H), 3.63-3.90 (m, 5 H), 2.80-3.14 (m, 2 H),

1.83-2.08 (m, 4 H)

677
(DMSO-d₆) δ 12.11-12.29 (m, 1 H), 8.42-8.62 (m, 1 H), 8.09-
458.1
99.4%

8.28 (m, 1 H), 7.59-7.68 (m, 3 H), 7.48-7.58 (m, 1 H), 7.16-
[M + H]⁺

7.30 (m, 1 H), 6.65 (s, 1 H), 4.71-5.21 (m, 1 H), 3.93-3.95 (m,

3 H), 3.41-3.79 (m, 1 H), 2.80-3.14 (m, 2 H), 2.38-2.45 (m, 3

H)

678
(DMSO-d₆) δ 12.01-12.33 (m, 1 H), 8.40-8.57 (m, 1 H), 8.09-
458.2
98.3%

8.29 (m, 1 H), 7.60-7.68 (m, 3 H), 7.44-7.59 (m, 1 H), 7.17-
[M + H]⁺

7.26 (m, 1 H), 6.58-6.99 (m, 1 H), 4.92-5.19 (m, 1 H), 3.93-

3.96 (m, 3 H), 3.42-3.79 (m, 1 H), 2.81-3.14 (m, 2 H), 2.38-

2.44 (m, 3 H)

679
(CD₃OD) δ 8.59-8.69 (m, 1 H), 7.85-7.98 (m, 1 H), 7.71-7.78
446.1
93.0%

(m, 2 H), 7.37-7.59 (m, 2 H), 7.17-7.26 (m, 1 H), 6.89 (br s, 1
[M + H]⁺

H), 5.02-5.24 (m, 1 H), 3.97 (br s, 1 H), 2.83-3.25 (m, 2 H),

2.42-2.55 (m, 3 H)

680
(CD₃OD) δ 8.63-8.69 (m, 1 H), 7.94 (q, 1 H), 7.68-7.81 (m, 2
446.2
95.3%

H), 7.44-7.60 (m, 2 H), 7.16-7.26 (m, 1 H), 6.93 (s, 1 H),
[M + H]⁺

5.03-5.27 (m, 1 H), 3.46-4.04 (m, 2 H), 2.84-3.30 (m, 2 H),

2.40-2.56 (m, 3 H)

681
(CD₃OD) δ 8.82-8.96 (m, 1 H), 8.29-8.40 (m, 1 H), 7.34-7.87
467.2
100%

(m, 5 H), 7.16-7.24 (m, 1 H), 6.87 (br s, 1 H), 5.05-5.37 (m, 1
[M + H]⁺

H), 3.45-4.07 (m, 1 H), 2.81-3.25 (m, 2 H), 2.45-2.58 (m, 3 H)

682
(CD₃OD) δ 8.86-8.96 (m, 1 H), 8.26-8.38 (m, 1 H), 7.41-7.83
467.2
99.5%

(m, 5 H), 7.10-7.28 (m, 1 H), 6.88 (br s, 1 H), 5.03-5.36 (m, 1
[M + H]⁺

H), 3.44-4.05 (m, 1 H), 2.72-3.24 (m, 2 H), 2.44-2.54 (m, 3 H)

683
(CD₃OD) δ 7.59-7.78 (m, 3 H), 7.30-7.49 (m, 2 H), 6.79-7.24
418.1
100%

(m, 1 H), 5.11 (br dd, 0.3 H), 4.76 (br dd, 0.7 H), 4.17 (s, 3 H),
[M + H]⁺

3.52-3.98 (m, 1 H), 2.96-3.28 (m, 1 H), 2.84 (br d, 1 H)

684
(CD₃OD) δ 7.48-7.63 (m, 3 H), 7.23-7.38 (m, 2 H), 6.69-7.05
418.1
100%

(m, 1 H), 4.99 (dd, 0.3 H), 4.64 (dd, 0.7 H), 4.02-4.08 (m, 3
[M + H]⁺

H), 3.37-3.86 (m, 1 H), 2.81-3.15 (m, 1 H), 2.63-2.80 (m, 1 H)

685
(CD₃OD) δ 7.68-7.76 (m, 1 H), 7.45-7.54 (m, 1 H), 7.20-7.32
432.2
100%

(m, 2 H), 6.82-7.15 (m, 1 H), 5.10 (br dd, 0.3 H), 4.76 (dd, 0.7
[M + H]⁺

H), 4.17 (s, 3 H), 3.91 (br t, 0.7 H), 3.61 (br t, 0.3 H), 2.95-

3.29 (m, 1 H), 2.75-2.93 (m, 1 H), 2.49-2.62 (m, 3 H)

686
(CD₃OD) δ 7.57-7.64 (m, 1 H), 7.34-7.41 (m, 1 H), 7.08-7.20
432.2
98.7%

(m, 2 H), 6.60-7.05 (m, 1 H), 4.98 (dd, 0.3 H), 4.64 (dd, 0.7
[M + H]⁺

H), 4.05 (s, 3 H), 3.75-3.83 (m, 0.7 H), 3.49 (td, 0.3 H), 2.84-

3.16 (m, 1 H), 2.67-2.81 (m, 1 H), 2.37-2.49 (m, 3 H)

687
(CD₃OD) δ 7.56-8.10 (m, 4 H), 7.45 (br s, 1 H), 6.98-7.38 (m,
484.2
98.8%

2 H), 6.78 (br s, 1 H), 4.92-5.08 (m, 0.4 H), 4.69 (br s, 0.6 H),
[M + H]⁺

4.11 (br s, 3.7 H), 3.73 (br s, 0.3 H), 3.16 (br s, 1 H), 2.91 (br

s, 1 H)

688
(CD₃OD) δ 7.57-8.11 (m, 4 H), 7.45 (br s, 1 H), 6.98-7.38 (m,
484.2
98.5%

2 H), 6.78 (br s, 1 H), 4.93-5.09 (m, 0.4 H), 4.70 (br s, 0.6 H),
[M + H]⁺

4.11 (br s, 3.7 H), 3.75 (br s, 0.3 H), 3.02-3.28 (m, 1 H), 2.90

(br s, 1 H)

689
(CD₃OD) δ 7.61-7.76 (m, 2 H), 7.43 (dd, 1 H), 6.96-7.32 (m,
474.2
99.2%

2 H), 6.75 (br s, 1 H), 4.94-5.12 (m, 0.5 H), 4.58 (br s, 0.5 H),
[M + H]⁺

3.57-4.07 (m, 1 H), 2.94-3.25 (m, 1 H), 2.87 (br d, 1 H), 2.53-

2.81 (m, 2 H), 2.18-2.51 (m, 2 H), 1.54-2.11 (m, 2 H)

690
(CD₃OD) δ 7.59-7.80 (m, 2 H), 7.43 (dd, 1 H), 6.94-7.31 (m,
474.2
100%

2 H), 6.75 (br s, 1 H), 4.93-5.12 (m, 0.4 H), 4.58 (br s, 0.6 H),
[M + H]⁺

3.52-4.11 (m, 1 H), 2.94-3.23 (m, 1 H), 2.87 (br d, 1 H), 2.53-

2.81 (m, 2 H), 2.12-2.51 (m, 2 H), 1.49-2.10 (m, 2 H)

691
(CD₃OD) δ 7.64-8.13 (m, 3 H), 7.56 (br s, 1 H), 7.40 (br d, 1
484.1
100%

H), 7.01-7.35 (m, 2 H), 6.82 (s, 1 H), 4.93-5.08 (m, 0.5 H),
[M + H]⁺

4.71 (br s, 0.5 H), 4.11 (br s, 3.7 H), 3.76 (br s, 0.3 H), 3.15

(br s, 1 H), 2.92 (br s, 1 H)

692
(CD₃OD) δ 7.64-8.15 (m, 3 H), 7.56 (br s, 1 H), 7.40 (br d, 1
484.2
99.5%

H), 7.01-7.35 (m, 2 H), 6.82 (s, 1 H), 4.91-5.12 (m, 0.5 H),
[M + H]⁺

4.72 (br s, 0.5 H), 4.11 (br s, 3.8 H), 3.77 (br s, 0.2 H), 3.02-

3.27 (m, 1 H), 2.92 (br s, 1 H)

693
(CD₃OD) δ 9.47 (br s, 1 H), 8.36-8.95 (m, 2 H), 7.72 (br s, 1
482.1
99.7%

H), 7.55 (br d, 1 H), 7.05-7.47 (m, 3 H), 6.85 (br s, 1 H), 5.04
[M + H]⁺

(br s, 0.3 H), 4.76 (br d, 0.7 H), 4.05 (br s, 0.7 H), 3.78 (br s,

0.3 H), 3.28 (br s, 0.8 H), 3.03 (br s, 0.2 H), 2.94 (br d, 1 H)

694
(CD₃OD) δ 9.46 (br s, 1 H), 8.39-8.92 (m, 2 H), 7.72 (br s, 1
482.1
99.4%

H), 7.55 (br d, 1 H), 7.04-7.46 (m, 3 H), 6.85 (br s, 1 H), 5.02
[M + H]⁺

(br s, 0.3 H), 4.77 (br d, 0.7 H), 4.05 (br s, 0.6 H), 3.79 (br s,

0.4 H), 3.28 (br s, 0.7 H), 3.01-3.13 (m, 0.3 H), 2.93 (br d, 1

H)

695
(CD₃OD) δ 8.25-8.43 (m, 1 H), 7.45-7.84 (m, 4 H), 7.15-7.31
467.2
81.1%

(m, 2 H), 6.89 (br s, 1 H), 5.04-5.35 (m, 1 H), 3.43-4.07 (m, 1
[M + H]⁺

H), 2.79-3.28 (m, 2 H), 2.39-2.52 (m, 3 H)

696
(CD₃OD) δ 8.16-8.50 (m, 1 H), 7.45-7.84 (m, 4 H), 7.11-7.34
467.2
81.1%

(m, 2 H), 6.88 (br s, 1 H), 5.03-5.34 (m, 1 H), 3.51-4.04 (m, 1
[M + H]⁺

H), 2.78-3.28 (m, 2 H), 2.39-2.51 (m, 3 H)

697
(CD₃OD) δ 7.71 (s, 1 H), 7.22-7.36 (m, 2 H), 6.98-7.11 (m,
448.2
99.1%

1.3 H), 6.90 (s, 0.7 H), 5.07 (dd, 0.3 H), 4.74 (dd, 0.7 H),
[M + H]⁺

4.12-4.22 (m, 3 H), 3.98-4.07 (m, 3 H), 3.80-3.94 (m, 0.7 H),

3.40-3.54 (m, 0.3 H), 2.95-3.29 (m, 1 H), 2.77-2.93 (m, 1 H)

698
(CD₃OD) δ 7.71 (s, 1 H), 7.21-7.37 (m, 2 H), 6.98-7.15 (m,
448.2
98.3%

1.3 H), 6.90 (br s, 0.7 H), 5.07 (dd, 0.3 H), 4.74 (dd, 0.7 H),
[M + H]⁺

4.12-4.21 (m, 3 H), 3.99-4.05 (m, 3 H), 3.88 (br t, 0.7 H),

3.42-3.54 (m, 0.3 H), 2.95-3.28 (m, 1 H), 2.79-2.93 (m, 1 H)

699
(CD₃OD) δ 8.31 (br s, 1 H), 8.11 (s, 1 H), 7.83 (d, 1 H), 7.69
520.2
98.2%

(s, 1 H), 7.46 (dd, 1 H), 7.34 (br d, 1 H), 7.16 (td, 1 H), 6.77
[M + H]⁺

(s, 1 H), 4.75 (br dd, 1 H), 3.75-4.09 (m, 2 H), 3.48-3.61 (m, 2

H), 3.06-3.23 (m, 1 H), 2.80-2.97 (m, 3 H), 2.03 (br d, 2 H),

1.59-1.81 (m, 2 H)

700
(CD₃OD) δ 8.30 (br s, 1 H), 8.11 (s, 1 H), 7.83 (d, 1 H), 7.69
520.2
94.3%

(s, 1 H), 7.46 (dd, 1 H), 7.34 (br d, 1 H), 7.16 (td, 1 H), 6.77
[M + H]⁺

(s, 1 H), 4.75 (br dd, 1 H), 3.72-4.04 (m, 2 H), 3.46-3.60 (m, 2

H), 3.07-3.20 (m, 1 H), 2.80-3.01 (m, 3 H), 2.03 (br d, 2 H),

1.61-1.82 (m, 2 H)

701
(CD₃OD) δ 8.35 (br s, 1 H), 8.12 (s, 1 H), 7.85 (d, 1 H), 7.69
498.3
100%

(s, 1 H), 7.45 (d, 2 H), 7.30 (t, 1 H), 7.20 (d, 1 H), 6.80 (br s, 1
[M + H]⁺

H), 4.76 (br d, 1 H), 3.94 (br s, 1 H), 3.76-3.86 (m, 1 H), 3.46-

3.61 (m, 2 H), 3.05-3.19 (m, 1 H), 2.80-3.00 (m, 3 H), 2.59 (s,

3 H), 1.97-2.10 (m, 2 H), 1.63-1.82 (m, 2 H)

702
(CD₃OD) δ 8.35 (br s, 1 H), 8.11 (s, 1 H), 7.85 (d, 1 H), 7.69
498.3
100%

(s, 1 H), 7.45 (d, 2 H), 7.30 (t, 1 H), 7.19 (d, 1 H), 6.80 (br s, 1
[M + H]⁺

H), 4.71-4.82 (m, 1 H), 3.95 (br s, 1 H), 3.80 (tt, 1 H), 3.48-

3.57 (m, 2 H), 3.02-3.21 (m, 1 H), 2.82-2.97 (m, 3 H), 2.59 (s,

3 H), 1.98-2.06 (m, 2 H), 1.63-1.81 (m, 2 H)

703
(CD₃OD) δ 8.28-8.35 (m, 1 H), 7.62-7.83 (m, 2 H), 7.39-7.57
467.2
100%

(m, 3 H), 7.16-7.25 (m, 2 H), 6.90 (s, 1 H), 5.02-5.30 (m, 1
[M + H]⁺

H), 3.87-4.01 (m, 1 H), 3.44-3.66 (m, 1 H), 2.78-3.25 (m, 2

H), 2.44-2.52 (m, 3 H)

704
(CD₃OD) δ 8.29-8.36 (m, 1 H), 7.63-7.83 (m, 2 H), 7.41-7.59
467.2
99.1%

(m, 3 H), 7.16-7.24 (m, 2 H), 6.90 (s, 1 H), 5.04-5.32 (m, 1
[M + H]⁺

H), 3.86-4.03 (m, 1 H), 3.42-3.65 (m, 1 H), 2.80-3.25 (m, 2

H), 2.45-2.51 (m, 3 H)

705
(CD₃OD) δ 7.96-8.09 (m, 1 H), 7.64-7.72 (m, 2.7 H), 7.51-
378.2
99.7%

7.62 (m, 0.3 H), 7.30-7.47 (m, 2 H), 6.83-6.99 (m, 1 H), 4.92-
[M + H]⁺

5.13 (m, 1.3 H), 4.37 (dd, 0.7 H), 3.78-3.91 (m, 0.7 H), 3.47

(td, 0.3 H), 2.93-3.21 (m, 1 H), 2.71-2.91 (m, 1 H), 1.38-1.52

(m, 6 H)

706
(CD₃OD) δ 7.98-8.07 (m, 1 H), 7.62-7.73 (m, 2.8 H), 7.53-
378.2
98.1%

7.59 (m, 0.2 H), 7.32-7.46 (m, 2 H), 6.84-6.98 (m, 1 H), 4.92-
[M + H]⁺

5.14 (m, 1.4 H), 4.37 (dd, 0.6 H), 3.78-3.91 (m, 0.7 H), 3.47

(td, 0.3 H), 2.92-3.21 (m, 1 H), 2.73-2.91 (m, 1 H), 1.37-1.52

(m, 6 H)

707
(CD₃OD) δ 7.96-8.09 (m, 1 H), 7.70 (s, 1 H), 7.43-7.56 (m, 1
396.2
100%

H), 7.31-7.40 (m, 1 H), 7.15-7.27 (m, 1 H), 6.86-7.06 (m, 1
[M + H]⁺

H), 4.92-5.12 (m, 1.4 H), 4.38 (dd, 0.6 H), 3.78-3.92 (m, 0.7

H), 3.48 (td, 0.3 H), 2.95-3.20 (m, 1 H), 2.73-2.94 (m, 1 H),

1.42-1.53 (m, 6 H)

708
(CD₃OD) δ 7.96-8.10 (m, 1 H), 7.70 (s, 1 H), 7.44-7.58 (m, 1
396.2
99.1%

H), 7.28-7.43 (m, 1 H), 7.12-7.27 (m, 1 H), 6.84-7.07 (m, 1
[M + H]⁺

H), 4.97-5.12 (m, 1.3 H), 4.38 (dd, 0.7 H), 3.85 (br t, 0.7 H),

3.41-3.54 (m, 0.3 H), 2.96-3.20 (m, 1 H), 2.74-2.91 (m, 1 H),

1.42-1.53 (m, 6 H)

709
(CD₃OD) δ 7.90-7.94 (m, 1 H), 7.69-7.75 (m, 1 H), 7.51 (br d,
417.2
98.5%

1 H), 7.23-7.32 (m, 2 H), 6.75-6.98 (m, 1.8 H), 6.11 (s, 0.2 H),
[M + H]⁺

5.00 (br dd, 0.3 H), 3.83-4.05 (m, 1.5 H), 3.46-3.63 (m, 0.2

H), 2.88-3.05 (m, 1 H), 2.71-2.87 (m, 1 H), 2.49-2.60 (m, 3 H)

710
(CD₃OD) δ 7.90-7.94 (m, 1 H), 7.69-7.75 (m, 1 H), 7.51 (br d,
417.2
96.9%

1 H), 7.23-7.32 (m, 2 H), 6.76-7.00 (m, 1.8 H), 6.11 (s, 0.2 H),
[M + H]⁺

5.00 (br dd, 0.3 H), 3.81-4.06 (m, 1.5 H), 3.48-3.61 (m, 0.2

H), 2.88-3.10 (m, 1 H), 2.72-2.86 (m, 1 H), 2.52-2.59 (m, 3 H)

711
(CD₃OD) δ 7.65-7.76 (m, 3 H), 7.56 (s, 1 H), 7.37-7.48 (m, 2
349.2
100%

H), 6.40-6.94 (m, 2 H), 4.34 (br s, 1 H), 3.95 (br s, 4 H), 2.98-
[M + H]⁺

3.08 (m, 1 H), 2.75-2.89 (m, 1 H)

712
(CD₃OD) δ 7.63-7.73 (m, 3 H), 7.56 (s, 1 H), 7.37-7.47 (m, 2
349.2
99.2%

H), 6.42-6.93 (m, 2 H), 4.34 (br s, 1 H), 3.95 (s, 4 H), 2.99-
[M + H]⁺

3.08 (m, 1 H), 2.76-2.86 (m, 1 H)

713
(CD₃OD) δ 7.62-7.85 (m, 2 H), 7.53 (br d, 1 H), 7.39 (td, 1
412.2
93.3%

H), 7.18-7.30 (m, 1 H), 6.70-6.86 (m, 1 H), 4.75 (br s, 1 H),
[M + H]⁺

3.98 (br s, 1 H), 3.15 (br s, 1 H), 2.89 (br d, 1 H), 1.65 (br s, 6

H)

714
(CD₃OD) δ 7.64-7.87 (m, 2 H), 7.53 (br d, 1 H), 7.39 (td, 1
412.1
98.8%

H), 7.18-7.30 (m, 1 H), 6.80 (br s, 1 H), 4.74 (br s, 1 H), 3.98
[M + H]⁺

(br s, 1 H), 3.15 (br s, 1 H), 2.89 (br d, 1 H), 1.65 (br s, 6 H)

715
(CD₃OD) δ 7.67 (s, 1 H), 6.94-7.25 (m, 2 H), 6.58-6.89 (m, 2
492.2
98.6%

H), 4.90-5.02 (m, 0.5 H), 4.55 (m, 0.5 H), 4.00 (s, 3 H), 3.53-
[M + H]⁺

3.98 (m, 1 H), 2.82-3.21 (m, 2 H), 1.54-1.72 (m, 6 H)

