Picolinamides as fungicides

Abstract
This disclosure relates to picolinamides of Formula I and their use as fungicides.
Description
BACKGROUND & SUMMARY

Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.


The present disclosure relates to picolinamides and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.


One embodiment of the present disclosure may include compounds of Formula I:




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wherein:


Q is




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X is hydrogen or C(O)R4;


Y is hydrogen or C(O)R4;


Z is N or N+→O and W is O or S;


R1 is hydrogen or alkyl, substituted with 0, 1 or multiple R7;


R2 is methyl;


R3 is chosen from alkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R7;


R4 is chosen from alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R7;


R5 is chosen from hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R7;


R6 is chosen from hydrogen, —C(O)R8, or —CH2OC(O)R8;


R7 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R9;


R8 is chosen from alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R7;


R9 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl; and


R10 is chosen from hydrogen or alkyl, each substituted with 0, 1 or multiple R7.


Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.


Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.


It will be understood by those skilled in the art that the following terms may include generic “R”-groups within their definitions, e.g., “the term alkoxy refers to an —OR substituent”. It is also understood that within the definitions for the following terms, these “R” groups are included for illustration purposes and should not be construed as limiting or being limited by substitutions about Formula I.


The term “alkyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.


The term “alkenyl” refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.


The terms “aryl” and “Ar” refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms.


The term “heterocyclyl” refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms


The term “alkoxy” refers to an —OR substituent.


The term “acyloxy” refers to an —OC(O)R substituent.


The term “cyano” refers to a —C≡N substituent.


The term “hydroxyl” refers to a —OH substituent.


The term “amino” refers to an —N(R)2 substituent.


The term “arylalkoxy” refers to —O(CH2)nAr where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.


The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.


The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.


The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.


The term “nitro” refers to a —NO2 substituent.


The term thioalkyl refers to a —SR substituent.


Throughout the disclosure, reference to the compounds of Formula I is read as also including all stereoisomers, for example diastereomers, enantiomers, and mixtures thereof. In another embodiment, Formula (I) is read as also including salts or hydrates thereof. Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, hydroiodide, trifluoroacetate, and trifluoromethane sulfonate.


It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.


Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.


Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.







DETAILED DESCRIPTION

The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.


Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.


The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and used as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water-suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.


Wettable powders, which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.


Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.


Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oilsoluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated-polyglycol ether.


Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.


Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.


The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.


Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.


The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%)+emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9-C11 alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12-C16) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG (400) dioleate-99. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.


The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.


The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, aminopyrifen, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxide, copper octanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin, enestroburin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluindapyr, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxapiprolin, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), inpyrfluxam, iodocarb, ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isofetamide, isoflucypram, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxium-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb, mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl iodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl, oxathiapiprolin, oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenyl laurate, penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium hydroxyquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pydiflumetofen, pyrametostrobin, pyraoxystrobin, pyraclostrobin, pyraziflumid, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp., (RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide, 1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide, 2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl, bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, climbazole, copper bis(3-phenylsalicylate), copper zinc chromate, coumoxystrobin, cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlobentiazox, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipymetitrone, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, enoxastrobin, ESBP, etaconazole, etem, ethirim, fenaminstrobin, fenaminosulf, fenapanil, fenitropan, fenpicoxamid, florylpicoxamid, flufenoxystrobin, fluopimomide, fluotrimazole, furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos, ICIA0858, ipfentrifluconazole, ipflufenoquin, isopamphos, isovaledione, mandestrobin, mebenil, mecarbinzid, mefentrifluconazole, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, metyltetraprole, milneb, mucochloric anhydride, myclozolin, N-3,5-dichlorophenyl-succinimide, N-3-nitrophenylitaconimide, natamycin, N-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyrapropoyne, pyridachlometyl, pyridinitril, pyrisoxazole, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, quinofumelin, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, triclopyricarb, triflumezopyrim, urbacid, zarilamid, and any combinations thereof.


Additionally, the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests. When used in conjunction with other pesticides, the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s). Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, acynonapyr, afidopyropen, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, benzpyrimoxan, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, broflanilide, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chloroprallethrin, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclaniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalodiamide, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicloromezotiaz, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, epsilon-metofluthrin, epsilon-momfluorothrin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flometoquin, flonicamid, fluazaindolizine, flubendiamide, flucofuron, flucycloxuron, flucythrinate, fluensulfone, flufenerim, flufenoxuron, flufenprox, flufiprole, fluhexafon, flupyradifurone, flupyrimin, fluvalinate, fluxametamide, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, furathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptafluthrin, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isocycloseram, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kappa-bifenthrin, kappa-tefluthrin, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan, mercurous chloride, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene, methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, momfluorothrin, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxazosulfyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocssene II, precocene III, primidophos, profenofos, profluralin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pyflubumide, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyriminostrobin, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad, spiromesifen, spiropidion, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachlorantraniliprole, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, tetraniliprole, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tioxazafen, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumezopyrim, triflumuron, trimethacarb, triprene, tyclopyrazoflor, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos, and any combinations thereof.


Additionally, the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants. When used in conjunction with herbicides, the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s). Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, beflubutamid-M, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac, bixlozone, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole chlorprocarb, carfentrazone, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clacyfos, clethodim, cliodinate, clodinafop, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenquinotrione, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M, flazasulfuron, florasulam, florpyrauxifen, fluazifop, fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate, halauxifen, halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iofensulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lancotrione, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, napropamide-M, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiafenacil, tiocarbazil, tioclorim, tolpyralate, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr, tridiphane, trietazine, trifloxysulfuron, trifludimoxazin, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate, and xylachlor.


Another embodiment of the present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.


The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.


It will be understood by those skilled in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.


The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch (Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust (Puccinia striiformis), scab of apple (Venturia inaequalis), powdery mildew of grapevine (Uncinula necator), barley scald (Rhynchosporium secalis), blast of rice (Magnaporthe grisea), rust of soybean (Phakopsora pachyrhizi), glume blotch of wheat (Parastagonospora nodorum), powdery mildew of wheat (Blumeria graminis f. sp. tritici), powdery mildew of barley (Blumeria graminis f. sp. hordei), powdery mildew of cucurbits (Erysiphe cichoracearum), anthracnose of cucurbits (Glomerella lagenarium), leaf spot of beet (Cercospora beticola), early blight of tomato (Alternaria solani), and spot blotch of barley (Cochliobolus sativus). The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.


The compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount. The term “disease-inhibiting and phytologically acceptable amount” refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m2).


Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.


The compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.


General Schemes


The following schemes illustrate approaches to generating picolinamide compounds of Formula (I). The following descriptions and examples are provided for illustrative purposes and should not be construed as limiting in terms of substituents or substitution patterns.


Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, can be prepared by the method shown in Scheme 1, step a. Submission of racemic epoxide mixtures of Formulas 1.0-Rac and 1.4-Rac, to reaction with an organometallic nucleophile, such




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as an aryl magnesium halide, in the presence of a metal halide, such as copper iodide, in a polar, aprotic solvent, such as tetrahydrofuran (THF) or diethyl ether (Et2O), at a temperature of about −78° C. to 55° C., affords racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, and shown in step a.


Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, can be separated into their individual enantiomers utilizing a lipase-catalyzed kinetic resolution described by Akita (Tetrahedron: Asymmetry 2009, 20, 1286-1294) and outlined in Scheme 2, steps a and b. Subjection of racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, to Candida antarctica lipase B (CAL-B) in an




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acetylating solvent, such as vinyl acetate, at a temperature of about 25° C. to about 60° C., affords the unreacted secondary alcohols of Formulas 1.2-Abs and 1.5-Abs, wherein R3 is as originally defined, and the acetylated compounds of Formulas 2.1-Abs and 2.3-Abs, wherein R3 is as originally defined. The mixtures can be purified via silica gel chromatography using a hexane-ethyl acetate mixture as the mobile phase giving the resolved secondary alcohols and acetates of Formulas 1.2-Abs, 1.5-Abs, 2.1-Abs and 2.3-Abs, wherein R3 is as originally defined, and in high enantiomeric excess. The lipase recognition of the secondary alcohol of 1.2-Rac, 1.3-Rac, 1.5-Rac and 1.6-Rac, wherein R3 is as originally defined, was similar to the empirical rule for the kinetic resolution of secondary alcohols (Bornscheuer and Kazlauskus, Hydrolases in Organic Synthesis; Wiley-VCH, 2006). Treatment of acetates of Formulas 2.1-Abs and 2.3-Abs, wherein R3 is as originally defined, with a carbonate base, such as potassium carbonate, in an alcoholic solvent, such as methanol, at a temperature of about 25° C. to about 60° C., affords the resolved secondary alcohols of Formulas 2.2-Abs and 2.4-Abs, wherein R3 is as originally defined.


Compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, may be prepared according to the method outlined in Scheme 3, step a. Alcohols of Formula 3.0, wherein R2 and R3, are as originally defined, can be treated with compounds of Formula 3.1, wherein R1 and R10 are as originally defined, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDT), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as (CH2Cl2) or THF to afford compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, as shown in step a.




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Compounds of Formula 4.5, wherein R1, R2, R3, R5, and R10, are as originally defined, can be prepared according to the methods outlined in Scheme 4, steps a-d. Compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, can be treated with an acid, such as a 4 Normal (N) solution of hydrogen chloride (HCl) in dioxane, in a halogenated solvent such as CH2Cl2 to afford compounds of Formula 4.1, wherein R1, R2, R3, and R10, as shown in step a. Compounds of Formula 4.2, wherein R1, R2, R3, and R10, are as originally defined, can be prepared by treating compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, with an acid, such as 2,2,2-trifluoroacetic acid, in a halogenated solvent such as CH2Cl2, as shown in step c. Compounds of Formulas 4.1 and 4.2, wherein R1, R2, R3, and R10, are as originally defined, can be treated with compounds of Formula 4.3, wherein R5 is as originally defined, in the presence of a base, such as diisopropylethylamine, and a peptide coupling reagent, such as benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) or O-(7-azabenzo-triazol-1-yl)-N,N,N′,N′tetramethyluronium hexafluorophosphate (HATU), in a halogenated solvent such as CH2Cl2, to afford compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, as shown in steps b and d.




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Compounds of Formula 5.1, wherein R1, R2, R3, R5 and R10, are as originally defined, can be prepared according to the method outlined in Scheme 5, steps a orb. Compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, can be treated with an appropriate alkyl halide, with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na2CO3) or potassium carbonate (K2CO3), in a solvent such as acetone, at a temperature of about 25° C. to about 50° C., as shown in step a. Or, alternatively, by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, triethylamine (NEt3), DMAP, or mixtures thereof, in an aprotic solvent, such as CH2Cl2, to afford compounds of Formula 5.1, wherein R1, R2, R3, R5, R6, and R10, are as originally defined, as shown in step b.




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Compounds of Formula 6.1 and 6.2, wherein R1, R2, R3, R5, R6, and R10, are as originally defined, can be prepared according to the method outlined in Scheme 6, steps a and b. Compounds of Formula 4.5, wherein R1, R2, R3, R5, and R10, are as originally defined, can be treated with a thionating reagent such as phosphorus pentasulfide, an additive, such as hexamethyldisiloxane, optionally in a polar aprotic solvent such as acetonitrile (CH3CN), at a temperature of about 0° C. to 80° C. to afford compounds of Formula 6.1, wherein R1, R2, R3, R5 and R10, are as originally defined, and shown in step a. It will be understood by those skilled in the art that compounds such as Formula 6.1 may also be prepared using other thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson's reagent, ammonium O,O′-diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent. Additives can include, but not limited to, aluminum oxide (Al2O3); inorganic bases, such as potassium carbonate and sodium bicarbonate; organic bases, such as triethylamine, diethylaniline, pyridine and morpholine. Optional solvents can include, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons, such as hexane, cyclohexane or toluene; halogenated hydrocarbons, such as dichloromethane, 1,2-dichloroethane and chlorobenzene; ethers, such as diethyl ether, 1,4-dioxane, THF and 1,2-dimethoxyethane; and other polar aprotic solvents such as pyridine and hexamethylphosphoramide (HMPA). In step b, treatment of compounds of Formula 6.1, wherein R1, R2, R3, R5 and R10, are as originally defined, with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium carbonate (Na2CO3) or potassium carbonate (K2CO3), in a polar aprotic solvent, such as acetone, at a temperature of about 55° C., or by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, Et3N, DMAP, or mixtures thereof, in an optional aprotic solvent such as CH2Cl2, at a temperature of about 23° C., can afford compounds of Formula 6.2 wherein R1, R2, R3, R5, R6, and R10, are as originally defined.




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Compounds of Formula 7.1, wherein R1, R2, R3, R5 and R10, are as originally defined, can be prepared according to the method outlined in Scheme 7, step a. Compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, can be treated with a oxidizing reagent such as m-chloroperbenzoic acid (mCPBA) in a polar solvent such as CH2Cl2, at a temperature of about 0° C. to 50° C., to give compounds of Formula 7.1, wherein R1, R2, R3, R5 and R10, are as previously defined, and shown in a. It will be understood by those skilled in the art that compounds of Formula 7.1, wherein R1, R2, R3, R5 and R10, are as originally defined, may also be prepared using other oxidizing agents, including, but not limited to: hydrogen peroxide, hydrogen




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peroxide-urea complex, magnesium monoperoxyphthalate hexahydrate (MMPP), peroxyacetic acid, oxone, sodium perchlorate or dimethyl dioxirane.


Compounds of Formula 8.1 wherein R1, R2, R3, R5 and R10, are as originally defined, can be prepared according to the method outlined in Scheme 8, step a. Compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, can be treated with a deactivated carbonyl reagent such as triphosgene, with a base, such as pyridine, and in a polar solvent, such as CH2Cl2, at a temperature of about 0° C. to 50° C. to afford compounds of Formula 8.1, wherein R1, R2, R3, R5 and R10, are as originally defined, as depicted in a.




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EXAMPLES
Example 1A: Preparation of Racemic threo-3-(2,4-dimethylphenyl)butan-2-ol



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To a suspension of freshly activated magnesium metal shavings (1.14 g, 46.80 mmol) in anhydrous Et2O (20 mL) was added dropwise 1-bromo-2,4-dimethylbenzene (8 g, 43.20 mmol). The mixture was gently heated at slight reflux (36° C.) for 5 hours (hr). The resulting dark brown solution was added via syringe to a flask containing copper (I) iodide (4.12 g, 21.61 mmol) suspended in Et2O (50 mL) at −20° C. The dark yellow suspension was stirred for 15 minutes (min) at −20° C. and then cooled to −50° C. Racemic trans-butene epoxide (1.3 g, 18.01 mmol) was slowly added dropwise followed by warming the reaction to room temperature and stirring overnight. The mixture was then cooled to 0° C. and slowly quenched by the addition of a saturated aqueous ammonium chloride (NH4Cl) solution. The mixture was filtered through a pad of Celite and the pad was rinsed thoroughly with ethyl acetate. The organic solution was washed with saturated NH4Cl solution and brine. The solution was dried (magnesium sulfate (MgSO4)), filtered and concentrated under reduced pressure. The residue was purified via automated flash column chromatography (SiO2, 0-40% ethyl acetate/hexanes gradient) to give racemic threo-3-(2,4-dimethylphenyl)butan-2-ol as a yellow oil (813 mg, 25%): 1H NMR (500 MHz, CDCl3) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.94-3.82 (m, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.29 (d, J=7.7 Hz, 6H), 1.50 (d, J=3.9 Hz, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 139.99, 135.49, 135.38, 131.31, 126.81, 126.18, 71.92, 41.42, 21.25, 20.87, 19.85, 16.06; EIMS m/z 178.


Example 1B: Preparation of Racemic erythro-3-(o-tolyl)butan-2-ol



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To a −20° C. suspension of copper(I) iodide (4.15 g, 21.60 mmol) in anhydrous Et2O (40 mL) was added 2-methylphenylmagnesium bromide (2.0 M in Et2O, 22.5 mL, 43.20 mmol) slowly dropwise. After stirring for 30 min, the orange suspension was cooled to −78° C., and racemic cis-butene epoxide (1.3 g, 18.01 mmol) was slowly added. The dry ice bath was removed and the mixture was allowed to slowly warm to ambient temperature and stirred overnight. The mixture was cooled with an ice bath to 0° C. and quenched slowly by the dropwise addition of a saturated aqueous NH4Cl solution. The mixture was warmed to room temperature and filtered through Celite, followed by rinsing the pad with ethyl acetate (EtOAc). The resulting filtrate was washed with saturated aqueous NH4Cl solution and brine. The solution was then dried (MgSO4) and concentrated under reduced pressure. The residue was purified automated flash column chromatography (SiO2, 0-30% ethyl acetate/hexanes gradient) to give racemic erythro-3-(o-tolyl)butan-2-ol (2.05 g, 69%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.34-7.01 (m, 4H), 3.92 (p, J=6.3 Hz, 1H), 3.01 (p, J=7.1 Hz, 1H), 2.36 (s, 3H), 1.47 (s, 1H), 1.28 (d, J=6.1 Hz, 3H), 1.19 (d, J=7.0 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 142.14, 136.84, 130.61, 126.49, 125.81, 72.33, 42.62, 20.47, 19.93, 17.88; EIMS m/z 164.


Example 1C: Preparation of Racemic threo-3-phenylbutan-2-ol



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To a suspension of copper (I) iodide (1.86 g, 9.76 mmol) in ethyl ether (18.0 mL) was added dropwise phenyllithium (1.9 M in butyl ether, 10.3 mL, 19.53 mmol) at 0° C. under a nitrogen atmosphere. After stirring at 0° C. for 1 hr, racemic trans-2,3-dimethyloxirane (0.64 g, 8.88 mmol) was added dropwise followed by removal of the ice bath and warming to room temperature with stirring over 2 hr. The reaction mixture was quenched with water (20 mL), filtered through a pad of Celite, and extracted with ethyl ether (3×20 mL). The organics were passed through a phase separator and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-25% acetone/hexanes gradient) to furnish racemic threo-3-phenylbutan-2-ol (1.33 g, 8.85 mmol, 99%) as orange oil: 1H NMR (400 MHz, CDCl3) δ 7.38-7.12 (m, 5H), 3.91-3.84 (m, 1H), 2.80-2.68 (m, 1H), 1.43 (s, 1H), 1.33 (d, J=7.1 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H). The spectral data was consistent with those reported in the literature: Tetrahedron 1981, 37, 709-713.


Example 2: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol and (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol
Step 1: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol and (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate



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A vial containing a solution of the racemic trans-3-(2,4-dimethylphenyl)butan-2-ol (800 mg, 4.49 mmol) dissolved in vinyl acetate (15 mL) was charged with beads of Novozym 435 Lipase (CAL-B, 1.6 g, 4.49 mmol). The vial was placed in an orbital shaker and was shaken at 200 rpm and heated at 55° C. for 7.5 hrs. The reaction was cooled and filtered through a frit disk with an EtOAc rinse. The eluent was concentrated under reduced pressure to give 906 mg of a crude yellow oil. The residue was purified via flash column chromatography (SiO2, 0-20% ethyl acetate/hexanes gradient) to afford (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate (clear oil, 466 mg, 47%) followed by (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol (clear yellow oil, 357 mg, 43%). Acetate: 1H NMR (500 MHz, CDCl3) δ 7.07 (d, J=7.7 Hz, 1H), 7.01-6.97 (m, 2H), 5.08 (dq, J=8.5, 6.3 Hz, 1H), 3.16-3.05 (m, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 2.06 (s, 3H), 1.21 (d, J=6.9 Hz, 3H), 1.06 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 170.80, 138.92, 135.56, 135.42, 131.22, 126.93, 126.33, 75.09, 39.48, 21.34, 20.89, 19.88, 18.34, 17.96; EIMS m/z 220. Alcohol: 1H NMR (500 MHz, CDCl3) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.88 (tt, J=9.2, 4.7 Hz, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 1.49 (d, J=3.5 Hz, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 140.00, 135.49, 135.38, 131.31, 126.82, 126.18, 71.92, 41.43, 21.25, 20.87, 19.85, 16.07; EIMS m/z 178. The enatiomeric ratio of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol was determined to be 96:4 by analysis via enatiomeric HPLC separation (210 nm wavelength).


Step 2: Preparation of (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol



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To a solution containing (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate prepared above (458 mg, 2.08 mmol) dissolved in methanol (4.2 mL) was added potassium carbonate (431 mg, 3.12 mmol). The mixture was stirred at ambient temperature for 1.5 hr, then heated to 50° C. for 2 hr. The reaction was cooled and concentrated under reduced pressure. The residue was diluted with acetone and passed through a small plug of silica gel, washing the pad well with acetone. The solvent was concentrated in vacuo to give (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol (332 mg, 90%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.88 (p, J=6.3 Hz, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 1.49 (s, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 140.00, 135.49, 135.38, 131.31, 126.82, 126.18, 71.92, 41.43, 21.26, 20.87, 19.85, 16.07; EIMS m/z 178. The enatiomeric ratio of the alcohol was determined to be 7:93 via analysis by enatiomeric HPLC.


Example 3: Preparation of (2S,3S)-3-phenylbutan-2-ol (tert-butoxycarbonyl)-L-alaninate



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To a solution of (2S,3S)-3-phenylbutan-2-ol (0.23 g, 1.53 mmol) dissolved in methylene chloride (7.7 mL) was added N-ethyl-N-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.59 g, 3.06 mmol) and N,N-dimethylpyridin-4-amine (19 mg, 0.15 mmol). The reaction mixture was purged with nitrogen, stirred over 16 hr, followed by concentration in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-20% ethyl acetate/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (tert-butoxycarbonyl)-L-alaninate (0.43 g, 1.34 mmol, 83% yield) as colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.35-7.25 (m, 2H), 7.27-7.15 (m, 3H), 5.12-5.01 (m, 2H), 4.35-4.26 (m, 1H), 2.95-2.83 (m, 1H), 1.45 (s, 9H), 1.37 (d, J=7.2 Hz, 3H), 1.29 (d, J=7.1 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 172.9, 155.0, 143.0, 128.5, 127.8, 126.7, 79.7, 76.1, 49.5, 45.1, 28.3, 18.9, 18.3, 17.5; IR (thin film) 3355, 2978, 2934, 1711, 1495, 1452, 1366, 1161, 1087, 1065, 701 cm−1.


Example 4: Preparation of (2S,3S)-3-phenylbutan-2-yl(3-hydroxy-4-methoxypicolinoyl)-L-alaninate
Step 1: Preparation of (2S,3S)-3-phenylbutan-2-yl-L-alaninate-hydrochloride



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To neat (2S,3S)-3-phenylbutan-2-ol (tert-butoxycarbonyl)-L-alaninate (0.42 g, 1.31 mmol) was added dropwise a solution of HCl dissolved in dioxane (4 M, 3.3 mL, 13.07 mmol) under nitrogen. Upon stirring for 16 hr, the reaction mixture was concentrated in vacuo to afford crude (2S,3S)-3-phenylbutan-2-yl-L-alaninate-hydrogen chloride as white solid, which was directly carried to the next step: HRMS-ESI (m/z) [M+H]+ calc'd for C13H20NO2, 222.1489; found, 222.1485.


Step 2: Preparation of (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate



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To a solution of (2S,3S)-3-phenylbutan-2-yl-L-alaninate-hydrogen chloride, 3-hydroxy-4-methoxypicolinic acid (0.24 g, 1.44 mmol), and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (0.75 g, 1.44 mmol) dissolved in methylene chloride (6.5 mL) was added dropwise N,N-diisopropylethylamine (0.75 mL, 4.31 mmol) under nitrogen. Upon stirring for 16 hr, the reaction mixture was concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-45% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (0.46 g, 1.173 mmol, 90% yield) as colorless oil: 1H NMR (500 MHz, CDCl3) δ 12.16 (s, 1H), 8.50 (d, J=8.0 Hz, 1H), 8.01 (d, J=5.2 Hz, 1H), 7.32-7.27 (m, 2H), 7.24-7.16 (m, 3H), 6.88 (d, J=5.2 Hz, 1H), 5.11 (dq, J=7.7, 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H), 2.97-2.87 (m, 1H), 1.54 (d, J=7.2 Hz, 3H), 1.31 (d, J=7.0 Hz, 3H), 1.13 (d, J=6.3 Hz, 3H); IR (thin film) 2978, 2937, 1733, 1647, 1527, 1451, 1262, 1147, 701 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C20H25N2O5, 373.1758; found, 373.1752.


Example 5A: Preparation of (2S,3S)-3-phenylbutan-2-yl(3-acetoxy-4-methoxypicolinoyl)-L-alaninate



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To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (84 mg, 0.23 mmol) dissolved in pyridine (1.0 mL) was added dropwise acetic anhydride (0.25 mL, 2.65 mmol) under nitrogen. Upon stirring for 30 min, the reaction mixture was concentrated in vacuo, followed by azeotroping with toluene (10 mL). The crude residue was purified via automated flash column chromatography (SiO2, 0-40% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl(3-acetoxy-4-methoxypicolinoyl)-L-alaninate (90 mg, 0.21 mmol, 91% yield) as colorless oil: 1H NMR (500 MHz, CDCl3) δ 8.56 (s, 1H), 8.34 (d, J=5.5 Hz, 1H), 7.32-7.27 (m, 2H), 7.24-7.16 (m, 3H), 7.01 (d, J=5.5 Hz, 1H), 5.09 (dq, J=7.7, 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.91 (s, 3H), 2.96-2.86 (m, 1H), 2.41 (s, 3H), 1.49 (d, J=7.2 Hz, 3H), 1.30 (d, J=7.0 Hz, 3H), 1.10 (d, J=6.3 Hz, 3H); IR (thin film) 3377, 2980, 2938, 1770, 1732, 1674, 1507, 1310, 1198, 1174, 702 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C22H27N2O6, 415.1864; found, 415.1859.


