Indazoles as hematopoietic progenitor kinase 1 (HPK1) inhibitors and methods using same

Information

  • Patent Grant
  • 11649255
  • Patent Number
    11,649,255
  • Date Filed
    Monday, September 27, 2021
    3 years ago
  • Date Issued
    Tuesday, May 16, 2023
    a year ago
Abstract
The present disclosure provides a compound of Formula (I) or pharmaceutically acceptable salts thereof, a composition comprising the compound, methods of using the compound for the treatment of various disorders associated with HPK1, and methods of preparing these compounds.
Description
FIELD

The present disclosure is directed to inhibitors of hematopoietic progenitor kinase 1 (HPK1), pharmaceutical compositions comprising the inhibitors, methods of using the inhibitors for the treatment of various disorders associated with HPK1, and methods of preparing these compounds.


BACKGROUND

Immunotherapy is treatment that uses the human body's own immune system to help fight cancer and other disorders. This relatively new approach has achieved remarkable clinical successes in the treatment of a variety of tumor types in recent years, especially with the treatment of immune checkpoint inhibitors and chimeric antigen T-cell therapy. The most investigated checkpoint inhibitors including CTLA4, PD-1, or PD-L1 inhibitors have demonstrated significant antitumor activity by overcoming immunosuppressive mechanisms at the tumor site.


Hematopoietic progenitor kinase 1 (HPK1, MAP4K1) is a serine/threonine kinase and a member of MAP4K. HPK1 is prominently expressed in subsets of hematopoietic cell lineages. HPK1 is a newly identified as a critical negative regulator in the activation of T lymphocytes and dendritic cells. It has been recently demonstrated that the important roles for kinase activity of HPK1 in anticancer immunity as a new intracellular checkpoint molecule as well as potential advantages of combination therapy with current checkpoint regimens. HPK1 inhibition is expected to have dual functions, 1. prolonged activation of T cells; 2. enhanced APC functions by dendritic cells. This dual targeting may synergistically work together for efficient immune responses in tumor microenvironment. Thus, HPK1 has been validated as a novel target for anticancer immunotherapy. Examples of cancers that are treatable using the compounds of the present disclosure include, but are not limited to, all forms of carcinomas, melanomas, blastomas, sarcomas, lymphomas and leukemias, including without limitation, bladder carcinoma, brain tumors, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrial cancer, hepatocellular carcinoma, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal carcinoma and thyroid cancer, acute lymphocytic leukemia, acute myeloid leukemia, ependymoma, Ewing's sarcoma, glioblastoma, medulloblastoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, rhabdoid cancer, and nephroblastoma (Wilm's tumor).


Inhibition of HPK1 with small molecule inhibitors has the potential for the treatment of cancer and other disorders [Hernandez, S., et. al. (2018) Cell Reports 25, 80-94].


SUMMARY

The present disclosure provides novel indazole compounds and pharmaceutically acceptable salts as effective HPK1 inhibitors and dual activators of T cell and dendritic cell.


One embodiment of the invention is a compound represented by Formula (I):




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or a pharmaceutically acceptable salt, hydrate, solvate thereof, wherein R1, R2, R3, R4, R5, Het, M, and L are as defined in the detailed descriptions.


In another embodiment, there is provided a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound of Formula (I) or a pharmaceutically acceptable salt thereof.


In yet another embodiment, there is provided a method of treating a subject with a disease or disorder associated with modulation of HPK1 comprising: administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.







DETAILED DESCRIPTION

The following description is merely exemplary in nature and is not intended to limit the present disclosure, application, or uses.


Definitions

The generic terms used in the present disclosure are herein defined for clarity.


This specification uses the terms “substituent”, “radical”, “group”, “moiety”, and “fragment” interchangeably.


As used herein, the term “alkenyl” refers to a straight or branched hydrocarbonyl group with at least one site of unsaturation, i.e., a carbon-carbon, sp2 double bond. In an embodiment, alkenyl has from 2 to 12 carbon atoms. In some embodiments, alkenyl is a C2-C10 alkenyl group or a C2-C6 alkenyl group. Examples of alkenyl group include, but are not limited to, ethylene or vinyl (—CH═CH2), allyl (—CH2CH═CH2), cyclopentenyl (—C5H7), and 5-hexenyl (—CH2CH2CH2CH2CH═CH2).


As used herein, the term “alkoxy” is RO— where R is alkyl. Non-limiting examples of alkoxy groups include methoxy, ethoxy and propoxy.


As used herein, the term “alkoxyalkyl” refers to an alkyl moiety substituted with an alkoxy group. Examples of alkoxyalkyl groups include methoxymethyl, methoxyethyl, methoxypropyl and ethoxyethyl.


As used herein, the term “alkoxycarbonyl” is ROC(O)—, where R is an alkyl group as defined herein. In various embodiments, R is a C1-C10 alkyl group or a C1-C6 alkyl group.


As used herein, the term “alkyl” refers to a straight or branched chain hydrocarbonyl group. In an embodiment, alkyl has from 1 to 12 carbon atoms. In some embodiments, alkyl is a C1-C10 alkyl group or a C1-C6 alkyl group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl. “lower alkyl” means alkyl having from 1 to 4 carbon atoms.


As used herein, if the term “C1-C6” is used, it means the number of carbon atoms is from 1 to 6. For example, C1-C6 alkyl means an alkyl which carbon number is any integer of from 1 to 6.


As used herein, the term “alkylamino” refers to an amino group substituted with one or more alkyl groups. “N-(alkyl)amino” is RNH— and “N,N-(alkyl)2amino” is R2N—, where the R groups are alkyl as defined herein and are the same or different. In various embodiments, R is a C1-C10 alkyl group or a C1-C6 alkyl group. Examples of alkylamino groups include methylamino, ethylamino, propylamino, butylamino, dimethylamino, diethylamino, and methylethylamino.


As used herein, the term “alkylaminoalkyl” refers to an alkyl moiety substituted with an alkylamino group, wherein alkylamino is as defined herein. Examples of alkylaminoakyl groups include methylaminomethyl and ethylaminomethyl.


As used herein, the term “alkynyl” refers to a straight or branched carbon-chain group with at least one site of unsaturation, i.e., a carbon-carbon, sp triple bond. In an embodiment, alkynyl has from 2 to 12 carbon atoms. In some embodiments, alkynyl is a C2-C10 alkynyl group or a C2-C6alkynyl group. Examples of alkynyl groups include acetylenic (—C≡CH) and propargyl (—CH2CE CH).


As used herein, the term “aryl” refers to any monocyclic or bicyclic carbon ring of up to 7 atoms in each ring, wherein at least one ring is aromatic, or an aromatic ring system of 5 to 14 carbon atoms which includes a carbocyclic aromatic group fused with a 5- or 6-membered cycloalkyl group. Representative examples of aryl groups include, but are not limited to, phenyl, tolyl, xylyl, naphthyl, tetrahydronaphthyl, anthracenyl, fluorenyl, indenyl, azulenyl and indanyl. A carbocyclic aromatic group can be unsubstituted or optionally substituted.


As used herein, the term “cycloalkyl” is a hydrocarbyl group containing at least one saturated or partially unsaturated ring structure, and attached via a ring carbon. In various embodiments, it refers to a saturated or a partially unsaturated C3-C12cyclic moiety, examples of which include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl and cyclooctyl. “Cycloalkyloxy” is RO—, where R is cycloalkyl.


As used herein, the terms “halogen” and “halo” refers to chloro (—Cl), bromo (—Br), fluoro (—F) or iodo (—I). “Haloalkoxy” refers to an alkoxy group substituted with one or more halo groups and examples of haloalkoxy groups include, but are not limited to, —OCF3, —OCHF2 and —OCH2F. “Haloalkoxyalkyl” refers to an alkyl moiety substituted with a haloalkoxy group, wherein haloalkoxy is as defined herein. Examples of haloalkoxyalkyl groups include trifluoromethoxymethyl, trifluoroethoxymethyl and trifluoromethoxyethyl. “Haloalkyl” refers to an alkyl moiety substituted with one or more halo groups. Examples of haloalkyl groups include —CF3 and —CHF2.


As used herein, the term “heteroalkyl” refers to a straight- or branched-chain alkyl group having from 2 to 14 carbons (in some embodiments, 2 to 10 carbons) in the chain, one or more of which has been replaced by a heteroatom selected from S, O, P and N. Exemplary heteroalkyls include alkyl ethers, secondary and tertiary alkyl amines, amides, alkyl sulfides, and the like.


As used herein, the term “heterocyclyl” includes the heteroaryls defined below and refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic group of 2 to 14 ring-carbon atoms and, in addition to ring-carbon atoms, 1 to 4 heteroatoms selected from P, N, O and S. In various embodiments the heterocyclic group is attached to another moiety through carbon or through a heteroatom, and is optionally substituted on carbon or a heteroatom. Examples of heterocyclyl include azetidinyl, benzoimidazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydroisoquinolinyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, and tetrahydrothienyl, and N-oxides thereof “Heterocyclyloxy” is RO—, where R is heterocyclyl. “Heterocyclylthio” is RS—, where R is heterocyclyl.


As used herein, the term “3- or 4-membered heterocyclyl” refers to a monocyclic ring having 3 or 4 ring atoms wherein at least one ring atom is heteroatom selected from the group consisting of N, O and S. Non-limiting examples of 3- or 4-membered heterocyclyl include aziridinyl, 2H-azirinyl, oxiranyl, thiiranyl, azetidinyl, 2,3-dihyroazetyl, azetyl, 1,3-diazetidinyl, oxetanyl, 2H-oxetyl, thietanyl, and 2H-thietyl.


As used herein, the term “heteroaryl” refers to a monocyclic, bicyclic or tricyclic ring having up to 7 atoms in each ring, wherein at least one ring is aromatic and contains from 1 to 4 heteroatoms in the ring selected from the group consisting of N, O and S. Non-limiting examples of heteroaryl include pyridyl, thienyl, furanyl, pyrimidyl, imidazolyl, pyranyl, pyrazolyl, thiazolyl, thiadiazolyl, isothiazolyl, oxazolyl, isoxazoyl, pyrrolyl, pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, benzofuranyl, dibenzofuranyl, dibenzothiophenyl, benzothienyl, indolyl, benzothiazolyl, benzooxazolyl, benzimidazolyl, isoindolyl, benzotriazolyl, purinyl, thianaphthenyl and pyrazinyl. Attachment of heteroaryl can occur via an aromatic ring, or, if heteroaryl is bicyclic or tricyclic and one of the rings is not aromatic or contains no heteroatoms, through a non-aromatic ring or a ring containing no heteroatoms. “Heteroaryl” is also understood to include the N-oxide derivative of any nitrogen containing heteroaryl. “Heteroaryloxy” is RO—, where R is heteroaryl.


As used herein, the term “hydroxyalkoxy” refers to an alkoxy group substituted with a hydroxyl group (—OH), wherein alkoxy is as defined herein. An example of hydroxyalkoxy is hydroxyethoxy.


As used herein, the term “hydroxyalkyl” refers to a linear or branched monovalent C1-C10 hydrocarbon group substituted with at least one hydroxy group and examples of hydroxyalkyl groups include, but are not limited to, hydroxymethyl, hydroxyethyl, hydroxypropyl and hydroxybutyl.


As used herein, the term “pharmaceutically acceptable” means suitable for use in pharmaceutical preparations, generally considered as safe for such use, officially approved by a regulatory agency of a national or state government for such use, or being listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans.


As used herein, the term “pharmaceutically acceptable carrier” refers to a diluent, adjuvant, excipient, or carrier, or other ingredient which is pharmaceutically acceptable and with which a compound of the invention is administered.


As used herein, the term “pharmaceutically acceptable salt” refers to a salt which may enhance desired pharmacological activity. Examples of pharmaceutically acceptable salts include acid addition salts formed with inorganic or organic acids, metal salts and amine salts. Examples of acid addition salts formed with inorganic acids include salts with hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid. Examples of acid addition salts formed with organic acids such as acetic acid, propionic acid, hexanoic acid, heptanoic 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, o-(4-hydroxy-benzoyl)-benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethane-sulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, 4-methyl-bicyclo[2.2.2]oct-2-ene1-carboxylic acid, gluco-heptonic acid, 4,4′-methylenebis(3-hydroxy-2-naphthoic) acid, 3-phenylpropionic acid, trimethyl-acetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxy-naphthoic acids, salicylic acid, stearic acid and muconic acid. Examples of metal salts include salts with sodium, potassium, calcium, magnesium, aluminum, iron, and zinc ions. Examples of amine salts include salts with ammonia and organic nitrogenous bases strong enough to form salts with carboxylic acids.


As used herein, the term “substituted” means any of above groups (i.e., alkyl, aryl, heteroaryl, heterocycle or cycloalkyl) wherein at least one hydrogen atom of the moiety being substituted is replaced with a substituent. In one embodiment, each carbon atom of the group being substituted is substituted with no more than two substituents. In another embodiment, each carbon atom of the group being substituted is substituted with no more than one substituent. In the case of a keto substituent, two hydrogen atoms are replaced with an oxygen which is attached to the carbon via a double bond. Unless specifically defined, substituents include halo, hydroxyl, (lower) alkyl, haloalkyl, mono- or di-alkylamino, aryl, heterocycle, —NO2, B(OH)2, BPin, —NRaRb, —NRaC(═O)Rb, —NRaC(═O)NRaRb, —NRaC(═O)ORb, —NRaSO2Rb, —ORa, —CN, —C(═O)Ra, —C(═O)ORa, —C(═O)NRaRb, —OC(═O)Ra, —OC(═O)ORa, —OC(═O)NRaRb, —NRaSO2Rb, —PO3Ra, —PO(ORa)(ORb), —SO2Ra, —S(O)Ra, —SO(N)Ra (e.g., sulfoximine), —(Ra)S═NRb (e.g., sulfilimine) and —SRa, wherein Ra and Rb are the same or different and independently —H, halo, amino, alkyl, haloalkyl, aryl or heterocycle, or wherein Ra and Rb taken together with the nitrogen atom to which they are attached form a heterocycle. Ra and Rb may be in the plural based on atoms which those are attached to.


As used herein, the term “therapeutically effective amount” means when applied to a compound of the invention is intended to denote an amount of the compound that is sufficient to ameliorate, palliate, stabilize, reverse, slow or delay the progression of a disorder or disease state, or of a symptom of the disorder or disease. In an embodiment, the method of the present invention provides for administration of combinations of compounds. In such instances, the “therapeutically effective amount” is the amount of a compound of the present invention in the combination sufficient to cause the intended biological effect.


As used herein, the term “treatment” or “treating” as used herein means ameliorating or reversing the progress or severity of a disease or disorder, or ameliorating or reversing one or more symptoms or side effects of such disease or disorder. “Treatment” or “treating”, as used herein, also means to inhibit or block, as in retard, arrest, restrain, impede or obstruct, the progress of a system, condition or state of a disease or disorder. For purposes of this invention, “treatment” or “treating” further means an approach for obtaining beneficial or desired clinical results, where “beneficial or desired clinical results” include, without limitation, alleviation of a symptom, diminishment of the extent of a disorder or disease, stabilized (i.e., not worsening) disease or disorder state, delay or slowing of a disease or disorder state, amelioration or palliation of a disease or disorder state, and remission of a disease or disorder, whether partial or total.


Compounds


The present disclosure provides a compound of Formula (I):




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or a pharmaceutically acceptable salt, hydrate, or solvate, thereof, wherein:

  • X is O or S;
  • L is a bond, —O—, —S—, or —NR6—;
  • R1 is alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein R1 is optionally substituted with one or more substituents independently selected from R7;
  • R6 is —H or C1-6 alkyl;
  • R7 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, oxo, cyano, hydroxy, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —OR9, —OC(O)R9, —OC(O)NR10R11, —SR9, —S(O)R9, —S(O)2R9, —S(O)(═NH)R10, —S(O)2NR10R11, —NR10R11, —N(R6)NR10R11, —N(R6)OR9, —N(R6)C(O)R9, —N(R6)C(O)OR9, —N(R6)C(O)NR10R11, —N(R6)S(O)2R9, —N(R6)S(O)2NR10R11, or —P(O)R12R13;
  • R9 is —H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl;
  • Each R10 and R11 is independently —H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl, or R10 and R11 are taken together with the nitrogen atom to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with one or more groups selected from the group consisting of halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, —CN, —NO2, —NR10R11, —NR10C(═O)R9, —NR10C(═O)NR10R11, —NR10C(═O)OR9, —OR9, —C(═O)R9, —C(═O)OR9, —C(═O)NR10R11, —OC(═O)R9, —OC(═O)OR9, and —OC(═O)NR10R11;
  • Each R12 and R13 is independently C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl, or R12 and R13 are taken together with the phosphorus atom to which they are attached to form a 4- to 8-membered heterocyclyl optionally substituted with one or more groups selected from the group consisting of halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, —CN, —NO2, —NR10R11, —NR10C(═O)R9, —NR10C(═O)NR10R11, —NR10C(═O)OR9, —OR9, —C(═O)R9, —C(═O)OR9, —C(═O)NR10R11, —OC(═O)R9, —OC(═O)OR9, and —OC(═O)NR10R11; Het is selected from the group consisting of:




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  • Each of Ra, Rb and Rc is independently —H, -D, halo, CF3, CF2H, CH2F, CN, OR9 or NR10R11;

  • R2 is —H, -D, —CD3, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, hydroxyl, —CD2OH, —CN, —NO2, haloalkyl, trimethylsilylethoxymethyl, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —OR9, —OC(O)R9, —OC(O)NR10R11, —SR9, —S(O)R9, —S(O)2R9, —S(O)(═NH)R10, —S(O)2NR10R11, —NR10R11, —N(R6)NR10R11, —N(R6)OR9, —N(R6)C(O)R9, —N(R6)C(O)R9, —N(R6)C(O)OR9, —N(R6)C(O)NR10R11, —N(R6)S(O)2R9, —N(R6)S(O)2NR10R11, or —P(O)R12R13 wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more groups selected from the group consisting of halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, —CN, —NO2, —NR10R11, —NR10C(═O)R9, —NR10C(═O)NR10R11, —NR10C(═O)OR9, —OR9, —C(═O)R9, —C(═O)OR9, —C(═O)NR10R11, —OC(═O)R9, —OC(═O)OR9, and —OC(═O)NR10R11;

  • R3 is —H, -D, —CD3, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, cyano, hydroxy, —CH2OH, —CD2OH, —OH, —CN, —NO2, haloalkyl, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —OR9, —OC(O)R9, —OC(O)NR10R11, —SR9, —S(O)R9, —S(O)2R9, —S(O)(═NH)R10, —S(O)2NR10R11, —NR10R11, —N(R6)NR10R11, —N(R6)OR9, —N(R6)C(O)R9, —N(R6)C(O)OR9, —N(R6)C(O)NR10R11, —N(R6)S(O)2R9, —N(R6)S(O)2NR10R11, or —P(O)R12R13;

  • M is a bond, —O—, —S—, or —NR6—;

  • R6 is —H or C1-6 alkyl;

  • R4 is —H, -D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, cyano, hydroxy, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —S(O)2R9, —S(O)(═NH)R10, —S(O)2NR10R11, or —P(O)R12R13, wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more groups selected from the group consisting of halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, —CN, —CD3, —NO2, —NR10R11, —NR10C(═O)R9, —NR10C(═O)NR10R11, —NR10C(═O)OR9, —NR10S(O)2R9, —OR9, —C(═O)R9, —C(═O)OR9, —C(═O)NR10R11, —OC(═O)R9, —OC(═O)OR9, and —OC(═O)NR10R11; and

  • R5 is —H, -D, —CD3, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, halo, hydroxyl, —CH2OH, —CD2OH, —CN or haloalkyl.



In various embodiments, L is a bond, and R1 is cycloalkyl which is optionally substituted with one or more groups selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, halo, cyano, hydroxy, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —OR9, —OC(O)R9, —OC(O)NR10R11, —NR10R11, —N(R6)NR10R11, —N(R6)OR9, —N(R6)C(O)R9, —N(R6)C(O)OR9, and —N(R6)C(O)NR10R11. In various embodiments, each of R2 and R3 is independently —H, halo, alkylthio, haloalkyl, or alkyl. In various embodiments, M is a bond, —O—, or —NR6—; and R4 is —H, -D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, cyano, hydroxy, —C(O)R9, —C(O)NR10R11, —S(O)2R9, —S(O)(═NH)R10, or —S(O)2NR10R11, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more groups selected from the group consisting of halo, hydroxy, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, —CN, —CD3, —NR10R11, —NR10S(O)2R9, and —NR10C(═O)R9.


In another embodiment, there is provided a compound represented by Formula (II):




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wherein R1, R2, R3, R4, R5, Ra, Rb, M, and L are as defined above for Formula (I).


In various embodiments, L is a bond, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkylthio, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, hydroxyalkyl, haloalkyl, haloalkenyl, cycloalkyl, cyanoalkyl, dimethylamino, dimethylaminoethyl, dimethylaminocarbonyl, methylaminooxoethyl, aminocarbonylalkyl, acetamindoethyl, propionamidoethyl, formamidoethyl, aminoalkyl, methylaminocarbonylmethyl, alkoxyalkyl, azetidinyl, or azetidinylmethyl; and R5 is —H, alkyl, or halo.


Non-limiting exemplary compounds of Formula (II) include the compound of Examples 1-145 of Table 1. In particular embodiments, the compound is selected from the group consisting of: the compounds of Examples 58, 80, 82, 85, 87, 92, 94, 97, 98, 110, 111, 118, 123, 125, 129, and 134.


In another embodiment, there is provided a compound represented by Formula (III):




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wherein R1, R2, R3, R4, R5, Ra, Rb, M, and L are as defined above for Formula (I).


In some embodiments, L is a bond, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, hydroxyalkyl, dimethylamino, dimethylaminoethyl, dimethylaminocarbonyl, methylaminooxoethyl, aminocarbonylalkyl, acetamindoethyl, or alkoxyalkyl; and R5 is —H, alkyl, or halo.


Non-limiting exemplary compounds of Formula (III) include the compound of Examples 146-218 of Table 1. In particular embodiments, the compound is selected from the group consisting of the compounds of Examples 149, 152, 156, 159, 161-163, 167, 169, 170, 172-175, 178, 184, 193, 194, 196, 199, and 218.


In another embodiment, there is provided a compound represented by Formula (IV):




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wherein R1, R2, R3, R4, R5, Ra, Rb, M, and L are as defined above for Formula (I).


In some embodiments, L is a bond, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, hydroxyalkyl, haloalkyl, haloalkenyl, cycloalkyl, cyanoalkyl, dimethylamino, dimethylaminoethyl, dimethylaminocarbonyl, methylaminooxoethyl, aminocarbonylalkyl, acetamindoethyl, propionamidoethyl, formamidoethyl, cycloalkylalkyl, cycloalkyl(hydroxy)alkyl, hydroxycycloalkyl, methoxycycloalkyl, cycloalkyl(methoxy)methyl, alkoxyalkyl, alkenyl, methylsulfonamidoethyl, imidazolylethyl, dioxanyl, cyclobutanylcarbonylaminoethyl, difluoroacetamidoethyl, trifluoroacetamidoethyl, methylthiomethyl, methylthioethyl, azetidinyl, azetidinylmethyl, cyclopropylcarbonylamino(cyano)methyl, cyano(difluoroacetamido)methyl, propanyl-1,1,1,3,3,3-d6)amino, tetrahydrofuranyl, methylimidazolylethyl, furanyl, pyrrolyl, methylpyrrolyl, isoxazolyl, tetrazolylalkyl, methylpyrazolyl, or methylpyrazolylmethyl; and R5 is —H, alkyl, or halo.


Non-limiting exemplary compounds of Formula (IV) include the compound of Examples 219 and 220 of Table 1.


In another embodiment, there is provided a compound represented by Formula (V):




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wherein R1, R2, R3, R4, R5, Ra, Rb, M, and L are as defined above for Formula (I).


In some embodiments, L is a bond, and R1 is cycloalkyl which is optionally substituted with one or more groups selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, halo, cyano, hydroxy, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —OR9, —OC(O)R9, —OC(O)NR10R11, —NR10R11, —N(R6)NR10R11, —N(R6)OR9, —N(R6)C(O)R9, —N(R6)C(O)OR9, and —N(R6)C(O)NR10R11. In some other embodiments, R1 is cycloalkyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl.


Non-limiting exemplary compounds of Formula (V) include the compound of Examples 221-445 of Table 1.


In some embodiments, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-C3 alkyl, C1-C3 hydroxyalkyl and C1-C3 haloalkyl; R2 is —H, alkyl, alkylthio, haloalkyl, or halo; R3 is —H, alkyl, or halo; M is a bond, —O—, or —NR6—; R4 is —H, halo, alkyl, monoalkylamino, or dialkylamino; R5 is —H, alkyl, or halo. Non-limiting exemplary compounds include one selected from the group consisting of:

  • (1S,2S)—N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;
  • (1S,2S)—N-(6-(7-(dimethylamino)-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;
  • (1S,2S)—N-(6-(7-(dimethylamino)-6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;
  • (1S,2S)—N-(6-(7-(dimethylamino)-6-fluoro-5-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;
  • (1S,2S)—N-(6-(5-chloro-6-fluoro-7-(isopropylamino)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and
  • (1S,2S)—N-(6-(5-chloro-6-fluoro-7-isopropyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.


In some embodiments, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, hydroxyalkyl, haloalkyl, haloalkenyl, cycloalkyl, monoalkylamino, or dialkylamino; and R5 is —H, alkyl, or halo. Non-limiting exemplary compounds include one selected from the group consisting of: the compounds of Examples 258, 261, 265, 266, 269, 272, 275, 280, 288, 291, 293, 296, 297, 300, 304, 306, 310, 318, 320, 324, 327, 329, 330, 332, 334, 336, 341, 345, 349, 353, 356, 358, 359, 361, 366, 371, 372, 374, 390, 391, 393, 404, 405, 408, 410, 414, 417, 419, 422, 423, 425, 426, 428, 430, 433, 434, 436, 439, 441, and 445.


In some embodiments, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, alkylcarbonyl, dialkylaminocarbonyl, oxopyrrolidinyl, hydroxyalkyl, haloalkyl, haloalkenyl, cycloalkyl, pyridinyl, monoalkylamino, or dialkylamino; and R5 is —H, alkyl, or halo. Non-limiting exemplary compounds include one selected from the group consisting of the compounds of Examples 258, 261, 265, 266, 268, 269, 271-273 275, 280, 281, 288, 290, 291, 293, 296-298, 300, 304, 306, 307, 310, 316, 318, 320, 324, 326, 327, 329, 330-334, 336, 339, 341, 345, 346, 349, 353, 356, 358, 359, 361-363, 365-367, 370-374, 377-379, 383, 388, 390, 391, 393, 398, 401, 404-406, 408-410, 414, 415, 417, 419, 421-426, 428, 430, 433, 434, 436, 439, 441, and 445.


In another embodiment, there is provided a compound represented by Formula (VI):




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wherein R1, R2, R3, R4, R5, Ra, Rb, M, and L are as defined above for Formula (I).


In some embodiments, L is a bond, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, hydroxyalkyl, haloalkyl, haloalkylamidoalkyl, haloalkylcarbonylaminoalkyl, alkylamidoalkyl, hydroxyhaloalkyl, haloalkenyl, cycloalkyl, cyano, cyanoalkyl, dimethylamino, dimethylaminoethyl, methylaminocarbonyl, dimethylaminocarbonyl, methylaminooxoethyl, aminocarbonylalkyl, acetamindoethyl, dialkylaminocycloalkyl, aminocycloalkyl, methylaminocycloalkyl, cycloalkylalkyl, cycloalkyl(hydroxy)alkyl, cycloalkylamidoalkyl, cycloalkylaminocarbonyl, hydroxycycloalkyl, methoxycycloalkyl, cycloalkyl(methoxy)methyl, alkoxycarbonyl, alkylcarbonyl, alkylamidoalkyl, alkoxyalkyl, alkenyl, methylsulfonamidoethyl, imidazolylethyl, dioxanyl, azetidinyl, azetidinylmethyl, tetrahydrofuranyl, furanyl, pyrimidinyl, pyridinyl, pyrrolyl, halopyrrolidinyl, pyrrolidinyl, methylpyrrolyl, isoxazolyl, tetrazolylalkyl, triazinyl, methylpyrazolyl, or methylpyrazolylmethyl; and R5 is —H, alkyl, or halo.


Non-limiting exemplary compounds of Formula (VI) include the compound of Examples 446-666 of Table 1. In particular embodiments, the compound is selected from the group consisting of the compounds of Examples 464, 466, 467, 476, 477, 480, 484, 485, 487, 488, 490-494, 496, 497, 502-505, 509, 513, 514, 519-521, 523-525, 529-532, 534, 541, 543, 548, 550, 552, 556-558, 561-565, 568-574, 577, 579, 581, 585, 586, 588, 592, 596-600, 602, 607, 612, 615, 617-619, 621, 623, 625, 629, 634, 636-642, 644, 646, 650-652, 655-657, and 659-665.


In an embodiment, there is provided a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound of Formula (I) or a pharmaceutically acceptable salt thereof.


Medical Uses and Methods of Treatment Using the Compounds


The present disclosure provides a method of treating a subject with a disease or disorder associated with modulation of HPK1 comprising: administering to the subject in need thereof a therapeutically effective amount of the compound of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or disorder associated with modulation of HPK1 is a cancer, metastasis, inflammation, or immune disease including autoimmune disease.


In some other embodiments, the disease is cancer, metastasis, inflammation or auto-immune disease. In particular embodiments, the cancer is selected from the group consisting of carcinomas, melanomas, blastomas, sarcomas, lymphomas and leukemias, including without limitation, bladder carcinoma, brain tumors, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrial cancer, hepatocellular carcinoma, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal carcinoma and thyroid cancer, acute lymphocytic leukemia, acute myeloid leukemia, ependymoma, Ewing's sarcoma, glioblastoma, medulloblastoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, rhabdoid cancer, and nephroblastoma (Wilm's tumor).


In some embodiments, the autoimmune disease is an inflammatory bowel disease, Addison's disease, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, hemolytic anemia, autoimmune hepatitis, Behcet's disease, Berger's disease, bullous pemphigoid, cardiomyopathy, celiac sprue, chronic fatigue immune dysfunction syndrome (CFIDS), chronic inflammatory demyelinating polyneuropathy, Churg-Strauss syndrome, cicatricial pemphigoid, cold agglutinin disease, type 1 diabetes, discoid lupus, essential mixed cryoglobulinemia, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, hypothyroidism, autoimmune lymphoproliferative syndrome (ALPS), idiopathic pulmonary fibrosis, idiopathic thrombocytopenia purpura (ITP), juvenile arthritis, lichen planus, lupus erythematosus, Meniere's disease, mixed connective tissue disease, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, pernicious anemia, polychondritis, autoimmune polyglandular syndromes, polymyalgia rheumatica, polymyositis, dermatomyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, psoriatic arthritis, Raynaud's phenomenon, Reiter's syndrome, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma, Sjogren's syndrome, stiff-man syndrome, Takayasu arteritis, giant cell arteritis, ulcerative colitis, uveitis, vasculitis, or granulomatosis with polyangiitis.


In another embodiment, there is provided the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for inhibiting HPK1 activity in a subject in need of inhibition of HPK1 activity. In some embodiments, the use includes treatment of cancer.


Suitable subjects to be treated according to the present disclosure include mammalian subjects. Mammals according to the present disclosure include, but are not limited to, human, canine, feline, bovine, caprine, equine, ovine, porcine, rodents, lagomorphs, primates, and the like, and encompass mammals in utero. Subjects may be of either gender and at any stage of development. In one embodiment, the suitable subject to be treated according to the present disclosure is human.


The compounds of the present disclosure are generally administered in a therapeutically effective amount. The compounds of the present disclosure can be administered by any suitable route in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended. An effective dosage is typically in the range of about 0.01 to about 1000 mg per kg body weight per day, preferably about 0.01 to about 500 mg/kg/day, in single or divided doses. Depending on age, species and disease or condition being treated, dosage levels below the lower limit of this range may be suitable. In other cases, still larger doses may be used without harmful side effects. Larger doses may also be divided into several smaller doses, for administration throughout the day. Methods for determining suitable doses are well known in the art to which the present disclosure pertains. For example, Remington: The Science and Practice of Pharmacy, Mack Publishing Co., 20th ed., 2000 can be used.


Pharmaceutical Compositions, Dosage Forms and Administration Routes


For the treatment of the diseases or conditions referred to above, the compounds described herein or pharmaceutically acceptable salts thereof can be administered as follows:


Oral Administration


The compounds of the present disclosure may be administered orally, including by swallowing, so that the compound enters the gastrointestinal tract, or absorbed into the blood stream directly from the mouth (e.g., buccal or sublingual administration). Suitable compositions for oral administration include solid, liquid, gel or powder formulations, and have a dosage form such as tablet, lozenge, capsule, granule or powder. Compositions for oral administration may be formulated as immediate or modified release, including delayed or sustained release, optionally with enteric coating. Liquid formulations can include solutions, syrups and suspensions, which can be used in soft or hard capsules. Such formulations may include a pharmaceutically acceptable carrier, for example, water, ethanol, polyethylene glycol, cellulose, or an oil. The formulation may also include one or more emulsifying agents and/or suspending agents.


In a tablet dosage form the amount of drug present may be from about 0.05% to about 95% by weight, more typically from about 2% to about 50% by weight of the dosage form. In addition, tablets may contain a disintegrant, comprising from about 0.5% to about 35% by weight, more typically from about 2% to about 25% of the dosage form. Examples of disintegrants include, but are not limited to, lactose, starch, sodium starch glycolate, crospovidone, croscarmellose sodium, maltodextrin, or mixtures thereof.


Suitable lubricants, for use in a tablet, may be present in amounts from about 0.1% to about 5% by weight, and include, but are not limited to, talc, silicon dioxide, stearic acid, calcium, zinc or magnesium stearate, sodium stearyl fumarate and the like.


Suitable binders, for use in a tablet, include, but are not limited to, gelatin, polyethylene glycol, sugars, gums, starch, polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxypropylmethyl cellulose and the like. Suitable diluents, for use in a tablet, include, but are not limited to, mannitol, xylitol, lactose, dextrose, sucrose, sorbitol, microcrystalline cellulose and starch.


Suitable solubilizers, for use in a tablet, may be present in amounts from about 0.1% to about 3% by weight, and include, but are not limited to, polysorbates, sodium lauryl sulfate, sodium dodecyl sulfate, propylene carbonate, diethyleneglycol monoethyl ether, dimethyl isosorbide, polyethylene glycol (natural or hydrogenated) castor oil, HCOR™ (Nikkol), oleyl ester, Gelucire™, caprylic/caprylic acid mono/diglyceride, sorbitan fatty acid esters, and Solutol HS™.


Parenteral Administration


Compounds of the present disclosure may be administered directly into the blood stream, muscle, or internal organs. Suitable means for parenteral administration include intravenous, intra-muscular, subcutaneous intraarterial, intraperitoneal, intrathecal, intracranial, and the like. Suitable devices for parenteral administration include injectors (including needle and needle-free injectors) and infusion methods.


Compositions for parenteral administration may be formulated as immediate or modified release, including delayed or sustained release. Most parenteral formulations are aqueous solutions containing excipients, including salts, buffering agents and isotonic agents. Parenteral formulations may also be prepared in a dehydrated form (e.g., by lyophilization) or as sterile non-aqueous solutions. These formulations can be used with a suitable vehicle, such as sterile water. Solubility-enhancing agents may also be used in preparation of parenteral solutions.


Transdermal Administration


Compounds of the present disclosure may be administered topically to the skin or transdermally. Formulations for this topical administration can include lotions, solutions, creams, gels, hydrogels, ointments, foams, implants, patches and the like. Pharmaceutically acceptable carriers for topical administration formulations can include water, alcohol, mineral oil, glycerin, polyethylene glycol and the like. Topical or transdermal administration can also be performed by electroporation, iontophoresis, phonophoresis and the like. Compositions for topical administration may be formulated as immediate or modified release, including delayed or sustained release.


Combination Therapy


A pharmaceutical composition according to the present disclosure may contain one or more additional therapeutic agents, for example, to increase the efficacy or decrease the side effects. In some embodiments, accordingly, a pharmaceutical composition further contains one or more additional therapeutic agents selected from active ingredients useful to treat or inhibit diseases mediated directly or indirectly by HPK1. Examples of such active ingredients are, without limitation, agents to treat cancer, metastasis, inflammation, or auto-immune pathogenesis. In some embodiments, the compound of Formula (I) is administered with anti-PD-1 agent, anti-PD-L1 agent, or anti-CTLA4 agent.


References for Preparing Pharmaceutical Compositions


Methods for preparing pharmaceutical compositions for treating or preventing a disease or condition are well known in the art to which the present disclosure pertains. For example, based on Handbook of Pharmaceutical Excipients (7th ed.), Remington: The Science and Practice of Pharmacy (20th ed.), Encyclopedia of Pharmaceutical Technology (3rd ed.), or Sustained and Controlled Release Drug Delivery Systems (1978), pharmaceutically acceptable excipients, carriers, additives and so on can be selected and then mixed with the compounds of the present disclosure for making the pharmaceutical compositions.


The present disclosure provides a compound having various pharmacological effects by inhibiting HPK1 activity, a pharmaceutical composition having the compound as an effective agent, a medical use, particularly for treating a disease or disorder modulated by HPK1, of the compound, and a method of treatment or prevention comprising administering the compound to a subject in need of such treatment or prevention. The compounds of the present disclosure and pharmaceutically acceptable salts thereof have good safety and high selectivity for HPK1, and thus exhibit superior property as a drug.


Compound Preparation


The following Preparative Examples illustrate the preparation of intermediate compounds that are useful for preparing compounds of formula (I). The novel intermediate compounds described herein, as well as the synthetic processes useful for preparing the intermediate compounds represent embodiments of the current invention.


Intermediate 1A. 1-(tetrahydro-2H-pyran-2-yl)-5-(thiophen-2-yl)-1H-indazol-4-yl trifluoromethanesulfonate



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Step 1) 3-bromo-4-chloro-5-fluoro-2-methylaniline

To a solution of 3-bromo-5-fluoro-2-methylaniline (50 g, 245 mmol, 1 eq) in AcOH (100 mL) was added N-chlorosuccinimide (36 g, 270 mmol, 1.1 eq). The mixture was stirred at 25° C. for 16 hr. The mixture was concentrated under vacuum and the residue was extracted with Dichloromethane (200 mL*2). The combined organic layers were washed with sat. NaHCO3 200 mL, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The crude product (66 g, crude) was obtained as a black oil.


Step 2) 4-bromo-5-chloro-6-fluoro-1H-indazole

To a solution of 3-bromo-4-chloro-5-fluoro-2-methylaniline (25.8 g, 108 mmol, 1 eq) in AcOH (1.96 L, 0.05 M), H2O (0.065 L, 1.5 M) was added sodium nitrite (8.96 g, 130 mmol, 1.2 eq). The mixture was stirred at 25° C. for 16 hr. The mixture was concentrated under vacuum and the residue was extracted with Dichloromethane (1 L*2). The combined organic layers were washed with sat. NaHCO3 (1 L), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The crude product (23.6 g, crude) was obtained as a brown solid.


Step 3) 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a solution of 4-bromo-5-chloro-6-fluoro-1H-indazole (1.98 g, 7.97 mmol, 1 eq) in THP (40 mL) was added 3,4-dihydro-2H-pyran (2.18 ml, 23.9 mmol, 3 eq) and p-toluenesulfonic acid monohydrate (300 mg, 1.59 mmol, 0.2 eq). The reaction mixture was stirred 70° C. for 14 hours. The reaction mixture was extracted with Ethyl Acetate and dried over MgSO4. The organic residue was purified by column chromatography (silical gel, Hex:Ethyl acetate=1:0 to 4:1). 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (1.51 g, 4.54 mmol, 57% yield) was obtained.



1H NMR (400 MHz, DMSO-d6) δ 8.16 (s, 1H), 8.00 (dd, J=9.3, 1.1 Hz, 1H), 5.85 (dd, J=9.6, 2.5 Hz, 1H), 3.87 (d, J=12.6 Hz, 1H), 3.79-3.72 (m, 1H), 2.38-2.30 (m, 1H), 2.04-1.94 (m, 2H), 1.77-1.55 (m, 3H).


Intermediate 1B. 4-bromo-5-chloro-6-fluoro-7-iodo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole



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Step 1) 4-bromo-5-chloro-6-fluoro-7-iodo-1H-indazole

To a solution of 4-bromo-5-chloro-6-fluoro-1H-indazole (2 g, 8.02 mmol) in sulfuric acid (1.7 mL) was added N-iodosuccinimide (2.7 g, 12.03 mmol) portionwise. The mixture was stirred at 0° C. for 3 h. After the reaction completed, the mixture was poured into ice water and quenched by solid NaOH and then extracted with Dichloromethane. The combined organic residue was concentrated in vacuo. (2.99 g, crude).



1H NMR (400 MHz, DMSO-d6) δ 13.91 (s, 1H), 8.27 (d, J=1.6 Hz, 1H).


Step 2) 4-bromo-5-chloro-6-fluoro-7-iodo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

To a solution of 4-bromo-5-chloro-6-fluoro-7-iodo-1H-indazole (2.99 g, 7.97 mmol, 1 eq) in THF (40 mL) was added 3,4-dihydro-2H-pyran (2.18 ml, 23.9 mmol, 3 eq) and p-toluenesulfonic acid monohydrate (300 mg, 1.59 mmol, 0.2 eq). The reaction mixture was stirred 60° C. for 16 hours. The reaction mixture was extracted with Ethyl Acetate and dried over MgSO4. The organic residue was purified by column chromatography (silical gel, Hex:Ethyl acetate=1:0 to 4:1). 4-bromo-5-chloro-6-fluoro-7-iodo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (1.64 g, 7.97 mmol, 60.7% yield) was obtained.



1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 5.80 (dd, J=9.9, 2.7 Hz, 1H), 5.66 (s, 1H), 4.02 (t, J=6.6 Hz, 1H), 3.85-3.70 (m, 1H), 2.33-2.21 (m, 1H), 2.08-1.91 (m, 2H), 1.79-1.45 (m, 4H).


Intermediate 1C. 4-bromo-5-chloro-6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-7-amine



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Step 1) 4-bromo-5-chloro-6-fluoro-7-nitro-1H-indazole

To a mixture of HNO3 (12.63 g, 200.43 mmol, 9.02 mL, 5 eq) in H2SO4 (50 mL) stirred at 0° C. was added 4-bromo-5-chloro-6-fluoro-1H-indazole (10 g, 40.09 mmol, 1 eq) slowly. After the addition the mixture was stirred at 0° C. for 2 hr. TLC (Petroleum ether:Ethyl acetate=3:1) showed all the reactant was consumed and a main new point showed up. Poured the mixture into ice-water, extracted with ethyl acetate (50 mL*3), the combined organic phase was dried over Na2SO4, filtered and the filtrate was concentrated to obtain 4-bromo-5-chloro-6-fluoro-7-nitro-1H-indazole (12 g, crude) as a yellow solid.


Step 2) 4-bromo-5-chloro-6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

To a solution of 4-bromo-5-chloro-6-fluoro-7-nitro-1H-indazole (2.34 g, 7.97 mmol, 1 eq) in THF (40 mL) was added 3,4-dihydro-2H-pyran (2.18 ml, 23.9 mmol, 3 eq) and p-toluenesulfonic acid monohydrate (300 mg, 1.59 mmol, 0.2 eq). The reaction mixture was stirred 60° C. for 14 hours. The reaction mixture was extracted with Ethyl Acetate and dried over MgSO4. The organic residue was purified by column chromatography (silical gel, Hex:Ethyl acetate=1:0 to 4:1). 4-bromo-5-chloro-6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (1.65 g, 4.35 mmol, 54.7% yield) was obtained.


Step 3) 4-bromo-5-chloro-6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-7-amine

To a solution of 4-bromo-5-chloro-6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (600 mg, 1.58 mmol, 1 eq) in EtOH (5 mL) and H2O (5 mL) were added NH4Cl (508.66 mg, 9.51 mmol, 6 eq) and Fe (531.04 mg, 9.51 mmol, 6 eq), then the reaction mixture was stirred at 80° C. for 1 hour. The reaction mixture was filtered, and the filtrate was diluted with ethyl acetate (20 mL), and the mixture was washed with water (20 mL*2), after then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO2, Petroleum ether/Ethyl acetate=1:1). 4-bromo-5-chloro-6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-7-amine (390 mg, 1.12 mmol, 70.59% yield) was obtained as a yellow oil.



1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 5.85 (br s, 2H), 5.71 (br d, J=8.0 Hz, 1H), 4.00 (br d, J=11.3 Hz, 1H), 3.77-3.59 (m, 1H), 2.29-2.17 (m, 1H), 2.10-1.91 (m, 2H), 1.78-1.54 (m, 3H).


Intermediate 1D. 4-bromo-5-chloro-6-fluoro-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-amine



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Step 1) 4-bromo-5-chloro-6-fluoro-7-nitro-1H-indazole

To a solution of Intermediate 1A (900 mg, 3.61 mmol, 1 eq) in H2SO4 (10 mL) (98% purity) was added HNO3 (419.69 mg, 4.33 mmol, 299.78 uL, 1.2 eq) (65% purity) dropwise at −15° C., then the reaction mixture was stirred at 0° C. for 2 hours. The reaction mixture was slowly poured into ice water (20 mL), then the mixture's pH was adjusted to pH=7 by using saturated aqueous solution of NaOH, after then the mixture was extracted with ethyl acetate (30 mL*2), the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 4-bromo-5-chloro-6-fluoro-7-nitro-1H-indazole (900 mg, crude) was obtained as a yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 14.36 (br s, 1H), 8.37 (br s, 1H).


Step 2) 4-bromo-5-chloro-6-fluoro-7-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a solution of 4-bromo-5-chloro-6-fluoro-7-nitro-1H-indazole (900 mg, 3.06 mmol, 1 eq) (crude) in DCM (10 mL) were added TsOH.H2O (58.14 mg, 305.64 umol, 0.1 eq) and DHP (771.27 mg, 9.17 mmol, 838.34 uL, 3 eq), then the reaction mixture was stirred at 20° C. for 2 hours. The reaction mixture was diluted with dichloromethane (20 mL), and the mixture was washed with saturated aqueous solution of NaHCO3 (15 mL*2), the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=40/1 to 25:1, 4-bromo-5-chloro-6-fluoro-7-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole came out at Petroleum ether/Ethyl acetate=40/1, 4-bromo-5-chloro-6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole came out at Petroleum ether/Ethyl acetate=25/1). 4-bromo-5-chloro-6-fluoro-7-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (200 mg, 528.29 umol, 17.28% yield) was obtained as a brown solid. 4-bromo-5-chloro-6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (600 mg, 1.58 mmol, 51.85% yield) was obtained as a yellow solid.


4-bromo-5-chloro-6-fluoro-7-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole


1HNMR (400 MHz, DMSO-d6) δ 8.43 (s, 1H), 5.50 (dd, J=2.8, 7.8 Hz, 1H), 3.45-3.38 (m, 2H), 2.35-2.27 (m, 1H), 2.23-2.14 (m, 1H), 1.92 (td, J=4.6, 13.6 Hz, 1H), 1.68 (ddt, J=4.0, 10.1, 13.9 Hz, 1H), 1.59-1.36 (m, 2H).


4-bromo-5-chloro-6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole


1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 5.86 (dd, J=2.7, 9.7 Hz, 1H), 4.08-3.96 (m, 1H), 3.81-3.68 (m, 1H), 2.28-2.14 (m, 1H), 2.14-2.02 (m, 1H), 2.02-1.89 (m, 1H), 1.78-1.67 (m, 1H), 1.64-1.56 (m, 2H).


Step 3) 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-amine

To a solution of 4-bromo-5-chloro-6-fluoro-7-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (200 mg, 528.29 umol, 1 eq) in EtOH (5 mL) and H2O (5 mL) were added NH4Cl (169.55 mg, 3.17 mmol, 6 eq) and Fe (177.03 mg, 3.17 mmol, 6 eq), then the reaction mixture was stirred at 80° C. for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated to remove EtOH, then the mixture was diluted with ethyl acetate (20 mL), and the mixture was washed with water (20 mL*2), after then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-amine (140 mg, crude) was obtained as a yellow solid.


Step 4) 4-bromo-5-chloro-6-fluoro-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-amine

To a solution of 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-amine (120 mg, 344.24 umol, 1 eq) in THF (5 mL) was added NaH (34.42 mg, 860.59 umol, 60% purity, 2.5 eq) in portions at 0° C. under N2, then the mixture was stirred at 0° C. for 30 mins under N2, after then Mel (293.16 mg, 2.06 mmol, 128.58 uL, 6 eq) was added dropwise, and the reaction mixture was stirred at 20° C. for 12 hours under N2. The reaction mixture was poured into saturated aqueous solution of NH4Cl (20 mL), then the mixture was extracted with ethyl acetate (20 mL*2), the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO2, Petroleum ether/Ethyl acetate=5:1). Intermediate 1E (30 mg, 78.06 umol, 22.68% yield, 98% purity) was obtained as a yellow oil.


Intermediate 1E. 4-bromo-5-chloro-6-fluoro-N-isopropyl-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-7-amine



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To a solution of Intermediate 1B (100 mg, 0.218 mmol, 1 eq) in 2-methyl-2-butanol (1.09 mL) was added Xantphos Pd G3 (21 mg, 21.8 μmol, 0.1 eq) and Cs2CO3 (142 mg, 0.436 mmol, 2.0 eq). The mixture was degassed and purged with N2 for 3 times, and then propan-2-amine (0.19 mL, 2.18 mmol, 10 eq) was added. The mixture was stirred at 90° C. for 3 hr in sealed tube. The reaction mixture was diluted with H2O (40 mL), and then the mixture was extracted with DCM (50 mL*3). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated in vacuum to give a residue. The residue was purified by silica gel chromatography (product came out at Hexane/Ethyl acetate=10/1) to afford Intermediate 1E (47 mg, 0.120 mmol, 55% yield) as beige color solid.



1H NMR (400 MHz, DMSO-d6) δ 8.43 (s, 1H), 5.74 (dd, J=9.6, 2.5 Hz, 1H), 5.29 (dd, J=9.9, 3.3 Hz, 1H), 4.63-4.57 (m, 1H), 3.99 (d, J=11.0 Hz, 1H), 3.74-3.68 (m, 1H), 2.23-2.17 (m, 1H), 2.05-1.95 (m, 2H), 1.74-1.57 (m, 3H), 1.23-1.18 (m, 6H).


Intermediate 1F. 4-bromo-5-chloro-6-fluoro-N-isopropyl-N-methyl-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-7-amine



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To a solution of Intermediate 1E (600 mg, 1.54 mmol, 1.0 eq) in Methanol (7.7 mL) was added formaldehyde (0.572 mL, 7.68 mmol, 5.0 eq) and acetic acid (88 μL, 1.54 mmol, 1.0 eq). The mixture was stirred at room temperature for 10 min. Sodium cyanoborohydride (290 mg, 4.61 mmol, 3.0 eq) was added and then the mixture was stirred room temperature for 16 hr. The reaction mixture was quenched by H2O and extracted with Ethyl acetate (150 mL*3). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated in vacuum to give a residue. The residue was purified by silica gel chromatography (product came out at Hexane/Ethyl acetate=100/4) to afford Intermediate 1F (292 mg, 0.722 mmol, 47% yield) as brown color oil.



1H NMR (400 MHz, DMSO-d6) δ 8.51 (s, 1H), 5.75 (dd, J=9.3, 2.7 Hz, 1H), 4.14-4.05 (m, 1H), 4.00-3.93 (m, 1H), 3.78-3.67 (m, 1H), 2.92 (d, J=4.4 Hz, 3H), 2.23-2.20 (m, 1H), 2.05-1.95 (m, 2H), 1.75-1.60 (m, 3H), 1.17 (d, J=6.6 Hz, 6H).


Intermediate 1G. 4-bromo-5-chloro-N-ethyl-6-fluoro-N-methyl-1H-indazol-7-amine



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Step 1) 4-bromo-5-chloro-6-fluoro-1H-indazol-7-amine

To a solution of 4-bromo-5-chloro-6-fluoro-7-nitro-1H-indazole (12 g, 40.75 mmol, 1 eq) in EtOH (100 mL) and H2O (40 mL) was added Fe (6.83 g, 122.26 mmol, 3 eq) and NH4Cl (6.54 g, 122.26 mmol, 3 eq). The reaction mixture was heated to 80° C. and reacted for 2 hr. The reaction mixture was filtered through a celite cake, the filtrate was concentrated to give the crude product. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=20/1 to 3/1). 4-bromo-5-chloro-6-fluoro-1H-indazol-7-amine (5 g, 18.90 mmol, 46.39% yield) was obtained as a yellow solid.


Step 2) N-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)acetamide

To a solution 4-bromo-5-chloro-6-fluoro-1H-indazol-7-amine (3 g, 11.34 mmol, 1 eq) in AcOH (30 mL) was added Ac2O (1.39 g, 13.61 mmol, 1.27 mL, 1.2 eq), the reaction mixture was heated to 80° C. and reacted for 3 hr. The solvent was removed under vacuum. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=50/1 to 4/1) to obtain N-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)acetamide (3 g, 9.79 mmol, 86.29% yield) as a yellow solid.


Step 3) 4-bromo-5-chloro-N-ethyl-6-fluoro-1H-indazol-7-amine

To a solution of LAH (520.00 mg, 13.70 mmol, 1.5 eq) in THF (50 mL) was added a solution of N-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)acetamide (2.8 g, 9.13 mmol, 1 eq) in THF (100 mL) drop-wise under N2 at 0° C., after the addition, the reaction mixture was allowed to warm to 25° C., and reacted for 16 hr. The mixture was poured into water (500 mL), extracted with ethyl acetate (100 mL*2), the combined organic phase was dried over Na2SO4, filtered and the filtrate was concentrated to give the crude. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=50/1 to 2/1) to obtain 4-bromo-5-chloro-N-ethyl-6-fluoro-1H-indazol-7-amine (1 g, 3.42 mmol, 37.42% yield) as a yellow solid.


Step 4) 4-bromo-5-chloro-N-ethyl-6-fluoro-N-methyl-1H-indazol-7-amine

To a solution of 4-bromo-5-chloro-N-ethyl-6-fluoro-1H-indazol-7-amine (1.4 g, 4.79 mmol, 1 eq) and HCHO (718.48 mg, 23.93 mmol, 659.16 uL, 5 eq) in MeOH (50 mL) was added NaBH3CN (902.21 mg, 14.36 mmol, 3 eq) and AcOH (287.38 mg, 4.79 mmol, 273.70 uL, 1 eq). The reaction mixture was stirred at 25° C. for 16 hr. The solvent was removed under vacuum. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=50/1 to 5/1) to obtain 4-bromo-5-chloro-N-ethyl-6-fluoro-N-methyl-1H-indazol-7-amine (1.4 g, 4.57 mmol, 95.42% yield) as a white solid.


Intermediate 1H. 4-bromo-5-chloro-6-fluoro-7-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole



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To a solution of 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.5 g, 1.50 mmol, 1 eq) in THF (10 mL) was added dropwise LDA (2 M, 1.87 mL, 2.5 eq) at −78° C. After addition, the mixture was stirred at this temperature for 2.5 hr, and then Mel (319.12 mg, 2.25 mmol, 139.97 uL, 1.5 eq) was added dropwise at −78° C. The resulting mixture was stirred at 20° C. for 16 hr. The mixture was poured into saturated NH4Cl and extracted with EA 20 mL. The organic layer was concentrated. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=20/1 to 10/1). We got the desired product 4-bromo-5-chloro-6-fluoro-7-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.38 g, 1.09 mmol, 72.93% yield) was obtained as white solid.


Intermediate 1I. 4-bromo-6-fluoro-N,N-dimethyl-5-(methylthio)-1H-indazol-7-amine



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Step 1) 4-bromo-6-fluoro-7-nitro-1H-indazole

To a solution of 4-bromo-6-fluoro-1H-indazole (10 g, 46.51 mmol, 1 eq) in H2SO4 (80 mL) (98% purity) was added KNO3 (4.70 g, 46.51 mmol, 1 eq) at 0° C. in portions, then the mixture was stirred at 0° C. for 1 h. The reaction mixture was then poured into ice water (200 mL), and the mixture was extracted with ethyl acetate (100 mL*2), the combined organic layers were washed with saturated aqueous solution of NaHCO3 (100 mL*2) and brine (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel chromatography (200-300 mesh silica gel, Petroleum ether/Ethyl acetate=15/1 to 1/1, product 4-bromo-6-fluoro-7-nitro-1H-indazole came out at Petroleum ether/Ethyl acetate=8/1) to afford 4-bromo-6-fluoro-7-nitro-1H-indazole (2.7 g, 10.38 mmol, 22.32% yield) as yellow solid and crude product. The cured product was purified by MPLC (Petroleum ether/Ethyl acetate) to afford 4-bromo-6-fluoro-7-nitro-1H-indazole (3.57 g, 13.73 mmol, 29.52% yield) as yellow solid.


Step 2) 4-bromo-6-fluoro-5-iodo-7-nitro-1H-indazole

To a solution of 4-bromo-6-fluoro-7-nitro-1H-indazole (2.7 g, 10.38 mmol, 1 eq) in H2SO4 (30 mL) was added NIS (7.01 g, 31.15 mmol, 3 eq) at 25° C. The reaction mixture was stirred at 50° C. for 16 h. The reaction mixture was quenched by ice water (50 mL). Then the mixture was extracted with ethyl acetate (50 mL*3). The combined organic layers were washed with Na2SO3 aqueous solution (20 mL*2), NaHCO3 aqueous solution (20 mL*2) and brine (20 mL), dried over sodium sulfate, filtered and the filtrate was concentrated in vacuum to give 4-bromo-6-fluoro-5-iodo-7-nitro-1H-indazole (3.4 g, 8.81 mmol, 84.85% yield) as yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 14.28 (br s, 1H), 8.30 (s, 1H).


Step 3) 4-bromo-6-fluoro-5-iodo-1H-indazol-7-amine

To a solution of 4-bromo-6-fluoro-5-iodo-7-nitro-1H-indazole (3.4 g, 8.81 mmol, 1 eq) in EtOH (50 mL) and H2O (25 mL) was added NH4Cl (2.83 g, 52.86 mmol, 6 eq), then Fe (2.95 g, 52.86 mmol, 6 eq) was added in portions at 60° C. The mixture was stirred at 80° C. for 1 h. The reaction mixture was filtered through celite while it was still hot. Then the filtrate was concentrated in vacuum to remove EtOH. The resulting aqueous phase was extracted with ethyl acetate (50 mL*2). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered and the filtrate was concentrated in vacuum to give a residue. The residue was purified by silica gel chromatography (MPLC, Petroleum ether/Ethyl acetate=5/1 to 2/1, product came out at Petroleum ether/Ethyl acetate=2/1) to afford 4-bromo-6-fluoro-5-iodo-1H-indazol-7-amine (2.2 g, 6.18 mmol, 70.16% yield) as gray solid.



1H NMR (400 MHz, DMSO-d6) δ 13.09 (br s, 1H), 7.86 (d, J=1.7 Hz, 1H), 5.62 (s, 2H).


Step 4) 4-bromo-6-fluoro-5-iodo-N,N-dimethyl-1H-indazol-7-amine

To a solution of 4-bromo-6-fluoro-5-iodo-1H-indazol-7-amine (2.2 g, 6.18 mmol, 1 eq) in MeOH (50 mL) was added AcOH (1.11 g, 18.54 mmol, 1.06 mL, 3 eq), HCHO (5.02 g, 61.81 mmol, 4.60 mL, 10 eq), then NaBH3CN (3.88 g, 61.81 mmol, 10 eq) was added in portions under 40° C. Gas released and the temperature rise. The suspension was stirred at 25° C. for 16 h. The reaction mixture was poured into water (50 mL), then the mixture was concentrated to remove MeOH, after then the mixture was extracted with ethyl acetate (50 mL*2), and the combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel chromatography (200-300 mesh silica gel, Petroleum ether/Ethyl acetate=15/1 to 8/1, product came out at Petroleum ether/Ethyl acetate=8/1) to afford 4-bromo-6-fluoro-5-iodo-N,N-dimethyl-1H-indazol-7-amine (2.05 g, 5.34 mmol, 86.37% yield) as off-white solid.


Step 5) 4-bromo-6-fluoro-N,N-dimethyl-5-(methylthio)-1H-indazol-7-amine

To a 100 mL bottle equipped with a magnetic stir bar was added 4-bromo-6-fluoro-5-iodo-N,N-dimethyl-1H-indazol-7-amine (1.2 g, 3.13 mmol, 1 eq), NaSMe (328.56 mg, 4.69 mmol, 1.5 eq), Xantphos (361.65 mg, 625.02 umol, 0.2 eq), K2CO3 (1.30 g, 9.38 mmol, 3 eq), dioxane (20 mL) and Pd2(dba)3 (286.17 mg, 312.51 umol, 0.1 eq) sequentially. The bottle was evacuated and backfilled with nitrogen. Then the mixture was stirred at 90° C. for 16 h under nitrogen atmosphere. The residue was purified by silica gel chromatography (200-300 mesh silica gel, Petroleum ether/Ethyl acetate=20/1 to 8/1, product came out at Petroleum ether/Ethyl acetate=10/1) to afford 4-bromo-6-fluoro-N,N-dimethyl-5-(methylthio)-1H-indazol-7-amine (540 mg, 1.78 mmol, 56.81% yield) as orange solid.



1H NMR (400 MHz, DMSO-d6) δ 13.59 (br s, 1H), 8.00 (d, J=1.6 Hz, 1H), 2.91 (d, J=2.4 Hz, 6H), 2.39 (s, 3H).


Intermediate 1J. 4-bromo-6-fluoro-N,N-dimethyl-5-(trifluoromethyl)-1H-indazol-7-amine



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To a solution of 4-bromo-6-fluoro-5-iodo-N,N-dimethyl-1H-indazol-7-amine (1.0 g, 2.61 mmol, 1 eq) and methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (1.00 g, 5.22 mmol, 664.45 uL, 2 eq) in DMF (10 mL) was added CuI (994.63 mg, 5.22 mmol, 2 eq). The mixture was stirred at 100° C. for 6 hr under N2 atmosphere. The reaction mixture was filtered and the filtrate was diluted with water 50 mL and extracted with Ethyl acetate (50 mL*2). The combined organic layers were washed with brine (50 mL*3), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silical gel column chromatography (Petroleum ether:Ethyl acetate=1:0 to 10:1). 4-bromo-6-fluoro-N,N-dimethyl-5-(trifluoromethyl)-1H-indazol-7-amine (502 mg, 1.54 mmol, 58.91% yield) was obtained as a yellow solid.


Intermediate 1K. 4-bromo-5-ethyl-6-fluoro-1H-indazole



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Step 1) 4-bromo-5-ethyl-6-fluoro-2-trityl-2H-indazole

To a solution of diisopropylamine (132.75 mg, 1.31 mmol, 185.41 uL, 1.2 eq) in THF (5 mL) was added slowly n-BuLi (2.5 M, 481.04 uL, 1.1 eq) at −78° C. for 0.5 hr under N2 atmosphere. Then a solution of 4-bromo-6-fluoro-2-trityl-2H-indazole (500 mg, 1.09 mmol, 1 eq) in THF (2 mL) was added dropwise to the solution. After the mixture was stirred at −78° C. for 0.5 hr, a solution of EtI (204.62 mg, 1.31 mmol, 104.93 uL, 1.2 eq) in THF (2 mL) was added to the mixture and the solution were warmed to 15° C. and stirred for 2 hr under N2 atmosphere. The reaction mixture was quenched by addition with saturated NH4Cl aqueous 3 mL at 15° C., was diluted with water 20 mL and extracted with Ethyl acetate (30 mL*2). The combined organic layers were washed with brine (30 mL*2), dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. 4-bromo-5-ethyl-6-fluoro-2-trityl-2H-indazole (500 mg, crude) was obtained as a yellow solid.


Step 2) 4-bromo-5-ethyl-6-fluoro-1H-indazole

To a solution of 4-bromo-5-ethyl-6-fluoro-2-trityl-2H-indazole (500 mg, 1.03 mmol, 1 eq) in DCM (6 mL) was added TFA (3.08 g, 27.01 mmol, 2.00 mL, 26.22 eq). The mixture was stirred at 15° C. for 4 hr. The reaction mixture pH was adjusted to 7 with saturated NaHCO3 aqueous, and the mixture was extracted with Dichloromethane (30 mL*2). The combined organic layers were washed with brine (30 mL*2), dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna C18 150*40 mm*15 um; mobile phase: [water (0.1% TFA)-ACN]; B %: 40%-70%, 10 min). The fraction was concentrated under reduced pressure to remove ACN, the aqueous pH was adjusted to 7 with saturated NaHCO3 aqueous. The aqueous was extracted with Ethyl acetate (10 mL*2). The combined organic layers were washed with brine (10 mL*2), dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a product. 4-bromo-5-ethyl-6-fluoro-1H-indazole (70 mg, 287.98 umol, 27.96% yield) was obtained as a yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 13.39 (br s, 1H), 8.01-7.98 (m, 1H), 7.41 (d, J=9.9 Hz, 1H), 2.83 (dq, J=2.4, 7.5 Hz, 2H), 1.14 (t, J=7.5 Hz, 3H).


Intermediate 1L. 4-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine



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Step 1) 6-fluoro-5-nitro-1H-indazole

To a solution of 6-fluoro-1H-indazole (4.4 g, 32.32 mmol, 1 eq) in H2SO4 (30 mL) was added HNO3 (2.44 g, 38.79 mmol, 1.75 mL, 1.2 eq) dropwise at −15° C., the reaction mixture was stirred at 0° C. for 2 hours. The reaction mixture was slowly poured into ice water (100 mL), then the mixture was extracted with ethyl acetate (100 mL*2), the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give 6-fluoro-5-nitro-1H-indazole (5.4 g, crude) was obtained as a yellow solid.


Step 2) 6-fluoro-5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a mixture of 6-fluoro-5-nitro-1H-indazole (4.9 g, 27.05 mmol, 1 eq) (crude) in DCM (50 mL) were added DHP (6.83 g, 81.16 mmol, 7.42 mL, 3 eq) and TsOH.H2O (514.60 mg, 2.71 mmol, 0.1 eq), and the reaction mixture was stirred at 15° C. for 1 hour. The reaction mixture was poured into saturated solution of NaHCO3 (100 mL), then the mixture was extracted with dichloromethane (50 mL*2), the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=20/1 to 15:16-fluoro-5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (3 g, 11.31 mmol, 41.81% yield) was obtained as a yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J=7.3 Hz, 1H), 8.41 (s, 1H), 7.97 (d, J=12.1 Hz, 1H), 5.90 (dd, J=2.1, 9.7 Hz, 1H), 3.94-3.85 (m, 1H), 3.82-3.72 (m, 1H), 2.43-2.28 (m, 1H), 2.10-1.93 (m, 2H), 1.82-1.34 (m, 3H).


Step 3) 6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine

To a solution of 6-fluoro-5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (2.9 g, 10.93 mmol, 1 eq) in MeOH (30 mL) was added wet Pd/C (300 mg, 10% purity) under N2 atmosphere. The suspension was degassed and purged with H2 for 3 times. The mixture was stirred under H2 (15 Psi) at 15° C. for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=15/1 to 8:1). 6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (1.5 g, 5.87 mmol, 53.65% yield, 92% purity) was obtained as a brick-red solid.



1H NMR (400 MHz, DMSO-d6) δ 7.82 (s, 1H), 7.43 (d, J=11.6 Hz, 1H), 6.98 (d, J=8.6 Hz, 1H), 5.66 (dd, J=2.3, 9.7 Hz, 1H), 4.91 (s, 2H), 3.85 (br d, J=12.1 Hz, 1H), 3.77-3.62 (m, 1H), 2.42-2.27 (m, 1H), 2.07-1.96 (m, 1H), 1.95-1.86 (m, 1H), 1.76-1.63 (m, 1H), 1.59-1.51 (m, 2H); LCMS (electrospray) m/z 236.1 (M+H)+.


Step 4) 4-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine

To a solution of 6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (1.45 g, 5.67 mmol, 1 eq) in MeCN (10 mL) was added NBS (1.21 g, 6.80 mmol, 1.2 eq) in portions at 0° C. The mixture was stirred at 0° C. for 2 hours. The reaction mixture was concentrated to give a residue. Then the residue was dissolved in ethyl acetate (30 mL), and the mixture was washed with brine (15 mL*2), the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=20/1). 4-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (1.3 g, 4.14 mmol, 72.98% yield) was obtained as a brown solid.



1H NMR (400 MHz, DMSO-d6) δ 7.80 (s, 1H), 7.60 (d, J=10.6 Hz, 1H), 5.71 (dd, J=2.5, 9.6 Hz, 1H), 5.15 (s, 2H), 3.88-3.82 (m, 1H), 3.76-3.68 (m, 1H), 2.36-2.27 (m, 1H), 2.02 (br dd, J=4.6, 8.5 Hz, 1H), 1.96-1.90 (m, 1H), 1.76-1.65 (m, 1H), 1.60-1.52 (m, 2H).


Intermediate 1M. 3-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)cyclopentan-1-ol



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Step 1) 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-7-carbaldehyde

To a mixture of Intermediate 1A (3 g, 8.99 mmol, 1 eq) in THF (60 mL) was added LDA (2 M, 17.99 mL, 4 eq) dropwise at −78° C. under N2. The mixture was stirred at −78° C. for 1 h. After then, HCO2Et (3.17 g, 35.97 mmol, 3.52 mL, 4 eq) in THF (8 mL) was added dropwise at −78° C., then the mixture was stirred at −78° C. for 2 h. The reaction mixture was quenched by addition of saturated NH4Cl solution (20 mL) at −78° C., and then extracted with EA (30 mL*3). The combined organic layers were washed with brine (30 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=30/1 to 20/1). 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-7-carbaldehyde (2.78 g, 7.69 mmol, 85.49% yield) was obtained as an off-white solid.



1H NMR (400 MHz, DMSO-d6) δ 10.40 (s, 1H), 8.35 (s, 1H), 6.09 (dd, J=2.6, 8.9 Hz, 1H), 3.71-3.63 (m, 1H), 3.63-3.52 (m, 1H), 2.42-2.30 (m, 1H), 2.21-2.10 (m, 1H), 2.07-1.95 (m, 1H), 1.77-1.63 (m, 2H), 1.60-1.40 (m, 2H); LCMS (electrospray) m/z 278.9 (M+H)+.