716
(CD₃OD) δ 7.67 (s, 1 H), 6.95-7.24 (m, 2 H), 6.55-6.89 (m, 2
492.2
94.0%

H), 4.90-4.98 (m, 0.5 H), 4.55 (m, 0.5 H), 4.00 (s, 3 H), 3.45-
[M + H]⁺

3.98 (m, 1 H), 2.80-3.20 (m, 2 H), 1.54-1.72 (m, 6 H)

717
(CD₃OD) δ 8.44 (s, 1 H), 7.68 (s, 1 H), 6.94-7.26 (m, 2 H),
434.1
98.8%

6.60-6.88 (m, 2 H), 4.90-4.96 (m, 0.5 H), 4.53 (m, 0.5 H),
[M + H]⁺

4.00 (s, 4 H), 2.82-3.12 (m, 2 H)

718
(CD₃OD) δ 8.44 (s, 1 H), 7.68 (s, 1 H), 6.93-7.26 (m, 2 H),
434.1
93.5%

6.62-6.88 (m, 2 H), 4.89-5.01 (m, 0.5 H), 4.53 (m, 0.5 H),
[M + H]⁺

4.00 (s, 4 H), 2.81-3.12 (m, 2 H)

719
(CD₃OD) δ 7.67 (s, 1 H), 7.43 (dd, 1 H), 6.97-7.24 (m, 2 H),
476.2
98.0%

6.74 (br s, 1 H), 4.90-5.01 (m, 0.5 H), 4.48-4.56 (m, 0.5 H),
[M + H]⁺

3.58-4.10 (m, 1 H), 2.82-3.21 (m, 2 H), 2.46 (d, 3 H), 1.53-

1.72 (m, 6 H)

720
(CD₃OD) δ 7.67 (s, 1 H), 7.43 (dd, 1 H), 6.97-7.25 (m, 2 H),
476.2
95.9%

6.46-6.89 (m, 1 H), 4.90-5.05 (m, 0.5 H), 4.51-4.58 (m, 0.5
[M + H]⁺

H), 3.57-4.06 (m, 1 H), 2.80-3.16 (m, 2 H), 2.46 (d, 3 H),

1.52-1.71 (m, 6 H)

721
(CD₃OD) δ 8.44 (br s, 1 H), 7.68 (s, 1 H), 7.43 (dd, 1 H),
418.1
97.8%

6.99-7.26 (m, 2 H), 6.76 (br s, 1 H), 4.46-4.59 (m, 1 H), 3.99
[M + H]⁺

(br s, 1 H), 2.82-3.10 (m, 2 H), 2.45 (d, 3 H)

722
(CD₃OD) δ 8.44 (br s, 1 H), 7.68 (s, 1 H), 7.43 (dd, 1 H),
418.1
98.1%

6.99-7.26 (m, 2 H), 6.76 (br s, 1 H), 4.57 (br d, 1 H), 4.00 (br
[M + H]⁺

s, 1 H), 2.82-3.12 (m, 2 H), 2.45 (d, 3 H)

723
(CD₃OD) δ 7.69 (s, 1 H), 6.95-7.29 (m, 3 H), 6.57-6.81 (m, 1
476.2
99.3%

H), 4.46-4.72 (m, 1 H), 3.52-4.09 (m, 1 H), 2.80-3.25 (m, 2
[M + H]⁺

H), 2.51 (s, 3 H), 1.48-1.73 (m, 6 H)

724
(CD₃OD) δ 7.69 (s, 1 H), 6.92-7.32 (m, 3 H), 6.75 (br s, 1 H),
476.2
98.8%

4.60 (s, 1 H), 3.59-4.15 (m, 1 H), 2.79-3.23 (m, 2 H), 2.51 (s,
[M + H]⁺

3 H), 1.48-1.75 (m, 6 H)

725
(CD₃OD) δ 7.61-7.81 (m, 3 H), 7.52 (s, 1 H), 7.38-7.49 (m, 2
375.2
99.7%

H), 6.93 (br s, 0.7 H), 6.59 (s, 1 H), 6.22 (br s, 0.3 H), 5.02 (br
[M + H]⁺

s, 0.2 H), 4.08-4.25 (m, 0.8 H), 3.92 (br s, 0.7 H), 3.47-3.74

(m, 1.3 H), 3.00 (br s, 1 H), 2.72-2.91 (m, 1 H), 0.80-1.19 (m,

4 H)

726
(CD₃OD) δ 7.61-7.86 (m, 3 H), 7.53 (d, 1 H), 7.36-7.49 (m, 2
375.2
99.7%

H), 6.93 (br s, 0.7 H), 6.59 (s, 1 H), 6.22 (br s, 0.3 H), 5.01 (br
[M + H]⁺

s, 0.3 H), 4.07-4.21 (m, 0.7 H), 3.94 (br d, 0.7 H), 3.46-3.75

(m, 1.3 H), 3.00 (br s, 1 H), 2.69-2.91 (m, 1 H), 0.78-1.17 (m,

4 H)

727
(CD₃OD) δ 7.72 (s, 1 H), 7.49-7.61 (m, 2 H), 7.40 (td, 1 H),
393.2
99.2%

7.21-7.31 (m, 1 H), 6.92 (br s, 0.7 H), 6.60 (d, 1 H), 6.14-6.42
[M + H]⁺

(m, 0.3 H), 4.95-5.13 (m, 0.3 H), 4.16 (br s, 0.7 H), 3.92 (br s,

0.7 H), 3.44-3.79 (m, 1.3 H), 2.93-3.12 (m, 1 H), 2.83 (br s, 1

H), 1.09-1.22 (m, 1 H), 0.83-1.09 (m, 3 H)

728
(CD₃OD) δ 7.72 (s, 1 H), 7.50-7.63 (m, 2 H), 7.40 (td, 1 H),
393.2
99.2%

7.21-7.31 (m, 1 H), 6.91 (br s, 0.7 H), 6.60 (d, 1 H), 6.15-6.41
[M + H]⁺

(m, 0.3 H), 5.01 (br s, 0.3 H), 4.17 (br d, 0.7 H), 3.92 (br s, 0.7

H), 3.42-3.80 (m, 1.3 H), 3.01 (br s, 1 H), 2.82 (br d, 1 H),

0.82-1.20 (m, 4 H)

729
(CD₃OD) δ 7.75-7.96 (m, 3 H), 7.66-7.74 (m, 1 H), 7.56-7.64
430.2
99.1%

(m, 1.6 H), 7.41-7.48 (m, 1 H), 7.27-7.36 (m, 1 H), 7.09-7.23
[M + H]⁺

(m, 1 H), 6.94-7.01 (m, 1 H), 6.71-6.77 (m, 1 H), 6.02 (s, 0.4

H), 5.07 (dd, 0.3 H), 3.62-4.00 (m, 1.7 H), 2.66-3.16 (m, 2 H)

730
(CD₃OD) δ 7.63-7.83 (m, 3 H), 7.53-7.61 (m, 1 H), 7.43-7.52
430.2
98.0%

(m, 1.6 H), 7.29-7.37 (m, 1 H), 7.14-7.25 (m, 1 H), 6.97-7.10
[M + H]⁺

(m, 1 H), 6.82-6.89 (m, 1 H), 6.58-6.65 (m, 1 H), 5.83-5.93

(m, 0.4 H), 4.95 (br dd, 0.3 H), 3.51-3.86 (m, 1.7 H), 2.54-

3.04 (m, 2 H)

731
(CD₃OD) δ 7.61-7.75 (m, 3 H), 7.34-7.47 (m, 2 H), 6.57-6.95
399.2
100%

(m, 3 H), 4.29 (br s, 1 H), 3.96 (br s, 4 H), 2.94-3.11 (m, 1 H),
[M + H]⁺

2.81 (br d, 1 H)

732
(CD₃OD) δ 7.58-7.78 (m, 3 H), 7.29-7.51 (m, 2 H), 6.58-7.00
399.2
99.0%

(m, 3 H), 4.31 (br d, 1 H), 3.96 (br s, 4 H), 3.03 (br t, 1 H),
[M + H]⁺

2.81 (br d, 1 H)

733
(CD₃OD) δ 7.70 (s, 1 H), 7.53 (br d, 1 H), 7.37 (td, 1 H),
417.2
100%

7.15-7.29 (m, 1 H), 6.57-6.95 (m, 3 H), 4.30 (br s, 1 H), 3.97
[M + H]⁺

(s, 4 H), 3.04 (br t, 1 H), 2.82 (br d, 1 H)

734
(CD₃OD) δ 7.70 (s, 1 H), 7.53 (br d, 1 H), 7.38 (td, 1 H),
417.2
99.4%

7.18-7.28 (m, 1 H), 6.60-6.95 (m, 3 H), 4.30 (br s, 1 H), 3.97
[M + H]⁺

(s, 4 H), 2.94-3.14 (m, 1 H), 2.83 (br d, 1 H)

735
(CD₃OD) δ 7.70 (s, 1 H), 7.49 (br d, 1 H), 7.16-7.34 (m, 2 H),
413.2
99.3%

6.80-6.94 (m, 2 H), 6.61-6.79 (m, 1 H), 4.30 (br s, 1 H), 3.96
[M + H]⁺

(br s, 4 H), 2.95-3.11 (m, 1 H), 2.82 (br d, 1 H), 2.56 (s, 3 H)

736
(CD₃OD) δ 7.70 (s, 1 H), 7.49 (br d, 1 H), 7.17-7.32 (m, 2 H),
413.2
92.8%

6.81-6.95 (m, 2 H), 6.62-6.80 (m, 1 H), 4.28 (br s, 1 H), 3.96
[M + H]⁺

(br s, 4 H), 3.02 (br d, 1 H), 2.82 (br d, 1 H), 2.56 (s, 3 H)

737
(CD₃OD) δ 8.47-8.84 (m, 1 H), 7.87-8.39 (m, 2 H), 7.60-7.77
477.2
99.3%

(m, 2 H), 7.48-7.58 (m, 2 H), 7.06-7.42 (m, 2 H), 6.83 (br s, 1
[M + H]⁺

H), 4.74 (br d, 1 H), 3.64-4.13 (m, 1 H), 3.15 (s, 1 H), 2.91 (br

d, 1 H), 2.48 (s, 3 H)

738
(CD₃OD) δ 8.47-8.85 (m, 1 H), 7.87-8.38 (m, 2 H), 7.58-7.76
477.2
97.5%

(m, 2 H), 7.47-7.57 (m, 2 H), 7.07-7.37 (m, 2 H), 6.83 (br s, 1
[M + H]⁺

H), 4.75 (br d, 1 H), 3.66-4.09 (m, 1 H), 3.15 (br s, 1 H), 2.91

(br d, 1 H), 2.48 (s, 3 H)

739
(CD₃OD) δ 8.43-8.92 (m, 1 H), 7.88-8.40 (m, 2 H), 7.52-7.78
463.2
97.1%

(m, 4 H), 7.05-7.50 (m, 3 H), 6.86 (br s, 1 H), 4.76 (br d, 1 H),
[M + H]⁺

3.64-4.07 (m, 1 H), 2.99-3.31 (m, 1 H), 2.92 (br d, 1 H)

740
(CD₃OD) δ 8.32-8.73 (m, 1 H), 7.74-8.25 (m, 2 H), 7.40-7.66
463.2
97.8%

(m, 4 H), 6.93-7.39 (m, 3 H), 6.74 (br s, 1 H), 4.63 (br d, 1 H),
[M + H]⁺

3.53-3.97 (m, 1 H), 2.89-3.18 (m, 1 H), 2.80 (br d, 1 H)

741
(CD₃OD) δ 9.42-9.57 (m, 2 H), 9.36 (s, 1 H), 7.49-7.78 (m, 2
482.2
99.5%

H), 7.41 (br s, 1.4 H), 7.17-7.32 (m, 1.6 H), 6.81-7.15 (m, 1
[M + H]⁺

H), 4.94-5.04 (m, 0.5 H), 4.75 (br d, 0.5 H), 3.69-4.19 (m, 1

H), 2.78-3.29 (m, 2 H)

742
(CD₃OD) δ 9.49 (br s, 2 H), 9.36 (s, 1 H), 7.50-7.79 (m, 2 H),
482.1
99.3%

7.41 (br s, 1.4 H), 7.16-7.31 (m, 1.6 H), 6.77-7.15 (m, 1 H),
[M + H]⁺

4.95-5.06 (m, 0.5 H), 4.74 (br d, 0.5 H), 3.72-4.15 (m, 1 H),

2.84-3.28 (m, 2 H)

743
(CD₃OD) δ 8.45 (s, 1 H), 7.70 (br s, 1 H), 6.94-7.31 (m, 3 H),
418.2
98.7%

6.76 (br s, 1 H), 4.58 (br d, 1 H), 3.98 (br s, 1 H), 2.77-3.19
[M + H]⁺

(m, 2 H), 2.51 (br s, 3 H)

744
(CD₃OD) δ 8.45 (s, 1 H), 7.69 (s, 1 H), 6.97-7.30 (m, 3 H),
418.1
99.0%

6.76 (br s, 1 H), 4.59 (s, 1 H), 3.99 (br s, 1 H), 2.79-3.21 (m, 2
[M + H]⁺

H), 2.51 (s, 3 H)

745
(CD₃OD) δ 7.93-8.07 (m, 1 H), 7.71 (s, 1 H), 7.43-7.56 (m, 2
364.2
98.8%

H), 7.16-7.29 (m, 1.3 H), 6.88 (s, 0.7 H), 5.09 (dd, 0.3 H),
[M + H]⁺

4.71 (dd, 0.7 H), 4.04-4.11 (m, 3 H), 3.79-3.89 (m, 0.7 H),

3.48 (td, 0.3 H), 3.14-3.24 (m, 0.7 H), 2.93-3.05 (m, 0.3 H),

2.75-2.90 (m, 1 H), 2.43-2.50 (m, 3 H)

746
(CD₃OD) δ 7.92-8.08 (m, 1 H), 7.71 (s, 1 H), 7.43-7.57 (m, 2
364.2
98.0%

H), 7.16-7.31 (m, 1.3 H), 6.88 (s, 0.7 H), 5.09 (dd, 0.3 H),
[M + H]⁺

4.71 (br dd, 0.7 H), 4.02-4.13 (m, 3 H), 3.78-3.92 (m, 0.7 H),

3.48 (td, 0.3 H), 3.15-3.25 (m, 0.7 H), 2.94-3.05 (m, 0.3 H),

2.75-2.90 (m, 1 H), 2.42-2.50 (m, 3 H)

747
(CD₃OD) δ 7.66-7.75 (m, 1 H), 7.45-7.60 (m, 2 H), 7.18-7.32
363.2
99.3%

(m, 2 H), 6.66 (s, 2 H), 4.23-4.45 (m, 1 H), 3.94 (br s, 4 H),
[M + H]⁺

2.83 (br s, 2 H), 2.56 (br s, 3 H)

748
(CD₃OD) δ 7.70 (s, 1 H), 7.44-7.59 (m, 2 H), 7.19-7.31 (m, 2
363.2
98.2%

H), 6.66 (s, 2 H), 4.21-4.50 (m, 1 H), 3.94 (br s, 4 H), 2.75-
[M + H]⁺

3.11 (m, 2 H), 2.56 (br s, 3 H)

749
(CD₃OD) δ 7.68 (s, 1 H), 7.55 (d, 1 H), 7.21-7.36 (m, 2 H),
379.2
98.2%

7.01 (d, 1 H), 6.15-6.92 (m, 2 H), 4.17-4.46 (m, 1 H), 3.43-
[M + H]⁺

4.06 (m, 7 H), 2.77-3.05 (m, 2 H)

750
(CD₃OD) δ 7.68 (s, 1 H), 7.54 (d, 1 H), 7.21-7.36 (m, 2 H),
379.2
98.4%

7.01 (d, 1 H), 6.29-6.91 (m, 2 H), 4.24-4.41 (m, 1 H), 3.50-
[M + H]⁺

4.05 (m, 7 H), 2.77-3.05 (m, 2 H)

751
(CD₃OD) δ 7.50-7.78 (m, 4 H), 7.29-7.48 (m, 2 H), 6.86 (br s,
377.2
99.6%

1 H), 6.56 (s, 1 H), 4.48-4.85 (m, 2 H), 3.80-4.35 (m, 1 H),
[M + H] +

2.70-3.07 (m, 2 H), 1.46 (br s, 6 H)

752
(CD₃OD) δ 7.53-7.73 (m, 4 H), 7.33-7.48 (m, 2 H), 6.86 (br s,
377.2
99.3%

1 H), 6.56 (s, 1 H), 4.40-4.86 (m, 2 H), 4.22 (br d, 1 H), 3.88
[M + H]⁺

(br s, 1 H), 3.63-4.04 (m, 1 H), 2.69-3.05 (m, 2 H), 1.46 (br s,

6 H)

753
(CD₃OD) δ 7.66 (dd, 2 H), 7.43 (br s, 1 H), 6.53-7.26 (m, 3
460.2
98.8%

H), 4.93-5.02 (m, 1 H), 4.52 (br s, 1 H), 3.59-4.03 (m, 1 H),
[M + H]⁺

2.81-3.18 (m, 2 H), 1.23-1.50 (m, 9 H)

754
(CD₃OD) δ 7.66 (dt, 2 H), 7.43 (br s, 1 H), 6.55-7.29 (m, 3
460.2
85.0%

H), 4.91-4.94 (m, 1 H), 4.53 (br s, 1 H), 3.59-4.02 (m, 1 H),
[M + H]⁺

2.74-3.18 (m, 2 H), 1.24-1.53 (m, 9 H)

755
(CD₃OD) δ 7.63-7.81 (m, 2 H), 7.46-7.52 (m, 2 H), 7.04-7.32
480.2
98.5%

(m, 2 H), 6.68-7.02 (m, 2 H), 4.91-5.03 (m, 0.5 H), 4.70 (m,
[M + H]⁺

0.5 H), 3.59-4.04 (m, 4 H), 2.83-3.24 (m, 2 H), 2.45 (s, 3 H)

756
(CD₃OD) δ 7.62-7.82 (m, 2 H), 7.46-7.53 (m, 2 H), 7.05-7.32
480.2
98.2%

(m, 2 H), 6.66-7.04 (m, 2 H), 4.96 (br s, 0.5 H), 4.70 (m, 0.5
[M + H]⁺

H), 3.65-4.06 (m, 4 H), 2.83-3.25 (m, 2 H), 2.45 (s, 3 H)

757
(CD₃OD) δ 7.37-8.12 (m, 5 H), 6.73-7.36 (m, 3 H), 4.72 (br s,
480.2
99.3%

1 H), 3.60-4.16 (m, 4 H), 2.86-3.24 (m, 2 H), 2.40-2.51 (m, 3
[M + H]⁺

H)

758
(CD₃OD) δ 7.37-8.05 (m, 5 H), 6.64-7.36 (m, 3 H), 4.70 (br s,
480.2
98.8%

1 H), 3.64-4.15 (m, 4 H), 2.82-3.25 (m, 2 H), 2.39-2.54 (m, 3
[M + H]⁺

H)

759
(CD₃OD) δ 7.86-8.45 (m, 2 H), 7.63-7.83 (m, 3 H), 6.99-7.55
466.2
98.5%

(m, 3 H), 6.81 (s, 1 H), 4.73 (br s, 1 H), 3.99 (br s, 4 H), 2.79-
[M + H]⁺

3.28 (m, 2 H)

760
(CD₃OD) δ 7.88-8.41 (m, 2 H), 7.64-7.74 (m, 3 H), 6.99-7.48
466.2
98.8%

(m, 3 H), 6.80 (s, 1 H), 4.71 (br s, 1 H), 3.97 (br d, 4 H), 2.82-
[M + H]⁺

3.26 (m, 2 H)

761
(CD₃OD) δ 7.63-7.81 (m, 4 H), 7.36-7.45 (m, 2 H), 7.04-7.32
466.2
99.0%

(m, 1 H), 6.68-7.03 (m, 2 H), 4.97 (br s, 0.5 H), 4.71 (m, 0.5
[M + H]⁺

H), 3.62-4.08 (m, 4 H), 2.79-3.28 (m, 2 H)

762
(CD₃OD) δ 7.59-7.80 (m, 4 H), 7.37-7.45 (m, 2 H), 7.05-7.32
466.2
97.4%

(m, 1 H), 6.67-7.01 (m, 2 H), 4.97 (br s, 0.5 H), 4.73 (br s, 0.5
[M + H]⁺

H), 3.66-4.08 (m, 4 H), 2.79-3.29 (m, 2 H)