Example 5B: Preparation of (2S,3R)-3-(o-tolyl)butan-2-yl(3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate



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To a solution containing (2S,3R)-3-(o-tolyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate dissolved in 0.7 mL of acetone was added potassium carbonate (39 mg, 0.279 mmol) followed by bromomethyl acetate (27 μL, 0.279 mmol). The solution was heated at 50° C. for 1.5 hr. The reaction mixture was cooled and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-80% acetone/hexanes gradient) to afford (2S,3R)-3-(o-tolyl)butan-2-yl(3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate (63 mg, 93% yield) as a thick oil: 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J=5.4 Hz, 1H), 8.22 (t, J=7.4 Hz, 1H), 7.22-7.03 (m, 4H), 6.93 (d, J=5.4 Hz, 1H), 5.73 (dd, J=5.6, 1.8 Hz, 2H), 5.16 (dq, J=8.1, 6.3 Hz, 1H), 4.58-4.51 (m, 1H), 3.90 (s, 3H), 3.31-3.22 (m, 1H), 2.37 (s, 3H), 2.06 (s, 3H), 1.31 (d, J=6.2 Hz, 3H), 1.24 (d, J=7.0 Hz, 3H), 1.03 (d, J=7.2 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 172.26, 170.26, 162.87, 160.25, 145.68, 143.94, 142.57, 141.57, 136.03, 130.21, 126.16, 125.94, 109.49, 89.57, 75.57, 56.16, 48.08, 39.48, 20.87, 19.84, 17.92, 17.77, 17.05; HRMS-ESI (m/z) [M+H]+ calc'd for C24H30N2O7, 459.2126; found, 459.2121.


Example 5C: Preparation of 4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-ylisobutyrate



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To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl(3-hydroxy-4-methoxypicolinoyl)-L-alaninate (283.9 mg, 0.645 mmol) and N,N-dimethylpyridin-4-amine (15.75 mg, 0.129 mmol) was prepared in CH2Cl2 (2 mL). To this solution was added triethylamine (0.180 mL, 1.289 mmol) followed by isobutyryl chloride (0.102 mL, 0.967 mmol). The resultant clear reaction was stirred at ambient temperature overnight. The reaction was concentrated under reduced pressure to afford an orange oil under a stream of N2. The crude residue was purified via automated flash column chromatography (SiO2, 0-100% ethyl acetate/hexanes gradient) to afford 4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate (252.3 mg, 0.494 mmol, 77% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J=7.4 Hz, 1H), 8.34 (d, J=5.4 Hz, 1H), 7.64 (dd, J=8.0, 1.3 Hz, 1H), 7.54-7.47 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.31 (t, J=7.5 Hz, 1H), 6.99 (d, J=5.4 Hz, 1H), 5.26-5.11 (m, 1H), 4.76 (p, J=7.3 Hz, 1H), 3.89 (s, 3H), 3.34 (p, J=6.6 Hz, 1H), 2.96 (hept, J=7.0 Hz, 1H), 1.54 (d, J=7.2 Hz, 3H), 1.36 (dd, J=7.0, 1.3 Hz, 6H), 1.28 (d, J=6.8 Hz, 3H), 1.10 (d, J=6.3 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.25; IR (thin film) 3383, 2981, 1737, 1679, 1505, 1310, 1114, 1045, 732 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C25H30F3N2O6, 511.2050; found, 511.2048.


Example 6: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
Step 1: Preparation of (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl(3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate



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To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (120.1 mg, 0.273 mmol) dissolved in acetonitrile (2.73 mL) was added phosphorus pentasulfide (121 mg, 0.545 mmol) followed by 1,1,1,3,3,3-hexamethyldisiloxane (291 μL, 1.363 mmol) added in one portion. The reaction was heated to 45° C. for 30 min. The reaction was cooled, diluted with CH2Cl2 (10 mL) and quenched by the addition of saturated aqueous NaHCO3 (10 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic layers were passed through a phase separator and concentrated to a yellow oil. The crude material was purified via automated flash column chromatography (SiO2, 0-50% acetone/hexanes gradient) to afford (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl(3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (104.7 mg, 0.229 mmol, 84% yield) as a yellow semisolid; 1H NMR (400 MHz, CDCl3) δ 12.93 (s, 1H), 10.74 (d, J=7.6 Hz, 1H), 8.00 (d, J=5.1 Hz, 1H), 7.73-7.59 (m, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 6.89 (d, J=5.1 Hz, 1H), 5.30-5.18 (m, 1H), 5.14 (p, J=7.2 Hz, 1H), 3.96 (s, 3H), 3.37 (p, J=6.8 Hz, 1H), 1.69 (dd, J=7.2, 3.2 Hz, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.14 (d, J=6.3 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.23; IR (thin film) 3087, 2984, 1737, 1513, 1484, 1311, 1151, 1118, 800, 771 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C21H24F3N2O4S, 457.1403; found, 457.1399.


Step 2: Preparation of (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate



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To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl(3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (53.9 mg, 0.118 mmol) and N,N-dimethylpyridin-4-amine (2.89 mg, 0.024 mmol) dissolved in CH2Cl2 (2 mL) was added triethylamine (0.041 mL, 0.295 mmol) followed by acetyl chloride (9.23 μL, 0.130 mmol). The resultant light orange reaction was stirred at ambient temperature for 18 hr. The reaction was concentrated under reduced pressure to afford an orange oil under a stream of N2. The crude residue was purified via automated flash column chromatography (SiO2, 0-50% acetone/hexanes gradient) to afford (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl(3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (51.7 mg, 0.104 mmol, 88% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 9.96 (d, J=7.3 Hz, 1H), 8.34 (d, J=5.5 Hz, 1H), 7.71-7.59 (m, 1H), 7.59-7.47 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.39-7.28 (m, 1H), 7.00 (d, J=5.5 Hz, 1H), 5.28-5.15 (m, 2H), 3.91 (s, 3H), 3.42-3.29 (m, 1H), 2.37 (s, 3H), 1.64 (d, J=7.2 Hz, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.12 (d, J=6.3 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.23; HRMS-ESI (m/z) [M+H]+ calc'd for C23H26F3N2O5S, 499.1509; found, 499.1508.


Example 7: Preparation of 3-hydroxy-4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-phenylbutan-2-yl)oxy)propan-2-yl)carbamoyl)pyridine 1-oxide



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To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (54 mg, 0.15 mmol) dissolved in methylene chloride (1.0 mL) was added m-CPBA (50 mg, 0.29 mmol). Upon stirring for 30 min at room temperature, the reaction mixture was concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-50% acetone/hexanes gradient) to afford 3-hydroxy-4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-phenylbutan-2-yl)oxy)propan-2-yl)carbamoyl)pyridine 1-oxide (51 mg, 0.13 mmol, 86% yield) as viscous, pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 14.39 (s, 1H), 12.82 (d, J=6.9 Hz, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.25-7.15 (m, 3H), 6.78 (d, J=7.2 Hz, 1H), 5.10 (dq, J=8.1, 6.3 Hz, 1H), 4.75-4.64 (m, 1H), 3.97 (s, 3H), 2.96-2.86 (m, 1H), 1.56 (d, J=7.2 Hz, 3H), 1.30 (d, J=6.9 Hz, 3H), 1.12 (d, J=6.2 Hz, 3H); IR (thin film) 2978, 2937, 1735, 1643, 1569, 1479, 1452, 1211, 1154, 729, 702 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C20H25N2O6, 389.1707; found, 389.1703.


Example 8: Preparation of (2S,3S)-3-phenylbutan-2-yl (S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3 (4H)-yl)propanoate



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To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (54 mg, 0.15 mmol) and triphosgene (86 mg, 0.29 mmol) dissolved in methylene chloride (1.0 mL) was added pyridine (0.1 mL, 1.24 mmol). Upon stirring for 45 min, the reaction mixture was quenched with saturated sodium bicarbonate solution (5 mL) and extracted with methylene chloride (3×5 mL). The organics were passed through a phase separator and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-40% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3(4H)-yl)propanoate (41 mg, 0.10 mmol, 67% yield) as an off-white foam: 1H NMR (500 MHz, CDCl3) δ 8.61 (d, J=5.3 Hz, 1H), 7.24-7.17 (m, 2H), 7.17-7.06 (m, 4H), 5.61 (q, J=7.1 Hz, 1H), 5.16-5.06 (m, 1H), 4.06 (s, 3H), 2.93-2.83 (m, 1H), 1.70 (d, J=7.1 Hz, 3H), 1.27 (d, J=7.1 Hz, 3H), 1.04 (d, J=6.3 Hz, 3H); IR (thin film) 2978, 2942, 1769, 1712, 1602, 1501, 1371, 1242, 1081, 702 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C21H23N2O6, 399.1551; found, 399.1549.


Example A: Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Zymoseptoria tritici; Bayer Code SEPTTR)

Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 110 ppm Triton X-100. The fungicide solutions were applied onto wheat seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling. All fungicides were evaluated using the aforementioned method for their activity vs. all target diseases, unless stated otherwise. Wheat leaf blotch and brown rust activity were also evaluated using track spray applications, in which case the fungicides were formulated as EC formulations, containing 0.1% Trycol 5941 in the spray solutions.


Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. When disease symptoms were fully expressed on the 1st leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.


Example B: Evaluation of Fungicidal Activity: Wheat Brown Rust (Puccinia triticina; Synonym: Puccinia recondita f. sp. tritici; Bayer Code PUCCRT)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22° C. with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.


Example C: Evaluation of Fungicidal Activity: Asian Soybean Rust (Phakopsora pachyrhizi; Bayer Code PHAKPA)

Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 0.011% Tween 20. The fungicide solutions were applied onto soybean seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling.


Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two week old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22° C. and 100% relative humidity then transferred to a growth room at 23° C. for disease to develop. Disease severity was assessed on the sprayed leaves.


Example D: Evaluation of Fungicidal Activity: Tomato Early Blight (Alternaria solani; Bayer Code ALTESO)

Tomato plants (variety Outdoor Girl) were propagated in soil-less Metro mix, with each pot having one plant, and used when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Alternaria solani 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.


Example E: Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets (Cercospora beticola; Bayer Code CERCBE)

Sugar beet plants (variety HH88) were grown in soil-less Metro mix and trimmed regularly to maintain a uniform plant size prior to test. Plants were inoculated with a spore suspension 24 hr after fungicide treatments. Inoculated plants were kept in a dew chamber at 22° C. for 48 hr then incubated in a greenhouse set at 24° C. under a clear plastic hood with bottom ventilation until disease symptoms were fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.


Example F: Evaluation of Fungicidal Activity: Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotrichum lagenarium; Bayer Code COLLLA)

Cucumber seedlings (variety Bush Pickle) were propagated in soil-less Metro mix, with each pot having one plant, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Colletotrichum lagenarium 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room set at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.


Example G: Evaluation of Fungicidal Activity: Wheat Glume Blotch (Parastagonospora nodorum; Bayer Code LEPTNO)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Parastagonospora nodorum 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.


Example H: Evaluation of Fungicidal Activity: Cucumber Downy Mildew (Pseudoperonospora cubensis; Bayer Code PSPECU)

Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metro mix, with one plant per pot, and used in the test when 12 to 14 days old. Plants were inoculated with a spore suspension 24 hr following fungicide treatments. Test plants were inoculated with an aqueous spore suspension of Pseudoperonospora cubensis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 24 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. until disease was fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.


Example I: Evaluation of Fungicidal Activity: Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae; Bayer Code PYRIOR)

Rice seedlings (variety Japonica) were propagated in soil-less Metro mix, with each pot having 8 to 14 plants, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Pyricularia oryzae 24 hr after fungicide treatments. After inoculation, the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.


Example J: Evaluation of Fungicidal Activity: Barley Scald (Rhyncosporium secalis; Bayer Code RHYNSE)

Barley seedlings (variety Harrington) were propagated in soil-less Metro mix, with each pot having 8 to 12 plants, and used in the test when first leaf was fully emerged. Test plants were inoculated by an aqueous spore suspension of Rhyncosporium secalis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 20° C. with 100% relative humidity for 48 hr. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.


Example K: Evaluation of Fungicidal Activity: Grape Powdery Mildew (Uncinula necator; Bayer Code UNCINE)

Grape seedlings (variety Carignane) were grown in soil-less Metro mix, with one plant per pot, and used in the test when approximately 1 month old. Plants were inoculated 24 hr after fungicide treatment by shaking spores from infected leaves over test plants. Plants were maintained in a greenhouse set at 20° C. until disease was fully developed. Fungicide formulation, application and disease assessment on sprayed leaves followed the procedures as described in the Example A.









TABLE 1







Compound Structure, Appearance, and Preparation Method












As Prepared



Cmpd.

According



No.
Structure
To
Appearance













1


embedded image


Example 1A Example 2 Example 3
Oil





2


embedded image


Example 1A Example 2 Example 3
Oil





3


embedded image


Example 1A Example 2 Example 3
Oil





4


embedded image


Example 1A Example 2 Example 3
Oil





5


embedded image


Example 1A Example 2 Example 3
Oil





6


embedded image


Example 1A Example 2 Example 3
Oil





7


embedded image


Example 1A Example 2 Example 3
Oil





8


embedded image


Example 1A Example 2 Example 3
Oil





9


embedded image


Example 1B Example 2 Example 3
Oil





10


embedded image


Example 1B Example 2 Example 3
Oil





11


embedded image


Example 1B Example 2 Example 3
Oil





12


embedded image


Example 1B Example 2 Example 3
Oil





13


embedded image


Example 1B Example 2 Example 3
Oil





14


embedded image


Example 1B Example 2 Example 3
Oil





15


embedded image


Example 1B Example 2 Example 3
Oil





16


embedded image


Example 1B Example 2 Example 3
Oil





17


embedded image


Example 1B Example 2 Example 3
Oil





18


embedded image


Example 1B Example 2 Example 3
Oil





19


embedded image


Example 1B Example 2 Example 3
Oil





20


embedded image


Example 1B Example 2 Example 3
Oil





21


embedded image


Example 1B Example 2 Example 3
Oil





22


embedded image


Example 1A Example 2 Example 3
Oil





23


embedded image


Example 1A Example 2 Example 3
Oil





24


embedded image


Example 1A Example 2 Example 3
Oil





25


embedded image


Example 1A Example 2 Example 3
Oil





26


embedded image


Example 1A Example 2 Example 3
Oil





27


embedded image


Example 1A Example 2 Example 3
Oil





28


embedded image


Example 1A Example 2 Example 3
Oil





29


embedded image


Example 1B Example 2 Example 3
Oil





30


embedded image


Example 1B Example 2 Example 3
Oil





31


embedded image


Example 1B Example 2 Example 3
Oil





32


embedded image


Example 1B Example 2 Example 3
Oil





33


embedded image


Example 1B Example 2 Example 3
Oil





34


embedded image


Example 1B Example 2 Example 3
Oil





35


embedded image


Example 1B Example 2 Example 3
Oil





36


embedded image


Example 1B Example 2 Example 3
Oil





37


embedded image


Example 1B Example 2 Example 3
Oil





38


embedded image


Example 1B Example 2 Example 3
Oil





39


embedded image


Example 1B Example 2 Example 3
Oil





40


embedded image


Example 1B Example 2 Example 3
Oil





41


embedded image


Example 1A Example 2 Example 3
Light Yellow Oil





42


embedded image


Example 1A Example 2 Example 3
Clear Oil





43


embedded image


Example 1A Example 2 Example 3
Reddish Brown Oil





44


embedded image


Example 1A Example 2 Example 3
Orange Oil





45


embedded image


Example 1A Example 2 Example 3
Yellow Oil





46


embedded image


Example 1A Example 2 Example 3
Yellow Oil





47


embedded image


Example 1A Example 3
Clear, Colorless Oil





48


embedded image


Example 1A Example 3
Pale Yellow Oil





49


embedded image


Example 1A Example 2 Example 3
Clear, Colorless Oil





50


embedded image


Example 1A Example 2 Example 3
Pale Yellow Oil





51


embedded image


Example 1A Example 2 Example 3
Clear, Colorless Oil





52


embedded image


Example 1A Example 2 Example 3
Clear, Colorless Oil





53


embedded image


Example 1B Example 2 Example 3
Colorless Oil





54


embedded image


Example 1C Example 2 Example 3
Colorless Oil





55


embedded image


Example 1B Example 2 Example 3
Yellow Oil





56


embedded image


Example 1B Example 2 Example 3
Colorless Oil





57


embedded image


Example 1B Example 2 Example 3
Residue





58


embedded image


Example 4 Step 1
Oil





59


embedded image


Example 4 Step 1
Oil





60


embedded image


Example 4 Step 1
Oil





61


embedded image


Example 4 Step 1
Oil





62


embedded image


Example 4 Step 1
Oil





63


embedded image


Example 4 Step 1
Oil





64


embedded image


Example 4 Step 1
Oil





65


embedded image


Example 4 Step 1
Oil





66


embedded image


Example 4 Step 1
Oil





67


embedded image


Example 4 Step 1
Oil





68


embedded image


Example 4 Step 1
Oil





69


embedded image


Example 4 Step 1
Oil





70


embedded image


Example 4 Step 1
Oil





71


embedded image


Example 4 Step 1
Oil





72


embedded image


Example 4 Step 1
Oil





73


embedded image


Example 4 Step 1
Oil





74


embedded image


Example 4 Step 1
Oil





75


embedded image


Example 4 Step 1
Oil





76


embedded image


Example 4 Step 1
Oil





77


embedded image


Example 4 Step 1
Oil





78


embedded image


Example 4 Step 1
Oil





79


embedded image


Example 4 Step 1
Oil





80


embedded image


Example 4 Step 1
Oil





81


embedded image


Example 4 Step 1
Oil





82


embedded image


Example 4 Step 1
Oil





83


embedded image


Example 4 Step 1
Oil





84


embedded image


Example 4 Step 1
Oil





85


embedded image


Example 4 Step 1
Oil





86


embedded image


Example 4 Step 1
Oil





87


embedded image


Example 4 Step 1
Oil





88


embedded image


Example 4 Step 1
Oil





89


embedded image


Example 4 Step 1
Oil





90


embedded image


Example 4 Step 1
Oil





91


embedded image


Example 4 Step 1
Oil





92


embedded image


Example 4 Step 1
Oil





93


embedded image


Example 4 Step 1
Oil





94


embedded image


Example 4 Step 1
Oil





95


embedded image


Example 4 Step 1
Oil





96


embedded image


Example 4 Step 1
Oil





97


embedded image


Example 4 Step 1
Oil





98


embedded image


Example 4 Step 1
Dark Yellow Oil





99


embedded image


Example 4 Step 1
Dark Yellow Oil





100


embedded image


Example 4 Step 1
Brown Semisolid





101


embedded image


Example 4 Step 1
Light Brown Semisolid





102


embedded image


Example 1A Example 2 Example 3 Example 4 Step 1
Pale Yellow Oil





103


embedded image


Example 4 Step 1
Orange Semisolid





104


embedded image


Example 4 Step 1
Orange Semisolid





105


embedded image


Example 1A Example 2 Example 3 Example 4 Step 1
White Semisolid





106


embedded image


Example 4 Step 1
White Semisolid





107


embedded image


Example 4 Step 1
Pale Yellow Oil





108


embedded image


Example 4 Step 1
White Semisolid





109


embedded image


Example 4 Step 1
Clear, Colorless Glass





110


embedded image


Example 4 Step 1
Clear, Colorless Oil





111


embedded image


Example 4 Step 1
Clear, Colorless Oil





112


embedded image


Example 4 Step 1
Colorless Oil





113


embedded image


Example 4 Step 1
White Solid





114


embedded image


Example 4 Step 1
Yellow Oil





115


embedded image


Example 4 Step 1
Colorless Oil





116


embedded image


Example 4 Step 2
Thick Clear Oil





117


embedded image


Example 4 Step 2
Thick Clear Oil





118


embedded image


Example 4 Step 2
White Solid





119


embedded image


Example 4 Step 2
White Solid





120


embedded image


Example 4 Step 2
Thick Oil





121


embedded image


Example 4 Step 2
Thick Oil





122


embedded image


Example 4 Step 2
Thick Oil





123


embedded image


Example 4 Step 2
White Solid





124


embedded image


Example 4 Step 2
Thick Oil





125


embedded image


Example 4 Step 2
Thick Oil





126


embedded image


Example 4 Step 2
White Solid





127


embedded image


Example 4 Step 2
Thick Oil





128


embedded image


Example 4 Step 2
White Solid





129


embedded image


Example 4 Step 2
Thick Oil





130


embedded image


Example 4 Step 2
White Solid





131


embedded image


Example 4 Step 2
Thick Oil





132


embedded image


Example 4 Step 2
Thick Oil





133


embedded image


Example 4 Step 2
Thick Oil





134


embedded image


Example 4 Step 2
Thick Oil





135


embedded image


Example 4 Step 2
Think Oil





136


embedded image


Example 4 Step 2
Thick Oil





137


embedded image


Example 4 Step 2
Thick Oil





138


embedded image


Example 4 Step 2
White Solid





139


embedded image


Example 4 Step 2
Thick Oil





140


embedded image


Example 4 Step 2
Thick Oil





141


embedded image


Example 4 Step 2
White Solid





142


embedded image


Example 4 Step 2
Thick Oil





143


embedded image


Example 4 Step 2
Thick Oil





144


embedded image


Example 4 Step 2
Thick Oil





145


embedded image


Example 4 Step 2
Think Oil





146


embedded image


Example 4 Step 2
Thick Oil





147


embedded image


Example 4 Step 2
Thick Oil





148


embedded image


Example 4 Step 2
Thick Oil





149


embedded image


Example 4 Step 2
Thick Oil





150


embedded image


Example 4 Step 2
Thick Oil





151


embedded image


Example 4 Step 2
Thick Oil





152


embedded image


Example 4 Step 2
Thick Oil





153


embedded image


Example 4 Step 2
White Solid





154


embedded image


Example 4 Step 2
Thick Oil





155


embedded image


Example 4 Step 2
White Solid





156


embedded image


Example 4 Step 2
Thick Oil





157


embedded image


Example 4 Step 2
Thick Oil





158


embedded image


Example 4 Step 2
Orange Oil





159


embedded image


Example 4 Step 2
Orange Oil





160


embedded image


Example 4 Step 2
Pale Yellow Oil





161


embedded image


Example 4 Step 2
Yellow Oil





162


embedded image


Example 4 Step 2
Yellow Oil





163


embedded image


Example 4 Step 2
Clear, Colorless Oil





164


embedded image


Example 4 Step 2
Yellow Oil





165


embedded image


Example 4 Step 2
Orange Oil





166


embedded image


Example 4 Step 2
Clear, Colorless Oil





167


embedded image


Example 4 Step 2
Yellow Oil





168


embedded image


Example 4 Step 2
Clear, Colorless Oil





169


embedded image


Example 4 Step 2
Yellow Oil





170


embedded image


Example 4 Step 2
Colorless Oil





171


embedded image


Example 4 Step 2
Colorless Oil





172


embedded image


Example 4 Step 2
Pale Yellow Oil





173


embedded image


Example 4 Step 2
Colorless Oil





174


embedded image


Example 4 Step 2
Clear Oil





175


embedded image


Example 4 Step 2
Colorless Foam





176


embedded image


Example 4 Step 2
Residue





177


embedded image


Example 5A
Thick Oil





178


embedded image


Example 5A
Thick Oil





179


embedded image


Example 5C
Thick Oil





180


embedded image


Example 5C
Thick Oil





181


embedded image


Example 5A
Thick Oil





182


embedded image


Example 5A
Thick Oil





183


embedded image


Example 5A
Thick Oil





184


embedded image


Example 5A
Thick Oil





185


embedded image


Example 5A
Thick Oil





186


embedded image


Example 5A
Thick Oil





187


embedded image


Example 5A
Thick Oil





188


embedded image


Example 5A
Thick Oil





189


embedded image


Example 5A
Thick Oil





190


embedded image


Exampel 5A
Thick Oil





191


embedded image


Example 5A
Thick Oil





192


embedded image


Example 5A
Thick Oil





193


embedded image


Example 5A
Thick Oil





194


embedded image


Example 5A
Thick Oil





195


embedded image


Example 5A
Thick Oil





196


embedded image


Example 5C
Thick Oil





197


embedded image


Example 5C
Thick Oil





198


embedded image


Example 5C
Thick Oil





199


embedded image


Example 5C
Thick Oil





200


embedded image


Example 5C
Thick Oil





201


embedded image


Example 5C
Thick Oil





202


embedded image


Example 5C
Thick Oil





203


embedded image


Example 5C
Thick Oil





204


embedded image


Example 5C
Thick Oil





205


embedded image


Example 5C
Thick Oil





206


embedded image


Example 5C
Thick Oil





207


embedded image


Example 5C
Thick Oil





208


embedded image


Example 5C
Thick Oil





209


embedded image


Example 5C
Thick Oil





210


embedded image


Example 5C
Thick Oil





211


embedded image


Example 5C
Thick Oil





212


embedded image


Example 5C
Thick Oil





213


embedded image


Example 5C
Thick Oil





214


embedded image


Example 5C
Thick Oil





215


embedded image


Example 5C
Thick Oil





216


embedded image


Example 5C
Thick Oil





217


embedded image


Example 5C
Thick Oil





218


embedded image


Example 5C
Thick Oil





219


embedded image


Example 5C
Thick Oil





220


embedded image


Example 5A
Thick Oil





221


embedded image


Example 5C
Thick Oil





222


embedded image


Example 5C
Thick Oil





223


embedded image


Example 5C
Thick Oil





224


embedded image


Example 5C
Thick Oil





225


embedded image


Example 5C
Thick Oil





226


embedded image


Example 5C
Thick Oil





227


embedded image


Example 5C
Thick Oil





228


embedded image


Example 5C
Thick Oil





229


embedded image


Example 5C
Thick Oil





230


embedded image


Example 5C
Thick Oil





231


embedded image


Example 5B
Thick Oil





232


embedded image


Example 5B
Thick Oil





233


embedded image


Example 5B
Thick Oil





234


embedded image


Example 5C
Yellow Oil





235


embedded image


Example 5C
Pale Yellow Oil





236


embedded image


Example 5C
Yellow Oil





237


embedded image


Example 5C
Clear, Colorless Oil





238


embedded image


Example 5C
Clear, Colorless Oil





239


embedded image


Example 5C
Clear, Colorless Oil





240


embedded image


Example 5C
Clear, Colorless Oil





241


embedded image


Example 5C
Clear, Colorless Oil





242


embedded image


Example 5C
Clear, Colorless Oil





243


embedded image


Example 5C
Clear, Colorless Oil





244


embedded image


Example 5C
Clear, Colorless Oil





245


embedded image


Example 5C
Yellow Oil





246


embedded image


Example 5C
Pale Yellow Oil





247


embedded image


Example 5C
Clear, Colorless Oil





248


embedded image


Example 5C
Clear, Colorless Oil





249


embedded image


Example 5C
Clear, Colorless Oil





250


embedded image


Example 5C
Clear, Colorless Oil





251


embedded image


Example 5C
Clear, Colorless Oil





252


embedded image


Example 5C
Clear, Colorless Oil





253


embedded image


Example 5C
Clear, Colorless Oil





254


embedded image


Example 5C
Clear, Colorless Oil





255


embedded image


Example 5C
Clear, Colorless Oil





256


embedded image


Example 5C
Clear, Colorless Oil





257


embedded image


Example 5A
Colorless Oil





258


embedded image


Example 5A
Colorless Oil





259


embedded image


Example 5A
Pale Yellow Oil





260


embedded image


Example 5A
Colorless Oil





261


embedded image


Example 8
Off-White Foam





262


embedded image


Example 8
Tan Foam





263


embedded image


Example 5A
Clear Oil





264


embedded image


Example 5A
Clear Oil





265


embedded image


Example 5C
Clear Oil





266


embedded image


Example 5C
Colorless Oil





267


embedded image


Example 6 Step 1
Yellow Semisolid





268


embedded image


Example 6 Step 1
Yellow Semisolid





269


embedded image


Example 6 Step 1
Orange Semisolid





270


embedded image


Example 6 Step 2
Yellow Oil





271


embedded image


Example 6 Step 2
Yellow Oil





272


embedded image


Example 6 Step 2
Yellow Oil





273


embedded image


Example 7
Yellow Oil





274


embedded image


Example 7
Pale Yellow Oil





275


embedded image


Example 7
Pale Yellow Oil





276


embedded image


Example 7
Pale Yellow Oil





277


embedded image


Example 7
Pale Yellow Oil





278


embedded image


Example 5C
White Solid





279


embedded image


Example 5C
White Solid





280


embedded image


Example 5C
Yellow Oil





281


embedded image


Example 5C
Clear Oil





282


embedded image


Example 5C
White Solid





284


embedded image


Example 5C
Thick Yellow Oil





285


embedded image


Example 5C
Glassy Solid





*Cmpd. No.-Compound Number













TABLE 2







Analytical Data












Melting





Cmpd.
Point


No.
(° C.)
IR (cm−1)
MASS SPEC
NMR














1


ESIMS m/z 362.3






([M + Na]+)