Step 2) 1-(4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-yl)but-3-en-1-ol

To a mixture of 4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-7-carbaldehyde (2.2 g, 6.08 mmol, 1 eq) in THF (60 mL) was added allyl magnesium bromide (1 M, 9.13 mL, 1.5 eq) dropwise at 0° C. under N2. The mixture was stirred at 0° C. for 2 h. The reaction mixture was quenched by addition of saturated NH4Cl solution (20 mL) at 0° C., and then extracted with EA (30 mL*3). The combined organic layers were washed with brine (30 mL*2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=10/1 to 5/1). 1-(4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-yl)but-3-en-1-ol (2 g, 4.95 mmol, 81.43% yield) was obtained as a colorless oil.



1H NMR (400 MHz, DMSO-d6) δ 8.25-8.21 (m, 1H), 8.20-8.18 (m, 1H), 6.61 (br d, J=9.0 Hz, 1H), 6.23 (d, J=4.0 Hz, 1H), 6.18 (br d, J=8.3 Hz, 1H), 5.95 (d, J=5.0 Hz, 1H), 5.90-5.75 (m, 2H), 5.36 (dt, J=4.3, 7.5 Hz, 1H), 5.30 (td, J=5.9, 7.9 Hz, 1H), 5.10-4.97 (m, 4H), 3.97 (br d, J=11.5 Hz, 1H), 3.89 (br d, J=11.3 Hz, 1H), 3.69-3.55 (m, 2H), 2.87-2.74 (m, 2H), 2.70-2.55 (m, 4H), 2.06 (br d, J=10.8 Hz, 3H), 1.96-1.87 (m, 1H), 0.90-0.78 (m, 1H); LCMS (electrospray) m/z 302.9 (M+H)+.


Step 3) 4-bromo-7-(3-bromocyclopentyl)-5-chloro-6-fluoro-1H-indazole

To a mixture of 1-(4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-yl)but-3-en-1-ol (2 g, 4.95 mmol, 1 eq) in DCM (20 mL) was added Br2 (1.19 g, 7.43 mmol, 383.11 uL, 1.5 eq) in DCM (2 mL) dropwise at −20° C. under N2. The mixture was stirred at −10° C. for 3 h. The mixture was quenched by addition of Na2SO3 solution (30 mL), and then diluted with DCM (30 mL). The organic layer was washed with Na2SO3 solution (30 mL*2), dried over anhydrous Na2SO4, filtered and concentrated to obtain a residue. The residue was dissolved in MeOH (15 mL), and then K2CO3 (2.05 g, 14.86 mmol, 3 eq) was added and the resulting mixture was stirred at 20° C. for 16 h. The reaction was quenched by addition of water (20 mL), and extracted with EA (30 mL*3), dried by Na2SO4, filtered and concentrated to obtain a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=10/1 to 3:1). The crude product was purified by reversed-phase HPLC (0.1% FA condition). 4-bromo-7-(3-bromocyclopentyl)-5-chloro-6-fluoro-1H-indazole (300 mg, 752.91 umol, 15.20% yield) was obtained as a white solid.



1H NMR (400 MHz, DMSO-d6) δ 13.44-13.37 (m, 2H), 8.14-8.11 (m, 2H), 5.71-5.67 (m, 1H), 5.44 (dt, J=1.2, 7.5 Hz, 1H), 4.97 (s, 1H), 4.83-4.76 (m, 2H), 4.47 (dd, J=3.7, 10.1 Hz, 1H), 4.22 (dd, J=5.5, 10.1 Hz, 1H), 4.15 (dd, J=2.3, 10.6 Hz, 1H), 3.20-3.13 (m, 1H), 2.69-2.64 (m, 1H), 2.34-2.27 (m, 2H); LCMS (electrospray) m/z 398.8 (M+H)+.


Step 4) 3-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)cyclopentyl acetate

To a mixture of 4-bromo-7-(3-bromocyclopentyl)-5-chloro-6-fluoro-1H-indazole (100 mg, 250.97 umol, 1 eq) in DMSO (2 mL) was added KOAc (73.89 mg, 752.91 umol, 3 eq) in one portion at 20° C. under N2. The mixture was then heated to 70° C. and stirred for 3 h. The reaction was quenched by addition of water (15 mL), and then extracted with EA (20 mL*3), the combined organic layers were washed with brine (20 mL*2), dried by Na2SO4, filtered and concentrated to give a residue. 3-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)cyclopentyl acetate (100 mg, crude, brown oil) was used directly in the next step without further purification.


LCMS (electrospray) m/z 378.8 (M+H)+.


Step 5) 3-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)cyclopentan-1-ol

To a mixture of 3-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)cyclopentyl acetate (80 mg, 211.87 umol, 1 eq) in MeOH (4 mL) and H2O (0.8 mL) was added K2CO3 (442.15 mg, 3.20 mmol, 15.1 eq) in one portion at 20° C. under N2. The mixture was stirred at 20° C. for 2 h. The reaction mixture was quenched by addition of water (15 mL) at 20° C., and then extracted with ethyl acetate (20 mL*3). The combined organic layers were washed with brine (20 mL*1), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=3/1 to 1/2). 3-(4-bromo-5-chloro-6-fluoro-1H-indazol-7-yl)cyclopentan-1-ol (50 mg, 149.01 umol, 70.33% yield) was obtained as a white solid.


LCMS (electrospray) m/z 336.9 (M+H)+.


Intermediate 1N. 4-bromo-6-fluoro-N-isopropyl-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine



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Step 1) 5-fluoro-2-iodo-4-(trifluoromethyl)aniline

To a solution of 3-fluoro-4-(trifluoromethyl)aniline (4 g, 22.33 mmol, 1 eq) in MeCN (40 mL) was added NIS (5.53 g, 24.57 mmol, 1.1 eq) at 15° C., then reaction mixture was stirred at 15° C. for 15 h. The reaction mixture was diluted with H2O (100 mL) and extracted with EtOAc (100 mL*3). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 5-fluoro-2-iodo-4-(trifluoromethyl)aniline (5.6 g, crude) was obtained as a brown oil.


LCMS (electrospray) m/z 305.9 (M+H)+.


Step 2) 5-fluoro-2-methyl-4-(trifluoromethyl)aniline

To a solution of 5-fluoro-2-iodo-4-(trifluoromethyl)aniline (6.0 g, 19.67 mmol, 1 eq) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (8.82 g, 29.51 mmol, 9.82 mL, 42% purity, 1.5 eq) in DME (60 mL) were added Pd(PPh3)4 (1.14 g, 983.57 umol, 0.05 eq) and K2CO3 (8.16 g, 59.01 mmol, 3 eq) at 15° C., then reaction mixture was stirred at 100° C. for 60 h. The reaction mixture was concentrated under reduced pressure to afford the residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=5/1 to 3/1, Petroleum ether/Ethyl acetate=2:1, Rf=0.3). 5-fluoro-2-methyl-4-(trifluoromethyl)aniline (1.6 g, 4.06 mmol, 20.64% yield, 49% purity) was obtained as a yellow oil.


LCMS (electrospray) m/z 194.1.9 (M+H)+.


Step 3) 6-fluoro-5-(trifluoromethyl)-1H-indazole

To a solution of 5-fluoro-2-methyl-4-(trifluoromethyl)aniline (1 g, 5.18 mmol, 1 eq) in AcOH (15 mL) were added NaNO2 (357.25 mg, 5.18 mmol, 1 eq) and H2O (3 mL) at 0° C., then the reaction mixture was stirred at 15° C. for 2 h. The reaction was quenched by addition of H2O (60 mL) at 20° C. and the resulting mixture was extracted with EtOAc (50 mL*3). The combined organic layers were washed with H2O (50 mL*3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. Residue was purified by column (SiO2, Petroleum ether/Ethyl acetate=10/1 to 5/1, Petroleum ether/Ethyl acetate=3:1, Rf=0.5). 6-fluoro-5-(trifluoromethyl)-1H-indazole (500 mg, 2.45 mmol, 47.31% yield) was obtained as a yellow solid.


LCMS (electrospray) m/z 205.2 (M+H)+.


Step 4) 6-fluoro-7-nitro-5-(trifluoromethyl)-1H-indazole

To a solution of 6-fluoro-5-(trifluoromethyl)-1H-indazole (500 mg, 2.45 mmol, 1 eq) in H2SO4 (5 mL, 95% purity) was added KNO3 (249 mg, 2.46 mmol, 1.01 eq) at 0° C., then the reaction mixture was stirred at 15° C. for 15 hr. The reaction mixture was diluted with water (100 mL) and extracted with Ethyl acetate (50 mL*2). The combined organic layers were treated with saturated sodium bicarbonate solution until pH=7, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 6-fluoro-7-nitro-5-(trifluoromethyl)-1H-indazole (500 mg) was obtained as a yellow solid.


LCMS (electrospray) m/z 250.2 (M+H)+.


Step 5) 6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazole

To a solution of 6-fluoro-7-nitro-5-(trifluoromethyl)-1H-indazole (500 mg, 2.01 mmol, 1 eq) in THF (10 mL) was added PPTS (50.44 mg, 200.71 umol, 0.1 eq) and DHP (844.13 mg, 10.04 mmol, 917.53 uL, 5 eq) at 0° C., then the reaction mixture was stirred at 60° C. for 15 hr. The reaction mixture was diluted with solvent H2O (50 mL) and extracted with EtOAc (50 mL*3). The combined organic layers were washed with H2O (50 mL*3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazole (1 g, crude) was obtained as yellow oil.


Step 6) 6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine

To a solution of 6-fluoro-7-nitro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazole (800 mg, 2.40 mmol, 1 eq) and H2O (2 mL) in EtOH (10 mL) was added NH4Cl (642.08 mg, 12.00 mmol, 5 eq) and Fe (268.13 mg, 4.80 mmol, 2 eq) at 0° C., then the reaction mixture was stirred at 60° C. for 1 hr. The reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (20 mL*3). The combined organic layers were washed with H2O (30 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=10/1 to 5/1, Petroleum ether:Ethyl acetate=3:1, Rf=0.3). 6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine (500 mg, 1.65 mmol, 68.68% yield) was obtained as a yellow solid


LCMS (electrospray) m/z 220.2 (M+H)+.


Step 7) 4-bromo-6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine

To a solution of 6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine (200 mg, 659.51 umol, 1 eq) in DMF (1 mL) was added NBS (129.12 mg, 725.46 umol, 1.1 eq) at 20° C., then the reaction mixture was stirred at 20° C. for 2 hr. The reaction mixture was diluted with H2O (10 mL) and extracted with EtOAc (10 mL*3). The combined organic layers were washed with H2O (10 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 4-bromo-6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine (120 mg, crude) was obtained as a yellow solid.


LCMS (electrospray) m/z 297.9 (M+H)+.


Step 8) 4-bromo-6-fluoro-N-isopropyl-5-(trifluoromethyl)-1H-indazol-7-amine

To a solution of 4-bromo-6-fluoro-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine (100 mg, 335.53 umol, 1 eq) in MeOH (1 mL) were added AcOH (40.30 mg, 671.06 umol, 38.38 uL, 2 eq) and acetone (97.44 mg, 1.68 mmol, 123.34 uL, 5 eq) at 20° C., NaBH3CN (105.42 mg, 1.68 mmol, 5 eq) was then added and the reaction mixture was stirred at 20° C. for 2 hr. After then, acetone (97.44 mg, 1.68 mmol, 123.34 uL, 5 eq), NaBH3CN (105.43 mg, 1.68 mmol, 5 eq) and AcOH (60.45 mg, 1.01 mmol, 57.57 uL, 3 eq) were added to the mixture and the reaction mixture was stirred at 20° C. for 20 hr. The reaction mixture was diluted with H2O (10 mL) and extracted with EtOAc (10 mL*3). The combined organic layers were washed with H2O (10 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (Petroleum ether:Ethyl acetate=3:1, Rf=0.4). 4-bromo-6-fluoro-N-isopropyl-5-(trifluoromethyl)-1H-indazol-7-amine (60 mg, 165.83 umol, 49.42% yield, 94% purity) was obtained as a white solid.


LCMS (electrospray) m/z 340.1 (M+H)+.


Step 9) 4-bromo-6-fluoro-N-isopropyl-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine

To a solution of 4-bromo-6-fluoro-N-isopropyl-5-(trifluoromethyl)-1H-indazol-7-amine (50 mg, 147.01 umol, 1 eq) in THF (1 mL) were added PPTS (3.69 mg, 14.70 umol, 0.1 eq) and DHP (61.83 mg, 735.05 umol, 67.21 uL, 5 eq) at 0° C., then the reaction mixture was stirred at 60° C. for 2 hr. The reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (50 mL*3). The combined organic layers were washed with H2O (50 mL*3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. Residue was purified by prep-TLC (Petroleum ether:Ethyl acetate=5:1, Rf=0.6). 4-bromo-6-fluoro-N-isopropyl-2-(tetrahydro-2H-pyran-2-yl)-5-(trifluoromethyl)-2H-indazol-7-amine (50 mg, 117.86 umol, 80.17% yield) was obtained as a yellow oil.


LCMS (electrospray) m/z 424.1 (M+H)+.


Intermediate IO. 4-bromo-5-cyclopropyl-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole



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Step 1) 3-bromo-5-fluoro-2-methylaniline

To a mixture of 1-bromo-5-fluoro-2-methyl-3-nitrobenzene (23 g, 98.28 mmol, 1 eq) in EtOH (80 mL) and H2O (80 mL) was added Fe (27.44 g, 491.41 mmol, 5 eq) and NH4Cl (26.29 g, 491.41 mmol, 5 eq). The mixture was stirred at 100° C. for 3 h. The mixture was filtered and the filtrate was concentrated at reduced pressure to remove EtOH. The resulting mixture was extracted with DCM (50 mL*3). The combined organic phase was washed with brine (50 mL*2), dried over Na2SO4, filtered and concentrated at reduced pressure to give a residue to give 3-bromo-5-fluoro-2-methylaniline (20.6 g, crude) as yellow liquid.



1H NMR (400 MHz, DMSO-d6) δ 6.59 (br d, J=8.4 Hz, 1H), 6.42 (br d, J=11.2 Hz, 1H), 5.51 (br s, 2H), 2.09 (s, 3H).


Step 2) 3-bromo-5-fluoro-4-iodo-2-methylaniline

To a mixture of 3-bromo-5-fluoro-2-methylaniline (18 g, 88.22 mmol, 1 eq) (crude) in CH3CN (150 mL) was added NIS (19.85 g, 88.22 mmol, 1 eq) in portions at 0° C. The mixture was stirred at 30° C. for 3 h. After 3 h, LCMS showed compound 2 was remained and desired mass was detected, too. Then the mixture was stirred at 30° C. for another 12 h. LCMS showed there was no compound 2 remained and one main peak with desired mass was detected. The mixture was quenched with saturated Na2SO3 (200 mL) and the resulting mixture was extracted with EtOAc (50 mL*3). The combined organic phase was washed with brine (50 mL*2), dried over Na2SO4, filtered and concentrated at reduced pressure to give a residue. The residue was purified by silica gel chromatography (1000 mesh silica gel, Petroleum ether/Ethyl acetate=50/1, 30/1; TLC (Petroleum ether:Ethyl acetate=10:1; Rf=0.28)) to give 3-bromo-5-fluoro-4-iodo-2-methylaniline (22 g, 66.68 mmol, 75.58% yield) as brown solid.



1H NMR (400 MHz, DMSO-d6) δ 6.55 (d, J=10.5 Hz, 1H), 5.67 (s, 2H), 2.25 (d, J=0.8 Hz, 3H).


Step 3) 4-bromo-6-fluoro-5-iodo-1H-indazole

To a mixture of 3-bromo-5-fluoro-4-iodo-2-methylaniline (22 g, 66.68 mmol, 1 eq) in CH3COOH (200 mL) was added NaNO2 (5.52 g, 80.02 mmol, 1.2 eq) which was dissolved water (40 mL) at 0° C. The mixture was stirred at 30° C. for 16 h. The mixture was poured into saturated NaHCO3 (1000 mL) and the resulting mixture was extracted with EtOAc (200 mL*3). The combined organic phase was washed with brine (100 mL*2), dried over Na2SO4, filtered and concentrated at reduced pressure to give a residue. The residue was purified by silica gel chromatography (1000 mesh silica gel, Petroleum ether/Ethyl acetate=15/1, 5/1) to give 4-bromo-6-fluoro-5-iodo-1H-indazole (7.5 g, 22.00 mmol, 32.99% yield) as brown solid.



1HNMR (400 MHz, DMSO-d6) δ 13.58 (br s, 1H), 8.00 (s, 1H), 7.51 (d, J=8.1 Hz, 1H), 3.32 (s, 1H).


Step 4) 4-bromo-6-fluoro-5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a mixture of 4-bromo-6-fluoro-5-iodo-1H-indazole (7.5 g, 22.00 mmol, 1 eq) and 4-methylbenzenesulfonic acid; hydrate (418.47 mg, 2.20 mmol, 0.1 eq) in DCM (100 mL) was added DHP (5.55 g, 66.00 mmol, 6.03 mL, 3 eq) slowly. The mixture was stirred at 30° C. for 1 h. The mixture was washed with saturated NaHCO3 (30 mL*3) and brine (30 mL*3). The organic phase was dried over Na2SO4, filtered and concentrated at reduced pressure to give a residue. The residue was purified by silica gel chromatography (1000 mesh silica gel, Petroleum ether/Ethyl acetate=100/1, 50/1) to give 4-bromo-6-fluoro-5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (7.4 g, 17.41 mmol, 79.14% yield) as yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.80 (dd, J=0.7, 8.4 Hz, 1H), 5.83 (dd, J=2.4, 9.6 Hz, 1H), 3.88-3.85 (m, 1H), 3.80-3.70 (m, 2H), 2.40-2.27 (m, 1H), 2.07-1.94 (m, 2H), 1.81-1.63 (m, 2H), 1.62-1.53 (m, 2H).


Step 5) 4-bromo-5-cyclopropyl-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a mixture of 4-bromo-6-fluoro-5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (1.5 g, 3.53 mmol, 1 eq) and cyclopropylboronic acid (303.14 mg, 3.53 mmol, 1 eq) in dioxane (10 mL) and H2O (2.5 mL) was added Na2CO3 (748.10 mg, 7.06 mmol, 2 eq) and Pd(dppf)Cl2 (258.23 mg, 352.91 umol, 0.1 eq) under N2. The mixture was stirred at 80° C. for 16 h. The mixture was concentrated at reduced pressure to give a residue. The residue was purified by prep-TLC (Petroleum ether:Ethyl acetate=20:1) to give 4-bromo-5-cyclopropyl-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.21 g, 619.10 umol, 17.54% yield) as colorless oil.



1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=0.6 Hz, 1H), 7.20 (d, J=10.4 Hz, 1H), 5.61 (dd, J=2.8, 9.1 Hz, 1H), 4.03-3.94 (m, 1H), 3.76-3.69 (m, 1H), 2.55-2.42 (m, 1H), 2.19-2.06 (m, 2H), 1.91-1.86 (m, 1H), 1.81-1.64 (m, 3H), 1.12-1.05 (m, 2H), 0.87-0.81 (m, 2H).


Intermediate 1P. 4-bromo-6-fluoro-5-isopropyl-1H-indazole



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Step 1) 4-bromo-6-fluoro-5-(prop-1-en-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a mixture of 4-bromo-6-fluoro-5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (1.5 g, 3.53 mmol, 1 eq) and potassium; trifluoro(isopropenyl)boranuide (626.67 mg, 4.23 mmol, 1.2 eq) in dioxane (10 mL) and H2O (2 mL) was added Pd(dppf)Cl2 (258.23 mg, 352.91 umol, 0.1 eq) and Na2CO3 (748.10 mg, 7.06 mmol, 2 eq) under N2. The mixture was stirred at 80° C. for 16 h. The mixture was concentrated at reduced pressure to give a residue. The residue was purified by silica gel chromatography (1000 mesh silica gel, Petroleum ether/Ethyl acetate=100/1, 50/1; TLC (Petroleum ether:Ethyl acetate=10:1; Rf=0.61)) to give 0.9 g of yellow oil. This oil was purified by prep-TLC (Petroleum ether:Ethyl acetate=20:1) to give 4-bromo-6-fluoro-5-(prop-1-en-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.55 g, 1.62 mmol, 45.94% yield) as yellow oil.



1H NMR (400 MHz, CDCl3) δ 8.00 (d, J=0.6 Hz, 1H), 7.28 (d, J=0.9 Hz, 0.5H), 7.26 (d, J=0.7 Hz, 0.5H), 5.64 (dd, J=2.8, 9.0 Hz, 1H), 5.46 (t, J=1.6 Hz, 1H), 5.01 (s, 1H), 4.05-3.97 (m, 1H), 3.80-3.69 (m, 1H), 2.57-2.42 (m, 1H), 2.19-2.09 (m, 2H), 2.07 (s, 3H), 1.81-1.66 (m, 4H).


Step 2) 4-bromo-6-fluoro-5-isopropyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a solution of 4-bromo-6-fluoro-5-(prop-1-en-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.4 g, 1.18 mmol, 1 eq) in MeOH (10 mL) was added PtO2 under N2. The suspension was degassed under vacuum and purged with H2 several times. The mixture was stirred under H2 (15 Psi) at 30° C. for 2.5 h. The mixture was filtered and the filtrate was concentrated at reduced pressure to give a residue The residue was purified by silica gel chromatography (300-400 mesh silica gel, Petroleum ether/Ethyl acetate=50/1) to give 4-bromo-6-fluoro-5-isopropyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.3 g, 879.20 umol, 74.56% yield) as colorless oil.


Step 3) 4-bromo-6-fluoro-5-isopropyl-1H-indazole

To a solution of 4-bromo-6-fluoro-5-isopropyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.3 g, 879.20 umol, 1 eq) in DCM (1 mL) was added TFA (2.30 g, 20.14 mmol, 1.49 mL, 22.91 eq). The mixture was stirred at 30° C. for 0.5 h. The mixture was concentrated at reduced pressure to give a residue. The residue was diluted with DCM (10 mL) and the resulting mixture was adjusted pH to about 8 with TEA. The mixture was concentrated at reduced pressure to give a residue. The residue was purified by silica gel chromatography (300-400 mesh silica gel, Petroleum ether/Ethyl acetate=30/1, 5/1) to give 4-bromo-6-fluoro-5-isopropyl-1H-indazole (0.2 g, 777.90 umol, 88.48% yield) as colorless oil.



1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 7.11 (d, J=11.2 Hz, 1H), 3.75-3.63 (m, 1H), 1.38 (dd, J=1.7, 7.1 Hz, 6H).


Intermediate 1Q. 4-bromo-6-fluoro-5-methoxy-1H-indazole



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Step 1) 2-bromo-4-fluoro-3-methoxy-1-methylbenzene

To a solution of 2-bromo-6-fluoro-3-methylphenol (4.8 g, 23.41 mmol, 1 eq) in acetone (50 mL) were added K2CO3 (6.47 g, 46.82 mmol, 2 eq) and iodomethane (9.97 g, 70.24 mmol, 4.37 mL, 3 eq), and the mixture was stirred at 25° C. for 1 hour. The reaction mixture was concentrated to give a residue. The residue was dissolved in ethyl acetate (50 mL), and the mixture was filtered, and the filtrate was concentrated to give a residue (4.6 g, 21.00 mmol, 89.70% yield) as a yellow oil.



1H NMR (400 MHz, CHLOROFORM-d) δ 7.05-6.85 (m, 2H), 3.95 (d, J=1.2 Hz, 3H), 2.38 (s, 3H).


Step 2) 3-bromo-1-fluoro-2-methoxy-4-methyl-5-nitrobenzene

To a solution of 2-bromo-4-fluoro-3-methoxy-1-methylbenzene (4.4 g, 20.09 mmol, 1 eq) in H2SO4 (40 mL) (98%) was added KNO3 (2.23 g, 22.10 mmol, 1.1 eq) in portions at 0° C., and the mixture was stirred at 25° C. for 1 hour. The reaction mixture was poured slowly into ice water (200 mL), then the mixture was extracted with ethyl acetate (200 mL*2), the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 3-bromo-1-fluoro-2-methoxy-4-methyl-5-nitrobenzene (4.6 g, crude) was obtained as a brown oil.



1H NMR (400 MHz, CHLOROFORM-d) δ 7.70 (d, J=10.9 Hz, 1H), 4.08 (d, J=2.7 Hz, 3H), 2.61 (d, J=1.1 Hz, 3H).


Step 3) 3-bromo-5-fluoro-4-methoxy-2-methylaniline

To a solution of 3-bromo-1-fluoro-2-methoxy-4-methyl-5-nitrobenzene (4.6 g, 17.42 mmol, 1 eq) in EtOH (30 mL) and H2O (30 mL) were added Fe (5.84 g, 104.53 mmol, 6 eq) and NH4Cl (5.59 g, 104.53 mmol, 6 eq), and the mixture was stirred at 80° C. for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated to remove EtOH, then the mixture was diluted with EA (50 mL), and the mixture was washed with water (20 mL*2), after then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. 3-bromo-5-fluoro-4-methoxy-2-methylaniline (3.5 g, crude) was obtained as a brown oil.



1H NMR (400 MHz, CHLOROFORM-d) δ 6.44 (d, J=11.9 Hz, 1H), 3.83 (s, 3H), 3.76-3.48 (m, 2H), 2.24 (d, J=1.0 Hz, 3H).


Step 4) 4-bromo-6-fluoro-5-methoxy-1H-indazole

To a mixture of 3-bromo-5-fluoro-4-methoxy-2-methylaniline (3.5 g, 14.95 mmol, 1 eq) (crude) in AcOH (20 mL) was added a solution of NaNO2 (1.24 g, 17.94 mmol, 1.2 eq) in H2O (4 mL) dropwise at 0° C., then the mixture was stirred at 25° C. for 12 hr. The reaction mixture was diluted with ice water (100 mL), and the mixture was adjusted to pH 7 by using KOH, then the mixture was extracted with EA (100 mL*2), the combined organic layers were washed with brine (50 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=20/1 to 15:1). 4-bromo-6-fluoro-5-methoxy-1H-indazole (600 mg, 2.45 mmol, 16.37% yield) was obtained as a brown solid.



1H NMR (400 MHz, DMSO-d6) δ 13.44 (br s, 1H), 8.00 (s, 1H), 7.52 (br d, J=10.4 Hz, 1H), 3.84 (s, 3H).


Synthesis of Formula (I) Compounds


Synthetic methods A to J were used to prepare the compounds of the following. Below, the illustrating synthetic examples of some compounds of the present disclosure are described, and other compounds can be prepared by the similar method to the one described below with different starting or reacting materials.


Synthetic Method A
Example 2. (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indazol-4-yl)benzo[d]thiazol-2-yl)cyclopropane-1-carboxamide



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To a solution of Compound 1 (0.2 g, 0.462 mmol, 1 eq) (5-methyl-1H-indazol-4-yl)boronic acid (0.081 g, 0.462 mmol, 1 eq) in dioxane (4 mL) and H2O (1 mL) was added Na2CO3 (0.146 g, 1.38 mmol, 3 eq) and Pd(dppf)Cl2 (33 mg, 0.046 mmol, 0.1 eq). The mixture was stirred at 110° C. for 16 hr. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (10 mL×2). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography to get Example 2 (135 mg, 0.369 mmol, 80% yield) was obtained as a yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 13.04 (s, NH), 12.76 (s, CONH), 8.05 (s, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.63 (s, 2H), 7.49-7.44 (m, 2H), 7.31 (d, J=8.4 Hz, 1H), 5.05 (td, J12=3.3 Hz, J13=65.7 Hz, 1H), 2.24 (s, 3H), 2.23-2.24 (m, 1H), 1.78-1.73 (m, 1H), 1.31-1.23 (m, 1H); LCMS (electrospray) m/z 367.1 (M+H)+.


Synthetic Method B
Example 58. (1S,2S)—N-(6-(5-chloro-6-fluoro-7-(methylthio)-1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-fluorocyclopropane-1-carboxamide. 2 TFA



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Step 1) (1S,2S)—N-(6-(5-chloro-6-fluoro-7-(methylthio)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-fluorocyclopropane-1l-carboxamide

To a solution of Compound 3 (4.4 g, 11.59 mmol, 1 eq) in dioxane (100 mL) and H2O (20 mL) was added Compound 2 (4.20 g, 11.59 mmol, 1 eq), Pd(dppf)Cl2 (847.97 mg, 1.16 mmol, 0.1 eq) and Na2CO3 (2.46 g, 23.18 mmol, 2 eq) under N2. The reaction mixture was stirred at 90° C. for 12 hr. Water (100 mL) was added and the aqueous phase was extracted with EA (200 mL*2). The combined organic phase was washed with saturated brine (200 mL*2), and concentrated in vacuum. The mixture was purified by column chromatography on silica gel (Petroleum ether:Ethyl acetate=10:1 to 1:1) to give product. Compound 4 (3.9 g, 7.29 mmol, 62.90% yield) as a light yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 8.00-7.95 (m, 2H), 7.92-7.85 (m, 1H), 7.59 (dd, J=1.8, 8.4 Hz, 1H), 5.70 (dd, J=2.5, 9.5 Hz, 1H), 5.07-4.79 (m, 1H), 3.82-3.63 (m, 1H), 2.72 (d, J=0.9 Hz, 3H), 2.35-2.23 (m, 1H), 2.04-1.94 (m, 2H), 1.81-1.48 (m, 4H), 1.46-1.33 (m, 2H).


Step 2) (1S,2S)—N-(6-(5-chloro-6-fluoro-7-(methylthio)-1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-fluorocyclopropane-1-carboxamide. 2 TFA salt

To a solution of Compound 4 (3.80 g, 7.10 mmol, 1 eq) in DCM (100 mL) was added TFA (9.86 g, 86.51 mmol, 6.41 mL, 12.18 eq) under N2. The reaction mixture was stirred at 20° C. for 4 hr. DCM (10 ml) was added, Then the MeOH (200 ml) was slowly added. The reaction mixture was stirred at 20° C. for 0.5 hr. The reaction mixture was filtered and the filter cake was concentrated to give product. The filtrate was concentrated in vacuum to give product. Then the crude product was lyophilized to afford Example 58 (3.1 g, 4.26 mmol, 59.98% yield, 2 TFA) as a light yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 13.76 (br s, 1H), 12.82 (br s, 1H), 8.19 (d, J=1.7 Hz, 1H), 7.96-7.82 (m, 2H), 7.59 (dd, J=1.8, 8.4 Hz, 1H), 5.26-4.85 (m, 1H), 2.57 (s, 3H), 2.30-2.19 (m, 1H), 1.84-1.69 (m, 1H), 1.33 (tdd, J=6.4, 9.0, 12.9 Hz, 1H); LCMS (electrospray) m/z 450.8 (M+H)+.


Synthetic Method C
Example 149. (1S,2S)—N-(5-(5-chloro-7-ethoxy-6-fluoro-1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide. 2 TFA



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Step 1) (1S,2S)-2-fluoro-N-(5-(tributylstannyl)thiazolo[5,4-b]pyridin-2-yl)cyclopropane-1-carboxamide

To a solution of Compound 5 (2.5 g, 7.91 mmol, 1 eq) in dioxane (30 mL) was added (SnBu3)2 (6.88 g, 11.86 mmol, 5.93 mL, 1.5 eq), Pd(PPh3)4 (913.78 mg, 790.77 umol, 0.1 eq) and LiCl (1.01 g, 23.72 mmol, 485.85 uL, 3 eq). The mixture was stirred at 110° C. for 16 hr under N2 atmosphere. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Silical gel, Petroleum ether:Ethyl acetate=10:1 to 3:1). Compound 6 (1.3 g, 2.47 mmol, 31.24% yield) was obtained as a yellow oil.


Step 2) (1S,2S)—N-(5-(5-chloro-7-ethoxy-6-fluoro-1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide. 2 TFA

To a solution of 4-bromo-5-chloro-7-ethoxy-6-fluoro-1H-indazole (100 mg, 264.81 umol, 1 eq) in dioxane (2 mL) were added Compound 6 (167.24 mg, 317.77 umol, 1.2 eq), Pd(PPh3)4 (30.60 mg, 26.48 umol, 0.1 eq) and LiCl (33.68 mg, 794.42 umol, 16.27 uL, 3 eq). The mixture was stirred at 140° C. for 2 hr under microwave. After then, the reaction mixture was added with saturated K2CO3 aqueous 10 mL and stirred at 20° C. for 15 min. The mixture was diluted with water 10 mL and extracted with Ethyl acetate (20 mL*2). The combined organic layers were washed with brine (20 mL*2), dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (Silical gel plate, Petroleum ether:Ethyl acetate=1:2) to give a crude product. The crude product was purified by prep-HPLC (column: Phenomenex luna C18 150*25 mm*10 um; mobile phase: [water (0.1% TFA)-ACN]; B %: 55%-85%, 10 min). Example 149 (60 mg, 112.36 umol, 42.43% yield) was obtained as a yellow oil.



1H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 8.28 (d, J=8.4 Hz, 1H), 7.95 (s, 1H), 7.81 (d, J=8.4 Hz, 1H), 6.12-6.06 (m, 1H), 5.20-4.96 (m, 1H), 4.46-4.34 (q, J=7.0 Hz, 2H), 3.97 (m, 1H), 3.73-3.61 (m, 1H), 2.47-2.40 (m, 1H), 2.32-2.22 (m, 1H), 2.04 (m, 2H), 1.83-1.69 (m, 2H), 1.57 (m, 2H), 1.49 (t, J=7.0 Hz, 3H), 1.41-1.28 (m, 1H).


Synthetic Method D
Example 152. (1S,2S)—N-(5-(5-ethyl-6-fluoro-1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide



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To a solution of Intermediate 1K (45 mg, 185.13 umol, 1 eq) in EtOH (2 mL) were added Compound 6 (116.92 mg, 222.15 umol, 1.2 eq) and Ad2nBuP-Pd-G3 (13.48 mg, 18.51 umol, 0.1 eq). The mixture was stirred at 80° C. for 16 hr under N2 atmosphere. The reaction mixture was diluted with water 20 mL and extracted with Ethyl acetate (20 mL*2). The combined organic layers were washed with brine (20 mL*2), dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna C18 150*25 mm*10 um; mobile phase: [water (0.1% TFA)-ACN]; B %: 33%-63%, 10 min) to give a crude product. The crude product was purified by prep-TLC (Silical gel plate, Petroleum ether:Ethyl acetate=1:1). Example 152 (9.7 mg, 24.29 umol, 13.12% yield, 100% purity) was obtained as a white solid.



1H NMR (400 MHz, DMSO-d6) δ 13.18 (br s, 1H), 12.94 (br s, 1H), 8.26 (d, J=8.2 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.42 (d, J=10.1 Hz, 1H), 5.20-4.95 (m, 1H), 2.65 (dq, J=2.4, 7.2 Hz, 2H), 2.27 (m, 1H), 1.85-1.69 (m, 1H), 1.34 (m, 1H), 1.11 (t, J=7.0 Hz, 3H); LCMS (electrospray) m/z 400.4 (M+H)+.


Synthetic Method E
Example 221. (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide



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Step 1) (1S,2S)-2-fluoro-N-(6-iodoimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

A mixture of Compound 7 (5.890 g, 22.737 mmol), (1S,2S)-2-fluorocyclopropane-1-carboxylic acid (3.076 g, 29.558 mmol) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 6.538 g, 34.105 mmol) in dichloromethane (100 mL) was treated at the room temperature with N,N-diisopropylethylamine (2.376 mL, 13.642 mmol), stirred at the same temperature for 40 hr. The precipitates were collected by filtration, washed by dichloromethane, and dried to give Compound 8 as beige solid (3.870 g, 49.3%).



1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 8.87 (s, 1H), 8.02 (s, 1H), 7.36˜7.23 (m, 2H), 4.97˜4.77 (m, 1H), 2.09˜2.07 (m, 1H), 1.65˜1.57 (m, 1H), 1.16˜1.09 (m, 1H).


Step 2) (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

Compound 8 (0.750 g, 2.173 mmol), (5-methyl-1H-indazol-4-yl)boronic acid (0.459 g, 2.608 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2, 0.159 g, 0.217 mmol) and cesium carbonate (1.416 g, 4.346 mmol) in tetrahydrofuran (15 mL)/water (4 mL) was mixed at the room temperature and then heated at 120° C. under the microwaves for 1 hr, cooled down to the room temperature, filtered through a celite pad to remove solids, and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried (anhydrous MgSO4), filtered, and concentrated in vacuo. The residue was chromatographed (SiO2, 30 g cartridge; ethyl acetate/hexane=100%) to give the crude product which was crystallized at the room temperature using diethylether (5 mL). The resulting precipitates were filtered, washed by diethylether, and dried to give Example 221 as light yellow solid (0.550 g, 72.4%).



1H NMR (400 MHz, DMSO-d6) δ 12.77 (s, 1H), 9.70 (s, 1H), 9.00 (s, 1H), 8.66 (d, J=9.2 Hz, 1H), 8.59 (s, 1H), 8.55 (d, J=9.2 Hz, 1H), 8.33 (d, J=8.0 Hz, 1H), 8.14 (d, J=8.8 Hz, 1H), 5.91˜5.71 (m, 1H), 3.11 (s, 3H), 3.05˜3.00 (m, 1H), 2.54˜2.48 (m, 1H), 2.07˜2.03 (m, 1H); LCMS (electrospray) m/z 350.0 (M+H)+.


Synthetic Method F
Example 223. N-(6-(5-chloro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide. dihydrochloride



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Step 1) (2-amino-6-iodoimidazo[1,2-a]pyridin-3-yl)(cyclopropyl)methanone

To a solution of cyclopropanecarboxylic acid (3.17 g, 36.78 mmol, 2.91 mL, 1.3 eq) in DCM (50 mL) was added EDCI (6.51 g, 33.95 mmol, 1.2 eq), HOBt (4.59 g, 33.95 mmol, 1.2 eq) and TEA (8.59 g, 84.89 mmol, 11.82 mL, 3 eq). The mixture was stirred at 20° C. for 1 hr. then added Compound 7 (6 g, 28.30 mmol, 1 eq). The final mixture was stirred at 20° C. for 18 hr. The mixture was poured into H2O (200 mL) and extracted with Ethyl acetate (300 mL*3), the organic phase was washed with brine (500 mL*2) and dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated in vacuum. The residue was purified by trituration with Ethyl acetate (50 mL), filtered and the filter cake was concentrated. Compound 9 (1.9 g, 6.78 mmol, 23.96% yield) was obtained as yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 9.70 (d, J=1.2 Hz, 1H), 7.60 (dd, J=2.1, 9.3 Hz, 1H), 7.32 (d, J=9.3 Hz, 1H), 6.62 (s, 2H), 2.46-2.37 (m, 1H), 1.02-0.90 (m, 4H).


Step 2) (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide dihydrochloride

To a solution of Compound 9 (10.22 g, 31.27 mmol, 1 eq) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (11.12 g, 43.78 mmol, 1.4 eq) in dioxane (100 mL) was added KOAc (9.21 g, 93.82 mmol, 3 eq) and Pd(dppf)Cl2 (1.14 g, 1.56 mmol, 0.05 eq). The mixture was heated to 90° C. for 3 hr. The residue was poured into water (200 mL). The aqueous phase was extracted with ethyl acetate (200 mL*2). The combined organic phase was washed with brine (300 mL), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. TLC (Petroleum ether/Ethyl acetate=0:1) showed a main spot. The residue was purified by silica gel chromatography eluted with Petroleum ether/Ethyl acetate=0:1. Compound 10 (11 g, crude) was obtained as yellow solid. The crude was purified by triturated with Petroleum ether (20 mL) and Ethyl acetate (4 mL), filtered and the filter cake was concentrated. Compound 10 (6.3 g, 19.26 mmol, 48.46% yield) was obtained as white solid.


Step 3) N-(6-(5-chloro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide. Dihydrochloride

To a solution of Compound 10 (100 mg, 305.64 umol, 1 eq) and 4-bromo-5-chloro-1H-indazole (84.90 mg, 366.76 umol, 1.2 eq) in dioxane (3 mL) and H2O (1 mL) was added Na2CO3 (97.18 mg, 916.91 umol, 3 eq) and Pd(dppf)Cl2 (11.18 mg, 15.28 umol, 0.05 eq). The mixture was stirred at 90° C. for 10 hr. The mixture was poured into Petroleum ether (10 mL), filtered with silica gel and the filtrate was concentrated in vacuum. The residue was purified by prep-HPLC (column: Phenomenex Synergi C18 150*25*10 um; mobile phase: [water (0.05% HCl)-ACN]; B %: 14%-34%, 9 min), followed by lyophilization. Example 223 (36.8 mg, 85.95 umol, 28.12% yield, 99.2% purity, 2 HCl) was obtained as white solid.



1H NMR (400 MHz, METHANOL-d4) δ 8.92 (s, 1H), 8.13 (s, 1H), 7.99-7.91 (m, 3H), 7.68 (dd, J=1.0, 8.9 Hz, 1H), 7.58 (d, J=8.9 Hz, 1H), 1.95-1.87 (m, 1H), 1.12-1.07 (m, 2H), 1.05-0.98 (m, 2H); LCMS (electrospray) m/z 352.0 (M+H)+.


Synthetic Method G
Example 231. N-(6-(5-bromo-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide. 2 TFA salt



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A mixture of CuBr (137.29 mg, 957.04 umol, 29.15 uL, 1 eq) and t-BuONO (98.69 mg, 957.04 umol, 113.83 uL, 1 eq) in MeCN (5 mL) was stirred at 0° C. for 30 mins, after then a solution of Example 227 (662 mg, 957.04 umol, 1 eq) in MeCN (1 mL) was added, and the mixture was stirred at 20° C. for 2 hours, after then CuBr (137.29 mg, 957.04 umol, 29.15 uL, 1 eq) and t-BuONO (98.69 mg, 957.04 umol, 113.83 uL, 1 eq) were added, and the mixture was stirred at 20° C. for another 12 hours. The reaction mixture was concentrated to give a residue, then the residue was dissolved in ethyl acetate (50 mL), after then the mixture was washed with diluted ammonium hydroxide (3%, 20 mL*2), the organic layer was washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex Synergi C18 150*25*10 um; mobile phase: [water (0.1% TFA)-ACN]; B %: 20%-50%, 9 min). Example 231 (14 mg, 22.01 umol, 2.3% yield, 2TFA) was obtained as a yellow solid.



1H NMR (400 MHz, DMSO-d6) δ 13.49 (br s, 1H), 11.05 (s, 1H), 8.78 (s, 1H), 8.14 (s, 1H), 7.92 (s, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.57 (d, J=9.2 Hz, 1H), 7.32 (dd, J=1.7, 9.2 Hz, 1H), 2.05-1.86 (m, 1H), 0.85-0.79 (m, 4H); LCMS (electrospray) m/z 414.1 (M+H)+.


Synthetic Method H
Example 258. (1S,2S)—N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide



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Step 1) (1S,2S)—N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

To a solution of Intermediate 1D (30 mg, 78.06 umol, 1 eq) and Compound 11 (32.33 mg, 93.67 umol, 1.2 eq) in dioxane (1 mL) and H2O (0.2 mL) were added Pd(dppf)Cl2 (5.71 mg, 7.81 umol, 0.1 eq) and Na2CO3 (24.82 mg, 234.17 umol, 3 eq), then the mixture was stirred at 80° C. for 12 hours under N2. The reaction mixture was concentrated to give a residue. The residue was purified by prep-TLC (SiO2, Dichloromethane:Methanol=10:1). Compound 12 (34 mg, 57.44 umol, 73.59% yield, 87% purity) was obtained as a yellow oil.


Step 2) (1S,2S)—N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

To a solution of Compound 12 (34 mg, 57.44 umol, 1 eq) in dioxane (1 mL) was added HCl/dioxane (4 M, 1 mL, 69.64 eq), then the mixture was stirred at 20° C. for 2 hours under N2. The reaction mixture was diluted with ethyl acetate (20 mL), and the mixture was washed with saturated aqueous solution of NaHCO3 (15 mL*2), the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna C18 150*25 10u; mobile phase: [water (0.1% TFA)-ACN]; B %: 23%-53%, 10 min). Example 258 (8.7 mg, 13.05 umol, 22.72% yield, 2 TFA) was obtained as a white solid.



1H NMR (400 MHz, DMSO-d6) δ 13.55 (br s, 1H), 11.21 (s, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.43 (d, J=9.2 Hz, 1H), 5.08-4.77 (m, 1H), 3.01 (s, 3H), 3.00 (s, 3H), 2.16 (td, J=7.0, 13.8 Hz, 1H), 1.76-1.57 (m, 1H), 1.27-1.11 (m, 1H); LCMS (electrospray) m/z 431.2 (M+H)+.


Synthetic Method I
Example 393. (1S,2S)—N-(6-(7-(1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide



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Step 1) 1-(4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-yl)ethan-1-one

To a solution of Intermediate 1A (3.29 g, 9.86 mmol, 1 eq) in THF (49 mL) was cooled to −78° C. then, LDA (7.39 mL, 14.7 mmol, 1.5 eq) was added slowly to reaction mixture, stirred at the same temperature for 30 min. Then acetic anhydride (1.11 mL, 11.8 mmol, 1.2 eq) was added dropwise and the reaction mixture was stirred at rt for 2 hrs. After the Intermediate 1A was consumed, quenched with water and extracted with DCM, separated, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (product came out at Hexane/Ethyl acetate=10/1) to afford Compound 13 (1.86 g, 4.95 mmol, 50.2% yield) as an orange solid.


Step 2) 1-(4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-7-yl)ethan-1-ol

To a solution of Compound 13 (1.86 mg, 4.95 mmol, 1 eq) in MeOH (24 mL) were cooled to 0° C. then sodium borohydride (375 mg, 9.90 mmol, 2 eq) was added portionwise. The reaction mixture was stirred at rt for 2 hrs. After the Compound 13 was consumed, the reaction mixture was concentrated and extracted with DCM, washed with water, separated, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (product came out at Hexane/Ethyl acetate=7/3) to afford Compound 14 (615 mg, 1.62 mmol, 32% yield) as an ivory solid.


Step 3) 7-(1-(2H-tetrazol-2-yl)ethyl)-4-bromo-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

To a solution of Compound 14 (100 mg, 0.265 mmol, 1.0 eq) in THF (1.33 mL) was added 1H-tetrazole (0.89 mL, 0.398 mmol, 1.5 eq) and PPh3 (104 mg, 0.398 mmol, 1.5 eq). The mixture was cooled to 0° C. and DEAD (0.181 mL, 0.398 mmol, 1.5 eq) was added slowly at 0° C. The mixture was stirred at room temperature for 1 hr. The reaction mixture was extracted with DCM (30 mL*3). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated in vacuum. The crude product was purified by silica gel chromatography (product came out Hexane/Ethyl acetate=10/2) to afford Compound 15 (62 mg, 0.144 mmol, 54% yield) as a white color solid.


Step 4) (1S,2S)—N-(6-(7-(1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

To a solution of Compound 15 (62 mg, 0.144 mmol, 1 eq) in 1,4-Dioxane (0.577 mL)/H2O (0.144 mL) were added Compound 11 (54 mg, 0.159 mmol, 1.1 eq), Pd(dppf)Cl2 (5 mg, 0.007 mmol, 0.05 eq), Na2CO3 (30 mg, 0.289 mmol, 2 eq). The mixture was degassed and purged with N2 for 3 times. The mixture was stirred at 120° C. for 30 min in microwave reactor. The reaction mixture was filtered through celite and filtrate was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated in vacuum to give a residue. The residue was purified by silica gel chromatography (product came out at Hexane/Ethyl acetate=2/8) to afford Compound 16 (68 mg, 0.120 mmol, 83%) as a yellow solid.


Step 5) (1S,2S)—N-(6-(7-(1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

To a solution of Compound 16 (66 mg, 0.116 mmol, 1 eq) in Ethyl acetate (0.6 mL) was added 1 N HCl in EA solution (1.16 mL, 1.16 mmol, 10 eq). The mixture was stirred at room temperature for 1 hr. The reaction mixture was quenched by saturated NaHCO3 and extracted with EA, dried over Na2SO4, filtered and the filtrate was concentrated in vacuum. The crude product was purified by silica gel chromatography (product came out at DCM/MeOH=10/1) to afford Example 393 (4 mg, 0.008 mmol, 7%) as an ivory solid.



1H NMR (400 MHz, DMSO-d6) δ 13.77 (s, 1H), 11.07 (s, 1H), 8.99 (s, 1H), 8.80 (s, 1H), 8.14-8.04 (m, 2H), 7.58-7.54 (m, 1H), 7.35 (dd, J=9.3, 1.6 Hz, 1H), 6.74 (q, J=7.1 Hz, 1H), 5.00-4.79 (m, 1H), 2.23 (d, J=7.2 Hz, 3H), 2.16-2.09 (m, 1H), 1.68-1.57 (m, 1H), 1.18-1.09 (m, 1H)); LCMS (electrospray) m/z 485.10 (M+H)+.


Synthetic Method J
Example 446. (1S,2S)-2-fluoro-N-(5-(5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide



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Step 1) (1S,2S)—N-(5-bromopyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

To a mixture of Compound 17 (3.1 g, 14.62 mmol, 1 eq) and (1S,2S)-2-fluorocyclopropanecarboxylic acid (1.67 g, 16.08 mmol, 1.1 eq) in CH3CN (40 mL) was added MsCl (3.35 g, 29.24 mmol, 2.26 mL, 2 eq) and 3-methylpyridine (6.81 g, 73.10 mmol, 7.12 mL, 5 eq) slowly at 0° C. under N2. The mixture was stirred at 30° C. for 3 h. The mixture was concentrated at reduced pressure. The residue was dissolved with ethyl acetate (200 mL) and the resulting mixture was washed with 10% citric acid (30 mL*2), saturated Na2CO3 (30 mL*2), brine (30 mL*2), dried over Na2SO4, filtered and concentrated at reduced pressure to give a residue. The residue was purified by silica gel chromatography (1000 mesh silica gel, Petroleum ether/Ethyl acetate=5/1, 3/1) to give Compound 18 (2.3 g, 7.72 mmol, 52.81% yield) as white solid.


Step 2) (1S,2S)-2-fluoro-N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide

Compound 18 (0.345 g, 1.159 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane, 0.588 g, 2.318 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2, 0.084 g, 0.115 mmol) and potassium acetate (0.398 g, 4.056 mmol) were mixed at the room temperature in DMSO (10 mL) and then stirred at 90° C. for 18 h, cooled down to the room temperature, filtered through a celite pad to remove solids, and partitioned between ethyl acetate and water. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (SiO2, 12 g cartridge; ethyl acetate/hexane=0% to 100%) to give Compound 19 as brown solid (0.289 g, 72.3%).


Step 3) (1S,2S)-2-fluoro-N-(5-(5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

To a mixture of Compound 19 (6 g*, 17.34 mmol, 1 eq) and 4-bromo-5-methyl-1H-indazole (3.6 g, 17.34 mmol, 1 eq) in dioxane (120 mL) and H2O (24 mL) was added Na2CO3 (3.67 g, 34.68 mmol, 2 eq) and Pd(dppf)Cl2 (1.28 g, 1.73 mmol, 0.1 eq) under N2. The mixture was stirred at 90° C. for 4 h. The mixture was concentrated at reduced pressure to give a residue. The residue was purified by silica gel chromatography (1000 mesh silica gel, Petroleum ether/Ethyl acetate=5/1, 1/1; TLC (Petroleum ether:Ethyl acetate=1:1; Rf=0.08) to give 2.5 g of yellow solid. This solid was triturated with CH3CN (10 mL) for two times. The mixture was filtered and the filtered cake was collected. The cake was dispersed with H2O/CH3CN (5:1; 10 mL) and the resulting mixture was lyophilizated for third times to give Example 446 (1.53 g, 4.37 mmol, 25.20% yield, 96.98% purity) as pale solid.



1H NMR (400 MHz, DMSO-d6) δ 13.09 (s, 1H), 11.13 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.74 (s, 1H), 7.63 (d, J=0.9 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.32 (d, J=8.6 Hz, 1H), 6.91 (s, 1H), 6.86 (dd, J=1.9, 7.0 Hz, 1H), 5.06-4.98 (m, 1H), 4.88-4.84 (m, 1H), 2.34 (s, 3H), 2.15 (td, J=6.9, 13.8 Hz, 1H), 1.74-1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (electrospray) m/z 350.1 (M+H)+.


Table 1 below shows the compounds of Examples along with general synthetic methods used to make the compound and characterization data.









TABLE 1







Compounds of Examples













Meth-


Ex #
Structure/Name

1H NMR/MS (M + 1)

od













1


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1H NMR (400 MHz, DMSO-d6) δ 13.04 (s, NH), 12.69 (s, CONH), 8.03 (s, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.63 (s, 1H), 7.48-7.44 (m, 1H), 7.31 (d, J = 8.4 Hz, 1H), 2.30 (s, 3H), 2.02 (t, J = 5.6 Hz, 1H), 0.97 (t, J = 4.0 Hz, 4H); LCMS (electrospray) m/z 349.0 (M + H)+.

A






N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







2


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1H NMR (400 MHz, DMSO-d6) δ 13.04 (s, NH), 12.76 (s, CONH), 8.05 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.63 (s, 2H), 7.49-7.44 (m, 2H), 7.31 (d, J = 8.4 Hz, 1H), 5.05 (td, J12 = 3.3 Hz, J13 = 65.7 Hz, 1H), 2.24 (s, 3H), 2.23-2.24 (m, 1H), 1.78-1.73 (m, 1H), 1.31-1.23 (m, 1H); LCMS (electrospray) m/z 367.1 (M + H)+.

A






(1S,2S)-2-fluoro-N-(6-(5-methyl-1H-





indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide







3


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1H NMR (400 MHz, DMSO-d6) δ 13.03 (s, 1H), 11.80 (s, 1H), 7.99 (s, 1H), 7.78 (d, 8.4 Hz, 1H), 7.63 (s, 1H), 7.46-7.42 (m, 2H), 7.31 (d, 8.4 Hz, 1H), 2.30 (s, 3H), 1.52 (s, 9H); LCMS (electrospray) m/z 381.1 (M + H)+.

A






tert-butyl (6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)carbamate







4


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1H NMR (400 MHz, DMSO-d6) δ 13.02 (br s, 1H), 12.28 (br s, 1H), 8.04 (d, J = 1.3 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.63 (s, 1H), 7.50-7.43 (m, 2H), 7.31 (d, J = 8.4 Hz, 1H), 3.44 (quin, J = 8.5 Hz, 1H), 2.32-2.13 (m, 7H), 2.06-1.92 (m, 1H), 1.90-1.78 (m, 1H); LCMS (electrospray) m/z 363.2 (M + H)+.

A






N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclobutanecarboxamide. 2 TFA







5


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1H NMR (400 MHz, DMSO-d6) δ 13.21-12.83 (m, 2H), 8.08 (d, J = 1.2 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.64 (s, 1H), 7.52-7.43 (m, 2H), 7.32 (d, J = 8.6 Hz, 1H), 3.02 (td, J = 9.5, 13.0 Hz, 1H), 2.30 (s, 3H), 2.23-2.11 (m, 2H); LCMS (electrospray) m/z 385.0 (M + H)+.

A






2,2-difluoro-N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide. 2 TFA salt







6


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1H NMR (400 MHz, DMSO-d6) δ 13.05 (br s, 1H), 12.50 (s, 1H), 8.06 (d, J = 1.3 Hz, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.63 (s, 1H), 7.50-7.44 (m, 2H), 7.32 (d, J = 8.6 Hz, 1H), 5.19-4.95 (m, 1H), 2.97- 2.85 (m, 1H), 2.66-2.57 (m, 2H), 2.45-2.35 (m, 2H), 2.30 (s, 3H); LCMS (electrospray) m/z 381.1 (M + H)+.

A






(1S,3S)-3-fluoro-N-(6-(5-methyl-1H-





indazol-4-yl)benzo[d]thiazol-2-





yl)cyclobutane-1-carboxamide. 2 TFA







7


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1H NMR (400 MHz, DMSO-d6) δ 13.03 (br s, 1H), 12.48 (s, 1H), 8.06 (d, J = 1.3 Hz, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.63 (s, 1H), 7.50-7.43 (m, 2H), 7.32 (d, J = 8.6 Hz, 1H), 5.37-5.15 (m, 1H), 3.45 (br d, J = 3.1 Hz, 1H), 2.65-2.55 (m, 2H), 2.45-2.35 (m, 2H), 2.30 (s, 3H); LCMS (electrospray) m/z 381.1 (M + H)+.

A






(1R,3R)-3-fluoro-N-(6-(5-methyl-1H-





indazol-4-yl)benzo[d]thiazol-2-





yl)cyclobutane-1-carboxamide. 2 TFA







8


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1H NMR (400 MHz, DMSO-d6) δ 13.04(s, 1H), 12.93(s, 1H), 8.16(dd, J = 8.4 Hz, J = 2.0 Hz, 2H), 8.10(s, 1H), 7.91(d, J = 7.6 Hz, 1H), 7.70-7.65(m, 2H), 7.60-7.57(m, 2H), 7.53(dd, J = 8.4 Hz, 2.0 Hz, 1H), 7.47(d, J = 8.4 Hz, 1H), 7.32(d, J = 8.8 Hz, 1H), 2.32(s, 3H); LCMS (electrospray) m/z 385.1 (M + H)+.

A






N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)benzamide







9


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1H NMR (400 MHz, DMSO-d6) δ 12.99 (s, NH), 12.31 (s, NH), 7.99 (s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.44-7.40 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 2.26 (s, 3H), 1.59 (m, 2H), 1.31-1.29 (m, 2H), 0.89-0.85 (m, 3H); LCMS (electrospray) m/z 365.1 (M + H)+.

A






N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)pentanamide







10


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1H NMR (400 MHz, DMSO-d6) δ 12.98 (s, NH), 12.32 (s, NH), 7.99 (s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.44-7.40 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 2.96 (m, 1H), 2.26 (s, 3H), 1.89 (m, 2H), 1.79-1.49 (m, 4H), 1.24-1.20 (m, 1H), 0.83- 0.80 (m, 1H); LCMS (electrospray) m/z 377.1 (M + H)+.

A






N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopentanecarboxamide







11


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1H NMR (400 MHz, DMSO-d6) δ 13.08 (br s, 1H), 12.60 (br s, 1H), 8.07 (d, J = 1.3 Hz, 1H), 7.86 (d, J = 8.2 Hz, 1H), 7.64 (s, 1H), 7.51-7.43 (m, 2H), 7.32 (d, J = 8.6 Hz, 1H), 3.38-3.25 (m, 1H), 2.98- 2.81 (m, 4H), 2.30 (s, 3H); LCMS (electrospray) m/z 377.1 (M + H)+.

A






3,3-difluoro-N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclobutane-1-





carboxamide. 2 TFA







12


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1H NMR (400 MHz, DMSO-d6) d 13.00 (s, 1H), 12.17 (s, 1H), 8.82 (d, J = 4.4 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.16-8.12 (m, 2H), 7.93 (d, J = 8.8 Hz, 1H), 7.76 (dd, J = 7.2, 4.8 Hz, 1H), 7.64 (s, 1H), 7.52 (dd, J = 8.4, 1.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 2.32 (s, 3H); LCMS (electrospray) m/z 386.1 (M + H)+.

A






N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)picolinamide







13


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1H NMR (400 MHz, DMSO-d6) δ 13.31(s, 1H), 12.74(brs, 1H), 8.43(s, 1H), 7.93(d, J = 1.6 Hz, 1H), 7.73(d, J = 2.4 Hz, 1H), 7.71(s, 1H), 7.60(d, J = 3.2 Hz, 2H), 7.36-7.34(m, 1H), 7.31(dd, J = 8.4 Hz, J = 1.2 Hz, 1H), 6.92-6.89(m, 1H), 6.86-6.85(m, 1H), 2.03-1.98(m, 1H), 0.99-0.95(m, 4H); LCMS (electrospray) m/z 417.0 (M + H)+.

B






N-(6-(5-(thiophen-2-yl)-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







14


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1H NMR (400 MHz, DMSO-d6) δ 13.07(s, 1H), 12.62(s, 1H), 8.25(s, 1H), 8.08(s, 1H), 8.03(s, 1H), 7.77-7.67(m, 3H), 7.59(d, J = 8.0 Hz, 1H), 2.00- 1.96(m, 1H), 0.96-0.92(m, 4H); LCMS (electrospray) m/z 335.1 (M + H)+.

A






N-(6-(1H-indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







15


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1H NMR (400 MHz, DMSO-d6) δ 13.27(s, 1H), 12.69(s, 1H), 8.21(s, 1H), 8.00(s, 1H), 7.84(d, J = 8.4 Hz, 1H), 7.65(dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.54(dd, J = 10.8 Hz, J = 9.2 Hz, 1H), 2.02-1.96(m 1H), 0.95-0.93(m, 4H); LCMS (electrospray) m/z 353.1 (M + H)+.

B






N-(6-(5-fluoro-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







16


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1H NMR (400 MHz, DMSO-d6) δ 13.38(s, 1H), 12.74(s, 1H), 8.09(d, J = 1.6 Hz, 1H), 7.83(d, J = 8.8 Hz, 1H), 7.72(s, 1H), 7.55(d, J = 8.8 Hz, 1H), 7.51(dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.46(d, J = 8.8 Hz, 1H), 2.02-1.97(m, 1H), 0.97-0.93(m, 4H); LCMS (electrospray) m/z 369.0 (M + H)+.

B






N-(6-(5-chloro-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







17


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1H NMR (400 MHz, DMSO-d6) δ 13.58(s, 1H), 12.74(s, 1H), 8.03(d, J = 1.6 Hz, 1H), 7.84(d, J = 8.0 Hz, 1H), 7.75(s, 2H), 7.71(s, 1H), 7.44(dd, J = 8.8 Hz, 1.6 Hz, 1H), 20.4-2.00(m, 1H), 0.99-0.96(m, 4H); LCMS (electrospray) m/z 403.0 (M + H)+.

B






N-(6-(5-(trifluoromethyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







18


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1H NMR (400 MHz, DMSO-d6) δ 13.19(s, 1H), 12.64(s, 1H), 7.84(s, 1H), 7.75(s, 1H), 7.65(d, J = 8.0 Hz, 1H), 7.55(d, J = 8.0 Hz, 1H), 7.48(d, J = 8.0 Hz, 1H), 7.29-7.20(m, 3H), 6.63(d, J = 4.0 Hz, 1H), 3.66-3.62(m, 1H), 2.01-1.92(m, 1H), 0.98-0.85(m, 4H); LCMS (electrospray) m/z 417.1 (M + H)+.

B






N-(6-(5-(thiophen-3-yl)-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







19


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1H NMR (400 MHz, DMSO-d6) δ 13.75(s, 1H), 12.71(s, 1H), 8.35(s, 2H), 7.86(d, J = 6.8 Hz, 1H), 7.79(s, 1H), 7.53(d, J = 6.8 Hz, 1H), 7.28(d, J = 6.0 Hz, 1H), 2.05-1.95(m, 1H), 1.10-0.90(m, 4H); LCMS (electrospray) m/z 369.0 (M + H)+.

B






N-(6-(7-chloro-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







20


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1H NMR (400 MHz, DMSO-d6) δ 13.36(s, 1H), 12.73(s, 1H), 8.39(s, 1H), 8.27(s, 1H), 7.88- 7.81(m, 2H), 7.62(s, 1H), 7.31(s, 1H), 2.04- 1.99(m, 1H), 0.99-0.97(m, 4H); LCMS (electrospray) m/z 369.0 (M + H)+.

B






N-(6-(6-chloro-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







21


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, NH), 12.70(s, NH), 7.95 (s, 1H), 7.84-7.82 (m, 2H), 7.75 (d, J = 8.4 Hz, 1H), 7.60(d, J = 9.6 Hz, 1H), 7.44(d, J = 10.0 Hz, 1H), 2.02-1.98(m, 1H), 1.08 (s, 9 H), 0.98-0.96 (m, 4H); LCMS (electrospray) m/z 435.1 (M + H)+.

B






tert-butyl 4-(2-





(cyclopropanecarboxamido)benzo[d]thiazol-





6-yl)-1H-indazole-5-carboxylate







22


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1H NMR (400 MHz, DMSO-d6) δ 13.28(s, 1H), 12.74(s, 1H), 8.43(s, 1H), 8.23(s, 1H), 7.88- 7.87(m, 2H), 7.72-7.71(m, 2H), 7.61-7.59(m, 2H), 7.19(dd, J = 5.2 Hz, J = 3.2 Hz, 1H), 2.07-2.00(m, 1H), 1.01-0.97(m, 4H); LCMS (electrospray) m/z 417.0 (M + H)+.

B






N-(6-(6-(thiophen-2-yl)-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







23


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1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, NH), 12.71 (s, NH), 8.45-8.42 (m, 1H), 8.02 (s, 1H), 7.90 (s, 1H), 7.72-7.70 (d, J = 8.0 Hz, 1H), 7.48- 7.50 (d, J = 8.4 Hz, 1H), 7.46 (m, 4H), 6.76 (m, 1H), 4.24 (d, J = 5.2 Hz, 1H), 2.03-2.01 (m, 1H), 0.99-0.97 (m, 4H); LCMS (electrospray) m/z 474.1 (M + H)+.

B






4-(2-





(cyclopropanecarboxamido)benzo[d]thiazol-





6-yl)-N-(thiophen-3-ylmethyl)-1H-





indazole-5-carboxamide







24


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1H NMR (400 MHz, DMSO-d6) δ 13.03(s, 1H), 12.67(s, 1H), 8.11(d, J = 3.2 Hz, 1H), 7.82-7.80(m, 2H), 7.60(dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.53(d, J = 9.2 Hz, 1H), 7.34(d, J = 8.4 Hz, 1H), 3.75(s, 3H), 2.05-1.98(m, 1H), 0.98-0.96(m, 4H); LCMS (electrospray) m/z 365.1 (M + H)+.

B






N-(6-(5-methoxy-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







25


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1H NMR (400 MHz, DMSO-d6) δ 13.13(s, 1H), 12.72(s, 1H), 8.07(d, J = 1.6 Hz, 1H), 7.84(d, J = 8.0 Hz, 1H), 7.71(s, 1H), 7.58-7.53(m, 3H), 5.15- 5.08(m, 1H), 4.45(d, J = 5.2 Hz, 2H), 2.04-1.99(m, 1H), 1.02-0.96(m, 4H); LCMS (electrospray) m/z 365.0 (M + H)+.

B






N-(6-(5-(hydroxymethyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







26


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1H NMR (400 MHz, DMSO-d6) δ 13.03 (s, NH), 12.77 (s, NH), 7.97 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.49-7.38 (m, 3H), 4.20 (br, NH2), 2.10 (m, 1H), 1.99 (s, 3H), 0.99-0.96 (m, 4H); LCMS (electrospray) m/z 364.1 (M + H)+.

B






N-(6-(3-amino-5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide. 3 HCl







27


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1H NMR (400 MHz, DMSO-d6) δ 12.85 (s, 1H), 12.61 (s, 1H), 9.02 (s, 1H), 8.11 (s, 1H), 7.77-7.75 (m, 2H), 7.65 (d, J = 9.2 Hz, 1H), 7.34 (d, J = 8.6 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 1.97 (quin, J = 6.2 Hz, 1H), 0.94 (d, J = 6.0 Hz, 4H); LCMS (electrospray) m/z 351.40 (M + H)+.

B






N-(6-(5-hydroxy-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







28


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1H NMR (400 MHz, DMSO-d6) δ 13.04(s, 1H), 12.69(s, 1H), 7.99(d, J = 1.2 Hz, 1H), 7.84(d, J = 8.4 Hz, 1H), 7.55(s, 1H), 7.50(d, J = 8.4 Hz, 1H), 7.42(dd, J = 7.6 Hz, 1.6 Hz, 1H), 7.35(d, J = 9.2 Hz, 1H), 2.0(q, J = 7.6 Hz, 2H), 2.05-1.99(m, 1H), 1.08(t, J = 7.6 Hz, 3H), 0.98-0.96(m, 4H); LCMS (electrospray) m/z 363.1 (M + H)+.

B






N-(6-(5-ethyl-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







29


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1H NMR (400 MHz, DMSO-d6) δ 13.68(s, 1H), 12.76(s, 1H), 8.28(d, J = 1.6 Hz, 1H), 8.07(s, 1H), 7.89(d, J = 8.4 Hz, 1H), 7.75(d, J = 9.2 Hz, 1H), 7.69(dd, J = 8.4 Hz, J = 1.6 Hz, 2H), 2.03-1.96(m, 1H), 0.96-0.94(m, 4H); LCMS: m/z = 403.0 (M + H+)LCMS (electrospray) m/z 360.1 (M + H)+.

B






N-(6-(5-cyano-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide







30


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1H NMR (400 MHz, DMSO-d6) 13.37(s, 1H), 12.76(s, 1H), 8.15(d, J = 1.6 Hz, 1H), 7.88(d, J = 8.4 Hz, 1H), 7.77(brs, 1H), 7.60-7.55(m, 2H), 7.50(d, J = 9.2 Hz, 1H), 5.16-4.95(m, 1H), 2.28-2.21(m, 1H), 1.81-1.71(m, 1H), 1.38-1.28(m, 1H); LCMS (electrospray) m/z 387.0 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







31


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1H NMR (400 MHz, DMSO-d6) 12.85(s, 1H), 12.76(s, 1H), 8.19 (s, 1H), 7.81-7.78 (m, 2H), 7.68 (d, J = 9.2 Hz, 1H), 7.56 (d, J = 8.6 Hz, 1H), 7.34 (d, J = 8.6 Hz, 1H), 5.16-4.95 (m, 1H), 4.26 (t, J = 4.4 Hz, 2H), 3.32 (t, J = 4.4 Hz, 2H), 2.45 (s, 6H), 2.28- 2.21(m, 1H), 1.78-1.68 (m, 1H), 1.38-1.28(m, 1H); LCMS (electrospray) m/z 440.10 (M + H)+.

B






(1S,2S)-N-(6-(5-(2-





(dimethylamino)ethoxy)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 3 HCl







32


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1H NMR (400 MHz, DMSO-d6) δ 14.14 (s, NH), 13.08 (s, NH), 8.12 (s, 1H), 7.94-7.92 (m, 1H), 7.65 (s, 1H), 7.55 (dd, J12 = 1.6 Hz, J13 = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H), 2.75 (m, 1H), 2.31 (s, 3H), 1.21-1.17 (m, 4H); LCMS (electrospray) m/z 365.0 (M + H)+.