763
(CD₃OD) δ 7.59-7.96 (m, 5 H), 7.42 (br t, 2 H), 6.98-7.35 (m,
466.2
98.4%

1 H), 6.78 (br s, 1 H), 4.67 (br s, 1 H), 3.88-4.18 (m, 3.7 H),
[M + H]⁺

3.71 (br s, 0.3 H), 2.86-3.25 (m, 2 H)

764
(CD₃OD) δ 7.59-7.99 (m, 5 H), 7.42 (br t, 2 H), 7.01-7.36 (m,
466.2
98.3%

1 H), 6.78 (br s, 1 H), 4.68 (br s, 1 H), 3.89-4.19 (m, 3.7 H),
[M + H]⁺

3.75 (br s, 0.3 H), 2.78-3.24 (m, 2 H)

765
(CD₃OD) δ 7.68 (s, 1 H), 7.58 (d, 1 H), 7.28 (dt, 2 H), 7.00
407.2
99.8%

(dd, 1 H), 6.88 (br s, 1 H), 6.55 (d, 1 H), 4.75 (br s, 2 H), 4.18
[M + H]⁺

(br d, 0.5 H), 4.01 (s, 3 H), 3.82 (br s, 0.5 H), 2.74-3.05 (m, 2

H), 1.46 (br s, 6 H)

766
(CD₃OD) δ 7.68 (s, 1 H), 7.58 (d, 1 H), 7.16-7.38 (m, 2 H),
407.2
99.7%

7.01 (d, 1 H), 6.88 (br s, 1 H), 6.55 (d, 1 H), 4.75 (br s, 2 H),
[M + H]⁺

4.19 (br s, 0.5 H), 4.01 (s, 3 H), 3.82 (br s, 0.5 H), 2.70-3.10

(m, 2 H), 1.46 (br s, 6 H)

767
(CD₃OD) δ 7.71 (s, 1 H), 7.53 (d, 1 H), 7.22-7.40 (m, 2 H),
405.2
99.7%

7.03 (d, 1 H), 6.94 (br s, 0.7 H), 6.58 (br s, 1 H), 6.24 (br s,
[M + H]⁺

0.3 H), 4.96-5.05 (m, 0.3 H), 4.12 (br d, 0.7 H), 4.02 (s, 3 H),

3.81-3.95 (m, 0.7 H), 3.69 (br s, 1 H), 3.50 (br s, 0.3 H), 2.99

(br s, 1 H), 2.72-2.92 (m, 1 H), 0.80-1.20 (m, 4 H)

768
(CD₃OD) δ 7.71 (s, 1 H), 7.53 (d, 1 H), 7.23-7.41 (m, 2 H),
405.2
99.7%

7.03 (d, 1 H), 6.94 (br s, 0.7 H), 6.58 (br s, 1 H), 6.24 (br s,
[M + H]⁺

0.3 H), 4.96-5.10 (m, 0.4 H), 4.12 (br d, 0.6 H), 4.02 (s, 3 H),

3.88 (br s, 0.7 H), 3.69 (br s, 1 H), 3.50 (br s, 0.3 H), 2.99 (br

s, 1 H), 2.69-2.92 (m, 1 H), 0.80-1.18 (m, 4 H)

769
(CD₃OD) δ 7.83 (s, 1 H), 7.54 (br d, 1 H), 7.40 (td, 1 H),
381.2
89.4%

7.10-7.31 (m, 1 H), 6.89 (br s, 1 H), 6.46 (s, 1 H), 4.38 (br s, 1
[M + H]⁺

H), 3.88 (s, 4 H), 2.80-3.12 (m, 2 H), 2.29 (s, 3 H)

770
(CD₃OD) δ 7.63 (s, 1 H), 7.42 (br d, 1 H), 7.27 (td, 1 H), 7.13
381.2
95.7%

(t, 1 H), 6.74 (br s, 1 H), 6.33 (s, 1 H), 4.25 (br s, 1 H), 3.75 (s,
[M + H]⁺

4 H), 2.61-3.04 (m, 2 H), 2.17 (s, 3 H)

771
(CD₃OD) δ 8.27-8.48 (m, 0.5 H), 7.86-8.24 (m, 1.5 H), 7.45-
480.2
99.9%

7.82 (m, 3 H), 7.01-7.37 (m, 2 H), 6.78 (br s, 1 H), 4.72 (br s,
[M + H]⁺

1 H), 3.61-4.14 (m, 4 H), 2.79-3.27 (m, 2 H), 2.41-2.54 (m, 3

H)

772
(CD₃OD) δ 8.38 (br s, 0.5 H), 7.83-8.23 (m, 1.5 H), 7.43-7.77
480.2
99.4%

(m, 3 H), 6.99-7.38 (m, 2 H), 6.78 (s, 1 H), 4.60-4.85 (m, 1
[M + H]⁺

H), 4.00 (br s, 4 H), 2.81-3.28 (m, 2 H), 2.48 (s, 3 H)

773
(CD₃OD) δ 9.38 (br s, 0.7 H), 8.91-9.17 (m, 1.3 H), 8.17-8.38
482.2
99.6%

(m, 1 H), 7.64-7.84 (m, 1 H), 7.48-7.62 (m, 1 H), 7.05-7.47
[M + H]⁺

(m, 3 H), 6.86 (br s, 1 H), 5.03 (br s, 0.2 H), 4.75 (br d, 0.8 H),

4.05 (br s, 0.6 H), 3.80 (br d, 0.4 H), 3.22-3.31 (m, 0.6 H),

3.05 (br s, 0.4 H), 2.94 (br d, 1 H)

774
(CD₃OD) δ 9.26 (br s, 0.7 H), 8.78-9.06 (m, 1.3 H), 8.05-8.28
482.2
98.5%

(m, 1 H), 7.61 (br s, 1 H), 7.36-7.50 (m, 1 H), 6.92-7.35 (m, 3
[M + H]⁺

H), 6.74 (br s, 1 H), 4.89 (br d, 0.2 H), 4.63 (br d, 0.8 H), 3.92

(br s, 0.6 H), 3.67 (br s, 0.4 H), 3.07-3.19 (m, 0.6 H), 2.92 (br

s, 0.4 H), 2.82 (br d, 1 H)

775
(CD₃OD) δ 7.96-8.03 (m, 1 H), 7.67-7.73 (m, 1 H), 7.20-7.33
380.2
97.0%

(m, 2 H), 6.97-7.02 (m, 1 H), 5.05 (br dd, 0.4 H), 4.68 (dd, 0.6
[M + H]⁺

H), 3.92-4.14 (m, 6 H), 3.79-3.88 (m, 0.6 H), 3.36-3.45 (m,

0.4 H), 2.74-3.23 (m, 3 H)

776
(CD₃OD) δ 7.92-8.07 (m, 1 H), 7.65-7.79 (m, 1 H), 7.19-7.34
380.1
94.7%

(m, 2 H), 6.94-7.04 (m, 1 H), 5.05 (dd, 0.4 H), 4.68 (dd, 0.6
[M + H]⁺

H), 3.96-4.10 (m, 6 H), 3.75-3.90 (m, 0.6 H), 3.35-3.49 (m,

0.4 H), 2.73-3.25 (m, 3 H)

777
(CD₃OD) δ 7.68 (s, 1 H), 7.20-7.34 (m, 2 H), 7.00 (d, 1 H),
429.2
99.5%

6.81-6.94 (m, 2 H), 6.60-6.79 (m, 0.8 H), 6.39 (br s, 0.2 H),
[M + H]⁺

4.18-4.37 (m, 1 H), 3.98 (d, 7 H), 2.95-3.09 (m, 1 H), 2.72-

2.87 (m, 1 H)

778
(CD₃OD) δ 7.69 (s, 1 H), 7.21-7.34 (m, 2 H), 7.00 (d, 1 H),
429.2
98.3%

6.80-6.94 (m, 2 H), 6.59-6.79 (m, 0.8 H), 6.39 (br s, 0.2 H),
[M + H]⁺

4.27 (br s, 1 H), 3.98 (d, 7 H), 2.92-3.10 (m, 1 H), 2.81 (br d,

1 H)

779
(CD₃OD) δ 7.61-7.79 (m, 3 H), 7.36-7.53 (m, 2 H), 6.85 (br s,
363.2
99.3%

1 H), 6.44 (s, 1 H), 4.25-4.69 (m, 1.5 H), 3.87 (br s, 3.8 H),
[M + H]⁺

2.78-3.12 (m, 2 H), 2.29 (br s, 3 H)

780
(CD₃OD) δ 7.64-7.79 (m, 3 H), 7.34-7.51 (m, 2 H), 6.85 (br s,
363.2
98.2%

1 H), 6.44 (s, 1 H), 4.27-4.69 (m, 1.3 H), 3.87 (br s, 3.7 H),
[M + H]⁺

2.73-3.13 (m, 2 H), 2.29 (br s, 3 H)

781
(CD₃OD) δ 7.60 (s, 1 H), 7.38 (br d, 1 H), 6.95-7.24 (m, 2 H),
377.2
97.8%

6.74 (br s, 1 H), 6.33 (s, 1 H), 4.16-4.60 (m, 1 H), 3.63-3.93
[M + H]⁺

(m, 4 H), 2.62-2.99 (m, 2 H), 2.45 (s, 3 H), 2.17 (s, 3 H)

782
(CD₃OD) δ 7.72 (s, 1 H), 7.50 (br d, 1 H), 7.15-7.35 (m, 2 H),
377.2
96.4%

6.86 (br s, 1 H), 6.45 (s, 1.1 H), 4.37 (br d, 1 H), 3.87 (br s, 4
[M + H]⁺

H), 2.77-3.10 (m, 2 H), 2.57 (s, 3 H), 2.29 (s, 3 H)

783
(CD₃OD) δ 7.75-8.02 (m, 1 H), 7.69 (s, 1 H), 7.43-7.55 (m, 2
480.2
95.8%

H), 7.00-7.32 (m, 2 H), 6.79 (br s, 1 H), 4.77 (br s, 2 H), 3.64-
[M + H]⁺

4.08 (m, 4 H), 2.78-3.28 (m, 2 H), 2.45 (s, 3 H)

784
(CD₃OD) δ 7.78-8.02 (m, 1 H), 7.69 (s, 1 H), 7.44-7.54 (m, 2
480.2
97.9%

H), 7.02-7.33 (m, 2 H), 6.79 (s, 1 H), 4.76 (br s, 2 H), 3.58-
[M + H]⁺

4.07 (m, 4 H), 2.80-3.27 (m, 2 H), 2.45 (s, 3 H)

785
(CD₃OD) δ 7.77-8.02 (m, 1 H), 7.63-7.75 (m, 3 H), 7.36-7.46
466.2
99.1%

(m, 2 H), 6.98-7.34 (m, 1 H), 6.82 (s, 1 H), 4.78 (br s, 2 H),
[M + H]⁺

3.64-4.09 (m, 4 H), 2.81-3.29 (m, 2 H)

786
(CD₃OD) δ 7.79-8.01 (m, 1 H), 7.59-7.75 (m, 3 H), 7.41 (qd,
466.2
98.3%

2 H), 7.01-7.33 (m, 1 H), 6.81 (br s, 1 H), 4.78 (br s, 2 H),
[M + H]⁺

3.70-4.09 (m, 4 H), 2.78-3.28 (m, 2 H)

787
(CD₃OD) δ 7.55-7.82 (m, 3 H), 7.42 (dd, 1 H), 7.20 (td, 1 H),
502.2
99.1%

6.67-6.99 (m, 1.7 H), 6.30 (br s, 0.3 H), 4.98 (br d, 0.4 H),
[M + H]⁺

4.20 (br dd, 0.6 H), 3.79-4.05 (m, 3.7 H), 3.63-3.74 (m, 0.3

H), 2.77-3.16 (m, 2 H)

788
(CD₃OD) δ 7.56-7.81 (m, 3 H), 7.42 (dd, 1 H), 7.20 (td, 1 H),
502.2
99.2%

6.68-7.02 (m, 1.7 H), 6.29 (br s, 0.3 H), 4.99 (br d, 0.3 H),
[M + H]⁺

4.20 (br dd, 0.7 H), 3.79-4.06 (m, 3.8 H), 3.60-3.73 (m, 0.2

H), 2.78-3.14 (m, 2 H)

789
(CD₃OD) δ 7.97 (s, 1 H), 7.81 (s, 1 H), 7.56-7.77 (m, 2 H),
502.2
98.7%

7.43 (dd, 1 H), 7.22 (td, 1 H), 6.82 (br s, 0.6 H), 6.26 (br s, 0.1
[M + H]⁺

H), 4.19 (br dd, 1 H), 3.95 (br t, 0.8 H), 3.71-3.87 (m, 3 H),

3.55-3.69 (m, 0.2 H), 2.79-3.17 (m, 2 H)

790
(CD₃OD) δ 7.97 (s, 1 H), 7.80 (s, 1 H), 7.56-7.76 (m, 2 H),
502.2
99.2%

7.43 (dd, 1 H), 7.22 (td, 1 H), 6.82 (s, 0.6 H), 6.27 (br s, 0.1
[M + H]⁺

H), 4.19 (br dd, 1 H), 3.95 (br t, 0.8 H), 3.72-3.86 (m, 3 H),

3.64 (br s, 0.2 H), 2.80-3.17 (m, 2 H)

791
(CD₃OD) δ 7.78-7.99 (m, 2 H), 7.59-7.75 (m, 2 H), 7.39-7.52
502.2
100%

(m, 1 H), 7.14-7.29 (m, 1 H), 6.27-6.90 (m, 1 H), 4.24 (br dd,
[M + H]⁺

0.6 H), 3.90-4.12 (m, 4 H), 3.71 (br d, 0.4 H), 2.94-3.11 (m, 1

H), 2.79-2.91 (m, 1 H)

792
(CD₃OD) δ 7.78-7.97 (m, 2 H), 7.59-7.75 (m, 2 H), 7.38-7.51
502.2
99.4%

(m, 1 H), 7.16-7.28 (m, 1 H), 6.31-6.85 (m, 1 H), 4.24 (br dd,
[M + H]⁺

0.6 H), 3.89-4.13 (m, 4 H), 3.69 (br s, 0.4 H), 2.94-3.12 (m, 1

H), 2.78-2.92 (m, 1 H)

793
(CD₃OD) δ 8.25 (s, 1 H), 7.58-7.75 (m, 3 H), 7.27-7.51 (m, 2
350.2
100%

H), 6.73 (br s, 1 H), 4.20-4.59 (m, 1 H), 3.88 (br s, 1 H), 2.77-
[M + H]⁺

3.16 (m, 2 H), 2.39 (s, 3 H)

794
(CD₃OD) δ 8.27 (s, 1 H), 7.58-7.76 (m, 3 H), 7.30-7.51 (m, 2
350.1
99.5%

H), 6.75 (br s, 1 H), 4.49-4.60 (m, 1 H), 3.75-4.02 (m, 1 H),
[M + H]⁺

2.80-3.18 (m, 2 H), 2.41 (s, 3 H)

795
(CD₃OD) δ 8.52 (s, 1 H), 7.74 (s, 1 H), 7.10-7.31 (m, 2 H),
440.1
98.0%

6.86 (s, 1 H), 4.97-5.06 (m, 0.2 H), 4.05-4.14 (m, 0.8 H), 3.92-
[M + H]⁺

4.04 (m, 0.9 H), 3.64 (br s, 0.1 H), 2.83-3.11 (m, 2 H)

796
(CD₃OD) δ 8.27-8.77 (m, 1 H), 7.79 (s, 1 H), 7.06-7.37 (m, 2
440.2
96.2%

H), 6.13-7.02 (m, 1 H), 4.99 (br s, 0.3 H), 4.05-4.16 (m, 0.8
[M + H]⁺

H), 3.89-4.03 (m, 0.8 H), 3.63 (br s, 0.2 H), 2.82-3.07 (m, 2

H)

797
(CD₃OD) δ 8.41-8.62 (m, 1 H), 7.60-7.79 (m, 3 H), 7.36-7.51
404.1
99.3%

(m, 2 H), 6.87 (br s, 1 H), 4.99 (br d, 0.3 H), 3.85-4.10 (m, 1.5
[M + H]⁺

H), 2.70-3.12 (m, 2 H)

798
(CD₃OD) δ 8.50 (s, 1 H), 7.58-7.84 (m, 3 H), 7.30-7.51 (m, 2
404.1
98.7%

H), 6.87 (br s, 1 H), 4.92-5.06 (m, 0.3 H), 3.82-4.15 (m, 1.7
[M + H]⁺

H), 2.77-3.08 (m, 2 H)

799
(CD₃OD) δ 8.55-8.74 (m, 1 H), 7.89-8.00 (m, 1 H), 7.83-7.89
468.2
99.4%

(m, 1 H), 7.73-7.81 (m, 1 H), 7.56 (s, 0.3 H), 7.21-7.31 (m, 1
[M + H]⁺

H), 7.12-7.20 (m, 1 H), 6.99 (s, 0.7 H), 5.13-5.34 (m, 1 H),

3.67-4.09 (m, 1 H), 2.86-3.29 (m, 2 H)

800
(CD₃OD) δ 8.76-8.80 (m, 1 H), 8.63-8.71 (m, 1 H), 7.91-8.02
468.2
97.6%

(m, 1 H), 7.74-7.83 (m, 1 H), 7.25-7.36 (m, 2 H), 7.15-7.25
[M + H]⁺

(m, 1 H), 5.13-5.48 (m, 1 H), 3.56-3.95 (m, 1 H), 3.04-3.17

(m, 1 H), 2.89-3.04 (m, 1 H)

801
(CD₃OD) δ 8.93 (d, 1 H), 8.34-8.39 (m, 1 H), 7.63-7.86 (m, 2
489.1
96.0%

H), 7.44-7.61 (m, 0.5 H), 7.11-7.29 (m, 2 H), 6.92 (br s, 0.5
[M + H]⁺

H), 5.08-5.43 (m, 1 H), 3.64-4.13 (m, 1 H), 2.86-3.28 (m, 2 H)

802
(CD₃OD) δ 8.91-8.96 (m, 1 H), 8.34-8.39 (m, 1 H), 7.80 (t, 1
489.2
96.5%

H), 7.46-7.70 (m, 1 H), 7.12-7.29 (m, 2 H), 6.95 (s, 1 H),
[M + H]⁺

5.07-5.42 (m, 1 H), 3.66-4.10 (m, 1 H), 2.84-3.28 (m, 2 H)

803
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.54 (d, 1 H), 7.39
418.1
96.7%

(td, 1 H), 6.65-7.31 (m, 3 H), 4.50 (br d, 1 H), 3.38-3.77 (m, 1
[M + H]⁺

H), 3.23 (br s, 1 H), 1.36 (d, 3 H)

804
(CD₃OD) δ 8.49 (br s, 1 H), 7.70 (s, 1 H), 7.52 (d, 1 H), 7.38
418.2
100%

(td, 1 H), 6.63-7.30 (m, 3 H), 4.73-4.84 (m, 0.3 H), 4.40 (br d,
[M + H]⁺

0.7 H), 3.62-4.24 (m, 1 H), 3.19 (br s, 1 H), 1.36 (br d, 3 H)

805
(CD₃OD) δ 8.49 (br s, 1 H), 7.70 (s, 1 H), 7.52 (d, 1 H), 7.38
418.2
99.0%

(td, 1 H), 6.78-7.29 (m, 3 H), 4.79-4.85 (m, 0.3 H), 4.41 (br d,
[M + H]⁺

0.7 H), 3.67-4.21 (m, 1 H), 3.20 (br s, 1 H), 1.36 (br d, 3 H)

806
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.54 (d, 1 H), 7.39
418.2
97.2%

(td, 1 H), 6.76-7.30 (m, 3 H), 4.50 (br d, 1 H), 3.57 (br s, 1 H),
[M + H]⁺

3.24 (br s, 1 H), 1.36 (d, 3 H)

807
(CD₃OD) δ 8.28 (s, 1 H), 7.70 (s, 1 H), 7.04-7.37 (m, 2 H),
386.2
99.7%

6.71 (br s, 1 H), 4.61 (br s, 1 H), 3.98 (br s, 1 H), 2.79-3.22
[M + H]⁺

(m, 2 H), 2.42 (s, 3 H)

808
(CD₃OD) δ 8.28 (s, 1 H), 7.69 (s, 1 H), 7.09-7.31 (m, 2 H),
386.2
99.3%

6.71 (br s, 1 H), 4.61 (br s, 1 H), 3.97 (br s, 1 H), 2.76-3.19
[M + H]⁺

(m, 2 H), 2.42 (s, 3 H)