2


ESIMS m/z 354.3





([M + H]+)


3


ESIMS m/z 382.3





([M + H]+)


4


ESIMS m/z 376.3





([M + Na]+)


5


ESIMS m/z 362.3





([M + Na]+)


6


ESIMS m/z 354.3





([M + H]+)


7


ESIMS m/z 382.3





([M + H]+)


8


ESIMS m/z 354.3





([M + H]+)


9


ESIMS m/z 344.3





([M + Na]+)


10


ESIMS m/z 336.5





([M + H]+)


11


ESIMS m/z 364.3





([M + H]+)


12


ESIMS m/z 336.2





([M + H]+)


13


ESIMS m/z 348.2





([M + Na]+)


14


ESIMS m/z 340.5





([M + H]+)


15


ESIMS m/z 390.3





([M + Na]+)


16


ESIMS m/z 340.2





([M + H]+)


17


ESIMS m/z 374.3





([M + Na]+)


18


ESIMS m/z 366.3





([M + H]+)


19


ESIMS m/z 394.3





([M + H]+)


20


ESIMS m/z 366.3





([M + H]+)


21


ESIMS m/z 362.3





([M + Na]+)


22


ESIMS m/z 376.3





([M + Na]+)


23


ESIMS m/z 382.3





([M + H]+)


24


ESIMS m/z 354.3





([M + H]+)


25


ESIMS m/z 362.3





([M + Na]+)


26


ESIMS m/z 376.3





([M + Na]+)


27


ESIMS m/z 382.3





([M + H]+)


28


ESIMS m/z 376.3





([M + Na]+)


29


ESIMS m/z 344.3





([M + Na]+)


30


ESIMS m/z 336.2





([M + H]+)


31


ESIMS m/z 364.3





([M + H]+)


32


ESIMS m/z 336.3





([M + H]+)


33


ESIMS m/z 348.2





([M + Na]+)


34


ESIMS m/z 340.3





([M + H]+)


35


ESIMS m/z 368.3





([M + H]+)


36


ESIMS m/z 340.3





([M + H]+)


37


ESIMS m/z 374.3





([M + Na]+)


38


ESIMS m/z 366.3





([M + H]+)


39


ESIMS m/z 394.4





([M + H]+)


40


ESIMS m/z 366.3





([M + H]+)


41


ESIMS m/z 372.3





([M + Na]+)


42


ESIMS m/z 372.3





([M + Na]+)


43

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3355,
[M + Na]+ calcd for
7.64 (dd, J = 7.8, 1.4 Hz, 1H), 7.52 (td, J = 7.6,




2981, 1711,
C19H26F3NNaO4,
1.3 Hz, 1H), 7.43 (d, J = 7.9 Hz,




1310, 1150,
412.1706; found,
1H), 7.35-7.28 (m, 1H),




1116, 1046,
412.1698
5.25-5.13 (m, 1H), 5.08 (d, J = 7.9 Hz, 1H),




770 cm−1

4.42-4.28 (m, 1H), 3.41-3.27 (m, 1H),






1.46 (s, 9H), 1.43 (d, J = 7.2 Hz, 3H),






1.27 (d, J = 6.8 Hz, 3H), 1.07 (d, J = 6.3 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −58.25.



44

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3362,
[M + Na]+ calcd for
7.42 (dd, J = 8.8, 5.4 Hz, 1H), 7.35 (dd, J = 9.2,




2982, 1711,
C19H25F4NNaO4,
2.8 Hz, 1H), 7.23 (td, J = 8.2, 2.8 Hz,




1499, 1314,
430.1612; found,
1H), 5.18-5.09 (m, 1H), 5.07 (d,




1154, 1121,
430.1607
J = 7.6 Hz, 1H), 4.41-4.27 (m, 1H),




1046, 909,

3.36-3.24 (m, 1H), 1.46 (s, 9H),




879 cm−1

1.42 (d, J = 7.3 Hz, 3H), 1.26 (d, J = 6.8 Hz,






3H), 1.08 (d, J = 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.81,







−114.05.


45

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3364,
[M + Na]+ calcd for
7.64 (dd, J = 8.0, 1.3 Hz, 1H), 7.52 (td, J = 7.6,




2981, 1712,
C19H26F3NNaO4,
1.3 Hz, 1H), 7.43 (d, J = 7.8 Hz,




1310, 1150,
412.1706; found,
1H), 7.32 (t, J = 7.6 Hz, 1H),




1116, 1046,
412.1699
5.25-5.13 (m, 1H), 5.04 (d, J = 7.8 Hz, 1H),




770 cm−1

4.42-4.26 (m, 1H), 3.40-3.26 (m,






1H), 1.46 (s, 9H), 1.41 (d, J = 7.3 Hz,






3H), 1.29 (d, J = 6.7 Hz, 3H), 1.05 (d, J = 6.2 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −58.25.



46

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 2981,
[M + Na]+ calcd for
7.42 (dd, J = 8.8, 5.3 Hz, 1H), 7.35 (dd, J = 9.2,




1711, 1498,
C19H25F4NNaO4,
2.8 Hz, 1H), 7.23 (td, J = 8.3, 2.9 Hz,




1314, 1154,
430.1612; found,
1H), 5.20-5.09 (m, 1H), 5.02 (d,




1120, 1045,
430.1603
J = 7.8 Hz, 1H), 4.42-4.23 (m, 1H),




909, 879,

3.29 (tt, J = 7.6, 6.0 Hz, 1H), 1.46 (s,




739 cm−1

9H), 1.40 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 6.8 Hz,






3H), 1.07 (d, J = 6.4 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.78,







−58.80, −114.19.


47

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3357,
[M + NH4]+ calcd
7.05-6.91 (m, 3H), 5.58 (ddq, J = 10.5, 8.3,




2977, 1713,
for C20H35N2O4,
6.2 Hz, 1H), 5.11 (s, 1H),




1500, 1452,
367.2587; found,
4.42-4.28 (m, 1H), 3.49-3.33 (m, 1H),




1365, 1162,
367.2587
2.44-2.33 (m, 6H), 1.46 (d, J = 1.1 Hz, 9H),




1055, 1006,

1.45-1.39 (m, 3H), 1.27 (dd, J = 7.1,




769 cm−1

3.5 Hz, 3H), 1.02 (dd, J = 7.7, 6.2 Hz,






3H).


48

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3357,
[M + Na]+ calcd for
6.70 (ddd, J = 16.1, 9.4, 2.9 Hz, 2H),




2978, 1712,
C20H30FNNaO4,
5.53 (ddq, J = 10.5, 8.6, 6.2 Hz, 1H),




1366, 1162,
390.2051; found,
5.11 (s, 1H), 4.41-4.26 (m, 1H),




1057, 1023,
390.2048
3.44-3.27 (m, 1H), 2.40 (d, J = 1.7 Hz, 3H),




1006, 857 cm−1

2.35 (s, 3H), 1.46 (s, 9H),






1.45-1.38 (m, 3H), 1.25 (dd, J = 7.2, 3.8 Hz, 3H),






1.01 (dd, J = 7.6, 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.37,







−118.44.


49

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3361,
[M + Na]+ calcd for
7.04-6.93 (m, 3H), 5.58 (ddq, J = 10.4, 8.3,




2977, 1713,
C20H31NNaO4,
6.2 Hz, 1H), 5.10 (d, J = 7.3 Hz, 1H),




1365, 1162,
372.2145; found,
4.43-4.27 (m, 1H), 3.48-3.29 (m,




1056, 1006,
372.2144
1H), 2.41 (d, J = 1.6 Hz, 3H), 2.37 (s,




769 cm−1

3H), 1.46 (d, J = 1.1 Hz, 9H),






1.45-1.39 (m, 3H), 1.27 (dd, J = 7.1, 3.5 Hz,






3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H).


50

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3359,
[M + Na]+ calcd for
6.70 (ddd, J = 16.2, 9.4, 2.9 Hz, 2H),




2978, 1712,
C20H30FNNaO4,
5.53 (ddq, J = 10.5, 8.6, 6.2 Hz, 1H),




1450, 1366,
390.2051; found,
5.09 (s, 1H), 4.43-4.28 (m, 1H), 3.34 (dp,




1163, 1057,
390.2050
J = 10.3, 6.9 Hz, 1H), 2.40 (d, J = 1.7 Hz,




1023, 1006,

3H), 2.35 (s, 3H), 1.46 (s, 9H),




858, 732 cm−1

1.45-1.36 (m, 3H), 1.26 (d, J = 3.8 Hz,






3H), 1.01 (dd, J = 7.6, 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.40,







−118.46.


51

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3356,
[M + Na]+ calcd for
7.03-6.94 (m, 3H), 5.58 (ddq, J = 10.5, 8.3,




2977, 1713,
C20H31NNaO4,
6.2 Hz, 1H), 5.10 (d, J = 7.1 Hz, 1H),




1500, 1452,
372.2145; found,
4.43-4.27 (m, 1H), 3.50-3.34 (m,




1163, 1056,
372.2137
1H), 2.41 (d, J = 1.6 Hz, 3H), 2.37 (s,




769 cm−1

3H), 1.46 (d, J = 1.1 Hz, 9H),






1.45-1.36 (m, 3H), 1.27 (dd, J = 7.2, 3.5 Hz,






3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H).


52

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3358,
[M + Na]+ calcd for
6.70 (ddd, J = 16.0, 9.4, 2.9 Hz, 2H),




2978, 1712,
C20H30FNNaO4,
5.53 (ddq, J = 10.5, 8.5, 6.2 Hz, 1H),




1366, 1163,
390.2051; found,
5.11 (s, 1H), 4.33 (q, J = 7.3 Hz, 1H),




1058, 1023,
390.2051
3.35 (ddq, J = 13.0, 10.4, 7.1, 6.5 Hz, 1H),




1006, 858,

2.40 (d, J = 1.8 Hz, 3H), 2.35 (s, 3H),




733 cm−1

1.46 (s, 9H), 1.45-1.39 (m, 3H),






1.25 (dd, J = 7.2, 3.8 Hz, 3H), 1.01 (dd, J = 7.6,






6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.39,







−118.45.


53

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3357,
[M + Na]+ calcd for
7.23-7.12 (m, 2H), 6.96-6.79 (m, 2H),




2977, 2936,
C19H29NO5Na,
5.24 (dq, J = 7.7, 6.3 Hz, 1H), 5.00 (d, J = 6.6 Hz,




2837, 1711,
374.1938; found,
1H), 4.19-4.10 (m, 1H),




1493, 1241,
374.1944
3.81 (s, 3H), 3.43 (p, J = 7.3 Hz, 1H),




1161, 1052,

1.42 (s, 9H), 1.25-1.20 (m, 6H), 0.99 (d, J = 7.1 Hz,




752 cm−1

3H).


54

IR (thin


1H NMR (400 MHz, CDCl3) δ





film) 3355,

7.35-7.25 (m, 2H), 7.27-7.15 (m, 3H),




2978, 2934,

5.12-5.01 (m, 2H), 4.35-4.26 (m, 1H),




1711, 1495,

2.95-2.83 (m, 1H), 1.45 (s, 9H),




1452, 1366,

1.37 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 7.1 Hz,




1161, 1087,

3H), 1.09 (d, J = 6.3 Hz, 3H).




1065, 701 cm−1


13C NMR (126 MHz, CDCl3) δ 172.9,







155.0, 143.0, 128.5, 127.8, 126.7, 79.7,






76.1, 49.5, 45.1, 28.3, 18.9, 18.3, 17.5.


55

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3365,
[M + Na]+ calcd for
6.64-6.53 (m, 2H), 5.11-5.05 (m, 1H),




2977, 2933,
C17H27NO4SNa,
5.06-4.95 (m, 1H), 4.35-4.26 (m, 1H),




1712, 1500,
364.1553; found,
3.20-3.08 (m, 1H), 2.43 (d, J = 1.2 Hz,




1449, 1365,
364.1551
3H), 1.45 (s, 9H), 1.38 (d, J = 7.2 Hz,




1161, 1065,

3H), 1.31 (d, J = 7.1 Hz, 3H),




796 cm−1

1.16 (d, J = 6.3 Hz, 3H).


56

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ





film) 3365,
[M + Na]+ calcd for
7.08 (dd, J = 8.5, 6.7 Hz, 1H),




2978, 2937,
C19H28FNO5Na,
6.65-6.53 (m, 2H), 5.16-5.07 (m, 1H), 5.05 (d, J = 7.6 Hz,




1708, 1601,
392.1844; found,
1H), 4.30-4.23 (m, 1H),




1502, 1163,
392.1839
3.80 (s, 3H), 3.38-3.29 (m, 1H),




1035, 952,

1.45 (s, 9H), 1.35 (d, J = 7.2 Hz, 3H),




834 cm−1

1.23 (d, J = 7.1 Hz, 3H), 1.10 (d, J = 6.3 Hz,






3H).


57




1H NMR (300 MHz, CDCl3) δ







7.13-6.95 (m, 2H), 6.77-6.52 (m, 2H),






5.11 (d, J = 7.8 Hz, 1H), 5.00 (dq, J = 8.2,






6.2 Hz, 1H), 4.31 (t, J = 7.4 Hz, 1H),






2.92 (s, 6H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz,






3H), 1.31-1.17 (m, 4H),






1.08 (d, J = 6.3 Hz, 3H).







13C NMR (75 MHz, CDCl3) δ 172.95,







171.16, 155.04, 149.48, 130.86,






128.41, 112.69, 60.40, 49.51, 44.14,






40.70, 28.35, 18.93, 18.27, 17.82,






14.21.


58


ESIMS m/z 240.2





([M + H]+)


59


ESIMS m/z 240.2





([M + H]+)


60


ESIMS m/z 222.2





([M + H]+)


61


ESIMS m/z 248.9





([M + Na]+)


62


ESIMS m/z 252.2





([M + H]+)


63


ESIMS m/z 240.2





([M + H]+)


64


ESIMS m/z 240.2





([M + H]+)


65


ESIMS m/z 222.2





([M + H]+)


66


ESIMS m/z 226.2





([M + H]+)


67


ESIMS m/z 252.2





([M + H]+)


68


ESIMS m/z 254.2





([M + H]+)


69


ESIMS m/z 254.2





([M + H]+)


70


ESIMS m/z 236.2





([M + H]+)


71


ESIMS m/z 240.2





([M + H]+)


72


ESIMS m/z 266.3





([M + H]+)


73


ESIMS m/z 254.2





([M + H]+)


74


ESIMS m/z 254.2





([M + H]+)


75


ESIMS m/z 236.2





([M + H]+)


76


ESIMS m/z 240.2





([M + H]+)


77


ESIMS m/z 266.3





([M + H]+)


78


ESIMS m/z 282.3





([M + H]+)


79


ESIMS m/z 282.2





([M + H]+)


80


ESIMS m/z 264.3





([M + H]+)


81


ESIMS m/z 268.2





([M + H]+)


82


ESIMS m/z 294.3





([M + H]+)


83


ESIMS m/z 282.2





([M + H]+)


84


ESIMS m/z 282.2





([M + H]+)


85


ESIMS m/z 264.3





([M + H]+)


86


ESIMS m/z 268.2





([M + H]+)


87


ESIMS m/z 294.3





([M + H]+)


88


ESIMS m/z 254.2





([M + H]+)


89


ESIMS m/z 254.2





([M + H]+)


90


ESIMS m/z 236.2





([M + H]+)


91


ESIMS m/z 240.2





([M + H]+)


92


ESIMS m/z 266.3





([M + H]+)


93


ESIMS m/z 254.2





([M + H]+)


94


ESIMS m/z 254.2





([M + H]+)


95


ESIMS m/z 236.2





([M + H]+)


96


ESIMS m/z 240.2





([M + H]+)


97


ESIMS m/z 266.3





([M + H]+)


98


ESIMS m/z 250.3





([M + H]+)


99


ESIMS m/z 250.3





([M + H]+)


100


ESIMS m/z 290.2





([M + H]+)


101


ESIMS m/z 308.1





([M + H]+)


102


ESIMS m/z 214.2





([M + H]+)


103


ESIMS m/z 290.2





([M + H]+)


104


ESIMS m/z 308.1





([M + H]+)


105


ESIMS m/z 214.2





([M + H]+)


106


ESIMS m/z 250.2





([M + H]+)


107


ESIMS m/z 268.2





([M + H]+)


108


ESIMS m/z 250.2





([M + H]+)


109


ESIMS m/z 268.2





([M + H]+)


110


ESIMS m/z 250.2





([M + H]+)


111


ESIMS m/z 268.2





([M + H]+)


112


HRMS-ESI (m/z)





[M + H]+ calcd for





C14H22NO3,





252.1600; found,





252.1443


113


HRMS-ESI (m/z)





[M + H]+ calcd for





C13H20NO2,





222.1489; found,





222.1485


114

IR (thin




film) 2854,




1740, 1233,




1203, 1118,




1078, 872,




796 cm−1


115


HRMS-ESI (m/z)





[M + H]+ calcd for





C14H21FNO3,





270.1500; found,





270.1501


116


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.16 (s, 1H), 8.52 (d, J = 7.8 Hz, 1H),





C22H29N2O5,
8.00 (d, J = 5.2 Hz, 1H), 7.09-7.03 (m,





401.2071; found,
1H), 7.00-6.94 (m, 2H), 6.88 (d, J = 5.1 Hz,





401.2067
1H), 5.13 (dq, J = 8.4, 6.2 Hz,






1H), 4.79-4.67 (m, 1H), 3.95 (s, 3H),






3.16 (dq, J = 8.9, 7.0 Hz, 1H), 2.31 (s,






3H), 2.28 (s, 3H), 1.57 (d, J = 7.2 Hz,






3H), 1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.2 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.86,







168.68, 155.38, 148.77, 140.50,






138.63, 135.76, 135.33, 131.31,






130.52, 126.97, 126.26, 109.44, 56.08,






48.18, 39.45, 20.89, 19.87, 18.48,






18.46, 17.56.


117


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.17 (d, J = 0.6 Hz, 1H), 8.50 (d, J = 7.9 Hz,





C22H29N2O5,
1H), 8.01 (d, J = 5.2 Hz, 1H),





401.2071; found,
7.10-7.02 (m, 1H), 6.97 (d, J = 6.9 Hz, 2H),





401.2064
6.88 (d, J = 5.2 Hz, 1H), 5.16 (dq, J = 8.4,






6.2 Hz, 1H), 4.77-4.68 (m, 1H),






3.95 (s, 3H), 3.19-3.09 (m, 1H),






2.31 (s, 3H), 2.27 (s, 3H), 1.54 (d, J = 7.2 Hz,






3H), 1.23 (d, J = 6.9 Hz, 3H),






1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.87,







168.72, 155.38, 148.76, 140.50,






138.60, 135.72, 135.36, 131.29,






130.53, 127.00, 126.28, 109.44, 56.08,






47.99, 39.42, 20.87, 19.88, 18.31,






18.26, 17.65.


118


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.04 (s, 1H), 8.46 (t, J = 5.8 Hz, 1H),





C20H23FN2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.18-7.06 (m,





391.1664; found,
1H), 6.93-6.79 (m, 3H), 5.15 (dq, J = 8.0,





391.1662
6.3 Hz, 1H), 4.21 (dd, J = 5.7, 3.2 Hz,






2H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz,






1H), 2.33 (s, 3H), 1.24 (d, J = 6.9 Hz,






3H), 1.15 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.32,







168.74, 161.97, 160.03, 155.39,






148.70, 140.61, 137.91, 137.20,






130.40, 127.85, 117.11, 116.95,






113.07, 112.90, 109.54, 76.40, 56.10,






41.03, 39.10, 20.00, 18.22, 17.42.


119


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.01 (s, 1H), 8.34 (t, J = 5.8 Hz, 1H),





C20H23FN2O5,
7.99 (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 9.5,





391.1664; found,
5.8 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H),





391.1660
6.85-6.75 (m, 2H), 5.24-5.10 (m,






1H), 4.23-3.92 (m, 5H), 3.23 (p, J = 7.1 Hz,






1H), 2.33 (s, 3H), 1.25 (m,






6H).







13C NMR (126 MHz, CDCl3) δ 169.19,







168.38, 161.97, 160.02, 155.38,






148.68, 140.55, 138.37, 136.63,






130.36, 127.68, 116.81, 116.65,






112.86, 112.70, 109.52, 75.82, 56.09,






40.88, 38.65, 19.86, 17.20, 16.64.


120


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.03 (s, 1H), 8.34 (t, J = 5.8 Hz, 1H),





C20H24N2O5,
7.99 (d, J = 5.2 Hz, 1H), 7.20 (dd, J = 7.6,





373.1758; found,
1.3 Hz, 1H), 7.16-7.06 (m, 3H),





373.1754
6.87 (d, J = 5.2 Hz, 1H), 5.24-5.17 (m,






1H), 4.16-3.89 (m, 2H), 3.95 (s, 3H),






3.29 (p, J = 7.1 Hz, 1H), 2.35 (s, 3H),






1.27 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 169.15,







168.40, 155.35, 148.66, 140.97,






140.52, 136.10, 130.41, 130.27,






126.30, 126.20, 126.14, 109.48, 75.92,






56.08, 40.85, 39.18, 19.79, 17.18,






16.37.


121


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.04 (s, 1H), 8.46 (t, J = 5.8 Hz, 1H),





C19H21FN2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 8.6,





377.1507; found,
5.5 Hz, 2H), 7.01-6.94 (m, 2H),





377.1504
6.89 (d, J = 5.2 Hz, 1H), 5.16-5.05 (m,






1H), 4.21 (dd, J = 5.8, 2.1 Hz, 2H),






3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H),






1.28 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 169.33,







168.65, 162.66, 160.72, 155.40,






148.71, 140.61, 138.35, 130.40,






129.27, 129.21, 115.36, 115.19,






109.55, 76.35, 56.10, 44.12, 41.06,






17.83, 17.27.


122


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.06 (s, 1H), 8.47 (t, J = 5.8 Hz, 1H),





C21H26N2O6,
8.01 (d, J = 5.2 Hz, 1H), 7.08 (d, J = 8.4 Hz,





403.1864; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





403.1835
6.77-6.66 (m, 2H), 5.15 (dq, J = 8.2, 6.3 Hz,






1H), 4.22 (dd, J = 5.7, 2.0 Hz, 2H),






3.95 (s, 3H), 3.77 (s, 3H),






3.18-3.07 (m, 1H), 2.32 (s, 3H), 1.23 (d, J = 6.9 Hz,






3H), 1.14 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.30,







168.80, 157.71, 155.38, 148.69,






140.60, 136.96, 133.70, 130.44,






127.36, 115.97, 111.49, 109.52, 76.84,






56.09, 55.12, 41.05, 39.03, 20.17,






18.27, 17.59.