A






N-(6-(5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarbothioamide







33


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1H NMR (400 MHz, DMSO-d6) δ 13.50(s, 1H), 12.85(s, 1H), 8.11(s, 1H), 7.91(d, J = 8.4 Hz, 2H), 7.85(s, 1H), 7.72(d, J = 4.0 Hz, 2H), 7.50(d, J = 8.8 Hz, 1H), 6.82(t, J = 55.2 Hz, 1H), 5.14-4.98(m, 1H), 2.25-2.22(m, 1H), 1.82-1.72(m, 1H), 1.37-1.30(m, 1H); 19F NMR (400 MHz, DMSO-d6) δ −102.50(d, J = 56.8 Hz, 1H), −103.08(d, J = 56.8 Hz, 1H), 219.66-219.92(m, 1H); LCMS (electrospray) m/z = 403.0 (M + H+)

B






(1S,2S)-N-(6-(5-(difluoromethyl)-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







34


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1H NMR (400 MHz, DMSO-d6) 12.85(s, 1H), 12.77(s, 1H), 8.21 (s, 1H), 7.86 (s, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.32 (d, J = 9.2 Hz, 1H), 5.13-4.96 (m, 1H), 4.08 (t, J = 4.6 Hz, 2H), 3.53 (t, J = 4.4 Hz, 2H), 3.21 (s, 3H), 2.29-2.22(m, 1H), 1.80-1.70 (m, 1H), 1.36-1.27(m, 1H); LCMS (electrospray) m/z 427.10 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(5-(2-





methoxyethoxy)-1H-indazol-4-yl)





benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide. 2 HCl







35


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1H NMR (400 MHz, DMSO-d6) δ 13.22(s, 1H), 12.78(s, 1H), 8.02(d, J = 1.6 Hz, 1H), 7.86(d, J = 8.0 Hz, 1H), 7.77(d, J = 8.8 Hz, 1H), 7.70(s, 1H), 7.55(d, J = 8.8 Hz, 1H), 7.43(dd, J = 8.4 Hz, J = 2.0 Hz, 1H), 6.69(dd, J = 17.6 Hz, J = 10.8 Hz, 1H), 5.76(d, J = 16.4 Hz, 1H), 5.16(d, J = 12.0 hz, 1H), 5.13-4.94(m, 1H), 2.24-2.20(m, 1H), 1.72-1.71(m, 1H), 1.35-1.28(m, 1H); LCMS (electrospray) m/z = 379.1 (M + H+)

B






(1S,2S)-2-fluoro-N-(6-(5-vinyl-1H-





indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide







36


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1H NMR (400 MHz, DMSO-d6) δ 12.77(s, 1H), 8.13(dd, J = 4.4 Hz, 1.6 Hz, 1H), 7.92(dd, J = 8.4 Hz, 6.4 Hz, 1H), 7.88(d, J = 7.6 Hz, 1H), 7.64-7.54(m, 3H), 5.10-4.92(m, 1H), 5.39-5.27(m, 1H), 4.73- 4.60(m, 1H), 2.22-2.21(m, 1H), 1.69-1.68(m, 1H), 1.30-1.25(m, 1H); LCMS (electrospray) m/z = 383.1. (M + H+)

B






(1S,2S)-2-fluoro-N-(6-(5-(fluoromethyl)-





1H-indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide. 2 HCl







37


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1H NMR (400 MHz, DMSO-d6) δ 13.01(s, 1H), 12.74(s, 1H), 8.07(s, 1H), 7.83(dd, J = 8.4 Hz, 1H), 7.58(s, 1H), 7.51(d, J = 8.0 Hz, 1H), 7.41(d, J = 8.8 Hz, 1H), 6.95(dd, J = 8.4 Hz, 1.2 Hz, 1H), 5.10- 4.92(m, 1H), 2.21-2.17(m, 1H), 1.94-1.90(m, 1H), 1.74-1.69(m, 1H), 1.30-1.11(m, 1H), 0.82-0.75(m, 1H), 0.60-0.59(m, 1H); LCMS (electrospray) m/z = 393.1 (M + H+)

B






(1S,2S)-N-(6-(5-cyclopropyl-1H-indazol-





4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







38


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1H NMR (400 MHz, DMSO-d6) δ 12.79(s, 1H), 8.06(d, J = 2.0 Hz, 1H), 7.84(d, J = 8.0 Hz, 1H), 7.67(s, 1H), 7.55-7.53(m, 2H), 7.48(d, J = 8.8 Hz, 1H), 7.39(d, J = 1.2 Hz, 1H), 7.16(d, J = 8.8 Hz, 1H), 6.18-6.17(m, 1H), 5.29(s, 2H), 5.10-4.93(m, 1H), 2.23-2.20(m, 1H), 1.76-1.68(m, 1H), 1.31-1.27(m, 1H); LCMS (electrospray) m/z = 433.1 (M + H+)

B






(1S,2S)-N-(6-(5-((1H-pyrazol-1-





yl)methyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







39


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1H NMR (400 MHz, DMSO-d6) δ 13.35(s, 1H), 12.77(s, 1H), 8.20(d, J = 2.0 Hz, 1H), 7.87(s, 1H), 7.83(d, J = 8.4 Hz, 1H), 7.66(dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.51(d, J = 3.2 Hz, 1H), 5.12-4.91(m, 1H), 3.91(s, 1H), 2.21-2.18(m, 1H), 1.75-1.68(m, 1H), 1.29-1.23(m, 1H); LCMS (electrospray) m/z = 377.1 (M + H+)

B






(1S,2S)-N-(6-(5-ethynyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







40


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1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, NH), 12.80 (s, NH), 8.09 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 9.6 Hz, 1H), 4.96-5.15 (m, 1H), 2.25-2.22 (m, 1H), 2.18 (s, 3H), 1.79-1.72 (m, 1H), 1.33-1.31 (m, 1H); LCMS (electrospray) m/z 385.1 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





1H-indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide







41


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1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, NH), 12.80 (s, NH), 8.09 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 9.6 Hz, 1H), 4.96-5.15 (m, 1H), 2.25-2.22 (m, 1H), 2.18 (s, 3H), 1.79-1.72 (m, 1H), 1.33-1.31 (m, 1H); LCMS (electrospray) m/z 385.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







42


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1H NMR (400 MHz, DMSO-d6) δ 13.46 (s, NH), 12.83 (s, NH), 8.19 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.80 (s, 1H), 7.64 (d, J = 8.8 Hz, 1H), 5.16- 4.95 (m, 1H), 2.28-2.21 (m, 1H), 1.79-1.72 (m, 1H), 1.35-1.28 (m, 1H); LCMS (electrospray) m/z = 405.0 (M + H+)

B






(1S,2S)-N-(6-(5-bromo-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







43


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1H NMR (400 MHz, DMSO-d6) δ 13.59 (s, NH), 12.79 (s, NH), 8.05 (s, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.71 s, 1H), 7.46-7.40 (m, 2H), 6.48 (dd, J12 = 11.8 Hz, J13 = 17.8 Hz, 1H), 5.35 (dd, J12 = 2.6 Hz, J13 = 14.2 Hz, 1H), 5.16-4.95 (m, 1H), 2.26-2.21 (m, 1H), 1.79-1.72 (m, 1H), 1.35-1.29 (m, 1H); LCMS (electrospray) m/z 449.0 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-vinyl-





1H-indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide







44


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1H NMR (400 MHz, DMSO-d6) δ 13.34 (s, 1H), 12.77 (d, J = 3.2 Hz, 1H), 7.88 (d, J = 1.6 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 9.6 Hz, 1H), 7.30 (dd, J = 2.0, 6.4 Hz, 1H), 5.10 (m, 0.5H), 4.93 (m, 0.5H), 2.20 (m, 1H), 2.00 (m, 3H), 1.71 (m, 1H), 1.28 (m, 1H), LCMS (electrospray) m/z 419.05 (M + H)+.

B






(1S,2S)-N-(6-(3-chloro-6-fluoro-5-methyl-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







45


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1H NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 12.79 (d, J = 3.6 Hz, 1H), 7.87 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.41 (d, J = 10.0 Hz, 1H), 7.28 (dd, J = 1.6 Hz, 1H), 5.14 (m, 0.5H), 4.97 (m, 0.5H), 2.23 (m, 1H), 2.00 (m, 3H), 1.76 (m, 1H), 1.31 (m, 1H), LCMS (electrospray) m/z 511.00 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-3-iodo-5-





methyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)cyclopropane-1-carboxamide







46


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1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, NH), 12.80 (s, NH), 8.04 (s, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.44 (d, J = 8.4 Hz, 1H), 5.15-4.96 (m, 1H), 2.58-2.54 (m, 2H), 2.25-2.22 (m, 1H), 1.78- 1.72 (m, 1H), 1.33-1.30 (m, 1H), 1.06 (t, 3H); LCMS (electrospray) m/z 399.1 (M + H)+.

B






(1S,2S)-N-(6-(5-ethyl-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







47


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1H NMR (400 MHz, DMSO-d6) δ 13.41(s, 1H), 12.78(s, 1H), 8.23(d, J = 1.6 Hz, 1H), 7.89(s, 1H), 7.84(d, J = 8.4 Hz, 1H), 7.67(d, J = 8.4 Hz, 1H), 7.46(d, J = 9.6 Hz, 1H), 5.11-4.92(m, 1H), 4.19(s, 1H), 2.21-2.18(m, 1H), 1.77-1.67(m, 1H), 1.33- 1.25(m, 1H); LCMS (electrospray) m/z 395.1 (M + H+)

B






(1S,2S)-N-(6-(5-ethynyl-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







48


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1H NMR (400 MHz, DMSO-d6) δ 13.34(s, 1H), 12.77(s, 1H), 8.01(d, J = 2.0 Hz, 1H), 7.84(d, J = 8.4 Hz, 1H), 7.60(s, 1H), 7.45(d, J = 8.4 Hz, 1H), 7.41(dd, J = 8.4 Hz, J = 1.2 Hz, 1H), 5.12-4.92(m, 1H), 2.21-2.19(m, 1H), 1.76-1.69(m, 1H), 1.31- 1.26(m, 1H); LCMS (electrospray) m/z 497.0 (M + H+)

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-iodo-





1H-indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide







49


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1H NMR (400 MHz, DMSO-d6) δ 13.49 (s, 1H), 12.78 (d, J = 3.6 Hz, 1H), 7.89 (d, J = 1.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 10 Hz, 1H), 7.31 (dd, J = 1.6, 6.8 Hz, 1H), 5.14 (m, 0.5H), 4.95 (m, 0.5H), 2.24 (m, 1H), 2.02 (t, J = 2.4 Hz, 3H), 1.75 (m, 1H), 1.31 (m, 1H); LCMS (electrospray) m/z 464.00 (M + H)+.

B






(1S,2S)-N-(6-(3-bromo-6-fluoro-5-methyl-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







50


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1H NMR (400 MHz, DMSO-d6) δ 13.67(s, 1H), 12.82(s, 1H), 8.03(s, 1H), 7.82(d, J = 8.4 Hz, 1H), 7.66-7.64(m, 1H), 7.41(d, J = 8.4 Hz, 1H), 5.15- 4.95(m, 1H), 2.26-2.23(m, 1H), 1.79-1.72(m, 1H), 1.34-1.28(m, 1H); LCMS (electrospray) LCMS: m/z 439.1 (M + H+)

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-





(trifluoromethyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide







51


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1H NMR (400 MHz, DMSO-d6) δ 13.75 (s, 1H), 12.82 (s, 1H), 8.09 (d, J = 1.6 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.79 (brs, 1H), 7.50 (dd, J = 1.6, 6.4 Hz, 1H), 5.14 (m, 0.5H), 4.97 (m, 0.5H), 2.23 (m, 4H), 1.76 (m, 1H), 1.32 (m, 1H); LCMS (electrospray) m/z 419.00 (M + H)+.

B






(1S,2S)-N-(6-(7-chloro-6-fluoro-5-methyl-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







52


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1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 12.81 (s, 1H), 7.91 (d, J = 1.6 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.33 (m, 2H), 5.73 (m, 1H), 5.59 (m, 1H), 5.14 (m, 0.5H), 4.97 (m, 0.5H), 4.84 (m, 1H), 2.25 (m, 1H), 2.01 (t, J = 2.4 Hz, 3H) 1.76 (m, 1H), 1.32 (m, 1H); LCMS (electrospray) m/z 411.10 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





3-vinyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)cyclopropane-1-carboxamide







53


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1H NMR (400 MHz, DMSO-d6) δ 14.00(s, 1H), 12.80(s, 1H), 7.92(d, J = 1.2 Hz, 1H), 7.84(d, J = 8.4 Hz, 1H), 7.34(dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 5.15- 4.97(m, 1H), 2.26-2.24(m, 1H), 2.08(s, 3H), 1.79- 1.76(m, 1H), 1.32-1.27(m, 1H); LCMS (electrospray) m/z 454.0 (M + H+)

B






(1S,2S)-N-(6-(3,7-dichloro-6-fluoro-5-





methyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)-2-fluorocyclopropane-1-carboxamide







54


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1H NMR (400 MHz, DMSO-d6) δ 14.03(s, 1H), 13.21(s, 1H), 7.94(d, J = 1.6 Hz, 1H), 7.50(d, J = 1.6 Hz, 1H), 5.14-4.95(m, 1H), 2.25-2.22(m, 1H), 2.09(s, 3H), 1.80-1.70(m, 1H), 1.36-1.29(m, 1H); LCMS (electrospray) m/z 487.0 (M + H+)

B






(1S,2S)-N-(4-chloro-6-(3,7-dichloro-6-





fluoro-5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







55


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1H NMR (400 MHz, DMSO-d6) δ 13.33(s, 1H), 12.80(s, 1H), 8.06(s, 1H), 7.84(d, J = 8.0 Hz, 1H), 7.43-7.41(m, 1H), 5.13-4.97(m, 1H), 2.23-2.20(m, 1H), 2.16(s, 3H), 1.77-1.72(m, 1H), 1.44-1.41(m, 1H); LCMS (electrospray): m/z 421.0 (M + H+)

B






(1S,2S)-2-fluoro-N-(6-(3,6,7-trifluoro-5-





methyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)cyclopropane-1-carboxamide







56


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1H NMR (400 MHz, DMSO-d6) δ 12.78 (s, 1H), 12.60 (s, 1H), 8.09 (s, 1H), 8.06 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.43-7.41 (m, 1H), 5.13-4.97 (m, 1H), 2.23-2.20 (m, 1H), 2.16 (s, 3H), 1.77-1.72 (m, 1H), 1.44-1.41 (m, 1H); LCMS (electrospray): m/z 403.0 (M + H)+.

B






(1S,2S)-N-(6-(6,7-difluoro-5-methyl-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







57


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1H NMR (400 MHz, DMSO-d6) δ 13.59 (s, 1H), 12.81 (s, 1H), 8.15 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.34 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 5.18-5.12 (m, 0.5H), 5.01-4.96 (m, 0.5H), 2.50 (t, J = 1.6 Hz, 3H), 2.29-2.21 (m, 1H), 1.85-1.72 (m, 1H), 1.38-1.29 (m, 1H); LCMS (electrospray) m/z 419.0 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-methyl-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







58


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1H NMR (400 MHz, DMSO-d6) δ 13.76 (br s, 1H), 12.82 (br s, 1H), 8.19 (d, J = 1.7 Hz, 1H), 7.96-7.82 (m, 2H), 7.59 (dd, J = 1.8, 8.4 Hz, 1H), 5.26-4.85 (m, 1H), 2.57 (s, 3H), 2.30-2.19 (m, 1H), 1.84- 1.69 (m, 1H), 1.33 (tdd, J = 6.4, 9.0, 12.9 Hz, 1H); LCMS (electrospray) m/z 450.8 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







59


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1H NMR (400 MHz, DMSO-d6) δ 13.36 (s, 1H), 12.77 (br s, 1H), 8.04 (s, 1H), 7.87 (dd, J12 = 4.8 Hz, J13 = 8.4 Hz, 1H), 7.66 (s, 1H), 7.45 (d, J = 7,6 Hz, 1H), 5.14-4.95 (m, 1H), 2.49 (d, J = 1.7 Hz, 3H), 2.21 (d, J = 2.8 Hz, 3H), 2.18-2.10 (m, 1H), 1.75-1.61 (m, 1H), 1.27-1.10 (m, 1H); LCMS (electrospray) m/z 399.1 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-





dimethyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)cyclopropane-1-carboxamide. 2 TFA







60


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1H NMR (400 MHz, DMSO-d6) δ 12.87 (s, 1H), 12.85 (s, 1H), 8.22 (s, 1H), 7.88 (m, 2H), 7.60 (dd, J12 = 1.8 Hz, J13 = 8.2 Hz, 1H), 5.13-4.97 (m, 1H), 2.28-2.21 (m, 1H), 1.95 (s, 3H), 1.92 (s, 3H), 1.81- 1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (electrospray) m/z 481.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-7-





(dimethylphosphoryl)-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







61


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1H NMR (400 MHz, DMSO-d6) δ 13.70 (s, 1H), 12.82 (s, 1H), 8.19 (d, J = 2.0 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.59 (dd, J = 6.8 Hz, J = 2.0 Hz, 1H), 7.10 (q, J = 12.4 Hz, 1H), 6.22 (brs, 1H), 5.81 (d, J = 11.6 Hz, 1H), 5.16-5.12 (m, 0.5H), 4.99-4.96 (m, 0.5H), 2.28-2.21 (m, 1H), 1.81-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (electrospray) m/z 431.0 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-vinyl-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







62


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1H NMR (400 MHz, DMSO-d6) δ 13.37 (s, 1H), 12.79 (s, 1H), 8.08 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.11-7.09 (m, 1H), 6.16 (d, J = 18.4 Hz, 1H), 5.70 (d, J = 12.0 Hz, 1H), 5.14-4.97 (m, 1H), 2.28-2.21 (m, 1H), 2.20 (s, 3H), 1.81-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (electrospray) m/z 411.1 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-vinyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)cyclopropane-1-carboxamide







63


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1H NMR (400 MHz, DMSO-d6) δ 12.85 (s, 1H), 8.22 (s, 1H), 7.96-7.89 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.11-7.09 (m, 1H), 7.60 (d, J = 8.0 Hz, 1H), 5.14-4.97 (m, 1H), 3.19 (s, 3H), 2.28-2.21 (m, 1H), 1.79-1.73 (m, 1H), 1.37-1.28 (m, 1H); LCMS (electrospray) m/z 467.0 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methylsulfinyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 HCl





salt







64


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1H NMR (400 MHz, DMSO-d6) δ 12.79 (br s, 1H), 8.08 (s, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.73 (s, 1H), 7.49 (d, J = 9.6 Hz, 1H), 5.14-4.96 (m, 1H), 3.17 (s, 3H), 2.54 (s, 3H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS (electrospray) m/z 431.0 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide







65


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1H NMR (400 MHz, METHANOL-d4) δ 8.44- 8.32 (m, 2H), 7.84-7.76 (m, 1H), 7.42-7.25 (m, 5H), 5.07-5.01 (m, 1H), 3.27-2.97 (m, 5H), 2.24- 2.15 (m, 1H), 2.06 (br d, J = 2.2 Hz, 3H), 1.96- 1.81 (m, 1H), 1.38-1.28 (m, 1H); LCMS (electrospray) m/z 490.2 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





1H-indazol-4-yl)-7-(2-(pyridin-4-





yl)ethyl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide. 3 TFA







66


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1H NMR (400 MHz, DMSO-d6) δ 13.36 (br s, 1H), 12.81 (s, 1H), 8.12 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 5.14-4.96 (m, 1H), 3.13 (s, 3H), 2.32 (s, 3H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS (electrospray) m/z 447.1 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(methylsulfinyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide. 2 HCl







67


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1H NMR (400 MHz, DMSO-d6) δ 13.35 (s, 1H), 12.79 (s, 1H), 8.08 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.83 (br s, 1H), 7.48 (dd, J = 1.6, 6.8 Hz, 1H), 5.14- 4.96 (m, 1H), 2.26-2.18 (m, 4H), 1.82-1.71 (m, 1H), 1.36-1.28 (m, 1H); LCMS (electrospray) m/z 511.00 (M + H)+.

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-iodo-5-





methyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)cyclopropane-1-carboxamide







68


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1H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 12.76 (s, 1H), 8.08 (d, J = 1.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.71 (s, 1H), 7.52 (dd, J = 2.4, 6.4 Hz, 1H), 5.69 (s, 2H), 5.16-4.94 (m, 1H), 2.27- 2.20 (m, 1H), 1.81-1.70 (m, 1H), 1.36-1.27 (m, 1H); LCMS (electrospray) m/z 420.00 (M + H)+.

B






(1S,2S)-N-(6-(7-amino-5-chloro-6-fluoro-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







69


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (s, 1H), 12.79 (s, 1H), 8.13 (d, J = 1.6 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.76 (s, 1H), 7.55 (dd, J = 1.6, 6.8 Hz, 1H), 5.16-4.95 (m, 1H), 2.99 (s, 6H), 2.28- 2.21 (m, 1H), 1.81-1.71 (m, 1H), 1.36-1.28 (m, 1H); LCMS (electrospray) m/z 448.10 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







70


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1H NMR (400 MHz, DMSO-d6) δ 13.70 (br s, 1H), 12.81 (s, 1H), 8.15 (s, 1H), 7.96 (br s, 2H), 7.90- 7.86 (m, 2H), 7.55 (d, J = 8.4 Hz, 1H), 5.11-4.92 (m, 1H), 3.14 (m, 2H), 2.88 (m, 2H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.25- 1.11 (m, 1H); LCMS (electrospray) m/z 480.1 (M + H)+.

B






(1S,2S)-N-(6-(7-((2-aminoethyl)thio)-5-





chloro-6-fluoro-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 3 HCl







71


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1H NMR (400 MHz, DMSO-d6) δ 13.76 (s, 1H), 12.82 (s, 1H), 8.17 (d, J = 0.8 Hz, 1H), 7.88 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.58 (dd, J = 1.6, 6.8 Hz, 1H), 5.14-4.94 (m, 1H), 3.50 (t, J = 6.0 Hz, 2H), 3.20 (s, 3H), 3.17 (t, J = 6.4 Hz, 2H), 2.26-2.19 (m, 1H), 1.80-1.70 (m, 1H), 1.35-1.26 (m, 1H); LCMS (electrospray) m/z 495.10 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((2-





methoxyethyl)thio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







72


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1H NMR (400 MHz, DMSO-d6) δ 13.29 (s, 1H), 10.42 (s, 1H), 7.80 (s, 1H), 7.75 (d, J = 1.6 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.31 (dd, J = 1.6, 6.8 Hz, 1H), 6.58 (q, J = 10 Hz, 1H), 6.32 (dd, J = 1.6, 15.2 HZ, 1H), 5.83 (d, J = 10 Hz, 1H), 4.86-4.65 (m, 1H), 1.95 (d, J = 14 Hz, 1H), 1.85 (m, 1H), 1.69- 1.55 (m, 1H), 0.95-0.87 (m, 1H); LCMS (electrospray) m/z 474.00 (M + H)+.

B






(1S,2S)-N-(6-(7-acrylamido-5-chloro-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropane-1-carboxamide







73


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1H NMR (400 MHz, DMSO-d6) δ 13.78 (br s, 1H), 12.81 (s, 1H), 8.18 (s, 1H), 7.99 (t, J = 5.2 Hz, 1H), 7.89-7.87 (m, 2H), 7.59 (d, J = 8.4 Hz, 1H), 5.13- 4.96 (m, 1H), 3.29 (m, 2H), 3.00 (m, 2H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 1.75 (s, 3H), 1.74-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS (electrospray) m/z 522.1 (M + H)+.

B






(1S,2S)-N-(6-(7-((2-acetamidoethyl)thio)-





5-chloro-6-fluoro-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







74


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1H NMR (400 MHz, DMSO-d6) δ 13.50 (br s, 1H), 12.82 (s, 1H), 8.14 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.81 (s, 1H), 7.55 (d, J = 8.4 Hz, 1H), 5.14-4.76 (m, 1H), 3.83 (m, 4H), 3.28 (m, 4H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS (electrospray) m/z 490.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





morpholino-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 HCl







75


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1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H), 12.82 (s, 1H), 8.13 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.84 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H), 5.16-4.97 (m, 1H), 3.55 (br s, 6H), 3.39 (br s, 2H), 2.90 (d, J = 8.0 Hz, 3H), 2.19-2.10 (m, 1H), 1.73-1.60 (m, 1H), 1.35-1.28 (m, 1H); LCMS (electrospray) m/z 503.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(4-





methylpiperazin-1-yl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 3 HCl







76


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1H NMR (400 MHz, DMSO-d6) δ 13.56 (s, 1H), 12.82 (s, 1H), 8.71 (br s, 1H), 8.13 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.84 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H), 5.13-4.98 (m, 1H), 3.38 (br s, 4H), 2.66 (br s, 4H), 2.19-2.10 (m, 1H), 1.79-1.73 (m, 1H), 1.35-1.28 (m, 1H); LCMS (electrospray) m/z 489.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(piperazin-1-yl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 3 TFA







77


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1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 12.78 (s, 1H), 8.08 (s, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 7.51 (d, J = 8.4 Hz, 1H), 5.12-4.96 (m, 1H), 3.65 (br s, 4H), 2.19-2.10 (m, 1H), 1.95 (br s, 4H), 1.77-1.73 (m, 1H), 1.35-1.28 (m, 1H); LCMS (electrospray) m/z 473.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(pyrrolidin-1-yl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







78


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1H NMR (400 MHz, DMSO-d6) δ 13.17 (s, 1H), 12.79 (s, 1H), 8.09 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.83 (d, J = 6.4, Hz, 1H), 5.14-4.97 (m, 2H), 4.41 (s, 1H), 3.97 (s, 2H), 3.73-3.35 (m, 2H), 2.29-2.18 (m, 1H), 2.10-1.98 (m, 1H), 1.94- 1.85 (m, 1H), 1.82-1.70 (m, 1H), 1.38-1.27 (m, 1H); LCMS (electrospray) m/z 490.10 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-





hydroxypyrrolidin-1-yl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







79


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1H NMR (400 MHz, DMSO-d6) δ 13.75 (s, 1H), 12.84 (s, 1H), 8.20 (s, 1H), 7.94-7.82 (m, 2H), 7.60 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 6.4, Hz, 1H), 5.18-4.87 (m, 2H), 3.52 (q, J = 5.2 Hz, 2H), 3.06 (t, J = 5.6 Hz, 2H), 2.29-2.18 (m, 1H), 1.83-1.69 (m, 1H), 1.39-1.27 (m, 1H); LCMS (electrospray) m/z 481.05 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((2-





hydroxyethyl)thio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







80


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1H NMR (400 MHz, DMSO-d6) δ 13.78 (br s, 1H), 12.81 (s, 1H), 8.14 (d, J = 1.4 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.86-7.79 (m, 1H), 7.55 (dd, J = 1.8, 8.4 Hz, 1H), 5.25-4.85 (m, 1H), 4.15 (s, 3H), 2.30- 2.18 (m, 1H), 1.85-1.68 (m, 1H), 1.33 (tdd, J = 6.4, 9.0, 12.7 Hz, 1H); LCMS (electrospray) m/z 435.3 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





methoxy-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







81


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1H NMR (400 MHz, DMSO-d6) δ13.77 (s, 1H), 12.82 (s, 1H), 8.16 (d, J = 1.5 Hz, 1H), 7.92-7.87 (m, 1H), 7.84-7.80 (m, 1H), 7.62-7.53 (m, 1H), 5.27-4.92 (m, 1H), 4.38 (q, J = 7.0 Hz, 2H), 2.30- 2.20 (m, 1H), 1.88-1.71 (m, 1H), 1.42 (t, J = 7.0 Hz, 3H), 1.38-1.29 (m, 1H); LCMS (electrospray) m/z 449.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-7-ethoxy-6-fluoro-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







82


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1H NMR (400 MHz, DMSO-d6) δ 7.91 (s, 1H), 7.74 (s, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.40 (dd, J = 1.6, 6.8, Hz, 1H), 5.02-4.78 (m, 1H), 3.23 (t, J = 5.6 Hz, 2H), 2.99 (d, J = 4 Hz, 3H), 2.80 (t, J = 6.0 2H), 2.09-1.99 (m, 1H), 1.74-1.62 (m, 1H), 1.16-1.07 (m, 1H); LCMS (electrospray) m/z 477.10 (M + H)+.

B






(1S,2S)-N-(6-(7-((2-





aminoethyl)(methyl)amino)-5-chloro-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropane-1-carboxamide







83


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1H NMR (400 MHz, DMSO-d6) δ 8.07 (d, J = 1.6 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.78 (s, 1H), 7.51 (dd, J = 2.0, 6.4 Hz, 1H), 5.14-4.91 (m, 1H), 3.48 (m, 2H), 3.16 (t, J = 12 Hz 2H), 2.87-2.78(m, 1H), 2.24-2.15 (m, 1H), 1.85 (d, J = 10.4 Hz, 2H), 1.80- 1.68 (m, 1H), 1.66-1.54 (m, 2H), 1.33-1.24 (m, 1H); LCMS (electrospray) m/z 503.10 (M + H)+.

B






(1S,2S)-N-(6-(7-(4-aminopiperidin-1-yl)-





5-chloro-6-fluoro-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







84


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1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, J = 1.6 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.53 (dd, J = 1.6, 8.0 Hz, 1H), 5.15-4.93 (m, 1H), 3.26- 3.17 (m, 2H), 3.12-2.96 (m, 2H), 2.89-2.81 (m, 1H), 2.26-2.17 (m, 1H), 1.91-1.68 (m, 4H), 1.35- 1.23 (m, 2H); LCMS (electrospray) m/z 503.1 (M + H)+.

B






(1S,2S)-N-(6-(7-(3-aminopiperidin-1-yl)-





5-chloro-6-fluoro-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







85


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1H NMR (400 MHz, DMSO-d6) δ 13.94 (s, 1H), 12.83 (s, 1H), 8.15 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 5.14-4.97 (m, 1H), 3.61 (s, 3H), 3.41-3.38 (m, 2H), 2.87- 2.84 (m, 2H), 2.78 (s, 6H), 2.26-2.23 (m, 1H), 1.73- 1.65 (m, 1H), 1.31-1.23 (m, 1H); LCMS (electrospray) m/z 505.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-7-((2-





(dimethylamino)ethyl)(methyl)amino)-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropane-1-carboxamide.





3 HCl







86


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1H NMR (400 MHz, DMSO-d6) δ 13.94 (s, 1H), 12.85 (s, 1H), 8.19 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.60 (d, J = 8.0 Hz, 1H), 5.14-4.97 (m, 1H), 3.61-3.57 (m, 2H), 3.04-3.01 (m, 2H), 2.87-2.84 (m, 2H), 2.26-2.23 (m, 1H), 1.73-1.65 (m, 1H), 1.64-1.61 (m, 2H), 1.31-1.23 (m, 1H); LCMS (electrospray) m/z 495.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((3-





hydroxypropyl)thio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropanecarboxamide. 2 HCl







87


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1H NMR (400 MHz, DMSO-d6) δ 13.86 (s, 1H), 12.84 (s, 1H), 8.19 (d, J = 1.6 Hz, 1H), 8.13-8.05 (m, 1H), 7.95-7.85 (m, 2H), 7.59 (dd, J = 1.6, 8.4 Hz, 1H), 5.18-4.95 (m, 1H), 3.66 (s, 2H), 2.58 (d, J = 1.4 Hz, 3H), 2.29-2.21 (m, 1H), 1.83-1.69 (m, 1H), 1.38-1.28 (m, 1H); LCMS (electrospray) m/z 509.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((2-





(methylamino)-2-oxoethyl)thio)-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropanecarboxamide







88


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1H NMR (400 MHz, DMSO-d6) δ 13.56 (s, 1H), 12.83 (s, 1H), 8.19 (d, J = 1.6 Hz, 1H), 7.93-7.81 (m, 2H), 7.59 (dd, J = 2.0, 8.0 Hz, 1H), 7.20 (s, 1H), 5.17-4.95 (m, 2H), 4.01 (s, J = 8.8 Hz, 1H), 3.91-3.82 (m, 1H), 3.67-3.60 (m, 1H), 3.55 (t, J = 5.2 Hz, 2H), 2.29-2.21 (m, 1H), 1.83-1.70 (m, 1H), 1.38-1.28 (m, 1H); LCMS (electrospray) m/z 519.1 (M + H)+.

B






(1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-1H-





indazol-7-yl)azetidin-3-yl)carbamic acid







89


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1H NMR (400 MHz, DMSO-d6) δ 13.25 (s, 1H), 12.78 (s, 1H), 8.09 (d, J = 1.6 Hz, 1H), 7.90-7.70 (m, 2H), 7.52 (dd, J = 1.6, 8.4 Hz, 1H), 7.20 (s, 1H), 5.67-5.47 (s, 1H), 5.17-4.93 (m, 1H), 4.43- 4.16 (m, 2H), 4.04-3.96 (m, 1H), 3.89-3.52 (m, 2H), 2.86 (s, 3H), 2.29-2.20 (m, 1H), 1.83-1.68 (m, 1H), 1.38-1.27 (m, 1H); LCMS (electrospray) m/z 533.1 (M + H)+

B






(1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-1H-





indazol-7-yl)azetidin-3-





yl)(methyl)carbamic acid







90


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1H NMR (400 MHz, DMSO-d6) δ 13.13 (s, 1H), 12.78 (s, 1H), 8.10 (d, J = 1.6 Hz, 1H), 7.89-7.68 (m, 2H), 7.52 (dd, J = 2.4, 8.8 Hz, 1H), 7.21 (s, 1H), 5.82-5.62 (s, 1H), 5.17-4.94 (m, 1H), 4.33- 4.23 (m, 1H), 4.15-4.06 (m, 1H), 3.67-3.43 (m, 2H), 3.34-3.26 (m, 1H), 3.12-3.05 (m, 1H), 2.31- 2.15 (m, 2H), 1.84-1.69 (m, 1H), 1.39-1.26 (m, 1H); LCMS (electrospray) m/z 533.1 (M + H)+.

B






((1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-1H-





indazol-7-yl)azetidin-3-





yl)methyl)carbamic acid







91


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1H NMR (400 MHz, DMSO-d6) δ 7.85 (s, 1H), 7.76 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.36 (dd, J = 1.6, 8.4 Hz, 1H), 5.02-4.78 (m, 1H), 4.04-3.87 (m, 1H), 3.78-3.61 (m, 2H), 3.58-3.48 (m, 1H), 2.72-2.59 (m, 2H), 2.34-2.26 (m, 1H), 2.09-1.92 (m, 2H), 1.74-1.61 (m, 4H), 1.15-1.02 (m, 1H); LCMS (electrospray) m/z 503.1 (M + H)+.

B






(1S,2S)-N-(6-(7-(3-





(aminomethyl)pyrrolidin-1-yl)-5-chloro-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropanecarboxamide







92


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 12.82 (s, 1H), 8.22 (s, 1H), 8.14 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.85 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 5.14-4.97 (m, 1H), 2.89 (m, 2H), 2.65 (t, J = 5.2 Hz, 2H), 2.26-2.23 (m, 1H), 1.73-1.65 (m, 1H), 1.31-1.23 (m, 1H); LCMS (electrospray) m/z 491.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methyl(2-(methylamino)ethyl)amino)-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







93


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 12.81 (s, 1H), 8.22 (s, 1H), 8.14 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 5.14-4.96 (m, 1H), 3.64-3.61 (m, 2H), 3.35- 3.32 (m, 2H), 3.02 (s, 3H), 2.26-2.23 (m, 1H), 1.73- 1.65 (m, 1H), 1.31-1.23 (m, 1H); LCMS (electrospray) m/z 478.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((2-





hydroxyethyl)(methyl)amino)-1H-indazol-





4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropanecarboxamide. 2 HCl







94


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1H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 12.82 (s, 1H), 8.49 (br, 1H), 8.38 (br, 1H), 8.14 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.72 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 5.16-4.97 (m, 1H), 3.96-3.91 (m, 2H), 3.67-3.64 (m, 2H), 2.90 (s, 3H), 2.26-2.23 (m, 1H), 1.79-1.72 (m, 1H), 1.37-1.30 (m, 1H), 1.08 (t, J = 7.2 Hz, 1H); LCMS (electrospray) m/z 503.1 (M + H)+.

B






(1S,2S)-N-(6-(7-((azetidin-3-





ylmethyl)(methyl)amino)-5-chloro-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropanecarboxamide. 3





TFA







95


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1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 12.78 (s, 1H), 8.57 (br, 2H), 8.08 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.51 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 5.16-4.95 (m, 1H), 4.00 (m, 2H), 3.92 (m, 2H), 3.71 (br, 2H), 3.05 (br, 1H), 2.25- 2.20 (m, 1H), 1.78-1.68 (m, 1H), 1.36-1.28 (m, 1H), 1.08 (t, J = 7.2 Hz, 1H); LCMS (electrospray) m/z 489.1 (M + H)+.

B






(1S,2S)-N-(6-(7-((azetidin-3-





ylmethyl)amino)-5-chloro-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropanecarboxamide. 3 TFA







96


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1H NMR (400 MHz, DMSO-d6) δ 13.26 (br s, 1H), 12.74 (s, 1H), 8.00 (d, J = 1.4 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.60 (s, 1H), 7.44 (dd, J = 1.7, 8.3 Hz, 1H), 6.81 (s, 1H), 5.16-4.94 (m, 1H), 3.98 (s, 3H), 2.31 (s, 3H), 2.27-2.19 (m, 1H), 1.82-1.68 (m, 1H), 1.32 (tdd, J = 6.3, 9.0, 12.8 Hz, 1H); LCMS(electrospray) m/z 397.4 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(7-methoxy-5-





methyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)cyclopropanecarboxamide. 2 TFA







97


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (br s, 1H), 12.76 (s, 1H), 8.04 (d, J = 1.3 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.69 (s, 1H), 7.46 (dd, J = 1.7, 8.3 Hz, 1H), 5.18-4.89 (m, 1H), 4.08 (d, J = 0.9 Hz, 3H), 2.29-2.22 (m, 1H), 2.20 (d, J = 3.2 Hz, 3H), 1.83-1.69 (m, 1H), 1.32 (tdd, J = 6.4, 8.8, 12.8 Hz, 1H); LCMS(electrospray) m/z 415.4 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-





methoxy-5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-





yl)cyclopropanecarboxamide. 2 TFA







98


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1H NMR (400 MHz, DMSO-d6) 13.42 (br s, 1H), 12.78 (s, 1H), 8.05 (d, J = 1.3 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.68 (s, 1H), 7.47 (dd, J = 1.5, 8.3 Hz, 1H), 5.22-4.90 (m, 1H), 4.30 (br d, J = 7.1 Hz, 2H), 2.23 (br d, J = 7.0 Hz, 1H), 2.19 (d, J = 3.1 Hz, 3H), 1.80-1.70 (m, 1H), 1.39 (t, J = 7.0 Hz, 3H), 1.35-1.28 (m, 1H); LCMS(electrospray) m/z 429.4 (M + H+).

B






(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-





methyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)-2-fluorocyclopropanecatboxamide. 2





TFA







99


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1H NMR (400 MHz, DMSO-d6) δ 13.76 (s, 1H), 12.84 (s, 1H), 8.19 (d, J = 2.0 Hz, 1H), 7.94-7.84 (m, 2H), 7.59 (dd, J = 1.6, 8.0 Hz, 1H), 5.17-4.95 (m, 1H), 4.03 (s, 2H), 3.01 (s, 3H), 2.81 (s, 3H), 2.29-2.20 (m, 1H), 1.82-1.70 (m, 1H), 1.38-1.28 (m, 1H); LCMS (electrospray) m/z 522.10 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-7-((2-





(dimethylamino)-2-oxoethyl)thio)-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropane-1-carboxamide







100


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 12.80 (s, 1H), 8.12 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.54 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 5.14-4.96 (m, 1H), 3.62 (s, 2H), 3.37 (s, 6H), 3.15 (s, 3H), 2.25-2.20 (m, 1H), 1.78-1.68 (m, 1H), 1.34-1.28 (m, 1H); LCMS (electrospray) m/z 519.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-7-((2-





(dimethylamino)-2-





oxoethyl)(methyl)amino)-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







101


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1H NMR (400 MHz, DMSO-d6) δ 13.22 (br s, 1H), 12.74 (s, 1H), 8.00 (d, J = 1.3 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.60 (s, 1H), 7.44 (dd, J = 1.8, 8.3 Hz, 1H), 6.79 (s, 1H), 5.17-4.93 (m, 1H), 4.27 (q, J = 7.1 Hz, 2H), 2.29 (s, 3H), 2.27-2.20 (m, 1H), 1.82- 1.69 (m, 1H), 1.46 (t, J = 7.0 Hz, 3H), 1.32 (tdd, J = 6.4, 8.9, 12.8 Hz, 1H); LCMS(electrospray) m/z 410.9 (M + H+).

B






(1S,2S)-N-(6-(7-ethoxy-5-methyl-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







102


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1H NMR (400 MHz, DMSO-d6) δ 13.16 (br s, 1H), 12.77 (s, 1H), 8.00 (d, J = 1.6 Hz, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.55 (s, 1H), 7.42 (dd, J = 1.6, 8.3 Hz, 1H), 5.18-4.93 (m, 1H), 2.96 (s, 3H), 2.96 (s, 3H), 2.56-2.52 (m, 2H), 2.29-2.20 (m, 1H), 1.82- 1.71 (m, 1H), 1.32 (tdd, J = 6.6, 9.0, 12.8 Hz, 1H), 1.07 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 442.2 (M + H+).

B






(1S,2S)-N-(6-(7-(dimethylamino)-5-ethyl-





6-fluoro-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







103


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (br s, 1H), 12.80 (s, 1H), 8.05 (d, J = 1.3 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.64 (s, 1H), 7.45 (dd, J = 1.8, 8.3 Hz, 1H), 5.18-4.92 (m, 1H), 2.59 (br d, J = 6.9 Hz, 2H), 2.52 (br s, 3H), 2.29-2.20 (m, 1H), 1.82- 1.70 (m, 1H), 1.37-1.28 (m, 1H), 1.08 (t, J = 7.3 Hz, 3H); LCMS(electrospray) m/z 445.3 (M + H+).

B






(1S,2S)-N-(6-(5-ethyl-6-fluoro-7-





(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







104


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1H NMR (400 MHz, DMSO-d6) δ 13.15 (br s, 1H), 12.77 (br s, 1H), 8.03 (s, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.64 (s, 1H), 7.46 (br d, J = 8.3 Hz, 1H), 5.18- 4.89 (m, 1H), 2.95 (s, 6H), 2.28-2.22 (m, 1H), 2.16 (br d, J = 3.2 Hz, 3H), 1.83-1.69 (m, 1H), 1.38- 1.24 (m, 1H); LCMS(electrospray) m/z 428.2 (M + H+).

B






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







105


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1H NMR (400 MHz, CHLOROFORM-d) δ 12.79 (br s, 1H), 8.09 (d, J = 1.6 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.71 (s, 1H), 7.51 (dd, J = 1.8, 8.3 Hz, 1H), 7.48 (d, J = 9.3 Hz, 1H), 5.21-4.92 (m, 1H), 2.28-2.22 (m, 1H), 2.21 (s, 3H), 1.83-1.69 (m, 1H), 1.32 (ddd, J = 2.6, 6.4, 12.8 Hz, 1H); LCMS(electrospray) m/z 417.1 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-





(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide. 2 TFA







106


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1H NMR (400 MHz, DMSO-d6) δ 13.84 (br s, 1H), 12.79 (s, 1H), 8.03 (d, J = 1.6 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.70 (br s, 1H), 7.43 (dd, J = 1.8, 8.3 Hz, 1H), 5.23-4.89 (m, 1H), 2.61 (br d, J = 6.0 Hz, 2H), 2.29-2.20 (m, 1H), 1.82-1.69 (m, 1H), 1.37- 1.27 (m, 1H), 1.09 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 417.1 (M + H+).

B






(1S,2S)-N-(6-(5-ethyl-6,7-difluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







107


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1H NMR (400 MHz, DMSO-d6) δ 13.43 (s, 1H), 12.78 (s, 1H), 8.02 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.59 (s, 1H), 7.45-7.42 (m, 1H), 5.15-4.97 (m, 1H), 4.34-4.28 (m, 2H), 2.59-2.53 (m, 2H), 2.27- 2.23 (m, 1H), 1.85-1.75 (m, 1H), 1.40 (t, J = 6.8 Hz, 3H), 1.36-1.32 (m, 1H), 1.09 (t, J = 7.2 Hz, 3H); LCMS(electrospray) m/z 443.2 (M + H+).

B






(1S,2S)-N-(6-(7-ethoxy-5-ethyl-6-fluoro-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







108


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1H NMR (400 MHz, DMSO-d6) δ 13.27 (s, 1H), 12.82 (s, 1H), 10.11 (s, 1H), 8.20 (d, J = 1.6 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 1.1 Hz, 1H), 7.60 (dd, J = 1.7, 8.3 Hz, 1H), 5.18-4.96 (m, 1H), 2.26 (ddd, J = 2.2, 4.5, 6.5 Hz, 1H), 2.19 (s, 3H), 1.77 (tdd, J = 3.2, 6.8, 19.9 Hz, 1H), 1.33 (tdd, J = 6.3, 9.0, 12.8 Hz, 1H); LCMS(electrospray) m/z 462.1 (M + H+).

B






(1S,2S)-N-(6-(7-acetamido-5-chloro-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropane-1-carboxamide.





1 TFA







109


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1H NMR (400 MHz, DMSO-d6) δ 14.35-13.37 (m, 1H), 12.79 (s, 1H), 8.07 (d, J = 1.6 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.79 (br s, 1H), 7.48 (dd, J = 1.8, 8.3 Hz, 1H), 5.22-4.90 (m, 1H), 2.27-2.19 (m, 4H), 1.83-1.69 (m, 1H), 1.32 (tdd, J = 6.4, 9.0, 12.9 Hz, 1H); LCMS(electrospray) m/z 403.2 (M + H+).

B






(1S,2S)-N-(6-(6,7-difluoro-5-methyl-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







110


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1H NMR (400 MHz, DMSO-d6) δ 13.36 (br s, 1H), 12.77 (s, 1H), 8.04 (d, J = 1.5 Hz, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.67 (s, 1H), 7.48 (dd, J = 1.7, 8.3 Hz, 1H), 5.16-4.94 (m, 1H), 2.97 (d, J = 2.1 Hz, 6H), 2.27-2.22 (m, 1H), 2.20 (s, 3H), 1.83-1.69 (m, 1H), 1.39-1.26 (m, 1H); LCMS(electrospray) m/z 460 (M + H+).

B






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







111


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1H NMR (400 MHz, DMSO-d6) δ 13.77-13.52 (m, 1H), 12.80 (s, 1H), 8.09 (d, J = 1.5 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.52 (dd, J = 1.8, 8.3 Hz, 1H), 5.20-4.93 (m, 1H), 2.55 (s, 3H), 2.30-2.24 (m, 1H), 2.22 (s, 3H), 1.83-1.70 (m, 1H), 1.32 (tdd, J = 6.4, 8.9, 12.8 Hz, 1H); LCMS(electrospray) m/z 462.05 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-





bis(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide. 1 TFA







112


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1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 12.83 (s, 1H), 8.14 (d, J = 1.5 Hz, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 1.2 Hz, 1H), 7.53 (dd, J = 1.7, 8.3 Hz, 1H), 5.19-4.94 (m, 1H), 3.50 (s, 3H), 2.29 (br s, 1H), 2.24 (d, J = 2.9 Hz, 3H), 1.85-1.69 (m, 1H), 1.41-1.24 (m, 1H); LCMS(electrospray) m/z 463.1 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(methylsulfonyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide







113


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1H NMR (400 MHz, DMSO-d6) δ 12.94-12.86 (m, 1H), 12.83-12.74 (m, 1H), 9.90 (br s, 1H), 8.09 (br s, 1H), 7.88 (br d, J = 7.9 Hz, 1H), 7.66 (br s, 1H), 7.49 (br d, J = 7.4 Hz, 1H), 5.19-4.95 (m, 1H), 2.28-2.23 (m, 1H), 2.20 (br s, 3H), 2.16 (br s, 3H), 1.84-1.69 (m, 1H), 1.42-1.25 (m, 1H); LCMS(electrospray) m/z 442.0 (M + H+).

B






(1S,2S)-N-(6-(7-acetamido-6-fluoro-5-





methyl-1H-indazol-4-yl)benzo[d]thiazol-





2-yl)-2-fluorocyclopropane-1-carboxamide







114


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1H NMR (400 MHz, DMSO-d6) δ 13.05 (s, 1H), 10.78 (s, 1H), 8.08 (s, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.72 (s, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 12.4 Hz, 1H), 5.14-4.95 (m, 1H), 3.37 (s, 3H), 2.25-2.20 (m, 1H), 1.78-1.68 (m, 1H), 1.34-1.28 (m, 10H); LCMS (electrospray) m/z 549.1 (M + H)+.

B






tert-butyl 2-(5-chloro-6-fluoro-4-(2-





((1S,2S)-2-fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-1H-





indazol-7-yl)-1-methylhydrazine-1-





carboxylate







115


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1H NMR (400 MHz, DMSO-d6) δ 12.88 (s, 1H), 12.79 (s, 1H), 8.25 (s, 1H), 8.11 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.76 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 12.4 Hz, 1H), 5.13-4.96 (m, 1H), 4.04-3.99 (m, 1H), 3.23 (s, 3H), 2.25-2.20 (m, 1H), 1.78-1.68 (m, 1H), 1.34-1.28 (m, 1H); LCMS (electrospray) m/z 449.1 (M + H)+.

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





methylhydrazineyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







116


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1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 12.87-12.78 (m, 1H), 8.14 (d, J = 1.5 Hz, 1H), 7.91 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 1.3 Hz, 1H), 7.53 (dd, J = 1.8, 8.4 Hz, 1H), 5.18-4.95 (m, 1H), 3.98 (s, 3H), 2.21 (d, J = 3.1 Hz, 3H), 1.91-1.88 (m, 1H), 1.69 (br d, J = 2.8 Hz, 1H), 1.34-1.29 (m, 1H); LCMS(electrospray) m/z 443.1(M + H+).

B






methyl 6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-5-





methyl-1H-indazole-7-carboxylate. 1 TFA







117


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1H NMR (400 MHz, DMSO-d6) δ 14.07 (br s, 1H), 12.81 (s, 1H), 8.08 (d, J = 1.5 Hz, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.50 (dd, J = 1.8, 8.3 Hz, 1H), 5.19- 4.94 (m, 1H), 2.29-2.20 (m, 4H), 1.84-1.68 (m, 1H), 1.38-1.26 (m, 1H); LCMS(electrospray) m/z 435.1 (M + H+).

B






(1S,2S)-N-(6-(6,7-difluoro-5-(methylthio)-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide 2,2,2-





trifluoroacetate. 1 TFA







118


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1H NMR (400 MHz, DMSO-d6) δ 13.87-13.43 (m, 1H), 12.78 (s, 1H), 8.07 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 7.50 (dd, J = 1.3, 8.4 Hz, 1H), 5.21-4.93 (m, 1H), 4.35 (q, J = 7.0 Hz, 2H), 2.30-2.19 (m, 4H), 1.84-1.70 (m, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.37-1.27 (m, 1H); LCMS(electrospray) m/z 461.2 (M + H+).

B






(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-





(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







119


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 12.87 (s, 1H), 8.24 (d, J = 1.6 Hz, 1H), 8.00 (s, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.62 (dd, J = 1.8, 8.4 Hz, 1H), 5.17-4.95 (m, 1H), 3.56 (s, 3H), 2.29-2.22 (m, 1H), 1.83-1.71 (m, 1H), 1.37-1.29 (m, 1H); LCMS(electrospray) m/z 483 (M + H+).

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methylsulfonyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







120


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1H NMR (400 MHz, DMSO-d6) δ 11.22-11.13 (m, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.95-7.87 (m, 1H), 7.72-7.70 (m, 1H), 6.96-6.93 (m, 1H), 6.92- 6.89 (m, 1H), 5.07-4.81 (m, 1H), 3.21 (s, 3H), 2.30-2.25 (m, 3H), 2.25-2.23 (m, 1H), 2.20-2.09 (m, 1H), 1.79 (s, 3H), 1.74-1.63 (m, 1H), 1.28- 1.09 (m, 1H); LCMS(electrospray) m/z 456.1 (M + H+)

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(N-methylacetamido)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide. 1 TFA







121


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1H NMR (400 MHz, DMSO-d6) δ 13.45 (br s, 1H), 12.85 (s, 1H), 8.23 (d, J = 1.6 Hz, 1H), 7.94-7.88 (m, 2H), 7.62 (dd, J = 1.8, 8.4 Hz, 1H), 5.21-4.90 (m, 1H), 2.29-2.17 (m, 1H), 1.85-1.62 (m, 1H), 1.42-1.26 (m, 1H); LCMS(electrospray) m/z 449.2 (M + H+).

B






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-1H-





indazole-7-carboxylic acid. 1 TFA







122


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1H NMR (400 MHz, DMSO-d6) δ 13.57 (s, 1H), 12.86 (s, 1H), 8.36-8.16 (m, 1H), 7.96-7.91 (m, 2H), 7.63 (dd, J = 1.8, 8.4 Hz, 1H), 5.22-4.90 (m, 1H), 4.00 (s, 3H), 2.30-2.20 (m, 1H), 1.83-1.68 (m, 1H), 1.45-1.21 (m, 1H); LCMS(electrospray) m/z 463.1 (M + H+).

B






methyl 5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-1H-





indazole-7-carboxylate. 1 TFA







123


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1H NMR (400 MHz, DMSO-d6) δ 14.06-13.79 (m, 1H), 12.83 (s, 1H), 8.21 (d, J = 1.6 Hz, 1H), 7.91-7.89 (m, 1H), 7.63 (d, J = 1.7 Hz, 1H), 7.62- 7.59 (m, 1H), 5.15-4.96 (m, 1H), 3.23 (s, 3H), 2.27-2.23 (m, 1H), 1.82 (s, 3H), 1.76-1.69 (m, 1H), 1.36-1.30 (m, 1H); LCMS(electrospray) m/z 476.1 (M + H+).

B






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(N-





methylacetamido)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







124


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1H NMR (400 MHz, DMSO-d6) δ 12.94 (br s, 1H), 8.10 (d, J = 1.5 Hz, 1H), 7.91(d, J = 8.3 Hz, 1H), 7.68 (s, 1H), 7.51 (dd, J = 1.7, 8.3 Hz, 1H), 5.19- 4.92 (m, 1H), 2.31-2.25 (m, 1H), 2.19 (d, J = 3.1 Hz, 3H), 1.82-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS(electrospray) m/z 429.1(M + H+).

B






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-5-





methyl-1H-indazole-7-carboxylic acid







125


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1H NMR (400 MHz, DMSO-d6) δ 13.86-13.55 (m, 1H), 8.21 (d, J = 1.5 Hz, 1H), 7.92 (s, 1H), 7.90 (s, 1H), 7.61 (dd, J = 1.8, 8.4 Hz, 1H), 5.17-4.94 (m, 1H), 3.13 (s, 3H), 2.94 (s, 3H), 2.28-2.22 (m, 1H), 1.81-1.72 (m, 1H), 1.36-1.28 (m, 1H); LCMS(electrospray) m/z 475.9 (M + H+).

B






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-N,N-





dimethyl-1H-indazole-7-carboxamide







126


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1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J = 1.6 Hz, 1H), 7.95 (d, J = 3.2 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.56 (dd, J = 1.8, 8.3 Hz, 1H), 5.18-4.93 (m, 1H), 2.29-2.20 (m, 1H), 1.83-1.70 (m, 1H), 1.32 (tdd, J = 6.4, 9.0, 12.8 Hz, 1H); LCMS(electrospray) m/z 423.1 (M + H+).

B






(1S,2S)-N-(6-(5-chloro-6,7-difluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







127


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1H NMR (400 MHz, DMSO-d6) δ 13.71-13.47 (s, 1H), 12.98-12.70 (s, 1H), 8.65-8.55 (s, 1H), 8.21 (s, 1H), 7.97-7.88 (m, 1H), 7.85 (s, 1H), 7.63- 7.56 (m, 1H), 5.20-4.91 (m, 1H), 2.91 (br d, J = 4.3 Hz, 3H), 2.30-2.21 (m, 1H), 1.84-1.69 (m, 1H), 1.41-1.28 (m, 1H); LCMS(electrospray) m/z 462.0 (M + H+).

B






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-N-





methyl-1H-indazole-7-carboxamide







128


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1H NMR (400 MHz, DMSO-d6) δ 13.69 (s, 1H), 12.86 (s, 1H), 8.24 (d, J = 1.5 Hz, 1H), 7.97-7.87 (m, 2H), 7.63 (dd, J = 1.7, 8.4 Hz, 1H), 5.22-4.92 (m, 1H), 2.77 (d, J = 6.2 Hz, 3H), 2.31-2.21 (m, 1H), 1.83-1.70 (m, 1H), 1.25-1.32 (m, J = 2.5, 6.3, 12.8 Hz, 1H); LCMS(electrospray) m/z 447.2 (M + H+).

B






(1S,2S)-N-(6-(7-acetyl-5-chloro-6-fluoro-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







129


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1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.92-7.82 (m, 2H), 7.59-7.51 (m, 1H), 5.18-4.92 (m, 1H), 4.51-4.40 (m, 1H), 4.11-3.85 (m, 3H), 2.94 (s, 3H), 2.89-2.16 (m, 1H), 2.03-1.88 (m, 1H), 1.83-1.68 (m, 1H), 1.38-1.27 (m, 1H); LCMS (electrospray) m/z 489.10 (M + H)+.

B






(1S,2S)-N-(6-(7-(azetidin-3-





yl(methyl)amino)-5-chloro-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







130


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1H NMR (400 MHz, DMSO-d6) δ 13.86-13.56 (m, 1H), 12.93-12.67 (m, 1H), 8.01 (s, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.63 (s, 1H), 7.40 (br d, J = 8.5 Hz, 1H), 5.20-4.90 (m, 1H), 3.01 (s, 6H), 2.28- 2.18 (m, 1H), 1.82-1.69 (m, 1H), 1.31 (ddd, J = 2.4, 6.4, 12.5 Hz, 1H); LCMS(electrospray) m/z 482.1 (M + H+).

B






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-5-(trifluoromethyl)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







131


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1H NMR (400 MHz, DMSO-d6) δ 13.39 (s, 1H), 12.82 (br d, J = 1.7 Hz, 1H), 8.13 (s, 1H), 7.91 (d, J = 8.3 Hz, 1H), 7.76 (s, 1H), 7.52 (dd, J = 1.4, 8.3 Hz, 1H), 5.18-4.92 (m, 1H), 2.74 (d, J = 6.2 Hz, 3H), 2.24 (br d, J = 3.2 Hz, 3H), 1.86-1.66 (m, 1H), 1.32 (tdd, J = 6.5, 8.8, 12.7 Hz, 1H); LCMS(electrospray) m/z 427.10 (M + H+).

B






(1S,2S)-N-(6-(7-acetyl-6-fluoro-5-methyl-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







132


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1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 12.81 (br s, 1H), 8.11 (d, J = 1.5 Hz, 1H), 7.90 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 1.1 Hz, 1H), 7.50 (dd, J = 1.7, 8.3 Hz, 1H), 5.18-4.93 (m, 1H), 2.90 (d, J = 4.5 Hz, 3H), 2.29-2.24 (m, 1H), 2.22 (d, J = 3.1 Hz, 3H), 1.87-1.67 (m, 1H), 1.33 (tdd, J = 6.4, 8.9, 12.7 Hz, 1H); LCMS(electrospray) m/z 442.1 (M + H+).

B






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-N,5-





dimethyl-1H-indazole-7-carboxamide







133


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1H NMR (400 MHz, DMSO-d6) δ 13.45 (br s, 1H), 12.81 (s, 1H), 8.15 (d, J = 1.5 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.57 (dd, J = 1.8, 8.4 Hz, 1H), 5.17-4.92 (m, 1H), 3.26 (q, J = 6.4 Hz, 2H), 2.98 (s, 3H), 2.30-2.21 (m, 1H), 1.85-1.70 (m, 1H), 1.33 (tdd, J = 6.5, 8.8, 12.8 Hz, 1H), 1.09 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 462.1(M + H+).

B






(1S,2S)-N-(6-(5-chloro-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







134


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1H NMR (400 MHz, DMSO-d6) δ 13.38 (br s, 1H), 8.10 (d J = 1.3 Hz, 1H), 7.88 (d J = 8.3 Hz, 1H), 7.74 (s, 1H), 7.51 (dd, J = 1.8, 8.4 Hz, 1H), 5.18- 4.91 (m, 1H), 3.12 (s, 3H), 2.93 (s, 3H), 2.24 (br d, J = 2.1 Hz, 1H), 2.21 (d, J = 2.8 Hz, 3H), 1.83- 1.67 (m, 1H), 1.31 (ddd, J = 2.8, 6.3, 12.7 Hz, 1H); LCMS(electrospray) m/z 455.9 (M + H+).

B






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-N,N,5-





trimethyl-1H-indazole-7-carboxamide







135


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1H NMR (400 MHz, DMSO-d6) δ 13.50 (s, 1H), 12.85 (s, 1H), 8.21 (d, J = 1.4 Hz, 1H), 8.04 (s, 2H), 7.92 (d, J = 8.4 Hz, 1H), 7.84 (s, 1H), 7.60 (dd, J = 1.7, 8.3 Hz, 1H), 5.20-4.94 (m, 1H), 2.32- 2.18 (m, 1H), 1.84-1.69 (m, 1H), 1.29~1.36(m, 1H); LCMS(electrospray) m/z 448.1 (M + H+).

B






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-1H-





indazole-7-carboxamide







136


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1H NMR (400 MHz, DMSO-d6) δ 13.12 (br s, 1H), 12.76 (br d, J = 12.7 Hz, 1H), 8.00 (s, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.54 (s, 1H), 7.43 (dd, J = 1.6, 8.2 Hz, 1H), 5.21-4.89 (m, 1H), 3.21 (q, J = 6.9 Hz, 2H), 2.94 (s, 3H), 2.55 (br d, J = 7.6 Hz, 2H), 2.28- 2.19 (m, 1H), 1.83-1.68 (m, 1H), 1.37-1.26 (m, 1H), 1.07 (dt, J = 4.0, 7.1 Hz, 6H); LCMS(electrospray) m/z 456.2 (M + H+).

B






(1S,2S)-N-(6-(5-ethyl-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







137


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1H NMR (400 MHz, DMSO-d6) δ 13.11 (s, 1H), 8.04 (d, J = 1.4 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.64 (s, 1H), 7.47 (dd, J = 1.8, 8.3 Hz, 1H), 5.19- 4.89 (m, 1H), 3.23-3.17 (m, 2H), 2.93 (d, J = 1.9 Hz, 3H), 2.28-2.20 (m, 1H), 2.17 (d, J = 3.1 Hz, 3H), 1.85-1.68 (m, 1H), 1.38-1.23 (m, 1H), 1.06 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 441.14 (M + H+).

B






(1S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







138


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1H NMR (400 MHz, DMSO-d6) δ 13.34 (br s, 1H), 8.04 (d, J = 1.3 Hz, 1H), 7.83 (d, J = 8.2 Hz, 1H), 7.68 (s, 1H), 7.49 (dd, J = 1.7, 8.3 Hz, 1H), 5.16- 4.94 (m, 1H), 3.23 (q, J = 7.1 Hz, 2H), 2.95 (d, J = 2.0 Hz, 3H), 2.28-2.22 (m, 1H), 2.20 (s, 3H), 1.82- 1.68 (m, 1H), 1.31 (tdd, J = 6.2, 8.9, 12.6 Hz, 1H), 1.07 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 474.1 (M + H+).

B






(1S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







139


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1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 12.77 (s, 1H), 8.33 (s, 1H), 8.24 (br s, 1H), 7.89- 7.81 (m, 1H), 7.80-7.74 (m, 1H), 7.13 (br d, J = 13.7 Hz, 1H), 5.17-4.92 (m, 1H), 2.95 (br s, 6H), 2.27-2.18 (m, 1H), 1.82-1.69 (m, 1H), 1.31 (br s, 1H); LCMS(electrospray) m/z 414.2 (M + H+).

B






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)benzo[d]thiazol-2-





yl)-2-fluorocyclopropane-1-carboxamide







140


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1H NMR (400 MHz, DMSO-d6) δ 14.04 (br s, 1H), 12.83 (br s, 1H), 8.47-8.36 (m, 2H), 7.92-7.83 (m, 2H), 7.45 (br d, J = 11.7 Hz, 1H), 5.19-4.95 (m, 1H), 2.30-2.20 (m, 1H), 1.84-1.70 (m, 1H), 1.34 (ddd, J = 2.4, 6.2, 12.9 Hz, 1H); LCMS(electrospray) m/z 455.2 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-





(trifluoromethoxy)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide







141


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1H NMR (400 MHz, DMSO-d6) δ 13.56 (s, 1 H) 12.81 (s, 1 H) 8.42 (s, 1 H) 8.34 (s, 1 H) 7.89-7.82 (m, 2 H) 7.29 (d, J = 10.4 Hz, 1 H) 5.14-4.97 (m, 1 H) 2.49 (s, 3 H) 2.28-2.23 (m, 1 H) 1.80-1.73 (m, 1 H) 1.35-1.30 (m, 1 H); LCMS(electrospray) m/z 416.9 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-





(methylthio)-1H-indazol-4-





yl)benzo[d]thiazol-2-yl)cyclopropane-1-





carboxamide







142


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1H NMR (400 MHz, DMSO-d6) δ 13.21-13.61 (m, 1 H) 12.76 (s, 1 H) 8.35 (d, J = 1.50 Hz, 1 H) 8.31 (s, 1 H) 7.85-7.89 (m, 1 H) 7.79 (dd, J = 8.38, 1.75 Hz, 1 H) 7.34-7.39 (m, 1 H) 7.27-7.32 (m, 1 H) 4.93-5.17 (m, 1 H) 3.17 (s, 1 H) 2.62 (s, 3 H) 2.20-2.29 (m, 1 H) 1.70-1.82 (m, 1 H) 1.32 (ddt, J = 12.77, 8.93, 6.35, 6.35 Hz, 1 H); LCMS(electrospray) m/z 399.0 (M + H+).

B






(1S,2S)-2-fluoro-N-(6-(7-(methylthio)-1H-





indazol-4-yl)benzo[d]thiazol-2-





yl)cyclopropane-1-carboxamide







143


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1H NMR (400 MHz, DMSO-d6) δ 12.77 (br s, 1H), 8.15-7.99 (m, 2H), 7.83 (br d, J = 8.3 Hz, 1H), 7.45 (br d, J = 8.1 Hz, 1H), 7.18 (br s, 1H), 5.17- 4.93 (m, 1H), 2.33 (s, 3H), 2.25 (br s, 1H), 1.84- 1.70 (m, 1H), 1.37-1.27 (m, 1H); LCMS(electrospray) m/z 346.1(M + H+).

B






(1S,2S)-N-(6-(5-chloro-7-cyano-6-fluoro-





1H-indazol-4-yl)benzo[d]thiazol-2-yl)-2-





fluorocyclopropane-1-carboxamide







144


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (br s, 1H), 12.82 (br s, 1H), 8.11 (s, 1H), 7.98 (s, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.55 (td, J = 2.1, 8.3 Hz, 1H), 7.47 (dd, J = 0.7, 9.7 Hz, 1H), 5.18-4.90 (m, 1H), 2.79 (s, 3H), 2.63 (d, J = 1.0 Hz, 3H), 2.24 (td, J = 6.9, 13.6 Hz, 1H), 1.85-1.67 (m, 1H), 1.39-1.25 (m, 1H); LCMS(electrospray) m/z 442.2 (M + H+).

B






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-N,N-





dimethyl-1H-indazole-7-carboxamide







145


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (br s, 1H), 12.82 (br s, 1H), 8.11 (s, 1H), 7.98 (s, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.55 (td, J = 2.1, 8.3 Hz, 1H), 7.47 (dd, J = 0.7, 9.7 Hz, 1H), 5.18-4.90 (m, 1H), 2.79 (s, 3H), 2.63 (d, J = 1.0 Hz, 3H), 2.24 (td, J = 6.9, 13.6 Hz, 1H), 1.85-1.67 (m, 1H), 1.39-1.25 (m, 1H); LCMS(electrospray) m/z 442.2 (M + H+).

B






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)benzo[d]thiazol-6-yl)-N,N-





dimethyl-1H-indazole-5-carboxamide







146


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1H NMR (400 MHz, DMSO-d6) δ 13.04 (s, 1H), 12.86 (s, 1H), 8.19 (d, J = 8.8 Hz, 1H), 7.74 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 5.14-4.93 (m, 1H), 2.35 (s, 3H), 2.29-2.20 (m, 1H), 1.77-1.70 (m, 1H), 1.35-1.26 (m, 1H); LCMS (electrospray) m/z 368.1 (M + H)+.

D






(1S,2S)-2-fluoro-N-(5-(5-methyl-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide







147


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1H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.80 (s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 10.0 Hz, 1H), 5.17-4.98 (m, 1H), 2.69 (s, 3H), 2.28-2.21 (m, 1H), 1.81-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (electrospray) m/z 386.1 (M + H)+.

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 3 HCl







148


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1H NMR (400 MHz, DMSO-d6) δ 13.10 (br s, 1H), 12.95 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 10.1 Hz, 1H), 5.18-4.97 (m, 1H), 2.27 (s, 3H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS (electrospray) m/z 432.1 (M + H)+.

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





3-(methylthio)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 3 HCl







149


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1H NMR (400 MHz, DMSO-d6) δ 13.77 (s, 1H), 12.97 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.93 (s, 1H), 7.82 (d, J = 8.5 Hz, 1H), 5.20-4.95 (m, 1H), 4.40 (q, J = 7.0 Hz, 2H), 2.31-2.23 (m, 1H), 1.85-1.71 (m, 1H), 1.41 (t, J = 6.9 Hz, 3H), 1.38-1.30 (m, 1H); LCMS (electrospray) m/z 450.2 (M + H)+.