809
(CD₃OD) δ 7.67-7.76 (m, 1 H), 7.46 (br s, 0.3 H), 7.21-7.30
433.2
95.6%

(m, 1 H), 7.09-7.20 (m, 1 H), 6.91 (br s, 0.7 H), 5.05-5.32 (m,
[M + H]⁺

1 H), 3.65-4.07 (m, 1 H), 2.84-3.27 (m, 2 H), 1.81-1.97 (m, 6

H)

810
(CD₃OD) δ 7.64-7.79 (m, 1 H), 7.46 (br s, 0.3 H), 7.21-7.31
433.2
91.0%

(m, 1 H), 7.08-7.19 (m, 1 H), 6.91 (br s, 0.7 H), 5.08-5.35 (m,
[M + H]⁺

1 H), 3.63-4.06 (m, 1 H), 2.85-3.27 (m, 2 H), 1.80-1.96 (m, 6

H)

811
(CD₃OD) δ 8.42-8.54 (m, 1 H), 8.04-8.22 (m, 1 H), 7.70-7.80
493.2
100%

(m, 1 H), 7.53-7.64 (m, 0.3 H), 7.10-7.31 (m, 2 H), 6.93 (s, 0.7
[M + H]⁺

H), 5.08-5.44 (m, 1 H), 4.94-5.04 (m, 1 H), 3.65-4.07 (m, 1

H), 2.85-3.28 (m, 2 H), 2.44-2.71 (m, 4 H), 1.88-2.02 (m, 2 H)

812
(CD₃OD) δ 8.45-8.53 (m, 1 H), 8.09-8.21 (m, 1 H), 7.69-7.76
493.2
96.5%

(m, 1 H), 7.59 (s, 0.3 H), 7.08-7.30 (m, 2 H), 6.92 (s, 0.7 H),
[M + H]⁺

5.10-5.43 (m, 1 H), 4.93-5.03 (m, 1 H), 3.67-4.09 (m, 1 H),

2.86-3.28 (m, 2 H), 2.45-2.71 (m, 4 H), 1.86-2.01 (m, 2 H)

813
(CD₃OD) δ 7.80-7.86 (m, 2 H), 7.60 (s, 0.2 H), 7.12-7.33 (m,
453.2
93.0%

2 H), 6.91-7.07 (m, 1.8 H), 5.10-5.43 (m, 1 H), 3.97-4.06 (m,
[M + H]⁺

3.7 H), 3.72 (td, 0.3 H), 2.77-3.30 (m, 2 H)

814
(CD₃OD) δ 7.80-7.87 (m, 2 H), 7.61 (s, 0.2 H), 7.09-7.32 (m,
453.2
86.1%

2 H), 6.87-7.05 (m, 1.8 H), 5.08-5.41 (m, 1 H), 3.93-4.09 (m,
[M + H]⁺

3.8 H), 3.65-3.77 (m, 0.2 H), 2.82-3.28 (m, 2 H)

815
(CD₃OD) δ 8.30-8.38 (m, 1 H), 7.48-7.89 (m, 2 H), 7.08-7.33
489.2
100%

(m, 3 H), 6.93 (br s, 1 H), 5.10-5.40 (m, 1 H), 3.65-4.15 (m, 1
[M + H]⁺

H), 2.83-3.29 (m, 2 H)

816
(CD₃OD) δ 8.31-8.38 (m, 1 H), 7.49-7.87 (m, 2 H), 7.08-7.34
489.2
99.3%

(m, 3 H), 6.94 (s, 1 H), 5.10-5.40 (m, 1 H), 3.68-4.15 (m, 1
[M + H]⁺

H), 2.85-3.29 (m, 2 H)

817
(CD₃OD) δ 7.87 (d, 1 H), 7.71-7.77 (m, 1 H), 7.55-7.65 (m, 1
453.2
97.3%

H), 7.41 (br s, 0.3 H), 7.08-7.19 (m, 1 H), 6.96-7.08 (m, 1 H),
[M + H]⁺

6.79 (br s, 0.7 H), 4.97-5.30 (m, 1 H), 3.82-4.06 (m, 4 H),

2.75-3.16 (m, 2 H)

818
(CD₃OD) δ 7.84-7.89 (m, 1 H), 7.70-7.78 (m, 1 H), 7.55-7.66
453.2
95.5%

(m, 1 H), 7.43 (br s, 0.3 H), 7.09-7.19 (m, 1 H), 6.96-7.07 (m,
[M + H]⁺

1 H), 6.80 (br s, 0.7 H), 4.94-5.34 (m, 1 H), 3.57-4.05 (m, 4

H), 2.73-3.16 (m, 2 H)

819
(CD₃OD) δ 7.68-7.76 (m, 1 H), 7.37-7.51 (m, 1 H), 7.25-7.35
378.2
99.9%

(m, 1 H), 6.82-7.21 (m, 2 H), 5.07 (br dd, 0.4 H), 4.62-4.72
[M + H]⁺

(m, 0.6 H), 3.46-4.05 (m, 4 H), 2.93-3.24 (m, 1 H), 2.76-2.92

(m, 1 H), 2.51-2.63 (m, 3 H), 2.31-2.43 (m, 3 H)

820
(CD₃OD) δ 7.71 (br d, 1 H), 7.37-7.48 (m, 1 H), 7.25-7.35 (m,
378.2
99.7%

1 H), 6.87-7.22 (m, 2 H), 5.07 (br dd, 0.4 H), 4.65 (dd, 0.6 H),
[M + H]⁺

3.46-4.01 (m, 4 H), 2.94-3.25 (m, 1 H), 2.77-2.94 (m, 1 H),

2.53-2.59 (m, 3 H), 2.31-2.43 (m, 3 H)

821
(CD₃OD) δ 7.68 (s, 1 H), 7.15-7.40 (m, 2 H), 7.01 (d, 1 H),
393.2
98.2%

6.84 (br s, 1 H), 6.42 (s, 1 H), 4.33 (br s, 0.6 H), 4.01 (s, 3 H),
[M + H]⁺

3.87-3.93 (m, 0.4 H), 3.85 (s, 3 H), 2.70-3.09 (m, 2 H), 2.27

(s, 3 H)

822
(CD₃OD) δ 7.70 (s, 1 H), 7.18-7.40 (m, 2 H), 7.03 (br d, 1 H),
393.2
96.7%

6.86 (br s, 1 H), 6.44 (s, 1 H), 4.34 (br s, 0.6 H), 4.03 (s, 3 H),
[M + H]⁺

3.89-3.97 (m, 0.4 H), 3.87 (s, 3 H), 2.78-3.10 (m, 2 H), 2.29

(s, 3 H)

823
(CD₃OD) δ 7.60-7.79 (m, 2 H), 7.45 (br s, 1 H), 6.91-7.34 (m,
476.2
95.3%

2 H), 6.75 (br s, 1 H), 4.61 (br s, 1 H), 3.56-4.00 (m, 3 H),
[M + H]⁺

2.98-3.28 (m, 1 H), 2.89 (br d, 1 H), 1.11-1.55 (m, 6 H)

824
(CD₃OD) δ 7.65-7.84 (m, 2 H), 7.44 (br d, 1 H), 6.95-7.34 (m,
476.2
93.8%

2 H), 6.76 (br s, 1 H), 4.61 (br s, 1 H), 3.58-4.03 (m, 3 H),
[M + H]⁺

2.99-3.25 (m, 1 H), 2.90 (br d, 1 H), 1.18-1.56 (m, 6 H)

825
(CD₃OD) δ 7.60-7.78 (m, 3 H), 7.43 (dd, 1 H), 7.20 (td, 1 H),
448.2
95.2%

6.54-6.99 (m, 2 H), 4.52-4.77 (m, 1 H), 3.66-4.07 (m, 4 H),
[M + H]⁺

2.82-3.25 (m, 2 H), 2.44 (s, 3 H)

826
(CD₃OD) δ 7.64-7.76 (m, 3 H), 7.42 (dd, 1 H), 7.20 (td, 1 H),
448.2
96.1%

6.58-6.94 (m, 2 H), 4.60 (s, 1 H), 3.79-4.09 (m, 4 H), 2.83-
[M + H]⁺

3.24 (m, 2 H), 2.44 (s, 3 H)

827
(CD₃OD) δ 7.66-7.75 (m, 1 H), 6.82-7.40 (m, 4 H), 5.05 (br
394.2
100%

dd, 0.2 H), 4.66 (br dd, 0.8 H), 3.94-4.03 (m, 6 H), 3.40-3.93
[M + H]⁺

(m, 1 H), 2.92-3.24 (m, 1 H), 2.71-2.91 (m, 1 H), 2.30-2.42

(m, 3 H)

828
(CD₃OD) δ 7.66-7.75 (m, 1 H), 6.79-7.41 (m, 4 H), 5.05 (br
394.2
99.7%

dd, 0.2 H), 4.66 (dd, 0.8 H), 3.95-4.03 (m, 6 H), 3.39-3.92 (m,
[M + H]⁺

1 H), 2.91-3.24 (m, 1 H), 2.74-2.91 (m, 1 H), 2.29-2.44 (m, 3

H)

829
(CD₃OD) δ 8.34-8.44 (m, 1 H), 8.05-8.14 (m, 1 H), 7.91-8.01
485.2
98.8%

(m, 1 H), 7.67-7.75 (m, 2 H), 7.50-7.61 (m, 1 H), 6.96 (s, 1
[M + H]⁺

H), 5.33 (dd, 0.6 H), 5.10 (dd, 0.4 H), 3.95-4.06 (m, 3.7 H),

3.61 (td, 0.3 H), 3.11-3.27 (m, 0.8 H), 2.83-3.07 (m, 1.2 H)

830
(CD₃OD) δ 8.35-8.43 (m, 1 H), 8.04-8.13 (m, 1 H), 7.92-8.01
485.2
99.0%

(m, 1 H), 7.66-7.74 (m, 2 H), 7.50-7.60 (m, 1 H), 6.95 (s, 1
[M + H]⁺

H), 5.33 (dd, 0.6 H), 5.10 (dd, 0.4 H), 3.96-4.06 (m, 3.7 H),

3.53-3.69 (m, 0.3 H), 3.14-3.26 (m, 0.8 H), 2.80-3.08 (m, 1.2

H)

831
(CD₃OD) δ 7.93-8.01 (m, 1 H), 7.78-7.84 (m, 1 H), 7.65-7.75
485.2
99.5%

(m, 2.4 H), 7.49-7.60 (m, 1 H), 6.94-7.02 (m, 1.6 H), 5.29 (dd,
[M + H]⁺

0.7 H), 5.11 (dd, 0.3 H), 3.97-4.07 (m, 3.7 H), 3.62 (td, 0.3 H),

3.17-3.28 (m, 0.7 H), 2.84-3.09 (m, 1.3 H)

832
(CD₃OD) δ 7.92-8.00 (m, 1 H), 7.77-7.83 (m, 1 H), 7.65-7.75
485.2
96.7%

(m, 2.4 H), 7.50-7.59 (m, 1 H), 6.92-7.02 (m, 1.6 H), 5.29 (dd,
[M + H]⁺

0.7 H), 5.11 (dd, 0.3 H), 3.95-4.07 (m, 3.7 H), 3.62 (td, 0.3 H),

3.15-3.28 (m, 0.7 H), 2.83-3.08 (m, 1.3 H)

833
(CD₃OD) δ 8.55-8.70 (m, 1 H), 7.87-7.98 (m, 1 H), 7.62-7.78
432.2
98.9%

(m, 4 H), 7.34-7.54 (m, 2.3 H), 6.93 (s, 0.7 H), 5.08-5.26 (m, 1
[M + H]⁺

H), 3.58-4.10 (m, 1 H), 2.84-3.29 (m, 2 H)

834
(CD₃OD) δ 8.55-8.70 (m, 1 H), 7.86-7.98 (m, 1 H), 7.62-7.80
432.2
90.4%

(m, 4 H), 7.33-7.57 (m, 2.3 H), 6.93 (s, 0.7 H), 5.07-5.29 (m, 1
[M + H]⁺

H), 3.56-4.06 (m, 1 H), 2.83-3.29 (m, 2 H)

835
(CD₃OD) δ 7.57-7.82 (m, 4 H), 7.42 (br t, 2 H), 6.63-6.98 (m,
399.2
99.7%

2 H), 5.93-6.55 (m, 1 H), 4.77 (br d, 2 H), 4.41 (br s, 1 H),
[M + H]⁺

3.43-3.98 (m, 1 H), 2.77-3.14 (m, 2 H)

836
(CD₃OD) δ 7.59-7.87 (m, 4 H), 7.35-7.52 (m, 2 H), 6.68-7.02
399.2
99.1%

(m, 2 H), 6.01-6.47 (m, 1 H), 4.77 (br d, 2 H), 4.41 (br s, 1 H),
[M + H]⁺

3.45-4.00 (m, 1 H), 2.72-3.19 (m, 2 H)

837
(CD₃OD) δ 8.66-8.87 (m, 1 H), 8.28-8.37 (m, 1 H), 8.06-8.16
482.2
99.3%

(m, 1 H), 7.95-8.03 (m, 1 H), 7.51-7.79 (m, 4.4 H), 6.99 (br s,
[M + H]⁺

0.6 H), 5.30 (dd, 0.7 H), 5.15 (br dd, 0.3 H), 3.59-4.17 (m, 1

H), 2.87-3.30 (m, 2 H)

838
(CD₃OD) δ 8.72-8.80 (m, 1 H), 8.27-8.32 (m, 1 H), 8.05-8.11
482.2
98.4%

(m, 1 H), 7.92-8.00 (m, 1 H), 7.51-7.76 (m, 4.6 H), 6.98 (s, 0.4
[M + H]⁺

H), 5.27 (br dd, 0.7 H), 5.10-5.15 (m, 0.3 H), 4.03 (br t, 0.7

H), 3.65 (br s, 0.3 H), 2.86-3.26 (m, 2 H)

839
(CD₃OD) δ 8.57-8.68 (m, 1 H), 7.86-8.03 (m, 2 H), 7.65-7.79
500.2
92.5%

(m, 3 H), 7.49-7.63 (m, 1.3 H), 6.97 (br s, 0.7 H), 5.07-5.29
[M + H]⁺

(m, 1 H), 3.57-4.13 (m, 1 H), 2.85-3.27 (m, 2 H)

840
(CD₃OD) δ 8.60-8.69 (m, 1 H), 7.89-8.03 (m, 2 H), 7.68-7.81
500.2
90.3%

(m, 3 H), 7.50-7.63 (m, 1.3 H), 6.99 (br s, 0.7 H), 5.09-5.31
[M + H]⁺

(m, 1 H), 3.56-4.18 (m, 1 H), 2.84-3.29 (m, 2 H)

841
(CD₃OD) δ 8.83-8.96 (m, 1 H), 8.27-8.38 (m, 1 H), 7.35-7.80
453.2
100%

(m, 6.5 H), 6.90 (br s, 0.5 H), 5.07-5.38 (m, 1 H), 3.58-4.05
[M + H]⁺

(m, 1 H), 2.83-3.26 (m, 2 H)

842
(CD₃OD) δ 8.76-9.02 (m, 1 H), 8.19-8.48 (m, 1 H), 7.34-7.80
453.2
99.3%

(m, 6.5 H), 6.91 (s, 0.5 H), 5.04-5.40 (m, 1 H), 3.55-4.04 (m, 1
[M + H]⁺

H), 2.83-3.26 (m, 2 H)

843
(CD₃OD) δ 7.78-7.84 (m, 1 H), 7.61-7.73 (m, 3.2 H), 7.33-
417.2
100%

7.47 (m, 2 H), 6.80-7.08 (m, 1.8 H), 5.07-5.32 (m, 1 H), 3.82-
[M + H]⁺

4.15 (m, 4 H), 2.76-3.27 (m, 2 H)

844
(CD₃OD) δ 7.77-7.84 (m, 1 H), 7.56-7.74 (m, 3.5 H), 7.32-
417.2
99.1%

7.48 (m, 2 H), 6.95-7.04 (m, 1 H), 6.91 (br s, 0.5 H), 5.03-5.38
[M + H]⁺

(m, 1 H), 4.00-4.04 (m, 3 H), 3.57-3.99 (m, 1 H), 2.84-3.26

(m, 2 H)

845
(CD₃OD) δ 8.33 (d, 1 H), 7.34-7.87 (m, 6.5 H), 7.02-7.24 (m,
453.2
100%

1 H), 6.91 (br s, 0.5 H), 5.04-5.37 (m, 1 H), 3.56-4.05 (m, 1
[M + H]⁺

H), 2.80-3.27 (m, 2 H)

846
(CD₃OD) δ 8.27-8.37 (m, 1 H), 7.34-7.84 (m, 6.5 H), 7.11-
453.2
98.0%

7.28 (m, 1 H), 6.92 (br s, 0.5 H), 5.05-5.36 (m, 1 H), 3.57-4.07
[M + H]⁺

(m, 1 H), 2.82-3.27 (m, 2 H)

847
(CD₃OD) δ 7.64-7.80 (m, 2 H), 7.53 (br d, 1 H), 7.39 (br d, 1
417.2
99.6%

H), 7.24 (br t, 1 H), 6.72-6.94 (m, 1 H), 6.63-7.01 (m, 1 H),
[M + H]⁺

5.93-6.56 (m, 1 H), 4.75 (br d, 2 H), 4.42 (br s, 1 H), 3.42-

4.08 (m, 1 H), 2.74-3.12 (m, 2 H)

848
(CD₃OD) δ 7.50-7.79 (m, 3 H), 7.11-7.44 (m, 2 H), 6.65-6.98
417.2
93.9%

(m, 2 H), 5.86-6.54 (m, 1 H), 4.75 (br d, 2 H), 4.41 (br s, 1 H),
[M + H]⁺

3.47-4.03 (m, 1 H), 2.72-3.12 (m, 2 H)

849
(CD₃OD) δ 7.58-7.76 (m, 2 H), 7.48-7.54 (m, 1 H), 7.38-7.48
417.2
100%

(m, 1 H), 7.17 (br t, 1 H), 6.66-6.93 (m, 2 H), 5.96-6.43 (m, 1
[M + H]⁺

H), 4.75 (br s, 2 H), 4.42 (br s, 1 H), 3.45-4.07 (m, 1 H), 2.74-

3.12 (m, 2 H)

850
(CD₃OD) δ 7.59-7.77 (m, 2 H), 7.48-7.54 (m, 1 H), 7.37-7.47
417.2
99.3%

(m, 1 H), 7.16 (br t, 1 H), 6.60-6.96 (m, 2 H), 5.95-6.50 (m, 1
[M + H]⁺

H), 4.75 (br s, 2 H), 4.42 (br s, 1 H), 3.45-3.98 (m, 1 H), 2.73-

3.13 (m, 2 H)

851
(CD₃OD) δ 7.68-7.75 (m, 1 H), 7.45 (br s, 0.3 H), 7.20-7.30
429.2
98.7%

(m, 1 H), 7.10-7.20 (m, 1 H), 6.89 (br s, 0.7 H), 5.05-5.34 (m,
[M + H]⁺

1 H), 3.64-4.08 (m, 1 H), 2.86-3.26 (m, 2 H), 1.50 (s, 6 H),

1.46 (s, 3 H)

852
(CD₃OD) δ 7.56-7.64 (m, 1 H), 7.25-7.40 (m, 0.4 H), 7.08-
429.2
99.1%

7.18 (m, 1 H), 6.99-7.07 (m, 1 H), 6.78 (br s, 0.6 H), 4.95-5.22
[M + H]⁺

(m, 1 H), 3.51-3.94 (m, 1 H), 2.72-3.13 (m, 2 H), 1.38 (s, 6

H), 1.34 (s, 3 H)

853
(CD₃OD) δ 8.29-8.37 (m, 1 H), 7.89-8.03 (m, 1 H), 7.48-7.86
521.2
94.8%

(m, 4.5 H), 7.16-7.26 (m, 1 H), 6.97 (s, 0.5 H), 5.07-5.35 (m, 1
[M + H]⁺

H), 3.94-4.12 (m, 0.7 H), 3.57-3.72 (m, 0.3 H), 2.84-3.28 (m,

2 H)

854
(CD₃OD) δ 8.31-8.36 (m, 1 H), 7.92-8.04 (m, 1 H), 7.48-7.85
521.2
78.2%

(m, 4.5 H), 7.18-7.27 (m, 1 H), 6.96 (br s, 0.5 H), 5.04-5.37
[M + H]⁺

(m, 1 H), 4.05 (br s, 0.7 H), 3.66 (br s, 0.3 H), 2.82-3.29 (m, 2

H)