123


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.04 (s, 1H), 8.46 (t, J = 5.8 Hz, 1H),





C20H23FN2O5,
8.00 (d, J = 5.2 Hz, 1H), 7.20-7.08 (m,





391.1664; found,
1H), 6.93-6.80 (m, 3H), 5.15 (dq, J = 7.9,





391.1662
6.3 Hz, 1H), 4.21 (dd, J = 5.7, 3.2 Hz,






2H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz,






1H), 2.33 (s, 3H), 1.24 (d, J = 6.9 Hz,






3H), 1.15 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.32,







168.75, 161.97, 160.03, 155.39,






148.70, 140.61, 137.91, 137.85,






137.20, 137.17, 130.40, 127.85,






127.78, 117.11, 116.95, 113.06,






112.90, 109.54, 76.40, 56.10, 41.03,






39.10, 19.99, 18.22, 17.42.


124


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.01 (d, J = 0.6 Hz, 1H), 8.34 (t, J = 5.8 Hz,





C20H23FN2O5,
1H), 7.99 (d, J = 5.2 Hz, 1H), 7.15 (dd,





391.1664; found,
J = 9.5, 5.8 Hz, 1H), 6.88 (d, J = 5.2 Hz,





391.1661
1H), 6.85-6.77 (m, 2H),






5.21-5.11 (m, 1H), 4.20-3.91 (m, 2H),






3.95 (s, 3H), 3.23 (p, J = 7.1 Hz, 1H),






2.33 (s, 3H), 1.30-1.20 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 169.19,







168.38, 161.97, 160.02, 155.38,






148.68, 140.55, 138.43, 136.66,






130.36, 127.75, 127.68, 116.81,






116.65, 112.86, 112.70, 109.52, 75.82,






56.09, 40.88, 38.65, 19.85, 17.20,






16.64.


125


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.03 (d, J = 0.6 Hz, 1H), 8.34 (t, J = 5.8 Hz,





C20H24N2O5,
1H), 7.99 (d, J = 5.2 Hz, 1H), 7.20 (dd,





373.1758; found,
J = 7.7, 1.3 Hz, 1H), 7.17-7.04 (m,





373.1755
3H), 6.87 (d, J = 5.2 Hz, 1H),






5.25-5.16 (m, 1H), 4.12 (dd, J = 18.2, 5.9 Hz,






1H), 3.95 (s, 3H), 3.98-3.89 (m,






1H), 3.29 (p, J = 7.1 Hz, 1H), 2.35 (s,






3H), 1.27 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 169.15,







168.41, 155.35, 148.66, 140.97,






140.52, 136.10, 130.41, 130.27,






126.30, 126.14, 109.48, 75.92, 56.08,






40.85, 39.18, 19.79, 17.18, 16.37.


126


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.04 (s, 1H), 8.46 (t, J = 5.9 Hz, 1H),





C19H21FN2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.22-7.08 (m,





377.1507; found,
2H), 6.98 (t, J = 8.7 Hz, 2H), 6.89 (d, J = 5.2 Hz,





377.1507
1H), 5.16-5.01 (m, 1H),






4.29-4.14 (m, 2H), 3.95 (s, 3H),






2.92 (p, J = 7.1 Hz, 1H), 1.28 (d, J = 7.0 Hz,






3H), 1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.33,







168.65, 162.67, 160.72, 155.41,






148.71, 140.61, 138.37, 130.40,






129.27, 129.21, 115.36, 115.19,






109.55, 76.36, 56.10, 44.12, 41.06,






17.83, 17.27.


127


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.06 (s, 1H), 8.47 (t, J = 5.7 Hz, 1H),





C21H26N2O6,
8.01 (d, J = 5.2 Hz, 1H), 7.08 (d, J = 8.4 Hz,





403.1864; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





403.1853
6.82-6.66 (m, 2H), 5.15 (dq, J = 8.1, 6.3 Hz,






1H), 4.29-4.15 (m, 2H), 3.95 (s, 3H),






3.77 (s, 3H), 3.17-3.08 (m, 1H),






2.32 (s, 3H), 1.23 (d, J = 6.9 Hz, 3H),






1.14 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.30,







168.80, 157.71, 155.38, 148.69,






140.60, 136.96, 133.70, 130.44,






127.36, 115.97, 111.49, 109.52, 76.84,






56.09, 55.12, 41.05, 39.03, 20.17,






18.27, 17.59.


128


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (d, J = 0.6 Hz, 1H), 8.49 (d, J = 7.9 Hz,





C24H25FN2O5,
1H), 8.00 (d, J = 5.2 Hz, 1H),





405.1820; found,
7.18-7.05 (m, 1H), 6.93-6.79 (m, 3H),





405.1819
5.11 (dq, J = 8.0, 6.3 Hz, 1H),






4.78-4.64 (m, 1H), 3.95 (s, 3H), 3.23-3.09 (m,






1H), 2.33 (s, 3H), 1.55 (d, J = 7.2 Hz,






3H), 1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.79,







168.69, 161.97, 160.03, 155.39,






148.77, 140.51, 137.87, 137.81,






137.33, 137.30, 130.47, 127.86,






127.79, 117.10, 116.94, 113.02,






112.85, 109.47, 76.32, 56.09, 48.13,






39.16, 20.00, 18.42, 18.36, 17.33.


129


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.09 (s, 1H), 8.35 (d, J = 7.9 Hz, 1H),





C21H25FN2O5,
7.98 (dd, J = 5.2, 3.6 Hz, 1H), 7.13 (dd, J = 8.4,





405.1820; found,
5.8 Hz, 1H), 6.94-6.73 (m, 3H),





405.1820
5.21-5.08 (m, 1H), 4.63-4.46 (m,






1H), 3.94 (s, 2H), 3.27-3.15 (m, 1H).







13C NMR (126 MHz, CDCl3) δ 171.55,







168.59, 161.91, 159.97, 155.37,






148.73, 140.44, 138.30, 137.15,






130.43, 127.47, 116.73, 116.57,






112.89, 112.73, 109.43, 75.74, 56.07,






47.87, 38.98, 19.90, 17.79, 17.32.


130


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.11 (s, 1H), 8.36 (d, J = 8.0 Hz, 1H),





C21H26N2O5,
7.97 (d, J = 5.2 Hz, 1H), 7.24-7.01 (m,





387.1914; found,
4H), 6.86 (d, J = 5.2 Hz, 1H),





387.1911
5.27-5.12 (m, 1H), 4.59-4.47 (m, 1H),






3.94 (s, 2H), 3.33-3.20 (m, 1H), 2.36 (s,






3H), 1.32 (d, J = 6.3 Hz, 3H), 1.24 (d, J = 7.1 Hz,






3H), 1.08 (d, J = 7.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.58,







168.54, 155.33, 148.71, 141.47,






140.41, 135.95, 130.49, 130.22,






126.20, 125.88, 109.39, 75.87, 56.06,






47.85, 39.52, 19.83, 17.83, 17.74,






17.14.


131


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (s, 1H), 8.47 (d, J = 8.0 Hz, 1H),





C20H23FN2O5,
8.00 (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 8.6,





391.1664; found,
5.4 Hz, 2H), 6.97 (t, J = 8.7 Hz, 2H),





391.1662
6.88 (d, J = 5.2 Hz, 1H),






5.11-5.02 (m, 1H), 4.71 (p, J = 7.3 Hz, 1H),






3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H),






1.53 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 7.1 Hz,






3H), 1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.67,







168.69, 162.64, 160.70, 155.40,






148.78, 140.51, 138.48, 130.46,






129.26, 129.19, 115.32, 115.16,






109.48, 76.31, 56.09, 48.12, 44.11,






18.38, 17.95, 17.16.


132


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.16 (s, 1H), 8.51 (d, J = 7.9 Hz, 1H),





C22H28N2O6,
8.00 (d, J = 5.2 Hz, 1H), 7.11-7.05 (m,





417.2020; found,
1H), 6.88 (d, J = 5.2 Hz, 1H), 6.70 (d, J = 6.7 Hz,





417.2007
2H), 5.11 (dq, J = 8.3, 6.3 Hz,






1H), 4.72 (p, J = 7.3 Hz, 1H),






3.95 (s, 3H), 3.77 (s, 3H), 3.18-3.06 (m,






1H), 2.32 (s, 3H), 1.56 (d, J = 7.2 Hz,






3H), 1.23 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.85,







168.67, 157.70, 155.38, 148.77,






140.50, 136.91, 133.86, 130.52,






127.36, 115.95, 111.48, 109.45, 56.08,






55.13, 48.17, 39.11, 20.18, 18.46,






17.57, 16.10.


133


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (s, 1H), 8.47 (d, J = 8.0 Hz, 1H),





C24H25FN2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.4,





405.1820; found,
5.8 Hz, 1H), 6.91-6.81 (m, 3H),





405.1819
5.12 (dq, J = 8.1, 6.3 Hz, 1H), 4.72 (p, J = 7.2 Hz,






1H), 3.95 (s, 3H),






3.20-3.10 (m, 1H), 2.33 (s, 3H), 1.54 (d, J = 7.1 Hz,






3H), 1.23 (d, J = 6.9 Hz, 3H),






1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.81,







168.74, 161.95, 160.01, 155.40,






148.78, 140.51, 137.89, 137.83,






137.29, 137.26, 130.48, 127.87,






127.81, 117.08, 116.91, 113.06,






112.90, 109.48, 76.19, 56.09, 47.96,






39.12, 20.02, 18.24, 18.12, 17.47.


134


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.12 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H),





C24H25FN2O5,
7.99 (d, J = 5.2 Hz, 1H), 7.18-7.12 (m,





405.1820; found,
1H), 6.88 (d, J = 5.2 Hz, 1H), 6.78 (t, J = 8.2 Hz,





405.1818
2H), 5.17-5.06 (m, 1H),






4.64-4.51 (m, 1H), 3.95 (s, 3H),






3.23 (p, J = 7.1 Hz, 1H), 2.33 (s, 3H),






1.38 (d, J = 7.1 Hz, 3H), 1.26-1.20 (m,






6H).







13C NMR (126 MHz, CDCl3) δ 171.29,







168.55, 161.93, 159.99, 155.38,






148.74, 140.44, 138.41, 138.35,






136.73, 136.71, 130.43, 127.71,






127.65, 116.77, 116.61, 112.81,






112.64, 109.45, 75.62, 56.09, 47.82,






38.64, 19.89, 19.88, 18.06, 17.22,






16.84.


135


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.15 (s, 1H), 8.30 (d, J = 8.0 Hz, 1H),





C21H26N2O5,
7.99 (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.8,





387.1914; found,
1.4 Hz, 1H), 7.15-7.00 (m, 3H),





387.1915
6.87 (d, J = 5.2 Hz, 1H), 5.20-5.12 (m,






1H), 4.59-4.50 (m, 1H), 3.95 (s, 3H),






3.29 (p, J = 7.1 Hz, 1H), 2.36 (s, 3H),






1.35 (d, J = 7.2 Hz, 3H),






1.29-1.22 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 171.30,







168.54, 155.35, 148.73, 141.04,






140.40, 136.09, 130.51, 130.26,






126.23, 126.11, 109.40, 75.73, 56.08,






47.88, 39.15, 19.83, 18.11, 17.16,






16.53.


136


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (s, 1H), 8.46 (d, J = 7.7 Hz, 1H),





C20H23FN2O5,
8.00 (dd, J = 5.2, 2.2 Hz, 1H), 7.15 (ddd, J = 9.9,





391.1664; found,
6.1, 3.4 Hz, 2H), 6.97 (td, J = 8.8,





391.1658
2.6 Hz, 2H), 6.88 (dd, J = 5.4, 1.5 Hz,






1H), 5.12-5.01 (m, 1H),






4.77-4.64 (m, 1H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz,






1H), 1.53 (d, J = 7.2 Hz, 3H),






1.28 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.72,







168.76, 162.65, 160.70, 155.41,






148.78, 140.51, 138.43, 138.40,






130.47, 129.29, 129.23, 115.33,






115.16, 109.48, 76.12, 56.09, 47.98,






44.09, 18.20, 17.69, 17.30.


137


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.17 (s, 1H), 8.50 (d, J = 7.9 Hz, 1H),





C22H28N2O6,
8.01 (d, J = 5.2 Hz, 1H), 7.09 (d, J = 8.4 Hz,





417.2020; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





417.2010
6.76-6.67 (m, 2H), 5.13 (dq, J = 8.3, 6.3 Hz,






1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s,






3H), 3.76 (s, 3H), 3.18-3.07 (m, 1H),






2.32 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H),






1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.86,







168.72, 157.68, 155.38, 148.76,






140.50, 136.94, 133.82, 130.53,






127.37, 115.97, 111.47, 109.45, 76.65,






56.08, 55.11, 47.99, 39.06, 20.19,






18.31, 18.20, 17.68.


138


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.16 (s, 1H), 8.50 (d, J = 9.4 Hz, 1H),





C23H29FN2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.11 (dd, J = 8.6,





433.2133; found,
5.8 Hz, 1H), 6.89 (d, J = 5.2 Hz, 1H),





433.2130
6.87-6.77 (m, 2H), 5.08 (dq, J = 8.0,






6.2 Hz, 1H), 4.65 (dd, J = 9.4, 4.8 Hz,






1H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz,






1H), 2.32 (s, 4H), 1.24 (d, J = 6.9 Hz,






3H), 1.14 (d, J = 6.2 Hz, 3H), 1.05 (d, J = 6.8 Hz,






3H), 0.96 (d, J = 6.8 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.73,







169.06, 161.95, 160.01, 155.42,






148.75, 140.52, 137.83, 137.77,






137.36, 130.51, 127.84, 127.78,






117.07, 116.91, 113.01, 112.85,






109.47, 76.43, 57.26, 56.09, 39.06,






31.35, 19.99, 19.48, 18.45, 17.38.


139


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.12 (s, 1H), 8.38 (d, J = 9.3 Hz, 1H),





C23H29FN2O5,
7.99 (t, J = 5.1 Hz, 1H), 7.14 (dd, J = 8.5,





433.2133; found,
5.9 Hz, 1H), 6.88 (dd, J = 7.6, 5.1 Hz,





433.213
1H), 6.84-6.72 (m, 3H), 5.13 (dq, J = 8.4,






6.3 Hz, 1H), 4.49 (td, J = 9.4, 4.9 Hz,






1H), 3.94 (s, 3H), 3.20 (p, J = 7.4 Hz,






1H), 2.33 (s, 3H), 1.94 (pd, J = 6.9,






4.6 Hz, 1H), 1.29 (d, J = 6.3 Hz, 3H),






1.21 (d, J = 7.1 Hz, 3H), 0.85 (d, J = 6.9 Hz,






3H), 0.68 (d, J = 6.8 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.52,







168.98, 161.96, 160.02, 155.39,






148.70, 140.45, 138.31, 138.25,






137.28, 137.25, 130.49, 127.46,






127.40, 116.75, 116.59, 112.92,






112.76, 109.42, 75.86, 56.97, 56.08,






38.86, 31.12, 19.89, 19.12, 17.79,






17.34, 17.02.


140


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.38 (d,






[M + H]+ calcd for
J = 9.4 Hz, 1H), 7.99 (d, J = 5.2 Hz,





C23H30N2O5,
1H), 7.20 (d, J = 7.7 Hz, 1H),





415.2227; found,
7.16-7.08 (m, 1H), 7.08-7.03 (m, 2H),





415.2222
6.86 (d, J = 5.2 Hz, 1H), 5.25-5.11 (m,






1H), 4.49 (dd, J = 9.4, 4.5 Hz, 1H),






3.94 (s, 3H), 3.37-3.18 (m, 1H),






2.34 (s, 3H), 1.91 (pd, J = 6.9, 4.5 Hz, 1H),






1.31 (d, J = 6.2 Hz, 3H), 1.23 (d, J = 7.1 Hz,






3H), 0.82 (d, J = 6.8 Hz, 3H),






0.64 (d, J = 6.8 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.54,







168.94, 155.34, 148.67, 141.56,






140.42, 135.94, 130.56, 130.25,






126.23, 125.89, 109.37, 75.96, 56.90,






56.07, 39.37, 31.11, 19.82, 19.14,






17.78, 17.11, 16.98.


141


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.16 (s, 1H), 8.48 (d, J = 9.4 Hz, 1H),





C22H27FN2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.19-7.10 (m,





419.1977; found,
2H), 6.94 (t, J = 8.7 Hz, 2H), 6.89 (d, J = 5.2 Hz,





419.1973
1H), 5.11-4.98 (m, 1H),






4.64 (dd, J = 9.4, 4.8 Hz, 1H), 3.95 (s,






3H), 2.92 (p, J = 7.1 Hz, 1H), 2.31 (pd,






J = 6.9, 4.8 Hz, 1H), 1.29 (d, J = 7.0 Hz,






3H), 1.12 (d, J = 6.3 Hz, 3H),






1.03 (d, J = 6.8 Hz, 3H), 0.95 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 170.57,







169.05, 162.62, 160.67, 155.43,






148.76, 140.52, 138.50, 130.50,






129.23, 129.16, 115.29, 115.13,






109.47, 77.27, 76.39, 57.25, 56.10,






43.96, 31.33, 19.41, 18.04, 17.40,






17.07.


142


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.18 (s, 1H), 8.52 (d, J = 9.4 Hz, 1H),





C24H32N2O6,
8.02 (d, J = 5.2 Hz, 1H), 7.06 (d, J = 8.4 Hz,





445.2333; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





445.2314
6.75-6.63 (m, 2H), 5.08 (dq, J = 8.3, 6.2 Hz,






1H), 4.66 (dd, J = 9.4, 4.8 Hz, 1H),






3.95 (s, 3H), 3.76 (s, 3H),






3.19-3.06 (m, 1H), 2.41-2.33 (m, 1H), 2.31 (s,






3H), 1.23 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.2 Hz,






3H), 1.05 (d, J = 6.9 Hz, 3H),






0.98 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.79,







169.06, 157.68, 155.40, 148.74,






140.51, 136.87, 133.93, 130.56,






127.33, 115.96, 111.46, 109.44, 76.90,






57.29, 56.08, 55.12, 39.01, 31.37,






20.17, 19.50, 18.52, 17.65, 17.40.


143


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.18 (s, 1H), 8.50 (d, J = 9.2 Hz, 1H),





C23H29FN2O5,
8.02 (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.5,





433.2133; found,
5.7 Hz, 1H), 6.89 (d, J = 5.2 Hz, 1H),





433.2142
6.87-6.82 (m, 2H), 5.12 (dq, J = 8.0,






6.3 Hz, 1H), 4.63 (dd, J = 9.3, 5.1 Hz,






1H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz,






1H), 2.41-2.25 (m, 4H), 1.24 (d, J = 6.9 Hz,






3H), 1.13 (d, J = 6.3 Hz, 3H),






1.03 (d, J = 6.9 Hz, 3H), 0.99 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 170.87,







169.06, 161.95, 160.01, 155.41,






148.74, 140.53, 137.86, 137.80,






137.31, 137.28, 130.54, 127.91,






117.05, 116.89, 113.06, 112.89,






109.46, 76.09, 57.04, 56.09, 39.11,






31.39, 20.00, 19.12, 18.25, 17.80,






17.41.


144


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.16 (s, 1H), 8.32 (d, J = 9.2 Hz, 1H),





C23H29FN2O5,
8.00 (d, J = 5.2 Hz, 1H), 7.16 (dd, J = 8.4,





433.2133; found,
5.8 Hz, 1H), 6.89 (d, J = 5.2 Hz, 1H),





433.2139
6.78 (ddd, J = 9.8, 7.0, 4.1 Hz, 2H),






5.17-5.05 (m, 1H), 4.48 (dd, J = 9.3,






5.3 Hz, 1H), 3.96 (s, 3H), 3.22 (p, J = 7.2 Hz,






1H), 2.33 (s, 3H), 2.18 (pd, J = 6.9,






5.2 Hz, 1H), 1.28-1.19 (m, 6H),






0.92 (d, J = 6.8 Hz, 3H), 0.86 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 170.29,







168.86, 161.96, 160.02, 155.40,






148.71, 140.46, 138.45, 138.39,






136.79, 136.76, 130.49, 127.77,






127.70, 116.77, 116.61, 112.79,






112.63, 109.43, 75.66, 57.06, 56.09,






38.58, 31.26, 19.91, 18.94, 17.61,






17.30, 16.84.


145


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.19 (s, 1H), 8.34 (d, J = 9.3 Hz, 1H),





C23H30N2O5,
8.00 (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.6,





415.2227; found,
1.7 Hz, 1H), 7.14-7.05 (m, 2H),





415.2224
7.02 (td, J = 7.2, 1.4 Hz, 1H), 6.88 (d, J = 5.2 Hz,






1H), 5.20-5.12 (m, 1H),






4.48 (dd, J = 9.3, 5.1 Hz, 1H), 3.95 (s, 3H),






3.28 (p, J = 7.1 Hz, 1H), 2.36 (s, 3H),






2.17 (pd, J = 6.9, 5.1 Hz, 1H),






1.29-1.22 (m, 6H), 0.90 (d, J = 6.8 Hz, 3H),






0.84 (d, J = 6.8 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.28,







168.84, 155.36, 148.69, 141.08,






140.42, 136.11, 130.59, 130.28,






126.23, 126.11, 109.39, 75.76, 57.06,






56.08, 39.06, 31.33, 19.83, 18.93,






17.59, 17.20, 16.50.


146


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.17 (s, 1H), 8.50 (d, J = 8.9 Hz, 1H),





C22H27FN2O5,
8.02 (d, J = 5.2 Hz, 1H), 7.19-7.10 (m,





419.1977; found,
3H), 7.00-6.93 (m, 2H), 6.89 (d, J = 5.2 Hz,





419.1974
1H), 5.11-5.02 (m, 1H),






4.67-4.58 (m, 1H), 3.95 (s, 4H), 2.92 (p, J = 7.1 Hz,






1H), 2.31 (pd, J = 6.9, 5.0 Hz,






1H), 1.28 (d, J = 7.0 Hz, 3H),






1.10 (d, J = 6.2 Hz, 3H), 1.02 (d, J = 6.9 Hz,






3H), 0.99 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.76,







169.06, 162.64, 160.70, 155.41,






148.74, 140.53, 138.48, 130.53,






129.28, 129.22, 115.33, 115.16,






109.46, 76.11, 57.07, 56.09, 44.09,






31.35, 19.09, 17.87, 17.82, 17.23.


147


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.20 (s, 1H), 8.53 (d, J = 9.2 Hz, 1H),





C24H32N2O6,
8.02 (d, J = 5.2 Hz, 1H), 7.10 (d, J = 8.4 Hz,





445.2333; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





445.2334
6.75-6.64 (m, 2H), 5.12 (dq, J = 8.2, 6.3 Hz,






1H), 4.65 (dd, J = 9.2, 5.0 Hz, 1H),






3.95 (s, 3H), 3.75 (s, 3H),






3.20-3.06 (m, 1H), 2.32 (s, 4H), 1.23 (d, J = 6.9 Hz,






3H), 1.13 (d, J = 6.2 Hz, 3H),






1.03 (d J = 6.9 Hz, 3H), 1.00 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 170.92,







169.04, 157.67, 155.39, 148.73,






140.52, 136.92, 133.85, 130.59,






127.40, 116.00, 111.44, 109.43, 76.56,






57.04, 56.08, 55.10, 39.05, 31.44,






20.18, 19.13, 18.32, 17.80, 17.65.


148


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (s, 1H), 8.47 (d, J = 7.9 Hz, 1H),





C21H25FN2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.5,





405.1820; found,
5.8 Hz, 1H), 6.91-6.80 (m, 3H),





405.1820
5.12 (dq, J = 8.1, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz,






1H), 3.95 (s, 3H),






3.21-3.10 (m, 1H), 2.33 (s, 3H), 1.54 (d, J = 7.2 Hz,






3H), 1.23 (d, J = 6.9 Hz, 3H),






1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.81,







168.74, 161.95, 160.01, 155.40,






148.78, 140.51, 137.89, 137.83,






137.29, 137.26, 130.48, 127.87,






127.81, 117.07, 116.91, 113.06,






112.90, 109.48, 76.19, 56.09, 47.96,






39.12, 20.01, 18.24, 18.13, 17.48.


149


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.12 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H),





C21H25FN2O5,
7.99 (d, J = 5.2 Hz, 1H), 7.22-7.09 (m,





405.1820; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





405.1820
6.83-6.74 (m, 2H), 5.19-5.06 (m, 1H),






4.62-4.50 (m, 1H), 3.95 (s, 3H),






3.31-3.17 (m, 1H) 2.33 (s, 3H) 1.38 (d, J = 7.2 Hz,






3H), 1.27-1.18 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 171.29,







168.55, 161.93, 159.99, 155.38,






148.74, 140.44, 138.41, 138.35,






136.73, 136.71, 130.43, 127.71,






127.64, 116.77, 116.61, 112.80,






112.64, 109.45, 75.62, 56.09, 47.82,






38.64, 18.06, 17.22, 16.84.