C






(1S,2S)-N-(5-(5-chloro-7-ethoxy-6-fluoro-





1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







150


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1H NMR (400 MHz, DMSO-d6) δ 12.93 (s, 1 H), 8.25 (d, J = 8.31 Hz, 1 H), 7.64-7.59 (m, 2 H), 7.39 (d, J = 11.62 Hz, 1 H), 5.19-4.96 (m, 1 H), 3.08 (dt, J = 14.15, 7.17 Hz, 1 H), 2.30-2.23 (m, 1 H), 1.83- 1.71 (m, 1 H), 1.40-1.32 (m, 1 H), 1.31-1.23 (m, 6 H); LCMS (electrospray) m/z 414.2 (M + H)+.

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





isopropyl-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







151


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1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1 H), 8.25 (d, J = 8.56 Hz, 1 H), 8.00 (s, 1 H), 7.95 (d, J = 8.44 Hz, 1 H), 7.40 (d, J = 10.88 Hz, 1 H), z, 1 H), 5.21-4.94 (m, 1 H), 2.30-2.23 (m, 1 H), 1.84- 1.69 (m, 1 H), 1.41-1.28 (m, 1 H); LCMS (electrospray) m/z 387.2 (M + H)+.

D






(1S,2S)-N-(5-(5-amino-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







152


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1H NMR (400 MHz, DMSO-d6) δ 13.18 (br s, 1H), 12.94 (br s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.42 (d, J = 10.1 Hz, 1H), 5.20-4.95 (m, 1H), 2.65 (dq, J = 2.4, 7.2 Hz, 2H), 2.27 (m, 1H), 1.85-1.69 (m, 1H), 1.34 (m, 1H), 1.11 (t, J = 7.0 Hz, 3H); LCMS (electrospray) m/z 400.4 (M + H)+.

D






(1S,2S)-N-(5-(5-ethyl-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







153


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1H NMR (400 MHz, DMSO-d6) δ 12.99 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 0.9 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.71 (dd, J = 0.9, 9.2 Hz, 1H), 5.20-4.96 (m, 1H), 2.31-2.23 (m, 1H), 1.84-1.71 (m, 1H), 1.40-1.31 (m, 1H); LCMS (electrospray) m/z 406.3 (M + H)+.

D






(1S,2S)-N-(5-(5-chloro-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







154


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (br s, 1H), 12.96 (s, 1H), 8.26 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.83 (d, J = 8.3 Hz, 1H), 5.21-4.95 (m, 1H), 3.30 (q, J = 6.4 Hz, 4H), 2.31-2.22 (m, 1H), 1.84-1.71 (m, 1H), 1.41-1.27 (m, 2H), 1.02 (t, J = 7.1 Hz, 6H); LCMS (electrospray) m/z 477.3 (M + H)+.

D






(1S,2S)-N-(5-(5-chloro-7-(diethylamino)-





6-fluoro-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







155


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1H NMR (400 MHz, DMSO-d6)) δ 12.93 (s, 1H), 8.25 (d, J = 8.6 Hz, 1H), 8.16 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 10.6 Hz, 1H), 5.22-4.93 (m, 1H), 3.73 (s, 3H), 2.31-2.22 (m, 1H), 1.85-1.70 (m, 1H), 1.41-1.28 (m, 1H); LCMS (electrospray) m/z 402.4 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





methoxy-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)cyclopropane-1-





carboxamide







156


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1H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 8.29-8.21 (m, 1H), 7.80 (d, J = 0.8 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.55 (dd, J = 0.8, 9.5 Hz, 1H), 5.20-4.95 (m, 1H), 2.32-2.27 (m, 1H), 2.26 (s, 3H), 1.84-1.71 (m, 1H), 1.35 (tdd, J = 6.4, 8.9, 13.0 Hz, 1H); LCMS(electrospray) m/z 418.3 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





(methylthio)-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)cyclopropane-1-





carboxamide







157


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1H NMR (400 MHz, DMSO-d6) δ 13.84 (br s, 1H), 13.07 (s, 1H), 8.39-8.30 (m, 2H), 8.08 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 9.5 Hz, 1H), 5.21-4.97 (m, 1H), 2.29 (td, J = 6.9, 13.4 Hz, 1H), 1.86-1.71 (m, 1H), 1.43-1.28 (m, 1H); LCMS(electrospray) m/z 397.4 (M + H+).

D






(1S,2S)-N-(5-(5-cyano-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







158


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1H NMR (400 MHz, DMSO-d6) δ 13.17 (br s, 1H), 12.83 (br s, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.87 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 10.2 Hz, 1H), 5.20-4.95 (m, 1H), 2.31-2.23 (m, 1H), 2.07- 1.98 (m, 1H), 1.84-1.69 (m, 1H), 1.34 (tdd, J = 6.4, 8.9, 12.8 Hz, 1H), 0.72-0.61 (m, 2H), 0.17- 0.06 (m, 2H); LCMS(electrospray) m/z 412.4 (M + H+).

D






(1S,2S)-N-(5-(5-cyclopropyl-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







159


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1H NMR (400 MHz, DMSO-d6) δ 12.93 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.93 (br s, 1H), 7.78 (d, J = 8.5 Hz, 1H), 5.19-4.96 (m, 1H), 2.31-2.22 (m, 1H), 1.84-1.70 (m, 1H), 1.39-1.27 (m, 1H), 1.22 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 449.3 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-7-(ethylamino)-6-





fluoro-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







160


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1H NMR (400 MHz, DMSO-d6) δ 13.46 (br s, 1H), 12.97 (s, 1H), 8.29 (d, J = 8.3 Hz, 1H), 7.83 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 5.20-4.96 (m, 1H), 2.31-2.23 (m, 1H), 1.84-1.71 (m, 1H), 1.35 (tdd, J = 6.4, 9.0, 13.0 Hz, 1H); LCMS(electrospray) m/z 452.0 (M + H+).

D






(1S,2S)-N-(5-(5-bromo-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







161


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1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.72 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 5.24-4.90 (m, 1H), 2.99 (s, 3H), 2.98 (s, 3H), 2.70-2.58 (m, 2H), 2.31-2.21 (m, 1H), 1.86- 1.67 (m, 1H), 1.41-1.26 (m, 1H), 1.12 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 443.2 (M + H+).

D






(1S,2S)-N-(5-(7-(dimethylamino)-5-ethyl-





6-fluoro-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







162


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 12.95 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.69 (d J = 8.3 Hz, 1H), 5.18-4.96 (m, 1H), 2.67- 2.64 (m, 2H), 2.53 (br s, 3H), 2.30-2.22 (m, 1H), 1.82-1.71 (m, 1H), 1.35 (tdd, J = 6.5, 8.8, 12.9 Hz, 1H), 1.12 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 446.3 (M + H+).

D






(1S,2S)-N-(5-(5-ethyl-6-fluoro-7-





(methylthio)-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







163


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1H NMR (400 MHz, CHLOROFORM-d) δ 13.46 (br s, 1H), 12.98 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.88 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 5.24-4.95 (m, 1H), 3.51 (br t, J = 6.9 Hz, 3H), 3.03 (br t, J = 6.6 Hz, 2H), 2.28 (br d, J = 2.6 Hz, 4H), 1.84-1.71 (m, 1H), 1.80-1.30 (m, 1H), 1.41-1.30 (m, 1H); LCMS(electrospray) m/z 462.1 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-





hydroxyethyl)thio)-5-methyl-1H-indazol-





4-yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 2TFA







164


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1H NMR (400 MHz, DMSO-d6) δ 13.65 (br s, 1H), 13.02 (s, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.10 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 11.2 Hz, 1H), 5.19-4.97 (m, 1H), 3.18 (d, J = 1.0 Hz, 3H), 2.31- 2.25 (m, 1H), 1.84-1.71 (m, 1H), 1.41-1.29 (m, 1H); LCMS(electrospray) m/z 434 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





(methylsulfinyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







165


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1H NMR (400 MHz, DMSO-d6) δ 13.52 (br s, 1H), 13.33 (br s, 1H), 12.97 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.09 (s, 1H), 7.81 (s, 1H), 7.71 (br s, 1H), 7.68 (d, J = 8.4 Hz, 1H), 5.25-4.96 (m, 1H), 3.97 (q, J = 7.1 Hz, 2H), 3.93-3.87 (m, 1H), 3.78 (s, 2H), 3.70 (s, 1H), 2.72-2.62 (m, 3H), 2.32-2.23 (m, 1H), 1.84-1.71 (m, 1H), 1.41-1.31 (m, 1H), 1.21 (t, J = 7.5 Hz, 1H), 1.12 (t, J = 7.4 Hz, 3H), 1.01 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.1 Hz, 1H); LCMS(electrospray) m/z 518.3 (M + H+).

D






ethyl 2-((5-ethyl-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





1H-indazol-7-yl)thio)acetate. 2 TFA







166


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1H NMR (400 MHz, DMSO-d6) δ 13.48 (s, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.81 (s, 1H), 7.58 (d, J = 8.2 Hz, 1H), 5.19-4.84 (m, 1H), 3.97 (s, 2H), 3.02 (s, 3H), 2.91-2.76 (m, 6H), 2.74-2.62 (m, 2H), 2.21-2.10 (m, 1H), 1.81-1.64(m, 1H), 1.29-1.19 (m, 1H), 1.13 (t, J = 7.3 Hz, 3H); LCMS(electrospray) m/z 517.1 (M + H+).

D






(1S,2S)-N-(5-(7-((2-(dimethylamino)-2-





oxoethyl)thio)-5-ethyl-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







167


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1H NMR (400 MHz, DMSO-d6) δ 7.82 (d, J = 7.9 Hz, 1H), 7.72 (s, 1H), 7.41 (d, J = 8.2 Hz, 1H), 5.03- 4.68 (m, 1H), 3.18 (s, 1H), 2.86 (s, 1H), 2.70- 2.63 (m, 2H), 2.01-1.91 (m, 1H), 1.72-1.57 (m, 1H), 1.12 (t, J = 7.3 Hz, 3H), 1.05-0.96 (m, 1H); LCMS(electrospray) m/z 503.3 (M + H+).

D






(1S,2S)-N-(5-(5-ethyl-6-fluoro-7-((2-





(methylamino)-2-oxoethyl)thio)-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







168


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1H NMR (400 MHz, DMSO-d6) δ 7.82 (d, J = 7.9 Hz, 1H), 7.72 (s, 1H), 7.41 (d, J = 8.2 Hz, 1H), 5.03- 4.68 (m, 1H), 3.18 (s, 1H), 2.86 (s, 1H), 2.70- 2.63 (m, 2H), 2.01-1.91 (m, 1H), 1.72-1.57 (m, 1H), 1.12 (t, J = 7.3 Hz, 3H), 1.05-0.96 (m, 1H); LCMS(electrospray) m/z 490.3 (M + H+).

D






2-((5-ethyl-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





1H-indazol-7-yl)thio)acetic acid







169


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1H NMR (400 MHz, CHLOROFORM-d) δ 8.15 (d, J = 8.3 Hz, 1H), 7.89 (br s, 1H), 7.60 (d, J = 8.3 Hz, 1H), 5.10-4.76 (m, 1H), 3.13 (d, J = 1.6 Hz, 6H), 2.35 (d, J = 3.4 Hz, 3H), 2.12-2.01 (m, 2H), 1.49- 1.33 (m, 1H); LCMS(electrospray) m/z429.1 (M + H+).

D






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







170


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1H NMR (400 MHz, DMSO-d6) δ 13.65 (s, 1H), 12.94 (br s, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.89- 7.84 (m, 1H), 7.75 (d, J = 8.3 Hz, 1H), 5.20-4.94 (m, 1H), 2.56 (s, 3H), 2.28 (s, 3H), 2.27-2.23 (m, 1H), 1.84-1.72 (m, 1H), 1.41-1.30 (m, 1H); LCMS(electrospray) m/z 464.0 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-





bis(methylthio)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







171


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1H NMR (400 MHz, DMSO-d6) δ 13.96 (s, 1H), 12.92 (s, 1H), 8.41 (d, J = 6.5 Hz, 1H), 8.38 (d, J = 1.2 Hz, 1H), 8.29 (d, J = 8.6 Hz, 1H), 8.15 (d, J = 7.7 Hz, 1H), 5.21-4.94 (m, 1H), 2.24 (s, 1H), 1.88- 1.69 (m, 1H), 1.41-1.29 (m, 1H); LCMS(electrospray) m/z 0.887, 440.1 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(5-fluoro-6-





(trifluoromethyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. TFA







172


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1H NMR (400 MHz, DMSO-d6) δ 13.56-13.42 (m, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.90 (br s, 1H), 7.79 (d, J = 8.4 Hz, 1H), 5.20-4.95 (m, 1H), 3.02 (br d, J = 1.7 Hz, 6H), 2.27 (ddd, J = 2.0, 4.6, 6.7 Hz, 1H), 1.85-1.71 (m, 1H), 1.38-1.30 (m, 1H), 1.30 (s, 1H); LCMS(electrospray) m/z 449.1 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







173


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1H NMR (400 MHz, DMSO-d6) δ 13.57-13.32 (m, 1H), 8.25 (dd, J = 3.0, 8.3 Hz, 1H), 7.86 (br s, 1H), 7.70 (dd, J = 2.9, 8.3 Hz, 1H), 5.22-4.91 (m, 1H), 2.53 (br s, 3H), 2.27 (br s, 3H), 1.83-1.70 (m, 1H), 1.40-1.27 (m, 1H), 1.21 (br d, J = 10.5 Hz, 2H); LCMS(electrospray) m/z 431.07 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylthio)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







174


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1H NMR (400 MHz, DMSO-d6) δ 13.76 (s, 1H), 12.98 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 1.3 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 5.21-4.96 (m, 1H), 2.58 (s, 3H), 2.31-2.25 (m, 1H), 1.84- 1.72 (m, 1H), 1.37-1.30 (m, 1H); LCMS(electrospray) m/z 452 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methylthio)-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







175


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1H NMR (400 MHz, DMSO-d6) δ 13.54-13.33 (m, 1H), 12.92 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.82 (s, 1H), 7.68 (d, J = 8.3 Hz, 1H), 5.19-4.96 (m, 1H), 4.33 (q, J = 7.0 Hz, 2H), 2.30-2.25 (m, 4H), 1.83-1.72 (m, 1H), 1.39 (t, J = 7.0 Hz, 3H), 1.36-1.32 (m, 1H); LCMS(electrospray) m/z 430.2 (M + H+).

D






(1S,2S)-N-(5-(7-ethoxy-6-fluoro-5-





methyl-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







176


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1H NMR (400 MHz, DMSO-d6) δ 13.90-13.81 (m, 1H), 12.94 (br s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.87-7.80 (m, 1H), 7.67 (d, J = 8.3 Hz, 1H), 5.17- 4.95 (m, 1H), 2.76-2.68 (m, 2H), 2.27-2.19 (m, 1H), 1.82-1.73 (m, 1H), 1.57-1.42 (m, 1H), 1.15- 1.11 (m, 3H); LCMS(electrospray) m/z 418 (M + H+).

D






(1S,2S)-N-(5-(5-ethyl-6,7-difluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







177


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1H NMR (400 MHz, DMSO-d6) δ 13.36 (s, 1H), 12.97 (s, 1H), 8.29 (d, J = 8.3 Hz, 1H), 7.92 (s, 1H), 7.74 (d, J = 8.3 Hz, 1H), 5.20-4.96 (m, 1H), 3.14 (s, 3H), 2.31-2.23 (m, 4H), 1.84-1.71 (m, 1H), 1.35 (tdd, J = 6.4, 8.9, 13.0 Hz, 1H); LCMS(electrospray) m/z 447.9 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylsulfinyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







178


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (s, 1H), 12.93 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.76 (s, 1H), 7.67-7.65 (m, 1H), 5.21-4.96 (m, 1H), 4.37-4.31 (m, 2H), 2.68-2.64 (m, 2H), 2.34-2.33 (m, 1H), 1.81-1.68 (m, 1H), 1.40 (t, J = 6.8 Hz, 3H), 1.19- 1.15 (m, 1H), 1.13 (t, J = 7.6 Hz, 3H); LCMS(electrospray) m/z 444.2 (M + H+).

D






(1S,2S)-N-(5-(7-ethoxy-5-ethyl-6-fluoro-





1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





1 TFA







179


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1H NMR (400 MHz, DMSO-d6) δ 13.27 (br s, 1H), 12.97 (s, 1H), 10.16 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H), 7.85 (d, J = 8.3 Hz, 1H), 5.18- 4.98 (m, 1H), 2.28 (ddd, J = 2.4, 4.3, 6.6 Hz, 1H), 2.19 (s, 3H), 1.82-1.73 (m, 1H), 1.35 (ddd, J = 2.6, 6.3, 12.9 Hz, 1H); LCMS(electrospray) m/z 463.1(M + H+).

D






(1S,2S)-N-(5-(7-acetamido-5-chloro-6-





fluoro-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







180


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1H NMR (400 MHz, DMSO-d6) δ 13.68 (br s, 1H), 13.02 (s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.05 (br s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 5.20-4.98 (m, 1H), 3.19 (s, 3H), 2.31-2.25 (m, 1H), 1.85-1.71 (m, 1H), 1.36 (tdd, J = 6.6, 8.8, 13.0 Hz, 1H); LCMS(electrospray) m/z 468 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methylsulfinyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







181


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1H NMR (400 MHz, DMSO-d6) δ 12.96-12.91 (m, 2H), 9.96 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.71 (d, J = 8.3 Hz, 1H), 5.20-4.94 (m, 1H), 2.27 (d, J = 2.9 Hz, 3H), 2.17 (s, 4H), 1.84- 1.71 (m, 1H), 1.42-1.30 (m, 1H); LCMS(electrospray) m/z 442.10 (M + H+).

D






(1S,2S)-N-(5-(7-acetamido-6-fluoro-5-





methyl-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







182


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1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 12.99 (s, 1H), 8.31 (d, J = 8.4 Hz, 1H), 7.97 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 5.21-4.95 (m, 1H), 3.51 (s, 3H), 2.33-2.25 (m, 4H), 1.85-1.71 (m, 1H), 1.41-1.28 (m, 1H); LCMS(electrospray) m/z 463.06 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylsulfonyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







183


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1H NMR (400 MHz, DMSO-d6) δ 13.44-13.24 (m, 1H), 12.99 (s, 1H), 8.30 (d, J = 8.3 Hz, 1H), 7.98-7.86 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H), 5.27- 4.90 (m, 1H), 3.99 (s, 3H), 2.31-2.24 (m, 4H), 1.82-1.70 (m, 1H), 1.44-1.27 (m, 1H); LCMS(electrospray) m/z 444.0 (M + H+).

D






methyl 6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





5-methyl-1H-indazole-7-carboxylate. 1





TFA







184


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1H NMR (400 MHz, DMSO-d6) δ 13.83-13.51 (m, 1H), 12.93 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.84 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 5.22-4.93 (m, 1H), 4.51-4.26 (m, 2H), 2.30-2.28 (m, 1H), 2.06-2.03 (m, 1H), 1.86-1.73 (m, 1H), 1.64-1.52 (m, 1H), 1.42 (t, J = 7.0 Hz, 3H), 1.33 (m, J = 6.7, 14.0 Hz, 1H); LCMS(electrospray) m/z 462.2 (M + H+).

D






(1S,2S)-N-(5-(7-ethoxy-6-fluoro-5-





(methylthio)-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







185


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1H NMR (400 MHz, DMSO-d6) δ 13.48 (s, 1H), 13.03 (s, 1H), 8.34 (d, J = 8.3 Hz, 1H), 8.09 (d, J = 1.3 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 5.20-4.98 (m, 1H), 3.57 (s, 3H), 2.31-2.25 (m, 1H), 1.85- 1.73 (m, 1H), 1.41-1.31 (m, 1H); LCMS(electrospray) m/z 484 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methylsulfonyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







186


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1H NMR (400 MHz, DMSO-d6) δ 13.92-13.91 (m, 1H), 13.91-13.90 (m, 1H), 13.86 (br s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.93 (br d, J = 2.7 Hz, 1H), 7.68 (d, J = 8.3 Hz, 1H), 5.17-4.95 (m, 1H), 2.32- 2.31 (m, 1H), 2.31 (d, J = 2.9 Hz, 2H), 2.26 (dt, J = 2.2, 4.5 Hz, 1H), 1.84-1.73 (m, 1H), 1.32-1.25 (m, 1H); LCMS(electrospray) m/z 404.2 (M + H+).

D






(1S,2S)-N-(5-(6,7-difluoro-5-methyl-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 1





TFA







187


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1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J = 8.3 Hz, 1H), 8.14 (d, J = 3.2 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 5.38-5.15 (m, 1H), 2.71-2.70 (m, 3H), 2.45 (br s, 1H), 2.03-1.89 (m, 1H), 1.41 (s, 1H); LCMS(electrospray) m/z 436.1 (M + H+).

D






(1S,2S)-N-(5-(6,7-difluoro-5-(methylthio)-





1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







188


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1H NMR (400 MHz, METHANOL-d4) δ 8.25 (d, J = 8.4 Hz, 1H), 7.84 (s, 1H), 7.71 (d, J = 8.3 Hz, 1H), 5.04 (dt, J = 3.9, 6.2 Hz, 1H), 2.32 (d, J = 3.3 Hz, 3H), 2.24-2.16 (m, 1H), 1.98-1.84 (m, 1H), 1.34-1.29 (m, 1H); LCMS(electrospray) m/z 429.9 (M + H+).

D






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





5-methyl-1H-indazole-7-carboxylic acid. 1





TFA







189


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1H NMR (400 MHz, DMSO-d6) δ 14.34 (s, 1H), 8.31-8.28 (m, 1H), 8.05 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 5.17-4.98 (m, 1H), 3.25 (s, 3H), 2.28 (ddd, J = 1.8, 4.7, 6.8 Hz, 1H), 1.83 (s, 3H), 1.75 (dt, J = 3.8, 6.9 Hz, 1H), 1.38-1.32 (m, 1H); LCMS(electrospray) m/z 477.0 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(N-





methylacetamido)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







190


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1H NMR (400 MHz, DMSO-d6) δ 13.61 (br s, 1H), 12.99-12.91 (m, 1H), 8.31-8.24 (m, 1H), 7.94- 7.88 (m, 1H), 7.77-7.70 (m, 1H), 5.23-4.96 (m, 1H), 3.22 (s, 3H), 2.30 (d, J = 2.8 Hz, 3H), 2.28- 2.23 (m, 1H), 1.80 (s, 3H), 1.77-1.70 (m, 1H), 1.41-1.29 (m, 1H); LCMS(electrospray) m/z 456.12 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(N-methylacetamido)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







191


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1H NMR (400 MHz, DMSO-d6) δ 12.90 (br, 2H), 8.20 (d, J = 8.0 Hz, 1H), 7.83 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.49 (s, 1H), 5.15-4.98 (m, 1H), 5.04 (d, J = 5.2 Hz, 1H), 3.24 (s, 3H), 2.32-2.26 (m, 2H), 1.80-1.73 (m, 1H), 1.35-1.23 (m, 1H); LCMS (electrospray) m/z 450.1 (M + H)+.

D






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(2-





methylhydrazineyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







192


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1H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 12.88 (s, 1H), 8.37 (s, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.90 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 5.15-4.98 (m, 1H), 2.60 (d, J = 5.2 Hz, 3H), 2.18-2.13 (m, 1H), 1.71-1.63 (m, 1H), 1.35-1.12 (m, 10H); LCMS (electrospray) m/z 550.1 (M + H)+.

D






tert-butyl 2-(5-chloro-6-fluoro-4-(2-





((1S,2S)-2-fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





1H-indazol-7-yl)-1-methylhydrazine-1-





carboxylate







193


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1H NMR (400 MHz, DMSO-d6) δ 13.87-13.62 (m, 1H), 8.29 (d, J = 8.5 Hz, 1H), 7.98 (s, 1H), 7.86 (d, J = 8.5 Hz, 1H), 5.18-4.95 (m, 1H), 3.12 (s, 3H), 2.93 (s, 3H), 2.27 (ddd, J = 2.0, 4.6, 6.7 Hz, 1H), 1.82-1.71 (m, 1H), 1.34 (ddd, J = 2.6, 6.3, 13.0 Hz, 1H); LCMS(electrospray) m/z 476.9 (M + H+).

D






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





N,N-dimethyl-1H-indazole-7-carboxamide







194


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1H NMR (400 MHz, DMSO-d6) δ 13.36 (br s, 1H), 12.90 (br s, 1H), 8.21 (d, J = 8.8 Hz, 1H), 7.77 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 5.19-4.95 (m, 1H), 2.99 (s, 6H), 2.27 (s, 4H), 1.84-1.70 (m, 1H), 1.40- 1.28 (m, 1H); LCMS(electrospray) m/z 461 (M + H+).

D






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







195


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1H NMR (400 MHz, DMSO-d6) δ 8.65 (br d, J = 3.3 Hz, 1H), 8.19-8.12 (m, 1H), 7.95 (s, 1H), 7.77 (d, J = 8.3 Hz, 1H), 5.17-4.89 (m, 1H), 2.91 (d, J = 4.5 Hz, 3H), 2.23-2.14 (m, 1H), 1.85-1.63 (m, 1H), 1.35-1.17 (m, 1H); LCMS(electrospray) m/z 462.9 (M + H+).

D






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





N-methyl-1H-indazole-7-carboxamide







196


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1H NMR (400 MHz, DMSO-d6) δ 13.53-13.38 (m, 1H), 13.59-13.37 (m, 1H), 8.31-8.23 (m, 1H), 7.96-7.87 (m, 1H), 7.85-7.76 (m, 1H), 5.21- 4.96 (m, 1H), 3.31 (br s, 2H), 3.09-2.92 (m, 3H), 2.35-2.23 (m, 1H), 1.87-1.72 (m, 1H), 1.42-1.30 (m, 1H), 1.14-1.05 (m, 3H); LCMS(electrospray) m/z 463.7 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







197


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1H NMR (400 MHz, DMSO-d6) δ 13.48-13.33 (m, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.86 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 5.19-4.93 (m, 1H), 3.12 (s, 3H), 2.92 (s, 3H), 2.28 (d, J = 2.9 Hz, 3H), 2.27- 2.22 (m, 1H), 1.82-1.69 (m, 1H), 1.39-1.28 (m, 1H); LCMS(electrospray) m/z 457.1 (M + H+).

D






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





N,N,5-trimethyl-1H-indazole-7-





carboxamide







198


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1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 5.17-4.91 (m, 1H), 2.30-2.19 (m, 1H), 1.83-1.69 (m, 1H), 1.39-1.28 (m, 1H); LCMS(electrospray) m/z 474.1 (M + H+).

D






(1S,2S)-N-(5-(7-chloro-6-fluoro-5-





(trifluoromethyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







199


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1H NMR (400 MHz, DMSO-d6) δ 13.01-12.83 (m, 1H), 8.30-8.14 (m, 1H), 7.98-7.94 (m, 1H), 7.80 (s, 1H), 7.71-7.59 (m, 1H), 5.28-4.88 (m, 1H), 2.49-2.48 (m, 3H), 2.27-2.24 (m, 4H), 1.83- 1.72 (m, 1H), 1.39-1.30 (m, 1H); LCMS(electrospray) m/z 400.0 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-





dimethyl-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)cyclopropane-1-





carboxamide. 1 TFA







200


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1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 13.03-12.78 (m, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.74-7.61 (m, 2H), 5.20-4.94 (m, 1H), 3.23 (br d, J = 7.1 Hz, 2H), 2.95 (d, J = 1.8 Hz, 3H), 2.63 (br d, J = 5.8 Hz, 2H), 2.29-2.24 (m, 1H), 1.83- 1.71 (m, 1H), 1.40-1.29 (m, 1H), 1.12 (t, J = 7.4 Hz, 3H), 1.06 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 457.0 (M + H+).

D






(1S,2S)-N-(5-(5-ethyl-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







201


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1H NMR (400 MHz, DMSO-d6) δ 13.19 (br s, 1H), 12.89 (br s, 1H), 8.24 (d, J = 8.5 Hz, 1H), 8.15 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.53 (d, J = 10.5 Hz, 1H), 5.19-4.96 (m, 1H), 3.91 (q, J = 7.0 Hz, 2H), 2.31-2.23 (m, 1H), 1.84-1.72 (m, 1H), 1.39-1.30 (m, 1H), 1.15 (t, J = 6.9 Hz, 3H); LCMS(electrospray) m/z 416.0 (M + H+).

D






(1S,2S)-N-(5-(5-ethoxy-6-fluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







202


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1H NMR (400 MHz, DMSO-d6) δ 13.20-13.00 (m, 1H), 12.95-12.86 (m, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.80 (s, 1H), 7.67 (d, J = 8.4 Hz, 1H), 6.98- 6.89 (m, 1H), 5.21-4.94 (m, 1H), 4.09 (br t, J = 5.9 Hz, 2H), 3.38-3.33 (m, 2H), 3.04-2.98 (m, 3H), 2.57-2.52 (m, 3H), 2.28 (br dd, J = 2.1, 4.4 Hz, 1H), 2.26-2.26 (m, 1H), 2.25 (d, J = 3.1 Hz, 3H), 1.83-1.71 (m, 1H), 1.39-1.30 (m, 1H); LCMS(electrospray) m/z 516.1 (M + H+).

D






2-((6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





5-methyl-1H-indazol-7-





yl)(methyl)amino)ethyl methylcarbamate







203


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1H NMR (400 MHz, DMSO-d6) δ 13.13 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.77 (s, 1H), 7.68 (d, J = 8.3 Hz, 1H), 5.23-4.94 (m, 1H), 3.22 (q, J = 6.9 Hz, 2H), 2.95 (d, J = 2.1 Hz, 3H), 2.30-2.27 (m, 1H), 2.25 (d, J = 3.2 Hz, 3H), 1.87-1.68 (m, 1H), 1.35 (tdd, J = 6.5, 8.7, 13.1 Hz, 1H), 1.06 (t, J = 7.2 Hz, 3H); LCMS(electrospray) m/z 442.14 (M + H+).

D






(1S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







204


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1H NMR (400 MHz, DMSO-d6) δ 13.27-13.06 (m, 1H), 8.21 (br d, J = 8.1 Hz, 1H), 7.78 (br s, 1H), 7.66 (br d, J = 8.4 Hz, 1H), 5.19-4.95 (m, 1H), 4.91 (br s, 1H), 3.65-3.55 (m, 2H), 3.27-3.14 (m, 2H), 3.04-2.94 (m, 3H), 2.28-2.19 (m, 4H), 1.82- 1.68 (m, 1H), 1.38-1.26 (m, 1H); LCMS(electrospray) m/z 459.1 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-





hydroxyethyl)(methyl)amino)-5-methyl-





1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide







205


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1H NMR (400 MHz, DMSO-d6) δ 13.63 (br s, 1H), 8.27 (d, J = 8.3 Hz, 1H), 7.99 (s, 1H), 7.74 (d, J = 8.3 Hz, 1H), 5.19-4.95 (m, 1H), 2.29 (d, J = 2.9 Hz, 3H), 2.28-2.22 (m, 1H), 1.84-1.70 (m, 1H), 1.39- 1.27 (m, 1H); LCMS(electrospray) m/z 454.2 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(trifluoromethyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide







206


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1H NMR (400 MHz, DMSO-d6) δ 13.24 (br d, J = 2.9 Hz, 1H), 8.50-8.44 (m, 1H), 8.18 (d, J = 8.3 Hz, 1H), 7.84 (s, 1H), 7.67 (d, J = 8.2 Hz, 1H), 5.17- 4.89 (m, 1H), 2.91 (d, J = 4.4 Hz, 3H), 2.29 (d, J = 2.8 Hz, 3H), 2.24-2.18 (m, 1H), 1.83-1.67 (m, 1H), 1.35-1.21 (m, 1H); LCMS(electrospray) m/z 442.10 (M + H+).

D






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)thiazolo[5,4-b]pyridin-5-yl)-





N,5-dimethyl-1H-indazole-7-carboxamide







207


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1H NMR (400 MHz, DMSO-d6) δ 13.86-13.56 (m, 1H), 12.95 (s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.73 (s, 1H), 7.62 (d, J = 8.3 Hz, 1H), 5.19-4.96 (m, 1H), 3.03 (d, J = 2.2 Hz, 6H), 2.32-2.21 (m, 1H), 1.83-1.71 (m, 1H), 1.41-1.31 (m, 1H); LCMS(electrospray) m/z 483.2 (M + H+).

D






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-5-(trifluoromethyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







208


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1H NMR (400 MHz, METHANOL-d4) δ 8.23 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 3.3 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 5.04 (dt, J = 3.9, 6.2 Hz, 1H), 2.20 (dtd, J = 4.3, 6.9, 9.1 Hz, 1H), 1.95-1.84 (m, 1H), 1.37-1.29 (m, 1H); LCMS(electrospray) m/z 424.1 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-6,7-difluoro-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide





2,2,2-trifluoroacetate. 1 TFA







209


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1H NMR (400 MHz, DMSO-d6) δ 1.27-1.40 (m, 1 H), 1.71-1.83 (m, 1 H), 2.27 (br s, 1 H), 4.95-5.19 (m, 1 H), 7.51 (s, 1 H), 7.65 (s, 1 H), 7.78 (br s, 1 H), 7.87 (br d, J = 8.68 Hz, 1 H), 8.05 (br s, 1 H), 8.21-8.38 (m, 1 H), 12.77-13.42 (m, 1 H), 13.77- 14.05 (m, 1 H); LCMS(electrospray) m/z 456.1 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-7-





(difluoromethyl)-6-fluoro-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







210


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1H NMR (400 MHz, DMSO-d6) δ 1.12 (br t, J = 7.40 Hz, 3 H), 1.27-1.42 (m, 1 H), 1.68-1.85 (m, 1 H), 2.22-2.31 (m, 1 H), 2.68 (br d, J = 7.28 Hz, 2 H), 4.90-5.23 (m, 1 H), 7.73 (d, J = 8.41 Hz, 1 H), 7.93 (br s, 1 H), 8.30 (d, J = 8.28 Hz, 1 H), 12.60-13.33 (m, 1 H), 13.48-13.91 (m, 1 H); LCMS(electrospray) m/z 468.2 (M + H+).

D






(1S,2S)-N-(5-(5-ethyl-6-fluoro-7-





(trifluoromethyl)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







211


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1H NMR (400 MHz, DMSO-d6) δ 13.79-13.40 (m, 1H), 13.10-12.67 (m, 1H), 8.75-8.46 (m, 1H), 8.39-8.10 (m, 1H), 8.01-7.71 (m, 1H), 5.24- 4.92 (m, 1H), 2.65-2.55 (m, 3H), 2.32-2.22 (m, 1H), 2.35-2.22 (m, 2H), 1.88-1.63 (m, 1H), 1.49- 1.19 (m, 2H); LCMS(electrospray) m/z 420.0 (M + H+).

D






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-methyl-





1H-indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







212


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1H NMR (400 MHz, DMSO-d6) δ 13.15-13.72 (m, 1 H) 12.88 (s, 1 H) 8.74 (s, 1 H) 8.13-8.21 (m, 2 H) 7.77 (d, J = 7.75 Hz, 1 H) 7.35 (d, J = 7.75 Hz, 1 H) 4.92-5.19 (m, 1 H) 3.17 (s, 1 H) 2.65 (s, 3 H) 2.23-2.31 (m, 1H) 1.74-1.84 (m, 2 H) 1.31-1.39 (m, 1 H); LCMS(electrospray) m/z 400.0 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(7-(methylthio)-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide







213


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1H NMR (400 MHz, DMSO-d6) δ 13.93 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.74 (d, J = 8.3 Hz, 1H), 5.25-4.89 (m, 1H), 2.31 (d, J = 2.8 Hz, 3H), 2.29-2.22 (m, 1H), 1.84-1.70 (m, 1H), 1.29-1.36 (m, J = 2.6, 6.2, 12.8 Hz, 1H); LCMS(electrospray) m/z 470.2 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(trifluoromethoxy)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide







214


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1H NMR (400 MHz, DMSO-d6) δ 13.27 (br s, 1H), 13.01-12.74 (m, 1H), 8.68 (br s, 1H), 8.55 (d, J = 8.6 Hz, 1H), 8.22 (d, J = 8.5 Hz, 1H), 8.15 (q, J = 8.6 Hz, 2H), 7.61 (d, J = 14.3 Hz, 1H), 5.18-4.96 (m, 1H), 2.99 (br s, 6H), 2.30-2.23 (m, 1H), 1.83- 1.72 (m, 1H), 1.38-1.31 (m, 1H); LCMS(electrospray) m/z 415.2 (M + H+).

D






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)thiazolo[5,4-





b]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







215


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1H NMR (400 MHz, DMSO-d6) δ 14.03 (s, 1H), 12.97 (s, 1H), 8.82 (s, 1H), 8.26 (s, 2H), 7.90 (d, J = 12.0 Hz, 1H), 5.24-4.94 (m, 1H), 2.28 (ddd, J = 2.0, 4.6, 6.7 Hz, 1H), 1.87-1.70 (m, 1H), 1.32- 1.36 (m, J = 2.6, 6.2, 12.7 Hz, 1H); LCMS(electrospray) m/z 456.2 (M + H+).

D






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-





(trifluoromethoxy)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-





yl)cyclopropane-1-carboxamide







216


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1H NMR (400 MHz, DMSO-d6) δ 13.30-12.94 (m, 1H), 8.73-8.65 (m, 1H), 8.15-8.08 (m, 1H), 8.07-8.01 (m, 1H), 7.66 (d, J = 7.9 Hz, 1H), 6.82- 6.73 (m, 1H), 5.29-4.92 (m, 1H), 3.13-2.82 (m, 6H), 2.29-2.18 (m, 1H), 2.07 (s, 1H), 1.84-1.69 (m, 1H), 1.39-1.25 (m, 1H); LCMS(electrospray) m/z 397.1 (M + H+).

D






(1S,2S)-N-(5-(7-(dimethylamino)-1H-





indazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







217


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1H NMR (400 MHz, DMSO-d6) δ 13.94-13.07 (m, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.92 (s, 1H), 7.74- 7.44 (m, 2H), 5.18-4.91 (m, 1H), 2.27 (d, J = 2.6 Hz, 3H), 2.26-2.22 (m, 1H), 1.82-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS(electrospray) m/z 436.1 (M + H+).

D






(1S,2S)-N-(5-(7-(difluoromethyl)-6-





fluoro-5-methyl-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







218


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1H NMR (400 MHz, DMSO-d6) δ 13.33 (br s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 5.19-4.95 (m, 1H), 3.25 (br d, J = 7.7 Hz, 2H), 2.97 (d, J = 1.6 Hz, 3H), 2.26 (s, 3H), 1.85- 1.70 (m, 1H), 1.40-1.21 (m, 2H), 1.10-1.04 (m, 3H); LCMS(electrospray) m/z 475 (M + H+).

D






(1S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)thiazolo[5,4-b]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







219


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1H NMR (400 MHz, DMSO-d6) δ 13.32 (s, 1H), 13.04 (s, 1H), 9.13 (s, 1H), 8.31 (s, 1H), 7.79 (s, 1H), 7.52 (d, J = 9.3 Hz, 1H), 5.23-4.94 (m, 1H), 2.35-2.17 (m, 4H), 1.86-1.68 (m, 1H), 1.41-1.29 (m, 1H); LCMS(electrospray) m/z 418.0 (M + H+).

D






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-





(methylthio)-1H-indazol-4-yl)thiazolo[4,5-





c]pyridin-2-yl)cyclopropane-1-





carboxamide







220


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1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H), 13.10 (s, 1H), 9.12 (s, 1H), 8.53 (s, 1H), 8.14 (s, 1H), 7.63 (d, J = 11.5 Hz, 1H), 5.19-4.96 (m, 1H), 3.17 (s, 3H), 2.29-2.21 (m, 1H), 1.86-1.68 (m, 1H), 1.39-1.29 (m, 1H); LCMS(electrospray) m/z 434.0 (M + H+).

D






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-





(methylsulfinyl)-1H-indazol-4-





yl)thiazolo[4,5-c]pyridin-2-





yl)cyclopropane-1-carboxamide







221


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1H NMR (400 MHz, DMSO-d6) δ 12.77 (s, 1H), 9.70 (s, 1H), 9.00 (s, 1H), 8.66 (d, J = 9.2 Hz, 1H), 8.59 (s, 1H), 8.55 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 5.91~5.71 (m, 1H), 3.11 (s, 3H), 3.05~3.00 (m, 1H), 2.54~ 2.48 (m, 1H), 2.07~2.03 (m, 1H); LCMS (electrospray) m/z 350.0 (M + H)+.

E






(1S,2S)-2-fluoro-N-(6-(5-methyl-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide







222


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1H NMR (400 MHz, DMSO-d6) δ 13.23 (s, 1H), 11.01 (s, 1H), 8.93 (s, 1H), 8.17 (s, 1H), 7.59~7.51 (m, 3H), 7.42 (t, J = 7.8 Hz, 1H), 7.26 (d, J = 6.4 Hz, 1H), 5.00~4.79 (m, 1H), 2.13~2.10 (m, 1H), 1.67~1.60 (m, 1H), 1.17~1.09 (m, 1H); LCMS (electrospray) m/z 335.9 (M + H)+.

E






(1S,2S)-N-(6-(1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







223


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1H NMR (400 MHz, METHANOL-d4) δ 8.92 (s, 1H), 8.13 (s, 1H), 7.99-7.91 (m, 3H), 7.68 (dd, J = 1.0, 8.9 Hz, 1H), 7.58 (d, J = 8.9 Hz, 1H), 1.95- 1.87 (m, 1H), 1.12-1.07 (m, 2H), 1.05-0.98 (m, 2H); LCMS (electrospray) m/z 352.0 (M + H)+.

F






N-(6-(5-chloro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







224


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1H NMR (400 MHz, METHANOL-d4) δ 8.98 (s, 1H), 8.17-8.09 (m, 3H), 7.94 (d, J = 9.2 Hz, 1H), 7.71 (d, J = 9.2 Hz, 1H), 7.54-7.48 (m, 1H), 3.90 (s, 3H), 1.94-1.85 (m, 1H), 1.12-1.06 (m, 2H), 1.05-0.99 (m, 2H); LCMS (electrospray) m/z 348.0 (M + H)+.

F






N-(6-(5-methoxy-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







225


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1H NMR (400 MHz, METHANOL-d4) δ 8.76 (s, 1H), 7.88-7.83 (m, 2H), 7.75 (dd, J = 1.5, 9.2 Hz, 1H), 7.66 (dd, J = 0.8, 8.9 Hz, 1H), 7.36 (d, J = 8.9 Hz, 1H), 1.96-1.88 (m, 1H), 1.09-1.04 (m, 2H), 1.02-0.95 (m, 2H); LCMS (electrospray) m/z 333.2

F






N-(6-(5-amino-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 3 TFA salt







226


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1H NMR (400 MHz, DMSO-d6) δ 11.43 (br s, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 7.93 (s, 1H), 7.84-7.76 (m, 2H), 7.69 (d, J = 9.4 Hz, 1H), 7.45 (br d, J = 8.9 Hz, 1H), 1.97 (quin, J = 6.2 Hz, 1H), 0.86 (d, J = 6.0 Hz, 4H); LCMS (electrospray) m/z 386.1 (M + H)+.

F






N-(6-(5-(trifluoromethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







227


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1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.83 (s, 1H), 8.14 (s, 1H), 7.75 (d, J = 9.0 Hz, 1H), 7.68 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.37 (d, J = 10.9 Hz, 1H), 6.90-5.46 (m, 6H), 1.94 (quin, J = 6.2 Hz, 1H), 0.95-0.82 (m, 4H); LCMS (electrospray) m/z 351.2 (M + H)+.

F






N-(6-(5-amino-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 3TFA salt







228


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1H NMR (400 MHz, METHANOL-d4) δ 8.56- 8.53 (m, 1H), 8.11 (s, 1H), 7.82 (s, 1H), 7.68 (d, J = 8.9 Hz, 1H), 7.58-7.50 (m, 2H), 7.38 (dd, J = 1.7, 9.2 Hz, 1H), 1.97-1.88 (m, 1H), 1.02-0.97 (m, 2H), 0.93-0.88 (m, 2H); LCMS (electrospray) m/z 397.9 (M + H)+.

F






N-(6-(5-bromo-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide







229


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1H NMR (400 MHz, METHANOL-d4) δ 8.82 (br s, 1H), 7.89 (br d, J = 8.8 Hz, 1H), 7.82-7.73 (m, 3H), 7.45 (d, J = 8.9 Hz, 1H), 2.98 (s, 3H), 1.98-1.86 (m, 1H), 1.12-0.95 (m, 4H); LCMS (electrospray) m/z 347.0 (M + H)+.

F






N-(6-(5-(methylamino)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 3 TFA salt







230


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1H NMR (400 MHz, METHANOL-d4) δ 8.60- 8.57 (m, 1H), 8.09 (s, 1H), 7.87 (s, 1H), 7.58-7.49 (m, 3H), 7.48-7.44 (m, 1H), 2.62 (s, 6H), 1.97- 1.89 (m, 1H), 1.03-0.97 (m, 2H), 0.94-0.88 (m, 2H); LCMS (electrospray) m/z 361.2 (M + H)+.

F






N-(6-(5-(dimethylamino)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide







231


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1H NMR (400 MHz, DMSO-d6) δ 13.49 (br s, 1H), 11.05 (s, 1H), 8.78 (s, 1H), 8.14 (s, 1H), 7.92 (s, 1H), 7.64 (d, J = 8.7 Hz, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.32 (dd, J = 1.7, 9.2 Hz, 1H), 2.05-1.86 (m, 1H), 0.85-0.79 (m, 4H); LCMS (electrospray) m/z 414.1 (M + H)+.

G






N-(6-(5-bromo-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 TFA salt







232


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1H NMR (400 MHz, METHANOL-d4) δ 9.17 (s, 1H), 8.22 (s, 1H), 8.21-8.18 (m, 1H), 8.06 (d, J = 9.3 Hz, 1H), 7.84 (s, 2H), 1.94-1.87 (m, 1H), 1.14-1.09 (m, 2H), 1.07-1.01 (m, 2H); LCMS (electrospray) m/z 343.0 (M + H)+.

F






N-(6-(5-cyano-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







233


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1H NMR (400 MHz, METHANOL-d4) δ 8.91 (s, 1H), 8.10 (s, 1H), 8.07-8.03 (m, 1H), 8.00-7.96 (m, 1H), 7.91 (s, 1H), 7.72-7.65 (m, 2H), 4.61 (s, 2H), 3.61 (s, 1H), 1.93-1.86 (m, 1H), 1.13-1.08 (m, 2H), 1.07-1.01 (m, 2H); LCMS (electrospray) m/z 348.2 (M + H)+.

F






N-(6-(5-(hydroxymethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







234


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1H NMR (400 MHz, METHANOL-d4) δ 8.82 (s, 1H), 8.10 (s, 1H), 8.01-7.95 (m, 1H), 7.95-7.89 (m, 1H), 7.78 (s, 1H), 7.64 (d, J = 8.7 Hz, 1H), 7.50 (d, J = 8.7 Hz, 1H), 2.69 (q, J = 7.5 Hz, 2H), 1.93- 1.85 (m, 1H), 1.19 (t, J = 7.5 Hz, 3H), 1.13-1.07 (m, 2H), 1.07-0.98 (m, 2H); LCMS (electrospray) m/z 346.2 (M + H)+.

F






N-(6-(5-ethyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







235


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1H NMR (400 MHz, DMSO-d6) δ 11.82 (br s, 1H), 8.90 (s, 1H), 8.19 (s, 1H), 7.91 (d, J = 0.6 Hz, 1H), 7.83 (d, J = 9.2 Hz, 1H), 7.63 (br d, J = 9.2 Hz, 1H), 7.50 (d, J = 11.4 Hz, 1H), 6.54 (dd, J = 11.9, 17.9 Hz, 1H), 5.63 (br d, J = 17.9 Hz, 1H), 5.42 (br d, J = 11.6 Hz, 1H), 2.06-1.94 (m, 1H), 0.95-0.85 (m, 4H); LCMS (electrospray) m/z 362.1 (M + H)+.

F






N-(6-(6-fluoro-5-vinyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







236


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1H NMR (400 MHz, DMSO-d6) δ 11.46 (br s, 1H), 8.82 (s, 1H), 8.20 (s, 1H), 7.94 (s, 1H), 7.85-7.76 (m, 2H), 7.71 (br d, J = 9.2 Hz, 1H), 7.47 (br d, J = 8.6 Hz, 1H), 5.11-4.85 (m, 1H), 2.20 (td, J = 6.9, 13.9 Hz, 1H), 1.77-1.63 (m, 1H), 1.31-1.16 (m, 1H), 1.31-1.16 (m, 1H); LCMS (electrospray) m/z 403.8 (M + H)+.

F






(1S,2S)-2-fluoro-N-(6-(5-





(trifluoromethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 HCl salt







237


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1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 11.05 (s, 1H), 8.77 (s, 1H), 8.16 (s, 1H), 7.91 (s, 1H), 7.62 (d, J = 9.7 Hz, 1H), 7.58-7.48 (m, 2H), 7.34 (dd, J = 1.7, 9.2 Hz, 1H), 5.04-4.80 (m, 1H), 2.20-2.10 (m, 1H), 1.73-1.59(m, 1H), 1.23-1.10 (m, 1H); LCMS (electrospray) m/z 370.1 (M + H)+.

F






(1S,2S)-N-(6-(5-chloro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







238


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1H NMR (400 MHz, DMSO-d6) δ 11.49 (br s, 1H), 8.88 (br s, 1H), 8.20 (s, 1H), 7.90 (s, 1H), 7.73 (br d, J = 9.2 Hz, 1H), 7.69-7.64 (m, 1H), 7.63-7.53 (m, 2H), 5.11-4.86 (m, 1H), 2.19 (br s, 1H), 1.77- 1.62 (m, 1H), 1.22 (br d, J = 2.9 Hz, 1H); LCMS (electrospray) m/z 415.8 (M + H)+.

F






(1S,2S)-N-(6-(5-bromo-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 HCl





salt







239


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1H NMR (400 MHz, DMSO-d6) δ 11.69 (br s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 8.04 (s, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.77 (br d, J = 9.0 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.59 (br d, J = 8.8 Hz, 1H), 2.40 (s, 3H), 2.03-1.95 (m, 1H), 0.95-0.87 (m, 4H); LCMS (electrospray) m/z 359.9 (M + H)+.

F






N-(6-(5-acetyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







240


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1H NMR (400 MHz, DMSO-d6) δ 12.27 (s, 1H), 8.99 (s, 1H), 8.21 (s, 1H), 7.98 (d, J = 9.2 Hz, 1H), 7.85 (dd, J = 1.5, 9.1 Hz, 1H), 7.69 (dd, J = 1.0, 8.1 Hz, 2H), 6.23-5.16 (m, 6H), 2.13-2.00 (m, 1H), 1.04-0.87 (m, 4H); LCMS (electrospray) m/z 367.0 (M + H+)

F






N-(6-(5-amino-6-chloro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 3 HCl salt







241


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1H NMR (400 MHz, DMSO-d6) δ 12.09 (br s, 1H), 9.04 (s, 1H), 8.22 (s, 1H), 7.97-7.86 (m, 3H), 7.41 (d, J = 10.5 Hz, 1H), 2.07-2.00 (m, 1H), 1.99-1.91 (m, 1H), 1.99-1.91 (m, 1H), 0.97-0.87 (m, 4H), 0.78-0.68 (m, 2H), 0.26 (br d, J = 4.5 Hz, 2H); LCMS (electrospray) m/z 376.1 (M + H+)

F






N-(6-(5-cyclopropyl-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







242


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1H NMR (400 MHz, DMSO-d6) δ 13.50 (br s, 1H), 11.17 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 7.79 (d, J = 1.0 Hz, 1H), 7.68 (dd, J = 0.9, 9.0 Hz, 1H), 6.97 (s, 1H), 6.96 (d, J = 2.0 Hz, 1H), 6.96- 6.93 (m, 1H), 2.13-2.00 (m, 1H), 1.04-0.87 (m, 4H); LCMS (electrospray)m/z 370.8 (M + H+)

F






N-(6-(5-chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







243


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1H NMR (400 MHz, DMSO-d6) δ 11.91-11.45 (m, 1H), 9.05-8.93 (m, 1H), 8.24 (br s, 1H), 8.00 (s, 1H), 7.87-7.59 (m, 3H), 5.07 (br s, 1H), 4.91 (br s, 1H), 2.22 (br s, 1H), 1.79-1.63 (m, 1H), 1.23 (br s, 1H); LCMS (electrospray) m/z 388.0 (M + H+)

F






(1S,2S)-N-(6-(5-chloro-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





HCl salt







244


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1H NMR (400 MHz, DMSO-d6) δ 11.99 (br s, 1H), 8.99 (s, 1H), 8.23 (s, 1H), 7.95-7.85 (m, 2H), 7.82 (d, J = 0.9 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.08 (d, J = 8.7 Hz, 1H), 2.07-1.89 (m, 2H), 0.98-0.90 (m, 4H), 0.87-0.81 (m, 2H), 0.69-0.63 (m, 2H); LCMS (electrospray) m/z 358.0 (M + H+)

F






N-(6-(5-cyclopropyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







245


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1H NMR (400 MHz, DMSO-d6) δ 11.27 (br s, 1H), 8.78 (s, 1H), 8.14 (s, 1H), 7.82 (s, 1H), 7.67 (br d, J = 9.0 Hz, 1H), 7.46 (br d, J = 9.0 Hz, 1H), 7.40 (br d, J = 9.8 Hz, 1H), 2.21 (br d, J = 1.2 Hz, 3H), 2.00- 1.88 (m, 1H), 0.86 (br d, J = 5.7 Hz, 4H); LCMS (electrospray) m/z 350.2 (M + H+)

F






N-(6-(6-fluoro-5-methyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 TFA salt







246


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1H NMR (400 MHz, DMSO-d6) δ 11.30 (s, 1H), 8.73 (s, 1H), 8.15 (s, 1H), 7.71-7.65 (m, 2H), 7.40 (br d, J = 11.8 Hz, 2H), 3.04 (td, J = 7.0, 14.1 Hz, 1H), 1.98-1.92 (m, 1H), 1.28 (dd, J = 6.9, 17.4 Hz, 6H), 0.87 (d, J = 6.1 Hz, 4H); LCMS (electrospray) m/z 378.1 (M + H+)

F






N-(6-(6-fluoro-5-isopropyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 TFA salt







247


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1H NMR (400 MHz, DMSO-d6) δ 12.22 (s, 1H), 8.99 (s, 1H), 8.24 (s, 1H), 7.98-7.91 (m, 1H), 7.90- 7.84 (m, 2H), 7.71-7.65 (m, 1H), 7.62-7.57 (m, 1H), 2.40 (s, 3H), 2.11-1.99 (m, 1H), 1.05-0.87 (m, 4H); LCMS (electrospray) m/z 364.1 (M + H+)

F






N-(6-(5-(methylthio)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







248


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1H NMR (400 MHz, DMSO-d6) δ 12.18 (s, 1H), 8.95 (s, 1H), 8.24 (s, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.81-7.74 (m, 2H), 7.46 (d, J = 10.3 Hz, 1H), 2.58 (q, J = 6.8 Hz, 2H), 2.09-2.00 (m, 1H), 1.09 (t, J = 7.3 Hz, 3H), 0.98-0.87 (m, 4H); LCMS (electrospray) m/z 364.1 (M + H+)

F






N-(6-(5-ethyl-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







249


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1H NMR (400 MHz, DMSO-d6) δ 13.53 (br s, 1H), 11.13 (s, 1H), 8.72 (s, 1H), 8.15 (s, 1H), 7.97 (s, 1H), 7.78-7.74 (m, 1H), 7.73-7.69 (m, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.34 (d, J = 9.0 Hz, 1H), 7.11- 6.80 (m, 1H), 2.00-1.91 (m, 1H), 0.87-0.81 (m, 4H); LCMS (electrospray) m/z 368.2 (M + H+)

F






N-(6-(5-(difluoromethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 TFA salt







250


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1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 11.06 (s, 1H), 8.70 (s, 1H), 8.15 (s, 1H), 7.80 (s, 1H), 7.56 (d, J = 9.2 Hz, 1H), 7.38 (d, J = 9.8 Hz, 1H), 7.29 (dd, J = 1.7, 9.2 Hz, 1H), 5.09-4.77 (m, 1H), 2.22 (d, J = 2.4 Hz, 3H), 2.18-2.11 (m, 1H), 1.75-1.58 (m, 1H), 1.24-1.06 (m, 1H); LCMS (electrospray) m/z 368.1 (M + H+)

F






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide







251


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1H NMR (400 MHz, DMSO-d6) δ 11.92 (br s, 1H), 8.99 (s, 1H), 8.21 (s, 1H), 7.96-7.81 (m, 3H), 7.46 (d, J = 9.9 Hz, 1H), 4.43 (s, 2H), 2.07-1.96 (m, 1H), 0.96-0.87 (m, 4H); LCMS (electrospray) m/z 366.1 (M + H+)

F






N-(6-(6-fluoro-5-(hydroxymethyl)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







252


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1H NMR (400 MHz, METHANOL-d4) δ 9.03 (s, 1H), 8.18-8.14 (m, 1H), 8.05 (s, 1H), 7.99 (d, J = 9.2 Hz, 1H), 7.49 (d, J = 10.6 Hz, 1H), 3.77 (s, 3H), 1.95-1.82 (m, 1H), 1.15-1.07 (m, 2H), 1.06- 1.00 (m, 2H); LCMS (electrospray) m/z 366.1 (M + H+)

F






N-(6-(6-fluoro-5-methoxy-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide. 2 HCl salt







253


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1H NMR (400 MHz, DMSO-d6) δ 13.64 (s, 1H), 11.16 (s, 1H), 8.76 (s, 1H), 8.19 (s, 1H), 7.98 (s, 1H), 7.66-7.57 (m, 2H), 7.29 (dd, J = 1.8, 9.1 Hz, 1H), 7.13-6.78 (m, 1H), 5.07-4.80 (m, 1H), 2.16 (td, J = 6.9, 13.9 Hz, 1H), 1.74-1.61 (m, 1H), 1.24- 1.13 (m, 1H); LCMS (electrospray) m/z 404.0 (M + H+)

F






(1S,2S)-N-(6-(5-(difluoromethyl)-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA salt







254


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1H NMR (400 MHz, DMSO-d6) δ 13.50 (s, 1H), 11.11 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.93 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.32 (dd, J = 1.6, 7.6 Hz, 1H), 5.02 (m, 0.5H), 4.85 (m, 0.5H), 2.16 (m, 1H), 1.66 (m, 1H), 1.16 (m, 1H), LCMS (electrospray) m/z 433.00 (M + H)+.

F






(1S,2S)-N-(6-(5-bromo-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







255


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1H NMR (400 MHz, DMSO-d6) δ 13.59 (br s, 1H), 11.04 (s, 1H), 8.72 (s, 1H), 8.15 (s, 1H), 7.97 (s, 1H), 7.62-7.56 (m, 2H), 7.23 (dd, J = 1.7, 9.1 Hz, 1H), 7.11-6.80 (m, 1H), 2.01-1.92 (m, 1H), 0.85- 0.79 (m, 4H); LCMS (electrospray) m/z 386.1 (M + H+)

F






N-(6-





(5-(difluoromethyl)-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropanecarboxamide







256


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1H NMR (400 MHz, DMSO-d6) δ 14.14 (s, 1H), 11.13 (s, 1H), 8.87-8.83 (m, 1H), 8.19 (s, 1H), 8.15 (br s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.40 (dd, J = 1.8, 9.2 Hz, 1H), 5.04-4.83 (m, 1H), 2.19- 2.13 (m, 1H), 1.72-1.62 (m, 1H), 1.23-1.15 (m, 1H); LCMS (electrospray) m/z 422.1 (M + H)+.

F






(1S,2S)-N-(6-(5,7-dichloro-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA salt







257


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1H NMR (400 MHz, DMSO-d6) δ 13.36 (s, 1H), 11.19 (br s, 1H), 8.72 (s, 1H), 8.16 (s, 1H), 7.80 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.37 (br d, J = 9.2 Hz, 1H), 5.10-4.79 (m, 1H), 2.48 (d, J = 1.7 Hz, 3H), 2.21 (d, J = 2.8 Hz, 3H), 2.18-2.10 (m, 1H), 1.75- 1.61 (m, 1H), 1.27-1.10 (m, 1H); LCMS (electrospray) m/z 382.4 (M + H)+.

F






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-





dimethyl-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA salt







258


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1H NMR (400 MHz, DMSO-d6)) δ 13.55 (br s, 1H), 11.21 (s, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.43 (d, J = 9.2 Hz, 1H), 5.08-4.77 (m, 1H), 3.01 (s, 3H), 3.00 (s, 3H), 2.16 (td, J = 7.0, 13.8 Hz, 1H), 1.76-1.57 (m, 1H), 1.27-1.11 (m, 1H); LCMS (electrospray) m/z 431.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA





salt







259


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1H NMR (400 MHz, DMSO-d6) δ 11.20 (br s, 1H), 8.88 (s, 1H), 8.21 (s, 1H), 8.09 (d, J = 1.1 Hz, 1H), 7.66 (br d, J = 8.3 Hz, 1H), 7.46 (br d, J = 8.8 Hz, 1H), 5.11-4.81 (m, 1H), 2.23-2.11 (m, 1H), 1.96 (s, 3H), 1.93 (s, 3H), 1.75-1.62 (m, 1H), 1.25- 1.13 (m, 1H); LCMS (electrospray) m/z 464.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-





(dimethylphosphoryl)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA salt







260


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1H NMR (400 MHz, DMSO-d6) δ 14.17-13.29 (m, 1H), 11.18 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.97 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.36 (dd, J = 1.3, 9.2 Hz, 1H), 5.12-4.77 (m, 1H), 2.26 (d, J = 2.9 Hz, 3H), 2.16 (td, J = 7.0, 14.0 Hz, 1H), 1.76- 1.58 (m, 1H), 1.25-1.10 (m, 1H); LCMS (electrospray) m/z 402.0 (M + H)+.

H






(1S,2S)-N-(6-(7-chloro-6-fluoro-5-methyl-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA salt







261


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1H NMR (400 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.89 (s, 1H), 8.20 (s, 1H), 8.17 (s, 1H), 7.67 (d, J = 9.0 Hz, 1H), 7.50 (br d, J = 9.4 Hz, 1H), 5.09- 4.82 (m, 1H), 2.18 (td, J = 6.9, 13.9 Hz, 1H), 1.75- 1.62 (m, 1H), 1.26-1.14 (m, 1H); LCMS (electrospray) m/z 466.1 (M + H)+.

H






(1S,2S)-N-(6-(7-bromo-5-chloro-6-fluoro-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 HCl salt







262


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1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.73 (s, 1H), 8.15 (s, 1H), 7.95 (br s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.35 (d, J = 7.8 Hz, 1H), 5.17-4.75 (m, 1H), 2.25 (d, J = 2.9 Hz, 3H), 2.28-2.12 (m, 1H), 1.72-1.59 (m, 1H), 1.24-1.10 (m, 1H); LCMS (electrospray) m/z 386.3 (M + H)+.

H






(1S,2S)-N-(6-(6,7-difluoro-5-methyl-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA salt







263


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1H NMR (400 MHz, METHANOL-d4) δ 8.78 (s, 1H), 7.93 (s, 1H), 7.85 (d, J = 9.2 Hz, 1H), 7.71 (d, J = 9.5 Hz, 1H), 5.06-4.94 (m, 1H), 2.31 (d, J = 3.1 Hz, 3H), 2.16-2.09 (m, 1H), 1.93-1.79 (m, 1H), 1.33-1.22 (m, 1H); LCMS (electrospray) m/z 436.0 (M + H)+.

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(trifluoromethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA salt







264


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1H NMR (400 MHz, DMSO-d6) δ 13.38 (br s, 1H), 11.28 (br s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.85 (s, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.52 (s, 1H), 7.44 (br d, J = 9.0 Hz, 1H), 7.14 (dd, J = 11.4, 17.7 Hz, 1H), 6.12 (br d, J = 17.9 Hz, 1H), 5.51 (d, J = 11.5 Hz, 1H), 5.07-4.86 (m, 1H), 2.34 (s, 3H), 2.16 (td, J = 7.0, 13.8 Hz, 1H), 1.76-1.60 (m, 1H), 1.20 (tdd, J = 6.4, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 376.1 (M + H)+.

H






(1S,2S)-2-fluoro-N-(6-(5-methyl-7-vinyl-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2TFA salt







265


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1H NMR (400 MHz, DMSO-d6) δ 13.09 (br s, 1H), 11.12 (s, 1H), 8.72 (s, 1H), 8.15 (s, 1H), 7.90 (br s, 1H), 7.56 (d, J = 9.2 Hz, 1H), 7.35 (br d, J = 9.2 Hz, 1H), 5.11-4.75 (m, 1H), 3.17 (br d, J = 2.1 Hz, 3H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS (electrospray) m/z 417.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methylamino)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA





salt







266


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1H NMR (400 MHz, DMSO-d6) δ 13.79 (br s, 1H), 11.14 (s, 1H), 8.84 (s, 1H), 8.19 (s, 1H), 8.06 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.41 (dd, J = 1.6, 9.3 Hz, 1H), 5.08-4.80 (m, 1H), 2.58 (s, 3H), 2.22- 2.11 (m, 1H), 1.74-1.60 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.4 Hz, 1H); LCMS (electrospray) m/z 434.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methylthio)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA salt







267


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1H NMR (400 MHz, DMSO-d6) δ 13.52 (br s, 1H), 11.19 (s, 1H), 8.90 (s, 1H), 8.22 (d, J = 3.4 Hz, 2H), 7.65 (d, J = 9.3 Hz, 1H), 7.44 (dd, J = 1.7, 9.3 Hz, 1H), 5.07-4.80 (m, 1H), 3.56 (s, 3H), 2.21-2.14 (m, 1H), 1.72-1.62 (m, 1H), 1.24-1.15 (m, 1H); LCMS (electrospray) m/z 466.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methylsulfonyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA





salt







268


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1H NMR (400 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.78 (s, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 7.65 (d, J = 9.1 Hz, 1H), 7.42 (dd, J = 1.6, 9.1 Hz, 1H), 5.08-4.84 (m, 1H), 2.26 (d, J = 3.0 Hz, 3H), 2.21- 2.11 (m, 1H), 1.75-1.62 (m, 1H), 1.20 (tdd, J = 6.3, 9.0, 12.4 Hz, 1H); LCMS (electrospray) m/z 446.2 (M + H)+.

H






(1S,2S)-N-(6-(7-bromo-6-fluoro-5-methyl-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA salt







269


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1H NMR (400 MHz, DMSO-d6) δ 11.22 (s, 1H), 8.76 (s, 1H), 8.16 (s, 1H), 7.89 (s, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.41 (dd, J = 1.6, 9.1 Hz, 1H), 5.06- 5.02 (m, 1H), 4.90-4.84 (m, 1H), 2.52 (s, 3H), 2.23 (d, J = 2.9 Hz, 3H), 2.20-2.12 (m, 1H), 1.75- 1.63 (m, 1H), 1.26-1.14 (m, 1H); LCMS (electrospray) m/z 414.1 (M + H)+.

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(methylthio)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA salt







270


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1H NMR (400 MHz, DMSO-d6) δ 13.23 (br s, 1H), 11.20 (s, 1H), 8.79 (s, 1H), 8.19 (s, 1H), 8.03 (s, 1H), 7.64 (d, J = 9.2 Hz, 1H), 7.37 (dd, J = 1.7, 9.1 Hz, 1H), 5.06-4.84 (m, 1H), 3.50 (br s, 3H), 2.27 (d, J = 2.8 Hz, 3H), 2.21-2.12 (m, 1H), 1.73-1.62 (m, 1H), 1.23-1.14 (m, 1H); LCMS (electrospray) m/z 446.2 (M + H)+.

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(methylsulfonyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA salt







271


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1H NMR (400 MHz, DMSO-d6) δ 13.54 (br s, 1H), 11.27 (s, 1H), 8.73 (s, 1H), 8.16 (s, 1H), 7.84 (s, 1H), 7.64 (d, J = 9.3 Hz, 1H), 7.41 (dd, J = 1.4, 9.1 Hz, 1H), 5.13-4.79 (m, 1H), 4.08 (d, J = 1.0 Hz, 3H), 2.22 (d, J = 3.1 Hz, 3H), 2.20-2.10 (m, 1H), 1.77-1.60 (m, 1H), 1.20 (tdd, J = 6.3, 9.1, 12.4 Hz, 1H); LCMS (electrospray) m/z 398.2 (M + H)+.

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-





methoxy-5-methyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA salt







272


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1H NMR (400 MHz, DMSO-d6) δ 13.81 (br s, 1H), 11.15 (s, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 8.00 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 1.6, 9.2 Hz, 1H), 5.12-4.81 (m, 1H), 4.16 (d, J = 1.5 Hz, 3H), 2.22-2.11 (m, 1H), 1.75-1.60 (m, 1H), 1.18 (tdd, J = 6.3, 9.1, 12.4 Hz, 1H); LCMS (electrospray) m/z 418.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





methoxy-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA salt







273


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1H NMR (400 MHz, DMSO-d6) δ 10.90 (br s, 1H), 8.63 (s, 1H), 8.13 (s, 1H), 7.73 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 5.03-4.80 (m, 1H), 3.00 (s, 6H), 2.19 (d, J = 2.9 Hz, 3H), 2.18- 2.14 (m, 1H), 1.78-1.65 (m, 1H), 1.24-1.14 (m, 1H); LCMS (electrospray) m/z 411.2 (M + H)+.

H






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA





salt







274


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1H NMR (400 MHz, DMSO-d6) δ 11.29 (s, 1H), 10.19 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.82 (s, 1H), 7.66 (s, 1H), 7.64 (s, 1H), 7.45 (br d, J = 9.9 Hz, 1H), 6.61-6.51 (m, 1H), 6.35 (dd, J = 1.8, 16.9 Hz, 1H), 5.89-5.84 (m, 1H), 5.08-5.03 (m, 1H), 4.89 (dt, J = 3.8, 6.3 Hz, 1H), 2.32 (s, 3H), 2.21- 2.12 (m, 1H), 1.76-1.60 (m, 1H), 1.27-1.14 (m, 1H); LCMS (electrospray) m/z 419.3 (M + H)+.