855
(CD₃OD) δ 7.69-7.73 (m, 1 H), 7.49 (br s, 0.3 H), 7.02-7.33
413.2
97.9%

(m, 2 H), 6.88 (s, 0.7 H), 5.04-5.32 (m, 1 H), 3.59-4.05 (m, 1
[M + H]⁺

H), 2.98-3.24 (m, 1 H), 2.78-2.94 (m, 1 H), 2.26-2.41 (m, 1

H), 1.18-1.32 (m, 4 H)

856
(CD₃OD) δ 7.66-7.78 (m, 1 H), 7.48 (br s, 0.3 H), 7.10-7.32
413.2
92.4%

(m, 2 H), 6.88 (br s, 0.7 H), 5.06-5.36 (m, 1 H), 3.60-4.06 (m,
[M + H]⁺

1 H), 2.82-3.24 (m, 2 H), 2.23-2.44 (m, 1 H), 1.14-1.38 (m, 4

H)

857
(CD₃OD) δ 8.40-8.91 (m, 1 H), 7.87-8.04 (m, 1 H), 7.70-7.80
446.2
100%

(m, 2 H), 7.46-7.54 (m, 1 H), 7.19-7.39 (m, 3 H), 6.64-7.14
[M + H]⁺

(m, 1 H), 5.24 (dd, 1 H), 4.02 (br t, 0.6 H), 3.69-3.90 (m, 0.5

H), 3.17-3.31 (m, 0.8 H), 2.85-3.02 (m, 1.2 H), 2.50-2.62 (m,

3 H)

858
(CD₃OD) δ 8.36-8.80 (m, 1 H), 7.83-8.04 (m, 1 H), 7.69-7.82
446.2
99.1%

(m, 2 H), 7.44-7.59 (m, 1.3 H), 7.19-7.37 (m, 2.7 H), 6.76-
[M + H]⁺

7.04 (m, 1 H), 5.24 (dd, 1 H), 4.02 (br t, 0.7 H), 3.72-3.88 (m,

0.4 H), 3.11-3.28 (m, 1 H), 2.84-2.97 (m, 1 H), 2.51-2.60 (m,

3 H)

859
(CD₃OD) δ 8.06-8.61 (m, 1 H), 7.61-7.94 (m, 2 H), 6.85-7.61
467.2
98.7%

(m, 5 H), 5.29 (br dd, 1 H), 3.53-4.43 (m, 1 H), 2.77-3.24 (m,
[M + H]⁺

2 H), 2.34-2.68 (m, 3 H)

860
(CD₃OD) δ 8.21-8.57 (m, 1 H), 7.58-8.00 (m, 2 H), 6.89-7.58
467.1
98.7%

(m, 5 H), 5.29 (br dd, 1 H), 3.53-4.20 (m, 1 H), 2.87-3.26 (m,
[M + H]⁺

2 H), 2.42-2.68 (m, 3 H)

861
(CD₃OD) δ 8.35 (d, 1 H), 7.69-7.87 (m, 1.6 H), 7.31-7.69 (m,
471.1
100%

3 H), 7.15-7.31 (m, 2 H), 6.94 (br s, 0.4 H), 5.04-5.35 (m, 1
[M + H]⁺

H), 3.60-4.16 (m, 1 H), 2.90-3.26 (m, 2 H)

862
(CD₃OD) δ 8.09-8.33 (m, 1 H), 7.57-7.73 (m, 1.6 H), 7.17-
471.1
95.1%

7.57 (m, 3 H), 6.99-7.17 (m, 2 H), 6.82 (br s, 0.4 H), 4.99-5.30
[M + H]⁺

(m, 1 H), 3.49-4.01 (m, 1 H), 2.77-3.17 (m, 2 H)

863
(CD₃OD) δ 8.34 (s, 1 H), 7.70 (s, 1 H), 7.53 (d, 1 H), 7.38 (td,
418.1
99.3%

1 H), 7.19-7.31 (m, 1 H), 6.78 (br s, 1 H), 6.00-6.42 (m, 1 H),
[M + H]⁺

4.95-5.18 (m, 1 H), 3.95 (br s, 1 H), 3.41 (td, 2 H), 3.12 (br d,

1 H), 2.87 (br d, 1 H)

864
(CD₃OD) δ 8.34 (s, 1 H), 7.70 (s, 1 H), 7.53 (d, 1 H), 7.38 (td,
418.1
98.5%

1 H), 7.14-7.30 (m, 1 H), 6.78 (br s, 1 H), 6.02-6.42 (m, 1 H),
[M + H]⁺

4.95-5.09 (m, 1 H), 3.65-4.13 (m, 1 H), 3.41 (td, 2 H), 3.12 (br

d, 1 H), 2.87 (br d, 1 H)

865
(CD₃OD) δ 8.34 (br s, 1 H), 7.59-7.84 (m, 2 H), 7.42 (dd, 1
418.1
98.4%

H), 7.21 (td, 1 H), 6.75 (br s, 1 H), 5.99-6.49 (m, 1 H), 4.50-
[M + H]⁺

4.61 (m, 1 H), 3.92 (br s, 1 H), 3.41 (td, 2 H), 3.11 (br d, 1 H),

2.85 (br d, 1 H)

866
(CD₃OD) δ 8.34 (br s, 1 H), 7.60-7.81 (m, 2 H), 7.42 (dd, 1
418.1
98.2%

H), 7.21 (td, 1 H), 6.75 (br s, 1 H), 6.01-6.45 (m, 1 H), 4.46-
[M + H]⁺

4.61 (m, 1 H), 3.93 (br s, 1 H), 3.41 (td, 2 H), 3.09 (br s, 1 H),

2.85 (br d, 1 H)

867
(CD₃OD) δ 8.55-8.74 (m, 1 H), 7.87-8.00 (m, 1 H), 7.69-7.81
450.1
99.0%

(m, 2 H), 7.48-7.62 (m, 1 H), 7.33-7.44 (m, 1 H), 7.12-7.32
[M + H]⁺

(m, 1 H), 6.95 (br s, 1 H), 5.12-5.32 (m, 1 H), 4.03 (br s, 0.7

H), 3.72 (br s, 0.3 H), 3.02-3.29 (m, 1 H), 2.94 (br d, 1 H)

868
(CD₃OD) δ 8.38-8.72 (m, 1 H), 7.75-7.96 (m, 1 H), 7.54-7.72
450.1
96.8%

(m, 2 H), 7.35-7.51 (m, 1 H), 7.19-7.34 (m, 1 H), 7.05-7.19
[M + H]⁺

(m, 1 H), 6.84 (s, 1 H), 4.96-5.24 (m, 1 H), 3.79-3.98 (m, 0.7

H), 3.53-3.68 (m, 0.3 H), 2.96-3.19 (m, 1 H), 2.76-2.91 (m, 1

H)

869
(CD₃OD) δ 7.79-7.90 (m, 1 H), 7.73 (s, 1 H), 7.38-7.65 (m,
431.1
100%

1.3 H), 7.17-7.38 (m, 2 H), 6.85-7.16 (m, 1.7 H), 5.12-5.34
[M + H]⁺

(m, 1.4 H), 3.96-4.08 (m, 3.6 H), 2.89-3.30 (m, 2 H), 2.50-

2.61 (m, 3 H)

870
(CD₃OD) δ 7.71 (d, 1 H), 7.61 (s, 1 H), 7.29-7.49 (m, 1.3 H),
431.2
98.5%

7.05-7.22 (m, 2 H), 6.65-6.95 (m, 1.7 H), 4.89-5.27 (m, 1.2
[M + H]⁺

H), 3.81-3.96 (m, 3.8 H), 2.74-3.18 (m, 2 H), 2.36-2.52 (m, 3

H)

871
(CD₃OD) δ 8.94 (s, 1 H), 8.14-8.67 (m, 1 H), 7.57-7.84 (m, 2
467.2
100%

H), 7.40-7.54 (m, 1.3 H), 7.13-7.37 (m, 2 H), 6.93 (br s, 0.7
[M + H]⁺

H), 5.33 (dd, 0.7 H), 5.12 (br dd, 0.3 H), 3.91-4.06 (m, 0.7 H),

3.67 (br s, 0.3 H), 2.85-3.28 (m, 2 H), 2.50-2.61 (m, 3 H)

872
(CD₃OD) δ 8.74-9.06 (m, 1 H), 8.25-8.49 (m, 1 H), 7.57-7.82
467.2
95.1%

(m, 2 H), 7.42-7.55 (m, 1.3 H), 7.10-7.34 (m, 2 H), 6.93 (s, 0.7
[M + H]⁺

H), 5.33 (dd, 0.7 H), 5.12 (br dd, 0.3 H), 3.92-4.10 (m, 0.7 H),

3.53-3.80 (m, 0.3 H), 2.88-3.28 (m, 2 H), 2.50-2.61 (m, 3 H)

873
(CD₃OD) δ 8.34 (br s, 1 H), 7.64-7.73 (m, 3 H), 7.42 (qd, 2
400.1
97.8%

H), 6.78 (br s, 1 H), 6.02-6.45 (m, 1 H), 4.49-4.61 (m, 0.4 H),
[M + H]⁺

3.89 (br s, 0.6 H), 3.35-3.48 (m, 2.5 H), 2.93-3.18 (m, 1.5 H),

2.86 (br d, 1 H)

874
(CD₃OD) δ 8.34 (br s, 1 H), 7.64-7.73 (m, 3 H), 7.42 (qd, 2
400.2
100%

H), 6.79 (br s, 1 H), 6.03-6.44 (m, 1 H), 4.51-4.60 (m, 0.3 H),
[M + H]⁺

3.91 (br s, 0.7 H), 3.35-3.49 (m, 2.4 H), 2.93-3.20 (m, 1.6 H),

2.86 (br d, 1 H)

875
(CD₃OD) δ 8.94 (s, 1 H), 8.22-8.51 (m, 1 H), 7.69-7.83 (m,
471.1
100%

1.3 H), 7.57-7.69 (m, 0.7 H), 7.49-7.56 (m, 1.3 H), 7.33-7.44
[M + H]⁺

(m, 1 H), 7.16-7.30 (m, 1 H), 6.94 (s, 0.7 H), 5.35 (dd, 0.7 H),

5.14 (dd, 0.3 H), 4.01 (br t, 0.7 H), 3.59-3.79 (m, 0.3 H), 2.84-

3.29 (m, 2 H)

876
(CD₃OD) δ 8.63-8.99 (m, 1 H), 8.11-8.35 (m, 1 H), 7.57-7.78
471.1
97.3%

(m, 1.3 H), 7.45-7.56 (m, 0.8 H), 7.37-7.43 (m, 1.3 H), 7.22-
[M + H]⁺

7.33 (m, 1 H), 7.07-7.19 (m, 1 H), 6.82 (s, 0.7 H), 5.23 (dd,

0.7 H), 5.02 (dd, 0.3 H), 3.89 (br t, 0.7 H), 3.56 (br d, 0.3 H),

2.76-3.14 (m, 2 H)

877
(CD₃OD) δ 8.62 (s, 1 H), 8.42 (br s, 1 H), 7.93 (d, 1 H), 7.67
443.0
95.2%

(s, 1 H), 7.47-7.53 (m, 2 H), 7.43 (dd, 1 H), 7.21-7.26 (m, 1
[M + H]⁺

H), 6.76 (br s, 1 H), 4.71 (br d, 1 H), 4.52 (s, 2 H), 3.87 (br s,

1 H), 3.43 (s, 3 H), 3.04-3.17 (m, 1 H), 2.83 (br d, 1 H), 2.45

(s, 3 H)

878
(CD₃OD) δ 8.63 (s, 1 H), 8.43 (br s, 1 H), 7.94 (d, 1 H), 7.67
443.0
73.8%

(s, 1 H), 7.48-7.54 (m, 2 H), 7.44 (dd, 1 H), 7.24 (dd, 1 H),
[M + H]⁺

6.76 (br s, 1 H), 4.72 (br d, 1 H), 4.53 (s, 2 H), 3.87 (br s, 1

H), 3.43 (s, 3 H), 3.04-3.17 (m, 1 H), 2.83 (br d, 1 H), 2.46 (s,

3 H)

879
(CD₃OD) δ 9.05 (br s, 1 H), 8.50 (br d, 1 H), 7.88-8.32 (m, 3
430.1
99.8%

H), 7.62-7.75 (m, 2 H), 7.33-7.52 (m, 2 H), 7.10-7.29 (m, 1
[M + H]⁺

H), 6.83 (br s, 1 H), 4.64 (s, 1 H), 3.72-4.18 (m, 1 H), 2.68-

3.25 (m, 2 H)

880
(CD₃OD) δ 8.92 (br s, 1 H), 8.37 (br d, 1 H), 7.76-8.12 (m, 3
430.0
99.2%

H), 7.54-7.71 (m, 2 H), 7.21-7.47 (m, 2 H), 7.10 (br t, 1 H),
[M + H]⁺

6.71 (br s, 1 H), 4.20-4.56 (m, 1 H), 3.89 (br s, 1 H), 2.60-3.07

(m, 2 H)

881
(CD₃OD) δ 8.23-8.31 (m, 1 H), 7.55-7.73 (m, 2.4 H), 7.37-
449.2
92.7%

7.45 (m, 1 H), 7.14-7.25 (m, 1 H), 6.87 (br s, 0.6 H), 5.33 (dd,
[M + H]⁺

0.7 H), 5.10 (dd, 0.3 H), 3.94-4.06 (m, 0.6 H), 3.87-3.93 (m, 3

H), 3.62 (br t, 0.3 H), 3.14-3.24 (m, 0.7 H), 2.94-3.05 (m, 0.4

H), 2.82-2.93 (m, 1 H), 2.47-2.57 (m, 3 H)

882
(CD₃OD) δ 8.23-8.31 (m, 1 H), 7.55-7.75 (m, 2.4 H), 7.37-
449.2
88.3%

7.45 (m, 1 H), 7.14-7.24 (m, 1 H), 6.87 (br s, 0.6 H), 5.33 (dd,
[M + H]⁺

0.7 H), 5.10 (dd, 0.3 H), 3.94-3.99 (m, 0.5 H), 3.89-3.92 (m, 3

H), 3.56-3.83 (m, 0.5 H), 3.11-3.22 (m, 0.6 H), 2.84-3.05 (m,

1.4 H), 2.48-2.56 (m, 3 H)

883
(CD₃OD) δ 8.45 (br s, 1 H), 7.69 (s, 1 H), 7.54 (d, 1 H), 7.46
400.20
98.2%

(s, 1 H), 6.94-7.31 (m, 2 H), 6.54-6.86 (m, 1 H), 4.53 (br d, 1
[M + H]⁺

H), 3.90 (br s, 1 H), 3.11 (br d, 1 H), 2.84 (br d, 1 H), 2.48 (s,

3 H)

884
(CD₃OD) δ 8.44 (br s, 1 H), 7.69 (s, 1 H), 7.54 (d, 1 H), 7.46
400.20
94.7%

(s, 1 H), 6.97-7.28 (m, 2 H), 6.76 (br s, 1 H), 4.53 (br d, 1 H),
[M + H]⁺

3.90 (br s, 1 H), 3.11 (br d, 1 H), 2.84 (br d, 1 H), 2.48 (s, 3 H)

885
(CD₃OD) δ 8.62-8.73 (m, 1 H), 7.55-7.74 (m, 2 H), 7.35-7.44
382.2
99.0%

(m, 1 H), 7.12-7.25 (m, 1 H), 6.85 (br s, 1 H), 5.10 (dd, 0.3
[M + H]⁺

H), 4.75 (dd, 0.7 H), 4.24-4.37 (m, 2 H), 3.80-3.96 (m, 0.7 H),

3.53 (br s, 0.3 H), 3.12-3.26 (m, 0.8 H), 2.93-3.05 (m, 0.3 H),

2.74-2.90 (m, 1 H), 1.37-1.49 (m, 3 H)

886
(CD₃OD) δ 8.63-8.75 (m, 1 H), 7.56-7.73 (m, 2 H), 7.36-7.43
382.2
97.9%

(m, 1 H), 7.12-7.24 (m, 1 H), 6.85 (br s, 1 H), 5.11 (br dd, 0.2
[M + H]⁺

H), 4.75 (br dd, 0.9 H), 4.24-4.37 (m, 2 H), 3.88 (br s, 0.7 H),

3.47-3.60 (m, 0.3 H), 3.11-3.26 (m, 0.8 H), 2.97 (br d, 0.3 H),

2.75-2.90 (m, 1 H), 1.37-1.53 (m, 3 H)

887
(CD₃OD) δ 7.62-7.80 (m, 2 H), 7.35-7.50 (m, 2 H), 7.08-7.19
382.3
100%

(m, 1 H), 6.93-7.06 (m, 1 H), 6.41-6.85 (m, 1 H), 4.91-4.97
[M + H]⁺

(m, 0.4 H), 4.37 (dd, 0.8 H), 3.83 (br s, 0.8 H), 3.12-3.27 (m, 4

H), 2.74-3.06 (m, 2 H)

888
(CD₃OD) δ 7.62-7.80 (m, 2 H), 7.35-7.51 (m, 2 H), 7.09-7.18
382.3
99.6%

(m, 1 H), 6.93-7.06 (m, 1 H), 6.42-6.84 (m, 1 H), 4.91-4.97
[M + H]⁺

(m, 0.4 H), 4.37 (dd, 0.8 H), 3.83 (br s, 0.8 H), 3.12-3.27 (m, 4

H), 2.74-3.06 (m, 2 H)

889
(CD₃OD) δ 8.44 (s, 1 H), 7.68 (s, 1 H), 6.97-7.29 (m, 3 H),
414.1
99.3%

6.78 (br s, 1 H), 4.49-4.63 (m, 1 H), 4.02 (br s, 1 H), 2.79-3.15
[M + H]⁺

(m, 2 H), 2.45-2.49 (m, 6 H)

890
(CD₃OD) δ 8.45 (s, 1 H), 7.68 (s, 1 H), 6.71-7.30 (m, 4 H),
414.2
99.3%

4.45-4.66 (m, 1 H), 3.50-4.14 (m, 1 H), 2.74-3.18 (m, 2 H),
[M + H]⁺

2.42-2.52 (m, 7 H)

891
(CD₃OD) δ 7.63-8.12 (m, 2.8 H), 7.54 (br d, 1 H), 7.34-7.46
484.1
98.6%

(m, 1 H), 7.00-7.34 (m, 2.2 H), 6.81 (br s, 1 H), 4.81 (br s, 1
[M + H]⁺

H), 3.61-4.19 (m, 4 H), 3.17-3.29 (m, 1 H), 2.91 (br d, 1 H)

892
(CD₃OD) δ 7.65-8.14 (m, 3 H), 7.54 (br d, 1 H), 7.39 (td, 1
484.2
98.5%

H), 7.00-7.34 (m, 2 H), 6.84 (br s, 1 H), 4.81 (br s, 1 H), 3.73-
[M + H]⁺

4.14 (m, 4 H), 3.25 (br s, 1 H), 2.91 (br d, 1 H)

893
(CD₃OD) δ 7.61-7.88 (m, 2 H), 7.48-7.55 (m, 1 H), 7.36-7.48
412.2
99.7%

(m, 1 H), 7.16 (br t, 1 H), 6.77 (s, 1 H), 4.61-4.86 (m, 1 H),
[M + H]⁺

3.44-4.17 (m, 1 H), 2.82-3.27 (m, 2 H), 1.66 (br s, 6 H)

894
(CD₃OD) δ 7.61-7.88 (m, 2 H), 7.49-7.57 (m, 1 H), 7.43 (td, 1
412.2
99.3%

H), 7.16 (t, 1 H), 6.77 (br s, 1 H), 4.59-4.85 (m, 1 H), 3.58-
[M + H]⁺

4.20 (m, 1 H), 2.79-3.22 (m, 2 H), 1.66 (br s, 6 H)

895
(CD₃OD) δ 8.30 (s, 1 H), 8.10 (s, 1 H), 7.80-7.97 (m, 2 H),
520.2
98.9%

7.45 (dd, 1 H), 7.09-7.30 (m, 2 H), 6.87 (s, 1 H), 4.76 (br dd, 1
[M + H]⁺

H), 3.73-4.04 (m, 2 H), 3.44-3.59 (m, 2 H), 3.08-3.24 (m, 1

H), 2.82-2.99 (m, 3 H), 1.93-2.12 (m, 2 H), 1.59-1.84 (m, 2 H)