150


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.15 (s, 1H), 8.30 (d, J = 7.9 Hz, 1H),





C21H26N2O5,
7.99 (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.8,





387.1914; found,
1.4 Hz, 1H), 7.15-7.01 (m, 4H),





387.1913
6.87 (d, J = 5.2 Hz, 1H), 5.23-5.08 (m,






1H), 4.58-4.49 (m, 1H), 3.95 (s, 3H),






3.28 (h, J = 7.3 Hz, 1H), 2.36 (s, 3H),






1.35 (d, J = 7.2 Hz, 3H),






1.28-1.22 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 171.29,







168.54, 155.35, 148.73, 141.04,






140.40, 136.09, 130.51, 130.26,






126.23, 126.11, 109.40, 75.73, 56.08,






47.88, 39.15, 19.83, 18.11, 17.16,






16.53.


151


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (d, J = 0.6 Hz, 1H), 8.46 (d, J = 7.9 Hz,





C20H23FN2O5,
1H), 8.01 (d, J = 5.2 Hz, 1H), 7.16 (dd,





391.1664; found,
J = 8.7, 5.4 Hz, 2H), 6.97 (t, J = 8.7 Hz,





391.1658
2H), 6.88 (d, J = 5.2 Hz, 1H),






5.07 (dq, J = 7.4, 6.3 Hz, 1H),






4.79-4.64 (m, 1H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz,






1H), 1.53 (d, J = 7.2 Hz, 3H),






1.28 (d, J = 7.1 Hz, 3H), 1.09 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.72,







168.76, 162.65, 160.70, 155.40,






148.78, 140.51, 138.43, 130.47,






129.29, 129.23, 115.33, 115.16,






109.48, 76.12, 56.09, 47.98, 44.09,






18.19, 17.69, 17.30.


152


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.17 (s, 1H), 8.50 (d, J = 7.9 Hz, 1H),





C22H28N2O6,
8.01 (d, J = 5.2 Hz, 1H), 7.09 (d, J = 8.3 Hz,





417.2020; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





417.2007
6.78-6.64 (m, 2H), 5.13 (dq, J = 8.4, 6.3 Hz,






1H), 4.73 (p, J = 7.3 Hz, 1H), 3.95 (s,






3H), 3.76 (s, 3H), 3.18-3.06 (m, 1H),






2.32 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H),






1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.86,







168.72, 157.68, 155.38, 148.76,






140.50, 136.94, 133.81, 130.53,






127.37, 115.97, 111.47, 109.45, 76.65,






56.08, 55.11, 47.99, 39.06, 20.19,






18.30, 18.19, 17.68.


153


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (s, 1H), 8.49 (d, J = 8.0 Hz, 1H),





C21H25FN2O5,
8.00 (d, J = 5.2 Hz, 1H), 7.17-7.08 (m,





405.1820; found,
1H), 6.91-6.81 (m, 4H), 5.11 (dq, J = 8.1,





405.1818
6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz,






1H), 3.95 (s, 3H), 3.20-3.10 (m, 1H),






2.33 (s, 3H), 1.55 (d, J = 7.2 Hz, 3H),






1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.80,







168.69, 161.97, 160.03, 155.39,






148.77, 140.51, 137.87, 137.81,






137.33, 137.30, 130.47, 127.86,






127.79, 117.10, 116.94, 113.02,






112.86, 109.47, 76.33, 56.09, 48.13,






39.16, 20.00, 18.41, 18.36, 17.33.


154


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.09 (s, 1H), 8.35 (d, J = 8.0 Hz, 1H),





C21H25FN2O5,
7.98 (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 8.4,





405.1820; found,
5.8 Hz, 1H), 6.86 (d, J = 5.2 Hz, 1H),





405.1816
6.80 (ddd, J = 9.5, 7.0, 4.1 Hz, 2H),






5.14 (dq, J = 8.2, 6.2 Hz, 1H),






4.60-4.49 (m, 1H), 3.94 (s, 3H),






3.27-3.16 (m, 1H), 2.34 (s, 3H), 1.30 (d, J = 6.3 Hz,






3H), 1.22 (d, J = 7.1 Hz, 3H),






1.14 (d, J = 7.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.55,







168.59, 161.91, 159.97, 155.37,






148.74, 140.44, 138.30, 138.24,






137.15, 137.13, 130.43, 127.46,






127.40, 116.74, 116.57, 112.90,






112.73, 109.43, 75.74, 56.08, 47.87,






38.98, 19.90, 19.89, 17.79, 17.32.


155


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.11 (d, J = 0.6 Hz, 1H), 8.36 (d, J = 8.0 Hz,





C21H26N2O5,
1H), 7.97 (d, J = 5.2 Hz, 1H), 7.19 (dd,





387.1914; found,
J = 7.5, 1.2 Hz, 1H), 7.12 (td, J = 7.8,





387.1912
7.0, 2.4 Hz, 1H), 7.09-7.02 (m, 2H),






6.86 (d, J = 5.2 Hz, 1H), 5.19 (dq, J = 8.3,






6.2 Hz, 1H), 4.60-4.45 (m, 1H),






3.94 (s, 3H), 3.33-3.20 (m, 1H),






2.36 (s, 3H), 1.32 (d, J = 6.2 Hz, 3H),






1.24 (d, J = 7.0 Hz, 3H), 1.08 (d, J = 7.2 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.58,







168.54, 155.33, 148.71, 141.47,






140.41, 135.95, 130.49, 130.22,






126.20, 125.88, 109.39, 75.87, 56.06,






47.85, 39.52, 19.83, 17.83, 17.74,






17.14.


156


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.14 (s, 1H), 8.47 (d, J = 7.7 Hz, 1H),





C20H23FN2O5,
8.00 (d, J = 5.2 Hz, 1H), 7.21-7.10 (m,





391.1664; found,
3H), 6.97 (td, J = 8.8, 2.6 Hz, 2H),





391.1661
6.88 (dd, J = 5.3, 1.7 Hz, 1H),






5.12-5.01 (m, 1H), 4.77-4.66 (m, 1H), 3.95 (d, J = 1.6 Hz,






4H), 2.92 (p, J = 7.1 Hz, 1H),






1.53 (d, J = 7.2 Hz, 4H), 1.29 (d, J = 7.0 Hz,






3H), 1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.67,







168.69, 162.64, 160.70, 155.40,






148.78, 140.51, 138.45, 130.46,






129.26, 115.32, 115.16, 109.48, 76.31,






56.09, 48.12, 44.11, 18.38, 17.95,






17.16.


157


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
12.16 (s, 1H), 8.51 (d, J = 7.9 Hz, 1H),





C22H28N2O6,
8.00 (d, J = 5.2 Hz, 1H), 7.12-7.06 (m,





417.2020; found,
1H), 6.88 (d, J = 5.2 Hz, 1H),





417.2006
6.76-6.67 (m, 2H), 5.11 (dq, J = 8.3, 6.3 Hz,






1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s,






3H), 3.77 (s, 3H), 3.19-3.07 (m, 1H),






2.32 (s, 3H), 1.61-1.51 (m, 4H),






1.23 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.86,







168.68, 157.70, 155.38, 148.77,






140.50, 136.91, 133.86, 130.51,






127.36, 115.95, 111.48, 109.45, 56.08,






55.13, 48.17, 39.11, 20.18, 18.46,






17.57.


158

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3369,
[M + H]+ calcd for
12.13 (s, 1H), 8.58-8.47 (m, 1H), 8.01 (d, J = 5.2 Hz,




2983, 1736,
C21H24F3N2O5,
1H), 7.68-7.61 (m, 1H),




1649, 1528,
441.1632; found,
7.51 (td, J = 7.7, 1.2 Hz, 1H), 7.43 (d, J = 7.7 Hz,




1310, 1148,
441.1627
1H), 7.38-7.29 (m, 1H),




1115, 770,

6.88 (d, J = 5.2 Hz, 1H),




731 cm−1

5.29-5.15 (m, 1H), 4.82-4.71 (m, 1H), 3.95 (s,






3H), 3.42-3.29 (m, 1H), 1.60 (d, J = 7.2 Hz,






3H), 1.29 (d, J = 6.8 Hz, 3H),






1.12 (d, J = 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.24.



159

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3370,
[M + H]+ calcd for
12.11 (s, 1H), 8.50 (d, J = 7.9 Hz, 1H),




2984, 1737,
C21H23F4N2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.42 (dd, J = 8.8,




1528, 1313,
459.1538; found,
5.3 Hz, 1H), 7.35 (dd, J = 9.2, 2.8 Hz,




1151, 1118,
459.1535
1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H),




1045, 908,

6.89 (d, J = 5.2 Hz, 1H), 5.24-5.09 (m,




799, 738 cm−1

1H), 4.82-4.67 (m, 1H), 3.95 (s, 3H),






3.41-3.26 (m, 1H), 1.59 (d, J = 7.2 Hz,






3H), 1.27 (d, J = 6.8 Hz, 3H),






1.12 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.78,







−113.91.


160

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3369,
[M + H]+ calcd for
12.17 (s, 1H), 8.53 (d, J = 7.8 Hz, 1H),




2944, 1732,
C19H29N2O5,
7.99 (d, J = 5.2 Hz, 1H), 6.87 (d, J = 5.2 Hz,




1648, 1526,
365.2071; found,
1H), 5.11 (qd, J = 6.4, 3.1 Hz, 1H),




1438, 1280,
365.2067
4.76-4.64 (m, 1H), 3.95 (s, 3H),




1263, 1216,

1.76 (dddd, J = 13.2, 10.4, 8.0, 6.4 Hz, 2H),




1149, 1057,

1.69-1.52 (m, 6H), 1.52-1.43 (m,




800 cm−1

1H), 1.43-1.35 (m, 1H), 1.24 (d, J = 6.4 Hz,






3H), 1.19-0.98 (m, 3H),






0.98-0.89 (m, 3H).







13C NMR (101 MHz, CDCl3) δ 171.76,







168.71, 155.39, 148.78, 140.46,






130.58, 109.43, 74.81, 56.08, 48.23,






43.31, 43.13, 31.22, 30.74, 25.15,






24.98, 18.51, 17.78, 12.50.


161


HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ






[M + H]+ calcd for
12.15 (s, 1H), 8.48 (d, J = 8.0 Hz, 1H),





C21H24F3N2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.64 (dd, J = 7.9,





441.1632; found,
1.3 Hz, 1H), 7.56-7.47 (m, 1H),





441.1624
7.44 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.5 Hz,






1H), 6.88 (d, J = 5.2 Hz, 1H),






5.27-5.17 (m, 1H), 4.83-4.68 (m, 1H),






3.95 (s, 3H), 3.42-3.28 (m, 1H), 1.58 (d, J = 7.2 Hz,






3H), 1.30 (d, J = 6.8 Hz, 3H),






1.10 (d, J = 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.24.



162

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 2983,
[M + H]+ calcd for
12.12 (s, 1H), 8.46 (d, J = 7.9 Hz, 1H),




1738, 1649,
C21H23F4N2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.43 (dd, J = 8.8,




1528, 1313,
459.1538; found,
5.3 Hz, 1H), 7.34 (dd, J = 9.2, 2.8 Hz,




1152, 1119,
459.1530
1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H),




1045, 909,

6.89 (d, J = 5.2 Hz, 1H), 5.18 (p, J = 6.6 Hz,




800, 732 cm−1

1H), 4.79-4.69 (m, 1H), 3.95 (s, 3H),






3.31 (p, J = 7.1 Hz, 1H), 1.57 (d, J = 7.2 Hz,






3H), 1.29 (d, J = 6.9 Hz, 3H),






1.12 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.78,







−114.01.


163

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3370,
[M + H]+ calcd for
12.18 (s, 1H), 8.52 (d, J = 7.8 Hz, 1H),




2944, 1732,
C19H29N2O5,
7.99 (d, J = 5.2 Hz, 1H), 6.87 (d, J = 5.2 Hz,




1649, 1526,
365.2071; found,
1H), 5.10 (qd, J = 6.4, 3.0 Hz, 1H),




1438, 1263,
365.2068
4.74-4.64 (m, 1H), 3.95 (s, 3H),




1216, 1150,

1.83-1.65 (m, 3H), 1.65-1.52 (m, 6H),




1058, 954,

1.52-1.34 (m, 2H), 1.23 (d, J = 6.4 Hz,




800, 731 cm−1

3H), 1.18-1.03 (m, 2H), 0.94 (d,






J = 6.9 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 171.75,







168.76, 155.39, 148.79, 140.46,






130.62, 109.44, 74.90, 56.08, 48.04,






43.11, 42.95, 31.26, 30.67, 25.14,






25.00, 18.33, 17.49, 12.53.


164

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3369,
[M + H]+ calcd for
12.17 (s, 1H), 8.58 (t, J = 7.7 Hz, 1H),




2971, 1733,
C22H29N2O5,
7.99 (d, J = 5.2 Hz, 1H), 7.14-6.90 (m,




1648, 1527,
401.2071; found,
3H), 6.87 (d, J = 5.3 Hz, 1H),




1438, 1263,
401.2072
5.72-5.58 (m, 1H), 4.86-4.71 (m, 1H),




1149, 1057,

3.93 (s, 3H), 3.44 (dp, J = 10.5, 7.1 Hz, 1H),




801, 770,

2.42 (d, J = 1.7 Hz, 3H), 2.38 (s, 3H),




730 cm−1

1.61 (dd, J = 14.3, 7.2 Hz, 3H),






1.29 (dd, J = 7.1, 2.7 Hz, 3H),






1.10-0.95 (m, 3H).


165

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3370,
[M + H]+ calcd for
12.15 (s, 1H), 8.69-8.42 (m, 1H), 8.00 (d, J = 5.2 Hz,




2975, 1734,
C22H28FN2O5,
1H), 6.88 (d, J = 5.2 Hz, 1H),




1649, 1527,
419.1977; found
6.70 (ddd, J = 14.6, 8.1, 2.5 Hz, 2H),




1480, 1262,
419.1975
5.59 (ddq, J = 12.4, 10.7, 6.2 Hz, 1H),




1148, 849,

4.76 (p, J = 7.2 Hz, 1H), 3.94 (d, J = 1.9 Hz,




799, 728 cm−1

3H), 3.38 (dp, J = 10.5, 7.0 Hz,






1H), 2.41 (d, J = 1.9 Hz, 3H), 2.36 (s,






3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H),






1.27 (dd, J = 7.1, 3.1 Hz, 3H), 1.04 (dt,






J = 11.6, 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.25,







−118.31.


166

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3369,
[M + H]+ calcd for
12.16 (d, J = 3.9 Hz, 1H), 8.56 (t, J = 7.7 Hz,




2971, 1733,
C22H29N2O5,
1H), 8.00 (d, J = 5.2 Hz, 1H),




1648, 1527,
401.2071; found,
7.07-6.90 (m, 3H), 6.88 (d, J = 5.2 Hz, 1H),




1438, 1280,
401.2066
5.73-5.53 (m, 1H), 4.76 (pd, J = 7.2,




1263, 1149,

1.1 Hz, 1H), 3.95 (s, 3H), 3.43 (dp, J = 10.5,




1056, 801,

7.2 Hz, 1H), 2.42 (d, J = 1.9 Hz,




770, 730 cm−1

3H), 2.38 (s, 3H), 1.61 (dd, J = 14.3,






7.2 Hz, 3H), 1.29 (dd, J = 7.2, 2.3 Hz,






3H), 1.06 (t, J = 6.0 Hz, 3H).


167

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3370,
[M + H]+ calcd for
12.15 (d, J = 3.3 Hz, 1H), 8.55 (t, J = 7.9 Hz,




2976, 1734,
C22H28FN2O5,
1H), 8.00 (d, J = 5.2 Hz, 1H), 6.88 (d, J = 5.2 Hz,




1649, 1527,
401.1977; found,
1H), 6.70 (ddd, J = 15.1, 9.4,




1480, 1263,
419.1971
2.6 Hz, 2H), 5.59 (ddq, J = 12.4, 10.5,




1149, 849,

6.2 Hz, 1H), 4.76 (p, J = 7.3 Hz, 1H),




800, 730 cm−1

3.95 (s, 3H), 3.38 (dp, J = 10.5, 7.0 Hz,






1H), 2.41 (d, J = 1.9 Hz, 3H), 2.36 (s,






3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H),






1.27 (dd, J = 7.2, 2.9 Hz, 3H), 1.05 (t, J = 5.9 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −118.26,







−118.27, −118.33.


168

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3370,
[M + H]+ calcd for
12.16 (d, J = 3.8 Hz, 1H), 8.56 (t, J = 7.6 Hz,




2971, 1734,
C22H29N2O5,
1H), 8.01 (d, J = 5.2 Hz, 1H),




1649, 1527,
401.2071; found,
7.05-6.91 (m, 3H), 6.88 (d, J = 5.2 Hz, 1H),




1451, 1263,
401.2070
5.70-5.57 (m, 1H), 4.76 (pd, J = 7.1,




1150, 801,

1.1 Hz, 1H), 3.95 (s, 3H), 3.43 (dp, J = 10.5,




770, 730 cm−1

7.2 Hz, 1H), 2.42 (d, J = 2.0 Hz,






3H), 2.38 (s, 3H), 1.61 (dd, J = 14.3,






7.2 Hz, 3H), 1.29 (dd, J = 7.2, 2.1 Hz,






3H), 1.06 (t, J = 6.0 Hz, 3H).


169

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3371,
[M + H]+ calcd for
12.15 (d, J = 3.3 Hz, 1H), 8.55 (t, J = 7.8 Hz,




2976, 1734,
C22H28FN2O5,
1H), 8.00 (d, J = 5.2 Hz, 1H), 6.88 (d, J = 5.2 Hz,




1649, 1527,
419.1977; found,
1H), 6.70 (ddd, J = 17.0, 9.4,




1480, 1280,
419.1971
2.8 Hz, 2H), 5.59 (ddq, J = 12.2, 10.8,




1262, 1157,

6.2 Hz, 1H), 4.76 (p, J = 7.3 Hz, 1H),




849, 800,

3.95 (s, 3H), 3.38 (dp, J = 10.4, 7.0 Hz,




731 cm−1

1H), 2.41 (d, J = 2.2 Hz, 3H), 2.36 (s,






3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H),






1.27 (dd, J = 7.2, 2.8 Hz, 3H), 1.05 (t, J = 5.9 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −118.29,







−118.36.


170


HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ






[M + H]+ calcd for
12.16 (s, 1H), 8.41 (d, J = 7.9 Hz, 1H),





C21H27N2O6,
7.97 (d, J = 5.2 Hz, 1H), 7.23-7.10 (m,





403.1864; found,
2H), 6.92-6.78 (m, 3H), 5.31 (dq, J = 7.8,





403.1827
6.3 Hz, 1H), 4.63-4.49 (m, 1H),






3.93 (s, 3H), 3.81 (s, 3H),






3.49-3.39 (m, 1H), 1.26 (d, J = 6.3 Hz, 3H),






1.23 (d, J = 7.2 Hz, 3H), 1.16 (d, J = 7.2 Hz,






3H).







13C NMR (101 MHz, CDCl3) δ 171.5,







168.6, 157.2, 155.3, 148.7, 140.4,






131.1, 130.6, 128.1, 127.4, 120.5,






110.5, 109.4, 75.1, 56.0, 55.4, 48.0,






37.6, 17.9, 17.8, 16.6.


171

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ





film) 2978,
[M + H]+ calcd for
12.16 (s, 1H), 8.50 (d, J = 8.0 Hz, 1H),




2937, 1733,
C20H25N2O5,
8.01 (d, J = 5.2 Hz, 1H), 7.32-7.27 (m,




1647, 1527,
373.1758; found,
2H), 7.24-7.16 (m, 3H), 6.88 (d, J = 5.2 Hz,




1451, 1262,
373.1752
1H), 5.11 (dq, J = 7.7, 6.3 Hz,




1147, 701 cm−1

1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H),






2.97-2.87 (m, 1H), 1.54 (d, J = 7.2 Hz,






3H), 1.31 (d, J = 7.0 Hz, 3H),






1.13 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.8,







168.7, 155.3, 148.7, 142.9, 140.5,






130.4, 128.5, 127.8, 126.8, 109.4, 76.5,






56.1, 48.1, 44.9, 18.4, 18.2, 17.2.


172

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ





film) 3368,
[M + H]+ calcd for
12.16 (s, 1H), 8.50 (d, J = 7.9 Hz, 1H),




2978, 1937,
C19H25N2O5S,
8.00 (d, J = 5.2 Hz, 1H), 6.88 (d, J = 5.2 Hz,




1734, 1648,
393.1479; found,
1H), 6.61 (d, J = 3.5 Hz, 1H), 6.55 (dq,




1527, 1480,
393.1473
J = 3.5, 1.1 Hz, 1H), 5.10-5.01 (m,




1438, 1262,

1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H),




797, 730 cm−1

3.22-3.12 (m, 1H), 2.42 (d, J = 1.1 Hz,






3H), 1.55 (d, J = 7.1 Hz, 3H),






1.33 (d, J = 7.0 Hz, 3H), 1.20 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.6,







168.7, 155.3, 148.7, 143.3, 140.5,






138.0, 130.5, 124.5, 124.1, 109.4, 76.1,






56.1, 48.1, 40.1, 18.4, 17.8, 17.2, 15.3.


173

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ





film) 3369,
[M + H]+ calcd for
12.19 (s, 1H), 8.49 (d, J = 7.9 Hz, 1H),




2977, 2939,
C21H26FN2O6,
8.01 (d, J = 5.2 Hz, 1H), 7.13-7.06 (m,




1733, 1649,
421.1769; found,
1H), 6.88 (d, J = 5.3 Hz, 1H),




1528, 1450,
421.1770
6.62-6.54 (m, 2H), 5.21-5.12 (m, 1H),




1278, 1262,

4.73-4.63 (m, 1H), 3.95 (s, 3H), 3.79 (s,




1149, 952 cm−1

3H), 3.42-3.32 (m, 1H), 1.51 (d, J = 7.2 Hz,






3H), 1.24 (d, J = 7.0 Hz, 3H),






1.14 (d, J = 6.3 Hz, 3H).







19F NMR (471 MHz, CDCl3) δ







−113.8-−113.9 (m).


174


ESIMS m/z 387.3

1H NMR (400 MHz, CDCl3) δ






[(M + H)+]
12.16 (d, J = 4.9 Hz, 1H), 8.50 (d, J = 7.8 Hz,






1H), 8.01 (dd, J = 5.2, 2.7 Hz, 1H),






7.21-7.01 (m, 4H), 6.88 (dd, J = 5.3,






1.9 Hz, 1H), 5.18 (dq, J = 8.3, 6.3 Hz,






1H), 4.73 (p, J = 7.3 Hz, 1H), 3.95 (d, J = 1.6 Hz,






3H), 3.19 (dq, J = 9.0, 6.9 Hz,






1H), 2.35 (s, 3H), 1.55 (d, J = 7.0 Hz,






3H), 1.26 (dd, J = 6.9, 3.8 Hz, 3H),






1.13 (dd, J = 9.0, 6.2 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 171.85,







168.74, 155.41, 148.80, 141.65,






140.49, 135.53, 130.54, 126.37,






126.31, 126.29, 109.46, 56.07, 53.40,






48.00, 39.74, 19.94, 18.28, 18.27,






17.52, −0.01.


175




1H NMR (400 MHz, CDCl3) δ







12.16 (d, J = 0.6 Hz, 1H), 8.51 (d, J = 7.9 Hz,






1H), 8.00 (d, J = 5.2 Hz, 1H),






7.22-7.02 (m, 5H), 6.88 (d, J = 5.2 Hz, 1H),






5.16 (dq, J = 8.3, 6.2 Hz, 1H),






4.78-4.65 (m, 1H), 3.95 (s, 3H), 3.20 (dq, J = 8.3,






6.9 Hz, 1H), 2.35 (s, 3H),






1.56 (d, J = 7.2 Hz, 3H), 1.26 (d, J = 6.9 Hz,






3H), 1.15 (d, J = 6.3 Hz, 3H).


176


ESIMS m/z 416

1H NMR (300 MHz, CDCl3) δ






([M + H]+)
12.18 (s, 1H), 8.52 (d, J = 7.9 Hz, 1H),






8.00 (d, J = 5.2 Hz, 1H), 7.13-7.01 (m,






2H), 6.88 (d, J = 5.2 Hz, 1H), 6.67 (d, J = 8.5 Hz,






2H), 5.12-4.98 (m, 1H),






4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H),






2.92 (s, 6H), 2.88-2.75 (m, 1H),






1.57 (s, 3H), 1.26 (dd, J = 7.1, 4.0 Hz, 3H),






1.11 (d, J = 6.2 Hz, 3H).







13C NMR (75 MHz, CDCl3) δ 148.75,







140.49, 130.54, 128.42, 112.68,






109.42, 40.70, 18.33 (d, J = 22.8 Hz),






0.01.


177


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.57 (s,






[M + H]+ calcd for
1H), 8.34 (d, J = 5.4 Hz, 1H), 7.07 (d, J = 8.6 Hz,





C24H30N2O6,
1H), 7.01 (d, J = 5.5 Hz, 1H),





443.2177; found,
6.97 (d, J = 6.7 Hz, 2H), 5.12 (dq, J = 8.5,





443.2170
6.3 Hz, 1H), 4.78-4.67 (m, 1H),






3.91 (s, 3H), 3.19-3.09 (m, 1H),






2.41 (s, 3H), 2.31 (s, 3H), 2.28 (s, 3H),






1.52 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz,






3H), 1.11 (d, J = 6.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.41,







168.96, 162.36, 159.42, 146.70,






141.53, 138.75, 137.46, 135.67,






135.33, 131.26, 126.95, 126.26,






109.75, 76.48, 56.29, 48.16, 39.45,






20.89, 20.78, 19.90, 18.76, 18.48,






17.67.