H






(1S,2S)-N-(6-(7-acrylamido-5-methyl-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA salt







275


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1H NMR (400 MHz, DMSO-d6) δ 13.80 (br s, 1H), 11.18 (s, 1H), 8.82 (s, 1H), 8.17 (s, 1H), 8.00 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.42 (dd, J = 1.5, 9.3 Hz, 1H), 5.11-4.81 (m, 1H), 4.40 (q, J = 7.1 Hz, 2H), 2.21-2.10 (m, 1H), 1.74-1.61 (m, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.25-1.09 (m, 1H); LCMS (electrospray) m/z 432.3 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-ethoxy-6-fluoro-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA salt







276


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1H NMR (400 MHz, DMSO-d6) δ 11.23-11.08 (m, 1H), 10.40-10.29 (m, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 8.01 (br d, J = 7.9 Hz, 2H), 7.59 (br d, J = 9.0 Hz, 1H), 7.46-7.36 (m, 1H), 6.66-6.49 (m, 1H), 6.41-6.36 (m, 1H), 5.95-5.85 (m, 1H), 5.12-4.78 (m, 1H), 2.22-2.08 (m, 1H), 1.77-1.58 (m, 1H), 1.27-1.10 (m, 1H); LCMS (electrospray) m/z 439.2 (M + H)+.

H






(1S,2S)-N-(6-(7-acrylamido-5-chloro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA salt







277


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1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 9.88 (br d, J = 6.7 Hz, 1H), 8.77 (dd, J = 1.0, 1.6 Hz, 1H), 8.19 (s, 1H), 8.03 (br s, 1H), 7.60 (d, J = 9.2 Hz, 1H), 7.36 (dd, J = 1.8, 9.2 Hz, 1H), 5.05- 5.00 (m, 1H), 4.86 (dt, J = 3.9, 6.2 Hz, 1H), 3.58 (br d, J = 11.0 Hz, 4H), 3.53-3.44 (m, 2H), 3.39- 3.26 (m, 2H), 2.93 (br d, J = 2.7 Hz, 3H), 2.20- 2.12 (m, 1H), 1.73-1.61 (m, 1H), 1.24-1.13 (m, 1H); LCMS (electrospray) m/z 486.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(4-





methylpiperazin-1-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 3 TFA







278


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1H NMR (400 MHz, DMSO-d6) δ 13.09 (br s, 1H), 10.92 (s, 1H), 8.64 (s, 1H), 8.13 (s, 1H), 7.75 (s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.48 (d, J = 8.3 Hz, 1H), 7.32 (d, J = 8.6 Hz, 1H), 7.26 (dd, J = 1.7, 9.2 Hz, 1H), 4.46 (t, J = 5.2 Hz, 1H), 3.69-3.60 (m, 1H), 3.55-3.48 (m, 1H), 2.32 (s, 3H), 2.08-1.99 (m, 1H), 1.49-1.39 (m, 1H), 1.02-0.96 (m, 1H), 0.95-0.90 (m, 1H); LCMS (electrospray) m/z 362.3 (M + H)+.

H






2-(hydroxymethyl)-N-(6-(5-methyl-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide







279


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1H NMR (400 MHz, DMSO-d6) δ 13.54 (br s, 1H), 11.21 (s, 1H), 8.81 (s, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.62 (d, J = 9.3 Hz, 1H), 7.43 (dd, J = 1.6, 9.2 Hz, 1H), 5.07-4.84 (m, 1H), 3.84-3.82 (m, 4H), 3.29 (br s, 4H), 2.21-2.12 (m, 1H), 1.74-1.61(m, 1H), 1.19 (tdd, J = 6.4, 9.1, 12.4 Hz, 1H); LCMS (electrospray) m/z 473.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





morpholino-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







280


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1H NMR (400 MHz, DMSO-d6) δ 11.23 (1 H, s) 8.78 (1 H, s) 8.16 (1 H, s) 7.93 (1 H, br s) 7.61 (1 H, d, J = 9.20 Hz) 7.44 (1 H, br d, J = 9.40 Hz) 5.16- 4.71 (1 H, m) 2.17 (1 H, dt, J = 14.07, 6.97 Hz) 1.76-1.61 (1 H, m) 1.27-1.17 (4 H, m); LCMS (electrospray) m/z 431.0 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(ethylamino)-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







281


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1H NMR (400 MHz, DMSO-d6) δ 13.50 (1 H, br s) 11.38-11.10 (1 H, m) 8.99-8.77 (1 H, m) 8.17 (1 H, s) 7.96 (1 H, s) 7.77-7.57 (1 H, m) 7.53-7.35 (1 H, m) 5.14-4.79 (1 H, m) 3.39-3.37 (1 H, m) 3.30 (4 H, q, J = 7.01 Hz) 2.17 (1 H, dt, J = 13.88, 7.00 Hz) 1.79-1.59 (1 H, m) 1.27-1.12 (1 H, m) 1.06-0.95 (6 H, m); LCMS (electrospray) m/z 459.0 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(diethylamino)-





6-fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







282


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1H NMR (400 MHz, DMSO-d6) δ 13.15 (br s, 1H), 11.16 (s, 1H), 8.74 (s, 1H), 8.16 (s, 1H), 7.93 (br s, 1H), 7.58 (d, J = 9.0 Hz, 1H), 7.37 (dd, J = 1.5, 9.2 Hz, 1H), 5.07-4.82 (m, 1H), 3.72 (br s, 4H), 2.21- 2.12 (m, 1H), 1.98-1.93 (m, 4H), 1.73-1.62 (m, 1H), 1.24-1.13 (m, 1H); LCMS (electrospray) m/z 457.3 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(pyrrolidin-1-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







283


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1H NMR (400 MHz, DMSO-d6) δ13.08 (br s, 1H), 11.08 (s, 1H), 8.70 (s, 1H), 8.14 (s, 1H), 7.89 (br s, 1H), 7.54 (d, J = 9.3 Hz, 1H), 7.30 (dd, J = 1.6, 9.3 Hz, 1H), 5.06-4.79 (m, 1H), 4.39 (br t, J = 5.7 Hz, 4H), 2.39-2.32 (m, 2H), 2.15 (td, J = 7.0, 13.7 Hz, 1H), 1.72-1.61 (m, 1H), 1.22-1.13 (m, 1H); LCMS (electrospray) m/z 443.4 (M + H)+.

H






(1S,2S)-N-(6-(7-(azetidin-1-yl)-5-chloro-





6-fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







284


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1H NMR (400 MHz, DMSO-d6) δ 11.22-11.10 (m, 1H), 8.76 (br s, 1H), 8.17 (s, 1H), 7.62-7.56 (m, 2H), 7.43-7.32 (m, 1H), 6.87 (s, 1H), 5.07- 4.83 (m, 1H), 2.21-2.10 (m, 1H), 1.75-1.60 (m, 1H), 1.25-1.13 (m, 1H); LCMS(electrospray) m/z 385.4 (M + H+).

H






(1S,2S)-N-(6-(6-amino-5-chloro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







285


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1H NMR (400 MHz, DMSO-d6) δ 13.36 (br s, 1H), 11.28 (s, 1H), 8.69 (s, 1H), 8.15 (s, 1H), 7.73 (s, 1H), 7.63 (d, J = 9.1 Hz, 1H), 7.43 (br d, J = 9.1 Hz, 1H), 6.83 (s, 1H), 5.08-4.86 (m, 1H), 3.99 (s, 3H), 2.32 (s, 3H), 2.21-2.12 (m, 1H), 1.75-1.63 (m, 1H), 1.27-1.12 (m, 1H); LCMS(electrospray) m/z 380.5 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(7-methoxy-5-





methyl-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







286


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1H NMR (400 MHz, DMSO-d6) δ 13.53-13.11 (m, 1H), 11.23-11.11 (m, 1H), 9.82 (s, 1H), 8.80 (br s, 1H), 8.17 (d, J = 11.5 Hz, 2H), 7.89 (s, 1H), 7.65-7.57 (m, 1H), 7.43-7.32 (m, 1H), 6.72 (dd, J = 10.3, 17.1 Hz, 1H), 6.32 (dd, J = 1.9, 17.0 Hz, 1H), 5.85-5.80 (m, 1H), 5.07-4.83 (m, 1H), 2.20- 2.12 (m, 1H), 1.73-1.61 (m, 1H), 1.23-1.14 (m, 1H); LCMS (electrospray) m/z 439.3 (M + H+).

H






(1S,2S)-N-(6-(6-acrylamido-5-chloro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







287


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1H NMR (400 MHz, DMSO-d6) δ 13.30 (br s, 1H), 11.29 (s, 1H), 8.69 (s, 1H), 8.15 (s, 1H), 7.73 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.43 (br d, J = 8.4 Hz, 1H), 6.82 (s, 1H), 5.07-4.86 (m, 1H), 4.28 (q, J = 6.9 Hz, 3H), 2.31 (s, 3H), 2.20-2.12 (m, 1H), 1.75-1.63 (m, 1H), 1.46 (t, J = 7.0 Hz, 3H), 1.21 (tdd, J = 6.3, 9.0, 12.5 Hz, 1H); LCMS(electrospray) m/z 394.1 (M + H+).

H






(1S,2S)-N-(6-(7-etho xy-5-methyl-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







288


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1H NMR (400 MHz, DMSO-d6) δ 13.48 (br s, 1H), 11.21 (s, 1H), 8.71 (s, 1H), 8.15 (s, 1H), 7.83 (s, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 1.3, 9.2 Hz, 1H), 5.12-4.79 (m, 1H), 4.31 (q, J = 7.0 Hz, 2H), 2.22 (d, J = 3.1 Hz, 3H), 2.20-2.11 (m, 1H), 1.74-1.60 (m, 1H), 1.39 (t, J = 7.0 Hz, 3H), 1.19 (tdd, J = 6.4, 9.1, 12.4 Hz, 1H); LCMS(electrospray) m/z 412.1 (M + H+).

H






(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-





methyl-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







289


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1H NMR (400 MHz, METHANOL-d4) δ 8.72 (s, 1H), 7.88-7.81 (m, 2H), 7.79 (s, 1H), 7.73 (br d, J = 8.8 Hz, 1H), 6.64-6.55 (m, 1H), 6.49-6.41 (m, 1H), 5.87 (br d, J = 11.6 Hz, 1H), 5.07-4.97 (m, 2H), 2.26 (s, 3H), 2.19-2.09 (m, 1H), 1.94- 1.81 (m, 1H), 1.35-1.23 (m, 1H); LCMS(electrospray) m/z 419.2 (M + H+).

H






(1S,2S)-N-(6-(6-acrylamido-5-methyl-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







290


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1H NMR (400 MHz, DMSO-d6) δ 13.80 (br s, 1H), 11.19 (s, 1H), 8.87 (s, 1H), 8.18 (s, 1H), 8.07 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.46 (dd, J = 1.7, 9.2 Hz, 1H), 5.06-4.83 (m, 1H), 3.51-3.50 (m, 2H), 3.08 (t, J = 6.7 Hz, 2H), 2.22-2.12 (m, 1H), 1.74- 1.61 (m, 1H), 1.19 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 464 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((2-





hydroxyethyl)thio)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







291


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1H NMR (400 MHz, DMSO-d6) δ 11.54-11.33 (m, 1H), 8.73 (br d, J = 3.3 Hz, 1H), 8.18 (d, J = 1.6 Hz, 1H), 7.78-7.61 (m, 2H), 7.47 (br t, J = 9.4 Hz, 1H), 5.12-4.85 (m, 1H), 2.98 (s, 3H), 2.97 (s, 3H), 2.56 (br d, J = 7.3 Hz, 2H), 2.17 (td, J = 6.9, 13.7 Hz, 1H), 1.78-1.59 (m, 1H), 1.29-1.21 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 425.2 (M + H+).

H






(1S,2S)-N-(6-(7-(dimethylamino)-5-ethyl-





6-fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







292


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1H NMR (400 MHz, DMSO-d6) δ 13.45 (br s, 1H), 11.22 (s, 1H), 8.77 (s, 1H), 8.16 (s, 1H), 7.90 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.41 (dd, J = 1.5, 9.2 Hz, 1H), 5.06-4.85 (m, 1H), 3.50 (t, J = 6.9 Hz, 2H), 3.02 (t, J = 6.9 Hz, 2H), 2.23 (d, J = 2.9 Hz, 3H), 2.19-2.13 (m, 1H), 1.74-1.60 (m, 1H), 1.19 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS(electrospray) m/z 444 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-((2-





hydroxyethyl)thio)-5-methyl-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







293


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1H NMR (400 MHz, DMSO-d6) δ 13.89-13.08 (m, 1H), 11.22 (br s, 1H), 8.72 (s, 1H), 8.17 (s, 1H), 7.81 (s, 1H), 7.63 (br d, J = 9.1 Hz, 1H), 7.35 (br d, J = 9.1 Hz, 1H), 5.07-4.83 (m, 1H), 2.62-2.58 (m, 2H), 2.53 (s, 3H), 2.16 (td, J = 6.9, 13.9 Hz, 1H), 1.74-1.60 (m, 1H), 1.24-1.15 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 428.3 (M + H+).

H






(1S,2S)-N-(6-(5-ethyl-6-fluoro-7-





(methylthio)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







294


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1H NMR (400 MHz, CHLOROFORM-d) δ 11.24 (s, 1H), 8.73 (s, 1H), 8.18 (s, 1H), 7.75 (s, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.42 (d, J = 10.4 Hz, 1H), 7.36 (br d, J = 9.0 Hz, 1H), 5.12-4.76 (m, 1H), 2.61 (br d, J = 7.3 Hz, 2H), 2.23-2.12 (m, 1H), 1.77-1.62 (m, 1H), 1.22-1.16 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 382.3 (M + H+).

H






(1S,2S)-N-(6-(5-ethyl-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







295


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1H NMR (400 MHz, METHANOL-d4) δ 8.51 (d, J = 7.2 Hz, 1H), 7.85 (s, 1H), 7.66 (s, 1H), 7.00- 6.91 (m, 2H), 5.03-4.96 (m, 1H), 2.16-2.07 (m, 1H), 1.89-1.78 (m, 1H), 1.30-1.17 (m, 1H); LCMS(electrospray) m/z 404.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





hydroxy-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







296


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1H NMR (400 MHz, CHLOROFORM-d) δ 11.23 (s, 1H), 8.77 (s, 1H), 8.17 (s, 1H), 7.90 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 9.3 Hz, 1H), 7.45 (br d, J = 9.3 Hz, 1H), 5.12-4.81 (m, 1H), 2.25 (s, 3H), 2.21-2.11 (m, 1H), 1.75-1.61 (m, 1H), 1.25-1.21 (m, 1H); LCMS(electrospray) m/z 400.2 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-





(methylthio)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







297


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1H NMR (400 MHz, DMSO-d6) δ 11.17 (s, 1H), 8.75 (d, J = 0.7 Hz, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.59 (br d, J = 9.2 Hz, 1H), 7.44-7.39 (m, 1H), 5.16-4.80 (m, 1H), 2.56-2.54 (m, 3H), 2.38-2.30 (m, 1H), 2.27 (s, 3H), 2.21-2.11 (m, 1H), 1.77- 1.62 (m, 1H), 1.25-1.12 (m, 1H); LCMS(electrospray) m/z 446.0 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-





bis(methylthio)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







298


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1H NMR (400 MHz, CHLOROFORM-d) δ 13.00 (s, 1 H), 8.34-8.22 (m, 2 H), 7.92 (d, J = 9.17 Hz, 1 H), 7.71-7.61 (m, 2 H), 5.01-4.74 (m, 1 H), 2.67 (br d, J = 7.34 Hz, 2 H), 2.20-2.15 (m, 1 H), 2.06-1.96 (m, 2 H), 1.33-1.23 (m, 1 H), 1.17 (t, J = 7.46 Hz, 3 H); LCMS(electrospray) m/z 400.0 (M + H+).

H






(1S,2S)-N-(6-(5-ethyl-6,7-difluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







299


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1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.74 (s, 1H), 8.18 (s, 1H), 7.97 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.36 (br d, J = 8.9 Hz, 1H), 5.09-4.78 (m, 1H), 3.13 (s, 3H), 2.23 (d, J = 2.8 Hz, 3H), 2.20- 2.11 (m, 1H), 1.73-1.62 (m, 1H), 1.24-1.12 (m, 1H); LCMS(electrospray) m/z 429.11 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(methylsulfinyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







300


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (br s, 1H), 11.22 (s, 1H), 8.71 (s, 1H), 8.16 (s, 1H), 7.86 (s, 1H), 7.60 (d, J = 9.2 Hz, 1H), 7.43 (br d, J = 9.0 Hz, 1H), 5.08-4.85 (m, 1H), 2.99 (d, J = 2.3 Hz, 6H), 2.27 (s, 3H), 2.21-2.12 (m, 1H), 1.76-1.61 (m, 1H), 1.26-1.16 (m, 1H); LCMS(electrospray) m/z 443 (M + H+).

H






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







301


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1H NMR (400 MHz, DMSO-d6) δ 11.20 (s, 1H), 10.15 (s, 1H), 8.87 (s, 1H), 8.19 (s, 1H), 7.98 (s, 1H), 7.64 (d, J = 9.3 Hz, 1H), 7.46 (dd, J = 1.5, 9.2 Hz, 1H), 5.08-4.82 (m, 1H), 2.18 (s, 3H), 2.17- 2.11 (m, 1H), 1.74-1.62 (m, 1H), 1.26-1.15 (m, 1H); LCMS(electrospray) m/z 445.2 (M + H+).

H






(1S,2S)-N-(6-(7-acetamido-5-chloro-6-





fluoro-1H-indazol-4-yfiimidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







302


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1H NMR (400 MHz, DMSO-d6) δ 13.38-13.09 (m, 1H), 11.19 (s, 1H), 8.80 (s, 1H), 8.19 (s, 1H), 8.03 (s, 1H), 7.64 (d, J = 9.1 Hz, 1H), 7.38 (dd, J = 1.6, 9.2 Hz, 1H), 5.09-4.78 (m, 1H), 3.50 (s, 3H), 2.27 (d, J = 2.8 Hz, 3H), 2.21-2.12 (m, 1H), 1.74- 1.61 (m, 1H), 1.19 (tdd, J = 6.3, 9.0, 12.4 Hz, 1H); LCMS(electrospray) m/z 446.0 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(methylsulfonyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







303


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1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.87 (d, J = 0.6 Hz, 1H), 8.20 (s, 1H), 8.15 (s, 1H), 7.63 (d, J = 9.3 Hz, 1H), 7.42 (dd, J = 1.7, 9.3 Hz, 1H), 5.07-4.82 (m, 1H), 3.19 (s, 3H), 2.21-2.11 (m, 1H), 1.74-1.61 (m, 1H), 1.24-1.12 (m, 1H); LCMS(electrospray) m/z 450 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methylsulfinyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







304


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1H NMR (400 MHz, DMSO-d6) δ 11.28 (br s, 1H), 8.77 (s, 1H), 8.17 (s, 1H), 8.05 (br d, J = 2.0 Hz, 1H), 7.63 (br d, J = 9.1 Hz, 1H), 7.45 (br d, J = 9.1 Hz, 1H), 5.06-5.02 (m, 1H), 4.89-4.87 (m, 1H), 2.30 (s, 3H), 2.21-2.12 (m, 1H), 1.75-1.61 (m, 1H), 1.24-1.13 (m, 1H); LCMS(electrospray) m/z 418 (M + H+).

H






(1S,2S)-N-(6-(6,7-difluoro-5-(methylthio)-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





1 TFA







305


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1H NMR (400 MHz, METHANOL-d4) δ 8.80 (s, 1H), 7.89-7.86 (m, 2H), 7.77 (d, J = 8.9 Hz, 1H), 5.05-4.96 (m, 1H), 4.06 (s, 3H), 2.30 (d, J = 3.1 Hz, 3H), 2.13 (ddd, J = 2.3, 4.5, 6.6 Hz, 1H), 1.91- 1.81 (m, 1H), 1.31-1.25 (m, 1H); LCMS(electrospray) m/z 426.2 (M + H+).

H






methyl 6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





5-methyl-1H-indazole-7-carboxylate







306


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1H NMR (400 MHz, DMSO-d6) δ 11.27 (s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.65 (d, J = 9.2 Hz, 1H), 7.49 (dd, J = 1.6, 9.2 Hz, 1H), 5.04 (dt, J = 3.8, 6.2 Hz, 1H), 4.89-4.85 (m, 1H), 3.27 (q, J = 6.9 Hz, 2H), 2.98 (d, J = 2.6 Hz, 3H), 2.20- 2.12 (m, 1H), 1.73-1.63 (m, 1H), 1.20 (tdd, J = 6.3, 9.0, 12.4 Hz, 1H), 1.08 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 445.2 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 1





TFA







307


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1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.68 (s, 1H), 8.13 (s, 1H), 7.86 (br d, J = 3.4 Hz, 1H), 7.55 (d, J = 9.2 Hz, 1H), 7.24 (d, J = 9.2 Hz, 1H), 5.06-4.79 (m, 1H), 3.02 (d, J = 2.0 Hz, 6H), 2.21-2.11 (m, 1H), 1.73-1.61 (m, 1H), 1.21 1.11 (m, 1H); LCMS(electrospray) m/z 465.1 (M + H+).

H






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-5-(trifluoromethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







308


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1H NMR (400 MHz, DMSO-d6) δ 13.14-12.81 (m, 1H), 11.30-11.11 (m, 1H), 9.94 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.80 (s, 1H), 7.66-7.59 (m, 1H), 7.43-7.32 (m, 1H), 5.07-4.81 (m, 1H), 2.22 (d, J = 2.9 Hz, 3H), 2.16 (s, 4H), 1.74-1.62 (m, 1H), 1.27-1.12 (m, 1H); LCMS(electrospray) m/z 424.15 (M + H+).

H






(1S,2S)-N-(6-(7-acetamido-6-fluoro-5-





methyl-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







309


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1H NMR (400 MHz, DMSO-d6) δ 13.29 (s, 1H), 11.07 (s, 1H), 8.74 (s, 1H), 8.41 (s, 1H), 7.93 (s, 1H), 7.54 (d, J = 9.2 Hz, 1H), 7.29 (d, J = 9.2 Hz, 1H), 5.01-4.83 (m, 1H), 3.22 (s, 3H), 2.23-2.16 (m, 1H), 1.78-1.61 (m, 1H), 1.23 (br, 9H), 1.28- 1.12 (m, 1H); LCMS (electrospray) m/z 532.1 (M + H)+.

H






tert-butyl 2-(5-chloro-6-fluoro-4-(2-





((1S,2S)-2-fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





1H-indazol-7-yl)-1-methylhydrazine-1-





carboxylate







310


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1H NMR (400 MHz, DMSO-d6) δ 14.02-13.34 (m, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.85 (s, 1H), 7.65 (s, 1H), 6.93 (s, 1H), 6.89 (dd, J = 1.8, 7.1 Hz, 1H), 5.11-4.78 (m, 1H), 4.35 (q, J = 7.0 Hz, 2H), 2.28 (s, 3H), 2.19-2.12 (m, 1H), 1.68 (m, J = 3.2, 6.8, 19.9 Hz, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.26-1.11 (m, 1H); LCMS(electrospray) m/z 444.2 (M + H+).

H






(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-





(methylthio)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







311


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1H NMR (400 MHz, DMSO-d6) δ 10.85 (br s, 1H), 8.70 (s, 1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.60 (d, J = 9.0 Hz, 1H), 7.36 (dd, J = 1.5, 9.1 Hz, 1H), 5.05- 4.79 (m, 2H), 2.27 (br d, J = 2.6 Hz, 3H), 1.80 (s, 3H), 1.77-1.63 (m, 1H), 1.18 (tdd, J = 6.3, 9.2, 12.2 Hz, 1H); LCMS(electrospray) m/z 438.16 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(N-methylacetamido)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







312


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1H NMR (400 MHz, METHANOL-d4) δ 8.78 (s, 1H), 7.91-7.83 (m, 3H), 7.80-7.75 (m, 1H), 5.01 (dt, J = 3.9, 6.2 Hz, 1H), 4.13 (br t, J = 6.5 Hz, 2H), 3.17 (br t, J = 6.7 Hz, 2H), 2.63 (s, 3H), 2.29 (d, J = 2.9 Hz, 3H), 2.17-2.09 (m, 1H), 1.92-1.81 (m, 1H), 1.31-1.26 (m, 1H); LCMS(electrospray) m/z501.3 (M + H+).

H






2-((6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





5-methyl-1H-indazol-7-yl)thio)ethyl





methylcarbamate. 1 TFA







313


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1H NMR (400 MHz, DMSO-d6) δ 13.19(br s, 1H), 11.16 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.91 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.36 (br d, J = 8.9 Hz, 1H), 5.04-4.85(m, 1H), 2.23 (d, J = 3.1 Hz, 3H), 2.19-2.16 (m, 1H), 1.72-1.63 (m, 1H), 1.18 (ddd, J = 2.6, 6.2, 9.2 Hz, 1H); LCMS(electrospray) m/z 412.1 (M + H+).

H






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





5-methyl-1H-indazole-7-carboxylic acid. 1





TFA







314


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1H NMR (400 MHz, DMSO-d6) δ 13.49 (br s, 1H), 11.13 (s, 1H), 8.88 (s, 1H), 8.19 (s, 1H), 8.08 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.41 (dd, J = 1.8, 9.2 Hz, 1H), 5.06-4.83 (m, 1H), 2.22-2.12 (m, 1H), 1.74-1.57 (m, 1H), 1.29-1.06 (m, 1H); LCMS(electrospray) m/z 432.2 (M + H+).

H






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





1H-indazole-7-carboxylic acid. 1 TFA







315


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1H NMR (400 MHz, DMSO-d6) δ 13.69-13.54 (m, 1H), 11.16 (s, 1H), 8.90 (s, 1H), 8.20 (s, 1H), 8.13 (s, 1H), 7.63 (br d, J = 9.2 Hz, 1H), 7.44 (br d, J = 9.4 Hz, 1H), 5.12 (d, J = 6.5 Hz, 1H), 4.01 (s, 3H), 2.23-2.11 (m, 1H), 1.76-1.61 (m, 1H), 1.28-1.08 (m, 1H); LCMS(electrospray) m/z 446.2 (M + H+).

H






methyl 5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





1H-indazole-7-carboxylate. 1 TFA







316


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1H NMR (400 MHz, DMSO-d6) δ 14.22-13.73 (m, 1H), 11.15 (s, 1H), 8.87-8.86 (m, 1H), 8.19 (s, 1H), 8.13 (s, 1H), 7.62 (d, J = 9.3 Hz, 1H), 7.47- 7.40 (m, 1H), 5.04-4.84 (m, 1H), 3.23 (s, 3H), 2.17 (ddd, J = 2.0, 5.0, 6.9 Hz, 1H), 1.82 (s, 3H), 1.71-1.63 (m, 1H), 1.19-1.13 (m, 1H); LCMS(electrospray) m/z 459.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(N-





methylacetamido)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







317


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1H NMR (400 MHz, DMSO-d6) δ 12.93 (s, 1H), 11.06 (s, 1H), 8.70 (s, 1H), 8.14 (s, 1H), 7.79 (s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.38 (s, 1H), 7.31 (d, J = 9.2 Hz, 1H), 5.01-4.83 (m, 1H), 5.01 (s, 1H), 2.60 (s, 3H), 2.23-2.16 (m, 1H), 1.78-1.61 (m, 1H), 1.28-1.12 (m, 1H); LCMS (electrospray) m/z 432.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





methylhydrazineyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







318


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1H NMR (400 MHz, DMSO-d6) δ 13.60-13.32 (m, 1H), 11.06 (s, 1H), 8.63 (s, 1H), 8.15 (s, 1H), 7.74 (s, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.21 (dd, J = 1.6, 9.1 Hz, 1H), 5.04-4.82 (m, 1H), 4.32 (q, J = 7.0 Hz, 2H), 2.60 (br d, J = 6.6 Hz, 2H), 2.20-2.11 (m, 1H), 1.72-1.61 (m, 1H), 1.39 (t, J = 6.9 Hz, 3H), 1.20-1.13 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 426.0 (M + H+).

H






(1S,2S)-N-(6-(7-ethoxy-5-ethyl-6-fluoro-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







319


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1H NMR (400 MHz, DMSO-d6) δ 13.73 (s, 1H), 11.13 (s, 1H), 8.89 (s, 1H), 8.22 (s, 1H), 8.10 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.40 (dd, J = 1.5, 9.2 Hz, 1H), 5.08-4.81 (m, 1H), 2.77 (d, J = 6.1 Hz, 3H), 2.25-2.12 (m, 1H), 1.76-1.61 (m, 1H), 1.13- 1.19 (m, J = 2.9, 6.1, 12.1 Hz, 1H); LCMS(electrospray) m/z 430.3(M + H+).

H






(1S,2S)-N-(6-(7-acetyl-5-chloro-6-fluoro-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







320


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1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.89 (s, 1H), 8.19 (s, 1H), 8.06 (s, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 1.7, 9.3 Hz, 1H), 5.10- 4.79 (m, 1H), 3.13 (s, 3H), 2.93 (s, 3H), 2.21-2.12 (m, 1H), 1.75-1.60 (m, 1H), 1.08 (s, 1H); LCMS(electrospray) m/z 459.0 (M + H+).

H






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N,N-dimethyl-1H-indazole-7-carboxamide







321


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1H NMR (400 MHz, DMSO-d6) δ 11.19-11.05 (m, 1H), 8.90-8.81 (m, 1H), 8.69-8.61 (m, 1H), 8.49-8.44 (m, 1H) 8.26-8.16 (m, 1H) 8.07-8.00 (m, 1H), 7.68-7.54 (m, 1H), 7.42-7.31 (m, 1H), 5.15-4.75 (m, 1H), 2.91 (d, J = 4.2 Hz, 3H), 2.23- 2.11 (m, 1H), 1.76 (br d, J = 4.8 Hz, 1H), 1.27- 1.10 (m, 1H); LCMS(electrospray) m/z 445.3 (M + H+).

H






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N-methyl-1H-indazole-7-carboxamide







322


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1H NMR (400 MHz, DMSO-d6) δ 13.43 (s, 1H), 11.10 (s, 1H), 8.77 (s, 1H), 8.18 (s, 1H), 7.92 (s, 1H), 7.59 (d, J = 9.2 Hz, 1H), 7.31 (dd, J = 1.6, 9.2 Hz, 1H), 5.08-4.79 (m, 1H), 2.74 (d, J = 6.2 Hz, 3H), 2.28 (d, J = 3.2 Hz, 3H), 2.16 (td, J = 6.9, 13.9 Hz, 1H), 1.75-1.58 (m, 1H), 1.17 (tdd, J = 6.3, 9.1, 12.2 Hz, 1H); LCMS(electrospray) m/z 409.14 (M + H+).

H






(1S,2S)-N-(6-(7-acetyl-6-fluoro-5-methyl-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







323


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1H NMR (400 MHz, DMSO-d6) δ 11.21-11.16 (m, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.15 (br s, 1H), 7.71-7.59 (m, 1H), 7.41 (dd, J = 1.6, 9.2 Hz, 1H), 5.06-4.83 (m, 1H), 2.22-2.11 (m, 1H), 1.74-1.59 (m, 1H), 1.19 (tdd, J = 6.4, 9.1, 12.4 Hz, 1H); LCMS(electrospray) m/z 406.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6,7-difluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







324


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1H NMR (400 MHz, DMSO-d6) δ 13.38 (br s, 1H), 11.06 (s, 1H), 8.66 (s, 1H), 8.13 (s, 1H), 7.84 (br s, 1H), 7.51 (d, J = 9.1 Hz, 1H), 7.30 (br d, J = 8.5 Hz, 1H), 5.06-4.81 (m, 1H), 3.25-3.20 (m, 2H), 2.95 (br s, 3H), 2.25 (s, 3H), 2.16-2.15 (m, 1H), 1.70-1.63 (m, 1H), 1.19-1.13 (m, 1H), 1.07 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 457 (M + H+).

H






(1S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







325


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1H NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 11.12 (s, 1H), 8.86 (s, 1H), 8.20 (s, 1H), 8.05 (d, J = 16.9 Hz, 3H), 7.61 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 1.6, 9.2 Hz, 1H), 5.11-4.79 (m, 1H), 2.24- 2.08 (m, 1H), 1.78-1.57 (m, 1H), 1.21-1.14 (m, 1H); LCMS(electrospray) m/z 431.1 (M + H+).

H






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





1H-indazole-7-carboxamide







326


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1H NMR (400 MHz, DMSO-d6) δ 13.16 (br s, 1H), 11.06 (s, 1H), 8.63 (s, 1H), 8.14 (s, 1H), 7.68 (s, 1H), 7.53 (d, J = 9.2 Hz, 1H), 7.22 (d, J = 9.3 Hz, 1H), 5.06-4.78 (m, 1H), 3.27-3.11 (m, 2H), 2.94 (s, 4H), 2.57 (br d, J = 6.8 Hz, 2H), 2.21-2.09 (m, 1H), 1.76-1.58 (m, 1H), 1.25-1.14 (m, 1H), 1.11- 1.04 (m, 6H); LCMS(electrospray) m/z 439.2 (M + H+).

H






(1S,2S)-N-(6-(5-ethyl-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







327


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1H NMR (400 MHz, DMSO-d6) δ 13.52 (br s, 1H), 11.08 (s, 1H), 8.76 (s, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.37 (d, J = 9.3 Hz, 1H), 3.00 (d, J = 1.7 Hz, 6H), 2.01-1.90 (m, 1H), 0.92-0.78 (m, 4H); LCMS(electrospray) m/z 413.0 (M + H+).

H






N-(6-(5-chloro-7-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)cyclopropanecarboxamide







328


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1H NMR (400 MHz, DMSO-d6) δ 13.24 (br s, 1H), 11.07 (s, 1H), 8.84 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H), 7.58-7.54 (m, 1H), 7.50-7.44 (m, 2H), 5.04- 4.81 (m, 1H), 3.85 (q, J = 7.0 Hz, 2H), 2.20-2.12 (m, 1H), 1.67 (tdd, J = 3.3, 6.8, 20.0 Hz, 1H), 1.21- 1.14 (m, 1H), 1.10 (t, J = 7.0 Hz, 3H); LCMS(electrospray) m/z 398.1 (M + H+).

H






(1S,2S)-N-(6-(5-ethoxy-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







329


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1H NMR (400 MHz, DMSO-d6) δ 13.41 (br s, 1H), 11.08 (s, 1H), 8.73 (s, 1H), 8.16 (s, 1H), 7.88 (s, 1H), 7.57 (d, J = 9.1 Hz, 1H), 7.31 (dd, J = 1.4, 9.3 Hz, 1H), 5.08-4.81 (m, 1H), 3.12 (s, 3H), 2.92 (s, 3H), 2.24 (d, J = 2.8 Hz, 3H), 2.19-2.11 (m, 1H), 1.72-1.59 (m, 1H), 1.19-1.15 (m, 1H); LCMS(electrospray) m/z 439.3 (M + H+).

H






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N,N,5-trimethyl-1H-indazole-7-





carboxamide







330


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1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 11.05 (s, 1H), 8.65 (s, 1H), 8.13 (s, 1H), 7.76 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.27 (dd, J = 1.6, 9.2 Hz, 1H), 5.07-4.79 (m, 1H), 3.20 (q, J = 6.6 Hz, 2H), 2.92 (s, 3H), 2.21-2.12 (m, 4H), 1.73-1.59 (m, 1H), 1.25-1.10 (m, 1H), 1.05 (t, J = 7.1 Hz, 3H); LCMS(electrospray) m/z 424.18 (M + H+).

H






(1S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







331


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1H NMR (400 MHz, DMSO-d6) δ 1.12-1.22 (m, 1 H), 1.60-1.73 (m, 1 H), 2.12-2.21 (m, 1 H), 4.81- 5.05 (m, 1 H), 7.39 (dd, J = 9.26, 1.75 Hz, 1 H), 7.50 (s, 1 H) 7.58-7.64 (m, 1 H), 7.77 (s, 1 H), 8.14 (s, 1 H), 8.19 (s, 1 H), 8.87 (s, 1 H), 11.11 (s, 1 H), 13.86-13.91 (m, 1 H); LCMS(electrospray) m/z 438.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-7-





(difluoromethyl)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







332


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1H NMR (400 MHz, DMSO-d6) δ 13.49 (br s, 1H), 11.19 (s, 1H), 8.74 (s, 1H), 8.11 (s, 1H), 8.00-7.84 (m, 1H), 7.56 (d, J = 9.3 Hz, 1H), 7.33 (dd, J = 1.4, 9.2 Hz, 1H), 5.04-4.78 (m, 1H), 3.00 (br s, 6H), 2.46-2.41 (m, 1H), 1.61-1.44 (m, 1H), 1.25 (qd, J = 6.6, 13.1 Hz, 1H); LCMS(electrospray) m/z 431.0 (M + H+).

H






(1R,2S)-N-(6-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







333


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1H NMR (400 MHz, DMSO-d6) δ 13.99-13.12 (m, 1H), 11.27 (s, 1H), 8.78 (s, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.39 (d, J = 9.3 Hz, 1H), 5.05-4.75 (m, 1H), 3.00 (d, J = 2.4 Hz, 6H), 2.44 (br s, 1H), 1.63-1.46 (m, 1H), 1.26 (qd, J = 6.4, 13.2 Hz, 1H); LCMS(electrospray) m/z 431.1 (M + H+).

H






(1S,2R)-N-(6-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







334


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1H NMR (400 MHz, DMSO-d6) δ 13.77-13.25 (m, 1H), 11.15 (s, 1H), 8.78 (s, 1H), 8.17 (s, 1H), 7.94 (s, 1H), 7.59 (d, J = 9.2 Hz, 1H), 7.38 (d, J = 9.3 Hz, 1H), 5.09-4.80 (m, 1H), 3.00 (d, J = 2.3 Hz, 6H), 2.16 (td, J = 6.8, 13.6 Hz, 1H), 1.73-1.58 (m, 1H), 1.24-1.10 (m, 1H); LCMS(electrospray) m/z 431.1 (M + H+).

H






(1R,2R)-N-(6-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







335


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1H NMR (400 MHz, DMSO-d6) δ 13.34 (br s, 1H), 11.05 (s, 1H), 8.93 (s, 1H), 8.29 (s, 1H), 8.19 (s, 1H), 7.60-7.56 (m, 1H), 7.55-7.51 (m, 1H), 7.15 (d, J = 13.7 Hz, 1H), 5.06-4.80 (m, 1H), 2.95 (d, J = 1.2 Hz, 6H), 2.22-2.09 (m, 1H), 1.75-1.59 (m, 1H), 1.16 (br s, 1H); LCMS(electrospray) m/z 397.2 (M + H+).

H






(1S,2S)-N-(6-(7-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







336


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1H NMR (400 MHz, DMSO-d6) δ 13.68 (s, 1H), 11.09 (s, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.08 (s, 1H), 7.59 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 9.0 Hz, J = 1.8 Hz, 1H), 5.03-4.83 (m, 1H), 3.84 (t, J = 6.8 Hz, 2H), 2.52 (t, J = 7.4 Hz, 2H), 2.31-2.24 (m, 2H), 2.18-2.13 (m, 1H), 1.71-1.63 (m, 1H), 1.23- 1.12 (m, 1H); LCMS (electrospray) m/z 471.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





oxopyrrolidin-1-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







337


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1H NMR (400 MHz, DMSO-d6) δ 13.62 (s, 1H), 11.06 (s, 1H), 8.82 (s, 1H), 8.16 (s, 1H), 8.11 (br, 1H), 8.08 (s, 1H), 7.59-7.55 (m, 2H), 7.38 (dd, J = 9.0 Hz, J = 1.8 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 6.54 (d, J = 8.0 Hz, 1H), 5.03-4.83 (m, 1H), 3.41 (s, 3H), 2.18-2.13 (m, 1H), 1.71-1.63 (m, 1H), 1.23-1.12 (m, 1H); LCMS (electrospray) m/z 494.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methyl(pyridin-2-yl)amino)-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







338


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1H NMR (400 MHz, DMSO-d6) δ 13.22 (s, 1H), 11.07 (s, 1H), 8.79-8.65 (m, 1H), 8.46-8.34 (m, 1H), 8.17 (s, 1H), 7.90-7.78 (m, 1H), 7.65-7.51 (m, 1H), 7.36-7.22 (m, 1H), 5.08-4.78 (m, 1H), 2.89 (br d, J = 4.5 Hz, 3H), 2.24 (br d, J = 2.8 Hz, 3H), 2.19-2.13 (m, 1H), 1.74-1.58 (m, 1H), 1.23- 1.11 (m, 1H); LCMS(electrospray) m/z 425.1 (M + H+).

H






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N,5-dimethyl-1H-indazole-7-carboxamide







339


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1H NMR (400 MHz, DMSO-d6) δ 13.67 (br s, 1H), 11.10 (s, 1H), 8.73 (s, 1H), 8.18 (s, 1H), 7.97 (s, 1H), 7.60 (d, J = 9.1 Hz, 1H), 7.27 (dd, J = 1.6, 9.1 Hz, 1H), 5.05-4.81 (m, 1H), 2.66 (br d, J = 7.3 Hz, 2H), 2.22-2.11 (m, 1H), 1.74-1.61 (m, 1H), 1.20-1.14 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 450.2 (M + H+).

H






(1S,2S)-N-(6-(5-ethyl-6-fluoro-7-





(trifluoromethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







340


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1H NMR (400 MHz, DMSO-d6) δ 13.48 (br s, 1H) 11.05 (s, 1 H) 8.94 (s, 1 H) 8.36 (br s, 1 H) 8.21 (s, 1 H) 7.52-7.62 (m, 2 H) 7.37 (br d, J = 7.25 Hz, 1 H) 7.29 (d, J = 7.50 Hz, 1 H) 4.81-5.04 (m, 1 H) 2.62 (s, 3 H) 2.12-2.20 (m, 1 H) 1.61-1.73 (m, 1 H) 1.12-1.23 (m, 1 H); LCMS(electrospray) m/z 382.1 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(7-(methylthio)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide







341


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1H NMR (400 MHz, DMSO-d6) δ 13.70 (s, 1 H), 11.06 (s, 1 H), 8.81 (s, 1 H), 8.14(s, 1 H), 8.01 (s, 1 H), 7.54 (s, 1 H), 7.37-7.34 (m, 1 H), 4.98-4.80 (m, 1 H), 3.23-3.17 (q, J = 7.0 Hz, 1H), 2.87 (s, 3 H), 2.14-2.10 (m, 1 H), 1.66-1.59 (m, 1 H), 1.16-1.10 (m, 1 H), 1.00 (t, J = 6.9 Hz, 3 H); LCMS(electrospray) m/z 473.1 (M + H+).

H






5-chloro-N-ethyl-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N-methyl-1H-indazole-7-carboxamide







342


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1H NMR (400 MHz, DMSO-d6) δ 13.63 (s, 1 H) 11.17 (s, 1 H) 9.07 (s, 1 H) 8.43(s, 1 H) 8.21 (s, 1 H) 7.72-7.61 (m, 2 H) 7.32 (d, J = 10.4 Hz, 1 H) 5.05-4.85 (m, 1 H) 2.51 (s, 3 H) 2.20-2.15 (m, 1 H) 1.72-1.65 (m, 1 H) 1.22-1.16 (m, 1 H); LCMS(electrospray) m/z 400.0 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-





(methylthio)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)cyclopropane-1-





carboxamide







343


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1H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 11.09 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.94 (d, J = 1.0 Hz, 1H), 7.73-7.43(m, 2H), 7.30 (dd, J = 1.6, 9.2 Hz, 1H), 5.10-4.79 (m, 1H), 2.24 (d, J = 2.6 Hz, 3H), 2.19-2.12 (m, 1H), 1.74-1.61 (m, 1H), 1.17 (ddd, J = 2.9, 6.2, 12.2 Hz, 1H); LCMS(electrospray) m/z 418.1 (M + H+).

H






(1S,2S)-N-(6-(7-(difluoromethyl)-6-





fluoro-5-methyl-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







344


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1H NMR (400 MHz, DMSO-d6) δ 14.08 (br s, 1H), 11.11 (s, 1H), 9.05 (s, 1H), 8.49 (s, 1H), 8.21 (s, 1H), 7.68-7.63 (m, 1H), 7.61-7.57 (m, 1H), 7.48 (d, J = 11.6 Hz, 1H), 5.12-4.84 (m, 1H), 2.25- 2.12 (m, 1H), 1.83-1.60 (m, 1H), 1.27-1.08 (m, 1H); LCMS(electrospray) m/z 438.2 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-





(trifluoromethoxy)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide







345


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1H NMR (400 MHz, DMSO-d6) δ 13.94 (s, 1H), 11.09 (s, 1H), 8.74 (s, 1H), 8.15 (s, 1H), 7.99 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.31 (dd, J = 1.7, 9.2 Hz, 1H), 5.08-4.77 (m, 1H), 2.26 (d, J = 2.8 Hz, 3H), 2.20-2.11 (m, 1H), 1.73-1.59 (m, 1H), 1.23- 1.10 (m, 1H); LCMS(electrospray) m/z 452.3 (M + H+).

H






(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-





7-(trifluoromethoxy)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-





yl)cyclopropane-1-carboxamide







346


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1H NMR (400 MHz, DMSO-d6) δ 13.61 (s, 1H), 11.10 (s, 1H), 8.86 (s, 1H), 8.63-8.47 (br, 2H), 8.20 (s, 1H), 8.03 (s, 1H), 7.60 (d, J = 9.6 Hz, 1H), 7.43 (t, J = 4.6 Hz, 1H), 6.86 (t, J = 6.0 Hz, 1H), 5.04- 4.83 (m, 1H), 3.53 (s, 3H), 2.20-2.13 (m, 1H), 1.72-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 495.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methyl(pyrimidin-2-yl)amino)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







347


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1H NMR (400 MHz, ACETONE-d6) δ 13.30 (s, 1H), 10.52 (s, 1H), 9.23 (s, 1H), 8.72 (s, 1H), 8.61 (s, 1H), 8.04 (d, J = 9.3 Hz, 1H), 7.90 (d, J = 9.1 Hz, 1H), 5.47-5.26 (m, 1H), 4.96-4.73 (m, 2H), 3.75 (s, 3H), 2.76-2.71 (m, 1H), 2.33-2.24 (m, 1H), 1.70-1.63 (m, 1H); LCMS(electrospray) m/z 527.1 (M + H+).

H






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N-methyl-N-(2,2,2-trifluoroethyl)-1H-





indazole-7-carboxamide







348


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1H NMR (400 MHz, DMSO-d6) δ 13.61 (s, 1H), 11.10 (s, 1H), 8.86 (s, 1H), 8.63 (br, 1H), 8.47 (br, 1H), 8.20 (s, 1H), 8.08 (s, 1H), 7.60 (d, J = 9.6 Hz, 1H), 7.55 (br, 1H), 7.42 (t, J = 8.0 Hz, 1H), 5.04- 4.83 (m, 1H), 3.48 (s, 3H), 2.20-2.15 (m, 1H), 1.72-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 495.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methyl(pyrimidin-4-yl)amino)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







349


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1H NMR (400 MHz, DMSO-d6) δ 13.66 (s, 1H), 11.09 (s, 1H), 8.77 (s, 1H), 8.59 (s, 1H), 8.46 (s, 1H), 8.20 (s, 1H), 7.96 (s, 1H), 7.82 (d, J = 6.8 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.34 (t, J = 8.2 Hz, 2H), 5.04-4.83 (m, 1H), 4.45 (s, 2H), 2.90 (s, 3H), 2.20-2.15 (m, 1H), 1.72-1.62 (m, 1H), 1.23- 1.13 (m, 1H); LCMS (electrospray) m/z 508.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methyl(pyridin-3-ylmethyl)amino)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







350


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1H NMR (400 MHz, DMSO-d6) δ 14.18-13.20 (m, 1H), 11.22 (s, 1H), 8.74 (d, J = 7.2 Hz, 1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.10-6.94 (m, 2H), 5.16-4.74 (m, 1H), 4.12 (s, 3H), 2.25-2.09 (m, 1H), 1.78-1.54 (m, 1H), 1.29-1.05 (m, 1H); LCMS(electrospray) m/z 470.2 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





methyl-1H-tetrazol-5-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







351


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1H NMR (400 MHz, DMSO-d6) δ 14.75-14.36 (m, 1H), 11.13 (s, 1H), 8.90 (s, 1H), 8.27 (s, 1H), 8.21 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.41 (dd, J = 1.5, 9.3 Hz, 1H), 5.09-4.80 (m, 1H), 2.22-2.13 (m, 1H), 1.74-1.59 (m, 1H), 1.12-1.20 (m, J = 2.9, 6.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 413.2 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-7-cyano-6-fluoro-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







352


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1H NMR (400 MHz, DMSO-d6) δ 13.25-13.17 (m, 1H), 11.02 (s, 1H), 8.84 (s, 1H), 8.31-8.24 (m, 1H), 8.18 (s, 1H), 7.57-7.50 (m, 2H), 7.16 (d, J = 7.6 Hz, 1H), 6.80 (br d, J = 3.8 Hz, 1H), 5.07-4.78 (m, 1H), 2.92 (br s, 6H), 2.23-2.09 (m, 1H), 1.76- 1.58 (m, 1H), 1.27-1.08 (m, 1H); LCMS(electrospray) m/z 379.1 (M + H+).

H






(1S,2S)-N-(6-(7-(dimethylamino)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







353


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1H NMR (400 MHz, DMSO-d6) δ 13.69 (s, 1H), 11.08 (s, 1H), 8.76 (s, 1H), 8.52 (s, 2H), 8.15 (s, 1H), 7.97 (s, 1H), 7.54 (s, 1H), 7.46 (s, 2H), 7.33 (br, 1H), 5.04-4.83 (m, 1H), 4.48 (s, 2H), 2.91 (s, 3H), 2.20-2.15 (m, 1H), 1.72-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 508.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methyl(pyridin-4-ylmethyl)amino)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







354


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1H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 11.10 (s, 1H), 8.71 (s, 1H), 8.20 (s, 1H), 8.09 (s, 1H), 7.52 (t, J = 9.7 Hz, 2H), 7.28 (td, J = 2.4, 8.9 Hz, 1H), 5.05-4.80 (m, 1H), 2.85 (s, 3H), 2.72 (s, 3H), 2.16 (br s, 1H), 1.74-1.58 (m, 1H), 1.23-1.12 (m, 1H); LCMS(electrospray) m/z 425.2 (M + H+).

H






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N,N-dimethyl-1H-indazole-7-carboxamide







355


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1H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 11.10 (s, 1H), 8.71 (s, 1H), 8.20 (s, 1H), 8.09 (s, 1H), 7.52 (t, J = 9.7 Hz, 2H), 7.28 (td, J = 2.4, 8.9 Hz, 1H), 5.05-4.80 (m, 1H), 2.85 (s, 3H), 2.72 (s, 3H), 2.16 (br s, 1H), 1.74-1.58 (m, 1H), 1.23-1.12 (m, 1H); LCMS(electrospray) m/z 425.2 (M + H+).

H






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





N,N-dimethyl-1H-indazole-5-carboxamide







356


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1H NMR (400 MHz, DMSO-d6) δ 13.98 (s, 1H), 11.08 (s, 1H), 8.81 (s, 1H), 8.23-8.18 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 5.03-4.82 (m, 1H), 3.88 (q, J = 7.0 Hz, 2H), 2.17- 2.14 (m, 1H), 1.70-1.63 (m, 1H), 1.19-1.16 (m, 1H), 1.10 (t, J = 7.0 Hz, 3H); LCMS(electrospray) m/z 416.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(trifluoromethoxy)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







357


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1H NMR (400 MHz, DMSO-d6) δ 13.98 (s, 1H), 11.08 (s, 1H), 8.81 (s, 1H), 8.23-8.18 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 5.03-4.82 (m, 1H), 3.88 (q, J = 7.0 Hz, 2H), 2.17- 2.14 (m, 1H), 1.70-1.63 (m, 1H), 1.19-1.16 (m, 1H), 1.10 (t, J = 7.0 Hz, 3H); LCMS(electrospray) m/z 416.1 (M + H+).

H






(1S,2S)-N-(6-(5-ethoxy-6,7-difluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







358


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1H NMR (400 MHz, DMSO-d6) δ 13.64 (s, 1H), 11.12 (s, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.03 (s, 1H), 7.59 (d, J = 9.6 Hz, 1H), 7.38 (dd, J = 1.6, 9.2 Hz, 1H), 5.03-4.84 (m, 1H), 3.83 (t, J = 7.8 Hz, 2H), 3.60 (t, J = 8.0 Hz, 2H), 2.82 (s, 3H), 2.16 (m, 1H), 1.69-1.64 (m, 1H), 1.21-1.15 (m, 1H); LCMS (electrospray) m/z 486.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-





methyl-2-oxoimidazolidin-1-yl)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







359


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1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1H), 11.08 (s, 1H), 8.73 (s, 1H), 8.14 (s, 1H), 7.90 (s, 1H), 7.53 (d, J = 9.2 Hz, 1H), 7.32 (dd, J = 1.6, 9.2 Hz, 1 H), 5.16 (dd, J = 2.6, 9.8 Hz, 1H), 5.03-4.83 (m, 1H), 4.08 (s, 1H), 2.19-2.12 (m, 1H), 1.71- 1.61 (m, 1H), 1.22 (d, J = 6.8 Hz, 6H), 1.19-1.12 (m, 1H); LCMS (electrospray) m/z 445.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(isopropylamino)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







360


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 11.11 (s, 1H), 8.78 (s, 1H), 8.16 (s, 1H), 7.95 (s, 1H), 7.56 (d, J = 9.2 Hz, 1H), 7.36 (dd, J = 1.8, 9.4 Hz, 1H), 5.02-4.85 (m, 1H), 3.54 (s, 1H), 2.89 (d, J = 3.2 Hz, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.21-1.13 (m, 7H); LCMS (electrospray) m/z 459.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(isopropyl(methyl)amino)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







361


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1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 11.10 (s, 1H), 8.77 (s, 1H), 8.15 (s, 1H), 7.92 (s, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.35 (dd, J = 9.2 Hz, J = 2.0 Hz, 1H), 5.03-4.83 (m, 1H), 3.01-2.98 (br, 4H), 2.17-2.14 (m, 1H), 1.69-1.62 (m, 1H), 1.19-1.14 (m, 1H) 0.64-0.59 (m, 2H), 0.48-0.45 (m, 2H); LCMS (electrospray) m/z 457.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-





(cyclopropyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







362


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1H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 11.10 (s, 1H), 8.81 (s, 1H), 8.18 (s, 1H), 7.96 (d, J = 1.6 Hz, 1H), 7.58 (d, J = 9.6 Hz, 1H), 7.35 (dd, J = 1.6, 9.2 Hz, 1H), 5.47 (t, J = 5.6 Hz, 1H), 5.03- 4.83 (m, 3H), 2.19-2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.19-1.12 (m, 1H); LCMS (electrospray) m/z 419.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(hydroxymethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







363


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1H NMR (400 MHz, DMSO-d6) δ 13.90 (s, 1H), 11.12 (s, 1H), 8.85 (s, 1H), 8.18 (s, 1H), 8.07 (d, J = 1.2 Hz, 1H), 7.59 (d, J = 9.6 Hz, 1H), 7.38 (dd, J = 2.0, 9.2 Hz, 1H), 5.93 (s, 1H), 5.81 (s, 1H), 5.04- 4.83 (m, 1H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.19-1.13 (m, 1H); LCMS (electrospray) m/z 420.05 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(fluoromethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







364


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1H NMR (400 MHz, DMSO-d6) δ 13.73 (s, 1H), 11.15 (s, 1H), 8.93 (s, 1H), 8.23 (s, 1H), 8.21 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.45 (d, J = 9.2 Hz, 1H), 5.03-4.84 (m, 1H), 2.55 (s, 3H), 2.16-2.14 (m, 1H), 1.69-1.63 (m, 1H), 1.20-1.15 (m, 1H); LCMS (electrospray) m/z 470.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-





methyl-1,2,4-oxadiazol-5-yl)-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







365


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1H NMR (400 MHz, DMSO-d6) δ 13.56-14.07 (1H), 11.12 (s, 1H), 8.84 (d, J = 1.1 Hz, 1H), 8.20 (s, 1H), 8.17 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.1, 1.9 Hz, 1H), 7.28 (s, 2H), 6.41 (t, J = 2.2 Hz, 2H), 5.04-4.84 (m, 1H), 2.20-2.13 (m, 1H), 1.70-1.64 (m, 1H), 1.20-1.13 (m, 1H); LCMS (electrospray) m/z 453.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1H-





pyrrol-1-yl)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







366


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1H NMR (400 MHz, DMSO-d6) δ 13.35 (s, 1H), 11.09 (s, 1H), 8.77 (s, 1H), 8.14 (s, 1H), 7.97 (s, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.35 (dd, J = 9.3, 1.6 Hz, 1H), 6.79-6.22 (m, 1H), 5.10-4.47 (m, 3H), 2.25-2.09 (m, 1H), 1.76-1.57 (m, 1H), 1.21-1.09 (m, 1H); LCMS (electrospray) m/z 442.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-





((cyanomethyl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







367


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1H NMR (400 MHz, DMSO-d6) δ 13.03 (s, 1H), 11.07 (s, 1H), 8.71 (s, 1H), 8.16 (d, J = 13.2 Hz, 1H), 7.86 (s, 1H), 7.53 (d, J = 9.3 Hz, 1H), 7.30 (dd, J = 8.8, 1.6 Hz, 1H), 6.08 (s, 1H), 5.09-4.81 (m, 1H), 3.12 (s, 1H), 2.17-2.08 (m, 1H), 1.66 (d, J = 23.1 Hz, 1H), 1.23-1.14 (m, 1H), 0.80 (d, J = 5.5 Hz, 2H), 0.63 (d, J = 3.3 Hz, 2H); LCMS(electrospray) m/z 443.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-7-





(cyclopropylamino)-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







368


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1H NMR (400 MHz, DMSO-d6) δ 13.96 (s, 1H), 11.12 (s, 1H), 8.93-8.83 (m, 1H), 8.17-8.12 (m, 2H), 7.69-7.57 (m, 1H), 7.46-7.36 (m, 1H), 5.04- 4.83 (m, 1H), 3.44 (qd, J = 7.2, 3.7 Hz, 1H), 2.19- 2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.13 (m, 1H), 0.98-0.55 (m, 4H); LCMS(electrospray) m/z 539.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-7-(N-cyclopropyl-





2,2,2-trifluoroacetamido)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







369


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1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 11.11 (s, 1H), 10.16 (s, 1H), 8.83 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 7.98 (d, J = 1.6 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 4.93 (ddd, J = 66.2, 9.9, 6.3 Hz, 1H), 4.76 (t, J = 5.5 Hz, 1H), 3.79 (q, J = 6.2 Hz, 2H), 2.65 (t, J = 6.6 Hz, 2H), 2.19-2.08 (m, 1H), 1.70-1.61 (m, 1H), 1.23- 1.13 (m, 1H); LCMS(electrospray) m/z 475.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-





hydroxypropanamido)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







370


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1H NMR (400 MHz, DMSO-d6) δ 13.12-13.48 (1H), 11.08 (s, 1H), 8.72 (s, 1H), 8.14 (s, 1H), 7.90 (s, 1H), 7.52 (d, J = 9.3 Hz, 1H), 7.31 (dd, J = 9.1, 1.9 Hz, 1H), 5.16 (d, J = 6.9 Hz, 1H), 5.03-4.83 (m, 1H), 3.90 (s, 1H), 2.19-2.12 (m, 1H), 1.71- 1.58 (m, 2H), 1.53-1.46 (m, 1H), 1.23-1.12 (m, 4H), 0.94 (t, J = 7.4 Hz, 3H); LCMS (electrospray) m/z 459.10 (M + H)+.

H






(1S,2S)-N-(6-(7-(sec-butylamino)-5-





chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







371


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1H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1H), 11.10 (s, 1H), 8.77 (d, J = 12.6 Hz, 1H), 8.14 (d, J = 8.2 Hz, 1H), 7.97 (s, 1H), 7.54 (t, J = 9.3 Hz, 1H), 7.35 (d, J = 9.3 Hz, 1H), 6.66-6.46 (m, 0.5H), 6.11 (d, J = 9.3 Hz, 1H), 5.99-5.80 (m, 0.5H), 5.10-4.77 (m, 2H), 2.24-2.09 (m, 1H), 1.81-1.58 (m, 4H), 1.21-1.06 (m, 1H); LCMS (electrospray) m/z 456.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-((1-





cyanoethyl)amino)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







372


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1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 11.11 (s, 1H), 8.80 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 9.1, 1.9 Hz, 1H), 5.83 (d, J = 3.8 Hz, 1H), 5.43-5.37 (m, 1H), 5.04-4.83 (m, 1H), 2.19- 2.12 (m, 1H), 1.70-1.62 (m, 1H), 1.54 (d, J = 6.6 Hz, 3H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 433.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





hydroxyethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







373


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1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 11.11 (s, 1H), 8.82 (t, J = 1.4 Hz, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 7.61-7.57 (m, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 5.07-4.83 (m, 2H), 3.23 (s, 3H), 2.19- 2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.57 (t, J = 6.3 Hz, 4H), 1.21-1.13 (m, 2H); LCMS (electrospray) m/z 447.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





methoxyethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







374


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1H NMR (400 MHz, DMSO-d6) δ 13.68 (s, 1H), 11.11 (s, 1H), 8.83 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 8.05 (s, 1H), 7.61-7.58 (m, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 6.43-6.27 (m, 1H), 5.04-4.83 (m, 1H), 2.20-2.13 (m, 1H), 1.83 (dd, J = 23.9, 6.3 Hz, 3H), 1.72-1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (electrospray) m/z 435.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





fluoroethyl)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







375


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1H NMR (400 MHz, DMSO-d6) δ 13.37 (s, 1H), 11.44 (s, 1H), 11.11 (s, 1H), 8.82 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 8.01 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.49 (s, 1H), 7.39 (dd, J = 9.1, 1.9 Hz, 1H), 7.01 (s, 1H), 6.68 (s, 1H), 5.04-4.84 (m, 1H), 2.20- 2.13 (m, 1H), 1.71-1-61 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 454.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1H-





pyrrol-3-yl)-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







376


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1H NMR (400 MHz, DMSO-d6) δ 13.35 (s, 1H), 11.11 (s, 1H), 8.82 (d, J = 1.6 Hz, 1H), 8.18 (s, 1H), 8.01 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.46 (s, 1H), 7.38 (dd, J = 9.1, 1.9 Hz, 1H), 6.96 (s, 1H), 6.64 (s, 1H), 5.04-4.83 (m, 1H), 3.75 (s, 3H), 2.20-2.13 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 468.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





methyl-1H-pyrrol-3-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







377


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (s, 1H), 11.12 (s, 1H), 8.87 (t, J = 1.4 Hz, 1H), 8.19 (s, 1H), 8.04 (s, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.42 (dd, J = 9.1, 1.9 Hz, 1H), 7.08 (s, 1H), 6.39-6.37 (m, 1H), 6.26 (t, J = 3.0 Hz, 1H), 5.04-4.84 (m, 1H), 3.54 (d, J = 1.1 Hz, 3H), 2.20-2.13 (m, 1H), 1.72-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 468.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





methyl-1H-pyrrol-2-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







378


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1H NMR (400 MHz, DMSO-d6) δ 13.57 (s, 1H), 11.12 (s, 1H), 8.88 (t, J = 1.1 Hz, 1H), 8.21 (s, 1H), 8.10 (s, 1H), 7.70 (d, J = 1.6 Hz, 1H), 7.62 (d, J = 9.3 Hz, 1H), 7.43 (dd, J = 9.1, 1.9 Hz, 1H), 6.64 (d, J = 1.4 Hz, 1H), 5.04-4.84 (m, 1H), 3.76 (s, 3H), 2.20-2.13 (m, 1H), 1.71-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 469.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





methyl-1H-pyrazol-5-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







379


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1H NMR (400 MHz, DMSO-d6) δ 13.94 (s, 1H), 11.11 (s, 1H), 9.01 (s, 1H), 8.86 (s, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.59 (d, J = 9.1 Hz, 1H), 7.39 (dd, J = 9.2, 1.5 Hz, 1H), 6.36 (s, 2H), 5.02-4.85 (m, 1H), 2.18-2.14 (m, 1H), 1.70-1.63 (m, 1H), 1.20-1.14 (m, 1H); LCMS (electrospray) m/z 470.10 (M + H)+.

I






(1S,2S)-N-(6-(7-((2H-tetrazol-2-





yl)methyl)-5-chloro-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







380


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1H NMR (400 MHz, DMSO-d6) δ 13.56 (s, 1H), 11.10 (s, 1H), 8.82 (d, J = 1.1 Hz, 1H), 8.17 (s, 1H), 7.96 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.36 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 1H), 3.91 (d, J = 1.1 Hz, 2H), 3.20 (q, J = 6.8 Hz, 4H), 2.19-2.12 (m, 1H), 2.00-1.93 (m, 2H), 1.71-1.61 (m, 1H), 1.23- 1.13 (m, 1H); LCMS (electrospray) m/z 457.10 (M + H)+.

H






(1S,2S)-N-(6-(7-(azetidin-1-ylmethyl)-5-





chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







381


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1H NMR (400 MHz, DMSO-d6) δ 13.50 (s, 1H), 11.11 (s, 1H), 8.82 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.84 (m, 1H), 4.00 (d, J = 1.1 Hz, 2H), 2.53-2.49 (m, 4H), 2.20-2.13 (m, 1H), 1.70-1.62 (m, 5H), 1.24-1.13 (m, 1H); LCMS (electrospray) m/z 472.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(pyrrolidin-1-ylmethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







382


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1H NMR (400 MHz, DMSO-d6) δ 13.41 (s, 1H), 11.11 (s, 1H), 8.83 (t, J = 1.1 Hz, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 1H), 3.84 (s, 2H), 2.44 (s, 4H), 2.19-2.12 (m, 1H), 1.70-1.62 (m, 1H), 1.51-1.37 (m, 6H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 486.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(piperidin-1-ylmethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







383


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1H NMR (400 MHz, DMSO-d6) δ 13.92 (s, 1H), 11.11 (s, 1H), 8.85 (d, J = 1.1 Hz, 1H), 8.17 (s, 1H), 8.07 (s, 1H), 7.81 (s, 2H), 7.58 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.1, 1.9 Hz, 1H), 6.07 (s, 2H), 5.04- 4.83 (m, 1H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (electrospray) m/z 469.10 (M + H)+.

I






(1S,2S)-N-(6-(7-((2H-1,2,3-triazol-2-





yl)methyl)-5-chloro-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







384


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1H NMR (400 MHz, DMSO-d6) δ 13.95 (s, 1H), 11.11 (s, 1H), 8.83 (t, J = 1.4 Hz, 1H), 8.31 (d, J = 1.4 Hz, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.75 (d, J = 1.1 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 6.03 (s, 2H), 5.04-4.83 (m, 1H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (electrospray) m/z 469.10 (M + H)+.

I






(1S,2S)-N-(6-(7-((1H-1,2,3-triazol-1-





yl)methyl)-5-chloro-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







385


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1H NMR (400 MHz, DMSO-d6) δ 13.92 (s, 1H), 11.11 (s, 1H), 8.83 (d, J = 1.1 Hz, 1H), 8.79 (s, 1H), 8.16 (s, 1H), 8.07 (s, 1H), 7.96 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 5.83 (s, 2H), 5.04-4.83 (m, 1H), 2.19-2.12 (m, 1H), 1.71- 1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (electrospray) m/z 469.10 (M + H)+.

I






(1S,2S)-N-(6-(7-((1H-1,2,4-triazol-1-





yl)methyl)-5-chloro-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







386


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1H NMR (400 MHz, DMSO-d6) δ 13.86 (s, 1H), 11.12 (s, 1H), 8.85 (s, 1H), 8.17 (s, 1H), 8.08 (s, 1H), 7.58 (d, J = 9.6 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 7.33 (d, J = 1.1 Hz, 1H), 6.93-6.91 (m, 1H), 5.04-4.83 (m, 1H), 3.80 (d, J = 15.4 Hz, 3H), 2.19-2.12 (m, 1H), 1.70-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 501.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((1-





methyl-1H-imidazol-2-yl)thio)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







387


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1H NMR (400 MHz, DMSO-d6) δ 13.20-13.84 (s, 1 H) 8.84 (s, 1 H) 8.71 (d, J = 9.4 Hz, 1 H) 7.92 (s, 1 H) 7.87 (s, 1 H) 7.49 (d, J = 9.13 Hz, 1 H) 7.27 (dd, J = 9.26, 1.75 Hz, 1 H) 6.87 (br s, 1 H) 3.00 (d, J = 2.38 Hz, 6 H) 2.66-2.70 (m, 1 H) 0.61-0.71 (m, 2 H) 0.39-0.46 (m, 2 H); LCMS (electrospray) m/z 428.1 (M + H+).

H






1-(6-(5-chloro-7-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-3-cyclopropylurea







388


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1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.89 (s, 1H), 8.21 (s, 1H), 8.15 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.44 (dd, J = 1.6, 9.3 Hz, 1H), 6.95 (br s, 1H), 6.27 (t, J = 3.1 Hz, 1H), 6.14 (br s, 1H), 5.13-4.80 (m, 1H), 2.18 (td, J = 7.0, 13.9 Hz, 1H), 2.07 (s, 3H), 1.74-1.61 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 467.1 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





methyl-1H-pyrrol-1-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







389


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1H NMR (400 MHz, DMSO-d6) δ 13.70-11.96 (m, 1H), 11.08 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.89 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.35 (dd, J = 1.7, 9.2 Hz, 1H), 6.56-5.57 (m, 1H), 5.21-4.65 (m, 1H), 2.25-2.09 (m, 1H), 1.69 (d, J = 1.4 Hz, 6H), 1.65-1.59 (m, 1H), 1.17 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 446.0 (M + H+).

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





hydroxypropan-2-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







390


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1H NMR (400 MHz, DMSO-d6) δ 13.66 (s, 1H), 11.11 (s, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.00 (d, J = 1.1 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 3H), 3.36 (s, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 432.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(methoxymethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







391


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1H NMR (400 MHz, DMSO-d6) δ 13.65 (s, 1H), 11.11 (s, 1H), 8.83 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 8.00 (d, J = 1.6 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 3H), 3.57 (q, J = 7.1 Hz, 2H), 2.19-2.12 (m, 1H), 1.66 (dtd, J = 23.3, 6.7, 3.5 Hz, 1H), 1.39 (s, 0H), 1.24- 1.13 (m, 4H); LCMS (electrospray) m/z 446.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(ethoxymethyl)-





6-fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







392


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1H NMR (400 MHz, DMSO-d6) δ 13.76-14.21 (1H), 11.11 (s, 1H), 9.64 (s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.38 (d, J = 8.8 Hz, 1H), 6.11 (s, 2H), 5.01-4.85 (m, 1H), 2.19-2.12 (m, 1H), 1.69-1.63 (m, 1H), 1.19- 1.13 (m, 1H); LCMS (electrospray) m/z 470.10 (M + H)+.