896
(CD₃OD) δ 8.52 (s, 1 H), 8.33 (s, 1 H), 8.13 (s, 1 H), 7.88 (d,
520.2
97.5%

1 H), 7.49 (dd, 1 H), 7.14-7.34 (m, 2 H), 7.06 (s, 1 H), 4.80 (br
[M + H]⁺

dd, 1 H), 3.71-3.91 (m, 2 H), 3.46-3.64 (m, 2 H), 3.13-3.28

(m, 1 H), 2.88-3.01 (m, 3 H), 1.95-2.11 (m, 2 H), 1.63-1.81

(m, 2 H)

897
(DMSO-d₆) δ 12.21 (br s, 1 H), 8.75 (br s, 1 H), 7.60-7.66 (m,
418.2
99.5%

1 H), 7.17-7.33 (m, 3 H), 6.57 (s, 1 H), 3.61-4.95 (m, 2 H),
[M + H]⁺

2.78-3.01 (m, 2 H), 2.46 (s, 3 H)

898
(DMSO-d₆) δ 12.20 (br s, 1 H), 8.75 (br s, 1 H), 7.59-7.66 (m,
418.1
98.7%

1 H), 7.13-7.33 (m, 3 H), 6.57 (s, 1 H), 3.52-4.93 (m, 2 H),
[M + H]⁺

2.80-2.98 (m, 2 H), 2.46 (s, 3 H)

899
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.53 (d, 1 H), 7.38
405.1
99.1%

(td, 1 H), 6.99-7.31 (m, 2 H), 4.58 (br d, 1 H), 3.58-4.12 (m, 1
[M + H]⁺

H), 3.13 (br s, 1 H), 2.88 (br d, 1 H)

900
(CD₃OD) δ 8.47 (br s, 1 H), 7.71 (s, 1 H), 7.53 (d, 1 H), 7.39
405.1
97.9%

(td, 1 H), 6.94-7.30 (m, 2 H), 4.58 (br d, 1 H), 3.58-4.06 (m, 1
[M + H]⁺

H), 3.12 (br s, 1 H), 2.88 (br d, 1 H)

901
(CD₃OD) δ 7.92-8.07 (m, 1 H), 7.68 (s, 1 H), 7.10-7.47 (m,
364.2
100%

3.4 H), 6.87 (br s, 0.6 H), 5.07 (dd, 0.3 H), 4.67 (dd, 0.7 H),
[M + H]⁺

4.06 (s, 3 H), 3.89 (br d, 0.7 H), 3.49 (br d, 0.3 H), 3.12-3.23

(m, 0.7 H), 2.74-3.04 (m, 1.3 H), 2.48-2.60 (m, 3 H)

902
(CD₃OD) δ 7.94-8.06 (m, 1 H), 7.68 (s, 1 H), 7.10-7.47 (m,
364.2
97.2%

3.4 H), 6.88 (s, 0.6 H), 5.07 (dd, 0.3 H), 4.67 (dd, 0.7 H), 4.06
[M + H]⁺

(s, 3 H), 3.85-3.96 (m, 0.7 H), 3.50 (td, 0.3 H), 3.13-3.22 (m,

0.7 H), 2.76-3.02 (m, 1.3 H), 2.50-2.60 (m, 3 H)

903
(CD₃OD) δ 7.92-8.08 (m, 1 H), 7.70 (s, 1 H), 7.30-7.42 (m, 1
380.2
100%

H), 7.15-7.28 (m, 1.3 H), 6.83-6.96 (m, 1.7 H), 5.08 (br dd,
[M + H]⁺

0.3 H), 4.69 (dd, 0.7 H), 4.06-4.10 (m, 3 H), 3.98-4.02 (m, 3

H), 3.81-3.93 (m, 0.7 H), 3.43-3.53 (m, 0.3 H), 3.15-3.24 (m,

0.8 H), 2.76-3.03 (m, 1.2 H)

904
(CD₃OD) δ 7.93-8.09 (m, 1 H), 7.70 (s, 1 H), 7.30-7.40 (m, 1
380.2
99.7%

H), 7.11-7.28 (m, 1.3 H), 6.80-6.97 (m, 1.7 H), 5.08 (dd, 0.3
[M + H]⁺

H), 4.69 (dd, 0.7 H), 4.05-4.13 (m, 3 H), 3.97-4.03 (m, 3 H),

3.87 (br t, 0.7 H), 3.48 (br s, 0.3 H), 3.15-3.25 (m, 0.7 H),

2.76-3.04 (m, 1.3 H)

905
(CD₃OD) δ 7.61-7.75 (m, 2 H), 7.43 (br d, 1 H), 6.94-7.32 (m,
463.2
98.2%

2 H), 4.57 (br s, 1 H), 3.60-4.09 (m, 1 H), 3.16 (br s, 1 H),
[M + H]⁺

2.88 (br d, 1 H), 1.51-1.77 (m, 6 H)

906
(CD₃OD) δ 7.58-7.77 (m, 2 H), 7.43 (dd, 1 H), 6.96-7.31 (m, 2
463.2
96.1%

H), 4.47-4.60 (m, 1 H), 3.59-4.07 (m, 1 H), 2.98-3.24 (m, 1
[M + H]⁺

H), 2.88 (br d, 1 H), 1.46-1.81 (m, 6 H)

907
(CD₃OD) δ 7.71 (s, 1 H), 7.46-7.56 (m, 1 H), 6.84-7.36 (m, 3
378.2
93.2%

H), 5.08 (dd, 0.3 H), 4.68 (dd, 0.7 H), 3.98 (s, 3 H), 3.40-3.94
[M + H]⁺

(m, 1 H), 2.92-3.25 (m, 1 H), 2.77-2.91 (m, 1 H), 2.30-2.63

(m, 6 H)

908
(CD₃OD) δ 7.69-7.84 (m, 1 H), 7.45-7.58 (m, 1 H), 6.86-7.33
378.2
85.0%

(m, 3 H), 5.08 (br dd, 0.3 H), 4.69 (dd, 0.7 H), 3.99 (s, 3 H),
[M + H]⁺

3.36-3.95 (m, 1 H), 2.95-3.24 (m, 1 H), 2.76-2.92 (m, 1 H),

2.30-2.59 (m, 6 H)

909
(CD₃OD) δ 7.65-7.79 (m, 1 H), 7.22-7.40 (m, 2 H), 6.86-7.17
394.2
100%

(m, 2 H), 5.04 (br dd, 0.4 H), 4.66 (dd, 0.6 H), 3.76-4.10 (m, 7
[M + H]⁺

H), 2.96-3.25 (m, 1 H), 2.77-2.94 (m, 1 H), 2.30-2.47 (m, 3 H)

910
(CD₃OD) δ 7.66-7.79 (m, 1 H), 7.22-7.37 (m, 2 H), 6.86-7.19
394.2
99.6%

(m, 2 H), 5.04 (br dd, 0.4 H), 4.66 (dd, 0.6 H), 3.84-4.07 (m, 7
[M + H]⁺

H), 2.94-3.22 (m, 1 H), 2.76-2.92 (m, 1 H), 2.29-2.42 (m, 3 H)

911
(CD₃OD) δ 8.44 (s, 1 H), 7.63 (br s, 1 H), 7.53 (d, 1 H), 7.38
430.2
92.6%

(td, 1 H), 7.19-7.30 (m, 1.4 H), 6.96-7.17 (m, 1 H), 6.87 (br s,
[M + H]⁺

0.6 H), 3.83-4.40 (m, 2 H), 0.95-1.34 (m, 4 H)

912
(CD₃OD) δ 8.44 (s, 1 H), 7.63 (br s, 1 H), 7.53 (d, 1 H), 7.38
430.1
89.3%

(td, 1 H), 7.17-7.29 (m, 1.4 H), 6.96-7.17 (m, 1 H), 6.88 (br s,
[M + H]⁺

0.6 H), 3.79-4.43 (m, 2 H), 0.95-1.34 (m, 4 H)

913
(CD₃OD) δ 7.51-7.79 (m, 4 H), 7.32-7.48 (m, 3 H), 6.85 (br s,
380.1
99.7%

0.7 H), 6.46 (br s, 0.3 H), 4.94-4.98 (m, 0.4 H), 4.36 (dd, 0.6
[M + H]⁺

H), 3.78 (br s, 0.7 H), 3.36-3.50 (m, 2.3 H), 3.08-3.26 (m, 2

H), 2.67-3.04 (m, 2 H)

914
(CD₃OD) δ 7.51-7.75 (m, 4 H), 7.32-7.48 (m, 3 H), 6.85 (br s,
380.1
99.2%

0.7 H), 6.46 (br s, 0.3 H), 4.93-4.99 (m, 0.4 H), 4.36 (dd, 0.6
[M + H]⁺

H), 3.77 (br t, 0.7 H), 3.37-3.53 (m, 2.3 H), 3.10-3.27 (m, 2

H), 2.66-3.03 (m, 2 H)

915
(CD₃OD) δ 8.72 (d, 1 H), 7.38-8.02 (m, 5 H), 7.19 (br t, 2 H),
471.0
97.6%

6.99 (br s, 1 H), 3.44-4.21 (m, 2 H), 2.56-3.00 (m, 2 H)
[M + H]⁺

916
(CD₃OD) δ 8.73 (br d, 1 H), 7.39-7.95 (m, 5 H), 7.20 (br t, 2
471.0
96.9%

H), 7.00 (br s, 1 H), 3.58-4.19 (m, 2 H), 2.61-2.99 (m, 2 H)
[M + H]⁺

917
(CD₃OD) δ 8.11 (br s, 1 H), 7.55-7.68 (m, 2 H), 7.34-7.44 (m,
394.2
97.3%

1 H), 7.17 (td, 2 H), 6.65 (br s, 1 H), 4.65 (br s, 1 H), 3.79 (br
[M + H]⁺

s, 1 H), 2.44-2.74 (m, 2 H), 1.31-1.68 (m, 4 H)

918
(CD₃OD) δ 8.11 (br d, 1 H), 7.58-7.67 (m, 2 H), 7.35-7.43 (m,
394.2
93.4%

1 H), 7.17 (td, 2 H), 6.65 (br s, 1 H), 4.63 (br s, 1 H), 3.78 (br
[M + H]⁺

s, 1 H), 2.46-2.76 (m, 2 H), 1.32-1.68 (m, 4 H)

919
(CD₃OD) δ 7.85 (s, 1 H), 7.62-7.82 (m, 1.8 H), 7.51 (br d, 1.2
399.0
95.3%

H), 7.21-7.33 (m, 2 H), 6.88 (br s, 1.8 H), 6.33 (br s, 0.2 H),
[M + H]⁺

4.22-4.35 (m, 0.8 H), 3.46-4.04 (m, 1.2 H), 2.99-3.11 (m, 1

H), 2.69-2.87 (m, 1 H), 2.57 (br s, 3 H)

920
(CD₃OD) δ 7.73 (s, 1 H), 7.46-7.69 (m, 1.8 H), 7.39 (br d, 1.2
399.0
99.3%

H), 7.09-7.21 (m, 2 H), 6.77 (br s, 1.8 H), 6.20 (br s, 0.2 H),
[M + H]⁺

4.18 (br d, 0.8 H), 3.31-3.91 (m, 1.2 H), 2.87-2.98 (m, 1 H),

2.71 (br d, 1 H), 2.46 (br s, 3 H)

921
(CD₃OD) δ 8.52 (s, 1H), 7.71 (br s, 1H), 7.66-7.57 (m, 2H),
372.1
98.7%

7.42-7.35 (m, 2H), 7.22 (s, 1H), 6.48 (s, 1H), 5.42-5.40 (d,
[M + H]⁺

1H), 5.27-5.24 (d, 1H).

922
(CD₃OD) δ 8.52 (s, 1H), 7.71 (br s, 1H), 7.66-7.57 (m, 2H),
372.1
96.5%

7.41-7.36 (m, 2H), 7.22 (s, 1H), 6.45 (s, 1H), 5.41 (s, 1H),
[M + H]⁺

5.27 (s, 1H).

923
(CD₃OD) δ 7.69-7.66 (m, 2H), 7.63-7.61 (d, 1H), 7.56 (s, 1H),
335.1
99.1%

7.41-7.31 (m, 2H), 6.91 (s, 1H), 6.51 (s, 1H), 5.16-5.12 (d,
[M + H]⁺

1H), 4.92-4.89 (d, 1H), 3.97 (s, 3H).

924
(CD₃OD) δ 7.70-7.66 (m, 2H), 7.63-7.61 (d, 1H), 7.56 (s, 1H),
335.1
96.0%

7.41-7.31 (m, 2H), 6.91 (s, 1H), 6.51 (s, 1H), 5.15-5.11 (d,
[M + H]⁺

1H), 4.92-4.88 (d, 1H), 3.97 (s, 3H).

925
Data Provided Above

926
Data Provided Above

927
(CD₃OD) δ 8.88 (s, 1H), 8.72-8.70 (d, 1H), 8.46 (s, 1H), 8.18-
332.1
99.5%

8.16 (d, 1H), 7.69 (s, 1H), 7.66-7.64 (m, 1H), 7.60-7.57 (m,
[M + H]⁺

1H), 7.43-7.39 (m, 2H), 6.52 (s, 1H), 5.06-5.03 (d, 1H), 4.70-

4.68 (d, 1H).

928
(CD₃OD) δ 8.88 (s, 1H), 8.72-8.70 (d, 1H), 8.46 (s, 1H), 8.18-
332.1
98.2%

8.16 (d, 1H), 7.69 (s, 1H), 7.66-7.64 (m, 1H), 7.60-7.57 (m,
[M + H]⁺

1H), 7.43-7.39 (m, 2H), 6.54 (s, 1H), 5.06-5.02 (dd, 1H), 4.71-

4.68 (d, 1H).

929
(CD₃OD) δ 8.63-8.58 (d, 2H), 8.15 (s, 1H), 7.71 (s, 1H), 7.62-
371.1
>99%

7.57 (m, 2H), 7.45-7.41 (t, 1H), 7.38-7.31 (m, 2H), 7.06 (br s,
[M + H]⁺

1H), 6.58 (s, 1H), 5.38 (s, 1H), 5.12-5.09 (d, 1H).

930
(CD₃OD) δ 8.63-8.58 (d, 2H), 8.15 (s, 1H), 7.71 (s, 1H), 7.63-
371.1
>99%

7.57 (m, 2H), 7.45-7.41 (t, 1H), 7.39-7.34 (m, 2H), 7.07 (br s,
[M + H]⁺

1H), 6.58 (s, 1H), 5.39 (s, 1H), 5.12-5.09 (d, 1H).

931
Data Provided Above

932
Data Provided Above

933
(CD₃OD) δ 8.74-8.73 (m, 1H), 8.38-8.37 (m, 1H), 7.70-7.68
333.1
>99%

(m, 3H), 7.66-7.64 (m, 1H), 7.48-7.33 (m, 2H), 7.27-7.26 (m,
[M + H]⁺

1H), 6.51-6.50 (d, 1H), 4.98-4.94 (m, 1H), 4.65-4.62 (d, 1H).

934
(CD₃OD) δ 8.74-8.73 (m, 1H), 8.38-8.37 (m, 1H), 7.70-6.67
332.2
86.9%

(m, 3H), 7.66-7.63 (m, 1H), 7.48-7.33 (m, 2H), 7.27-7.26 (m,
[M + H]⁺

1H), 6.50-6.51 (d, 1H), 4.98-4.93 (m, 1H), 4.65-4.62 (d, 1H).

935
(CD₃OD) δ 8.38 (s, 1H), 8.09 (s, 1H), 7.72 (s, 1H), 7.67-7.65
403.1
99.5%

(m, 1H), 7.62-7.59 (m, 1H), 7.41-7.37 (m, 2H), 6.52 (d, 1H),
[M + H]⁺

5.54-5.44 (m, 2H), 3.99 (s, 3H).

936
(CD₃OD) δ 8.38 (s, 1H), 8.09 (s, 1H), 7.72 (s, 1H), 7.67-7.65
403.1
98.6%

(m, 1H), 7.62-7.60 (m, 1H), 7.41-7.37 (m, 2H), 6.52 (d, 1H),
[M + H]⁺

5.54-5.44 (m, 2H), 3.99 (s, 3H).

937
(CD₃OD) δ 8.77-8.76 (dt, 1H), 8.31-8.29 (dt, 1H), 8.09-8.05
400.1
95.1%

(td, 1H), 7.74-7.72 (d, 1H), 7.68-7.61 (m, 3H), 7.41-7.35 (m,
[M + H]⁺

2H), 6.55 (s, 1H), 5.59-5.48 (m, 2H).

938
(CD₃OD) δ 8.78-8.76 (dt, 1H), 8.31-8.29 (m, 1H), 8.09-8.05
400.1
96.9%

(td, 1H), 7.74-7.72 (d, 1H), 7.67-7.59 (m, 3H), 7.41-7.35 (m,
[M + H]⁺

2H), 6.55 (s, 1H), 5.59-5.48 (q, 2H).

939
(CD₃OD) δ 8.03 (s, 1H), 7.67-7.65 (m, 1H), 7.61-7.59 (m,
336.1
96.7%

1H), 7.57-7.53 (m, 1H), 7.41-7.32 (m, 2H), 6.48 (s, 1H), 5.44-
[M + H]⁺

5.42 (d, 1H), 5.30-5.26 (d, 1H), 4.08 (s, 3H).

940
(CD₃OD) δ 8.03 (s, 1H), 7.67-7.65 (m, 1H), 7.61-7.59 (m,
336.1
97.8%

1H), 7.57-7.53 (m, 1H), 7.40-7.30 (m, 3H), 6.48 (s, 1H), 5.45-
[M + H]⁺

5.41 (d, 1H), 5.29-5.26 (d, 1H), 4.08 (s, 3H).

941
(CD₃OD) δ 8.31 (s, 1H), 7.65-7.59 (m, 3H), 7.39-7.34 (m,
336.1
>99%

2H), 6.45 (s, 1H), 5.37 (s, 1H), 5.19 (s, 1H), 2.41 (s, 3H).
[M + H]⁺

942
(CD₃OD) δ 8.31 (s, 1H), 7.65-7.59 (m, 3H), 7.39-7.36 (m,
336.1
96.3%

3H), 6.47 (s, 1H), 5.39-5.35 (d, 1H), 5.20-5.17 (d, 1H), 2.41
[M + H]⁺

(s, 3H).

943
(CD₃OD) δ 8.52-8.36 (2 s, 1H), 7.72 (br s, 1H), 7.68-7.50 (m,
390.1
>99%

2H), 7.42-7.34 (m, 2H), 6.53-6.49 (d, 1H), 5.22-5.19 (d, 1H),
[M + H]⁺

5.03-5.00 (d, 1H).

944
(CD₃OD) δ 8.52-8.36 (2 s, 1H), 7.72 (br s, 1H), 7.68-7.50 (m,
390.1
94.6%

2H), 7.43-7.32 (m, 2H), 6.53-6.49 (d, 1H), 5.23-5.20 (d, 1H),
[M + H]⁺

5.03-5.01 (d, 1H).

945
(CD₃OD) δ 7.74 (s, 1H), 7.70-7.67 (m, 1H), 7.63-7.61 (m,
363.0
95.8%

1H), 7.44-7.37 (m, 2H), 6.39 (s, 1H), 5.06-5.03 (d, 1H), 4.95-
[M + H]⁺

4.92 (d, 1H).

946
(CD₃OD) δ 7.74 (s, 1H), 7.70-7.67 (m, 1H), 7.63-7.59 (m,
363.1
95.9%

1H), 7.45-7.37 (m, 2H), 6.39 (s, 1H), 5.05-5.02 (d, 1H), 4.95-
[M + H]⁺

4.92 (d, 1H).

947
(CD₃OD) δ 7.71 (s, 1H), 7.66-7.57 (m, 2H), 7.41-7.35 (m,
430.1
>99%

2H), 7.19 (s, 1H), 6.48 (s, 1H), 5.45-5.42 (d, 1H), 5.28-5.25
[M + H]⁺

(d, 1H), 1.72 (s, 6H).

948
(CD₃OD) δ 7.71 (s, 1H), 7.66-7.57 (m, 2H), 7.40-7.35 (m,
430.1
96.2%

2H), 7.19 (s, 1H), 6.48 (s, 1H), 5.45-5.42 (d, 1H), 5.28-5.25
[M + H]⁺

(d, 1H), 1.72 (s, 6H).