178


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.57 (s,






[M + H]+ calcd for
1H), 8.35 (d, J = 5.5 Hz, 1H), 7.07 (d, J = 7.7 Hz,





C24H30N2O6,
1H), 7.01 (d, J = 5.5 Hz, 1H),





443.2177; found,
6.98 (d, J = 7.4 Hz, 2H), 5.12 (dq, J = 8.5,





443.2172
6.2 Hz, 1H), 4.72 (p, J = 7.2 Hz,






1H), 3.91 (s, 3H), 3.18-3.09 (m, 1H),






2.41 (s, 3H), 2.31 (s, 3H), 2.27 (s, 3H),






1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.9 Hz,






3H), 1.10 (d, J = 6.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.41,







168.97, 162.40, 159.43, 146.70,






141.52, 138.72, 137.46, 135.64,






135.37, 131.24, 126.98, 126.27,






109.75, 76.37, 56.29, 48.04, 39.38,






20.88, 20.78, 19.92, 18.59, 18.24,






17.73.


179


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.51 (s,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H),





C26H34N2O6,
7.09-7.04 (m, 1H), 7.02-6.94 (m, 3H),





471.2490; found,
5.11 (dq, J = 8.5, 6.2 Hz, 1H), 4.73 (p, J = 7.2 Hz,





471.2484
1H), 3.89 (s, 3H),






3.19-3.09 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H),






2.31 (s, 3H), 2.28 (s, 3H), 1.51 (d, J = 7.2 Hz,






3H), 1.36 (dd, J = 7.0, 1.4 Hz, 5H),






1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.73,







172.50, 162.34, 159.40, 146.59,






141.90, 138.78, 137.63, 135.66,






135.33, 131.25, 126.95, 126.28,






109.58, 76.41, 56.29, 48.13, 39.45,






33.94, 20.89, 19.90, 18.80, 18.48,






17.66.


180


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.50 (s,






[M + H]+ calcd for
1H), 8.34 (d, J = 5.4 Hz, 1H), 7.07 (d, J = 7.8 Hz,





C26H34N2O6,
1H), 7.03-6.93 (m, 3H),





471.2490; found,
5.12 (dq, J = 8.5, 6.2 Hz, 1H), 4.72 (p,





471.2490
J = 7.1 Hz, 1H), 3.89 (s, 3H),






3.20-3.09 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H),






2.31 (s, 3H), 2.27 (s, 3H), 1.49 (d, J = 7.1 Hz,






3H), 1.37 (dd, J = 6.9, 2.0 Hz,






6H), 1.22 (d, J = 6.9 Hz, 3H), 1.09 (d, J = 6.2 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.74,







172.50, 162.39, 159.41, 146.59,






141.90, 138.76, 137.63, 135.63,






135.37, 131.23, 126.98, 126.28,






109.58, 76.29, 56.29, 48.03, 39.40,






33.94, 20.88, 19.91, 18.81, 18.59,






18.25, 17.74.


181


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.37 (s,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H), 7.17 (dd,





C23H27FN2O6,
J = 8.4, 5.9 Hz, 1H), 7.01 (d, J = 5.4 Hz,





447.1926; found,
1H), 6.84-6.75 (m, 2H), 5.10 (p,





447.1923
J = 6.4 Hz, 1H), 4.57 (p, J = 7.2 Hz,






1H), 3.91 (s, 3H), 3.22 (p, J = 7.0 Hz,






1H), 2.40 (s, 2H), 2.33 (s, 3H), 1.34 (d,






J = 7.1 Hz, 2H), 1.27-1.18 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 171.87,







168.95, 162.24, 161.89, 159.95,






159.44, 146.62, 141.38, 138.44,






137.47, 136.77, 127.73, 116.74,






116.58, 112.79, 112.62, 109.75, 75.32,






56.29, 47.87, 38.50, 20.76, 19.89,






18.40, 17.06, 16.72.


182


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.53 (s,






[M + H]+ calcd for
1H), 8.35 (d, J = 5.5 Hz, 1H),





C22H25FN2O6,
7.22-7.13 (m, 2H), 7.05-6.93 (m, 3H),





433.1769; found,
5.05 (h, J = 6.5 Hz, 1H), 4.71 (ddt, J = 14.7,





433.1767
10.3, 5.3 Hz, 1H), 3.91 (s, 3H), 2.91 (p,






J = 6.8 Hz, 1H), 2.41 (s, 3H), 1.48 (d, J = 7.2 Hz,






3H), 1.27 (d, J = 7.2 Hz, 3H),






1.08 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.34,







167.06, 160.68, 160.54, 158.74,






157.59, 144.78, 139.51, 136.64,






136.61, 135.58, 127.40, 127.34,






113.37, 113.21, 107.93, 73.96, 54.42,






46.14, 42.14, 18.85, 16.52, 15.76,






15.38.


183


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.56 (s,






[M + H]+ calcd for
1H), 8.35 (d, J = 5.4 Hz, 1H), 7.09 (d, J = 8.4 Hz,





C24H30N2O7,
1H), 7.02 (d, J = 5.5 Hz, 1H),





459.2126; found,
6.75-6.66 (m, 2H), 5.15-5.05 (m,





459.2096
1H), 4.72 (pd, J = 7.3, 1.5 Hz, 1H),






3.92 (s, 3H), 3.76 (s, 3H),






3.16-3.07 (m, 1H), 2.41 (s, 3H), 2.32 (s, 3H),






1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.8 Hz,






3H), 1.10 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.45,







167.03, 160.47, 157.55, 155.65,






144.76, 139.57, 135.54, 135.02,






132.00, 125.43, 113.97, 109.50,






107.85, 74.52, 54.38, 53.17, 46.15,






37.09, 18.83, 18.29, 16.63, 16.24,






15.80.


184


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.52 (s,






[M + H]+ calcd for
1H), 8.36 (d, J = 5.5 Hz, 1H),





C25H31FN2O6,
7.11 (ddd, J = 7.5, 5.9, 1.5 Hz, 1H), 7.02 (d,





475.2239; found,
J = 5.5 Hz, 1H), 6.83 (t, J = 8.1 Hz,





475.2238
2H), 5.06 (dq, J = 8.1, 6.3 Hz, 1H),






4.66 (dd, J = 9.4, 4.7 Hz, 1H), 3.92 (s,






3H), 3.20-3.08 (m, 1H), 2.40 (s, 3H),






2.32 (d, J = 2.3 Hz, 3H), 2.29 (td, J = 6.9,






4.8 Hz, 1H), 1.23 (d, J = 6.9 Hz,






3H), 1.11 (d, J = 6.2 Hz, 3H), 1.01 (d, J = 6.8 Hz,






3H), 0.93 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.24,







168.92, 162.74, 161.89, 159.95,






159.47, 146.68, 141.59, 137.81,






137.76, 137.49, 127.86, 127.79,






117.00, 116.83, 113.00, 112.83,






109.75, 76.14, 57.17, 56.31, 39.04,






31.46, 20.79, 20.00, 19.38, 18.45,






17.47, 17.44.


185


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.41 (s,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H), 7.16 (dd,





C25H31FN2O6,
J = 9.0, 5.9 Hz, 1H), 7.01 (d, J = 5.4 Hz,





475.2239; found,
1H), 6.81 (t, J = 8.0 Hz, 2H),





475.2236
5.15-5.07 (m, 1H), 4.53 (dd, J = 9.5, 4.5 Hz,






1H), 3.90 (s, 3H), 3.24-3.16 (m,






1H), 2.38 (s, 3H), 2.34 (s, 3H),






1.88 (td, J = 6.9, 4.5 Hz, 1H), 1.26 (d, J = 6.2 Hz,






3H), 1.21 (d, J = 6.9 Hz, 3H)






0.81 (d, J = 6.8 Hz, 3H), 0.63 (d, J = 6.8 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 169.14,







167.00, 160.78, 160.02, 158.08,






157.53, 144.77, 139.62, 136.49,






135.51, 135.45, 125.64, 125.57,






114.82, 114.66, 110.95, 110.79,






107.84, 73.69, 54.92, 54.40, 36.84,






29.39, 18.86, 17.99, 17.09, 15.75,






15.30, 15.12.


186


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.43 (s,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H),





C25H32N2O6,
7.24-7.19 (m, 1H), 7.09 (dddd, J = 29.3,





457.2333; found,
14.6, 7.2, 2.9 Hz, 3H), 7.00 (d, J = 5.5 Hz,





457.2330
1H), 5.14 (dq, J = 8.2, 6.2 Hz, 1H),






4.53 (dd, J = 9.4, 4.3 Hz, 1H), 3.90 (s,






3H), 3.26 (q, J = 7.4 Hz, 1H), 2.38 (s,






3H), 2.36 (s, 3H), 1.91-1.78 (m, 1H),






1.27 (d, J = 6.2 Hz, 3H),






1.25-1.20 (m, 3H), 0.78 (d, J = 6.9 Hz, 3H),






0.58 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.16,







166.97, 160.75, 157.48, 144.73,






139.69, 135.46, 134.11, 128.31,






124.26, 124.06, 107.75, 73.76, 54.85,






54.36, 37.31, 29.36, 18.84, 17.91,






17.07, 15.67, 15.06, 15.00.


187


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.50 (d,






[M + H]+ calcd for
J = 9.8 Hz, 1H), 8.35 (d, J = 5.4 Hz,





C24H29FN2O6,
1H), 7.14 (dd, J = 8.6, 5.5 Hz, 2H),





461.2082; found,
7.03 (d, J = 5.5 Hz, 1H), 6.94 (t, J = 8.7 Hz,





461.2082
2H), 5.07-4.99 (m, 1H),






4.65 (dd, J = 9.4, 4.7 Hz, 1H), 3.92 (s, 3H),






2.93-2.86 (m, 1H), 2.40 (s, 3H),






2.26 (pd, J = 6.8, 4.7 Hz, 1H), 1.28 (d, J = 7.0 Hz,






3H), 1.10 (d, J = 6.3 Hz, 3H),






0.99 (d, J = 6.9 Hz, 3H), 0.92 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 169.14,







167.00, 160.80, 160.63, 158.69,






157.57, 144.75, 139.63, 136.70,






136.67, 135.57, 127.33, 127.27,






113.31, 113.14, 107.86, 74.15, 55.24,






54.40, 42.02, 29.52, 18.86, 17.37,






16.09, 15.54, 15.21.


188


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.53 (d,






[M + H]+ calcd for
J = 9.3 Hz, 1H), 8.36 (d, J = 5.5 Hz,





C26H34N2O7,
1H), 7.07 (d, J = 9.5 Hz, 1H), 7.02 (d, J = 5.5 Hz,





487.2439; found,
1H), 6.72-6.66 (m, 2H),





487.2427
5.06 (dq, J = 8.5, 6.3 Hz, 1H), 4.67 (dd,






J = 9.4, 4.6 Hz, 1H), 3.91 (s, 3H),






3.76 (s, 3H), 3.15-3.06 (m, 1H), 2.40 (s,






3H), 2.31 (m, 4H), 1.23 (d, J = 6.9 Hz,






3H), 1.10 (d, J = 6.2 Hz, 3H), 1.02 (d, J = 6.8 Hz,






3H), 0.94 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.38,







167.00, 160.80, 157.51, 155.65,






144.76, 139.71, 135.53, 134.94,






132.15, 125.41, 109.49, 107.80, 74.70,






55.25, 54.37, 53.18, 37.08, 29.56,






18.86, 18.27, 17.47, 16.60, 15.86,






15.53.


189


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.61-8.47 (m, 1H), 8.36 (d, J = 5.4 Hz, 1H),





C25H31FN2O6,
7.13 (dd, J = 9.6, 5.7 Hz, 1H), 7.02 (d,





475.2239; found,
J = 5.5 Hz, 1H), 6.88-6.79 (m, 2H),





475.2238
5.09 (dq, J = 8.0, 6.3 Hz, 1H), 4.64 (dd,






J = 9.1, 5.0 Hz, 1H), 3.92 (s, 3H),






3.13 (p, J = 7.1 Hz, 1H), 2.41 (s, 3H),






2.33 (s, 3H), 2.29 (qd, J = 7.0, 5.2 Hz, 1H),






1.23 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz,






3H), 0.99 (d, J = 6.8 Hz, 3H),






0.96 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.44,







167.00, 160.79, 159.96, 158.02,






157.53, 144.78, 139.68, 135.91,






135.53, 135.50, 125.99, 125.93,






115.05, 114.89, 111.11, 110.95,






107.83, 73.93, 55.11, 54.38, 37.14,






29.57, 18.86, 18.10, 17.03, 16.32,






16.00, 15.50.


190


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.40 (s,






[M + H]+ calcd for
1H), 8.34 (d, J = 5.4 Hz, 1H), 7.18 (dd,





C25H31FN2O6,
J = 9.5, 5.8 Hz, 1H), 7.02 (d, J = 5.5 Hz,





475.2239; found,
1H), 6.84-6.75 (m, 2H), 5.10 (p,





475.2235
J = 6.4 Hz, 1H), 4.51 (dd, J = 9.2, 5.1 Hz,






1H), 3.92 (s, 3H), 3.22 (p, J = 7.1 Hz,






1H), 2.40 (s, 3H), 2.33 (s, 3H),






2.15 (pd, J = 6.9, 5.0 Hz, 1H), 1.23 (d,






J = 7.1 Hz, 3H), 1.21 (d, J = 6.3 Hz,






3H), 0.88 (d, J = 6.9 Hz, 3H), 0.84 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 170.81,







168.93, 162.52, 161.93, 159.99,






159.45, 146.63, 141.52, 138.48,






138.42, 137.46, 136.82, 136.79,






127.88, 127.82, 116.75, 116.59,






112.77, 112.61, 109.71, 75.30, 57.02,






56.30, 38.43, 31.44, 20.78, 19.90,






18.78, 17.72, 17.08, 16.67.


191


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.42 (s,






[M + H]+ calcd for
1H), 8.35 (d, J = 5.4 Hz, 1H), 7.23 (dd,





C25H32N2O6,
J = 7.8, 1.4 Hz, 1H), 7.15-7.03 (m,





457.2333; found,
3H), 7.02 (d, J = 5.4 Hz, 1H), 5.13 (p, J = 6.4 Hz,





457.2331
1H), 4.53 (dd, J = 9.2, 4.9 Hz,






1H), 3.91 (s, 3H), 3.28 (p, J = 7.1 Hz,






1H), 2.40 (s, 3H), 2.36 (s, 3H),






2.14 (pd, J = 6.9, 4.9 Hz, 1H), 1.26 (d,






J = 7.2 Hz, 3H), 1.22 (d, J = 6.3 Hz,






3H), 0.86 (d, J = 6.9 Hz, 3H), 0.81 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 170.77,







168.93, 162.52, 159.43, 146.63,






141.61, 141.09, 137.44, 136.15,






130.25, 126.37, 126.20, 126.09,






109.69, 75.37, 57.02, 56.29, 38.88,






31.51, 20.79, 19.83, 18.77, 17.70,






16.91, 16.26.


192


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.58-8.45 (m, 1H), 8.36 (d, J = 5.5 Hz, 1H),





C24H29FN2O6,
7.16 (ddd, J = 10.8, 6.6, 3.7 Hz, 2H),





457.2333; found,
7.02 (d, J = 5.5 Hz, 1H),





457.2331
7.01-6.94 (m, 2H), 5.10-4.99 (m, 1H), 4.63 (dd,






J = 9.2, 5.0 Hz, 1H), 3.92 (s, 3H),






2.90 (p, J = 7.1 Hz, 1H), 2.40 (d, J = 2.1 Hz,






3H), 2.31-2.21 (m, 1H), 1.28 (d, J = 7.0 Hz,






3H), 1.09 (d, J = 6.4 Hz, 3H),






1.00-0.97 (m, 3H), 0.96 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 171.25,







168.93, 162.72, 162.58, 160.64,






159.46, 146.69, 141.58, 138.61,






138.59, 137.46, 129.30, 129.23,






115.28, 115.11, 109.76, 75.84, 57.06,






56.31, 44.06, 31.47, 20.79, 18.93,






17.96, 17.84, 17.26.


193


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.62-8.50 (m, 1H), 8.36 (d, J = 5.4 Hz, 1H),





C26H34N2O7,
7.10 (d, J = 8.4 Hz, 1H), 7.02 (d, J = 5.5 Hz,





487.2439; found,
1H), 6.75-6.67 (m, 2H),





487.2434
5.09 (dq, J = 8.4, 6.3 Hz, 1H), 4.65 (dd, J = 9.1,






4.9 Hz, 1H), 3.91 (s, 3H), 3.75 (s,






3H), 3.17-3.06 (m, 1H), 2.40 (s, 3H),






2.32 (m, 4H), 1.22 (d, J = 6.9 Hz, 3H),






1.11 (d, J = 6.2 Hz, 3H), 0.99 (d, J = 6.8 Hz,






3H), 0.97 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.50,







167.02, 160.80, 157.52, 155.67,






144.82, 139.74, 135.53, 135.01,






132.08, 125.49, 114.01, 109.51,






107.84, 74.46, 55.12, 54.40, 53.18,






37.11, 29.65, 18.89, 18.31, 17.06,






16.41, 16.02, 15.83.


194


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.45-8.36 (m, 1H), 8.33 (d, J = 5.5 Hz, 1H),





C23H28N2O6,
7.25-7.17 (m, 1H), 7.17-7.03 (m,





429.2020; found,
3H), 7.01 (d, J = 5.5 Hz, 1H),





429.2021
5.18-5.09 (m, 1H), 4.61-4.48 (m, 1H),






3.91 (s, 3H), 3.28 (p, J = 7.3 Hz, 1H),






2.39 (d, J = 5.8 Hz, 3H), 2.36 (s, 3H),






1.32 (d, J = 7.2 Hz, 3H), 1.26 (d, J = 7.0 Hz,






3H), 1.23 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 169.93,







167.04, 160.36, 157.55, 144.72,






139.53, 139.14, 135.53, 134.21,






128.32, 124.37, 124.31, 107.85, 73.52,






54.40, 46.07, 37.09, 18.84, 17.93,






16.51, 15.05, 14.45.


195


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.54 (d,






[M + H]+ calcd for
J = 7.4 Hz, 1H), 8.34 (d, J = 5.4 Hz,





C23H27FN2O6,
1H), 7.13 (dd, J = 9.5, 5.8 Hz, 1H),





447.1926; found,
7.02 (d, J = 5.5 Hz, 1H),





447.1922
6.88-6.81 (m, 2H), 5.09 (dq, J = 8.2, 6.3 Hz, 1H),






4.72 (p, J = 7.3 Hz, 1H), 3.91 (s, 3H),






3.20-3.09 (m, 1H), 2.41 (s, 3H),






2.33 (s, 3H), 1.50 (d, J = 7.1 Hz, 3H),






1.23 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 170.39,







167.02, 160.44, 159.98, 158.04,






157.54, 144.76, 139.53, 135.94,






135.88, 135.55, 135.49, 125.94,






125.88, 115.11, 114.94, 111.06,






110.90, 107.87, 74.14, 54.38, 46.21,






37.21, 18.84, 18.08, 16.77, 16.43,






15.46.


196


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.44 (s,






[M + H]+ calcd for
1H), 8.34 (d, J = 5.4 Hz, 1H),





C24H29FN2O6,
7.12 (ddd, J = 9.3, 4.5, 2.0 Hz, 1H), 7.00 (d,





461.2082; found,
J = 5.5 Hz, 1H), 6.86 (dd, J = 9.0, 6.7 Hz,





461.2082
2H), 5.12 (dq, J = 7.9, 6.3 Hz, 1H),






4.18 (dd, J = 5.7, 2.8 Hz, 2H), 3.90 (s,






3H), 3.14 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz,






1H), 2.32 (s, 3H), 1.37 (d, J = 7.0 Hz,






6H), 1.22 (d, J = 7.0 Hz, 3H),






1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







169.37, 163.02, 161.95, 160.00,






159.48, 146.62, 141.68, 137.91,






137.73, 137.35, 137.32, 127.89,






127.82, 117.05, 116.89, 113.04,






112.87, 109.72, 76.09, 56.31, 41.38,






39.11, 33.98, 20.01, 18.81, 18.22,






17.42.


197


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.34 (d,






[M + H]+ calcd for
J = 5.0 Hz, 1H), 8.32 (d, J = 5.4 Hz,





C24H29FN2O6,
1H), 7.21-7.10 (m, 1H), 6.99 (d, J = 5.4 Hz,





461.2082; found,
1H), 6.84-6.76 (m, 2H),





461.2082
5.13 (p, J = 6.4 Hz, 1H), 4.17-3.92 (m,






2H), 3.90-3.88 (s, 3H), 3.22 (p, J = 7.1 Hz,






1H), 2.94 (p, J = 7.0 Hz, 1H),






2.33 (s, 3H) 1.36 (d J = 7.0 Hz, 6H)






1.23 (dd, J = 6.7, 1.3 Hz, 6H).







13C NMR (126 MHz, CDCl3) δ 174.69,







169.03, 162.91, 161.95, 160.01,






159.46, 146.58, 141.61, 138.48,






137.71, 136.72, 136.69, 127.84,






127.77, 116.78, 116.62, 112.83,






112.67, 109.70, 75.49, 56.30, 41.22,






38.58, 33.96, 19.87, 19.86, 18.80,






17.11, 16.56.


198


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.33 (m,






[M + H]+ calcd for
2H), 7.21 (dd, J = 7.6, 1.5 Hz, 1H),





C24H30N2O6,
7.10 (ttd, J = 14.3, 7.8, 7.3, 1.8 Hz,





443.2177; found,
3H), 6.98 (d, J = 5.5 Hz, 1H), 5.17 (h, J = 6.5 Hz,





443.2174
1H), 4.14-3.90 (m, 2H),






3.89 (s, 3H), 3.33-3.23 (m, 1H),






2.94 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H),






1.36 (d, J = 7.0 Hz, 6H), 1.28-1.19 (m,






6H).







13C NMR (126 MHz, CDCl3) δ 174.69,







169.05, 162.90, 159.44, 146.58,






141.67, 141.02, 137.68, 136.17,






130.25, 126.30, 126.27, 126.11,






109.66, 75.58, 56.29, 41.22, 39.10,






33.97, 19.80, 18.80, 18.75, 17.05,






16.24.


199


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.44 (t,






[M + H]+ calcd for
J = 5.5 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C23H27FN2O6,
1H), 7.18-7.11 (m, 2H),





447.1926; found,
7.02-6.92 (m, 3H), 5.14-5.02 (m, 1H),





447.1926
4.22-4.13 (m, 2H), 3.90 (s, 3H),






3.02-2.84 (m, 2H), 1.37 (d, J = 7.0 Hz, 6H),






1.30-1.23 (m, 3H), 1.09 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







169.27, 163.03, 162.63, 160.69,






159.48, 146.62, 141.66, 138.52,






137.74, 129.30, 129.23, 115.31,






115.14, 109.73, 76.02, 56.31, 44.12,






41.41, 33.98, 18.81, 17.81, 17.26.


200


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.45 (t,






[M + H]+ calcd for
J = 5.4 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C25H32N2O7,
1H), 7.08 (d, J = 8.4 Hz, 1H), 7.00 (d, J = 5.5 Hz,





473.2282; found,
1H), 6.77-6.67 (m, 2H),





473.2275
5.12 (dq, J = 8.1, 6.2 Hz, 1H),






4.25-4.14 (m, 2H), 3.89 (s, 3H), 3.77 (s,






3H), 3.16-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz,






1H) 2.31 (s, 3H), 1.37 (d, J = 7.0 Hz,






6H), 1.22 (d, J = 7.0 Hz, 3H),






1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







169.43, 163.02, 159.46, 157.66,






146.63, 141.71, 137.71, 136.96,






133.86, 127.39, 115.94, 111.46,






109.70, 76.54, 56.30, 55.11, 41.41,






39.04, 33.98, 20.18, 18.81, 18.27,






17.62.


201


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.36 (s,






[M + H]+ calcd for
1H), 8.31 (d, J = 5.4 Hz, 1H),





C25H31FN2O6,
7.16 (ddd, J = 13.0, 8.8, 6.0 Hz, 1H),





475.2239; found,
6.97 (d, J = 5.4 Hz, 1H), 6.81 (t, J = 7.8 Hz,





475.2234
2H), 5.11 (dq, J = 8.3, 6.4 Hz, 1H),






4.56 (p, J = 7.3 Hz, 1H), 3.88 (s, 3H),






3.26-3.16 (m, 1H), 2.99-2.90 (m,






1H), 2.34 (s, 3H), 1.35 (d, J = 6.9 Hz,






6H), 1.27 (d, J = 6.3 Hz, 3H), 1.21 (d, J = 7.1 Hz,






3H), 1.08 (d, J = 7.1 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







172.20, 162.29, 161.91, 159.97,






159.42, 146.55, 141.88, 138.36,






138.30, 137.64, 137.22, 137.19,






127.57, 127.50, 116.70, 116.54,






112.85, 112.68, 109.58, 75.44, 56.28,






47.83, 38.90, 33.93, 19.91, 18.80,






18.20, 17.70, 17.22.


202


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.35 (dd, J = 8.2, 5.5 Hz, 1H), 8.31 (d, J = 5.4 Hz,





C25H32N2O6,
1H), 7.19 (dd, J = 7.7, 1.4 Hz,





457.2333; found,
1H), 7.09 (ttd, J = 14.5, 7.2, 1.7 Hz,





457.2331
3H), 6.97 (d, J = 5.4 Hz, 1H), 5.15 (dq,






J = 7.7, 6.1 Hz, 1H), 4.60-4.45 (m,






1H), 3.88 (s, 3H), 3.26 (dp, J = 14.7,






7.2 Hz, 1H), 2.93 (p, J = 7.1 Hz, 1H),






2.36 (s, 3H), 1.35 (d, J = 7.0 Hz, 6H),






1.28 (d, J = 6.3 Hz, 3H), 1.24 (d, J = 7.2 Hz,






3H), 1.01 (d, J = 7.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







172.25, 162.27, 159.39, 146.55,






141.96, 141.54, 137.60, 136.03,






130.21, 126.16, 125.98, 109.53, 77.28,






75.56, 56.27, 47.84, 39.44, 33.93,






19.84, 18.81, 18.14, 17.71, 17.01.