I






(1S,2S)-N-(6-(7-((1-tetrazol-1-





yl)methyl)-5-chloro-6-fluoro-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







393


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1H NMR (400 MHz, DMSO-d6) δ 13.54-13.94 (s, 1H), 11.06 (d, J = 7.7 Hz, 1H), 8.98 (d, J = 11.5 Hz, 1H), 8.80 (s, 1H), 8.12 (s, 2H), 7.58-7.54 (m, 1H), 7.35 (dd, J = 9.3, 1.6 Hz, 1H), 6.74 (q, J = 7.1 Hz, 1H), 5.00-4.79 (m, 1H), 2.24-2.20 (m, 3H), 2.16- 2.09 (m, 1H), 1.68-1.57 (m, 1H), 1.18-1.09 (m, 1H); LCMS (electrospray) m/z 485.10 (M + H)+.

I






(1S,2S)-N-(6-(7-(1-(2H-tetrazol-2-





yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







394


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 11.06 (d, J = 6.6 Hz, 1H), 8.71 (d, J = 7.7 Hz, 1H), 8.13 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 1.1 Hz, 1H), 7.52 (t, J = 8.5 Hz, 1H), 7.31 (dd, J = 9.3, 1.6 Hz, 1H), 5.56-5.52 (m, 1H), 5.03-4.82 (m, 2H), 3.09 (s, 3H), 2.85 (s, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.34 (d, J = 6.6 Hz, 3H), 1.21-1.12 (m, 1H); LCMS (electrospray) m/z 503.15 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-((1-





(dimethylamino)-1-oxopropan-2-





yl)amino)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







395


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1H NMR (400 MHz, DMSO-d6) δ13.01 (s, 1H), 11.09 (s, 1H), 8.81 (s, 1H), 8.16 (s, 1H), 7.94 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 1.7, 9.3 Hz, 1H), 5.08-4.80 (m, 1H), 3.18 (s, 3H), 2.15 (br d, J = 7.0 Hz, 1H), 1.71 (br d, J = 2.7 Hz, 6H), 1.64 (br s, 1H), 1.17 (br dd, J = 8.9, 12.1 Hz, 1H); LCMS (electrospray) m/z 460.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





methoxypropan-2-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







396


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1H NMR (400 MHz, DMSO-d6) δ 13.37-12.98 (m, 1H), 11.09 (s, 1H), 8.82 (s, 1H), 8.22 (s, 1H), 8.16 (s, 1H), 7.95 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.37 (dd, J = 1.7, 9.2 Hz, 1H), 5.03-4.82 (m, 1H), 3.87 (q, J = 6.6 Hz, 1H), 2.21 (s, 6H), 2.16 (br dd, J = 6.1, 7.6 Hz, 1H), 1.72-1.61 (m, 1H), 1.49 (d, J = 6.8 Hz, 3H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 459.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(1-





(dimethylamino)ethyl)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide.





Formaic acid salt







397


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1H NMR (400 MHz, DMSO-d6) δ 13.26-13.88 (1H), 11.08 (s, 1H), 8.71 (d, J = 1.6 Hz, 1H), 8.15 (s, 1H), 7.94 (s, 1H), 7.53 (d, J = 9.3 Hz, 1H), 7.30 (dd, J = 9.3, 1.6 Hz, 1H), 5.75 (d, J = 3.3 Hz, 1H), 5.03-4.83 (m, 1H), 4.42 (d, J = 4.4 Hz, 2H), 3.02 (s, 3H), 2.88 (s, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.12 (m, 1H); LCMS (electrospray) m/z 488.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-((2-





(dimethylamino)-2-oxoethyl)amino)-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







398


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1H NMR (400 MHz, DMSO-d6) δ 13.53-14.00 (1H), 11.12 (s, 1H), 9.77 (s, 1H), 8.83 (s, 1H), 8.20- 8.17 (m, 2H), 7.59 (d, J = 9.1 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 6.59 (q, J = 7.1 Hz, 1H), 5.04- 4.83 (m, 1H), 2.21 (d, J = 7.1 Hz, 3H), 2.17-2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.20-1.13 (m, 1H); LCMS (electrospray) m/z 484.10 (M + H)+.

I






(1S,2S)-N-(6-(7-(1-(1H-tetrazol-1-





yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







399


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1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.79 (s, 1H), 8.20 (d, J = 15.8 Hz, 2H), 8.00 (s, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.34 (dd, J = 1.8, 9.2 Hz, 1H), 5.03-4.84 (m, 1H), 4.81-4.75 (m, 1H), 2.22- 2.09 (m, 1H), 1.75-1.59 (m, 1H), 1.54 (d, J = 6.8 Hz, 3H), 1.27-1.12 (m, 1H); LCMS (electrospray) m/z 431.1 (M + H)+.

H






(1S,2S)-N-(6-(7-(1-aminoethyl)-5-chloro-





6-fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







400


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1H NMR (400 MHz, DMSO-d6) δ 14.12-13.82 (m, 1H), 11.11 (s, 1H), 8.84 (s, 1H), 8.27-8.14 (m, 1H), 7.64 (s, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.39 (dd, J = 9.1, 1.8 Hz, 1H), 7.27 (s, 1H), 6.66 (dd, J = 2.9, 1.6 Hz, 1H) 5.10-4.79 (m, 1H), 3.22-3.00 (m, 6H), 2.21-2.12 (m, 1H), 1.74-1.61(m, 1H), 1.24-1.12 (m, 1H); LCMS (electrospray) m/z 524.1 (M + H)+.

H






1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





1H-indazol-7-yl)-N,N-dimethyl-1H-





pyrrole-3-carboxamide







401


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1H NMR (400 MHz, DMSO-d6) δ 13.79 (s, 1 H) 11.18 (s, 1 H) 8.67 (d, J = 7.09 Hz, 1 H) 7.93 (s, 1 H) 7.77 (s, 1 H) 6.92-6.99 (m, 2 H) 4.82-5.08 (m, 1 H) 4.53 (s, 1 H) 2.15 (m, 1 H) 1.61-1.75 (m, 1 H) 1.12-1.27 (m, 1 H) 0.92 (br s, 2 H) 0.68- 0.77 (m, 2 H); LCMS (electrospray) m/z 444.0 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-cyclopropoxy-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







402


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1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 8.81 (s, 1H), 8.27 (br s, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 1.7, 9.3 Hz, 1H), 5.12-4.75 (m, 1H), 4.33 (d, J = 6.8 Hz, 1H), 2.22-2.12 (m, 4H), 1.74-1.59 (m, 1H), 1.47 (d, J = 6.7 Hz, 3H), 1.22-1.12 (m, 1H); LCMS (electrospray) m/z 445.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





(methylamino)ethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







403


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1H NMR (400 MHz, DMSO-d6) δ 13.35-13.11 (m, 1H), 10.33 (s, 1H), 8.40 (s, 1H), 7.96-7.72 (m, 1H), 7.44 (s, 2H), 6.36 (d, J = 1.4 Hz, 1H), 5.79 (s, 2H), 5.09 (dd, J = 2.4, 9.4 Hz, 1H), 5.05-4.81 (m, 1H), 4.17-3.92 (m, 1H), 4.14-2.74 (m, 1H), 2.17- 2.05 (m, 1H), 1.71-1.55 (m,12H), 1.23 (d, J = 6.3 Hz, 6H), 1.21-1.08 (m, 1H); LCMS (electrospray) m/z 460.2 (M + H)+.

H






(1S,2S)-N-(8-amino-6-(5-chloro-6-fluoro-





7-(isopropylamino)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1





formic acid







404


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1H NMR (400 MHz, DMSO-d6) δ 14.17-13.33 (m, 1H), 11.08 (s, 1H), 8.79 (s, 1H), 8.16 (s, 1H), 8.00 (s, 1H), 7.56 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.5, 9.2 Hz, 1H), 5.06-4.81 (m, 1H), 4.73 (br d, J = 1.1 Hz, 1H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 2.07 (s, 1H), 1.76-1.56 (m, 1H), 1.37 (d, J = 6.0 Hz, 6H), 1.17 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS (electrospray) m/z 446.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





isopropoxy-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







405


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1H NMR (400 MHz, DMSO-d6) δ 13.55 (br s, 1H), 11.08 (s, 1H), 8.78 (d, J = 1.0 Hz, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.8, 9.3 Hz, 1H), 5.05-4.80 (m, 1H), 3.67-3.55 (m, 1H), 2.16 (td, J = 7.0, 14.0 Hz, 1H), 1.73-1.59 (m, 1H), 1.45 (d, J = 7.0 Hz, 6H), 1.17 (tdd, J = 6.1, 9.1, 12.1 Hz, 1H); LCMS (electrospray) m/z 430.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





isopropyl-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







406


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1H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 11.11 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.96 (d, J = 1.1 Hz, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 3.61 (q, J = 8.8 Hz, 1H), 2.19-1.91 (m, 8H), 1.73-1.61 (m, 3H), 1.24-1.07 (m, 1H); LCMS (electrospray) m/z 456.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-cyclopentyl-6-





fluoro-1H-indazol-4-yl)imidazo[1,2-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







407


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1H NMR (400 MHz, DMSO-d6) δ 14.18-13.49 (m, 1H), 11.09 (s, 1H), 9.02 (s, 1H), 8.83 (s, 1H), 8.28-7.99 (m, 2H), 7.58 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 1.7, 9.2 Hz, 1H), 6.78 (q, J = 6.9 Hz, 1H), 5.10-4.74 (m, 1H), 2.27 (d, J = 7.0 Hz, 3H), 2.21- 2.11 (m, 1H), 1.74-1.59 (m, 1H), 1.22-1.12 (m, 1H); LCMS (electrospray) m/z 484.1 (M + H)+.

I






(1S,2S)-N-(6-(7-((R)-1-(2H-tetrazol-2-





yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







408


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1H NMR (400 MHz, DMSO-d6) δ 14.19-13.48 (m, 1H), 11.09 (s, 1H), 9.02 (s, 1H), 8.83 (s, 1H), 8.31-7.98 (m, 2H), 7.59 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 1.7, 9.2 Hz, 1H), 6.78 (q, J = 7.1 Hz, 1H), 5.09-4.68 (m, 1H), 2.27 (d, J = 7.0 Hz, 3H), 2.20- 2.10 (m, 1H), 1.67 (tdd, J = 3.2, 6.8, 19.9 Hz, 1H), 1.23-1.13 (m, 1H); LCMS (electrospray) m/z 484.1 (M + H)+.

I






(1S,2S)-N-(6-(7-((S)-1-(2H-tetrazol-2-





yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







409


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1H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1H), 11.10 (s, 1H), 8.86 (s, 1H), 8.17 (s, 1H), 8.01 (d, J = 1.6 Hz, 1H), 7.59 (q, J = 9.7 Hz, 2H), 7.40 (dd, J = 9.3, 1.6 Hz, 1H), 5.82-5.75 (m, 1H), 5.04-4.83 (m, 1H), 2.20-2.13 (m, 1H), 1.72-1.62 (m, 1H), 1.28-1.11 (m, 1H); LCMS (electrospray) m/z 487.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2,2,2-





trifluoro-1-hydroxyethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







410


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1H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 11.08 (s, 1H), 8.77 (s, 1H), 8.18 (s, 1H), 7.95 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.34 (dd, J = 9.3, 1.6 Hz, 1H), 5.03-4.83 (m, 2H), 4.50-4.42 (m, 3H), 3.51-3.38 (m, 6H), 2.20-2.07 (m, 3H), 1.99-1.83 (m, 3H), 1.72-1.61 (m, 2H), 1.23-1.13 (m, 4H); LCMS (electrospray) m/z 472.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





hydroxycyclopentyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







411


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1H NMR (400 MHz, DMSO-d6) δ 8.62-8.72 (m, 1 H) 8.12-8.25 (m, 1 H) 7.83-7.96 (m, 1 H) 7.56- 7.62 (m, 1 H) 7.43-7.52 (m, 1 H) 4.95-4.98 (m, 0.5 H) 4.77-4.81 (m, 0.5 H) 2.70-2.80 (m, 3 H) 2.07-2.17 (m, 1H) 1.73-1.88 (m, 1 H) 1.18-1.31 (m, 1 H); LCMS (electrospray) m/z 461.3 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-





ethanethioamido-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







412


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1H NMR (400 MHz, DMSO-d6) δ 13.54-12.76 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.36 (s, 1H), 8.17 (s, 1H), 8.07-7.97 (m, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.36 (br d, J = 9.0 Hz, 1H), 7.23 (br d, J = 6.8 Hz, 1H), 6.87 (br d, J = 5.0 Hz, 1H), 6.07 (q, J = 6.7 Hz, 1H), 5.82-5.67 (m, 1H), 5.13-4.80 (m, 1H), 3.02 (s, 3H), 2.78 (br s, 1H), 2.20-2.14 (m, 1H), 2.10-2.00 (m, 3H), 1.86-1.75 (m, 1H), 1.71- 1.64 (m, 3H), 1.28-1.07 (m, 1H); LCMS (electrospray) m/z 487.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(N-





methylacetamido)ethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







413


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1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 9.77 (s, 1H), 8.82 (s, 1H), 8.24-8.00 (m, 2H), 7.58 (d, J = 9.1 Hz, 1H), 7.37 (dd, J = 1.6, 9.3 Hz, 1H), 6.62 (d, J = 7.4 Hz, 1H), 5.11-4.74 (m, 1H), 2.25- 2.15 (m, 4H), 1.79-1.56 (m, 1H), 1.27-1.10 (m, 1H); LCMS (electrospray) m/z 484.1 (M + H)+.

I






(1S,2S)-N-(6-7-((R)-1-(1H-tetrazol-1-





yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







414


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1H NMR (400 MHz, DMSO-d6) δ 13.75 (br s, 1H), 11.09 (s, 1H), 9.75 (s, 1H), 8.82 (s, 1H), 8.17 (s, 1H), 8.08 (s, 1H), 7.59 (br d, J = 8.9 Hz, 1H), 7.37 (dd, J = 1.7, 9.2 Hz, 1H), 6.59 (br d, J = 6.8 Hz, 1H), 5.12-4.75 (m, 1H), 2.26-2.07 (m, 4H), 1.75- 1.60 (m, 1H), 1.21-1.15 (m, 1H); LCMS (electrospray) m/z 484.1 (M + H)+.

I






(1S,2S)-N-(6-(7-((S)-1-(1H-tetrazol-1-





yl)ethyl)-5-chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







415


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1H NMR (400 MHz, DMSO-d6) δ 13.40-13.49 (1H), 11.06-11.17 (1H), 8.83-8.91 (1H), 8.15-8.21 (1H), 8.02-8.09 (1H), 7.57-7.64 (1H), 7.38-7.46 (1H), 5.72-5.82 (1H), 4.82-5.07 (1H), 3.46-3.55 (3H), 2.12-2.21 (1H), 1.61-1.74 (1H), 1.13-1.22 (1H); LCMS (electrospray) m/z 501.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2,2,2-





trifluoro-1-methoxyethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







416


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1H NMR (400 MHz, DMSO-d6) δ 13.23 (s, 1H), 11.06 (s, 1H), 8.72 (s, 1H), 8.16 (s, 1H), 7.88 (d, J = 1.1 Hz, 1H), 7.54 (d, J = 9.3 Hz, 1H), 7.32 (dd, J = 9.3, 1.6 Hz, 1H), 5.60-5.58 (m, 1H), 5.04-4.83 (m, 1H), 4.55 (s, 1H), 3.95 (q, J = 7.7 Hz, 1H), 3.87 (dd, J = 9.1, 5.8 Hz, 1H), 3.79-3.71 (m, 2H), 2.27- 2.13 (m, 2H), 1.91 (s, 1H), 1.67 (dtd, J = 23.5, 6.9, 3.7 Hz, 1H), 1.22-1.13 (m, 1H); LCMS (electrospray) m/z 474.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





((tetrahydrofuran-3-yl)amino)-1H-indazol-





4-yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







417


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1H NMR (400 MHz, DMSO-d6) δ 13.67-13.49 (m, 1H), 11.10 (s, 1H), 8.79 (s, 1H), 8.52 (d, J = 6.8 Hz, 1H), 8.16 (s, 1H), 7.98 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.6, 9.3 Hz, 1H), 5.45 (quin, J = 7.1 Hz, 1H), 5.07-4.81 (m, 1H), 2.22- 2.11 (m, 1H), 1.85 (s, 3H), 1.73-1.61 (m, 1H), 1.55 (d, J = 7.3 Hz, 3H), 1.17 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 473.2 (M + H)+.

H






(1S,2S)-N-(6-(7-(1-acetamidoethyl)-5-





chloro-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







418


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1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 11.10 (s, 1H), 8.87 (s, 1H), 8.16-8.04 (m, 2H), 7.59 (d, J = 8.8 Hz, 1H), 7.41 (dd, J = 9.1, 1.9 Hz, 1H), 5.81 (q, J = 7.1 Hz, 1H), 5.04-4.83 (m, 1H), 3.79- 3.58 (m, 2H), 2.20-2.13 (m, 1H), 1.67 (dtd, J = 23.4, 6.8, 3.6 Hz, 1H), 1.23 (t, J = 7.1 Hz, 3H), 1.19-1.13 (m, 1H); LCMS (electrospray) m/z 514.7 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(1-ethoxy-2,2,2-





trifluoroethyl)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







419


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1H NMR (400 MHz, DMSO-d6) δ 13.78 (s, 1H), 11.12 (s, 1H), 8.89 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 8.12 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.42 (dd, J = 9.1, 1.9 Hz, 1H), 7.06 (dt, J = 41.2, 6.7 Hz, 1H), 5.05-4.84 (m, 1H), 2.21-2.14 (m, 1H), 1.68 (dtd, J = 23.5, 6.9, 3.5 Hz, 1H), 1.24-1.14 (m, 1H); LCMS (electrospray) m/z 488.7 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





(1,2,2,2-tetrafluoroethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







420


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1H NMR (400 MHz, DMSO-d6) δ 13.30 (br s, 1H), 11.05 (s, 1H), 8.72 (s, 1H), 8.14 (s, 1H), 7.87 (br s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.31 (dd, J = 1.5, 9.2 Hz, 1H), 5.34 (br s, 1H), 5.04-4.82 (m, 1H), 2.16 (td, J = 7.0, 13.9 Hz, 1H), 1.73-1.61 (m, 1H), 1.26 (d, J = 6.3 Hz, 3H), 1.16 (ddd, J = 2.8, 6.2, 12.1 Hz, 1H), 1.00 (br s, 1H), 0.46-0.37 (m, 2H), 0.30- 0.20 (m, 2H); LCMS (electrospray) m/z 471.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-((1-





cyclopropylethyl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







421


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1H NMR (400 MHz, DMSO-d6) δ 13.22 (br s, 1H), 11.06 (s, 1H), 8.71 (s, 1H), 8.14 (s, 1H), 7.86 (s, 1H), 7.52 (d, J = 9.1 Hz, 1H), 7.30 (d, J = 9.3 Hz, 1H), 5.57 (m, 1H), 4.92 (m, 1H), 3.30 (s, 2H), 2.15 (m, 1H), 1.66 (m, 1H), 1.16 (m, 1H), 1.07 (m, 1H), 0.48 (m, 2H), 0.27 (m, 2H); LCMS (electrospray) m/z 457.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-





((cyclopropylmethyl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







422


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1H NMR (400 MHz, DMSO-d6) δ 13.52-13.66 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 7.97 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.36 (dd, J = 1.6 Hz, 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 3.82- 3.74 (m, 3H), 3.68 (s, 1H), 2.20-2.14 (m, 1H), 1.71-1.63 (m, 1H), 1.22 (d, J = 7.4 Hz, 3H), 1.2- 1.14(m, 2H); LCMS (electrospray) m/z 460.0 (M + H)+; SFC RT = 0.640.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((R)-1-





methoxypropan-2-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







423


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1H NMR (400 MHz, DMSO-d6) δ 13.57 (s, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 7.98 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.35 (d, J = 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 3.82-3.74 (m, 3H), 2.20-2.14 (m, 1H), 1.41-1.39 (m, 1H), 1.22 (d, J = 14.4 Hz, 3H), 1.2-1.17(m, 2H); LCMS (electrospray) m/z 460.0 (M + H)+; SFC RT = 1.252.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((S)-1-





methoxypropan-2-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







424


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1H NMR (400 MHz, DMSO-d6) δ 13.64-13.32 (m, 1H), 11.09 (s, 1H), 8.79 (s, 1H), 8.32 (br d, J = 6.3 Hz, 1H), 8.16 (s, 1H), 7.98 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.7, 9.2 Hz, 1H), 5.46 (br t, J = 7.0 Hz, 1H), 5.05-4.81 (m, 1H), 2.19-2.07 (m, 3H), 1.74-1.60 (m, 1H), 1.55 (d, J = 7.3 Hz, 3H), 1.24-1.11 (m, 1H), 0.95 (t, J = 7.6 Hz, 3H); LCMS (electrospray) m/z 487.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





propionamidoethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







425


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1H NMR (400 MHz, DMSO-d6) δ 13.55-13.09 (m, 1H), 11.07 (s, 1H), 8.73 (s, 1H), 8.16 (s, 1H), 8.07- 7.83 (m, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.32 (dd, J = 1.7, 9.1 Hz, 1H), 6.30-5.95 (m, 1H), 5.65-5.44 (m, 1H), 5.11-4.76 (m, 1H), 4.54-3.95 (m, 1H), 2.20-2.12 (m, 1H), 1.75-1.59 (m, 1H), 1.33 (d, J = 6.7 Hz, 3H), 1.17 (ddt J = 6.2, 6.2, 9.1, 12.2 Hz, 1H); LCMS (electrospray) m/z 481.0 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-((1,1-





difluoropropan-2-yl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







426


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1H NMR (400 MHz, DMSO-d6) δ 13.66-13.47 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.67 (br d, J = 6.8 Hz, 1H), 8.16 (s, 1H), 8.06 (s, 1H), 8.00 (br s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.4, 9.3 Hz, 1H), 5.62-5.48 (m, 1H), 5.09-4.80 (m, 1H), 2.16 (quin, J = 6.9 Hz, 1H), 1.73-1.61 (m, 1H), 1.57 (d, J = 7.0 Hz, 3H), 1.22-1.10 (m, 1H); LCMS (electrospray) m/z 458.9 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





formamidoethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







427


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1H NMR (400 MHz, DMSO-d6) δ 13.74-13.07 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.43 (s, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.35 (dd, J = 1.7, 9.2 Hz, 1H), 5.06-4.80 (m, 1H), 4.60 (t, J = 6.4 Hz, 1H), 4.50-4.39 (m, 2H), 4.32 (t, J = 6.5 Hz, 1H), 4.15 (t, J = 6.2 Hz, 1H), 3.75 (br t, J = 6.7 Hz, 1H), 2.22-2.11 (m, 1H), 1.73- 1.60 (m, 1H), 1.49 (d, J = 6.7 Hz, 3H), 1.24-1.11 (m, 1H); LCMS (electrospray) m/z 487.3 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





(oxetan-3-ylamino)ethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







428


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1H NMR (400 MHz, DMSO-d6) δ 13.30 (br s, 1H), 11.19 (s, 1H), 10.04 (d, J = 4.5 Hz, 1H), 8.84 (s, 1H), 8.16 (s, 1H), 8.04 (s, 1H), 7.62 (d, J = 9.1 Hz, 1H), 7.49-7.39 (m, 1H), 5.70-5.46 (m, 1H), 5.11- 4.78 (m, 1H), 2.17 (td, J = 6.9, 13.8 Hz, 1H), 1.69 (d, J = 7.0 Hz, 3H), 1.67-1.59 (m, 1H), 1.29-1.09 (m, 1H); LCMS (electrospray) m/z 527.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





(2,2,2-trifluoroacetamido)ethyl)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







429


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1H NMR (400 MHz, DMSO-d6) δ 13.30 (br s, 1H), 11.05 (s, 1H), 8.72 (s, 1H), 8.14 (s, 1H), 7.91 (s, 1H), 7.58 (d, J = 9.0 Hz, 1H), 7.38-7.32 (m, 1H), 5.09-4.81 (m, 1H), 4.08-3.99 (m, 1H), 2.19-2.13 (m, 1H), 1.71-1.62 (m, 1H), 1.51 (d, J = 6.7 Hz, 3H), 1.32-1.23 (m, 1H), 1.21-1.13 (m, 1H), 1.04- 0.94 (m, 1H), 0.69-0.56 (m, 1H); LCMS (electrospray) m/z 496.3 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(1-((1-





cyanocyclopropyl)amino)ethyl)-6-fluoro-





1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







430


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1H NMR (400 MHz, DMSO-d6) δ 13.99-13.36 (m, 1H), 11.09 (s, 1H), 8.79 (s, 1H), 8.51-8.44 (m, 1H), 8.46 (s, 1H), 8.41 (br d, J = 6.7 Hz, 1H), 8.15 (s, 1H), 7.97 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.35 (dd, J = 1.7, 9.3 Hz, 1H), 5.45 (br t, J = 7.0 Hz, 1H), 5.07-4.76 (m, 1H), 3.14-3.03 (m, 1H), 2.10 (br d, J = 8.7 Hz, 1H), 2.21-2.01 (m, 1H), 2.00-1.81 (m, 4H), 1.64 (dt, J = 4.2, 6.7 Hz, 1H), 1.75-1.60 (m, 1H), 1.55 (br d, J = 7.2 Hz, 3H), 1.17 (ddd, J = 2.8, 6.2, 12.3 Hz, 1H); LCMS (electrospray) m/z 513.3 (M + H)+.

H






N-(1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)imidazo[1,2-a]pyridin-6-yl)-





1H-indazol-7-





yl)ethyl)cyclobutanecarboxamide







431


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1H NMR (400 MHz, DMSO-d6) δ 13.37 (br s, 1H), 11.25 (s, 1H), 8.92 (s, 1H), 8.81 (d, J = 5.7 Hz, 1H), 8.22 (s, 1H), 8.19 (s, 1H), 8.10 (s, 1H), 7.66 (d, J = 9.2 Hz, 1H), 7.49 (d, J = 9.4 Hz, 1H), 5.06-4.89 (m, 1H), 2.24-2.15 (m, 1H), 1.78-1.62 (m, 1H), 1.26-1.17 (m, 1H), 0.30-0.20 (m, 2H); LCMS (electrospray) m/z 453.9 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1H-





imidazol-5-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







432


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1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 11.08 (s, 1H), 8.68 (s, 1H), 8.19 (s, 1H), 7.81 (s, 1H), 7.54 (d, J = 9.3 Hz, 1H), 7.30 (dd, J = 9.3, 1.6 Hz, 1H), 6.48 (d, J = 18.1 Hz, 2H), 4.93 (ddd, J = 66.4, 10.0, 6.2 Hz, 1H), 3.40 (s, 4H), 2.19-2.12 (m, 1H), 1.71-1.62 (m, 1H), 1.19-1.12 (m, 1H); LCMS (electrospray) m/z 472.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-((4,5-dihydro-





1H-imidazol-2-yl)amino)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







433


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1H NMR (400 MHz, DMSO-d6) δ 1H-NMR (400 MHz, DMSO-D6) δ 13.31 (s, 1H), 11.11 (s, 1H), 8.79 (d, J = 1.6 Hz, 1H), 8.19 (s, 1H), 7.98 (d, J = 1.6 Hz, 1H), 7.94 (d, J = 4.9 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 9.1, 1.9 Hz, 1H), 4.93 (ddd, J = 66.2, 10.2, 6.3 Hz, 1H), 4.25 (q, J = 7.1 Hz, 1H), 2.67-2.60 (m, 3H), 2.19-2.08 (m, 1H), 1.71-1.61 (m, 1H), 1.55 (d, J = 7.1 Hz, 3H), 1.24- 1.10 (m, 1H); LCMS (electrospray) m/z 473.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





(methylamino)-1-oxopropan-2-yl)-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







434


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1H NMR (400 MHz, DMSO-d6) δ 13.70 (s, 1H), 11.13 (s, 1H), 8.85 (s, 1H), 8.18 (s, 1H), 8.04-8.01 (m, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.05-4.84 (m, 1H), 4.10 (d, J = 12.6 Hz, 2H), 2.20-2.13 (m, 1H), 2.08 (d, J = 9.3 Hz, 3H), 1.67 (dtd, J = 23.3, 6.8, 3.7 Hz, 1H), 1.24-1.14 (m, 1H), LCMS (electrospray) m/z 449.05 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





((methylthio)methyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







435


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.71 (s, 1H), 11.12 (s, 1H), 8.79 (s, 1H), 8.23 (s, 1H), 8.03 (d, J = 1.1 Hz, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.36 (dd, J = 9.3, 1.6 Hz, 1H), 6.42 (s, 1H), 5.04-4.84 (m, 1H), 3.21 (s, 3H), 2.58 (d, J = 4.4 Hz, 3H), 2.20-2.13 (m, 1H), 1.70-1.63 (m, 1H), 1.19-1.13 (m, 1H) m/z 474.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(1,3-





dimethylureido)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







436


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.58 (s, 1H), 11.12 (s, 1H), 8.82 (t, J = 1.4 Hz, 1H), 8.18 (d, J = 12.1 Hz, 1H), 8.01 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 4.64 (q, J = 7.1 Hz, 1H), 2.19-2.12 (m, 1H), 2.02- 1.96 (m, 3H), 1.81-1.77 (m, 3H), 1.66 (dtd, J = 23.3, 6.9, 3.8 Hz, 1H), 1.21-1.13 (m, 1H), LCMS (electrospray) m/z 463.00 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





(methylthio)ethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







437


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.71 (s, 1H), 11.12 (s, 1H), 8.85 (d, J = 1.1 Hz, 1H), 8.21-8.16 (m, 1H), 8.03 (d, J = 1.1 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 4.54-4.43 (m, 2H), 2.68 (d, J = 13.7 Hz, 3H), 2.20-2.13 (m, 1H), 1.67 (dtd, J = 23.3, 6.9, 3.8 Hz, 1H), 1.20-1.13 (m, 1H) LCMS (electrospray) m/z 465.00 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





((methylsulfinyl)methyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







438


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.69 (s, 1H), 11.12 (s, 1H), 8.85 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 3H), 3.11 (s, 3H), 2.19-2.12 (m, 1H), 1.66 (dtd, J = 23.5, 6.7, 3.5 Hz, 1H), 1.22-1.13 (m, 1H), LCMS (electrospray) m/z 481.00 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-





((methylsulfonyl)methyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







439


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.81 (s, 1H), 11.14 (s, 1H), 9.65 (d, J = 6.0 Hz, 1H), 8.86 (s, 1H), 8.21 (d, J = 8.8 Hz, 2H), 8.13 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.1, 1.4 Hz, 1H), 6.69 (d, J = 6.6 Hz, 1H), 5.05-4.84 (m, 1H), 2.21-2.14 (m, 1H), 1.73-1.62 (m, 1H), 1.22-1.14 (m, 1H), LCMS (electrospray) m/z 471.00 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-





(cyano(formamido)methyl)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







440


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1H NMR (400 MHz, DMSO-d6) δ 13.33 (s, 1H), 11.12 (s, 1H), 8.85 (t, J = 1.4 Hz, 1H), 8.16 (s, 1H), 7.97 (d, J = 0.8 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 2H), 3.93-3.87 (m, 1H), 3.38 (d, J = 3.3 Hz, 2H), 3.24 (s, 3H), 2.16 (dt, J = 14.4, 6.7 Hz, 1H), 1.66 (dtd, J = 23.2, 6.9, 3.8 Hz, 1H), 1.24-1.13 (m, 1H), 0.95 (d, J = 6.0 Hz, 3H); LCMS (electrospray) m/z 490.10 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-((1S,2R)-1,2-





dimethoxypropyl)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







441


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.60 (br s, 1H), 11.08 (s, 1H), 9.39 (br d, J = 6.5 Hz, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 8.02 (br s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.36 (dd, J = 1.8, 9.2 Hz, 1H), 6.28 (t, J = 53.6 Hz, 1H), 5.55 (br t, J = 6.8 Hz, 1H), 5.04- 4.81 (m, 1H), 2.23-2.10 (m, 1H), 1.73-1.67 (m, 1H), 1.65 (d, J = 7.2 Hz, 3H), 1.17 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 509.2 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(1-(2,2-





difluoroacetamido)ethyl)-6-fluoro-1H-





indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







442


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1H NMR (400 MHz, DMSO-d6) δ 13.20 (s, 1H), 12.37 (d, J = 1.3 Hz, 1H), 11.08 (s, 1H), 8.85 (s, 1H), 8.18 (s, 1H), 8.00 (s, 1H), 7.67 (d, J = 3.1 Hz, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.40 (dd, J = 1.7. 9.2 Hz, 1H), 4.93 (m, 1H), 2.48 (s, 3H), 2.16 (m, 2H), 1.67 (m, 2H), 1.17 (m, 2H); LCMS (electrospray) m/z 468.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-





methyl-1H-imidazol-5-yl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







443


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1H NMR (400 MHz, DMSO-d6) δ 13.68 (s, 1H), 11.11 (s, 1H), 8.81 (d, J = 1.1 Hz, 1H), 8.17 (d, J = 9.3 Hz, 1H), 8.05 (d, J = 1.1 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 5.04- 4.83 (m, 1H), 4.64-4.59 (m, 1H), 2.48 (s, 2H), 2.19-2.12 (m, 1H), 1.83-1.81 (m, 3H), 1.71-1.61 (m, 1H), 1.20-1.13 (m, 1H); LCMS (electrospray) m/z 478.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





(methylsulflnyl)ethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







444


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1H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 11.12 (s, 1H), 8.84 (s, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 5.15 (d, J = 7.1 Hz, 1H), 5.04-4.83 (m, 1H), 3.06 (s, 3H), 2.20-2.13 (m, 1H), 1.97-1.91 (m, 3H), 1.72-1.62 (m, 1H), 1.20-1.13 (m, 1H); LCMS (electrospray) m/z 494.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-





(methylsulfonyl)ethyl)-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







445


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1H), 11.08 (s, 1H), 8.79 (s, 1H), 8.18 (s, 1H), 8.00 (d, J = 23.6 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.35 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 1H), 4.24 (q, J = 7.1 Hz, 1H), 3.11 (td, J = 12.6, 7.1 Hz, 2H), 2.20- 2.13 (m, 1H), 1.70-1.63 (m, 1H), 1.54 (d, J = 7.1 Hz, 3H), 1.21-1.13 (m, 1H), 1.01 (t, J = 7.1 Hz, 3H); LCMS (electrospray) m/z 487.1 (M + H)+.

H






(1S,2S)-N-(6-(5-chloro-7-(1-(ethylamino)-





1-oxopropan-2-yl)-6-fluoro-1H-indazol-4-





yl)imidazo[1,2-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







446


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1H NMR (400 MHz, DMSO-d6) δ 13.09 (s, 1H), 11.13 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.74 (s, 1H), 7.63 (d, J = 0.9 Hz, 1H), 7.49 (d, J = 8.6 Hz, 1H), 7.32 (d, J = 8.6 Hz, 1H), 6.91 (s, 1H), 6.86 (dd, J = 1.9, 7.0 Hz, 1H), 5.06-4.98 (m, 1H), 4.88-4.84 (m, 1H), 2.34 (s, 3H), 2.15 (td, J = 6.9, 13.8 Hz, 1H), 1.74- 1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (electrospray) m/z 350.1 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(5-methyl-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







447


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.82 (s, 1H), 7.65 (d, J = 0.9 Hz, 1H), 7.45 (d, J = 11.5 Hz, 1H), 6.93 (s, 1H), 6.81 (dd, J = 1.8, 7.1 Hz, 1H), 6.56 (dd, J = 11.8, 17.9 Hz, 1H), 5.63 (br d, J = 18.0 Hz, 1H), 5.46-5.36 (m, 1H), 5.06-4.82 (m, 1H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.73-1.59 (m, 1H), 1.17 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H)); LCMS (electrospray) m/z 380.1 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-vinyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 HCl







448


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.88 (d, J = 1.0 Hz, 1H), 7.75 (d, J = 1.0 Hz, 1H), 7.63 (dd, J = 1.0, 8.8 Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H), 6.95 (s, 1H), 6.92 (dd, J = 2.0, 7.1 Hz, 1H), 5.05-4.83 (m, 1H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.17 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS (electrospray) m/z 370.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 HCl







449


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.56 (br d, J = 7.0 Hz, 1H), 7.90 (s, 1H), 7.74 (s, 1H), 7.58 (br d, J = 9.2 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 6.98 (br d, J = 7.1 Hz, 1H), 6.89 (s, 1H), 5.08- 4.80 (m, 1H), 3.80 (s, 3H), 2.19-2.08 (m, 1H), 1.75-1.60 (m, 1H), 1.26-1.07 (m, 1H); LCMS (electrospray) m/z 366.1 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(5-methoxy-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 HCl







450


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.18 (br s, 1H), 8.68 (br s, 1H), 8.12-7.54 (m, 5H), 7.04-6.85 (m, 2H), 5.05-4.84 (m, 1H), 3.10 (br s, 6H), 2.16 (td, J = 7.0, 14.0 Hz, 1H), 1.73-1.62 (m, 1H), 1.23-1.14 (m, 1H); LCMS (electrospray) m/z 379.1 (M + H)+.

J






(1S,2S)-N-(5-(5-(dimethylamino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 3





HCl







451


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1H NMR (400 MHz, DMSO-d6) δ 14.19-13.15 (m, 1H), 11.17 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.87 (s, 1H), 7.82-7.74 (m, 2H), 7.64 (s, 1H), 6.93 (s, 1H), 6.83 (dd, J = 1.8, 7.1 Hz, 1H), 5.08-4.81 (m, 1H), 2.20-2.10 (m, 1H), 1.74-1.59 (m, 1H), 1.17 (tdd, J = 6.2, 9.0, 12.4 Hz, 1H); LCMS (electrospray) m/z 404.1 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(5-





(trifluoromethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 HCl







452


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.10 (br s, 1H), 11.13 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.68 (s, 1H), 7.59 (d, J = 1.0 Hz, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.36 (d, J = 8.7 Hz, 1H), 6.90 (s, 1H), 6.81 (dd, J = 1.9, 7.0 Hz, 1H), 5.06-4.81 (m, 1H), 2.70-2.59 (m, 2H), 2.20-2.10 (m, 1H), 1.75-1.58 (m, 1H), 1.18 (td, J = 3.1, 6.1 Hz, 1H), 1.12 (t, J = 7.5 Hz, 3H); LCMS (electrospray) m/z 364.2 (M + H)+.

J






(1S,2S)-N-(5-(5-ethyl-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







453


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.97 (d, J = 0.7 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.69-7.64 (m, 1H), 7.61 (d, J = 1.1 Hz, 1H), 6.92 (s, 1H), 6.82 (dd, J = 2.0, 7.1 Hz, 1H), 5.06-4.82 (m, 1H), 2.33 (s, 3H), 2.21- 2.11 (m, 1H), 1.73-1.61 (m, 1H), 1.18 (tdd, J = 6.1, 8.9, 12.3 Hz, 1H); LCMS (electrospray) m/z 378.2 (M + H)+.

J






(1S,2S)-N-(5-(5-acetyl-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 HCl







454


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 8.58 (d, J = 7.1 Hz, 1H), 7.82 (s, 1H), 7.66 (s, 1H), 7.40 (d, J = 12.0 Hz, 1H), 6.93-6.87 (m, 2H), 5.05- 4.82 (m, 1H), 2.67 (s, 6H), 2.19-2.09 (m, 1H), 1.73-1.61 (m, 1H), 1.22-1.12 (m, 1H); LCMS (electrospray) m/z = 397.1 (M + H+)

J






(1S,2S)-N-(5-(5-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 3 TFA







455


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.43 (br s, 1H), 11.15 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.70 (dd, J = 0.8, 1.8 Hz, 1H), 7.67-7.63 (m, 1H), 7.58-7.55 (m, 1H), 6.95 (s, 1H), 6.88 (dd, J = 1.9, 7.2 Hz, 1H), 5.05-4.83 (m, 1H), 2.20-2.10 (m, 1H), 1.72-1.61 (m, 1H), 1.18 (qd, J = 6.2, 15.1 Hz, 1H); LCMS (electrospray) m/z = 414.0 (M + H+)

J






(1S,2S)-N-(5-(5-bromo-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







456


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.73 (d, J = 7.2 Hz, 1H), 8.19 (s, 1H), 7.94 (d, J = 1.2 Hz, 1H), 7.85-7.73 (m, 2H), 7.09 (dd, J = 2.0, 7.1 Hz, 1H), 7.02 (s, 1H), 5.08-4.82 (m, 1H), 2.16 (td, J = 7.0, 13.8 Hz, 1H), 1.74-1.62 (m, 1H), 1.18 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS (electrospray): m/z = 361.1 (M + H+)

J






(1S,2S)-N-(5-(5-cyano-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 HCl







457


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.74 (d, J = 0.9 Hz, 1H), 7.34 (d, J = 10.5 Hz, 1H), 6.98 (dd, J = 1.8, 7.1 Hz, 1H), 6.92 (s, 1H), 5.06-4.99 (m, 1H), 4.90- 4.82 (m, 1H), 2.15 (td, J = 7.0, 13.6 Hz, 1H), 2.01- 1.93 (m, 1H), 1.74-1.61 (m, 1H), 1.22-1.13 (m, 1H), 0.77-0.69 (m, 2H), 0.33-0.25 (m, 2H); LCMS (electrospray) m/z = 394.1 (M + H+)

J






(1S,2S)-N-(5-(5-cyclopropyl-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







458


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.50 (br s, 1H), 11.17 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 7.79 (d, J = 1.0 Hz, 1H), 7.68 (dd, J = 0.9, 9.0 Hz, 1H), 6.97 (s, 1H), 6.96 (d, J = 2.0 Hz, 1H), 6.96- 6.93 (m, 1H), 5.06-5.00 (m, 1H), 4.88-4.84 (m, 1H), 2.18-2.12 (m, 1H), 1.75-1.59 (m, 1H), 1.22- 1.14 (tdd, J = 6.2, 9.2, 12.4 Hz, 1H); LCMS (electrospray)m/z = 388.0 (M + H+)

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







459


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.75-7.67 (m, 2H), 7.48 (d, J = 8.8 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 6.96-6.88 (m, 2H), 5.07-4.82 (m, 1H), 2.20- 2.08 (m, 1H), 2.03-1.94 (m, 1H), 1.74-1.60 (m, 1H), 1.22-1.11 (m, 1H), 0.90-0.78 (m, 2H), 0.70- 0.60 (m, 2H); LCMS (electrospray) m/z = 376.1 (M + H+)

J






(1S,2S)-N-(5-(5-cyclopropyl-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







460


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.17 (br s, 1H), 11.15 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.77 (s, 1H), 7.67 (d, J = 0.9 Hz, 1H), 7.38 (d, J = 9.9 Hz, 1H), 6.93 (s, 1H), 6.87 (dd, J = 2.0, 7.1 Hz, 1H), 5.06-4.81 (m, 1H), 2.23 (d, J = 2.6 Hz, 3H), 2.15 (td, J = 6.9, 13.8 Hz, 1H), 1.75-1.59 (m, 1H), 1.17 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z = 368.1 (M + H+)

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







461


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.18 (br s, 1H), 11.14 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.82 (s, 1H), 7.69 (s, 1H), 7.58 (s, 2H), 6.94 (dd, J = 1.9, 7.0 Hz, 1H), 6.91 (s, 1H), 5.09-4.80 (m, 1H), 4.50 (s, 2H), 2.22-2.09 (m, 1H), 1.75-1.58 (m, 1H), 1.24-1.11 (m, 1H); LCMS (electrospray) m/z = 366.0 (M + H+)

J






(1S,2S)-2-fluoro-N-(5-(5-





(hydroxymethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







462


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.63 (d, J = 7.0 Hz, 1H), 7.64 (d, J = 3.1 Hz, 1H), 7.59 (d, J = 0.8 Hz, 1H), 7.36 (d, J = 12.3 Hz, 1H), 6.92 (s, 1H), 6.78 (dd, J = 1.8, 7.1 Hz, 1H), 5.07-4.97 (m, 1H), 4.88-4.84 (m, 1H), 3.13-3.00 (m, 1H), 2.18- 2.11 (m, 1H), 1.74-1.60 (m, 1H), 1.28 (dd, J = 7.1, 11.6 Hz, 6H), 1.21-1.08 (m, 1H); LCMS (electrospray) m/z = 396.1 (M + H+)

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





isopropyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







463


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.25 (br s, 1H), 11.33-10.98 (m, 1H), 11.13 (s, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.76 (s, 1H), 7.66-7.59 (m, 2H), 7.56-7.51 (m, 1H), 6.92 (s, 1H), 6.87 (dd, J = 1.8, 7.1 Hz, 1H), 5.23-4.71 (m, 1H), 2.39 (s, 3H), 2.20-2.10 (m, 1H), 1.75-1.58 (m, 1H), 1.17 (tdd, J = 6.2, 9.1, 12.2 Hz, 1H); LCMS (electrospray) m/z = 382.1 (M + H+)

J






(1S,2S)-2-fluoro-N-(5-(5-(methylthio)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







464


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.48 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.86 (s, 1H), 7.74 (d, J = 1.0 Hz, 1H), 7.66-7.61 (m, 1H), 6.96 (s, 1H), 6.90 (dd, J = 2.0, 7.1 Hz, 1H), 5.08-4.80 (m, 1H), 2.14 (br d, J = 7.2 Hz, 1H), 1.75-1.60 (m, 1H), 1.21-1.14 (m, 1H); LCMS (electrospray) m/z = 432.0 (M + H+)

J






(1S,2S)-N-(5-(5-bromo-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







465


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.52 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.0 Hz, 1H), 7.94 (s, 1H), 7.78-7.74 (m, 1H), 7.73-7.69 (m, 1H), 7.66 (s, 1H), 7.11-6.80 (m, 3H), 5.07-4.83 (m, 1H), 2.19- 2.10 (m, 1H), 1.74-1.62 (m, 1H), 1.18 (tdd, J = 6.4, 9.0, 12.3 Hz, 1H); LCMS (electrospray) m/z = 386.2 (M + H+)

J






(1S,2S)-N-(5-(5-(difluoromethyl)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







466


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.70 (s, 1H), 7.63 (s, 1H), 7.39 (d, J = 10.4 Hz, 1H), 6.93 (s, 1H), 6.82 (dd, J = 1.8, 7.0 Hz, 1H), 5.06-4.81 (m, 1H), 2.66-2.57 (m, 2H), 2.20-2.09 (m, 1H), 1.74-1.60 (m, 1H), 1.22-1.14 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS (electrospray) m/z = 382.1 (M + H+)

J






(1S,2S)-N-(5-(5-ethyl-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







467


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.27 (s, 1H), 11.15 (s, 1H), 8.67-8.61 (m, 1H), 7.97 (s, 1H), 7.84-7.80 (m, 1H), 7.56-7.48 (m, 1H), 7.05-6.99 (m, 1H), 6.95 (s, 1H), 5.08-4.82 (m, 1H), 3.67 (s, 2H), 3.71-3.63 (m, 1H), 2.07 (s, 1H), 1.75-1.61 (m, 1H), 1.26-1.09 (m, 1H); LCMS (electrospray) m/z = 384.1 (M + H+)

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





methoxy-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







468


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.60 (br s, 1H), 11.21 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.93 (s, 1H), 7.69 (s, 1H), 7.60 (d, J = 11.2 Hz, 1H), 7.09-6.79 (m, 3H), 5.08-4.81 (m, 1H), 2.19-2.11 (m, 1H), 1.73-1.61 (m, 1H), 1.23-1.14 (m, 1H); LCMS (electrospray) m/z = 404.1 (M + H+)

J






(1S,2S)-N-(5-(5-(difluoromethyl)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







469


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 11.14 (br d, J = 3.1 Hz, 1H), 8.62 (d, J = 7.0 Hz, 1H), 7.52 (s, 1H), 7.44 (d, J = 9.8 Hz, 1H), 6.90 (s, 1H), 6.74 (dd, J = 1.8, 7.1 Hz, 1H), 5.09-4.79 (m, 1H), 2.19-2.12 (m, 1H), 2.09 (t, J = 2.4 Hz, 3H), 1.75- 1.60 (m, 1H), 1.23-1.09 (m, 1H); LCMS (electrospray) m/z = 402.0 (M + H+)

J






(1S,2S)-N-(5-(3-chloro-6-fluoro-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







470


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.16 (d, J = 3.5 Hz, 1H), 8.63 (d, J = 7.0 Hz, 1H), 7.53 (d, J = 0.7 Hz, 1H), 7.29 (d, J = 10.0 Hz, 1H), 6.91 (s, 1H), 6.75 (dd, J = 1.8, 7.0 Hz, 1H), 5.11-4.79 (m, 1H), 2.15 (td, J = 6.8, 13.4 Hz, 1H), 2.07 (t, J = 2.4 Hz, 3H), 1.90 (d, J = 4.3 Hz, 3H), 1.74-1.59 (m, 1H), 1.24- 1.10 (m, 1H); LCMS (electrospray) m/z 382.0 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-3,5-





dimethyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA s







471


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.37 (s, 1H), 11.15 (s, 1H), 8.59 (d, J = 7.1 Hz, 1H), 7.60 (d, J = 1.0 Hz, 1H), 6.95 (d, J = 10.1 Hz, 1H), 6.91 (s, 1H), 6.88 (dd, J = 2.0, 7.1 Hz, 1H), 5.11-4.77 (m, 1H), 2.43 (s, 6H), 2.14 (td, J = 6.9, 13.9 Hz, 1H), 1.74-1.60 (m, 1H), 1.24-1.11 (m, 1H); LCMS (electrospray) m/z 414.4 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





3-(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







472


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.53 (s, 1H), 11.15 (br d, J = 5.6 Hz, 1H), 8.59 (d, J = 7.0 Hz, 1H), 7.52 (s, 1H), 7.45 (d, J = 9.7 Hz, 1H), 6.90 (s, 1H), 6.75 (dd, J = 1.7, 7.0 Hz, 1H), 5.09-4.80 (m, 1H), 3.79 (d, J = 2.9 Hz, 1H), 2.20-2.14 (m, 1H), 2.12 (br d, J = 1.7 Hz, 3H), 1.74-1.59 (m, 1H), 1.27- 1.08 (m, 1H); LCMS (electrospray) m/z 392.2 (M + H+)

J






(1S,2S)-N-(5-(3-ethynyl-6-fluoro-5-





methyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







473


embedded image



1H NMR (400 MHz, METHANOL-d4) δ 8.49 (d, J = 7.2 Hz, 1H), 7.51 (s, 1H), 7.17 (d, J = 9.7 Hz, 1H), 6.80 (br d, J = 5.4 Hz, 1H), 4.98-4.76 (m, 1H), 2.15 (s, 3H), 2.12-2.03 (m, 1H), 1.87-1.73 (m, 1H), 1.40-1.30 (m, 1H), 1.27-1.15 (m, 1H), 0.83-0.74 (m, 1H), 0.69 (br s, 1H), 0.55-0.40 (m, 2H); LCMS (electrospray) m/z 408.4 (M + H+)

J






(1S,2S)-N-(5-(3-cyclopropyl-6-fluoro-5-





methyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







474


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.17 (d, J = 4.4 Hz, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.53 (s, 1H), 7.37 (d, J = 9.8 Hz, 1H), 6.91 (s, 1H), 6.73 (dd, J = 1.8, 7.1 Hz, 1H), 6.04-5.92 (m, 1H), 5.85-5.75 (m, 1H), 5.06-4.82 (m, 2H), 2.15 (br d, J = 6.5 Hz, 1H), 2.07 (t, J = 2.4 Hz, 3H), 1.74-1.60 (m, 1H), 1.24-1.11 (m, 1H); LCMS (electrospray) m/z 394.3 (M + H+)

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





3-vinyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







475


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.16 (br d, J = 4.8 Hz, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.55 (s, 1H), 7.29 (d, J = 9.9 Hz, 1H), 6.90 (s, 1H), 6.76 (dd, J = 1.8, 7.0 Hz, 1H), 5.07-4.81 (m, 1H), 2.31-2.24 (m, 2H), 2.14 (br d, J = 6.7 Hz, 1H), 2.06 (t, J = 2.4 Hz, 3H), 1.75-1.59 (m, 1H), 1.24-1.09 (m, 1H), 0.90 (dt, J = 4.0, 7.5 Hz, 3H); LCMS (electrospray) m/z 396.3 (M + H+)

J






(1S,2S)-N-(5-(3-ethyl-6-fluoro-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







476


embedded image



1H NMR (400 MHz, DMSO-d6) δ 14.12 (br d, J = 0.7 Hz, 1H), 11.18 (s, 1H), 8.69 (d, J = 7.2 Hz, 1H), 8.04 (br s, 1H), 7.80 (s, 1H), 6.98 (s, 1H), 6.95 (dd, J = 1.8, 7.1 Hz, 1H), 5.05-4.84 (m, 1H), 2.18- 2.11 (m, 1H), 1.73-1.62 (m, 1H), 1.23-1.15 (m, 1H); LCMS (electrospray) m/z 422.1 (M + H)+.

J






(1S,2S)-N-(5-(5,7-dichloro-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







477


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.31 (br s, 1H), 11.14 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.77 (s, 1H), 7.63 (d, J = 1.0 Hz, 1H), 6.92 (s, 1H), 6.84 (dd, J = 1.8, 7.1 Hz, 1H), 5.11-4.75 (m, 1H), 2.47 (d, J = 1.6 Hz, 3H), 2.22 (d, J = 2.9 Hz, 3H), 2.15 (td, J = 6.8, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.17 (tdd, J = 6.3, 9.1, 12.4 Hz, 1H); LCMS (electrospray) m/z 382.4 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-





dimethyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







478


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.16-12.54 (m, 1H), 11.20 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.00 (s, 1H), 7.82 (s, 1H), 7.00 (s, 1H), 6.96 (dd, J = 1.8, 7.2 Hz, 1H), 5.11-4.79 (m, 1H), 2.15 (td, J = 6.9, 13.8 Hz, 1H), 1.96 (s, 3H), 1.92 (s, 3H), 1.76-1.60 (m, 1H), 1.18 (tdd, J = 6.4, 9.1, 12.2 Hz, 1H); LCMS (electrospray) m/z 464.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-





(dimethylphosphoryl)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







479


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.80 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.90 (br s, 1H), 7.69 (s, 1H), 6.94 (s, 1H), 6.87 (dd, J = 2.0, 7.1 Hz, 1H), 5.10-4.78 (m, 1H), 2.27 (d, J = 2.8 Hz, 3H), 2.19-2.07 (m, 1H), 1.74-1.60 (m, 1H), 1.24- 1.11 (m, 1H); LCMS (electrospray) m/z 402.0 (M + H)+.

J






(1S,2S)-N-(5-(7-chloro-6-fluoro-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







480


embedded image



1H NMR (400 MHz, DMSO-d6) δ 14.00 (br s, 1H), 11.18 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 8.08 (br s, 1H), 7.80 (d, J = 0.8 Hz, 1H), 6.98 (s, 1H), 6.95 (dd, J = 1.9, 7.2 Hz, 1H), 5.08-4.79 (m, 1H), 2.15 (td, J = 7.0, 13.6 Hz, 1H), 1.75-1.60 (m, 1H), 1.26- 1.09 (m, 1H); LCMS (electrospray) m/z 466.3 (M + H)+.

J






(1S,2S)-N-(5-(7-bromo-5-chloro-6-fluoro-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







481


embedded image



1H NMR (400 MHz, METHANOL-d4) δ 8.54 (d, J = 7.1 Hz, 1H), 7.85 (d, J = 3.2 Hz, 1H), 7.59 (s, 1H), 6.98 (s, 1H), 6.86 (dd, J = 1.9, 7.2 Hz, 1H), 5.00- 4.96 (m, 1H), 2.34 (d, J = 3.2 Hz, 3H), 2.20-2.16 (m, 1H), 1.92-1.72 (m, 1H), 1.30-1.15 (m, 1H); LCMS (electrospray) m/z 386.0 (M + H)+.

J






(1S,2S)-N-(5-(6,7-difluoro-5-methyl-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







482


embedded image



1H NMR (400 MHz, METHANOL-d4) δ 8.55 (d, J = 7.1 Hz, 1H), 7.89 (s, 1H), 7.63 (s, 1H), 7.00 (s, 1H), 6.87 (dd, J = 1.7, 7.1 Hz, 1H), 4.99-4.91 (m, 1H), 2.31 (d, J = 3.1 Hz, 3H), 2.14-2.04 (m, 1H), 1.87-1.75 (m, 1H), 1.27-1.16 (m, 1H); LCMS (electrospray) m/z 435.9 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(trifluoromethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







483


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.36 (br s, 1H), 11.16 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.81 (s, 1H), 7.65 (s, 1H), 7.52 (s, 1H), 7.15 (dd, J = 11.1, 18.0 Hz, 1H), 6.92 (s, 1H), 6.87 (dd, J = 1.8, 7.1 Hz, 1H), 6.11 (br d, J = 17.6 Hz, 1H), 5.51 (d, J = 11.6 Hz, 1H), 5.05-4.85 (m, 1H), 2.36 (s, 3H), 2.14 (br d, J = 8.1 Hz, 1H), 1.72-1.64 (m, 1H), 1.21-1.15 (m, 1H); LCMS (electrospray) m/z 376.1 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(5-methyl-7-vinyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







484


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.51 (br s, 1H), 11.16 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.87 (s, 1H), 7.73 (d, J = 1.0 Hz, 1H), 6.95 (s, 1H), 6.91 (dd, J = 1.9, 7.2 Hz, 1H), 5.10-4.78 (m, 1H), 3.00 (br s, 6H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.74-1.61 (m, 1H), 1.24-1.11 (m, 1H); LCMS (electrospray) m/z 431.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







485


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.79 (s, 1H), 11.17 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.98 (s, 1H), 7.79 (d, J = 1.0 Hz, 1H), 6.98 (s, 1H), 6.94 (dd, J = 2.0, 7.1 Hz, 1H), 5.08-4.77 (m, 1H), 2.57 (s, 3H), 2.15 (td, J = 6.9, 13.9 Hz, 1H), 1.74-1.61 (m, 1H), 1.18 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 434.2 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







486


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.51 (br s, 1H), 11.20 (s, 1H), 8.72 (d, J = 7.2 Hz, 1H), 8.10 (s, 1H), 7.84 (d, J = 1.0 Hz, 1H), 7.02 (s, 1H), 6.96 (dd, J = 1.9, 7.2 Hz, 1H), 5.07-4.77 (m, 1H), 3.56 (s, 3H), 2.15 (quin, J = 6.9 Hz, 1H), 1.75-1.58 (m, 1H), 1.18 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS (electrospray) m/z 466.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methylsulfonyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







487


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.69 (br s, 1H), 11.19 (s, 1H), 8.66 (d, J = 7.0 Hz, 1H), 7.92 (br s, 1H), 7.69 (d, J = 1.0 Hz, 1H), 6.94 (s, 1H), 6.87 (dd, J = 1.9, 7.1 Hz, 1H), 5.07-4.82 (m, 1H), 2.27 (d, J = 3.0 Hz, 3H), 2.20-2.10 (m, 1H), 1.74-1.60 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 448.1 (M + H)+.

J






(1S,2S)-N-(5-(7-bromo-6-fluoro-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







488


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.49 (s, 1H), 11.18 (s, 1H), 8.65 (d, J = 7.0 Hz, 1H), 7.84 (s, 1H), 7.68 (s, 1H), 6.93 (s, 1H), 6.87 (dd, J = 1.9, 7.1 Hz, 1H), 5.05-4.84 (m, 1H), 2.52 (br s, 3H), 2.24 (d, J = 2.9 Hz, 3H), 2.19-2.10 (m, 1H), 1.73-1.61 (m, 1H), 1.22-1.13 (m, 1H); LCMS (electrospray) m/z 414.2 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







489


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.23 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 7.95 (s, 1H), 7.74 (d, J = 0.9 Hz, 1H), 6.97 (s, 1H), 6.90 (dd, J = 1.9, 7.2 Hz, 1H), 5.05-4.84 (m, 1H), 3.50 (s, 3H), 2.27 (d, J = 2.8 Hz, 3H), 2.15 (td, J = 6.9, 13.9 Hz, 1H), 1.73-1.62 (m, 1H), 1.25-1.12 (m, 1H); LCMS (electrospray) m/z 446.2 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylsulfonyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







490


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.62 (d, J = 7.2 Hz, 1H), 7.75 (s, 1H), 7.61 (d, J = 1.0 Hz, 1H), 6.90 (s, 1H), 6.84 (dd, J = 1.9, 7.1 Hz, 1H), 5.05-5.00 (m, 1H), 4.88-4.83 (m, 1H), 2.96 (d, J = 2.0 Hz, 6H), 2.20 (d, J = 3.4 Hz, 3H), 2.17- 2.09 (m, 1H), 1.73-1.61 (m, 1H), 1.21-1.12 (m, 1H); LCMS (electrospray) m/z 411.2 (M + H)+.

J






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







491


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.49 (br s, 1H), 11.14 (s, 1H), 8.62 (d, J = 7.0 Hz, 1H), 7.79 (br s, 1H), 7.62 (d, J = 1.0 Hz, 1H), 6.91 (s, 1H), 6.84 (dd, J = 1.9, 7.1 Hz, 1H), 5.08-4.80 (m, 1H), 4.08 (s, 3H), 2.23 (d, J = 3.1 Hz, 3H), 2.15 (td, J = 6.9, 14.0 Hz, 1H), 1.75-1.59 (m, 1H), 1.24-1.11 (m, 1H); LCMS (electrospray) m/z 398.2 (M + H)+.

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-





methoxy-5-methyl-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







492


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1H NMR (400 MHz, DMSO-d6) δ 13.84 (br s, 1H), 11.16 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.94 (s, 1H), 7.77-7.72 (m, 1H), 6.96 (s, 1H), 6.91 (dd, J = 1.9, 7.1 Hz, 1H), 5.09-4.77 (m, 1H), 4.16 (d, J = 1.5 Hz, 3H), 2.15 (td, J = 6.9, 13.7 Hz, 1H), 1.74-1.59 (m, 1H), 1.24-1.10 (m, 1H); LCMS (electrospray) m/z 418.2 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





methoxy-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







493


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.80 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.94 (br s, 1H), 7.75 (s, 1H), 6.95 (s, 1H), 6.92 (dd, J = 1.8, 7.2 Hz, 1H), 5.13-4.78 (m, 1H), 4.39 (br d, J = 6.5 Hz, 2H), 2.21-2.09 (m, 1H), 1.74-1.60 (m, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.24-1.12 (m, 1H); LCMS (electrospray) m/z 432.4 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-ethoxy-6-fluoro-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







494


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.60 (d, J = 7.1 Hz, 1H), 7.88 (s, 1H), 7.68 (dd, J = 0.8, 1.8 Hz, 1H), 6.92 (s, 1H), 6.89 (dd, J = 2.0, 7.1 Hz, 1H), 5.08-4.78 (m, 1H), 3.17 (d, J = 2.8 Hz, 3H), 2.14 (td, J = 7.0, 13.9 Hz, 1H), 1.74-1.58 (m, 1H), 1.17 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS (electrospray) m/z 417.4 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methylamino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







495


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (br d, J = 2.8 Hz, 1H), 11.18 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 8.17 (s, 1H), 7.90 (br s, 1H), 7.77-7.68 (m, 1H), 6.95 (s, 1H), 6.91 (dd, J = 2.0, 7.1 Hz, 1H), 5.06- 4.83 (m, 1H), 3.30 (br s, 4H), 2.57 (br s, 4H), 2.28 (s, 3H), 2.19-2.10 (m, 1H), 1.73-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS (electrospray) m/z 486.2 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(4-





methylpiperazin-1-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 FA







496


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1H NMR (400 MHz, DMSO-d6) δ 11.16 (1 H, s) 8.62 (1 H, d, J = 7.20 Hz) 7.89 (1 H, br s) 7.70 (1 H, d, J = 1.00 Hz) 7.04-6.79 (2 H, m) 5.07-4.70 (1 H, m) 2.15 (1 H, dt, J = 13.85, 7.02 Hz) 1.73-1.61 (1 H, m) 1.25-1.16 (4 H, m); LCMS (electrospray) m/z 431.0 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-(ethylamino)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







497


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1H NMR (400 MHz, DMSO-d6) δ 13.78-13.23 (1 H, m) 11.18 (1 H, s) 8.66 (1 H, d, J = 7.20 Hz) 7.90 (1 H, s) 7.83-7.73 (1 H, m) 7.05-6.90 (2 H, m) 5.10-4.83 (1 H, m) 3.30 (4 H, q, J = 6.65 Hz) 2.15 (1 H, dt, J = 13.77, 6.98 Hz) 1.77-1.61 (1 H, m) 1.27-1.14 (1 H, m) 1.02 (6 H, t, J = 7.09 Hz); LCMS (electrospray) m/z 459.0 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-(diethylamino)-





6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







498


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1H NMR (400 MHz, DMSO-d6) δ 13.53 (br s, 1H), 11.16 (s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.90 (br s, 1H), 7.74 (d, J = 1.0 Hz, 1H), 6.95 (s, 1H), 6.93- 6.88 (m, 1H), 5.05-4.83 (m, 1H), 3.92-3.76 (m, 4H), 3.30-3.21 (m, 4H), 2.14 (td, J = 6.9, 13.9 Hz, 1H), 1.73-1.61 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 473.3 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





morpholino-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







499


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1H NMR (400 MHz, DMSO-d6) δ 13.24 (br s, 1H), 11.14 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.89 (br s, 1H), 7.69 (d, J = 1.0 Hz, 1H), 6.92 (s, 1H), 6.88 (dd, J = 2.0, 7.1 Hz, 1H), 5.07-4.82 (m, 1H), 3.72 (br s, 4H), 2.19-2.10 (m, 1H), 1.99-1.90 (m, 4H), 1.74-1.61 (m, 1H), 1.23-1.12 (m, 1H); LCMS (electrospray) m/z 457.3 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(pyrrolidin-1-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







500


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1H NMR (400 MHz, DMSO-d6) δ 13.61 (br s, 1H), 11.17 (s, 1H), 8.81 (br s, 2H), 8.67 (d, J = 7.1 Hz, 1H), 7.94 (br s, 1H), 7.73 (d, J = 1.0 Hz, 1H), 6.97 (s, 1H), 6.90 (dd, J = 1.9, 7.2 Hz, 1H), 5.08-4.81 (m, 1H), 3.62-3.40 (m, 8H), 2.22-2.09 (m, 1H), 1.74-1.59 (m, 1H), 1.26-1.11 (m, 1H); LCMS (electrospray) m/z 472.3 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(piperazin-1-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 3 TFA







501


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1H NMR (400 MHz, DMSO-d6) δ13.10 (br s, 1H), 11.14 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.88 (br s, 1H), 7.68 (d, J = 0.9 Hz, 1H), 6.92 (s, 1H), 6.88 (dd, J = 1.9, 7.1 Hz, 1H), 5.16-4.74 (m, 1H), 4.51-4.25 (m, 4H), 2.35 (quin, J = 7.3 Hz, 2H), 2.14 (td, J = 6.9, 13.9 Hz, 1H), 1.76-1.57 (m, 1H), 1.29-1.06 (m, 1H); LCMS (electrospray) m/z 443.3 (M + H)+.