949
(CD₃OD) δ 8.71 (s, 1H), 8.48 (s, 1H), 7.69 (s, 1H), 7.62-7.56
373.1
89.8%

(m, 2H), 7.39-7.34 (m, 2H), 6.43 (s, 1H), 5.02-5.00 (d, 2H).
[M + H]⁺

950
(CD₃OD) δ 8.71 (s, 1H), 8.48 (s, 1H), 7.69 (s, 1H), 7.62-7.56
373.1
86.9%

(m, 2H), 7.39-7.34 (m, 2H), 6.43 (s, 1H), 5.03-5.00 (m, 2H).
[M + H]⁺

951
(CD₃OD) δ 7.92-7.87 (m, 1H), 7.78 (s, 1H), 7.68-7.61 (dd,
371.0
95.8%

2H), 7.57-7.49 (dd, 1H), 7.43-7.38 (m, 2H), 7.14 (s, 1H), 6.53
[M + H]⁺

(s, 1H), 5.21-5.18 (d, 1H), 4.94-4.91 (d, 1H).

952
(CD₃OD) δ 7.92-7.87 (m, 1H), 7.78 (s, 1H), 7.68-7.61 (dd,
371.1
95.4%

2H), 7.57-7.49 (dd, 1H), 7.43-7.38 (m, 2H), 7.14 (s, 1H), 6.53
[M + H]⁺

(s, 1H), 5.21-5.18 (d, 1H), 4.94-4.91 (d, 1H).

953
(CD₃OD) δ 7.90 (s, 1H), 7.70-7.68 (d, 1H), 7.62-7.57 (m, 2H),
389.0
90.2%

7.44-7.35 (m, 2H), 7.04 (s, 1H), 6.46 (s, 1H), 4.96-4.92 (d,
[M + H]⁺

2H).

954
(CD₃OD) δ 7.90 (s, 1H), 7.70-7.68 (d, 1H), 7.62-7.57 (m, 2H),
389.1
85.7%

7.43-7.35 (m, 2H), 7.04 (s, 1H), 6.46 (s, 1H), 4.97-4.92 (d,
[M + H]⁺

2H).

Cell Based Phenylalanine Flux Assay

Cells expressing R408W PAH were made by transducing A375 cells with lentivirus encoding human PAH with the R408W mutation in pLVX-Puro, then selecting with puromycin until stable cell lines were generated. A375 R408W cells were seeded into 96 well plates in DMEM+10% FBS at a density of 40,000 cells/well one hour prior to compound addition. Compounds were resuspended in DMSO, and 2-fold serial dilutions were performed to generate a 10-point dose curve. Compounds were added to plated cells in a total volume of 100 μl, and a final DMSO concentration of 0.5%. Each compound was tested in duplicate. Following compound addition, cells were placed in a 5% CO₂, 37° C. tissue culture incubator for 24 hrs. After the incubation period, 20 μM sepiapterin and 800 μM 13C9,15N-Phenylalanine were added. After 4 hours, cell media was removed. An aliquot of 10 μl of cell media was combined with 200 μl of extraction buffer (80% acetonitrile/20% H₂O) for each well. Determination of ¹³C-Tyrosine concentration was assessed by liquid chromatography mass spectrometry.

Specific compounds disclosed herein were tested in the foregoing assay and they were determined to have an AC₅₀according to the following scores: (A) less than or equal to 0.500 μM, (B) greater than 0.500 and less than 1.000 PM, (C) greater than or equal to 1.000 and less than 5.000 μM, (D) greater than or equal to 5.000 μM, (E) no fit, and (NT) not tested, as shown below. Where a compound was tested multiple times, the average value of the tests is reported.

Ex. #
AC₅₀

1
B

2
D

3
A

4
D

5
A

6
C

7
B

8
C

9
A

10
C

11
B

12
C

13
A

14
C

15
B

16
C

17
A

18
C

19
C

20
D

21
A

22
C

23
A

24
C

25
A

26
B

27
A

28
C

29
C

30
D

31
B

32
C

33
B

34
C

35
B

36
C

37
C

38
C

39
B

40
C

41
A

42
C

43
A

44
C

45
A

46
A

47
C

48
D

49
A

50
A

51
A

52
B

53
A

54
B

55
B

56
C

57
A

58
A

59
B

60
C

61
B

62
C

63
A

64
A

65
C

66
D

67
C

68
C

69
B

70
C

71
B

72
D

73
B

74
D

75
B

76
C

77
B

78
C

79
B

80
C

81
B

82
D

83
C

84
A

85
A

86
C

87
C

88
B

89
C

90
B

91
B

92
D

93
B

94
C

95
B

96
C

97
A

98
C

99
B

100
C

101
B

102
C

103
C

104
D

105
C

106
C

107
A

108
C

109
C

110
B

111
B

112
C

113
C

114
C

115
B

116
C

117
C

118
A

119
B

120
C

121
C

122
A

123
C

124
B

125
C

126
B

127
B

128
C

129
B

130
D

131
B

132
C

133
B

134
D

135
C

136
D

137
A

138
A

139
B

140
D

141
B

142
C

143
A

144
A

145
A

146
B

147
A

148
A

149
A

150
A

151
A

152
C

153
B

154
C

155
A

156
C

157
B

158
C

159
A

160
B

161
A

162
C

163
A

164
C

165
A

166
D

167
A

168
C

169
A

170
B

171
A

172
A

173
A

174
A

175
B

176
C

177
A

178
D

179
B

180
C

181
A

182
C

183
B

184
C

185
B

186
C

187
A

188
C

189
B

190
C

191
B

192
C

193
A

194
A

195
A

196
C

197
B

198
C

199
A

200
C

201
B

202
C

203
B

204
C

205
A

206
C

207
A

208
C

209
D

210
B

211
B

212
C

213
B

214
A

215
B

216
C

217
A

218
C

219
A

220
D

221
B

222
C

223
C

224
C

225
C

226
A

227
A

228
C

229
A

230
C

231
B

232
C

233
C

234
C

235
C

236
B

237
C

238
C

239
B

240
C

241
C

242
D

243
A

244
B

245
A

246
A

247
B

248
C

249
B

250
D

251
C

252
A

253
A

254
A

255
A

256
C

257
A

258
C

259
B

260
D

261
B

262
B

263
A

264
B

265
B

266
D

267
C

268
B

269
B

270
D

271
C

272
A

273
C

274
B

275
B

276
D

277
B

278
C

279
B

280
C

281
B

282
C

283
A

284
C

285
B

286
C

287
B

288
C

289
B

290
C

291
A

292
A

293
A

294
C

295
B

296
C

297
A

298
C

299
A

300
C

301
A

302
C

303
A

304
C

305
A

306
C

307
A

308
A

309
A

310
B

311
A

312
B

313
A

314
B

315
A

316
C

317
A

318
B

319
B

320
D

321
B

322
C

323
A

324
C

325
A

326
C

327
A

328
A

329
A

330
A

331
B

332
C

333
A

334
C

335
A

336
B

337
A

338
B

339
B

340
C

341
A

342
B

343
C

344
C

345
A

346
C

347
B

348
C

349
B

350
A

351
A

352
B

353
A

354
A

355
B

356
C

357
B

358
C

359
B

360
C

361
A

362
C

363
A

364
C

365
B

366
C

367
C

368
B

369
A

370
C

371
B

372
C

373
A

374
A

375
B

376
C

377
B

378
A

379
A

380
B

381
C

382
A

383
A

384
C

385
A

386
D

387
B

388
D

389
A

390
C

391
C

392
A

393
A

394
B

395
B

396
C

397
B

398
D

399
B

400
C

401
A

402
C

403
B

404
C

405
B

406
A

407
A

408
B

409
B

410
C

411
A

412
B

413
B

414
C

415
B

416
B

417
A

418
A

419
B

420
A

421
A

422
B

423
A

424
A

425
A

426
A

427
A

428
C

429
A

430
B

431
A

432
A

433
A

434
A

435
A

436
B

437
A

438
A

439
A

440
C

441
C

442
B

443
B

444
A

445
A

446
A

447
A

448
C

449
A

450
C

451
A

452
C

453
A

454
C

455
A

456
C

457
A

458
A

459
A

460
A

461
A

462
A

463
A

464
B

465
A

466
B

467
A

468
B

469
C

470
A

471
B

472
C

473
B

474
C

475
A

476
C

477
A

478
D

479
B

480
A

481
B

482
A

483
B

484
C

485
C

486
B

487
A

488
C

489
B

490
C

491
B

492
C

493
A

494
A

495
C

496
C

497
C

498
C

499
A

500
A

501
A

502
A

503
D

504
B

505
B

506
C

507
B

508
D

509
A

510
C

511
B

512
C

513
B

514
C

515
B

516
C

517
C

518
A

519
B

520
A

521
C

522
B

523
B

524
C

525
C

526
A

527
A

528
C

529
A

530
B

531
A

532
A

533
A

534
A

535
A

536
A

537
A

538
C

539
A

540
C

541
A

542
C

543
A

544
C

545
C

546
B

547
B

548
C

549
B

550
C

551
B

552
C

553
B

554
C

555
B

556
C

557
A

558
C

559
A

560
A

561
B

562
C

563
A

564
C

565
B

566
C

567
A

568
C

569
A

570
C

571
A

572
A

573
A

574
A

575
C

576
C

577
B

578
C

579
A

580
B

581
A

582
C

583
A

584
C

585
A

586
C

587
A

588
A

589
A

590
A

591
A

592
B

593
C

594
A

595
C

596
A

597
A

598
C

599
A

600
C

601
B

602
B

603
A

604
C

605
A

606
A

607
A

608
A

609
B

610
C

611
B

612
C

613
A

614
C

615
A

616
A

617
A

618
B

619
C

620
A

621
B

622
C

623
C

624
A

625
C

626
A

627
C

628
C

629
B

630
C

631
A

632
A

633
A

634
A

635
B

636
A

637
A

638
A

639
A

640
C

641
A

642
C

643
A

644
A

645
C

646
C

647
B

648
A

649
A

650
B

651
A

652
C

653
A

654
C

655
A

656
C

657
A

658
A

659
A

660
C

661
C

662
C

663
A

664
A

665
A

666
A

667
A

668
A

669
A

670
A

671
C

672
C

673
A

674
C

675
A

676
A

677
A

678
C

679
B

680
C

681
B

682
D

683
C

684
C

685
B

686
C

687
B

688
C

689
A

690
C

691
B

692
A

693
A

694
A

695
A

696
C

697
B

698
C

699
C

700
D

701
A

702
D

703
B

704
C

705
A

706
B

707
A

708
B

709
E

710
A

711
C

712
C

713
B

714
C

715
A

716
C

717
B

718
A

719
A

720
B

721
C

722
A

723
A

724
C

725
A

726
E

727
B

728
D

729
B

730
E

731
A

732
D

733
A

734
C

735
A

736
C

737
A

738
C

739
B

740
A

741
A

742
A

743
A

744
A

745
B

746
C

747
A

748
C

749
A

750
C

751
C

752
A

753
A

754
C

755
A

756
C

757
C

758
A

759
C

760
A

761
A

762
C

763
C

764
A

765
A

766
E

767
A

768
E

769
C

770
C

771
A

772
B

773
A

774
A

775
B

776
C

777
A

778
B

779
C

780
C

781
A

782
B

783
A

784
A

785
D

786
B

787
A

788
C

789
C

790
B

791
B

792
C

793
A

794
C

795
A

796
B

797
A

798
B

799
B

800
A

801
A

802
B

803
A

804
A

805
C

806
C

807
A

808
C

809
A

810
A

811
A

812
B

813
A

814
A

815
B

816
A

817
B

818
C

819
B

820
D

821
A

822
C

823
C

824
A

825
C

826
D

827
C

828
D

829
C

830
B

831
B

832
A

833
A

834
B

835
A

836
B

837
B

838
A

839
B

840
A

841
A

842
C

843
A

844
B

845
C

846
A

847
A

848
B

849
A

850
C

851
B

852
A

853
B

854
A

855
A

856
B

857
C

858
A

859
C

860
B

861
B

862
A

863
A

864
A

865
A

866
B

867
B

868
A

869
A

870
C

871
C

872
B

873
A

874
B

875
A

876
A

877
C

878
D

879
C

880
C

881
C

882
C

883
B

884
A

885
C

886
C

887
B

888
E

889
E

890
A

891
C

892
A

893
C

894
C

895
C

896
D

897
E

898
A

899
A

900
B

901
B

902
C

903
C

904
D

905
A

906
D

907
C

908
C

909
C

910
D

911
A

912
B

913
B

914
E

915
A

916
E

917
C

918
E

919
A

920
E

921
C

922
C

923
E

924
C

925
D

926
E

927
D

928
E

929
C

930
E

931
C

932
C

933
E

934
E

935
D

936
E

937
C

938
C

939
C

940
B

941
C

942
C

943
C

944
C

945
D

946
C

947
D

948
E

949
C

950
E

951
C

952
E

953
C

954
E

Additionally, the following compounds were tested with an AC₅₀of C. D, or E:

Compound(s)
AC₅₀

4S and 4R enantiomers of 2-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-oxazol-5-yl}propan-2-ol

4S and 4R enantiomers of 1-[4-(6-bromo-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-5-yl]-3-(1,3-thiazol-2-yl)propan-1-one

4S and 4R enantiomers of 2-[5-(5-chloro-1,3-thiazole-2-carbonyl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 6-bromo-2-[5-(1,3-thiazole-2-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 6-methyl-2-[5-(1,3-thiazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 6-bromo-2-[5-(1,3-thiazole-5-carbonyl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 6-bromo-2-[5-[2-(1-methyl-1H-pyrazol-4-yl)-1,3-thiazole-5-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 6-bromo-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 6-bromo-2-[5-[2-(pyridin-2-yl)-1,3-thiazole-5-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(1,3-thiazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[2-(1-methyl-1H-pyrazol-4-yl)-1,3-oxazole-5-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(4-methyl-1,3-oxazole-5-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-thiazol-2-yl}propan-2-ol

4S and 4R enantiomers of 5-fluoro-2-[5-[4-methyl-2-(pyridin-2-yl)-1,3-thiazole-5-
D, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[4-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1,3-
C, D

thiazole-5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[4-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1,3-
C, D

oxazole-5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 5-fluoro-2-[5-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of ({3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}methyl)dimethylamine

4S and 4R enantiomers of 1-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-5-y1]-2-{pyrazolo[1,5-a]pyridin-3-yl}ethan-1-one

4S and 4R enantiomers of 2-[5-cyclopropanecarbonyl-1H,4H,5H,6H,7H-imidazo[4,5-
C, D

c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[4-(trifluoromethyl)-1,3-oxazole-2-carbonyl]-
C, C

3H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 6-methyl-2-[5-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-
D, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 6-methyl-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of dimethyl({3-[4-(6-methyl-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-

yl}methyl)amine

4S and 4R enantiomers of 5-methyl-2-[5-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-methyl-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 1-[4-(6-methyl-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-yl]-2-(1,3,4-thiadiazol-2-yl)ethan-1-one

4S and 4R enantiomers of dimethyl({3-[4-(5-methyl-1,3-benzoxazol-2-yl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-

yl}methyl)amine

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-yl}propan-2-ol

4′S and 4′R enantiomers of 4′-(5-fluoro-1,3-benzoxazol-2-yl)-5′-(4-methyl-1,3-oxazole-5-
C, D

carbonyl)-1′,4′,5′,6′-tetrahydrospiro[cyclopropane-1,7′-imidazo[4,5-c]pyridine]

4S and 4R enantiomers of 2-[5-[(1R)-2,2-difluorocyclopropanecarbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(morpholin-4-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(4-fluoropiperidin-1-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of [2-({3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}oxy)ethyl]dimethylamine

4S and 4R enantiomers of 4-(2-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}ethyl)piperazin-2-one

4S and 4R enantiomers of (4-(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-
E, E

c]pyridin-5(4H)-yl)(2-(pyridin-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

4S and 4R enantiomers of 2-[5-[6-(methoxymethyl)pyrazolo[1,5-a]pyridine-3-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-6-methyl-1,3-benzoxazole

4S and 4R enantiomers of 3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-N-(2-methoxyethyl)pyrazolo[1,5-a]pyridin-6-amine

4S and 4R enantiomers of N-cyclopropyl-5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-amine

4S and 4R enantiomers of (2-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)oxazol-5-yl)(4-
E, E

(6-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

4S and 4R enantiomers of 5-fluoro-2-[5-{6-[(morpholin-4-yl)methyl]pyrazolo[1,5-
C, D

alpyridine-3-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-{6-[2-(1H-pyrazol-1-yl)ethoxy]pyrazolo[1,5-
C, D

alpyridine-3-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of (3-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}propyl)dimethylamine

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(3-fluoroazetidin-1-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[2-(4-fluoropiperidin-1-yl)-1,3-oxazole-5-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]-2-(4-fluoropiperidin-1-yl)-1,3-oxazole-4-carbonitrile

4S and 4R enantiomers of (4-(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-
E, E

c]pyridin-5(4H)-yl)(2-(pyridin-2-yl)-4-(trifluoromethyl)oxazol-5-yl)methanone

4S and 4R enantiomers of dimethyl(2-{3-[4-(6-methyl-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-

yl}ethyl)amine

4S and 4R enantiomers of N-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
E, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}methanesulfonamide

4S and 4R enantiomers of 5-fluoro-2-[5-{6-[2-(3-fluoroazetidin-1-yl)ethyl]pyrazolo[1,5-
C, D

a]pyridine-3-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2,2-difluoro-1-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-5-y1]-2-(1-hydroxycyclobutyl)ethan-1-one

4S and 4R enantiomers of 5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazole-4-carbonitrile

4S and 4R enantiomers of 5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-N,N-dimethyl-1,3,4-oxadiazol-2-amine

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(4-methylpiperazin-1-yl)-1,3,4-oxadiazole-2-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of N-[2-(dimethylamino)ethyl]-3-[4-(5-fluoro-1,3-benzoxazol-2-
D, E

yl)-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-amine

4S and 4R enantiomers of methyl N-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-

yl}carbamate

4S and 4R enantiomers of 5-fluoro-2-[5-{6-[(3-fluoroazetidin-1-yl)methyl]pyrazolo[1,5-
C, D

a]pyridine-3-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[6-(3-methoxypropyl)pyrazolo[1,5-a]pyridine-3-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-[4-(6-methyl-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazole-4-carbonitrile

4S and 4R enantiomers of 5-fluoro-2-[5-[2-(4-fluoropiperidin-1-yl)-4-methyl-1,3-oxazole-
C, D

5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of ({5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}methyl)dimethylamine

4S and 4R enantiomers of 5-fluoro-2-[5-[6-(2-methoxyethoxy)pyrazolo[1,5-a]pyridine-3-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of [3-({3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-

yl}oxy)propyl]dimethylamine

4S and 4R enantiomers of 5-fluoro-2-[5-[2-(methoxymethyl)-1,3-thiazole-5-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-{6-[(3,3-difluoropyrrolidin-1-yl)methyl]pyrazolo[1,5-
C, D

alpyridine-3-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-

benzoxazole

4S and 4R enantiomers of 1-[2-({3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}oxy)ethyl]pyrrolidin-2-

one

4S and 4R enantiomers of 4-({3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}methyl)piperazin-2-one

4S and 4R enantiomers of 5-fluoro-2-[5-{6-[2-(morpholin-4-yl)ethyl]pyrazolo[1,5-
C, D

alpyridine-3-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[2-(methoxymethyl)-1,3-oxazole-5-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of ({5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}methyl)dimethylamine

4S and 4R enantiomers of 5-fluoro-2-[5-[6-(2-methoxyethyl)pyrazolo[1,5-a]pyridine-3-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-{6-fluoropyrazolo[1,5-a]pyridine-3-carbonyl}-
D, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-{6-chloropyrazolo[1,5-a]pyridine-3-carbonyl}-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-N-(2-methoxyethyl)-1,3,4-oxadiazol-2-amine

4S and 4R enantiomers of 2-[5-{5-[1-(difluoromethyl)-1H-pyrazol-4-yl]-1,3,4-oxadiazole-
C, C

2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-{5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-
C, C

1,3,4-oxadiazole-2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-

benzoxazole

4S and 4R enantiomers of 2-[5-[3-(difluoromethyl)-1-methyl-1H-pyrazole-5-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of (4-(5-fluorobenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-
E, E

c]pyridin-5(4H)-yl)(6-(2-methoxyethyl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-

yl)methanone

4S and 4R enantiomers of 2-[5-[5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[5-(5-fluoropyridin-2-yl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-6-methyl-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-{5-[5-(trifluoromethyl)pyridin-2-yl]-1,3,4-
C, C

oxadiazole-2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[1-(pyridin-2-yl)azetidine-3-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(1-methyl-1H-pyrazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of ({5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-yl}methyl)dimethylamine