203


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.46 (s,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H), 7.15 (dd,





C24H29FN2O6,
J = 8.6, 5.5 Hz, 2H), 7.01-6.92 (m,





461.2082; found,
3H), 5.09-5.00 (m, 1H), 4.71 (p, J = 7.3 Hz,





461.2082
1H), 3.89 (s, 3H),






3.00-2.86 (m, 2H), 1.47 (d, J = 7.1 Hz, 3H),






1.36 (dd, J = 7.0, 1.3 Hz, 6H), 1.27 (d, J = 7.0 Hz,






3H), 1.09 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







172.30, 162.61, 162.36, 160.67,






159.46, 146.57, 141.90, 138.63,






137.71, 129.29, 129.23, 115.27,






115.10, 109.62, 75.96, 56.30, 48.10,






44.13, 33.96, 18.81, 18.72, 17.93,






17.20.


204


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.50 (d,






[M + H]+ calcd for
J = 9.7 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C26H34N2O7,
1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, J = 5.5 Hz,





487.2439; found,
1H), 6.76-6.66 (m, 2H),





487.2431
5.08 (dq, J = 8.3, 6.2 Hz, 1H), 4.73 (p,






J = 7.3 Hz, 1H), 3.89 (s, 3H), 3.77 (s,






3H), 3.18-3.05 (m, 1H), 2.95 (p, J = 7.0 Hz,






1H), 2.32 (s, 3H), 1.50 (d, J = 7.2 Hz,






3H), 1.36 (dd, J = 7.0, 1.5 Hz,






6H), 1.22 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.70,







172.48, 162.36, 159.43, 157.65,






146.58, 141.96, 137.67, 136.91,






134.03, 127.40, 115.92, 111.45,






109.59, 76.46, 56.29, 55.12, 48.15,






39.14, 33.95, 20.19, 18.81, 18.43,






17.63.


205


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.51-8.39 (m, 1H), 8.34 (d, J = 5.3 Hz, 1H),





C25H31FN2O6,
7.13 (dd, J = 9.4, 5.8 Hz, 1H), 6.99 (d,





475.2239; found,
J = 5.4 Hz, 1H), 6.87-6.81 (m, 2H),





475.2239
5.09 (dq, J = 7.9, 6.2 Hz, 1H), 4.71 (p,






J = 7.3 Hz, 1H), 3.89 (s, 3H), 3.13 (p, J = 7.1 Hz,






1H), 2.95 (p, J = 7.0 Hz, 1H),






2.33 (s, 3H), 1.48 (d, J = 7.1 Hz, 3H),






1.39-1.33 (m, 6H), 1.22 (d, J = 6.9 Hz,






3H), 1.10 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







172.43, 162.41, 161.91, 159.97,






159.46, 146.57, 141.90, 137.88,






137.82, 137.47, 127.91, 127.85,






117.01, 116.84, 113.03, 112.87,






109.63, 75.88, 56.30, 48.01, 39.13,






33.96, 20.02, 18.81, 18.50, 18.12,






17.48.


206


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.35-8.27 (m, 2H), 7.22 (dd, J = 7.7, 1.4 Hz,





C25H32N2O6,
1H), 7.17-7.03 (m, 3H), 6.98 (d, J = 5.4 Hz,





457.2333; found,
1H), 5.14 (p, J = 6.5 Hz, 1H),





457.2332
4.56 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H),






3.28 (p, J = 7.0 Hz, 1H), 2.94 (p, J = 7.0 Hz,






1H), 2.35 (s, 3H),






1.39-1.34 (m, 6H) 1.31 (d, J = 7.2 Hz, 3H),






1.25 (d, J = 7.1 Hz, 3H), 1.22 (d, J = 6.4 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.70,







171.97, 162.25, 159.43, 146.50,






141.92, 141.08, 137.66, 136.14,






130.23, 126.33, 126.21, 126.09,






109.55, 75.33, 56.29, 47.95, 39.03,






33.95, 19.82, 18.81, 18.47, 16.96,






16.35.


207


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.45 (s,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H),





C24H29FN2O6,
7.20-7.12 (m, 2H), 7.02-6.94 (m, 3H),





461.2082; found,
5.10-4.99 (m, 1H), 4.70 (p, J = 7.3 Hz,





461.2082
1H), 3.89 (s, 3H), 2.94 (ddt, J = 15.3,






14.2, 7.1 Hz, 2H), 1.47 (d, J = 7.1 Hz,






3H), 1.38-1.34 (m, 6H), 1.27 (d, J = 6.9 Hz,






3H), 1.07 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.72,







172.36, 162.62, 162.44, 160.67,






159.46, 146.57, 141.88, 138.58,






137.70, 129.33, 129.26, 115.28,






115.11, 109.63, 75.77, 56.30, 48.03,






44.07, 33.96, 18.81, 18.46, 17.65,






17.30.


208


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.49 (d,






[M + H]+ calcd for
J = 5.7 Hz, 1H), 8.34 (d, J = 5.5 Hz,





C26H34N2O7,
1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, J = 5.4 Hz,





487.2439; found,
1H), 6.75-6.67 (m, 2H),





487.2432
5.09 (dq, J = 8.2, 6.2 Hz, 1H), 4.72 (p,






J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.76 (s,






3H), 3.15-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz,






1H), 2.32 (s, 3H), 1.49 (d, J = 7.2 Hz,






3H), 1.39-1.34 (m, 6H),






1.21 (d, J = 6.9 Hz, 3H), 1.09 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







172.49, 162.41, 159.44, 157.62,






146.58, 141.96, 137.67, 136.95,






134.00, 127.40, 115.94, 111.45,






109.60, 76.36, 56.29, 55.10, 48.06,






39.08, 33.96, 20.21, 18.82, 18.58,






18.19, 17.74.


209


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.44 (d,






[M + H]+ calcd for
J = 9.0 Hz, 1H), 8.34 (d, J = 5.4 Hz,





C27H35FN2O6,
1H), 7.16-7.08 (m, 1H), 6.99 (d, J = 5.5 Hz,





503.2552; found,
1H), 6.82 (t, J = 7.9 Hz, 2H),





503.2547
5.06 (dq, J = 8.0, 6.2 Hz, 1H), 4.66 (dd,






J = 9.4, 4.8 Hz, 1H), 3.89 (s, 3H),






3.20-3.09 (m, 1H), 2.95 (p, J = 7.0 Hz,






1H), 2.32 (s, 3H), 2.28 (qd, J = 7.0, 4.9 Hz,






1H), 1.39-1.32 (m, 6H), 1.23 (d,






J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz,






3H), 1.01 (d, J = 6.8 Hz, 3H), 0.92 (d, J = 6.8 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.67,







171.34, 162.74, 161.92, 159.98,






159.45, 146.56, 142.09, 137.82,






137.67, 137.55, 127.90, 127.83,






117.00, 116.83, 113.00, 112.84,






109.59, 76.07, 57.14, 56.29, 39.10,






33.94, 31.48, 19.99, 19.38, 18.82,






18.47, 17.46.


210


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.32 (m,






[M + H]+ calcd for
2H), 7.16 (dd, J = 9.5, 5.7 Hz, 1H),





C27H35FN2O7,
6.98 (d, J = 5.5 Hz, 1H),





503.2552; found,
6.83-6.76 (m, 2H), 5.10 (dq, J = 8.0, 6.3 Hz, 1H),





503.2554
4.54 (dd, J = 9.4, 4.5 Hz, 1H), 3.88 (s,






3H), 3.19 (p, J = 7.2 Hz, 1H), 2.93 (p, J = 7.0 Hz,






1H), 2.34 (s, 3H), 1.88 (pd, J = 6.9,






4.5 Hz, 1H), 1.34 (d, J = 7.0 Hz,






6H), 1.25 (d, J = 6.3 Hz, 3H), 1.21 (d, J = 7.1 Hz,






3H), 0.81 (d, J = 6.9 Hz, 3H),






0.63 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.66,







171.16, 162.69, 161.96, 160.03,






159.41, 146.55, 142.06, 138.40,






138.34, 137.62, 137.32, 127.61,






116.73, 116.57, 112.86, 112.70,






109.54, 75.49, 56.79, 56.28, 38.77,






33.92, 31.34, 19.89, 19.01, 18.82,






17.63, 17.17, 17.05.


211


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.38-8.27 (m, 2H), 7.21 (dd, J = 7.8, 1.3 Hz,





C25H36N2O6,
1H), 7.09 (dddd, J = 23.7, 14.5, 7.3, 1.6 Hz,





485.2646; found,
3H), 6.97 (d, J = 5.5 Hz, 1H),





485.2642
5.14 (dq, J = 6.8, 5.8, 5.3 Hz, 1H), 4.54 (dd,






J = 9.5, 4.4 Hz, 1H), 3.88 (s, 3H),






3.26 (dp, J = 14.6, 7.1 Hz, 1H), 2.93 (p, J = 6.9 Hz,






1H), 2.36 (d, J = 3.7 Hz, 3H),






1.85 (pd, J = 6.9, 4.4 Hz, 1H), 1.34 (d,






J = 7.0 Hz, 6H), 1.27 (d, J = 6.3 Hz,






3H), 1.23 (d, J = 7.1 Hz, 3H), 0.78 (d, J = 6.9 Hz,






3H), 0.58 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.65,







171.20, 162.68, 159.38, 146.55,






142.13, 141.63, 137.58, 136.06,






130.25, 126.19, 126.05, 109.49, 75.58,






56.75, 56.29, 39.27, 33.92, 31.33,






19.82, 19.02, 18.81, 17.57, 17.02,






16.89.


212


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.42 (d,






[M + H]+ calcd for
J = 9.0 Hz, 1H), 8.34 (d, J = 5.5 Hz,





C26H33FN2O6,
1H), 7.14 (dd, J = 8.6, 5.5 Hz, 2H),





489.2395; found,
7.00 (d, J = 5.5 Hz, 1H),





489.2391
6.97-6.89 (m, 2H), 5.03 (p, J = 6.4 Hz, 1H),






4.65 (dd, J = 9.4, 4.7 Hz, 1H), 3.89 (s, 3H),






3.00-2.85 (m, 2H), 2.25 (pd, J = 6.9,






4.7 Hz, 1H), 1.38-1.31 (m, 6H),






1.28 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz,






3H), 0.99 (d, J = 6.9 Hz, 3H), 0.91 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







171.17, 162.73, 162.59, 160.64,






159.46, 146.56, 142.06, 138.69,






137.69, 129.27, 129.21, 115.23,






115.07, 109.60, 76.00, 57.13, 56.30,






43.99, 33.94, 31.47, 19.30, 18.81,






18.02, 17.49, 17.14.


213


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.45 (d,






[M + H]+ calcd for
J = 8.6 Hz, 1H), 8.34 (d, J = 5.5 Hz,





C28H38N2O7,
1H), 7.07 (d, J = 9.4 Hz, 1H), 6.99 (d, J = 5.5 Hz,





515.2752; found,
1H), 6.72-6.65 (m, 2H),





515.2737
5.06 (dq, J = 8.3, 6.2 Hz, 1H), 4.67 (dd,






J = 9.3, 4.7 Hz, 1H), 3.89 (s, 3H),






3.76 (s, 3H), 3.16-3.05 (m, 1H), 2.95 (p, J = 7.0 Hz,






1H), 2.35-2.25 (m, 3H),






1.40-1.30 (m, 6H), 1.23 (d, J = 6.9 Hz,






3H), 1.10 (d, J = 6.3 Hz, 3H),






1.01 (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.67,







171.40, 162.75, 159.43, 157.63,






146.57, 142.14, 137.65, 136.86,






134.14, 127.37, 115.93, 111.45,






109.57, 76.57, 60.39, 57.17, 56.29,






55.12, 39.07, 33.94, 31.51, 20.18,






19.40, 18.82, 18.54, 17.77, 17.48,






14.20.


214


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.44 (d,






[M + H]+ calcd for
J = 9.1 Hz, 1H), 8.35 (d, J = 5.4 Hz,





C27H35FN2O6,
1H), 7.13 (dd, J = 9.6, 5.8 Hz, 1H),





503.2552; found,
7.00 (d, J = 5.4 Hz, 1H),





503.2549
6.88-6.78 (m, 2H), 5.09 (dq, J = 8.1, 6.3 Hz, 1H),






4.63 (dd, J = 9.1, 5.2 Hz, 1H), 3.89 (s,






3H), 3.13 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz,






1H), 2.32 (s, 3H), 2.26 (pd, J = 6.8,






4.9 Hz, 1H), 1.41-1.31 (m,






6H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.3 Hz,






3H), 0.99 (d, J = 7.0 Hz, 3H),






0.96 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







171.48, 162.75, 161.91, 159.97,






159.44, 146.59, 142.11, 137.84,






137.64, 137.49, 127.88, 116.98,






116.81, 113.04, 112.88, 109.58, 75.80,






57.04, 56.29, 39.14, 33.95, 31.48,






20.01, 19.00, 18.81, 18.26, 17.94,






17.46.


215


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.38-8.28 (m, 2H), 7.25-7.20 (m, 1H),





C27H36N2O6,
7.16-7.02 (m, 3H), 6.99 (d, J = 5.4 Hz,





485.2646; found,
1H), 5.13 (p, J = 6.4 Hz, 1H), 4.53 (dd,





485.2643
J = 9.1, 4.9 Hz, 1H), 3.89 (s, 3H),






3.28 (p, J = 7.1 Hz, 1H), 2.94 (h, J = 7.0 Hz,






1H), 2.35 (s, 3H), 2.21-2.09 (m, 1H),






1.35 (dd, J = 7.0, 1.2 Hz, 6H), 1.26 (d,






J = 7.1 Hz, 3H), 1.21 (d, J = 6.2 Hz,






3H), 0.86 (d, J = 6.9 Hz, 3H), 0.81 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







170.88, 162.55, 159.42, 146.51,






142.10, 141.12, 137.63, 136.16,






130.26, 126.41, 126.19, 126.09,






109.52, 75.28, 57.01, 56.29, 38.91,






33.94, 31.50, 19.81, 18.81, 17.71,






16.90, 16.26.


216


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.48-8.39 (m, 1H), 8.34 (d, J = 5.4 Hz, 1H),





C26H33FN2O6,
7.19-7.11 (m, 2H), 7.03-6.90 (m,





489.2395; found,
3H), 5.05 (m, 1H), 4.62 (dd, J = 9.1,





489.2391
5.1 Hz, 1H), 3.89 (s, 3H), 2.92 (dp, J = 26.1,






7.0 Hz, 2H), 2.25 (pd, J = 6.9, 4.2 Hz,






1H), 1.38-1.32 (m, 6H), 1.27 (d,






J = 7.1 Hz, 3H), 1.08 (d, J = 6.2 Hz,






3H), 0.98 (d, J = 6.9 Hz, 3H), 0.95 (d, J = 6.9 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







171.37, 162.76, 162.61, 160.67,






159.44, 146.59, 142.08, 138.67,






137.64, 129.32, 129.26, 115.27,






115.10, 109.59, 75.75, 57.06, 56.30,






44.10, 33.95, 31.45, 18.97, 18.81,






17.97, 17.84, 17.27.


217


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.46 (d,






[M + H]+ calcd for
J = 9.0 Hz, 1H), 8.35 (d, J = 5.4 Hz,





C28H38N2O7,
1H), 7.09 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 5.5 Hz,





515.2752; found,
1H), 6.75-6.66 (m, 2H),





515.2741
5.09 (dq, J = 8.3, 6.2 Hz, 1H), 4.65 (dd,






J = 9.1, 5.0 Hz, 1H), 3.89 (s, 3H),






3.75 (s, 3H), 3.16-3.04 (m, 1H), 2.95 (p, J = 7.0 Hz,






1H), 2.31 (s, 3H), 2.27 (qd, J = 6.9,






5.0 Hz, 1H), 1.39-1.32 (m,






6H), 1.22 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz,






3H), 0.99 (d, J = 6.8 Hz, 3H),






0.96 (d, J = 6.9 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







171.52, 162.73, 159.42, 157.61,






146.60, 142.18, 137.62, 136.92,






134.06, 127.42, 115.96, 111.44,






109.55, 76.31, 57.04, 56.29, 55.10,






39.09, 33.94, 31.54, 20.20, 19.00,






18.82, 18.33, 17.94, 17.77.


218


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.37-8.28 (m, 2H), 7.22-7.12 (m, 1H),





C25H31FN2O6,
6.99 (d, J = 5.5 Hz, 1H), 6.85-6.75 (m,





475.2239; found,
2H), 5.16-5.05 (m, 1H), 4.57 (h, J = 7.4 Hz,





475.2236
1H), 3.89 (s, 3H), 3.22 (pd, J = 7.3,






4.6 Hz, 1H), 3.00-2.89 (m, 1H),






2.33 (s, 3H), 1.39-1.30 (m, 9H),






1.22 (dd, J = 9.8, 6.7 Hz, 6H).







13C NMR (126 MHz, CDCl3) δ 174.70,







171.98, 162.25, 161.93, 159.99,






159.45, 146.51, 141.82, 138.46,






137.69, 136.79, 136.76, 127.85,






127.79, 116.74, 116.58, 112.79,






112.62, 109.59, 75.24, 56.30, 47.88,






38.53, 33.95, 19.88, 18.80, 18.41,






17.05, 16.71.


219


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.48 (d,






[M + H]+ calcd for
J = 6.9 Hz, 1H), 8.33 (d, J = 5.3 Hz,





C25H31FN2O6,
1H), 7.13 (dd, J = 9.4, 5.8 Hz, 1H),





475.2239; found,
6.99 (d, J = 5.5 Hz, 1H),





475.2238
6.88-6.81 (m, 2H), 5.09 (dp, J = 8.1, 6.5 Hz, 1H),






4.72 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H),






3.14 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz






1H), 2.33 (d, J = 2.4 Hz, 3H),






1.49 (d, J = 7.1 Hz, 3H),






1.38-1.33 (m, 6H), 1.23 (d, J = 6.9 Hz, 3H),






1.11 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







172.42, 162.36, 161.94, 159.99,






159.45, 146.58, 141.91, 137.86,






137.80, 137.69, 137.46, 127.91,






127.84, 117.04, 116.87, 113.00,






112.83, 109.62, 75.99, 56.30, 48.11,






39.18, 33.96, 20.00, 19.99, 18.85,






18.81, 18.36, 17.37.


220


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.56 (s,






[M + H]+ calcd for
1H), 8.35 (d, J = 5.4 Hz, 1H), 7.09 (d, J = 8.4 Hz,





C24H30N2O7,
1H), 7.02 (d, J = 5.5 Hz, 1H),





459.2126; found,
6.77-6.67 (m, 2H), 5.10 (dq, J = 8.3,





459.2103
6.3 Hz, 1H), 4.72 (tt, J = 8.8, 6.2 Hz,






1H), 3.91 (s, 3H), 3.76 (s, 3H),






3.15-3.06 (m, 1H), 2.41 (s, 3H), 2.32 (s,






3H), 1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.9 Hz,






3H), 1.10 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 170.46,







167.04, 160.48, 157.55, 155.66,






144.77, 139.57, 135.54, 135.03,






132.01, 125.44, 113.97, 109.50,






107.87, 74.52, 54.39, 53.17, 46.15,






37.09, 18.84, 18.30, 16.63, 16.25,






15.80.


221


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.44 (t,






[M + H]+ calcd for
J = 5.4 Hz, 1H), 8.34 (d, J = 5.4 Hz,





C24H29FN2O6,
1H), 7.12 (ddd, J = 10.1, 6.2, 3.4 Hz,





461.2082; found,
1H), 7.00 (d, J = 5.5 Hz, 1H),





461.2080
6.90-6.80 (m, 3H), 5.12 (dq, J = 7.7, 6.2 Hz,






1H), 4.18 (dd, J = 5.4, 2.8 Hz, 2H),






3.90 (s, 3H), 3.14 (p, J = 7.1 Hz, 1H),






2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H),






1.37 (d, J = 7.0 Hz, 6H), 1.22 (d, J = 6.9 Hz,






3H), 1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







169.37, 163.02, 161.95, 160.00,






159.48, 146.63, 141.67, 137.91,






137.85, 137.73, 137.32, 127.89,






127.82, 117.05, 116.89, 113.04,






112.87, 109.72, 76.09, 56.31, 41.38,






39.11, 33.98, 20.00, 18.81, 18.71,






18.22, 17.42.


222


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.36-8.27 (m, 2H), 7.21 (dd, J = 7.7, 1.4 Hz,





C24H30N2O6,
1H), 7.16-7.05 (m, 3H), 6.98 (d, J = 5.5 Hz,





443.2177; found,
1H), 5.17 (h, J = 6.6 Hz, 1H),





443.2176
4.13-3.89 (m, 2H), 3.89 (s, 3H),






3.28 (p, J = 7.1 Hz, 1H), 2.94 (p, J = 7.0 Hz,






1H), 2.35 (s, 3H), 1.36 (d, J = 7.0 Hz,






6H), 1.28-1.22 (m, 6H).







13C NMR (126 MHz, CDCl3) δ 174.69,







169.05, 162.90, 159.44, 146.58,






141.67, 141.02, 137.68, 136.17,






130.25, 126.29, 126.27, 126.11,






109.66, 75.58, 56.29, 41.22, 39.09,






33.97, 19.80, 18.81, 17.05, 16.23.


223


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.44 (t,






[M + H]+ calcd for
J = 5.5 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C23H27FN2O6,
1H), 7.18-7.11 (m, 2H),





447.1926; found,
7.03-6.92 (m, 3H), 5.14-5.01 (m, 1H), 4.17 (d, J = 5.4 Hz,





447.1923
2H), 3.90 (s, 3H),






3.00-2.86 (m, 2H), 1.37 (d, J = 7.0 Hz, 6H),






1.27 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.72,







169.28, 163.04, 162.64, 160.69,






159.48, 146.62, 141.66, 138.52,






137.74, 129.30, 129.24, 115.31,






115.14, 109.73, 76.02, 56.31, 44.12,






41.41, 33.98, 18.81, 17.81, 17.26.


224


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.45 (t,






[M + H]+ calcd for
J = 5.4 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C25H32N2O7,
1H), 7.08 (d, J = 8.5 Hz, 1H), 7.00 (d, J = 5.5 Hz,





473.2282; found,
1H), 6.76-6.67 (m, 2H),





473.2282
5.12 (dq, J = 8.3, 6.3 Hz, 1H),






4.24-4.14 (m, 2H), 3.89 (s, 3H), 3.77 (s,






3H), 3.16-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz,






1H) 2.31 (s, 3H) 1.37 (d, J = 7.0 Hz,






6H), 1.22 (d, J = 6.9 Hz, 3H),






1.12 (d, J = 6.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







169.43, 163.01, 159.46, 157.66,






146.63, 141.71, 137.71, 136.96,






133.86, 127.39, 115.94, 111.46,






109.70, 76.54, 56.30, 55.11, 41.41,






39.04, 33.98, 20.18, 18.81, 18.27,






17.62.


225


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.39-8.28 (m, 2H), 7.24-7.17 (m, 1H),





C25H32N2O6,
7.16-7.02 (m, 3H), 6.98 (d, J = 5.5 Hz,





457.2333; found,
1H), 5.14 (p, J = 6.6 Hz, 1H), 4.55 (dt,





457.2327
J = 10.4, 7.4 Hz, 1H), 3.89 (s, 3H),






3.28 (p, J = 7.1 Hz, 1H), 2.94 (p, J = 6.9 Hz,






1H), 2.36 (d, J = 4.9 Hz, 3H),






1.36 (dd, J = 7.0, 1.6 Hz, 6H), 1.31 (d,






J = 7.1 Hz, 3H), 1.25 (d, J = 7.2 Hz,






3H), 1.22 (d, J = 6.4 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.70,







171.96, 162.25, 159.42, 146.50,






141.92, 141.08, 137.65, 136.14,






130.23, 126.33, 126.21, 126.09,






109.55, 75.32, 56.29, 47.95, 39.03,






33.95, 19.82, 18.80, 18.47, 16.95,






16.35.


226


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.44 (s,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H),





C24H29FN2O6,
7.20-7.12 (m, 2H), 7.02-6.93 (m, 3H),





461.2082; found,
5.07-4.97 (m, 1H), 4.70 (p, J = 7.2 Hz,





461.2078
1H), 3.90 (s, 3H), 3.01-2.86 (m, 2H),






1.47 (d, J = 7.1 Hz, 3H),






1.39-1.34 (m, 6H), 1.27 (d, J = 7.0 Hz, 3H),






1.07 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.72,







172.36, 162.62, 162.44, 160.67,






159.46, 146.57, 141.88, 138.56,






137.70, 129.33, 129.26, 115.28,






115.11, 109.63, 75.77, 56.30, 48.03,






44.07, 33.96, 18.81, 18.46, 17.65,






17.30.


227


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.49 (d,






[M + H]+ calcd for
J = 8.6 Hz, 1H), 8.34 (d, J = 5.4 Hz,





C26H34N2O7,
1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, J = 5.4 Hz,





487.2439; found,
1H), 6.75-6.64 (m, 2H),





487.2425
5.09 (dq, J = 8.3, 6.2 Hz, 1H), 4.72 (p,






J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.76 (s,






3H), 3.16-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz,






1H), 2.32 (s, 3H), 1.49 (d, J = 7.1 Hz,






3H), 1.39-1.34 (m, 6H),






1.21 (d, J = 6.8 Hz, 3H), 1.09 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







172.49, 162.41, 159.44, 157.62,






146.58, 141.97, 137.67, 136.95,






134.01, 127.40, 115.94, 111.45,






109.59, 76.36, 56.29, 55.11, 48.06,






39.08, 33.96, 20.21, 18.82, 18.58,






18.19, 17.74.