J






(1S,2S)-N-(5-(7-(azetidin-1-yl)-5-chloro-





6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







502


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.45 (br s, 1H), 11.17 (s, 1H), 9.37 (br s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.90 (br s, 1H), 7.74 (d, J = 1.0 Hz, 1H), 6.96 (s, 1H), 6.92 (dd, J = 2.0, 7.1 Hz, 1H), 5.05-4.84 (m, 1H), 3.13 (br s, 2H), 2.92 (d, J = 2.4 Hz, 3H), 2.72 (s, 3H), 2.70 (s, 3H), 2.14 (br d, J = 7.1 Hz, 1H), 2.02 (br s, 4H), 1.73-1.62 (m, 1H), 1.48 (br s, 4H), 1.23-1.13 (m, 1H); LCMS(electrospray) m/z542.3 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-7-((4-





(dimethylamino)cyclohexyl)(methyl)amino)-





6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 3 TFA







503


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1H NMR (400 MHz, DMSO-d6) δ 13.94-13.16 (m, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.90 (s, 1H), 7.82-7.71 (m, 1H), 7.84-7.70 (m, 1H), 7.04-6.85 (m, 2H), 5.09-4.82 (m, 1H), 3.44- 3.32 (m, 1H), 3.24-3.06 (m, 1H), 2.95-2.81 (m, 3H), 2.23-2.07 (m, 1H), 1.90-1.76 (m, 3H), 1.74- 1.34 (m, 6H), 1.26-1.07 (m, 3H); LCMS(electrospray) m/z 515.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((4-





hydroxycyclohexyl)(methyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 3





TFA







504


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 8.37 (br s, 2H), 7.91 (s, 1H), 7.74 (d, J = 1.0 Hz, 1H), 6.96 (s, 1H), 6.92 (dd, J = 2.0, 7.2 Hz, 1H), 5.07-4.82 (m, 1H), 3.10 (br s, 1H), 2.91 (d, J = 2.6 Hz, 3H), 2.56- 2.52 (m, 5H), 2.15 (td, J = 6.9, 13.5 Hz, 1H), 2.06 (br d, J = 9.9 Hz, 2H), 1.99 (br d, J = 11.5 Hz, 2H), 1.72-1.61 (m, 1H), 1.54-1.44 (m, 2H), 1.38-1.26 (m, 2H), 1.21-1.14 (m, 1H); LCMS(electrospray) m/z 528.3 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methyl((1R,4R)-4-





(methylamino)cyclohexyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 3





TFA







505


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1H NMR (400 MHz, DMSO-d6) δ 13.35 (br s, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 8.33 (br s, 2H), 7.94 (s, 1H), 7.79-7.75 (m, 1H), 6.97 (s, 1H), 6.94 (dd, J = 2.0, 7.1 Hz, 1H), 5.06-4.84 (m, 1H), 3.08 (br s, 1H), 2.85 (s, 3H), 2.57 (t, J = 5.4 Hz, 3H), 2.54-2.52 (m, 2H), 2.15 (td, J = 7.2, 14.0 Hz, 1H), 1.83 (br s, 4H), 1.72-1.56 (m, 5H), 1.23-1.13 (m, 1H); LCMS(electrospray) m/z 528.3 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methyl((1S,4S)-4-





(methylamino)cyclohexyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 3





TFA







506


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1H NMR (400 MHz, DMSO-d6) δ 13.33 (br s, 1H), 11.11 (s, 1H), 8.58 (d, J = 7.0 Hz, 1H), 7.71 (s, 1H), 7.57 (d, J = 0.9 Hz, 1H), 6.88 (s, 1H), 6.84-6.79 (m, 2H), 5.07-4.80 (m, 1H), 3.99 (s, 3H), 2.35 (s, 3H), 2.14 (td, J = 7.1, 14.0 Hz, 1H), 1.73-1.61 (m, 1H), 1.17 (tdd, J = 6.2, 8.9, 12.3 Hz, 1H); LCMS(electrospray) m/z 380.2 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(7-methoxy-5-





methyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)cyclopropane-1-





carboxamide. 2 TFA







507


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.76 (br s, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.94 (br s, 1H), 7.75 (d, J = 1.0 Hz, 1H), 6.95 (s, 1H), 6.92 (dd, J = 2.0, 7.1 Hz, 1H), 5.06-4.83 (m, 1H), 4.33 (br s, 2H), 4.27-4.20 (m, 1H), 3.81-3.74 (m, 1H), 3.69 (dt, J = 6.1, 7.6 Hz, 1H), 2.18-2.10 (m, 1H), 2.07- 1.98 (m, 1H), 1.92-1.81 (m, 2H), 1.80-1.73 (m, 1H), 1.72-1.62 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 488.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





((tetrahydrofuran-2-yl)methoxy)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







508


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1H NMR (400 MHz, DMSO-d6) δ 13.30 (br s, 1H), 11.16 (s, 1H), 8.62 (br d, J = 7.1 Hz, 1H), 8.45 (br s, 2H), 7.85 (s, 1H), 7.70 (s, 1H), 6.93 (s, 1H), 6.89 (dd, J = 2.0, 7.1 Hz, 1H), 5.27 (br d, J = 8.9 Hz, 1H), 5.05-4.83 (m, 1H), 3.60 (br s, 1H), 2.99 (br s, 1H), 2.58 (br t, J = 5.2 Hz, 3H), 2.52 (br s, 1H), 2.18- 2.12 (m, 1H), 2.08 (br d, J = 9.8 Hz, 4H), 1.72-1.62 (m, 1H), 1.45-1.32 (m, 4H), 1.23-1.14 (m, 1H);

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((4-





(methylamino)cyclohexyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 3





TFA







509


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 11.16 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.79 (s, 1H), 7.64 (d, J = 0.9 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J = 2.0, 7.1 Hz, 1H), 5.10-4.81 (m, 1H), 4.31 (br d, J = 6.8 Hz, 2H), 2.23 (d, J = 3.1 Hz, 3H), 2.14 (td, J = 6.9, 13.9 Hz, 1H), 1.73-1.61 (m, 1H), 1.39 (t, J = 7.0 Hz, 3H), 1.17 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 412.2 (M + H+).

J






(1S,2S)-N-(5-(7-ethoxy-6-fluoro-5-





methyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







510


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.16-12.81 (m, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.72-7.66 (m, 1H), 6.95-6.86 (m, 2H), 6.00-5.59 (m, 2H), 5.17-4.76 (m, 1H), 2.21- 2.09 (m, 1H), 1.76-1.59 (m, 1H), 1.43-1.36 (m, 1H), 1.26-1.11 (m, 1H); LCMS(electrospray) m/z 403.1 (M + H+).

J






(1S,2S)-N-(5-(7-amino-5-chloro-6-fluoro-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







511


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 11.12 (s, 1H), 8.58 (d, J = 7.1 Hz, 1H), 7.70 (d, J = 1.2 Hz, 1H), 7.57 (dd, J = 0.9, 1.7 Hz, 1H), 6.87 (s, 1H), 6.84-6.79 (m, 2H), 5.05-4.83 (m, 1H), 4.27 (q, J = 7.0 Hz, 2H), 2.34 (s, 3H), 2.19-2.09 (m, 1H), 1.72-1.61 (m, 1H), 1.46 (t, J = 7.0 Hz, 3H), 1.17 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS(electrospray) m/z 393.9 (M + H+).

J






(1S,2S)-N-(5-(7-ethoxy-5-methyl-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







512


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.27 (br s, 1H), 11.15 (s, 1H), 9.49 (br s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.88 (br s, 1H), 7.69 (d, J = 1.0 Hz, 1H), 6.93 (s, 1H), 6.90 (dd, J = 2.0, 7.2 Hz, 1H), 5.33 (br s, 1H), 5.11-4.77 (m, 1H), 3.19 (br d, J = 9.0 Hz, 1H), 2.77 (s, 3H), 2.76 (s, 3H), 2.52 (d, J = 2.0 Hz, 1H), 2.12 (br d, J = 11.7 Hz, 3H), 2.04 (br d, J = 10.8 Hz, 2H), 1.72-1.61 (m, 1H), 1.61-1.51 (m, 2H), 1.46- 1.32 (m, 2H), 1.17 (tdd, J = 6.2, 9.0, 12.4 Hz, 1H); LCMS(electrospray) m/z 528.3 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-7-((4-





(dimethylamino)cyclohexyl)amino)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 3 TFA







513


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.49 (s, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.76 (s, 1H), 7.64 (s, 1H), 6.93 (s, 1H), 6.82 (d, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 2.69-2.62 (m, 2H), 2.50 (s, 3H), 2.16-2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.28- 1.12 (m, 1H), 1.12-1.08 (m, 3H); LCMS (electrospray) m/z 428.1 (M + H)+.

J






(1S,2S)-N-(5-(5-ethyl-6-fluoro-7-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide





dihydrochloride. 2 HCl







514


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.63-13.08 (m, 1H), 11.19 (s, 1H), 8.67 (td, J = 1.0, 7.1 Hz, 1H), 8.03-7.86 (m, 1H), 7.83-7.56 (m, 4H), 7.06- 6.86 (m, 2H), 5.14-4.81 (m, 2H), 3.24-3.15 (m, 1H), 2.95-2.84 (m, 4H), 2.15 (td, J = 7.0, 13.9 Hz, 1H), 2.02-1.91 (m, 2H), 1.86-1.74 (m, 2H), 1.73- 1.45 (m, 4H), 1.41-1.28 (m, 1H), 1.25-1.12 (m, 1H); LCMS(electrospray) m/z 514.1 (M + H+).

J






(1S,2S)-N-(5-7-((4-





aminocyclohexyl)(methyl)amino)-5-





chloro-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 3 TFA







515


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.32 (br d, J = 13.8 Hz, 1H), 11.16 (s, 1H), 8.63 (br d, J = 6.9 Hz, 1H), 7.95-7.60 (m, 5H), 6.99-6.79 (m, 2H), 5.35- 4.78 (m, 2H), 4.09-3.63 (m, 1H), 4.05-3.45 (m, 1H), 3.24-2.98 (m, 3H), 2.15 (td, J = 6.9, 13.7 Hz, 1H), 2.09-1.93 (m, 2H), 1.77 (br s, 3H), 1.72- 1.61 (m, 1H), 1.53-1.34 (m, 2H), 1.26-1.14 (m, 1H); LCMS(electrospray) m/z 500.4 (M + H+).

J






(1S,2S)-N-(5-(7-((4-





aminocyclohexyl)amino)-5-chloro-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 3 TFA







516


embedded image



1H NMR (400 MHz, DMSO-d6) δ 14.54-12.40 (m, 1H), 11.16 (s, 1H), 8.62 (d, J = 7.3 Hz, 1H), 7.98-7.77 (m, 1H), 7.71 (br s, 1H), 7.02-6.86 (m, 2H), 6.84-6.66 (m, 1H), 5.07-4.82 (m, 1H), 3.47 (br s, 2H), 3.26 (br s, 1H), 2.15 (td, J = 6.8, 13.6 Hz, 1H), 1.99 (br d, J = 10.3 Hz, 1H), 1.82 (br d, J = 10.4 Hz, 1H), 1.74-1.62 (m, 4H), 1.55 (br d, J = 10.4 Hz, 1H), 1.39 (d, J = 5.1 Hz, 9H), 1.36-1.11 (m, 3H); LCMS(electrospray) m/z 600.1 (M + H+).

J






tert-butyl (4-((5-chloro-6-fluoro-4-(2-





((1S,2S)-2-fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazol-7-





yl)amino)cyclohexyl)carbamate. 2 TFA







517


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.70-12.88 (m, 1H), 11.24-11.06 (m, 1H), 8.71-8.53 (m, 1H), 7.93-7.64 (m, 2H), 7.05-6.57 (m, 2H), 5.10-4.69 (m, 1H), 3.92-3.72 (m, 3H), 2.27-2.08 (m, 1H), 1.81-1.45 (m, 8H), 1.34-1.09 (m, 2H); LCMS(electrospray) m/z 501.1 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((4-





hydroxycyclohexyl)amino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







518


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.15 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.68 (br s, 1H), 7.62 (s, 1H), 6.91 (s, 1H), 6.83 (dd, J = 1.8, 7.1 Hz, 1H), 5.06-4.82 (m, 1H), 3.26 (br d, J = 6.1 Hz, 4H), 2.61 (br d, J = 7.1 Hz, 2H), 2.19-2.10 (m, 1H), 1.74-1.60 (m, 1H), 1.21-1.14 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H), 0.99 (t, J = 7.1 Hz, 6H); LCMS(electrospray) m/z 453.4(M + H+).

J






(1S,2S)-N-(5-(7-(diethylamino)-5-ethyl-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







519


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.99-12.38 (m, 1H), 11.14 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.68 (s, 1H), 7.58 (d, J = 0.9 Hz, 1H), 6.90 (s, 1H), 6.79 (dd, J = 1.9, 7.0 Hz, 1H), 5.11-4.76 (m, 1H), 2.97 (s, 3H), 2.97 (s, 3H), 2.65-2.53 (m, 2H), 2.14 (td, J = 6.9, 13.8 Hz, 1H), 1.75-1.60 (m, 1H), 1.22- 1.14 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z425.2 (M + H+).

J






(1S,2S)-N-(5-(7-(dimethylamino)-5-ethyl-





6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







520


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.79 (br s, 1H), 11.18 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 7.99 (br s, 1H), 7.80 (d, J = 0.7 Hz, 1H), 6.98 (s, 1H), 6.96 (dd, J = 1.9, 7.2 Hz, 1H), 5.06-4.82 (m, 1H), 3.53 (t, J = 6.7 Hz, 2H), 3.12-3.04 (m, 2H), 2.15 (td, J = 7.1, 13.8 Hz, 1H), 1.73-1.61 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 464 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((2-





hydroxyethyl)thio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







521


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.62 (s, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 8.07 (d, 1H), 7.78 (s, 1H), 7.65 (d, 1H), 6.94 (s, 1H), 6.83 (dd, 1H), 5.08-4.83 (m, 1H), 3.64 (s, 2H), 2.63 (d, 2H), 2.60 (d, 3H), 2.20-2.11 (m, 1H), 1.75-1.61 (m, 1H), 1.24-1.15 (m, 1H), 1.11 (t, 3H); LCMS(electrospray) m/z 485.2 (M + H+).

J






(1S,2S)-N-(5-(5-ethyl-6-fluoro-7-((2-





(methylamino)-2-oxoethyl)thio)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide





bis(2,2,2-trifluoroacetate). 2 TFA







522


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.72-13.26 (m, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.78 (s, 1H), 7.64 (d, J = 0.8 Hz, 1H), 6.95 (s, 1H), 6.82 (dd, J = 1.9, 7.1 Hz, 1H), 5.13-4.76 (m, 1H), 3.97 (s, 2H), 3.02 (s, 3H), 2.83 (s, 3H), 2.66-2.59 (m, 2H), 2.19-2.08 (m, 1H), 1.74-1.61 (m, 1H), 1.23-1.15 (m, 1H), 1.11 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 499.4 (M + H+).

J






(1S,2S)-N-(5-7-((2-(dimethylamino)-2-





oxoethyl)thio)-5-ethyl-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide





bis(2,2,2-trifluoroacetate). 2 TFA







523


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.46 (s, 1H), 11.16 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.68 (d, J = 0.7 Hz, 1H), 6.93 (s, 1H), 6.88 (dd, J = 2.0, 7.1 Hz, 1H), 5.08-4.81 (m, 2H), 3.51 (t, J = 6.9 Hz, 2H), 3.01 (br t, J = 6.8 Hz, 2H), 2.24 (d, J = 2.9 Hz, 3H), 2.15 (td, J = 6.9, 14.0 Hz, 1H), 1.73- 1.61 (m, 1H), 1.17 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS(electrospray) m/z 444.1 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-





hydroxyethyl)thio)-5-methyl-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







524


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.58 (d, J = 7.1 Hz, 1H), 7.67 (s, 1H), 7.55 (d, J = 0.8 Hz, 1H), 6.88 (s, 1H), 6.78 (dd, J = 1.9, 7.1 Hz, 1H), 5.06-4.82 (m, 1H), 3.50 (q, J = 7.0 Hz, 2H), 2.60 (br d, J = 7.6 Hz, 2H), 2.14 (td, J = 7.2, 13.9 Hz, 1H), 1.74-1.59 (m, 1H), 1.22-1.07 (m, 7H); LCMS(electrospray) m/z 425.2 (M + H+).

J






(1S,2S)-N-(5-(5-ethyl-7-(ethylamino)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







525


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.48-12.86 (m, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.0 Hz, 1H), 7.68 (s, 1H), 7.60 (d, J = 0.9 Hz, 1H), 6.91 (s, 1H), 6.81 (dd, J = 1.9, 7.0 Hz, 1H), 5.08-4.79 (m, 1H), 3.23 (q, J = 7.0 Hz, 2H), 2.95 (d, J = 1.6 Hz, 3H), 2.60 (br d, J = 7.1 Hz, 2H), 2.18-2.10 (m, 1H), 1.72-1.61 (m, 1H), 1.20-1.14 (m, 1H), 1.12-1.04 (m, 6H); LCMS(electrospray) m/z 439.2 (M + H+).

J






(1S,2S)-N-(5-(5-ethyl-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







526


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.70-13.32 (m, 1H), 13.12-12.20 (m, 1H), 11.17 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.79 (s, 1H), 7.65 (d, J = 0.9 Hz, 1H), 6.94 (s, 1H), 6.83 (dd, J = 2.0, 7.1 Hz, 1H), 5.07-4.82 (m, 1H), 3.77 (br s, 2H), 2.63 (br d, J = 6.8 Hz, 2H), 2.21-2.09 (m, 1H), 1.74-1.61 (m, 1H), 1.24-1.14 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(electrospray) m/z 472.1 (M + H+).

J






2-((5-ethyl-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazol-7-yl)thio)acetic acid. 2 TFA







527


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.64-13.45 (m, 1H), 11.24-11.12 (m, 1H), 8.72-8.62 (m, 1H), 8.02-7.73 (m, 4H), 7.03-6.89 (m, 2H), 5.13-4.83 (m, 1H), 2.88 (br d, J = 17.4 Hz, 2H), 2.08 (s, 5H), 2.04-1.93 (m, 2H), 1.75-1.58 (m, 3H), 1.28-1.18 (m, 3H); LCMS(electrospray) m/z 500.1 (M + H+).

J






(1S,2S)-N-(5-(7-((3-





aminocyclopentyl)(methyl)amino)-5-





chloro-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 2 TFA







528


embedded image



1H NMR (400 MHz, METHANOL-d4) δ 8.75 (s, 1H), 7.88 (s, 1H), 7.82-7.76 (m, 1H), 7.74-7.68 (m, 1H), 2.19-2.11 (m, 1H), 1.92-1.81 (m, 1H), 1.35-1.22 (m, 2H); LCMS(electrospray) m/z 404.1 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





hydroxy-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 2 TFA







529


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.68 (s, 1H), 11.16 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.88 (d, J = 1.3 Hz, 1H), 7.68 (d, J = 1.0 Hz, 1H), 6.94 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.07-4.82 (m, 1H), 2.54 (s, 3H), 2.28 (s, 3H), 2.19-2.10 (m, 1H), 1.79- 1.57 (m, 1H), 1.26-1.12 (m, 1H); LCMS(electrospray) m/z 446.0 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-





bis(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 2 TFA







530


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1H NMR (400 MHz, CHLOROFORM-d) δ 13.40 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.81 (s, 1H), 7.67 (dd, J = 0.7, 1.7 Hz, 1H), 7.52 (dd, J = 0.9, 9.3 Hz, 1H), 6.93 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.06-4.82 (m, 1H), 2.26 (s, 3H), 2.15 (td, J = 7.0, 13.9 Hz, 1H), 1.75-1.61 (m, 1H), 1.21-1.14 (m, 1H); LCMS(electrospray) m/z 400.1 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







531


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1H NMR (400 MHz, DMSO-d6) δ 13.48 (s, 1H), 11.16 (s, 1H), 8.63 (d, J = 6.8 Hz, 1H), 7.72 (s, 1H), 7.61 (s, 1H), 6.92 (s, 1H), 6.81 (dd, J = 7.2, 2.0 Hz, 1H), 5.04-4.85 (m, 1H), 4.34-4.29 (m, 2H), 2.64- 2.60 (m, 2H), 2.17-2.13 (m, 1H), 1.75-1.65 (m, 1H), 1.40 (t, J = 7.2 Hz, 3H), 1.19-1.15 (m, 1H), 1.12 (t, J = 7.2 Hz, 3H); LCMS(electrospray) m/z 426.2 (M + H+).

J






(1S,2S)-N-(5-(7-ethoxy-5-ethyl-6-fluoro-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





2 TFA







532


embedded image



1H NMR (400 MHz, CHLOROFORM-d) δ 8.46- 8.41 (m, 1 H), 8.37 (d, J = 7.09 Hz, 1 H), 7.80-7.74 (m, 1 H), 7.45 (d, J = 0.86 Hz, 1 H), 7.09 (s, 1 H), 6.73 (dd, J = 7.03, 1.90 Hz, 1 H), 5.00-4.72 (m, 1 H), 2.81-2.64 (m, 2 H), 2.01-1.94 (m, 1 H), 1.92- 1.89 (m, 1 H), 1.28-1.25 (m, 1 H), 1.18 (t, J = 7.46 Hz, 3 H); LCMS(electrospray) m/z 400.0 (M + H+).

J






(1S,2S)-N-(5-(5-ethyl-6,7-difluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 2





TFA







533


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1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 8.67 (d, J = 7.0 Hz, 1H), 7.91 (s, 1H), 7.71 (s, 1H), 6.96 (s, 1H), 6.89 (dd, J = 1.9, 7.1 Hz, 1H), 5.15- 4.65 (m, 1H), 3.13 (s, 3H), 2.24 (d, J = 2.8 Hz, 3H), 2.15 (td, J = 7.0, 14.1 Hz, 1H), 1.76-1.58 (m, 1H), 1.26-1.10 (m, 1H); LCMS(electrospray) m/z 429.11 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylsulfinyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







534


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.39 (br s, 1H), 14.04-12.74 (m, 1H), 11.15 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.80 (s, 1H), 7.64 (d, J = 0.9 Hz, 1H), 7.29 (dd, J = 2.0, 7.3 Hz, 1H), 6.96-6.90 (m, 1H), 6.86 (dd, J = 1.8, 7.1 Hz, 1H), 5.06-4.83 (m, 1H), 4.30 (br t, J = 4.9 Hz, 2H), 3.78 (t, J = 5.1 Hz, 2H), 2.24 (d, J = 3.1 Hz, 3H), 2.20-2.08 (m, 1H), 1.75- 1.58 (m, 1H), 1.25-1.13 (m, 1H); LCMS(electrospray) m/z 428.0 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-(2-





hydroxyethoxy)-5-methyl-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. TFA







535


embedded image



1H NMR (400 MHz, METHANOL-d4) δ 8.41 (d, J = 7.1 Hz, 1H), 7.66 (s, 1H), 7.44 (s, 1H), 6.83 (s, 1H), 6.74 (dd, J = 1.7, 7.1 Hz, 1H), 4.86 (td, J = 3.1, 6.3 Hz, 1H), 4.69 (dt, J = 3.9, 6.2 Hz, 1H), 4.46- 4.38 (m, 2H), 4.33-4.25 (m, 2H), 3.89-3.80 (m, 1H), 2.20-2.16 (m, 1H), 2.18 (d, J = 3.2 Hz, 2H), 2.00 (td, J = 6.9, 13.8 Hz, 1H), 1.78-1.62 (m, 1H), 1.19-1.04 (m, 1H); LCMS(electrospray) m/z 471.1 (M + H+).

J






2-((6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





5-methyl-1H-indazol-7-yl)oxy)ethyl





carbamate







536


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.67 (s, 1H), 6.96 (s, 1H), 6.87 (s, 1H), 6.79 (dd, J = 2.0, 7.2 Hz, 1H), 5.08- 4.79 (m, 1H), 2.19-2.08 (m, 1H), 1.74-1.59 (m, 1H), 1.28-1.09 (m, 2H); LCMS(electrospray) m/z 406.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6,7-difluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide. 1





TFA







537


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.31 (br s, 1H), 11.27-11.11 (m, 1H), 10.14 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.91 (s, 1H), 7.80 (d, J = 0.9 Hz, 1H), 6.97 (s, 1H), 6.95 (dd, J = 1.9, 7.2 Hz, 1H), 5.09- 4.82 (m, 1H), 2.18 (s, 3H), 2.16-2.10 (m, 1H), 1.75-1.61 (m, 1H), 1.18 (ddd, J = 2.7, 6.1, 12.5 Hz, 1H); LCMS(electrospray) m/z 445.2 (M + H+).

J






(1S,2S)-N-(5-(7-acetamido-5-chloro-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide. 1 TFA







538


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.73 (br s, 1H), 11.22 (s, 1H), 8.72 (d, J = 7.0 Hz, 1H), 8.06 (s, 1H), 7.83 (d, J = 1.0 Hz, 1H), 7.01 (s, 1H), 6.97 (dd, J = 2.0, 7.2 Hz, 1H), 5.08-4.83 (m, 1H), 3.20 (s, 3H), 2.16 (td, J = 7.0, 14.0 Hz, 1H), 1.75-1.60 (m, 1H), 1.24-1.13 (m, 1H); LCMS(electrospray) m/z 450 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methylsulfinyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







539


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.80 (s, 1H), 7.63 (d, J = 0.7 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J = 1.9, 7.2 Hz, 1H), 6.06-5.88 (m, 1H), 5.05-4.82 (m, 1H), 4.33 (br t, J = 5.4 Hz, 2H), 3.62 (br t, J = 5.8 Hz, 5H), 2.94 (s, 3H), 2.23 (d, J = 3.1 Hz, 3H), 2.18-2.11 (m, 1H), 1.73-1.61 (m, 1H), 1.20-1.14 (m, 1H); LCMS(electrospray) m/z 484.4 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(2-(1-methylureido)ethoxy)-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







540


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1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 11.16 (s, 1H), 9.93 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.76 (s, 1H), 7.67 (s, 1H), 6.93 (s, 1H), 6.87 (dd, J = 1.7, 7.1 Hz, 1H), 5.06-4.82 (m, 1H), 2.24 (d, J = 2.6 Hz, 3H), 2.20-2.10 (m, 4H), 1.73-1.60 (m, 1H), 1.17 (tdd, J = 6.4, 9.0, 12.3 Hz, 1H); LCMS(electrospray) m/z 424.15 (M + H+).

J






(1S,2S)-N-(5-(7-acetamido-6-fluoro-5-





methyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







541


embedded image



1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.96 (br s, 1H), 7.66 (d, J = 1.0 Hz, 1H), 6.94 (s, 1H), 6.88 (dd, J = 2.0, 7.1 Hz, 1H), 5.06-4.83 (m, 1H), 2.30 (s, 3H), 2.15 (td, J = 7.0, 14.0 Hz, 1H), 1.74-1.60 (m, 1H), 1.17 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS(electrospray) m/z 418 (M + H+).

J






(1S,2S)-N-(5-(6,7-difluoro-5-(methylthio)-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide.





1 TFA







542


embedded image



1H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 11.16 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.35 (s, 1H), 7.88 (s, 1H), 7.71 (s, 1H), 6.93 (s, 1H), 6.89 (d, J = 7.2 Hz, 1H), 5.04-4.85 (m, 1H), 3.23 (s, 3H), 2.16- 2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.28-1.12 (m, 1H); LCMS (electrospray) m/z 532.1 (M + H)+.

J






tert-butyl 2-(5-chloro-6-fluoro-4-(2-





((1S,2S)-2-fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazol-7-yl)-1-methylhydrazine-1-





carboxylate







543


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1H NMR (400 MHz, DMSO-d6) δ 14.02-13.34 (m, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.85 (s, 1H), 7.65 (s, 1H), 6.93 (s, 1H), 6.89 (dd, J = 1.8, 7.1 Hz, 1H), 5.11-4.78 (m, 1H), 4.35 (q, J = 7.0 Hz, 2H), 2.28 (s, 3H), 2.19-2.12 (m, 1H), 1.68 (m, J = 3.2, 6.8, 19.9 Hz, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.26-1.11 (m, 1H); LCMS(electrospray) m/z 444.2 (M + H+).

J






(1S,2S)-N-(5-(7-ethoxy-6-fluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







544


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1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.80 (s, 1H), 7.64 (d, J = 1.0 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J = 1.9, 7.1 Hz, 1H), 6.28 (br s, 1H), 5.14-4.71 (m, 1H), 4.22 (t, J = 5.4 Hz, 2H), 3.40 (br d, J = 4.1 Hz, 2H), 2.24 (d, J = 3.0 Hz, 3H), 2.19-2.09 (m, 1H), 1.73-1.59 (m, 1H), 1.24-1.07 (m, 1H); LCMS(electrospray) m/z 470.1 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(2-ureidoethoxy)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







545


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1H NMR (400 MHz, DMSO-d6) δ 11.24-11.04 (m, 1H), 8.74-8.52 (m, 1H), 7.85-7.75 (m, 1H), 7.64 (d, J = 0.9 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J = 1.8, 7.1 Hz, 1H), 6.27-6.15 (m, 1H), 6.03-5.80 (m, 1H), 5.09-4.80 (m, 1H), 4.31-4.12 (m, 2H), 3.47- 3.34 (m, 2H), 2.57 (s, 3H), 2.23 (d, J = 3.1 Hz, 3H), 2.19-2.08 (m, 1H), 1.75-1.60 (m, 1H), 1.25- 1.10 (m, 1H); LCMS(electrospray) m/z 484.2 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(2-(3-methylureido)ethoxy)-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







546


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1H NMR (400 MHz, DMSO-d6) δ 13.52-13.40 (m, 1H), 11.16 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.85 (br s, 1H), 7.68 (s, 1H), 6.94 (s, 1H), 6.89 (dd, J = 1.6, 7.0 Hz, 1H), 5.04-4.83 (m, 1H), 4.05 (br t, J = 6.7 Hz, 2H), 3.16 (br d, J = 5.5 Hz, 2H), 2.53 (br s, 3H), 2.25 (d, J = 2.7 Hz, 3H), 2.17-2.13 (m, 1H), 2.04 (td, J = 2.4, 4.9 Hz, 1H), 1.68 (tdd, J = 3.3, 6.6, 19.7 Hz, 1H), 1.17 (ddd, J = 2.6, 6.2, 12.3 Hz, 1H); LCMS(electrospray) m/z 501.2 (M + H+).

J






2-((6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





5-methyl-1H-indazol-7-yl)thio)ethyl





methylcarbamate. 1 TFA







547


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1H NMR (400 MHz, DMSO-d6) δ 13.67-13.25 (m, 1H), 11.16 (s, 1H), 9.63 (br t, J = 5.2 Hz, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.82 (s, 1H), 7.64 (d, J = 0.9 Hz, 1H), 6.92 (s, 1H), 6.85 (dd, J = 1.9, 7.2 Hz, 1H), 5.07-4.83 (m, 1H), 4.38 (s, 2H), 3.66 (q, J = 5.5 Hz, 3H), 2.23 (d, J = 3.1 Hz, 3H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.75-1.61 (m, 1H), 1.18-1.29 (m, J = 2.9, 6.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 523.3 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(2-(2,2,2-trifluoroacetamido)ethoxy)-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







548


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1H NMR (400 MHz, DMSO-d6) δ 13.32 (s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.89 (s, 1H), 7.73 (s, 1H), 6.96 (s, 1H), 6.89 (dd, J = 1.8, 7.1 Hz, 1H), 5.15-4.72 (m, 1H), 3.98 (s, 3H), 2.24 (d, J = 2.9 Hz, 3H), 2.20-2.09 (m, 1H), 1.76-1.59 (m, 1H), 1.18 (ddd, J = 2.8, 6.2, 12.2 Hz, 1H); LCMS(electrospray) m/z 426.2 (M + H+).

J






methyl 6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





5-methyl-1H-indazole-7-carboxylate







549


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1H NMR (400 MHz, DMSO-d6) δ 13.66-13.38 (m, 1H), 13.19 (br s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.85 (s, 1H), 7.72 (s, 1H), 6.96 (s, 1H), 6.89 (dd, J = 1.8, 7.1 Hz, 1H), 5.07-4.84 (m, 1H), 2.24 (d, J = 3.1 Hz, 3H), 2.18-2.13 (m, 1H), 1.72-1.62 (m, 1H), 1.20-1.14 (m, 1H); LCMS(electrospray) m/z 412.2 (M + H+).

J






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





5-methyl-1H-indazole-7-carboxylic acid. 1





TFA







550


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1H NMR (400 MHz, DMSO-d6) δ 11.22-11.13 (m, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.95-7.87 (m, 1H), 7.72-7.70 (m, 1H), 6.96-6.93 (m, 1H), 6.92-6.89 (m, 1H), 5.07-4.81 (m, 1H), 3.21 (s, 3H), 2.30- 2.25 (m, 3H), 2.25-2.23 (m, 1H), 2.20-2.09 (m, 1H), 1.79 (s, 3H), 1.74-1.63 (m, 1H), 1.28-1.09 (m, 1H); LCMS(electrospray) m/z 438.16 (M + H+)

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(N-methylacetamido)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide. 1 TFA







551


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 11.20 (s, 1H), 8.70 (d, J = 7.1 Hz, 1H), 7.99 (s, 1H), 7.83 (d, J = 0.9 Hz, 1H), 7.03-6.95 (m, 2H), 5.10- 4.82 (m, 1H), 2.22-2.09 (m, 1H), 1.79-1.60 (m, 1H), 1.26-1.11 (m, 1H); LCMS(electrospray) m/z 432.2 (M + H+).

J






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazole-7-carboxylic acid. 1 TFA







552


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1H NMR (400 MHz, DMSO-d6) δ 14.07-13.87 (m, 1H), 11.19 (s, 1H), 8.69 (br d, J = 7.1 Hz, 1H), 8.07-8.01 (m, 1H), 7.82 (d, J = 0.7 Hz, 1H), 6.99 (s, 1H), 6.97 (br d, J = 2.0 Hz, 1H), 5.05-4.83 (m, 1H), 3.23 (s, 3H), 2.18-2.11 (m, 1H), 1.82 (s, 3H), 1.71-1.64 (m, 1H), 1.22-1.13 (m, 1H); LCMS(electrospray) m/z 459.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(N-





methylacetamido)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide. 1 TFA







553


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1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 11.15 (s, 1H), 8.60 (d, J = 7.2 Hz, 1H), 7.77 (s, 1H), 7.68 (s, 1H), 7.42 (s, 1H), 6.91-6.88 (m, 2H), 5.02 (s, 1H), 5.04-4.85 (m, 1H), 2.66 (s, 3H), 2.16- 2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.28-1.12 (m, 1H); LCMS (electrospray) m/z 432.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(2-





methylhydrazineyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







554


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1H NMR (400 MHz, DMSO-d6) δ 11.22 (s, 1H), 8.71 (d, J = 7.1 Hz, 1H), 8.05 (s, 1H), 7.85 (d, J = 1.0 Hz, 1H), 7.00 (s, 1H), 6.97 (dd, J = 2.0, 7.2 Hz, 1H), 5.08-4.81 (m, 1H), 4.00 (s, 3H), 2.19-2.11 (m, 1H), 1.75-1.60 (m, 1H), 1.21-1.13 (m, 1H); LCMS(electrospray) m/z 446.0 (M + H+).

J






methyl 5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazole-7-carboxylate







555


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1H NMR (400 MHz, DMSO-d6) δ 13.49 (br s, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.0 Hz, 1H), 7.89 (s, 1H), 7.77 (s, 1H), 7.04-6.89 (m, 2H), 5.15-4.82 (m, 1H), 4.58 (d, J = 4.3 Hz, 1H), 4.08 (br d, J = 5.4 Hz, 1H), 3.70 (br s, 1H), 2.90 (s, 3H), 2.11 (dt, J = 7.0, 13.6 Hz, 2H), 1.81-1.62 (m, 5H), 1.59-1.43 (m, 2H), 1.25-1.13 (m, 1H); LCMS(electrospray) m/z 501.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((3-





hydroxycyclopentyl)(methyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







556


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1H NMR (400 MHz, DMSO-d6) δ 13.88-13.56 (m, 1H), 11.20 (s, 1H), 8.70 (d, J = 7.1 Hz, 1H), 8.00 (s, 1H), 7.82 (d, J = 0.7 Hz, 1H), 6.99 (s, 1H), 6.96 (d, J = 2.0 Hz, 1H), 5.05-4.85 (m, 1H), 3.13 (s, 3H), 2.93 (s, 3H), 2.18-2.11 (m, 1H), 1.72- 1.62 (m, 1H), 1.18 (ddd, J = 2.9, 6.1, 12.3 Hz, 1H); LCMS(electrospray) m/z459.1(M + H+).

J






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





N,N-dimethyl-1H-indazole-7-carboxamide







557


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1H NMR (400 MHz, DMSO-d6) δ 13.18 (br d, J = 2.5 Hz, 1H), 11.14 (s, 1H), 8.62 (d, J = 7.2 Hz, 1H), 7.74 (s, 1H), 7.62 (s, 1H), 6.90 (s, 1H), 6.87-6.81 (m, 1H), 5.17-4.73 (m, 2H), 3.65-3.57 (m, 2H), 3.28-3.18 (m, 2H), 2.97 (d, J = 2.3 Hz, 3H), 2.25- 2.10 (m, 4H), 1.76-1.58 (m, 1H), 1.26-1.11 (m, 1H); LCMS(electrospray) m/z 441.1 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-





hydroxyethyl)(methyl)amino)-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







558


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1H NMR (400 MHz, DMSO-d6) δ 13.43 (br s, 1H), 11.14 (s, 1H), 8.59 (d, J = 7.0 Hz, 1H), 7.78 (s, 1H), 7.62 (s, 1H), 6.91 (s, 1H), 6.87 (dd, J = 1.9, 7.1 Hz, 1H), 5.06-4.82 (m, 1H), 2.97 (d, J = 2.0 Hz, 6H), 2.26 (s, 3H), 2.19-2.10 (m, 1H), 1.73-1.61 (m, 1H), 1.22-1.12 (m, 1H); LCMS(electrospray) m/z 443 (M + H+).

J






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







559


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1H NMR (400 MHz, DMSO-d6) δ 13.29 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.0 Hz, 1H), 7.86 (br s, 1H), 7.71 (s, 1H), 7.00-6.86 (m, 2H), 5.44 (br s, 1H), 5.11-4.94 (m, 1H), 4.90-4.77 (m, 1H), 4.40- 4.11 (m, 2H), 2.25-2.09 (m, 2H), 2.04-1.86 (m, 1H), 1.84-1.57 (m, 5H), 1.30-1.08 (m, 1H); LCMS(electrospray) m/z 487.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((3-





hydroxycyclopentyl)amino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







560


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1H NMR (400 MHz, DMSO-d6) δ 13.68-13.53 (m, 1H), 11.24-11.17 (m, 1H), 8.70 (d, J = 7.1 Hz, 1H), 8.67-8.60 (m, 1H), 7.99-7.93 (m, 1H), 7.81 (d, J = 0.9 Hz, 1H), 6.99 (s, 1H), 6.97-6.92 (m, 1H), 5.07-4.81 (m, 1H), 2.91 (d, J = 4.4 Hz, 3H), 2.20-2.10 (m, 1H), 1.75-1.55 (m, 1H), 1.07 (s, 1H); LCMS(electrospray) m/z 445.1(M + H+).

J






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





N-methyl-1H-indazole-7-carboxamide







561


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1H NMR (400 MHz, DMSO-d6) δ 11.18 (br s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 7.09-6.87 (m, 2H), 5.08-4.84 (m, 1H), 3.87-3.71 (m, 1H), 3.59-3.43 (m, 1H), 3.60-3.42 (m, 1H), 2.89-2.81 (m, 3H), 2.46-2.39 (m, 2H), 2.21-2.09 (m, 1H), 2.24-2.07 (m, 1H), 2.20-1.95 (m, 1H), 1.99 (br d, J = 4.9 Hz, 1H), 1.79-1.62 (m, 3H), 1.26-1.12 (m, 2H); LCMS(electrospray) m/z 487.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((3-





hydroxycyclobutyl)(methyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







562


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 11.11 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.65 (s, 1H), 6.91 (s, 1H), 6.86 (dd, J = 1.9, 7.1 Hz, 1H), 2.24 (d, J = 2.9 Hz, 3H), 2.00-1.87 (m, 1H), 0.88-0.77 (m, 4H); LCMS(electrospray) m/z 395.12 (M + H+).

J






N-(5-(6-fluoro-5-methyl-7-(methylthio)-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropanecarboxamide







563


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1H NMR (400 MHz, METHANOL-d4) δ 8.55- 8.47 (m, 1H), 7.79-7.72 (m, 1H), 7.58-7.54 (m, 1H), 7.00-6.93 (m, 1H), 6.89-6.83 (m, 1H), 5.02- 4.93 (m, 1H), 4.60-4.56 (m, 1H), 3.29-3.24 (m, 2H), 3.01-2.94 (m, 3H), 2.33-2.25 (m, 3H), 2.17- 2.07 (m, 1H), 1.89-1.77 (m, 1H), 1.27-1.19 (m, 1H), 1.15-1.09 (m, 3H); LCMS(electrospray) m/z 425.2 (M + H+).

J






(1S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-





fluoro-5-methyl-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







564


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1H NMR (400 MHz, METHANOL-d4) δ 8.43- 8.38 (m, 1H), 7.77-7.72 (m, 1H), 7.59-7.54 (m, 1H), 6.89-6.86 (m, 1H), 6.85-6.81 (m, 1H), 4.88- 4.82 (m, 1H), 4.72-4.64 (m, 1H), 3.20-3.15 (m, 2H), 3.20 (br s, 1H), 2.90 (d, J = 1.8 Hz, 2H), 2.95- 2.88 (m, 1H), 2.04-1.94 (m, 1H), 1.78-1.65 (m, 1H), 1.17-1.07 (m, 1H), 1.05-0.99 (m, 3H); LCMS(electrospray) m/z 445.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-7-





(ethyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







565


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1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.80 (d, J = 4.8 Hz, 1H), 7.62 (d, J = 0.9 Hz, 1H), 6.92 (s, 1H), 6.80 (dd, J = 1.9, 7.1 Hz, 1H), 5.08-4.70 (m, 1H), 3.02 (d, J = 2.3 Hz, 6H), 2.20-2.12 (m, 1H), 1.73-1.62 (m, 1H), 1.22-1.14 (m, 1H); LCMS(electrospray) m/z 465.1 (M + H+).

J






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-5-(trifluoromethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







566


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (br s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.86 (s, 1H), 7.73 (s, 1H), 6.97 (s, 1H), 6.89 (dd, J = 1.9, 7.2 Hz, 1H), 5.07-4.80 (m, 1H), 2.74 (d, J = 6.4 Hz, 3H), 2.28 (d, J = 3.2 Hz, 3H), 2.20-2.09 (m, 1H), 1.74- 1.61 (m, 1H), 1.25-1.13 (m, 1H); LCMS(electrospray) m/z 409.14 (M + H+).

J






(1S,2S)-N-(5-(7-acetyl-6-fluoro-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







567


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 11.28 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.67 (s, 1H), 6.89 (s, 1H), 6.87 (d, J = 1.8 Hz, 1H), 5.03-4.81 (m, 1H), 2.23 (d, J = 2.8 Hz, 3H), 1.64- 1.45 (m, 1H), 1.27 (qd, J = 6.5, 13.1 Hz, 1H); LCMS(electrospray) m/z 413.11 (M + H+).

J






(1S,2R)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







568


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 11.28 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.67 (d, J = 0.7 Hz, 1H), 6.88 (s, 1H), 6.87 (d, J = 1.8 Hz, 1H), 5.04-4.79 (m, 1H), 2.49-2.40 (m, 3H), 2.23 (d, J = 2.8 Hz, 3H), 1.62-1.45 (m, 1H), 1.27 (qd, J = 6.4, 13.1 Hz, 1H); LCMS(electrospray) m/z 413.11 (M + H+).

J






(1R,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







569


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1H NMR (400 MHz, DMSO-d6) δ 13.45 (br s, 1H), 11.10 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.81 (s, 1H), 7.66 (s, 1H), 7.52 (d, J = 9.3 Hz, 1H), 6.91 (s, 1H), 6.88 (dd, J = 1.8, 7.1 Hz, 1H), 2.26 (s, 3H), 2.00- 1.88 (m, 1H), 0.90-0.77 (m, 4H); LCMS(electrospray) m/z 382.1(M + H+)

J






N-(5-(6-fluoro-5-(methylthio)-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropanecarboxamide







570


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1H NMR (400 MHz, DMSO-d6) δ 13.43 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.73-7.67 (m, 1H), 6.94 (s, 1H), 6.89 (dd, J = 2.0, 7.1 Hz, 1H), 5.16-4.74 (m, 1H), 3.12 (s, 3H), 2.92 (s, 3H), 2.24 (d, J = 2.9 Hz, 3H), 2.19-2.10 (m, 1H), 1.74-1.60 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 439.2 (M + H+).

J






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





N,N,5-trimethyl-1H-indazole-7-





carboxamide







571


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (br s, 1H), 11.28 (br s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.81 (s, 1H), 7.67 (s, 1H), 7.52 (d, J = 9.3 Hz, 1H), 6.93- 6.87 (m, 2H), 5.05-4.81 (m, 1H), 2.48-2.42 (m, 1H), 2.26 (s, 3H), 1.61-1.46 (m, 1H), 1.33-1.20 (m, 1H); LCMS(electrospray) m/z 400.1(M + H+).

J






(1R,2S)-2-fluoro-N-(5-(6-fluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







572


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1H NMR (400 MHz, DMSO-d6) δ 13.40 (br s, 1H), 11.28 (s, 1H), 8.63 (d, J = 7.0 Hz, 1H), 7.81 (s, 1H), 7.67 (s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 6.93-6.87 (m, 2H), 5.03-4.80 (m, 1H), 2.46-2.42 (m, 1H), 2.26 (s, 3H), 1.61-1.46 (m, 1H), 1.27 (qd, J = 6.3, 13.0 Hz, 1H); LCMS(electrospray) m/z 400.1(M + H+).

J






(1S,2R)-2-fluoro-N-(5-(6-fluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







573


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1H NMR (400 MHz, DMSO-d6) δ 13.42 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.0 Hz, 1H), 7.82 (s, 1H), 7.68 (s, 1H), 7.52 (d, J = 9.4 Hz, 1H), 6.93 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.06-4.83 (m, 1H), 2.26 (s, 3H), 2.15 (td, J = 7.1, 14.1 Hz, 1H), 1.74- 1.61 (m, 1H), 1.22-1.12 (m, 1H); LCMS(electrospray) m/z 400.1(M + H+).

J






(1R,2R)-2-fluoro-N-(5-(6-fluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







574


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1H NMR (400 MHz, DMSO-d6) δ 13.47 (br s, 1H), 11.16 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.67 (s, 1H), 6.93 (s, 1H), 6.87 (dd, J = 1.8, 7.1 Hz, 1H), 5.08-4.79 (m, 1H), 3.30 (s, 3H), 2.25-2.23 (m, 1H), 2.24 (d, J = 2.9 Hz, 3H), 2.14 (br dd, J = 6.0, 8.1 Hz, 1H), 1.76-1.60 (m, 1H), 1.24-1.13 (m, 1H); LCMS(electrospray) m/z 413.11 (M + H+).

J






(1R,2R)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







575


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1H NMR (400 MHz, DMSO-d6) δ 13.74 (s, 1H), 11.22 (s, 1H), 8.72 (d, J = 7.1 Hz, 1H), 8.40 (s, 1H), 8.02 (s, 1H), 7.85 (d, J = 1.0 Hz, 1H), 7.02 (s, 1H), 6.97 (dd, J = 1.9, 7.2 Hz, 1H), 5.14-4.76 (m, 1H), 2.77 (d, J = 6.1 Hz, 3H), 2.21-2.12 (m, 1H), 1.75- 1.61 (m, 1H), 1.26-1.12 (m, 2H); LCMS(electrospray) m/z 430.3 (M + H+).

J






(1S,2S)-N-(5-(7-acetyl-5-chloro-6-fluoro-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







576


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1H NMR (400 MHz, DMSO-d6) δ 13.70-13.43 (m, 1H), 11.22 (s, 1H), 8.71 (d, J = 6.8 Hz, 1H), 8.08 (s, 2H), 7.95 (s, 1H), 7.82 (s, 1H), 7.03-6.91 (m, 2H), 5.10-4.81 (m, 1H), 2.15 (d, J = 6.8 Hz, 1H), 1.76-1.59 (m, 1H), 1.18 (d, J = 7.2 Hz, 1H); LCMS(electrospray) m/z 431.1 (M + H+).

J






5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazole-7-carboxamide







577


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1H NMR (400 MHz, DMSO-d6) δ 13.38 (br s, 1H), 11.14 (s, 1H), 8.60 (d, J = 6.9 Hz, 1H), 7.78 (s, 1H), 7.64 (s, 1H), 6.91 (s, 1H), 6.88 (dd, J = 1.6, 7.1 Hz, 1H), 5.06-4.83 (m, 1H), 3.23 (q, J = 6.7 Hz, 2H), 2.95 (s, 3H), 2.26 (s, 3H), 2.19-2.10 (m, 1H), 1.74- 1.61 (m, 1H), 1.21-1.14 (m, 1H), 1.07 (t, J = 7.0 Hz, 3H); LCMS(electrospray) m/z 457 (M + H+).

J






(1S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-





fluoro-5-(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







578


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1H NMR (400 MHz, DMSO-d6) δ 13.62-12.96 (m, 1H), 11.16 (br s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.98 (s, 1H), 7.83 (s, 1H), 7.50 (d, J = 10.4 Hz, 1H), 7.04 (dd, J = 1.8, 7.1 Hz, 1H), 6.95 (s, 1H), 5.06- 4.81 (m, 1H), 3.86 (q, J = 6.9 Hz, 2H), 2.15 (td, J = 7.0, 13.6 Hz, 1H), 1.73-1.62 (m, 1H), 1.22- 1.15 (m, 1H), 1.11 (t, J = 7.0 Hz, 3H). LCMS: m/z 398.0 (M + H+)

J






(1S,2S)-N-(5-(5-ethoxy-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







579


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1H NMR (400 MHz, DMSO-d6) δ 11.31-11.12 (m, 1H), 8.82-8.55 (m, 1H), 8.00-7.87 (m, 1H), 7.85- 7.70 (m, 1H), 7.03-6.90 (m, 2H), 5.10-4.82 (m, 1H), 2.56-2.53 (m, 3H), 2.24-2.11 (m, 1H), 1.75- 1.61 (m, 1H), 1.26-1.13 (m, 1H); LCMS(electrospray) m/z 402.1 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







580


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1H NMR (400 MHz, DMSO-d6) δ 13.31-12.98 (m, 1H), 11.21-11.07 (m, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.78-7.71 (m, 1H), 7.64-7.58 (m, 1H), 6.93- 6.88 (m, 2H), 6.84 (br d, J = 7.1 Hz, 1H), 5.06- 4.82 (m, 1H), 4.07 (br t, J = 5.9 Hz, 2H), 3.35- 3.27 (m, 2H), 2.98 (s, 3H), 2.53 (d, J = 4.5 Hz, 3H), 2.20 (d, J = 3.0 Hz, 3H), 2.16-2.09 (m, 1H), 1.72- 1.61 (m, 1H), 1.20-1.13 (m, 1H); LCMS(electrospray) m/z = 498.2 (M + H+).

J






2-((6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





5-methyl-1H-indazol-7-





yl)(methyl)amino)ethyl methylcarbamate







581


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1H NMR (400 MHz, DMSO-d6) δ 1.12-1.24 (m, 1 H), 1.61-1.74 (m, 1 H), 2.11-2.20 (m, 1 H), 4.82- 5.07 (m, 1 H), 6.95-6.98 (m, 1 H), 6.99 (s, 1 H) 7.50 (s, 1 H), 7.63 (s, 1 H), 7.77 (s, 1 H), 7.83 (d, J = 1.00 Hz, 1 H), 8.06 (s, 1 H), 8.71 (d, J = 7.13 Hz, 1 H), 11.20 (s, 1 H), 13.85-13.92 (m, 1 H); LCMS(electrospray) m/z 438.1 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-7-





(difluoromethyl)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







582


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1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.69 (d, J = 7.1 Hz, 1H), 8.06 (s, 1H), 7.74 (s, 1H), 6.97 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.10- 4.72 (m, 1H), 2.26 (d, J = 2.6 Hz, 3H), 2.15 (td, J = 6.6, 13.5 Hz, 1H), 1.73-1.60 (m, 1H), 1.25- 1.13 (m, 1H); LCMS(electrospray) m/z 393.1 (M + H+).

J






(1S,2S)-N-(5-(7-cyano-6-fluoro-5-methyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







583


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1H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 8.29 (s, 1H), 7.93 (d, J = 1.0 Hz, 1H), 7.23 (d, J = 13.7 Hz, 1H), 7.16 (dd, J = 2.0, 7.2 Hz, 1H), 6.94 (s, 1H), 5.06- 4.83 (m, 1H), 2.95 (d, J = 2.0 Hz, 6H), 2.14 (br s, 1H), 1.77-1.57 (m, 1H), 1.17 (br s, 1H); LCMS(electrospray) m/z 397.2 (M + H+).

J






(1S,2S)-N-(5-(7-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







584


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1H NMR (400 MHz, DMSO-d6) δ 13.31-13.17 (m, 1H), 11.26-11.08 (m, 1H), 8.66 (d, J = 7.1 Hz, 1H), 8.49-8.38 (m, 1H), 7.85-7.76 (m, 1H), 7.70 (s, 1H), 6.95 (s, 1H), 6.88 (s, 1H), 5.07-4.82 (m, 1H), 2.90 (d, J = 4.6 Hz, 3H), 2.25 (d, J = 3.1 Hz, 3H), 2.15 (td, J = 6.7, 13.8 Hz, 1H), 1.74-1.62 (m, 1H), 1.21-1.09 (m, 1H); LCMS(electrospray) m/z 425.1 (M + H+).

J






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





N,5-dimethyl-1H-indazole-7-carboxamide







585


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1H NMR (400 MHz, DMSO-d6) δ 13.82-13.52 (m, 1H), 11.19 (s, 1H), 8.69 (d, J = 7.0 Hz, 1H), 7.91 (s, 1H), 7.70 (d, J = 0.9 Hz, 1H), 6.96 (s, 1H), 6.86 (dd, J = 1.9, 7.1 Hz, 1H), 5.06-4.83 (m, 1H), 2.68-2.63 (m, 2H), 2.19-2.10 (m, 1H), 1.74-1.62 (m, 1H), 1.20-1.14 (m, 1H), 1.10 (t, J = 7.5 Hz, 3H); LCMS(electrospray) m/z 450.2 (M + H+).

J






(1S,2S)-N-(5-(5-ethyl-6-fluoro-7-





(trifluoromethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







586


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1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.73 (d, J = 7.2 Hz, 1H), 8.24 (s, 1H), 7.86 (s, 1H), 7.02 (s, 1H), 6.97 (dd, J = 1.9, 7.2 Hz, 1H), 5.10- 4.78 (m, 1H), 2.22-2.10 (m, 1H), 1.76-1.58 (m, 1H), 1.22-1.15 (m, 1H); LCMS(electrospray) m/z 413.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-7-cyano-6-fluoro-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







587


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1H NMR (400 MHz, DMSO-d6) δ 14.11 (s, 1H), 11.17 (s, 1H), 8.68-8.66 (m, 1H), 8.45(s, 1H), 8.04 (s, 1H), 7.52 (d, J = 11.2 Hz, 1H), 7.22-7.21 (m, 1H), 6.99 (s, 1H), 5.02-4.86 (m, 1H), 2.15 (br s, 1H), 1.72-1.70 (m, 1 H) 1.19-1.18 (m, 1 H); LCMS(electrospray) m/z 438.2 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-





(trifluoromethoxy)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







588


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1H NMR (400 MHz, DMSO-d6) δ 13.84-13.52 (m, 1H), 11.32-11.10 (m, 1H), 8.75-8.60 (m, 1H), 7.97-7.76 (m, 1H), 7.72-7.64 (m, 1H), 6.99-6.91 (m, 1H), 6.89-6.80 (m, 1H), 5.09-4.81 (m, 1H), 4.26-4.07 (m, 2H), 2.75-2.62 (m, 2H), 2.24-2.10 (m, 1H), 1.77-1.62 (m, 1H), 1.23-1.15 (m, 1H), 1.15-1.09 (m, 3H); LCMS(electrospray) m/z 453.1 (M + H+).

J






(1S,2S)-N-(5-(7-((cyanomethyl)thio)-5-





ethyl-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







589


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1H NMR (400 MHz, DMSO-d6) δ 13.64 (s, 1 H) 11.17 (s, 1 H) 8.65 (d, J = 7.2 Hz, 1 H) 8.38 (s, 1 H) 8.02 (s, 1 H) 7.37 (d, J = 8.8 Hz, 1 H) 7.22-7.19 (m, 1 H) 6.98 (s, 1 H), 5.05-4.84 (m, 1 H) 2.52 (s, 3 H) 2.16-2.13 (m, 1H) 1.72-1.64 (m, 1H) 1.20- 1.15 (m, 1 H); LCMS(electrospray) m/z 400.1 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







590


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1H NMR (400 MHz, DMSO-d6) δ 13.74 (br s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.79 (s, 1H), 7.76 (d, J = 11.9 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H), 5.19-4.94 (m, 1H), 2.26 (td, J = 6.9, 13.6 Hz, 1H), 1.84-1.70 (m, 1H), 1.39-1.27 (m, 1H); LCMS(electrospray) m/z 440.2 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-





(trifluoromethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







591


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1H NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.89 (d, J = 0.7 Hz, 1H), 7.72-7.41 (m, 2H), 6.95 (s, 1H), 6.89 (dd, J = 1.8, 7.0 Hz, 1H), 5.09-4.81 (m, 1H), 2.24 (d, J = 2.6 Hz, 3H), 2.19-2.11 (m, 1H), 1.76-1.60 (m, 1H), 1.25-1.11 (m, 1H); LCMS(electrospray) m/z 418.1 (M + H+).

J






(1S,2S)-N-(5-(7-(difluoromethyl)-6-





fluoro-5-methyl-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







592


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1H NMR (400 MHz, DMSO-d6) δ 13.95 (s, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.94 (s, 1H), 7.72 (s, 1H), 6.95 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.11-4.78 (m, 1H), 2.28 (d, J = 2.8 Hz, 3H), 2.20-2.10 (m, 1H), 1.74-1.61 (m, 1H), 1.24-1.12 (m, 1H); LCMS(electrospray) m/z 452.2 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-





7-(trifluoromethoxy)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







593


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1H NMR (400 MHz, DMSO-d6) δ 13.43-13.58 (m, 1 H) 11.13 (s, 1 H) 8.62 (d, J = 7.13 Hz, 1 H) 8.36 (s, 1 H) 7.94 (d, J = 1.25 Hz, 1 H) 7.36 (s, 2 H) 7.17 (dd, J = 7.25, 2.00 Hz, 1 H) 6.95 (s, 1 H) 4.80- 5.07 (m, 1 H) 2.63 (s, 3 H) 2.10-2.18 (m, 1 H) 1.62-1.73 (m, 1 H) 1.17 (ddt, J = 12.32, 9.04, 6.27, 6.27 Hz, 1 H); LCMS(electrospray) m/z = 382.1 (M + H+).

J






(1S,2S)-2-fluoro-N-(5-(7-(methylthio)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)cyclopropane-1-carboxamide







594


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1H NMR (400 MHz, DMSO-d6) δ 13.69 (s, 1H), 11.14 (s, 1H), 8.93 (s, 1H), 8.26-8.23 (m, 2H), 7.65 (d, J = 9.3 Hz, 1H), 7.51-7.39 (m, 1H), 5.11-4.77 (m, 1H), 4.13 (s, 3H), 2.18 (td, J = 6.8, 13.8 Hz, 1H), 1.81-1.59 (m, 1H), 1.27-1.11 (m, 1H); LCMS(electrospray) m/z 470.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-





methyl-1H-tetrazol-5-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







595


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1H NMR (400 MHz, DMSO-d6) δ 13.26 (br s, 1H), 11.11 (s, 1H), 8.57 (br d, J = 7.1 Hz, 1H), 8.28 (s, 1H), 7.84 (s, 1H), 7.26 (br d, J = 7.7 Hz, 1H), 7.13 (dd, J = 2.0, 7.3 Hz, 1H), 6.90 (s, 1H), 6.80 (br d, J = 7.7 Hz, 1H), 5.08-4.79 (m, 1H), 2.93 (s, 6H), 2.14 (quin, J = 6.9 Hz, 1H), 1.74-1.60 (m, 1H), 1.17 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS(electrospray) m/z 379.1 (M + H+).

J






(1S,2S)-N-(5-(7-(dimethylamino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







596


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1H NMR (400 MHz, DMSO-d6) δ 13.63 (s, 1H), 11.19 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.45 (br, 1H), 7.97 (s, 1H), 7.84 (s, 1H), 6.99 (s, 1H), 6.85 (d, J = 7.2 Hz, 1H), 5.04-4.85 (m, 1H), 3.53 (s, 3H), 2.16-2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.28- 1.12 (m, 1H); LCMS (electrospray) m/z 495.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methyl(pyrimidin-2-yl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







597


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1H NMR (400 MHz, DMSO-d6) δ 13.67 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.82 (s, 1H), 7.69 (s, 1H), 6.94 (s, 1H), 6.85 (d, J = 7.2 Hz, 1H), 5.04-4.87 (m, 1H), 4.50 (q, J = 7.2 Hz, 1H), 2.69- 2.60 (m, 2H), 4.23 (s, 2H), 2.16-2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.60 (d, J = 12 Hz, 3H), 1.28- 1.11 (m, 4H); LCMS (electrospray) m/z 467.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-





((cyanomethyl)thio)-6-fluoro-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







598


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1H NMR (400 MHz, DMSO-d6) δ 14.15 (s, 1H), 11.17 (s, 1H), 8.63 (d, J = 7.6 Hz, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 6.94 (s, 1H), 6.88 (d, J = 7.2 Hz, 1H), 5.04-4.87 (m, 1H), 2.30 (s, 3H), 2.15-2.13 (m, 1H), 1.71-1.64 (m, 1H), 1.24-1.18 (m, 1H); LCMS (electrospray) m/z 418.10 (M + H)+.

J






(1R,2R)-N-(5-(6,7-difluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







599


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1H NMR (400 MHz, DMSO-d6) δ 14.13 (s, 1H), 11.29 (s, 1H), 8.64 (d, J = 6.0 Hz, 1H), 7.96 (s, 1H), 7.66 (s, 1H), 6.90-6.88 (m, 2H), 5.00-4.84 (m, 1H), 2.50-2.43 (m, 1H), 2.30 (s, 3H), 1.58-1.49 (m, 1H), 1.30-1.24 (m, 1H); LCMS (electrospray) m/z 418.10 (M + H)+.

J






(1S,2R)-N-(5-(6,7-difluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







600


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1H NMR (400 MHz, DMSO-d6) δ 14.11 (s, 1H), 11.29 (s, 1H), 8.64 (d, J = 7.2 Hz, 1H), 7.96 (s, 1H), 7.66 (s, 1H), 6.90-6.88 (m, 2H), 5.00-4.84 (m, 1H), 2.50- 2.43 (m, 1H), 2.30 (s, 3H), 1.57 (m, 1H), 1.29-1.24 (m, 1H); LCMS (electrospray) m/z 418.10 (M + H)+.

J






(1R,2S)-N-(5-(6,7-difluoro-5-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







601


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1H NMR (400 MHz, DMSO-d6) δ 13.39 (s, 1H), 11.19 (s, 1H), 9.49 (s, 1H), 8.69 (d, J = 7.2 Hz, 1 H), 8.42 (d, J = 4.4 Hz, 1H), 7.91 (s, 1H), 7.83- 7.82 (m, 1H), 6.99-6.97 (m, 1H), 6.86 (t, J = 5.0 Hz, 1H), 5.05-4.85 (m, 1H), 2.17-2.13 (m, 1H), 1.71-1.63 (m, 1H), 1.21-1.15 (m, 1H); LCMS (electrospray) m/z 481.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(pyrimidin-2-ylamino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







602


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1H NMR (400 MHz, DMSO-d6) δ 13.63 (s, 1H), 11.21 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.05 (s, 1H), 7.85 (s, 1H), 7.00 (s, 1H), 6.98 (d, J = 7.2 Hz, 1H), 5.04-4.87 (m, 1H), 4.23 (s, 2H), 2.16-2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.28-1.12 (m, 1H); LCMS (electrospray) m/z 459.1 (M + H)+.

J






(1S,2S)-N-(5-(7-((1-cyanoethyl)thio)-5-





ethyl-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







603


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1H NMR (400 MHz, DMSO-d6) δ 13.65 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.81 (s, 1H), 7.71 (s, 1H), 6.94 (s, 1H), 6.87 (d, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 2.66-2.63 (m, 2H), 2.18- 2.11 (m, 1H), 1.73 (s, 6H), 1.70-1.62 (m, 1H), 1.28-1.12 (m, 1H), 1.12 (t, J = 5.2 Hz, 3H); LCMS (electrospray) m/z 481.1 (M + H)+.

J






(1S,2S)-N-(5-(7-((2-cyanopropan-2-





yl)thio)-5-ethyl-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







604


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1H NMR (400 MHz, DMSO-d6) δ 13.93-13.02 (m, 1H), 11.17 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.05 (s, 1H), 7.69 (d, J = 1.0 Hz, 1H), 7.52 (dd, J = 0.8, 9.5 Hz, 1H), 6.96 (s, 1H), 6.89 (td, J = 2.2, 7.2 Hz, 1H), 5.14-4.72 (m, 1H), 2.85 (s, 3H), 2.72 (d, J = 1.6 Hz, 3H), 2.14 (td, J = 6.9, 13.8 Hz, 1H), 1.75-1.59 (m, 1H), 1.17 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 425.2 (M + H+).

J






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





N,N-dimethyl-1H-indazole-7-carboxamide







605


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1H NMR (400 MHz, DMSO-d6) δ 13.93-13.02 (m, 1H), 11.17 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.05 (s, 1H), 7.69 (d, J = 1.0 Hz, 1H), 7.52 (dd, J = 0.8, 9.5 Hz, 1H), 6.96 (s, 1H), 6.89 (td, J = 2.2, 7.2 Hz, 1H), 5.14-4.72 (m, 1H), 2.85 (s, 3H), 2.72 (d, J = 1.6 Hz, 3H), 2.14 (td, J = 6.9, 13.8 Hz, 1H), 1.75-1.59 (m, 1H), 1.17 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(electrospray) m/z 425.2 (M + H+

J






6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





N,N-dimethyl-1H-indazole-5-carboxamide







606


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1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.64 (br d, J = 7.1 Hz, 1H), 8.06 (s, 1H), 7.83 (s, 1H), 7.03 (br dd, J = 1.8, 7.1 Hz, 1H), 6.96 (s, 1H), 5.06-4.82 (m, 1H), 3.86 (br d, J = 7.0 Hz, 2H), 2.55 (s, 3H), 2.18-2.12 (m, 1H), 1.73-1.61 (m, 1H), 1.26-1.15 (m, 1H), 1.11 (br t, J = 6.9 Hz, 3H); LCMS(electrospray) m/z 444.2 (M + H+).

J






(1S,2S)-N-(5-(5-ethoxy-6-fluoro-7-





(methylthio)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







607


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1H NMR (400 MHz, DMSO-d6) δ 14.06-13.49 (m, 1H), 10.62 (br s, 1H), 9.03 (d, J = 7.0 Hz, 1H), 8.56 (s, 1H), 8.25 (s, 1H), 7.58 (s, 1H), 7.44 (dd, J = 1.8, 7.1 Hz, 1H), 5.46-5.25 (m, 1H), 2.69 (br s, 1H), 2.27- 2.21 (m, 1H), 1.69-1.61 (m, 1H); LCMS(electrospray) m/z 472.0 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(trifluoromethoxy)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







608


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1H NMR (400 MHz, DMSO-d6) δ 13.64 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.82 (s, 1H), 7.71 (s, 1H), 6.94 (s, 1H), 6.88 (d, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 2.66-2.63 (m, 2H), 2.18- 2.11 (m, 1H), 1.73-7.72 (m, 2H), 1.70-1.62 (m, 1H), 1.62-1.60 (m, 1H), 1.28-1.12 (m, 1H), 1.12 (t, J = 5.2 Hz, 3H); LCMS (electrospray) m/z 479.1 (M + H)+.

J






(1S,2S)-N-(5-(7-((1-





cyanocyclopropyl)thio)-5-ethyl-6-fluoro-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







609


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1H NMR (400 MHz, DMSO-d6) δ 13.63 (s, 1H), 11.20 (s, 1H), 8.99 (s, 1H), 8.69 (d, J = 7.2 Hz, 1H), 8.21 (d, J = 6.4 Hz, 2H), 7.99 (s, 1H), 7.83-7.82 (m, 1H), 7.01-6.98 (m, 2H), 6.62 (d, J = 4.8 Hz, 2H), 5.04-4.85 (m, 1H), 2.17-2.12 (m, 1H), 1.71- 1.63 (m, 1H), 1.21-1.16 (m, 1H); LCMS (electrospray) m/z 480.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(pyridin-4-ylamino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







610


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1H NMR (400 MHz, DMSO-d6) δ 13.28 (br s, 1H), 11.15 (s, 1H), 8.60 (d, J = 7.0 Hz, 1H), 7.96 (s, 1H), 7.77 (s, 1H), 7.01 (dd, J = 1.8, 7.3 Hz, 1H), 6.92 (s, 1H), 5.04-4.83 (m, 1H), 3.83 (q, J = 7.0 Hz, 2H), 2.98 (br s, 6H), 2.18-2.11 (m, 1H), 1.72-1.6 (m, 1H), 1.18 (br s, 1H), 1.11 (t, J = 7.0 Hz, 3H); LCMS(electrospray) m/z 441.1 (M + H+).

J






(1S,2S)-N-(5-(7-(dimethylamino)-5-





ethoxy-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







611


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1H NMR (400 MHz, DMSO-d6) δ 13.96 (s, 1H), 11.17 (s, 1H), 8.64 (d, J = 7.2 Hz, 1H), 8.18-8.12 (m, 1H), 7.81 (s, 1H), 7.02-6.93 (m, 2H), 5.04- 4.84 (m, 1H), 3.96-3.82 (m, 2H), 2.18-2.09 (m, 1H), 1.70-1.60 (m, 1H), 1.20-1.16 (m, 1H), 1.12 (t, J = 6.8 Hz, 3H); LCMS(electrospray) m/z 416.1 (M + H+).

J






(1S,2S)-N-(5-(5-ethoxy-6,7-difluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







612


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1H NMR (400 MHz, DMSO-d6) δ 13.85 (s, 1H), 11.22 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.01 (s, 1H), 7.82 (s, 1H), 6.99 (s, 1H), 6.97 (s, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 4.72 (s, 2H), 3.03 (s, 3H), 2.18-2.11 (m, 1H), 1.70-1.62 (m, 1H), 1.28-1.12 (m, 1H); LCMS (electrospray) m/z 484.1 (M + H)+.