4S and 4R enantiomers of ({3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}methyl)(methyl)amine

4S and 4R enantiomers of 3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-amine

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(methoxymethyl)-1,3,4-oxadiazole-2-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(2-fluoropropan-2-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of methyl 3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridine-5-carbonyl]azetidine-1-carboxylate

4S and 4R enantiomers of 5-fluoro-2-[5-[1-(pyridin-2-yl)-1H-pyrazole-5-carbonyl]-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[5-(difluoromethyl)-1H-pyrazole-4-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-{5-[1-(cyclopropanesulfonyl)-1H-pyrazol-4-yl]-1,3,4-
C, D

oxadiazole-2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-

benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}ethan-1-amine

4S and 4R enantiomers of 3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-N-methylpyrazolo[1,5-a]pyridin-6-amine

4S and 4R enantiomers of 2-[5-[5-(3,3-difluorocyclobutyl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-chloro-1-methyl-1H-pyrazole-4-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-{5-[1-(2,2-difluoroethyl)-1H-pyrazol-4-yl]-1,3,4-
C, C

oxadiazole-2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-

benzoxazole

4S and 4R enantiomers of (2-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}ethyl)(methyl)amine

4S and 4R enantiomers of 5-fluoro-2-[5-[1-(2,2,2-trifluoroethyl)azetidine-3-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of tert-butyl 3-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-yl}azetidine-1-

carboxylate

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(1H-pyrazol-4-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(1H-pyrazol-3-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[5-chloro-1-(pyridin-2-yl)-1H-pyrazole-4-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[3-chloro-1-(pyridin-2-yl)-1H-pyrazole-4-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of (2-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)oxazol-5-yl)(4-
E, E

(5-methylbenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-

yl)methanone

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(3-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole-
C, C

2-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[5-(1,5-dimethyl-1H-pyrazol-3-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[6-(morpholin-4-yl)pyrazolo[1,5-a]pyridine-3-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of (1S)-1-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}ethan-1-ol

4S and 4R enantiomers of 5-fluoro-2-[5-[2-(2-methoxypropan-2-yl)-4-methyl-1,3-
C, D

oxazole-5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 1-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}cyclobutan-1-ol

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1-methyl-1H-pyrazol-3-yl}propan-2-ol

4S and 4R enantiomers of tert-butyl 4-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-

yl}piperazine-1-carboxylate

4S and 4R enantiomers of 5-fluoro-2-[5-[6-(piperazin-1-yl)pyrazolo[1,5-a]pyridine-3-
D, E

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(6-{6-azaspiro[2.5]octan-6-yl}pyrazolo[1,5-a]pyridine-3-
C, D

carbonyl)-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 1-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}methanamine

4S and 4R enantiomers of 5-fluoro-2-[5-{6-[4-(2,2,2-trifluoroethyl)piperazin-1-
C, D

yl]pyrazolo[1,5-a]pyridine-3-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-

1,3-benzoxazole

4S and 4R enantiomers of ethyl 4-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperazine-1-carboxylate

4S and 4R enantiomers of 2-(1-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-yl)propan-2-ol

4S and 4R enantiomers of 1-{4-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]-1H-pyrazol-1-yl}propan-2-one

4S and 4R enantiomers of 1-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo [4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}cyclopropan-1-ol

4S and 4R enantiomers of dimethyl(2-{3-[4-(5-methyl-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-

yl}ethyl)amine

4S and 4R enantiomers of 5-fluoro-2-[5-{5-[3-(trifluoromethyl)-1H-pyrazol-4-yl]-1,3,4-
C, D

oxadiazole-2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[6-(4-fluoropiperidin-1-yl)pyrazolo[1,5-
C, D

alpyridine-3-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 1-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 4-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}-1lambda6-

thiomorpholine-1,1-dione

4S and 4R enantiomers of 1-{4-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]-1H-pyrazol-1-yl}-2-methylpropan-2-ol

4S and 4R enantiomers of 2-[5-[4-(difluoromethyl)-2-(2-methanesulfonylpropan-2-yl)-
C, C

1,3-oxazole-5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-

benzoxazole

4S and 4R enantiomers of 6-bromo-2-[5-[2-(1-methyl-1H-pyrazol-4-yl)-1,3-oxazole-5-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(6-{8-methyl-3,8-diazabicyclo[3.2.1]octan-3-
C, D

yl}pyrazolo[1,5-a]pyridine-3-carbonyl)-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-

1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(1H-pyrazole-4-carbonyl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(1H-pyrazole-5-carbonyl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-chloro-1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-{2-[(2S)-azetidin-2-yl]-4-(difluoromethyl)-1,3-oxazole-5-
C, C

carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(5-chloro-1H-pyrazole-4-carbonyl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(1-methyl-1H-pyrazole-3-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]-1-methyl-1H-pyrazol-3-amine

4S and 4R enantiomers of (2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}propan-2-yl)dimethylamine

4S and 4R enantiomers of 6-fluoro-2-[5-[5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole-
C, C

2-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of (2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}propan-2-yl)(methyl)amine

4S and 4R enantiomers of 1-(difluoromethyl)-5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1H-pyrazol-3-amine

4S and 4R enantiomers of 5-fluoro-2-[5-[1-methyl-3-(trifluoromethyl)-1H-1,2,4-triazole-
C, C

5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 6-fluoro-3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-5-amine

4S and 4R enantiomers of (1S)-1-{5-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}ethan-1-ol

4S and 4R enantiomers of 3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridine-6-carbonitrile

4S and 4R enantiomers of 2-{5-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo [4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of (1R)-1-{5-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo [4,5-c]pyridine-5-carbonyl]-4-methyl-1,3-oxazol-2-yl}ethan-1-ol

4S and 4R enantiomers of 6-fluoro-2-[5-[6-(methoxymethyl)pyrazolo[1,5-a]pyridine-3-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-thiazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-[4-(difluoromethyl)-5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1,3-thiazol-2-yl]propan-2-ol

4S and 4R enantiomers of 2-{4-bromo-5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1,3-thiazol-2-yl}propan-2-ol

4S and 4R enantiomers of 6-fluoro-2-[5-[1-methyl-3-(trifluoromethyl)-1H-1,2,4-triazole-
C, D

5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 4-fluoro-2-[5-[1-methyl-3-(trifluoromethyl)-1H-1,2,4-triazole-
C, C

5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 7-fluoro-2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 4-fluoro-2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 6-fluoro-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo [4,5-c]pyridine-5-carbonyl]-1,2-oxazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(7-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-oxazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-oxazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-{3-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-oxazol-5-yl}propan-2-ol

4S and 4R enantiomers of 2-{3-[4-(7-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-oxazol-5-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo [4,5-c]pyridine-5-carbonyl]-1,2,4-oxadiazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2,4-oxadiazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2,4-oxadiazol-3-yl}propan-2-ol

4S and 4R enantiomers of 6-fluoro-2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 6-fluoro-2-[5-(4-methyl-4H-1,2,4-triazole-3-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(4-cyclopropyl-4H-1,2,4-triazole-3-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-7-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(4-cyclopropyl-4H-1,2,4-triazole-3-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-4-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 4-fluoro-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{3-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-oxazol-5-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(7-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,2,4-oxadiazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-[5-[3-(difluoromethyl)-1-methyl-1H-1,2,4-triazole-5-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-6-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[3-(difluoromethyl)-1-methyl-1H-1,2,4-triazole-5-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-4-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[3-(difluoromethyl)-1-methyl-1H-1,2,4-triazole-5-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 7-fluoro-2-[5-(4-methyl-4H-1,2,4-triazole-3-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 4-fluoro-2-[5-(4-methyl-4H-1,2,4-triazole-3-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-(4-methyl-4H-1,2,4-triazole-3-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(4-cyclopropyl-4H-1,2,4-triazole-3-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-6-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(4-cyclopropyl-4H-1,2,4-triazole-3-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo [4,5-c]pyridine-5-carbonyl]-4-(difluoromethyl)-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-{3-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2,4-oxadiazol-5-yl}propan-2-ol

4S and 4R enantiomers of 2-{3-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,2,4-oxadiazol-5-yl}propan-2-ol

4S and 4R enantiomers of 2-{3-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo [4,5-c]pyridine-5-carbonyl]-1,2,4-oxadiazol-5-yl}propan-2-ol

4S and 4R enantiomers of 6-fluoro-2-[5-[5-(1H-pyrazol-4-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 6-fluoro-2-[5-[5-(1H-pyrazol-5-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(5-tert-butyl-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
E, E

imidazo[4,5-c]pyridine-5-carbonyl]-4-(difluoromethyl)-1,3-oxazol-2-yl}propan-2-ol

4′S and 4′R enantiomers of 2-[4-(difluoromethyl)-5-{[4′-(5-fluoro-1,3-benzoxazol-2-yl)-
C, C

1′,4′,5′,6′-tetrahydrospiro[cyclopropane-1,7′-imidazo[4,5-c]pyridin]-5′-yl]carbonyl}-1,3-

oxazol-2-yl]propan-2-ol

4S and 4R enantiomers of 4-fluoro-2-[5-[5-(1H-pyrazol-4-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-[4-(difluoromethyl)-5-[4-[5-(propan-2-yl)-1,3-benzoxazol-2-
E, E

yl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl]propan-2-ol

4S and 4R enantiomers of 5-tert-butyl-2-[5-[4-(difluoromethyl)-1,3-oxazole-5-carbonyl]-
E, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 1-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-5-y1]-3-(1,3-thiazol-2-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-yl]-3-(1,3-oxazol-2-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(7-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-yl]-3-(1,3-oxazol-5-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-y1]-3-(1,3-oxazol-5-yl)propan-1-one

4S and 4R enantiomers of 2-[5-[4-(difluoromethyl)-1,3-oxazole-5-carbonyl]-
E, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-(propan-2-yl)-1,3-benzoxazole

4S and 4R enantiomers of 1-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-y1]-3-(1,3-thiazol-2-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-y1]-3-(1,3-oxazol-2-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-yl]-3-(1,3-oxazol-5-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-yl]-3-(1,3-oxazol-5-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-y1]-3-(1,3-thiazol-5-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-yl]-3-(1,3-thiazol-5-yl)propan-1-one

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(pyridin-4-yl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 1-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-5-yl]-3-(1,3-thiazol-5-yl)propan-1-one

4S and 4R enantiomers of 1-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, E

imidazo[4,5-c]pyridin-5-yl]-2-(1,3-oxazol-5-yl)ethan-1-one

4S and 4R enantiomers of 6-methyl-2-[5-[5-(1H-pyrazol-4-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[(1,3-oxazol-5-yl)methyl]-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(4,7-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 4,6-difluoro-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(4,6-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-[5-[3-(difluoromethyl)-1-methyl-1H-1,2,4-triazole-5-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-4,6-difluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(pyrimidin-2-yl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 1-{3-[4-(4-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 6,7-difluoro-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(6,7-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-[5-[3-(difluoromethyl)-1-methyl-1H-1,2,4-triazole-5-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-6,7-difluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(1,3-benzoxazol-2-y1)-1H,4H,5H,6H,7H-imidazo[4,5-
C, C

c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 4,5-difluoro-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(4,5-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(5,7-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-[5-[3-(difluoromethyl)-1-methyl-1H-1,2,4-triazole-5-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-4,5-difluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[1-(difluoromethyl)-1H-pyrazole-5-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-4,5-difluoro-1,3-benzoxazole

4S and 4R enantiomers of 5-methoxy-2-[5-(1,3-oxazole-5-carbonyl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(5-methoxy-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(7-methyl-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(7-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1-methyl-1H-1,2,4-triazol-3-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-(4-methoxy-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 7-fluoro-2-[5-[1-methyl-3-(pyridin-2-yl)-1H-1,2,4-triazole-5-
C, D

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[5-(pyridin-2-yl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-(trifluoromethyl)-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(1-methyl-1H-imidazol-4-yl)-1,3,4-oxadiazole-
C, C

2-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[5-(1-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-(trifluoromethyl)-1,3-

benzoxazole

4S and 4R enantiomers of 2-[5-[5-(3-fluoropyridin-2-yl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-(trifluoromethyl)-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(1-methyl-1H-imidazol-5-yl)-1,3,4-oxadiazole-
C, D

2-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 1-{3-[4-(6,7-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 1-{3-[4-(1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-imidazo[4,5-
C, C

c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 2-[5-[5-(1-methyl-1H-pyrazol-3-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-(trifluoromethyl)-1,3-

benzoxazole

4S and 4R enantiomers of 2-[5-[5-(5-methoxypyridin-2-yl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-(trifluoromethyl)-1,3-benzoxazole

4S and 4R enantiomers of 2-[4-(difluoromethyl)-5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-7,7-
D, D

dimethyl-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl]propan-

2-ol

4S and 4R enantiomers of 1-{3-[4-(5-methoxy-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 2-[5-{5-[1-(difluoromethyl)-1H-pyrazol-4-yl]-1,3,4-oxadiazole-
D, D

2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-(trifluoromethyl)-1,3-

benzoxazole

4S and 4R enantiomers of (1-isopropyl-1H-1,2,4-triazol-5-yl)(4-(7-methylbenzo[d]oxazol-
E, E

2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

4S and 4R enantiomers of (1-isopropyl-1H-1,2,4-triazol-5-yl)(4-(7-
E, E

methoxybenzo[d]oxazol-2-yl)-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone

4S and 4R enantiomers of 7-methoxy-2-[5-[1-(trifluoromethyl)-1H-pyrazole-5-carbonyl]-
E, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 7-fluoro-2-[5-(1-methyl-1H-pyrazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(6-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3-oxazol-2-yl}propan-2-ol

4S and 4R enantiomers of 1-{3-[4-(7-methyl-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 2-[5-{5-[1-(difluoromethyl)-1H-pyrazol-3-yl]-1,3,4-oxadiazole-
C, C

2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-(trifluoromethyl)-1,3-

benzoxazole

4S and 4R enantiomers of 2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-7-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-7-methyl-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-7-methoxy-1,3-benzoxazole

4S and 4R enantiomers of 7-fluoro-2-[5-[1-(propan-2-yl)-1H-pyrazole-5-carbonyl]-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 7-methyl-2-[5-[1-(propan-2-yl)-1H-pyrazole-5-carbonyl]-
D, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[1-(pyridin-2-yl)-1H-pyrazole-5-carbonyl]-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 7-methyl-2-[5-[1-(pyridin-2-yl)-1H-pyrazole-5-carbonyl]-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 7-methoxy-2-[5-[1-(pyridin-2-yl)-1H-pyrazole-5-carbonyl]-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[4-(difluoromethyl)-5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-
C, C

1H,4H,5H,6H,7H,8H-imidazo[4,5-c]azepine-5-carbonyl]-1,3-oxazol-2-yl]propan-2-ol

4S and 4R enantiomers of 5-fluoro-2-[5-[5-(pyrimidin-4-yl)-1,3,4-oxadiazole-2-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 1-{3-[4-(4,6-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 2-[5-(1-cyclopropyl-1H-pyrazole-5-carbonyl)-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-7-methyl-1,3-benzoxazole

4S and 4R enantiomers of 5-fluoro-2-[5-[2-(1-methyl-1H-pyrazol-4-yl)-4-
E, E

(trifluoromethyl)-1,3-oxazole-5-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-

1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[4-(difluoromethyl)-1,3-oxazole-5-carbonyl]-7,7-dimethyl-
D, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-{ [4-(difluoromethyl)-1,3-oxazol-5-yl]methyl}-
D, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-5-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[4-(difluoromethyl)-5-{ [4-(5-fluoro-1,3-benzoxazol-2-yl)-
D, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-5-yl]methyl}-1,3-oxazol-2-yl]propan-2-ol

4S and 4R enantiomers of 1-{3-[4-(4,5-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
D, E

imidazo[4,5-c]pyridine-5-carbonyl]pyrazolo[1,5-a]pyridin-6-yl}piperidin-4-ol

4S and 4R enantiomers of 2-{5-[4-(5-methyl-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-{5-[4-[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]-
E, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-yl}propan-2-ol

4S and 4R enantiomers of 5-methoxy-2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
E, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 7-methyl-2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(1,3-dimethyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(1,3-dimethyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-4,7-difluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(1,3-dimethyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-4-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-pyrazole-5-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-pyrazole-5-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-7-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-pyrazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-7-methyl-1,3-benzoxazole

4S and 4R enantiomers of 4,7-difluoro-2-[5-(1-methyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[1-(pyridin-2-yl)-1H-pyrazole-3-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 7-fluoro-2-[5-[1-(pyridin-2-yl)-1H-pyrazole-3-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 7-methyl-2-[5-[1-(pyridin-2-yl)-1H-pyrazole-3-carbonyl]-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(3-tert-butyl-1-methyl-1H-pyrazole-5-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-7-methoxy-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-(1,3-dimethyl-1H-1,2,4-triazole-5-carbonyl)-
C, D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-methyl-1,3-benzoxazole

4S and 4R enantiomers of 4,7-difluoro-2-[5-[5-(1-methyl-1H-imidazol-5-yl)-1,3,4-
C, D

oxadiazole-2-carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(6-methyl-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, D

imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-[5-(1,3-dimethyl-1H-1,2,4-triazole-5-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-5-methoxy-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[5-(1-methyl-1H-imidazol-4-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-7-(trifluoromethyl)-1,3-

benzoxazole

4S and 4R enantiomers of 2-[5-[5-(1-methyl-1H-imidazol-5-yl)-1,3,4-oxadiazole-2-
C, C

carbonyl]-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-7-(trifluoromethyl)-1,3-

benzoxazole

4S and 4R enantiomers of 2-[5-[1-(2,2-difluoroethyl)-1H-pyrazole-3-carbonyl]-
C, E

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(4,7-difluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,3,4-oxadiazol-2-yl}propan-2-ol

4S and 4R enantiomers of 2-[5-{5-[1-(difluoromethyl)-1H-pyrazol-4-yl]-1,3,4-oxadiazole-
C, C

2-carbonyl}-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-7-(trifluoromethyl)-1,3-

benzoxazole

4S and 4R enantiomers of 2-[5-[1-(2,2-difluoroethyl)-1H-pyrazole-3-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-7-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 2-[5-[1-(2,2-difluoroethyl)-1H-pyrazole-3-carbonyl]-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl]-4-fluoro-1,3-benzoxazole

4S and 4R enantiomers of 4,7-difluoro-2-[5-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-
C, C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1]-1,3-benzoxazole

4S and 4R enantiomers of 2-{5-[4-(5-fluoro-1,3-benzoxazol-2-yl)-1H,4H,5H,6H,7H-
C, C

imidazo[4,5-c]pyridine-5-carbonyl]-1,2-oxazol-3-yl}propan-2-ol

(4S, 7S), (4S, 7R), (4R, 7S) and (4R, 7R) diastereomers of 2-[4-(difluoromethyl)-5-
C, C,

[(4R,7S)-4-(5-fluoro-1,3-benzoxazol-2-yl)-7-methyl-1H,4H,5H,6H,7H-imidazo[4,5-
C, D

c]pyridine-5-carbonyl]-1,3-oxazol-2-yl]propan-2-ol

5-fluoro-2-(5-{5-[2-(3-fluoroazetidin-1-yl)ethyl]-1,3,4-oxadiazole-2-carbonyl}-
D

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-yl)-1,3-benzoxazole

2-{5-[4-(difluoromethyl)-2-(2-hydroxypropan-2-yl)-1,3-oxazole-5-carbonyl]-
C

1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-4-y1}-1,3-benzoxazole-5-carbonitrile

Having now fully described the methods, compounds, and compositions of matter provided herein, it will be understood by those of skill in the art that the same can be performed within a wide and equivalent range of conditions, formulations, and other parameters without affecting the scope of the methods, compounds, and compositions provided herein or any embodiment thereof.

All patents, patent applications and publications cited herein are fully incorporated by reference herein in their entirety.

(4-BENZO[D]OXAZOL-2-YL)-6,7-DIHYDRO-1H-IMIDAZO[4,5-C]PYRIDINE-5(4H)-YL)METHANONE DERIVATIVES AS MUTANT PAH STABILIZERS FOR THE TREATMENT OF PHENYLKETONURIA

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