J






5-chloro-N-(cyanomethyl)-6-fluoro-4-(2-





((1S,2S)-2-fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





N-methyl-1H-indazole-7-carboxamide







613


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1H NMR (400 MHz, DMSO-d6) δ 13.62 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 8.55 (s, 1H), 7.98 (s, 1H), 7.84 (s, 1H), 7.00-6.99 (m, 2H), 5.03- 4.86 (m, 1H), 3.52 (s, 3H), 2.17-2.12 (m, 1H), 1.71-1.64 (m, 1H), 1.21-1.14 (m, 1H); LCMS (electrospray) m/z 513.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((5-





fluoropyrimidin-2-yl)(methyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







614


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1H NMR (400 MHz, DMSO-d6) δ 13.75 (s, 1H), 11.20 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.22 (d, J = 6.8 Hz, 1H), 8.04 (s, 1H), 7.84 (s, 1H), 7.01 (dd, J = 2.2, 7.0 Hz, 2H), 6.60 (d, J = 5.6 Hz, 1H), 5.06- 4.86 (m, 1H), 3.41 (s, 3H), 2.19-2.12 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.17 (m, 1H); LCMS (electrospray) m/z 494.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methyl(pyridin-4-yl)amino)-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







615


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1H NMR (400 MHz, DMSO-d6) δ 14.02 (s, 1H), 11.21 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.09 (s, 1H), 7.83 (s, 1H), 7.00 (s, 1H), 6.97 (s, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 4.79 (dd, J = 18 Hz, 110 Hz, 2H), 2.18-2.11 (m, 1H), 1.90 (s, 3H), 1.70-1.62 (m, 1H), 1.28-1.12 (m, 1H); LCMS (electrospray) m/z 484.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-(N-





(cyanomethyl)acetamido)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







616


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1H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 11.19 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 8.38 (dd, J = 1.6, 4.4 Hz, 2H), 7.89 (s, 1H), 7.73-7.72 (m, 1H), 7.21 (d, J = 6.0 Hz, 2H), 6.95 (s, 1H), 6.90 (dd, J = 2.4, 7.2 Hz, 1H), 5.05-4.84 (m, 1H), 3.54 (t, 2H), 3.06 (d, J = 2.0 Hz, 3H), 2.86 (t, J = 7.4 Hz, 2H), 2.18-2.11 (m, 1H), 1.72-1.64 (m, 1H), 1.21- 1.13 (m, 1H); LCMS (electrospray) m/z 522.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methyl(2-(pyridin-4-yl)ethyl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







617


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1H NMR (400 MHz, DMSO-d6) δ 13.70 (s, 1H), 11.21 (s, 1H), 8.91 (d, J = 0.8 Hz, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.58 (d, J = 2.0 Hz, 1H), 8.01 (s, 1H), 7.85 (s, 1H), 7.01-6.99 (m, 2H), 5.04-4.85 (m, 1H), 3.55 (s, 3H), 2.18-2.11 (m, 1H), 1.71-1.64 (m, 1H), 1.21-1.14 (m, 1H); LCMS (electrospray) m/z 496.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methyl(1,3,5-triazin-2-yl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







618


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1H NMR (400 MHz, DMSO-d6) δ 13.67 (s, 1H), 11.21 (s, 1H), 8.88 (d, J = 2.0 Hz, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.38 (s, 1H), 8.01 (s, 1H), 7.85 (s, 1H), 7.01-6.99 (m, 2H), 5.05-4.84 (m, 1H), 3.63 (s, 3H), 2.18-2.11 (m, 1H), 1.71-1.63 (m, 1H), 1.21- 1.11 (m, 1H); LCMS (electrospray) m/z 496.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(methyl(1,2,4-triazin-3-yl)amino)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







619


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1H NMR (400 MHz, DMSO-d6) δ 13.29 (s, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.3 Hz, 1H), 7.87 (s, 1H), 7.71 (s, 1H), 6.92-6.90 (m, 2H), 5.18-5.17 (m, 1H), 5.03-4.85 (m, 1H), 4.03 (s, 1H), 2.17-2.09 (m, 1H), 1.72-1.62 (m, 1H), 1.23 (d, J = 6.4 Hz, 6H), 1.20-1.15 (m, 1H); LCMS (electrospray) m/z 445.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(isopropylamino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







620


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1H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 11.19 (s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 6.94 (s, 1H), 6.92 (s, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 3.93 (t, J = 9.6 Hz, 1H), 2.84 (s, 3H), 2.18-2.07 (m, 3H), 1.96-1.86 (m, 2H), 1.72-1.57 (m, 3H), 1.28-1.12 (m, 1H); LCMS (electrospray) m/z 471.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-





(cyclobutyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







621


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1H NMR (400 MHz, DMSO-d6) δ 13.81 (s, 1H), 11.21 (s, 1H), 8.69 (d, J = 7.2 Hz, 1H), 7.88 (s, 1H), 7.81 (s, 1H), 6.97 (s, 1H), 6.95 (s, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 3.02 (q, J = 7.3 Hz, 2H), 2.18- 2.08 (m, 1H), 1.72-1.62 (m, 1H), 1.22-1.13 (m, 4H); LCMS (electrospray) m/z 448.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-(ethylthio)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







622


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (s, 1H), 11.20 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.89 (s, 1H), 7.76 (d, J = 1.2 Hz, 1H), 6.95-6.93 (m, 2H), 5.03- 4.84 (m, 1H), 3.56 (s, 1H), 2.89 (d, J = 3.6 Hz, 3H), 2.18-2.11 (m, 1H), 1.72-1.62 (m, 1H), 1.22- 1.15 (m, 7H); LCMS (electrospray) m/z 459.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(isopropyl(methyl)amino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







623


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1H NMR (400 MHz, DMSO-d6) δ 13.66 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 7.97 (s, 1H), 7.80 (m, 1H), 6.97-6.94 (m, 2H), 5.05-4.85 (m, 1H), 3.84 (t, J = 7.8 Hz, 2H), 3.60 (t, J = 8.0 Hz, 2H), 2.82 (s, 3H), 2.18-2.11 (m, 1H), 1.73-1.62 (m, 1H), 1.21-1.15 (m, 1H); LCMS (electrospray) m/z 486.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-





methyl-2-oxoimidazolidin-1-yl)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







624


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1H NMR (400 MHz, DMSO-d6) δ 13.13 (s, 1H), 11.17 (s, 1H), 8.62 (d, J = 6.8 Hz, 1H), 7.86 (s, 1H), 7.69 (d, J = 0.8 Hz, 1H), 6.96-6.86 (m, 2H), 5.05- 4.83 (m, 1H), 4.68-4.58 (m, 2H), 4.37-4.30 (m, 1H), 4.27-4.16 (m, 2H), 3.27 (s, 3H), 2.18-2.09 (m, 1H), 1.73-1.61 (m, 1H), 1.20-1.12 (m, 1H); LCMS (electrospray) m/z 473.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-





methoxyazetidin-1-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







625


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1H NMR (400 MHz, DMSO-d6) δ 13.41 (s, 1H), 11.19 (s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.87 (s, 1H), 7.76 (s, 1H), 6.94 (s, 1H), 6.92 (s, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 3.01-2.98 (m, 4H), 2.18-2.08 (m, 1H), 1.72-1.62 (m, 1H), 1.22-1.13 (m, 4H), 0.63-0.60 (m, 2H), 0.49-0.45 (m, 2H); LCMS (electrospray) m/z 457.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-





(cyclopropyl(methyl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







626


embedded image



1H NMR (400 MHz, DMSO-d6) δ 14.02 (s, 1H), 11.24 (s, 1H), 10.49 (s, 1H), 8.73 (d, J = 7.2 Hz, 1H), 8.07 (s, 1H), 7.89-7.87 (m, 1H), 7.02 (s, 1H), 7.00 (dd, J = 7.0, 1.8 Hz, 1H), 5.06-4.85 (m, 1H), 2.19-2.12 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.15 (m, 1H); LCMS (electrospray) m/z 416.05 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-formyl-





1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)-2-fluorocyclopropane-1-carboxamide







627


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.06 (s, 1H), 11.13 (s, 1H), 8.58 (d, J = 6.8 Hz, 1H), 7.81 (s, 1H), 7.64 (s, 1H), 6.90-6.81 (m, 2H), 5.02-4.80 (m, 1H), 4.49-4.40 (m, 2H), 4.20-4.04 (m, 2H), 3.53 (d, J = 6.4 Hz, 2H), 3.25 (s, 3H), 2.99-2.88 (m, 1H), 2.15-2.04 (m, 1H), 1.68-1.57 (m, 1H), 1.17- 1.09 (m, 1H); LCMS (electrospray) m/z 487.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-





(methoxymethyl)azetidin-1-yl)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







628


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1H NMR (400 MHz, DMSO-d6) δ 13.62 (s, 1H), 11.20 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 7.95 (d, J = 2.0 Hz, 1H), 7.74 (d, J = 1.2 Hz, 1H), 6.96 (s, 1H), 6.91 (dd, J = 1.6, 7.2 Hz, 1H), 5.06-4.84 (m, 1H), 3.69-3.61 (m, 4H), 3.47-3.39 (m, 4H), 2.18-2.10 (m, 1H), 1.73-1.61 (m, 1H), 1.21-1.12 (m, 1H); LCMS (electrospray) m/z 521.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-(1,1-





dioxidothiomorpholino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







629


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1H NMR (400 MHz, DMSO-d6) δ 13.57 (s, 1H), 11.20 (s, 1H), 10.49 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 8.07 (s, 1H), 7.89-7.87 (m, 1H), 7.02 (s, 1H), 7.00 (dd, J = 7.0, 1.8 Hz, 1H), 5.06-4.85 (m, 1H), 2.19-2.12 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.15 (m, 1H); LCMS (electrospray) m/z 416.05 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(hydroxymethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







630


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1H NMR (400 MHz, DMSO-d6) δ 13.41 (s, 1H), 11.19 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.91 (s, 1H), 7.76 (s, 1H), 6.94 (s, 1H), 6.87 (s, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 4.55-4.51 (m, 2H), 3.98-3.94 (m, 2H), 2.85-2.80 (m, 1H), 2.15-2.08 (m, 1H), 1.72-1.62 (m, 1H), 1.29-1.12 (m, 4H), 0.86-0.79 (m, 1H); LCMS (electrospray) m/z 457.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-





methylazetidin-1-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







631


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1H NMR (400 MHz, DMSO-d6) δ 13.49 (s, 1H), 11.19 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.91 (s, 1H), 7.74 (t, J = 1.2 Hz, 1H), 6.95 (s, 1H), 6.91 (dd, J = 2.4, 7.2 Hz, 1H), 5.06-4.84 (m, 1H), 3.53-3.39 (m, 4H), 2.90-2.82 (m, 4H), 2.19-2.09 (m, 1H), 1.73-1.61 (m, 1H), 1.21-1.12 (m, 1H); LCMS (electrospray) m/z 489.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





thiomorpholino-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







632


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1H NMR (400 MHz, DMSO-d6) δ 13.41 (s, 1H), 11.20 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 6.92 (s, 1H), 6.87 (s, J = 7.2 Hz, 1H), 5.04-4.84 (m, 1H), 4.55-4.44 (m, 4H), 2.15-2.08 (m, 1H), 1.72-1.62 (m, 1H), 1.66 (d, J = 22 Hz, 1H), 1.29-1.12 (m, 1H); LCMS (electrospray) m/z 475.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-





fluoro-3-methylazetidin-1-yl)-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







633


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.90 (br s, 1H), 11.23 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 7.99 (d, J = 17.2 Hz, 1H), 7.85-7.83 (m, 1H), 7.00 (s, 1H), 6.97 (dd, J = 7.0, 2.0 Hz, 1H), 5.06-4.85 (m, 1H), 2.18- 2.11 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.14 (m, 1H); LCMS (electrospray) m/z 439.05 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-7-((E)-2-





cyanovinyl)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







634


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1H NMR (400 MHz, DMSO-d6) δ 13.91 (s, 1H), 11.22 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 7.99 (s, 1H), 7.83-7.80 (m, 1H), 6.98 (s, 1H), 6.96 (dd, J = 7.0, 1.8 Hz, 1H), 5.93 (s, 1H), 5.81 (s, 1H), 5.05-4.84 (m, 1H), 2.18-2.11 (m, 1H), 1.72-1.62 (m, 1H), 1.20-1.13 (m, 1H); LCMS (electrospray) m/z 420.00 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





(fluoromethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







635


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.59 (s, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.93 (s, 1H), 7.75 (t, J = 1.4 Hz, 1H), 6.96 (s, 1H), 6.92 (dd, J = 7.1, 1.6 Hz, 1H), 5.08-4.80 (m, 1H), 3.89 (t, J = 11.5 Hz, 2H), 3.32-3.24 (m, 2H), 3.24-3.10 (m, 2H), 2.97 (d, J = 11.5 Hz, 2H), 2.22-2.09 (m, 1H), 1.77-1.61 (m, 1H), 1.22-1.11 (m, 1H); LCMS (electrospray) m/z 505.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-





oxidothiomorpholino)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







636


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1H NMR (400 MHz, DMSO-d6) δ 13.44 (s, 1H), 11.18 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.75 (s, 1H), 7.03-6.84 (m, 2H), 6.42 (s, 1H), 5.10-4.83 (m, 1H), 4.83-4.49 (m, 2H), 2.24-2.04 (m, 1H), 1.76-1.59 (m, 1H), 1.21-1.05 (m, 1H); LCMS (electrospray) m/z 442.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-





((cyanomethyl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







637


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1H NMR (400 MHz, DMSO-d6) δ 13.63-14.10 (1H), 11.21 (s, 1H), 8.71 (d, J = 7.1 Hz, 1H), 8.09 (s, 1H), 7.82 (t, J = 1.4 Hz, 1H), 7.28 (s, 2H), 6.99- 6.96 (m, 2H), 6.41 (t, J = 2.2 Hz, 2H), 5.06-4.85 (m, 1H), 2.19-2.12 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.14 (m, 1H); LCMS (electrospray) m/z 453.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1H-





pyrrol-1-yl)-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







638


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1H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 11.20 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.92 (s, 1H), 7.80 (d, J = 1.1 Hz, 1H), 7.02-6.87 (m, 2H), 5.76 (s, 1H), 5.09-4.81 (m, 1H), 2.23-2.07 (m, 1H), 1.75-1.61 (m, 7H), 1.21-1.10 (m, 2H); LCMS (electrospray) m/z 470.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-((2-





cyanopropan-2-yl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







639


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1H NMR (400 MHz, DMSO-d6) δ 13.67-13.30 (m, 1H), 11.18 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.94 (s, 1H), 7.79 (d, J = 1.0 Hz, 1H), 7.05-6.79 (m, 2H), 5.63 (s, 1H), 5.38 (s, 1H), 5.15-4.77 (m, 1H), 2.21 (s, 3H), 2.18-2.09 (m, 1H), 1.74-1.60 (m, 1H), 1.25-1.12 (m, 1H); LCMS (electrospray) m/z 428.1 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(prop-





1-en-2-yl)-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







640


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1H NMR (400 MHz, DMSO-d6) δ 13.61 (br d, J = 2.1 Hz, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 7.76 (d, J = 0.9 Hz, 1H), 7.07-6.84 (m, 2H), 5.10-4.76 (m, 1H), 3.62 (td, J = 7.0, 14.1 Hz, 1H), 2.15 (td, J = 6.9, 13.8 Hz, 1H), 1.76-1.59 (m, 1H), 1.44 (d, J = 7.0 Hz, 6H), 1.18 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS (electrospray) m/z 430.2 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





isopropyl-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







641


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1H NMR (400 MHz, DMSO-d6) δ 13.32 (s, 1H), 11.03 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.95 (s, 1H), 7.73 (s, 1H), 6.98-6.88 (m, 2H), 6.24-5.96 (m, 1H), 5.05-4.81 (m, 1H), 3.34-3.24 (m, 1H), 2.22-2.09 (m, 1H), 1.78-1.58 (m, 4H), 1.22-1.11 (m, 1H); LCMS (electrospray) m/z 456.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-((1-





cyanoethyl)amino)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







642


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1H NMR (400 MHz, DMSO-d6) δ 13.11 (s, 1H), 10.83 (s, 1H), 8.54 (d, J = 7.1 Hz, 1H), 7.90-7.72 (m, 1H), 7.62 (s, 1H), 6.88 (s, 1H), 6.86-6.79 (m, 1H), 5.56-5.24 (m, 1H), 5.00-4.74 (m, 1H), 4.34- 3.50 (m, 4H), 2.38-2.03 (m, 3H), 1.75-1.56 (m, 1H), 1.19-1.04 (m, 1H); LCMS (electrospray) m/z 475.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-





fluoropyrrolidin-1-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







643


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1H NMR (400 MHz, DMSO-d6) δ 13.83 (s, 1H), 11.08 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.99 (s, 1H), 7.82 (d, J = 5.5 Hz, 1H), 7.67-6.83 (m, 7H), 5.59- 5.07 (m, 3H), 5.05-4.79 (m, 1H), 2.23-2.09 (m, 1H), 1.79-1.62 (m, 2H), 1.43 (d, J = 7.1 Hz, 2H), 1.23-1.09 (m, 1H); LCMS (electrospray) m/z 591.20 (M + H)+.

J






benzyl (5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazol-7-yl)(1-cyanoethyl)carbamate







644


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1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.72 (d, J = 7.2 Hz, 1H), 8.07 (s, 1H), 7.87 (d, J = 1.0 Hz, 1H), 7.05-6.99 (m, 2H), 6.95 (br s, 1H), 6.27 (t, J = 3.2 Hz, 1H), 6.16-6.11 (m, 1H), 5.08-4.84 (m, 1H), 2.16 (td, J = 6.8, 14.1 Hz, 1H), 2.10-2.04 (m, 3H), 1.78-1.63 (m, 1H), 1.23-1.15 (m, 1H); LCMS (electrospray) m/z 467.1 (M + H+).

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(2-





methyl-1H-pyrrol-1-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







645


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1H NMR (400 MHz, DMSO-d6) δ 13.95-13.76 (m, 1H), 10.54 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 8.47 (s, 1H), 7.98 (s, 1H), 7.76 (d, J = 1.0 Hz, 1H), 6.91 (dd, J = 2.0, 7.1 Hz, 1H), 6.76 (s, 1H), 4.92- 4.85 (m, 1H), 4.03-3.91 (m, 2H), 3.76 (dd, J = 1.3, 10.6 Hz, 1H), 2.57 (s, 3H), 2.38-2.29 (m, 1H), 1.06 (d, J = 7.2 Hz, 3H); LCMS (electrospray) m/z 476.1(M + H+).

J






(3S,4R)-4-methyltetrahydrofuran-3-yl (5-





(5-chloro-6-fluoro-7-(methylthio)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-





yl)carbamate







646


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1H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 11.07 (s, 1H), 9.60-9.58 (m, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.87 (s, 1H), 7.72 (s, 1H), 7.53 (s, 1H), 7.28 (s, 1H), 6.94 (s, 1H), 6.90 (dd, J = 7.1, 1.8 Hz, 1H), 3.80 (s, 3H), 2.99 (7H), 2.32 (dd, J = 9.1, 4.3 Hz, 2H), 2.00-1.95 (m, 1H), 1.68-1.55 (m, 1H), 1.37-1.18 (m, 2H), 0.97 (d J = 6.2 Hz 3H). LCMS (electrospray) m/z 507.1 (M + H)+.

J






(1S,2R,3S)-N-(5-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-methyl-





3-(1-methyl-1H-pyrazol-4-





yl)cyclopropane-1-carboxamide







647


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1H NMR (400 MHz, DMSO-d6) δ 13.52 (s, 1H), 9.05 (s, 1H), 8.57 (d, J = 7.0 Hz, 1H), 7.87 (s, 1H), 7.65 (dd, J = 1.77, 0.79 Hz, 1H), 6.85-6.81 (m, 2H), 6.72 (s, 1H), 3.01 (s, 6H), 2.62-2.58 (m, 1H), 0.69- 0.65 (m, 2H), 0.46-0.44 (m, 2H); LCMS (electrospray) m/z 428.0 (M + H)+.

J






1-(5-(5-chloro-7-(dimethylamino)-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-3-cyclopropylurea







648


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1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.55 (s, 1H), 7.87 (s, 1H), 7.71 (s, 1H), 7.53 (s, 1H), 7.26 (s, 1H), 6.97 (s, 1H), 6.90 (dd , J = 7.1, 1.8 Hz, 1H), 3.77 (s, 3H), 3.02 (d, J = 2.2 Hz, 6H), 2.22-2.14 (m, 1H), 2.09 (d, J = 4.5 Hz, 3 H), 1.63-1.54 (m, 1H), 1.26 (d, J = 6.1 Hz, 5H), 1.06 (t, J = 7.0 Hz, 2H); LCMS (electrospray) m/z 507.1 (M + H)+.

J






(1S,2S,3S)-N-(5-(5-chloro-7-





(dimethylamino)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-methyl-





3-(1-methyl-1H-pyrazol-4-





yl)cyclopropane-1-carboxamide







649


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1H NMR (400 MHz, DMSO-d6) δ 11.20 (s, 1H), 8.71 (d, J = 7.1 Hz, 1H), 8.13 (s, 1H), 7.84-7.80 (m, 1H), 7.50-7.38 (m, 1H), 7.00 (s, 1H), 6.97 (dd , J = 7.19, 1.94 Hz, 1 H), 6.66 (dd, J = 2.94, 1.69 Hz, 1 H), 5.09-4.81 (m, 1H), 3.15-2.95 (m, 5H), 2.20- 2.11 (m, 1H), 1.75-1.61 (m, 1H), 1.22-1.12 (m, 1H); LCMS (electrospray) m/z 524.1 (M + H)+.

J






1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazol-7-yl)-N,N-dimethyl-1H-





pyrrole-3-carboxamide







650


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1H NMR (400 MHz, DMSO-d6) δ 14.17-13.20 (m, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.94 (s, 1H), 7.76 (s, 1H), 7.00-6.89 (m, 2H), 5.10- 4.80 (m, 1H), 4.74 (br s, 1H), 2.15 (quin, J = 6.9 Hz, 1H), 1.77-1.59 (m, 1H), 1.37 (d, J = 6.0 Hz, 6H), 1.26-1.09 (m, 1H); LCMS (electrospray) m/z 446.0 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-





isopropoxy-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







651


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1H NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.90 (d, J = 1.1 Hz, 1H), 7.76 (t, J = 1.1 Hz, 1H), 6.96-6.92 (m, 2H), 5.05-4.84 (m, 1H), 3.59 (q, J = 8.6 Hz, 1H), 2.18-1.91 (m, 8H), 1.72-1.62 (m, 3H), 1.24-1.06 (m, 1H); LCMS (electrospray) m/z 456.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-cyclopentyl-6-





fluoro-1H-indazol-4-yl)pyrazolo[1,5-





a]pyridin-2-yl)-2-fluorocyclopropane-1-





carboxamide







652


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1H NMR (400 MHz, DMSO-d6) δ 13.35 (s, 1H), 11.15 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.90 (s, 1H), 7.79 (t, J = 1.4 Hz, 1H), 7.59 (s, 1H), 6.93 (dd, J = 6.3, 2.5 Hz, 2H), 5.74 (t, J = 7.4 Hz, 1H), 5.01-4.80 (m, 1H), 2.15-2.08 (m, 1H), 1.64 (dtd, J = 23.2, 6.9, 3.8 Hz, 1H), 1.17-1.10 (m, 1H); LCMS (electrospray) m/z 487.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(2,2,2-





trifluoro-1-hydroxyethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







653


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.25 (br s, 1H), 11.14 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.85 (br s, 1H), 7.70 (s, 1H), 6.92 (s, 1H), 6.91-6.88 (m, 1H), 5.32 (br d, J = 9.5 Hz, 1H), 5.06-4.82 (m, 1H), 2.21-2.06 (m, 1H), 1.75-1.61 (m, 1H), 1.26 (d, J = 6.4 Hz, 3H), 1.21-1.14 (m, 1H), 1.04 (br s, 1H), 0.48-0.35 (m, 2H), 0.34-0.18 (m, 2H); LCMS (electrospray) m/z 471.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-((1-





cyclopropylethyl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







654


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.85 (m, 1H), 7.70 (d, J = 1.0 Hz, 1H), 6.91 (m, 2H), 5.65 (m, 1H), 4.95 (m, 1H), 3.31 (s, 2H), 2.14 (m, 1H), 1.67 (m, 1H), 1.18 (m, 1H), 1.08 (m, 1H), 0.48 (d, J = 7.1 Hz, 2H), 0.27 (m, 2H); LCMS (electrospray) m/z 457.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-





((cyclopropylmethyl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







655


embedded image



1H NMR (400 MHz, DMSO-d6) δ13.56 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.91 (s, 1H), 7.78 (s, 1H), 6.96 (br d, J = 2.2 Hz, 1H), 6.95-6.91 (m, 1H), 5.07-4.82 (m, 1H), 3.85-3.74 (m, 2H), 3.67 (br s, 1H), 3.25 (s, 3H), 2.21-2.09 (m, 1H), 1.74-1.60 (m, 1H), 1.40 (br d, J = 6.1 Hz, 3H), 1.22-1.12 (m, 1H); LCMS (electrospray) m/z 460.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((R)-1-





methoxypropan-2-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







656


embedded image



1H NMR (400 MHz, DMSO-d6) δ13.56 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.91 (s, 1H), 7.78 (d, J = 1.0 Hz, 1H), 6.96 (d, J = 2.6 Hz, 1H), 6.95-6.92 (m, 1H), 5.07-4.79 (m, 1H), 3.85-3.73 (m, 2H), 3.67 (br s, 1H), 3.25 (s, 3H), 2.15 (td, J = 6.8, 13.7 Hz, 1H), 1.73-1.61 (m, 1H), 1.40 (br d, J = 6.2 Hz, 3H), 1.18 (ddd, J = 2.8, 6.2, 12.3 Hz, 1H); LCMS (electrospray) m/z 460.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-((S)-1-





methoxypropan-2-yl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







657


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 8.04-7.83 (m, 1H), 7.71 (d, J = 1.0 Hz, 1H), 6.92 (s, 1H), 6.90 (dd, J = 7.1, 2.0 Hz, 1H), 6.33-5.92 (m, 1H), 5.67- 5.51 (m, 1H), 5.07-4.81 (m, 1H), 4.53-4.03 (m, 1H), 2.21-2.05 (m, 1H), 1.75-1.57 (m, 1H), 1.32 (d, J = 6.6 Hz, 3H), 1.17 (ddt, J = 12.26, 9.07, 6.16, 6.16 Hz, 1 H); LCMS (electrospray) m/z 481.0 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-((1,1-





difluoropropan-2-yl)amino)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







658


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.92 (s, 1H), 7.78 (d, J = 1.0 Hz, 1H), 6.98 (s, 1H), 6.94 (dd, J = 2.0, 7.1 Hz, 1H), 5.57 (dd, J = 5.4, 10.8 Hz, 1H), 5.18 (d, J = 3.4 Hz, 1H), 5.07-4.83 (m, 1H), 4.55 (dd, J = 3.7 Hz, 1H), 4.47 (dd, J = 4.6, 8.9 Hz, 1H), 3.72 (dd, J = 1.2, 9.0 Hz, 1H), 2.26 (dd, J = 5.4, 12.5 Hz, 1H), 2.20-2.02 (m, 2H), 1.76-1.62 (m, 1H), 1.28-1.12 (m, 2H); LCMS (electrospray) m/z 474.2 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(4-





hydroxytetrahydrofuran-2-yl)-1H-indazol-





4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







659


embedded image



1H NMR (400 MHz, DMSO-d6) δ13.80-13.56 (m, 1H), 11.18 (s, 1H), 8.77 (br d, J = 6.6 Hz, 1H), 8.67 (d, J = 7.1 Hz, 1H), 8.06 (s, 1H), 7.94 (s, 1H), 7.77 (d, J = 0.9 Hz, 1H), 6.96 (s, 1H), 6.93 (dd, J = 1.8, 7.2 Hz, 1H), 5.56 (br t, J = 7.2 Hz, 1H), 5.11-4.78 (m, 1H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.73-1.62 (m, 1H), 1.58 (d, J = 7.2 Hz, 3H), 1.18 (tdd, J = 6.4, 9.0, 12.4 Hz, 1H); LCMS (electrospray) m/z 459.2 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-





formamidoethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







660


embedded image



1H NMR (400 MHz, DMSO-d6) δ13.73-13.44 (m, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 8.46- 8.32 (m, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 6.96 (s, 1H), 6.93 (dd, J = 2.0, 7.2 Hz, 1H), 5.46 (br t, J = 7.0 Hz, 1H), 5.09-4.77 (m, 1H), 2.20-2.07 (m, 3H), 1.78-1.61 (m, 1H), 1.55 (br d, J = 7.2 Hz, 3H), 1.27-1.07 (m, 1H), 0.95 (t, J = 7.6 Hz, 3H); LCMS (electrospray) m/z 487.2 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-





propionamidoethyl)-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







661


embedded image



1H NMR (400 MHz, DMSO-d6) δ13.77-13.42 (m, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 8.54- 8.48 (m, 1H), 8.34 (br s, 1H), 7.91 (s, 1H), 7.77 (d, J = 0.7 Hz, 1H), 6.95 (s, 1H), 6.93 (dd, J = 2.0, 7.2 Hz, 1H), 5.45 (br t, J = 7.1 Hz, 1H), 5.05-4.83 (m, 1H), 3.08 (br t, J = 8.3 Hz, 1H), 2.19-2.01 (m, 3H), 1.99-1.83 (m, 3H), 1.75-1.61 (m, 2H), 1.55 (d, J = 7.2 Hz, 3H), 1.17 (ddd, J = 2.8, 6.1, 12.3 Hz, 1H); LCMS (electrospray) m/z 513.2 (M + H)+.

J






N-(1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-





fluorocyclopropane-1-





carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-





1H-indazol-7-





yl)ethyl)cyclobutanecarboxamide







662


embedded image



1H NMR (400 MHz, DMSO-d6) δ14.24-12.89 (m, 1H), 11.19 (s, 1H), 10.54-9.82 (m, 1H), 8.68 (d, J = 7.0 Hz, 1H), 7.97 (s, 1H), 7.00-6.92 (m, 2H), 5.56 (q, J = 7.0 Hz, 1H), 5.07-4.81 (m, 1H), 2.21- 2.08 (m, 1H), 1.69 (d, J = 7.0 Hz, 3H), 1.66-1.60 (m, 1H), 1.26-1.09 (m, 1H); LCMS (electrospray) m/z 527.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-





(2,2,2-trifluoroacetamido)ethyl)-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







663


embedded image



1H NMR (400 MHz, DMSO-d6) δ13.90-13.44 (m, 1H), 11.21-11.13 (m, 1H), 8.94-8.80 (m, 1H), 8.66 (d, J = 7.2 Hz, 1H), 8.56 (s, 1H), 7.96-7.86 (m, 1H), 7.80-7.73 (m, 1H), 6.95 (s, 1H), 6.94-6.91 (m, 1H), 5.54-5.41 (m, 1H), 4.93 (s, 1H), 2.22-2.09 (m, 1H), 1.90-1.82 (m, 3H), 1.73-1.61 (m, 1H), 1.54 (d, J = 7.0 Hz, 3H), 1.21-1.13 (m, 1H); LCMS (electrospray) m/z 473.1 (M + H)+.

J






(1S,2S)-N-(5-(7-(1-acetamidoethyl)-5-





chloro-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







664


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.73 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.1 Hz, 1H), 7.97 (s, 1H), 7.77 (s, 1H), 7.00 (s, 1H), 6.93 (dd, J = 7.1, 2.2 Hz, 1H), 6.40 (s, 1H), 5.05-4.85 (m, 1H), 3.20 (s, 3H), 2.58 (d, J = 4.4 Hz, 3H), 2.18-2.11 (m, 1H), 1.72- 1.64 (m, 1H), 1.21-1.15 (m, 1H) m/z 474.10 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-(1,3-





dimethylureido)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide







665


embedded image



1H NMR (400 MHz, DMSO-d6) δ 14.06-13.53 (m, 1H), 11.18 (s, 1H), 9.82-9.45 (m, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.95 (s, 1H), 7.78 (d, J = 0.9 Hz, 1H), 6.99-6.91 (m, 2H), 6.44-6.11 (m, 1H), 5.61-5.51 (m, 1H), 5.05-4.83 (m, 1H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.70 (dt, J = 3.7, 6.9 Hz, 1H), 1.65 (d, J = 7.2 Hz, 3H), 1.24-1.12 (m, 1H); LCMS (electrospray) m/z 509.2 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-(1-(2,2-





difluoroacetamido)ethyl)-6-fluoro-1H-





indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-





2-fluorocyclopropane-1-carboxamide







666


embedded image



1H NMR (400 MHz, DMSO-d6) δ 13.33 (s, 1H), 11.20 (s, 1H), 8.67 (t, J = 8.0 Hz, 1H), 7.91 (s, 1H), 7.82 (t, J = 1.1 Hz, 1H), 6.97 (dd, J = 7.1, 2.2 Hz, 2H), 5.04-4.85 (m, 2H), 3.90 (t, J = 6.3 Hz, 1H), 3.38 (d, J = 6.6 Hz, 3H), 3.25 (s, 3H), 2.14 (t, J = 8.0 Hz, 1H), 1.71-1.64 (m, 1H), 1.18 (dd, J = 12.1, 8.8 Hz, 1H), 0.95 (d, J = 6.6 Hz, 3H); LCMS (electrospray) m/z 490.1 (M + H)+.

J






(1S,2S)-N-(5-(5-chloro-7-((1S,2R)-1,2-





dimethoxypropyl)-6-fluoro-1H-indazol-4-





yl)pyrazolo[1,5-a]pyridin-2-yl)-2-





fluorocyclopropane-1-carboxamide









Evaluation of Compounds


HPK1 Kinase Assay


HPK1 kinase activity was measured by Promega's ADP-Glo™ kinase assay. In this assay, 5 ng of recombinant human HPK1 (signalchem) is incubated with 5 μL of compounds (0.5% DMSO), 5 μL of MBP (0.5 μg/μl) and 5 μL of ATP (25 μM) in buffer (40 mM Tris, 7.5; 20 mM MgCl2; 0.1 mg/ml BSA; 5 μM DTT). The assay was started by incubating the reaction mixture in a 96-well plate at 30′ C for 40 minutes. After the incubation, 25 uL ADP-Glo reagent was added and the reaction was incubated at room temperature for 40-min to stop the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 uL per well of detection reagent. Luminescence was detected after 30-min room temperature incubation with the Molecular device I3X plate reader. The IC50 values were calculated from a series of percent inhibition values determined at a range of inhibitor concentration using software routines as implemented in the GraphPad Prism 7 software and SigmaPlot13.0.


Table 2 shows IC50 values of the invented compounds which represent + for >1000 nM, ++ for 501-1000 nM, +++ for 101-500 nM, ++++ for <100 nM.









TABLE 2







In vitro activity against HPK1 data








Example
HPK1 IC50 (nM)











1
+++


2
+++


3
+


4
++


5
+++


6
+++


7
+++


8
+


9
+


10
+


11
++


12
+


13
+


14
+


15
+++


16
+++


17
+++


18
+


19
+


20
+


21
+


22
+


23
+


24
+++


25
++


26
+


27
+


28
+++


29
+++


30
+++


31
+


32
+++


33
+++


34
+


35
+++


36
+++


37
+++


38
+


39
+++


40
++++


41
+++


42
+++


43
++++


44
++


45
+


46
++++


47
++++


48
++++


49
++


50
++++


51
++++


52
+


53
+++


54
+


55
+++


56
++++


57
++++


58
++++


59
++++


60
+


61
++++


62
+++


63
++++


64
++++


65
++++


66
++++


67
++++


68
++++


69
++++


70
++++


71
++++


72
+++


73
++++


74
+++


75
+++


76
+++


77
++++


78
+++


79
++++


80
++++


81
++++


82
++++


83
+++


84
++++


85
++++


86
++++


87
++++


88
++++


89
++++


90
++++


91
+++


92
++++


93
++++


94
++++


95
++++


96
++++


97
++++


98
++++


99
++++


100
++++


101
++++


102
++++


103
++++


104
++++


105
++++


106
++++


107
++++


108
++++


109
++++


110
++++


111
++++


112
+++


113
++++


114
+++


115
++++


116
++++


117
++++


118
++++


119
+++


120
++++


121
+


122
++++


123
++++


124
+


125
++++


126
++++


127
++++


128
+++


129
++++


130
++++


131
+++


132
+++


133
++++


134
++++


135
+


136
++++


137
++++


138
++++


139
++++


140
+


141
+


142
+


143
++++


144
+++


145
+


146
+++


147
++++


148
+


149
++++


150
++++


151
+


152
++++


153
++++


154
++++


155
++++


156
++++


157
+++


158
+++


159
++++


160
++++


161
++++


162
++++


163
++++


164
+


165
++++


166
++++


167
++++


168
+++


169
++++


170
++++


171
+


172
++++


173
++++


174
++++


175
++++


176
++++


177
+++


178
++++


179
++++


180
+++


181
+++


182
+


183
++++


184
++++


185
+++


186
++++


187
++++


188
+


189
++++


190
++++


191
++++


192
++++


193
++++


194
++++


195
+++


196
++++


197
++++


198
++++


199
++++


200
++++


201
+


202
++++


203
++++


204
++++


205
++++


206
+++


207
++++


208
++++


209
++++


210
++++


211
++++


212
+


213
+


214
+


215
+


216
+


217
++++


218
++++


219
+++


220
+


221
+++


222
++


223
++++


224
+++


225
+


226
++++


227
+


228
+


229
++++


230
+


231
+


232
++++


233
++


234
+


235
++++


236
++++


237
++++


238
++++


239
++++


240
++


241
+


242
+++


243
++++


244
+++


245
++++


246
++++


247
++++


248
++++


249
+++


250
++++


251
+


252
++++


253
++++


254
++++


255
++++


256
++++


257
++++


258
++++


259
+


260
++++


261
++++


262
++++


263
++++


264
++++


265
++++


266
++++


267
+++


268
++++


269
++++


270
+++


271
++++


272
++++


273
++++


274
++++


275
++++


276
++++


277
+++


278
+


279
++++


280
++++


281
++++


282
++++


283
++++


284
+++


285
++++


286
+


287
++++


288
++++


289
+


290
++++


291
++++


292
++++


293
++++


294
++++


295
++++


296
++++


297
++++


298
++++


299
+++


300
++++


301
++++


302
+++


303
++++


304
++++


305
++++


306
++++


307
++++


308
+++


309
++++


310
++++


311
++++


312
++++


313
+


314
+


315
++++


316
++++


317
++++


318
++++


319
++++


320
++++


321
++++


322
+++


323
++++


324
++++


325
+


326
++++


327
++++


328
++++


329
++++


330
++++


331
++++


332
++++


333
++++


334
++++


335
++++


336
++++


337
++++


338
+++


339
++++


340
+++


341
++++


342
++++


343
++++


344
+++


345
++++


346
++++


347
++++


348
++++


349
++++


350
++++


351
++++


352
+++


353
++++


354
+


355
+


356
++++


357
++++


358
++++


359
++++


360
++++


361
++++


362
++++


363
++++


364
++++


365
++++


366
++++


367
++++


368
++++


369
++++


370
++++


371
++++


372
++++


373
++++


374
++++


375
++++


376
++++


377
++++


378
++++


379
++++


380
++++


381
++++


382
+++


383
++++


384
++++


385
++++


386
++++


387
++++


388
++++


389
++++


390
++++


391
++++


392
++++


393
++++


394
++++


395
++++


396
++++


397
++++


398
++++


399
++++


400
++++


401
++++


402
+++


403
+


404
++++


405
++++


406
++++


407
++++


408
++++


409
++++


410
++++


411
++++


412
++++


413
++++


414
++++


415
++++


416
++++


417
++++


418
++++


419
++++


420
++++


421
++++


422
++++


423
++++


424
++++


425
++++


426
++++


427
++++


428
++++


429
++++


430
++++


431
+++


432
++++


433
++++


434
++++


435
++++


436
++++


437
++++


438
++++


439
++++


440
++++


441
++++


442
++++


443
++++


444
++++


445
++++


446
++++


447
++++


448
++++


449
+++


450
+


451
++++


452
++++


453
++


454
+++


455
++++


456
++


457
++++


458
++++


459
+++


460
++++


461
+


462
++++


463
++++


464
++++


465
++++


466
++++


467
++++


468
++++


469
++++


470
+++


471
+++


472
+


473
+


474
+++


475
+


476
++++


477
++++


478
++


479
++++


480
++++


481
++++


482
++++


483
++++


484
++++


485
++++


486
++++


487
++++


488
++++


489
++++


490
++++


491
++++


492
++++


493
++++


494
++++


495
++++


496
++++


497
++++


498
++++


499
++++


500
+++


501
++++


502
++++


503
++++


504
++++


505
++++


506
++++


507
++++


508
++++


509
++++


510
++++


511
++++


512
++++


513
++++


514
++++


515
++++


516
++++


517
++++


518
++++


519
++++


520
++++


521
++++


522
++++


523
++++


524
++++


525
++++


526
++++


527
++++


528
++++


529
++++


530
++++


531
++++


532
++++


533
++++


534
++++


535
++++


536
++++


537
++++


538
++++


539
++++


540
++++


541
++++


542
++++


543
++++


544
++++


545
++++


546
++++


547
++++


548
++++


549
+


550
++++


551
+


552
++++


553
++++


554
++++


555
++++


556
++++


557
++++


558
++++


559
++++


560
++++


561
++++


562
++++


563
++++


564
++++


565
++++


566
+++


567
++++


568
++++


569
++++


570
++++


571
++++


572
++++


573
++++


574
++++


575
++++


576
+


577
++++


578
++++


579
++++


580
++++


581
++++


582
++++


583
++++


584
+++


585
++++


586
++++


587
++++


588
++++


589
++++


590
++++


591
++++


592
++++


593
++++


594
++++


595
+++


596
++++


597
++++


598
++++


599
++++


600
++++


601
++++


602
++++


603
++++


604
+++


605
+


606
++++


607
++++


608
++++


609
++++


610
++++


611
++++


612
++++


613
++++


614
++++


615
++++


616
++++


617
++++


618
++++


619
++++


620
++++


621
++++


622
++++


623
++++


624
++++


625
++++


626
++++


627
++++


628
++++


629
++++


630
++++


631
++++


632
++++


633
++++


634
++++


635
++++


636
++++


637
++++


638
++++


639
++++


640
++++


641
++++


642
++++


643
+++


644
++++


645
++++


646
++++


647
++++


648
++++


649
++++


650
++++


651
++++


652
++++


653
++++


654
++++


655
++++


656
++++


657
++++


658
++++


659
++++


660
++++


661
++++


662
++++


663
++++


664
++++


665
++++


666
+++









IFNγ and IL-2 Analysis of Human Peripheral Pan T Cells


Human peripheral blood pan T cells were purchased from STEMCELL™ Technologies Inc. Human peripheral blood pan T cells were thawed and suspended in DMEM media (10% FBS and 10 Penicillin/Streptomycin). 8×104 T cells were seeded in 96-well plate and incubated with various concentration of compounds and 100 nM Prostaglandin E2 for 1 hr. T cells were stimulated with Dynabeads Human T-Activator CD3/CD28 (Life Technologies) at a 1:3 cells: beads ratio. Cytokine secretion was measured after 24 hr post stimulation using MSD V-PLEX human cytokine kit as suggested by the manufacturer. Data were analyzed with an MESO Quickplex SQ120 (Mesoscale Discovery).


In Table 3, the values represent + for >1000 nM, ++ 200-1,000 nM, +++ for <200 nM and − for not determined.









TABLE 3







IFNγ and IL-2 secretion of the invented compounds in human


peripheral blood pan T cells











Example
IFNγ (EC50)
IL-2 (EC50)







104
++
+



105
++
+



107
++




110
+++




111
++




118
+++




123
++
+



125
+++




134
+++
+



152
++
++



156
++
++



161
++




162
++




163





167
++
+



169
++
+



170
++
+



172
++




173
++




174
++




175
+++




178





184
+++




193
++
+



194
++




196
++




199
++




258
+++
++



291
+++
++



293
+++




296
+++
++



297
+++
+++



316
++
+



320
++




324
+++
++



326
++
++



327
+++
++



329
++
++



330
++
++



332
++
++



333
++
++



334
++
++



359
++
++



361
++
+



484
+++
++



488
++




503
++




509
+++
++



520
++




521
+++
+++



523
+++




524
+++
+++



525
+++
++



529
+++
+++



530
++
++



531
+++
++



532
++




534
+++




541
++




543
+++
++



548





550
++
++



552
++
++



556
+++
++



557
+++
++



558
+++
++



561
++
++



562
++




563
++
++



564
++
++



565
++
++



569
++
+



570
+++
++



574
++
++



577
+++
++



579
+++
+



588
+++
+++









Claims
  • 1. A compound of Formula (I):
  • 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L is a bond, and R1 is cycloalkyl which is optionally substituted with one or more groups selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, halo, cyano, hydroxy, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —OR9, —OC(O)R9, —OC(O)NR10R11, —NR10R11, —N(R6)NR10R11, —N(R6)OR9, —N(R6)C(O)R9, —N(R6)C(O)OR9, and —N(R6)C(O)NR10R11.
  • 3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each of R2 and R3 is independently —H, halo, alkylthio, haloalkyl, or alkyl.
  • 4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein M is a bond, —O—, or —NR6—; and R4 is —H, -D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, cyano, hydroxy, —C(O)R9, —C(O)NR10R11, —S(O)2R9, —S(O)(═NH)R10, or —S(O)2NR10R11, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more groups selected from the group consisting of halo, hydroxy, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, —CN, —CD3, —NR10R11, —NR10S(O)2R9, and —NR10C(═O)R9.
  • 5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is a compound of Formula (V):
  • 6. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein L is a bond, and R1 is cycloalkyl which is optionally substituted with one or more groups selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, cycloalkyl, halo, cyano, hydroxy, —C(O)R9, —C(O)OR9, —C(O)NR10R11, —OR9, —OC(O)R9, —OC(O)NR10R11, —NR10R11, —N(R6)NR10R11, —N(R6)OR9, —N(R6)C(O)R9, —N(R6)C(O)OR9, and —N(R6)C(O)NR10R11.
  • 7. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R1 is cycloalkyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl.
  • 8. The compound of claim 5 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(6-(5-chloro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-methoxy-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-amino-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-amino-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-bromo-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-(methylamino)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-(dimethylamino)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-bromo-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-cyano-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-(hydroxymethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(6-fluoro-5-vinyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;(1S,2S)-2-fluoro-N-(6-(5-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-bromo-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(6-(5-acetyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-amino-6-chloro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-cyclopropyl-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(6-(5-cyclopropyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(6-fluoro-5-isopropyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-ethyl-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(5-(difluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;N-(6-(6-fluoro-5-(hydroxymethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;N-(6-(6-fluoro-5-methoxy-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;(1S,2S)-N-(6-(5-(difluoromethyl)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-bromo-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(6-(5-(difluoromethyl)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;(1S,2S)-N-(6-(5,7-dichloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-dimethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(dimethylphosphoryl)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-chloro-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-bromo-5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(6,7-difluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(5-methyl-7-vinyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylamino)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylsulfonyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-bromo-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(methylsulfonyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-methoxy-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-methoxy-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-acrylamido-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-ethoxy-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-acrylamido-5-chloro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(4-methylpiperazin-1-yl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;2-(hydroxymethyl)-N-(6-(5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-morpholino-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(ethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(diethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(pyrrolidin-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(azetidin-1-yl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(6-amino-5-chloro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(6-(7-methoxy-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(6-(6-acrylamido-5-chloro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-ethoxy-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-ethoxy-6-fluoro-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(6-acrylamido-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((2-hydroxyethyl)thio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(dimethylamino)-5-ethyl-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(6-(6-fluoro-7-(2-hydroxyethyl)thio)-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-ethyl-6-fluoro-7-(methylthio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-ethyl-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-hydroxy-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-bis(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-ethyl-6,7-difluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(methylsulfinyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-acetamido-5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(methylsulfonyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylsulfinyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(6,7-difluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;methyl 6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-5-methyl-1H-indazole-7-carboxylate;(1S,2S)-N-(6-(5-chloro-7-(ethyl(methyl)amino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-acetamido-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;tert-butyl 2-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1H-indazol-7-yl)-1-methylhydrazine-1-carboxylate;(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(N-methylacetamido)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;2-((6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-5-methyl-1 H-indazol-7-yl)thio)ethyl methylcarbamate;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-5-methyl-1 H-indazole-7-carboxylic acid;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1 H-indazole-7-carboxylic acid;methyl 5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1 H-indazole-7-carboxylate;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(N-methylacetamido)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-methylhydrazineyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-ethoxy-5-ethyl-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-acetyl-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N-dimethyl-1 H-indazole-7-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N-methyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(7-acetyl-6-fluoro-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6,7-difluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(5-ethyl-7-(ethyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;(1 S,2S)-N-(6-(5-ethoxy-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N,5-trimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-fluoro-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(difluoromethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2S)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2R)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2R)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-oxopyrrolidin-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyridin-2-yl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,5-dimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(5-ethyl-6-fluoro-7-(trifluoromethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(6-(7-(methylthio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;5-chloro-N-ethyl-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N-methyl-1 H-indazole-7-carboxamide;(1 S,2S)-2-fluoro-N-(6-(6-fluoro-7-(methylthio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(difluoromethyl)-6-fluoro-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(6-(6-fluoro-7-(trifluoromethoxy)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(trifluoromethoxy)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyrimidin-2-yl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N-methyl-N-(2,2,2-trifluoroethyl)-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyrimidin-4-yl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyridin-3-ylmethyl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methyl-1 H-tetrazol-5-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-cyano-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(dimethylamino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyridin-4-ylmethyl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N-dimethyl-1 H-indazole-7-carboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N-dimethyl-1 H-indazole-5-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(trifluoromethoxy)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-ethoxy-6,7-difluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-methyl-2-oxoimidazolidin-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(isopropylamino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(isopropyl(methyl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(cyclopropyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(hydroxymethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(fluoromethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-methyl-1,2,4-oxadiazol-5-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1 H-pyrrol-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((cyanomethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(cyclopropylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(N-cyclopropyl-2,2,2-trifluoroacetamido)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-hydroxypropanamido)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(sec-butylamino)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1-cyanoethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-hydroxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methoxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-fluoroethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1 H-pyrrol-3-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methyl-1 H-pyrrol-3-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methyl-1 H-pyrrol-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methyl-1 H-pyrazol-5-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7((2H-tetrazol-2-yl)methyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(azetidin-1-ylmethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(pyrrolidin-1-ylmethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(piperidin-1-ylmethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((2H-1,2,3-triazol-2-yl)methyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((1 H-1,2,3-triazol-1-yl)methyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((1 H-1,2,4-triazol-1-yl)methyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((1-methyl-1 H-imidazol-2-yl)thio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;1-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-3-cyclopropylurea;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-methyl-1 H-pyrrol-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-hydroxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methoxymethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(ethoxymethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((1 H-tetrazol-1-yl)methyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1-(dimethylamino)-1-oxopropan-2-yl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-methoxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(1-(dimethylamino)ethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((2-(dimethylamino)-2-oxoethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-(1 H-tetrazol-1-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-aminoethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;1-(5-chloro-6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1 H-indazol-7-yl)-N,N-dimethyl-1 H-pyrrole-3-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-cyclopropoxy-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylamino)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(8-amino-6-(5-chloro-6-fluoro-7-(isopropylamino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-isopropoxy-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-isopropyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-cyclopentyl-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((R)-1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((S)-1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2,2,2-trifluoro-1-hydroxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-hydroxycyclopentyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-ethanethioamido-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(N-methylacetamido)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((R)-1-(1 H-tetrazol-1-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((S)-1-(1 H-tetrazol-1-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2,2,2-trifluoro-1-methoxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((tetrahydrofuran-3-yl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-acetamidoethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(1-ethoxy-2,2,2-trifluoroethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1,2,2,2-tetrafluoroethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1-cyclopropylethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((cyclopropylmethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((R)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((S)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-propionamidoethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1,1-difluoropropan-2-yl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-formamidoethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(oxetan-3-ylamino)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(2,2,2-trifluoroacetamido)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide(1 S,2S)-N-(6-(5-chloro-7-(1-((1-cyanocyclopropyl)amino)ethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(1-(5-chloro-6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1 H-indazol-7-yl)ethyl)cyclobutanecarboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1H-imidazol-5-yl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-((4,5-dihydro-1H-imidazol-2-yl)amino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylamino)-1-oxopropan-2-yl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((methylthio)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(1,3-dimethylureido)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylthio)ethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((methylsulfinyl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((methylsulfonyl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(cyano(formamido)methyl)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-((1S,2R)-1,2-dimethoxypropyl)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(1-(2,2-difluoroacetamido)ethyl)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-methyl-1H-imidazol-5-yl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylsulfinyl)ethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylsulfonyl)ethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and(1S,2S)-N-(6-(5-chloro-7-(1-(ethylamino)-1-oxopropan-2-yl)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.
  • 9. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-C3 alkyl, C1-C3 hydroxyalkyl and C1-C3 haloalkyl; R2 is —H, alkyl, alkylthio, haloalkyl, or halo; R3 is —H, alkyl, or halo; M is a bond, —O—, or —NR6—; R4 is —H, halo, alkyl, monoalkylamino, or dialkylamino; R5 is —H, alkyl, or halo.
  • 10. The compound of claim 5 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(isopropylamino)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and(1S,2S)-N-(6-(5-chloro-6-fluoro-7-isopropyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.
  • 11. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, hydroxyalkyl, haloalkyl, haloalkenyl, cycloalkyl, monoalkylamino, or dialkylamino; and R5 is —H, alkyl, or halo.
  • 12. The compound of claim 5 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-bromo-5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylamino)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-methoxy-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-ethoxy-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(ethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-5-ethyl-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-ethyl-6-fluoro-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-bis(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(6,7-difluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(ethyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-ethoxy-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-ethoxy-5-ethyl-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N-dimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N,5-trimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-fluoro-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2S)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2R)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-oxopyrrolidin-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-N-ethyl-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N-methyl-1 H-indazole-7-carboxamide;(1 S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(trifluoromethoxy)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyridin-3-ylmethyl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyridin-4-ylmethyl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(trifluoromethoxy)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-methyl-2-oxoimidazolidin-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(isopropylamino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(cyclopropyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((cyanomethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1-cyanoethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-hydroxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-fluoroethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methoxymethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(ethoxymethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-isopropoxy-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-isopropyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((S)-1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-hydroxycyclopentyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((S)-1-(1 H-tetrazol-1-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-acetamidoethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1,2,2,2-tetrafluoroethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((R)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((S)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1,1-difluoropropan-2-yl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-formamidoethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(2,2,2-trifluoroacetamido)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(1-(5-chloro-6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1 H-indazol-7-yl)ethyl)cyclobutanecarboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylamino)-1-oxopropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((methylthio)methyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylthio)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(cyano(formamido)methyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(1-(2,2-difluoroacetamido)ethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and(1 S,2S)-N-(6-(5-chloro-7-(1-(ethylamino)-1-oxopropan-2-yl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.
  • 13. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxyalkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, alkylcarbonyl, dialkylaminocarbonyl, oxopyrrolidinyl, hydroxyalkyl, haloalkyl, haloalkenyl, cycloalkyl, pyridinyl, monoalkylamino, or dialkylamino; and R5 is —H, alkyl, or halo.
  • 14. The compound of claim 5 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-bromo-5-chloro-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylamino)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-bromo-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-7-methoxy-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-methoxy-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-ethoxy-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(ethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(diethylamino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-((2-hydroxyethyl)thio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-5-ethyl-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-ethyl-6-fluoro-7-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(6-(6-fluoro-5,7-bis(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-ethyl-6,7-difluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(6,7-difluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-7-(ethyl(methyl)amino)-6-fluoro-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-(dimethylamino)-6-fluoro-5-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(7-ethoxy-6-fluoro-5-(methylthio)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(6-(5-chloro-6-fluoro-7-(N-methylacetamido)-1H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-ethoxy-5-ethyl-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N-dimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-ethyl-7-(ethyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N,N,5-trimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(6-(7-(ethyl(methyl)amino)-6-fluoro-5-methyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(difluoromethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2S)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2R)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2R)-N-(6-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-oxopyrrolidin-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-ethyl-6-fluoro-7-(trifluoromethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-N-ethyl-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-N-methyl-1 H-indazole-7-carboxamide;(1 S,2S)-2-fluoro-N-(6-(6-fluoro-5-methyl-7-(trifluoromethoxy)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyrimidin-2-yl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyridin-3-ylmethyl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methyl(pyridin-4-ylmethyl)amino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(trifluoromethoxy)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(3-methyl-2-oxoimidazolidin-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(isopropylamino)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(cyclopropyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(hydroxymethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(fluoromethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1 H-pyrrol-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((cyanomethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(cyclopropylamino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(sec-butylamino)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1-cyanoethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-hydroxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methoxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-fluoroethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methyl-1 H-pyrrol-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-methyl-1 H-pyrazol-5-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7((2H-tetrazol-2-yl)methyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((2H-1,2,3-triazol-2-yl)methyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-methyl-1 H-pyrrol-1-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(methoxymethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(ethoxymethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-(1 H-tetrazol-1-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-cyclopropoxy-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-isopropoxy-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-isopropyl-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-cyclopentyl-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((S)-1-(2H-tetrazol-2-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2,2,2-trifluoro-1-hydroxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2-hydroxycyclopentyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-((S)-1-(1 H-tetrazol-1-yl)ethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(2,2,2-trifluoro-1-methoxyethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(7-(1-acetamidoethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1,2,2,2-tetrafluoroethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((cyclopropylmethyl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((R)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((S)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-propionamidoethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-((1,1-difluoropropan-2-yl)amino)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-formamidoethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(2,2,2-trifluoroacetamido)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(1-(5-chloro-6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-1 H-indazol-7-yl)ethyl)cyclobutanecarboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylamino)-1-oxopropan-2-yl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-((methylthio)methyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-6-fluoro-7-(1-(methylthio)ethyl)-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(cyano(formamido)methyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(6-(5-chloro-7-(1-(2,2-difluoroacetamido)ethyl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and(1 S,2S)-N-(6-(5-chloro-7-(1-(ethylamino)-1-oxopropan-2-yl)-6-fluoro-1 H-indazol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.
  • 15. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is a compound of Formula (VI):
  • 16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and the compound of claim 1 or a pharmaceutically acceptable salt thereof.
  • 17. The compound of claim 15 or a pharmaceutically acceptable salt thereof, wherein L is a bond, R1 is cyclopropyl which is optionally substituted with one or more groups selected from the group consisting of halo, C1-3 alkyl, C1-3 hydroxy alkyl and C1-3 haloalkyl; R2 is —H, alkyl, halo, haloalkyl, or alkylthio; R3 is —H, alkyl, or halo; M is a bond, —O—, —S— or —NR6—; R4 is —H, halo, alkyl, hydroxyalkyl, haloalkyl, haloalkylamidoalkyl, haloalkylcarbonylaminoalkyl, alkylamidoalkyl, hydroxyhaloalkyl, haloalkenyl, cycloalkyl, cyano, cyanoalkyl, dimethylamino, dimethylaminoethyl, methylaminocarbonyl, dimethylaminocarbonyl, methylaminooxoethyl, am inocarbonylalkyl, acetamindoethyl, dialkylaminocycloalkyl, aminocycloalkyl, methylaminocycloalkyl, cycloalkylalkyl, cycloalkyl(hydroxy)alkyl, cycloalkylamidoalkyl, cycloalkylaminocarbonyl, hydroxycycloalkyl, methoxycycloalkyl, cycloalkyl(methoxy)methyl, alkoxycarbonyl, alkylcarbonyl, alkylamidoalkyl, alkoxyalkyl, alkenyl, methylsulfonamidoethyl, imidazolylethyl, dioxanyl, azetidinyl, azetidin ylmethyl, tetrahydrofuranyl, furanyl, pyrimidinyl, pyridinyl, pyrrolyl, halopyrrolidinyl, pyrrolidinyl, methylpyrrolyl, isoxazolyl, tetrazolylalkyl, triazinyl, methylpyrazolyl, or methylpyrazolylmethyl; and R5 is —H, alkyl, or halo.
  • 18. The compound of claim 15 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-2-fluoro-N-(5-(5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-vinyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(5-methoxy-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-(dimethylamino)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(5-(trifluoromethyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-ethyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-acetyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-(dimethylamino)-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-bromo-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-cyano-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-cyclopropyl-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-cyclopropyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(5-(hydroxymethyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-isopropyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-bromo-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-(difluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methoxy-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-(difluoromethyl)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(3-chloro-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-3,5-dimethyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-3-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(3-ethynyl-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(3-cyclopropyl-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-3-vinyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(3-ethyl-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5,7-dichloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-dimethyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-7-(dimethylphosphoryl)-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(7-chloro-6-fluoro-5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(7-bromo-5-chloro-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(6,7-difluoro-5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(trifluoromethyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(5-methyl-7-vinyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-7-(dimethylamino)-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(methylthio)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(methylsulfonyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(7-bromo-6-fluoro-5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylthio)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylsulfonyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1S,2S)-N-(5-(7-(dimethylamino)-6-fluoro-5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-7-methoxy-5-methyl-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-methoxy-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-ethoxy-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methylamino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(4-methylpiperazin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(ethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(diethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-morpholino-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(pyrrolidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(piperazin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(azetidin-1-yl)-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((4-(dimethylamino)cyclohexyl)(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((4-hydroxycyclohexyl)(methyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl((1R,4R)-4-(methylamino)cyclohexyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl((1 S,4S)-4-(methylamino)cyclohexyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(7-methoxy-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((tetrahydrofuran-2-yl)methoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((4-(methylamino)cyclohexyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-ethoxy-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-amino-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-ethoxy-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((4-(dimethylamino)cyclohexyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6-fluoro-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide dihydrochloride;(1 S,2S)-N-(5-(7-((4-aminocyclohexyl)(methyl)amino)-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-((4-aminocyclohexyl)amino)-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;tert-butyl (4-((5-chloro-6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido) pyrazolo[1,5-a]pyridin-5-yl)-1 H-indazol-7-yl)amino)cyclohexyl)carbamate;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((4-hydroxycyclohexyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(diethylamino)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((2-hydroxyethyl)thio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6-fluoro-7-((2-(methylamino)-2-oxoethyl)thio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide bis(2,2,2-trifluoroacetate);(1 S,2S)-N-(5-(7-((2-(dimethylamino)-2-oxoethyl)thio)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide bis(2,2,2-trifluoroacetate);(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-hydroxyethyl)thio)-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-7-(ethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-7-(ethyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;2-((5-ethyl-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-1H-indazol-7-yl)thio)acetic acid;(1 S,2S)-N-(5-(7-((3-aminocyclopentyl)(methyl)amino)-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-hydroxy-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-bis(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-ethoxy-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6,7-difluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylsulfinyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-(2-hydroxyethoxy)-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;2-((6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-5-methyl-1 H-indazol-7-yl)oxy)ethyl carbamate;(1 S,2S)-N-(5-(5-chloro-6,7-difluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-acetamido-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methylsulfinyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(2-(1-methylureido)ethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-acetamido-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;tert-butyl 2-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido) pyrazolo[1,5-a]pyridin-5-yl)-1 H-indazol-7-yl)-1-methylhydrazine-1-carboxylate;(1 S,2S)-N-(5-(7-ethoxy-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(2-ureidoethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(2-(3-methylureido)ethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;2-((6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-5-methyl-1 H-indazol-7-yl)thio)ethyl methylcarbamate;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(2-(2,2,2-trifluoroacetamido)ethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;methyl 6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-5-methyl-1 H-indazole-7-carboxylate;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-5-methyl-1 H-indazole-7-carboxylic acid;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(N-methylacetamido)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-1 H-indazole-7-carboxylic acid;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(N-methylacetamido)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(2-methylhydrazineyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;methyl 5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido) pyrazolo[1,5-a]pyridin-5-yl)-1 H-indazole-7-carboxylate;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((3-hydroxycyclopentyl)(methyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N,N-dimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-hydroxyethyl)(methyl)amino)-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((3-hydroxycyclopentyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N-methyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((3-hydroxycyclobutyl)(methyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;(1 S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(ethyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-6-fluoro-5-(trifluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-acetyl-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2R)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1R,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N,N,5-trimethyl-1 H-indazole-7-carboxamide;(1R,2S)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2R)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1R,2R)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1R,2R)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-acetyl-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-1 H-indazole-7-carboxamide;(1 S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethoxy-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;2-((6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-5-methyl-1 H-indazol-7-yl)(methyl)amino)ethyl methylcarbamate;(1 S,2S)-N-(5-(5-chloro-7-(difluoromethyl)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-cyano-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N,5-dimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6-fluoro-7-(trifluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-cyano-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-(trifluoromethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-((cyanomethyl)thio)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-(trifluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(difluoromethyl)-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(trifluoromethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-methyl-1 H-tetrazol-5-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(pyrimidin-2-yl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((cyanomethyl)thio)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2R)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2R)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2S)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(pyrimidin-2-ylamino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-((1-cyanoethyl)thio)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-((2-cyanopropan-2-yl)thio)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N,N-dimethyl-1 H-indazole-7-carboxamide;6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N,N-dimethyl-1 H-indazole-5-carboxamide;(1 S,2S)-N-(5-(5-ethoxy-6-fluoro-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(trifluoromethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-((1-cyanocyclopropyl)thio)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(pyridin-4-ylamino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-5-ethoxy-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethoxy-6,7-difluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-N-(cyanomethyl)-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N-methyl-1 H-indazole-7-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((5-fluoropyrimidin-2-yl)(methyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(pyridin-4-yl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(N-(cyanomethyl)acetamido)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(2-(pyridin-4-yl)ethyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(1,3,5-triazin-2-yl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(1,2,4-triazin-3-yl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(isopropylamino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(cyclobutyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(ethylthio)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(isopropyl(methyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-methyl-2-oxoimidazolidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-methoxyazetidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(cyclopropyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-formyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-(methoxymethyl)azetidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(1,1-dioxidothiomorpholino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(hydroxymethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-methylazetidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-thiomorpholino-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-fluoro-3-methylazetidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((E)-2-cyanovinyl)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(fluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-oxidothiomorpholino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((cyanomethyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(1 H-pyrrol-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((2-cyanopropan-2-yl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(prop-1-en-2-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-isopropyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((1-cyanoethyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-fluoropyrrolidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;benzyl (5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-1 H-indazol-7-yl)(1-cyanoethyl)carbamate;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(2-methyl-1 H-pyrrol-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(3S,4R)-4-methyltetrahydrofuran-3-yl(5-(5-chloro-6-fluoro-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)carbamate;(1 S,2R,3S)-N-(5-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-methyl-3-(1-methyl-1 H-pyrazol-4-yl)cyclopropane-1-carboxamide;1-(5-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-3-cyclopropylurea;(1 S,2S,3S)-N-(5-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-methyl-3-(1-methyl-1 H-pyrazol-4-yl)cyclopropane-1-carboxamide;1-(5-chloro-6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-1H-indazol-7-yl)-N,N-dimethyl-1 H-pyrrole-3-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-isopropoxy-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-cyclopentyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(2,2,2-trifluoro-1-hydroxyethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((1-cyclopropylethyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((cyclopropylmethyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((R)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((S)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-7-((1,1-difluoropropan-2-yl)amino)-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(4-hydroxytetrahydrofuran-2-yl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-formamidoethyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-propionamidoethyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(1-(5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-1H-indazol-7-yl)ethyl)cyclobutanecarboxamide;(1S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-(2,2,2-trifluoroacetamido)ethyl)-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(7-(1-acetamidoethyl)-5-chloro-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-7-(1,3-dimethylureido)-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-chloro-7-(1-(2,2-difluoroacetamido)ethyl)-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and(1S,2S)-N-(5-(5-chloro-7-((1S,2R)-1,2-dimethoxypropyl)-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.
  • 19. The compound of claim 15 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-N-(5-(5-bromo-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-N-(5-(5-ethyl-6-fluoro-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1S,2S)-2-fluoro-N-(5-(6-fluoro-5-methoxy-1H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5,7-dichloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-dimethyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-bromo-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-bromo-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-methoxy-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-methoxy-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-ethoxy-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methylamino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(ethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(diethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((4-(dimethylamino)cyclohexyl)(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((4-hydroxycyclohexyl)(methyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl((1R,4R)-4-(methylamino)cyclohexyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl((1 S,4S)-4-(methylamino)cyclohexyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-ethoxy-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6-fluoro-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide dihydrochloride;(1 S,2S)-N-(5-(7-((4-aminocyclohexyl)(methyl)amino)-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((2-hydroxyethyl)thio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6-fluoro-7-((2-(methylamino)-2-oxoethyl)thio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide bis(2,2,2-trifluoroacetate;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-hydroxyethyl)thio)-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-7-(ethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-7-(ethyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5,7-bis(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-ethoxy-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6,7-difluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-(2-hydroxyethoxy)-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-ethoxy-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;methyl 6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-5-methyl-1 H-indazole-7-carboxylate;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(N-methylacetamido)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(N-methylacetamido)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N,N-dimethyl-1 H-indazole-7-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-7-((2-hydroxyethyl)(methyl)amino)-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(dimethylamino)-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((3-hydroxycyclobutyl)(methyl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;(1 S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-fluoro-5-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(ethyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,25)-N-(5-(7-(dimethylamino)-6-fluoro-5-(trifluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N,N,5-trimethyl-1 H-indazole-7-carboxamide;(1R,2S)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2R)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1R,2R)-2-fluoro-N-(5-(6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1R,2R)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(ethyl(methyl)amino)-6-fluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-methyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(difluoromethyl)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-ethyl-6-fluoro-7-(trifluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-cyano-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-((cyanomethyl)thio)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-2-fluoro-N-(5-(6-fluoro-5-methyl-7-(trifluoromethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(pyrimidin-2-yl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((cyanomethyl)thio)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2R)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2R)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1R,2S)-N-(5-(6,7-difluoro-5-(methylthio)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-((1-cyanoethyl)thio)-5-ethyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(trifluoromethoxy)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;5-chloro-N-(cyanomethyl)-6-fluoro-4-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-N-methyl-1H-indazole-7-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(N-(cyanomethyl)acetamido)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(1,3,5-triazin-2-yl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(methyl(1,2,4-triazin-3-yl)amino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(isopropylamino)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(ethylthio)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-methyl-2-oxoimidazolidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(cyclopropyl(methyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(hydroxymethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(fluoromethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((cyanomethyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(1 H-pyrrol-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((2-cyanopropan-2-yl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(prop-1-en-2-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-isopropyl-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((1-cyanoethyl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(3-fluoropyrrolidin-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(2-methyl-1 H-pyrrol-1-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2R,3S)-N-(5-(5-chloro-7-(dimethylamino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-methyl-3-(1-methyl-1 H-pyrazol-4-yl)cyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-isopropoxy-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-cyclopentyl-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(2,2,2-trifluoro-1-hydroxyethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((R)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-((S)-1-methoxypropan-2-yl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-((1,1-difluoropropan-2-yl)amino)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-formamidoethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-propionamidoethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;N-(1-(5-chloro-6-fluoro-4-(2-((1 S,2S)-2-fluorocyclopropane-1-carboxamido)pyrazolo[1,5-a]pyridin-5-yl)-1 H-indazol-7-yl)ethyl)cyclobutanecarboxamide;(1 S,2S)-N-(5-(5-chloro-6-fluoro-7-(1-(2,2,2-trifluoroacetamido)ethyl)-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(7-(1-acetamidoethyl)-5-chloro-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;(1 S,2S)-N-(5-(5-chloro-7-(1,3-dimethylureido)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and(1 S,2S)-N-(5-(5-chloro-7-(1-(2,2-difluoroacetamido)ethyl)-6-fluoro-1 H-indazol-4-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.
CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit and priority to U.S. Provisional Patent Application No. 63/084,059, filed on 28 Sep. 2020. The entire disclosure of the application identified in this paragraph is incorporated herein by reference.

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Related Publications (1)
Number Date Country
20220098193 A1 Mar 2022 US
Provisional Applications (1)
Number Date Country
63084059 Sep 2020 US