228


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ






[M + H]+ calcd for
8.40-8.33 (m, 1H), 8.31 (d, J = 5.4 Hz, 1H),





C25H32N2O6,
7.22-7.15 (m, 1H), 7.15-7.03 (m,





457.2333; found,
3H), 6.97 (d, J = 5.4 Hz, 1H), 5.15 (dq,





457.2329
J = 8.0, 6.2 Hz, 1H), 4.61-4.47 (m,






1H), 3.88 (s, 3H), 3.25 (p, J = 7.3 Hz,






1H), 2.93 (p, J = 7.0 Hz, 1H), 2.36 (d, J = 3.5 Hz,






3H), 1.35 (d, J = 7.0 Hz, 6H),






1.28 (d, J = 6.3 Hz, 3H), 1.24 (d, J = 7.0 Hz,






3H), 1.01 (d, J = 7.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 174.68,







172.25, 162.26, 159.39, 146.54,






141.96, 141.54, 137.60, 136.03,






130.21, 126.16, 125.98, 109.53, 75.56,






56.27, 47.84, 39.43, 33.93, 19.84,






18.80, 17.71, 17.01.


229


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.46 (d,






[M + H]+ calcd for
J = 8.6 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C24H29FN2O6,
1H), 7.18-7.10 (m, 2H),





461.2082; found,
7.01-6.89 (m, 3H), 5.09-5.00 (m, 1H), 4.71 (p, J = 7.3 Hz,





461.2077
1H), 3.89 (d, J = 1.2 Hz, 3H),






3.01-2.86 (m, 2H), 1.47 (dd, J = 7.2,






1.8 Hz, 3H), 1.39-1.34 (m, 6H),






1.27 (dd, J = 7.1, 1.6 Hz, 3H), 1.09 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







172.29, 162.61, 162.36, 160.66,






159.46, 146.57, 141.89, 138.63,






137.70, 129.33, 129.29, 129.26,






115.27, 115.10, 109.63, 75.95, 56.30,






48.10, 44.13, 33.96, 18.81, 18.71,






17.93, 17.20.


230


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.50 (d,






[M + H]+ calcd for
J = 8.7 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C26H34N2O7,
1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, J = 5.5 Hz,





487.2439; found,
1H), 6.77-6.66 (m, 2H),





X487.2423
5.08 (dq, J = 8.3, 6.2 Hz, 1H), 4.73 (p,






J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.77 (s,






3H), 3.17-3.05 (m, 1H), 2.95 (p, J = 7.0 Hz,






1H), 2.32 (s, 3H), 1.50 (d, J = 7.2 Hz,






3H), 1.38-1.33 (m, 6H),






1.22 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 174.71,







172.49, 162.36, 159.43, 157.65,






146.58, 141.97, 137.67, 136.91,






134.03, 127.40, 115.92, 111.45,






109.59, 76.46, 56.29, 55.12, 48.15,






39.14, 33.95, 20.19, 18.79, 18.43,






17.63.


231


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.26 (d,






[M + H]+ calcd for
J = 5.4 Hz, 1H), 8.22 (t, J = 7.4 Hz,





C24H30N2O7,
1H), 7.22-7.03 (m, 4H), 6.93 (d, J = 5.4 Hz,





459.2126; found,
1H), 5.73 (dd, J = 5.6, 1.8 Hz,





459.2121
2H), 5.16 (dq, J = 8.1, 6.3 Hz, 1H),






4.58-4.51 (m, 1H), 3.90 (s, 3H),






3.31-3.22 (m, 1H), 2.37 (s, 3H), 2.06 (s,






3H), 1.31 (d, J = 6.2 Hz, 3H), 1.24 (d, J = 7.0 Hz,






3H), 1.03 (d, J = 7.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.26,







170.26, 162.87, 160.25, 145.68,






143.94, 142.57, 141.57, 136.03,






130.21, 126.16, 125.94, 109.49, 89.57,






75.57, 56.16, 48.08, 39.48, 20.87,






19.84, 17.92, 17.77, 17.05.


232


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.33 (d,






[M + H]+ calcd for
J = 7.4 Hz, 1H), 8.29 (d, J = 5.3 Hz,





C23H27FN2O7,
1H), 7.20-7.12 (m, 2H),





463.1875; found,
7.01-6.93 (m, 3H), 5.79-5.71 (m, 2H),





463.1870
5.10-5.00 (m, 1H), 4.73 (p, J = 7.2 Hz, 1H),






3.92 (d, J = 2.0 Hz, 3H), 2.92 (p, J = 7.1 Hz,






1H), 2.07 (d, J = 1.6 Hz, 3H),






1.50 (d, J = 7.1 Hz, 3H), 1.29 (dd, J = 7.0,






2.5 Hz, 3H), 1.08 (d, J = 6.3 Hz,






3H).







13C NMR (126 MHz, CDCl3) δ 172.37,







170.29, 163.02, 162.63, 160.68,






160.30, 145.74, 144.03, 142.51,






138.55, 138.52, 129.32, 129.26,






115.30, 115.13, 109.59, 89.58, 75.82,






56.20, 48.22, 44.12, 20.88, 18.39,






17.69, 17.39.


233


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.38 (d,






[M + H]+ calcd for
J = 7.7 Hz, 1H), 8.29 (d, J = 5.3 Hz,





C25H32N2O8,
1H), 7.09 (d, J = 8.3 Hz, 1H), 6.96 (d, J = 5.3 Hz,





489.2231; found,
1H), 6.79-6.62 (m, 2H),





489.2220
5.76 (d, J = 2.2 Hz, 2H),






5.17-5.05 (m, 1H), 4.75 (p, J = 7.2 Hz, 1H),






3.92 (s, 3H), 3.76 (s, 3H), 3.22-3.03 (m,






1H), 2.32 (s, 3H), 2.07 (s, 3H), 1.52 (d,






J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz,






3H), 1.10 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.52,







170.29, 162.99, 160.29, 157.63,






145.74, 144.02, 142.57, 136.96,






133.96, 127.39, 115.93, 111.48,






109.55, 89.61, 76.42, 56.19, 55.11,






48.23, 39.10, 20.88, 20.21, 18.51,






18.21, 17.82.


234

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.50 (d,





film) 3383,
[M + H]+ calcd for
J = 7.4 Hz, 1H), 8.34 (d, J = 5.4 Hz,




2981, 1737,
C25H30F3N2O6,
1H), 7.64 (dd, J = 8.0, 1.3 Hz, 1H),




1679, 1505,
511.2050; found,
7.54-7.47 (m, 1H), 7.44 (d, J = 7.8 Hz,




1310, 1114,
511.2048
1H), 7.31 (t, J = 7.5 Hz, 1H),




1045, 732 cm−1

6.99 (d, J = 5.4 Hz, 1H), 5.26-5.11 (m,






1H), 4.76 (p, J = 7.3 Hz, 1H), 3.89 (s,






3H), 3.34 (p, J = 6.6 Hz, 1H),






2.96 (hept, J = 7.0 Hz, 1H), 1.54 (d, J = 7.2 Hz,






3H), 1.36 (dd, J = 7.0, 1.3 Hz, 6H),






1.28 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 6.3 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −58.25.



235

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.47 (d,





film) 3383,
[M + H]+ calcd for
J = 8.1 Hz, 1H), 8.34 (d, J = 5.4 Hz,




2982, 1761,
C25H29F4N2O6,
1H), 7.42 (dd, J = 8.8, 5.4 Hz, 1H),




1738, 1679,
529.1956; found,
7.34 (dd, J = 9.2, 2.8 Hz, 1H), 7.21 (td,




1500, 1312,
529.1954
J = 8.3, 2.8 Hz, 1H), 7.00 (d, J = 5.5 Hz,




1119, 909,

1H), 5.13 (p, J = 6.5 Hz, 1H),




732 cm−1

4.75 (dq, J = 9.3, 7.3 Hz, 1H), 3.89 (s, 3H),






3.36-3.24 (m, 1H), 2.95 (hept, J = 7.0 Hz,






1H), 1.53 (d, J = 7.2 Hz, 3H),






1.36 (dd, J = 7.0, 1.5 Hz, 6H), 1.26 (d, J = 6.8 Hz,






3H), 1.11 (d, J = 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.80,







−114.13.


236

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.53 (d,





film) 3383,
[M + H]+ calcd for
J = 7.7 Hz, 1H), 8.32 (d, J = 5.4 Hz,




2943, 1763,
C23H35N2O6,
1H), 6.98 (d, J = 5.4 Hz, 1H), 5.08 (qd,




1733, 1678,
435.2490; found,
J = 6.5, 3.0 Hz, 1H), 4.69 (dt, J = 7.9,




1504, 1310,
435.2483
7.0 Hz, 1H), 3.89 (s, 3H),




1210, 1090,

3.02-2.87 (m, 1H), 1.74 (dddd, J = 19.4, 17.2,




843, 731 cm−1

9.8, 5.1 Hz, 3H), 1.67-1.51 (m, 4H),






1.48 (d, J = 7.1 Hz, 3H), 1.36 (d, J = 7.0 Hz,






6H), 1.22 (d, J = 6.4 Hz, 3H),






1.18-1.02 (m, 3H), 0.94 (d, J = 6.9 Hz,






3H).


237

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.52 (s,





film) 3382,
[M + H]+ calcd for
1H), 8.34 (d, J = 5.4 Hz, 1H),




2976, 1762,
C26H34N2O6,
7.04-6.91 (m, 4H), 5.60 (dp, J = 10.5, 6.3 Hz,




1734, 1678,
471.2490; found,
1H), 4.84-4.67 (m, 1H), 3.89 (s,




1504, 1210,
471.2488
3H), 3.42 (dp, J = 10.6, 7.1 Hz, 1H),




1079, 730 cm−1

2.95 (hept, J = 7.0 Hz, 1H), 2.41 (d, J = 2.5 Hz,






3H), 2.37 (s, 3H), 1.55 (dd, J = 14.2,






7.1 Hz, 3H), 1.40-1.32 (m, 6H),






1.28 (d, J = 7.1 Hz, 3H), 1.03 (dd, J = 6.2,






3.0 Hz, 3H).


238

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.52 (d,





film) 3384,
[M + H]+ calcd for
J = 10.1 Hz, 1H), 8.34 (d, J = 5.4 Hz,




2977, 1762,
C26H34FN2O6,
1H), 6.99 (d, J = 5.4 Hz, 1H),




1735, 1679,
489.2395; found,
6.70 (ddd, J = 15.3, 9.4, 2.7 Hz, 2H),




1505, 1211,
489.2399
5.56 (dp, J = 10.4, 6.3 Hz, 1H),




1127, 861,

4.82-4.65 (m, 1H), 3.89 (s, 3H), 3.43-3.20 (m,




731 cm−1

1H), 2.95 (hept, J = 7.0 Hz, 1H),






2.40 (d, J = 2.4 Hz, 3H), 2.35 (s, 3H),






1.54 (dd, J = 13.5, 7.2 Hz, 3H), 1.36 (dd, J = 7.1,






1.6 Hz, 6H), 1.26 (dd, J = 7.2,






1.0 Hz, 3H), 1.02 (dd, J = 6.2, 2.9 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ







−118.50 (d, J = 25.8 Hz).


239

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.47 (d,





film) 3383,
[M + H]+ calcd for
J = 7.8 Hz, 1H), 8.33 (d, J = 5.4 Hz,




2982, 1762,
C25H30F3N2O6,
1H), 7.67-7.60 (m, 1H),




1739, 1681,
511.2050; found,
7.54-7.45 (m, 1H), 7.44 (d, J = 7.8 Hz, 1H),




1505, 1311,
511.2052
7.34-7.27 (m, 1H), 6.99 (d, J = 5.5 Hz,




1151, 1117,

1H), 5.25-5.14 (m, 1H),




772 cm−1

4.81-4.69 (m, 1H), 3.89 (s, 3H), 3.40-3.25 (m,






1H), 2.96 (hept, J = 7.0 Hz, 1H),






1.51 (d, J = 7.1 Hz, 3H), 1.37 (dd, J = 7.0,






1.8 Hz, 6H), 1.29 (d, J = 6.8 Hz, 3H),






1.09 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.26.



240

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.44 (d,





film) 3383,
[M + H]+ calcd for
J = 7.8 Hz, 1H), 8.33 (d, J = 5.4 Hz,




2982, 1761,
C25H29F4N2O6,
1H), 7.42 (dd, J = 8.8, 5.4 Hz, 1H),




1740, 1680,
529.1956; found,
7.33 (dd, J = 9.2, 2.8 Hz, 1H), 7.19 (td,




1500, 1312,
529.1958
J = 8.3, 2.8 Hz, 1H), 7.00 (d, J = 5.4 Hz,




1120, 909,

1H), 5.14 (p, J = 6.5 Hz, 1H),




732 cm−1

4.81-4.67 (m, 1H), 3.90 (s, 3H),






3.36-3.22 (m, 1H), 2.96 (hept, J = 7.0 Hz,






1H), 1.50 (d, J = 7.2 Hz, 3H), 1.37 (dd,






J = 7.0, 1.9 Hz, 6H), 1.28 (d, J = 6.9 Hz,






3H), 1.11 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.80,







−114.24.


241

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.52 (s,





film) 3382,
[M + H]+ calcd for
1H), 8.32 (d, J = 5.4 Hz, 1H), 6.98 (d, J = 5.4 Hz,




2944, 1764,
C23H35N2O6,
1H), 5.07 (qd, J = 6.5, 3.0 Hz,




1734, 1680,
435.2490; found,
1H), 4.73-4.62 (m, 1H), 3.89 (s,




1504, 1210,
435.2491
3H), 2.95 (hept, J = 7.0 Hz, 1H),




1090, 1040,

1.85-1.61 (m, 2H), 1.61-1.50 (m, 2H),




916, 843,

1.47 (d, J = 7.1 Hz, 3H), 1.43-1.29 (m,




732 cm−1

9H), 1.21 (d, J = 6.4 Hz, 3H),






1.17-1.01 (m, 3H), 0.93 (d, J = 6.9 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 174.69,







172.36, 162.38, 159.45, 146.55,






142.04, 137.69, 109.56, 74.50, 56.28,






48.04, 43.14, 42.93, 33.98, 31.24,






30.70, 25.13, 25.01, 18.82, 18.71,






17.48, 12.50.


242

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.49 (d,





film) 3383,
[M + H]+ calcd for
J = 8.4 Hz, 1H), 8.34 (d, J = 5.5 Hz,




2977, 1762,
C26H34FN2O6,
1H), 6.99 (d, J = 5.5 Hz, 1H),




1735, 1679,
489.2395; found
6.70 (ddd, J = 17.0, 9.4, 2.8 Hz, 2H),




1504, 1210,
489.2399
5.57 (dq, J = 10.4, 6.4 Hz, 1H),




1081, 914,

4.85-4.62 (m, 1H), 3.89 (s, 3H), 3.36 (dp, J = 10.4,




861, 731 cm−1

7.1 Hz, 1H), 2.95 (hept, J = 7.0 Hz,






1H), 2.40 (s, 3H), 2.35 (s, 3H),






1.52 (d, J = 7.2 Hz, 3H), 1.36 (dd, J = 7.0,






1.9 Hz, 6H), 1.26 (dd, J = 7.2, 1.0 Hz,






3H), 1.02 (d, J = 6.2 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.53.



243

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.54 (d,





film) 3383,
[M + H]+ calcd for
J = 12.1 Hz, 1H), 8.34 (d, J = 5.4 Hz,




2977, 1763,
C26H35N2O6,
1H), 7.04-6.94 (m, 4H), 5.60 (dp, J = 10.4,




1735, 1679,
471.2490; found,
6.3 Hz, 1H), 4.75 (ddq, J = 14.6,




1504, 1211,
471.2495
7.2, 3.5 Hz, 1H), 3.89 (s, 3H), 3.42 (dp,




1080, 914,

J = 10.6, 7.1 Hz, 1H), 2.96 (hept, J = 7.0 Hz,




731 cm−1

1H), 2.41 (d, J = 2.5 Hz, 3H),






2.38 (s, 3H), 1.55 (dd, J = 14.2, 7.1 Hz,






3H), 1.36 (dd, J = 7.1, 1.7 Hz, 6H),






1.28 (d, J = 7.1 Hz, 3H), 1.03 (dd, J = 6.2,






2.9 Hz, 3H).


244

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.49 (d,





film) 3383,
[M + H]+ calcd for
J = 9.5 Hz, 1H), 8.34 (d, J = 5.4 Hz,




2977, 1761,
C26H34FN2O6,
1H), 6.99 (d, J = 5.5 Hz, 1H),




1735, 1678,
489.2395; found,
6.82-6.61 (m, 2H), 5.56 (dp, J = 10.4, 6.3 Hz




1504, 1309,
489.2399
1H), 4.75 (pd, J = 7.2, 4.4 Hz, 1H),




1209, 1081,

3.89 (s, 3H), 3.36 (dp, J = 10.3, 7.0 Hz,




1059, 731 cm−1

1H), 2.95 (p, J = 7.0 Hz, 1H), 2.40 (d, J = 2.4 Hz,






3H), 2.35 (s, 3H), 1.54 (dd, J = 13.6,






7.2 Hz, 3H), 1.36 (dd, J = 7.0,






1.8 Hz, 6H), 1.26 (dd, J = 7.2, 1.1 Hz,






3H), 1.02 (dd, J = 6.2, 2.9 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.49







(d, J = 25.8 Hz).


245

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.56 (d,





film) 3379,
[M + H]+ calcd for
J = 7.5 Hz, 1H), 8.35 (d, J = 5.5 Hz,




2986, 1771,
C23H26F3N2O6,
1H), 7.64 (dd, J = 8.0, 1.4 Hz, 1H),




1736, 1676,
473.1737; found,
7.55-7.46 (m, 1H), 7.43 (d, J = 7.8 Hz,




1508, 1310,
483.1733
1H), 7.35-7.28 (m, 1H), 7.01 (d,




1149, 1116,

J = 5.5 Hz, 1H), 5.25-5.13 (m, 1H),




1046, 732 cm−1

4.81-4.70 (m, 1H), 3.91 (s, 3H),






3.43-3.29 (m, 1H), 2.40 (s, 3H), 1.55 (d, J = 7.2 Hz,






3H), 1.28 (d, J = 6.8 Hz, 3H),






1.10 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.25.



246

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3379,
[M + H]+ calcd for
8.61-8.44 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),




2986, 1771,
C23H25F4N2O6,
7.42 (dd, J = 8.8, 5.3 Hz, 1H), 7.34 (dd,




1737, 1677,
501.1643; found,
J = 9.2, 2.9 Hz, 1H), 7.21 (td, J = 8.2,




1500, 1312,
501.1642
2.8 Hz, 1H), 7.02 (d, J = 5.5 Hz, 1H),




1154, 1123,

5.19-5.07 (m, 1H), 4.82-4.69 (m,




1045, 909,

1H), 3.91 (s, 3H), 3.37-3.23 (m, 1H),




732 cm−1

2.41 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H),






1.27 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 6.2 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −58.80,







−114.08.


247

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.58 (s,





film) 3379,
[M + H]+ calcd for
1H), 8.33 (d, J = 5.5 Hz, 1H), 7.00 (d, J = 5.5 Hz,




2946, 1771,
C21H31N2O6,
1H), 5.09 (qd, J = 6.5, 3.0 Hz,




1732, 1676,
407.2177; found,
1H), 4.77-4.62 (m, 1H), 3.90 (s,




1506, 1310,
407.2173
3H), 2.40 (s, 3H), 1.83-1.68 (m, 3H),




1193, 1174,

1.59 (dddt, J = 19.6, 14.7, 7.5, 3.1 Hz,




1060, 906,

4H), 1.49 (d, J = 7.2 Hz, 3H),




731 cm −1

1.38 (dddd, J = 13.6, 9.7, 6.8, 3.0 Hz, 1H),






1.22 (d, J = 6.5 Hz, 3H),






1.18-1.02 (m, 2H), 0.95 (d, J = 6.8 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 172.30,







168.88, 162.36, 159.48, 146.65,






141.67, 137.52, 109.73, 74.49, 56.28,






48.23, 43.34, 43.11, 31.23, 30.75,






25.16, 24.98, 20.75, 18.87, 17.79,






12.49.


248

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.59 (d,





film) 3378,
[M + H]+ calcd for
J = 7.7 Hz, 1H), 8.35 (d, J = 5.4 Hz,




2980, 1770,
C24H31N2O6,
1H), 7.07-6.91 (m, 4H),




1733, 1676,
443.2177; found,
5.67-5.55 (m, 1H), 4.85-4.70 (m, 1H), 3.91 (s,




1506, 1310,
443.2176
3H), 3.42 (dp, J = 10.6, 7.1 Hz, 1H),




1195, 1175,

2.41 (s, 3H), 1.56 (dd, J = 14.4, 7.1 Hz,




1006, 907,

3H), 1.28 (d, J = 7.1 Hz, 3H), 1.04 (dd,




730 cm−1

J = 6.2, 2.8 Hz, 3H).


249


HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.57 (d,






[M + H]+ calcd for
J = 8.7 Hz, 1H), 8.35 (d, J = 5.5 Hz,





C24H30FN2O6,
1H), 7.01 (d, J = 5.5 Hz, 1H),





461.2082; found,
6.70 (ddd, J = 15.2, 9.3, 2.5 Hz, 2H),





461.2080
5.65-5.47 (m, 1H), 4.81-4.64 (m, 1H),






3.91 (s, 3H), 3.36 (dp, J = 10.5, 7.0 Hz, 1H),






2.40 (s, 6H), 2.35 (s, 3H), 1.55 (dd, J = 13.8,






7.2 Hz, 3H), 1.26 (d, J = 7.2 Hz,






3H), 1.03 (dd, J = 6.2, 2.7 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.43.



250

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.54 (d,





film) 3377,
[M + H]+ calcd for
J = 7.8 Hz, 1H), 8.34 (d, J = 5.4 Hz,




2985, 1771,
C23H26F3N2O6,
1H), 8.01 (d, J = 5.2 Hz, 0H), 7.63 (dt,




1737, 1677,
483.1737; found,
J = 8.0, 1.7 Hz, 1H), 7.55-7.47 (m,




1507, 1310,
483.1735
1H), 7.44 (d, J = 7.8 Hz, 1H), 7.31 (dt,




1149, 1116,

J = 9.6, 4.2 Hz, 1H), 7.01 (d, J = 5.5 Hz,




771, 731 cm−1

1H), 5.28-5.12 (m, 1H),






4.75 (dqd, J = 8.4, 7.2, 1.3 Hz, 1H), 3.91 (s,






3H), 3.41-3.28 (m, 1H), 2.41 (s, 3H),






1.52 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 6.8 Hz,






3H), 1.13-1.05 (m, 3H).







19F NMR (376 MHz, CDCl3) δ −58.25.



251

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.50 (d,





film) 2985,
[M + H]+ calcd for
J = 7.9 Hz, 1H), 8.34 (d, J = 5.4 Hz,




1771, 1738,
C23H25F4N2O6,
1H), 7.43 (dd, J = 8.8, 5.3 Hz, 1H),




1677, 1500,
501.1643; found,
7.34 (dd, J = 9.2, 2.8 Hz, 1H), 7.20 (td,




1312, 1193,
501.1640
J = 8.2, 2.9 Hz, 1H), 7.02 (d, J = 5.5 Hz,




1154, 1122,

1H), 5.15 (h, J = 6.5 Hz, 1H),




909, 732 cm−1

4.74 (dq, J = 8.1, 7.1 Hz, 1H), 3.92 (s, 3H),






3.30 (p, J = 6.9 Hz, 1H), 2.41 (s, 3H),






1.52 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 6.8 Hz,






3H), 1.11 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.80,







−114.19.


252

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.58 (s,





film) 3382,
[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H), 7.00 (d, J = 5.4 Hz,




2947, 1771,
C21H31N2O6,
1H), 5.08 (qd, J = 6.4, 3.0 Hz,




1732, 1676,
407.2177; found,
1H), 4.75-4.63 (m, 1H), 3.91 (s,




1505, 1310,
407.2176
3H), 2.40 (s, 3H), 1.85-1.63 (m, 4H),




1199, 1174,

1.63-1.51 (m, 2H), 1.48 (d, J = 7.2 Hz




1151, 1061,

3H), 1.45-1.32 (m, 2H), 1.21 (d,




906, 731 cm−1

J = 6.4 Hz, 3H), 1.17-1.00 (m, 2H),






0.94 (d, J = 6.9 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 172.27,







168.90, 162.40, 159.48, 146.66,






141.66, 137.53, 109.72, 74.58, 56.28,






48.07, 43.13, 42.93, 31.25, 30.69,






25.14, 25.01, 20.75, 18.69, 17.48,






12.50.


253

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.59 (d,





film) 3378,
[M + H]+ calcd for
J = 8.8 Hz, 1H), 8.35 (d, J = 5.4 Hz,




2979, 1770,
C24H31N2O6,
1H), 7.08-6.92 (m, 4H),




1733, 1676,
443.2177; found,
5.66-5.55 (m, 1H), 4.76 (p, J = 7.3 Hz, 1H),




1506, 1195,
443.2170
3.91 (s, 3H), 3.42 (dp, J = 10.5, 7.1 Hz, 1H),




1175, 1006,

2.41 (d, J = 1.7 Hz, 6H), 2.38 (s, 3H),




907, 730 cm−1

1.54 (d, J = 7.1 Hz, 3H), 1.28 (d, J = 7.2 Hz,






3H), 1.03 (d, J = 6.2 Hz, 3H).


254

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3379,
[M + H]+ calcd for
8.55 (dd, J = 16.7, 7.9 Hz, 1H), 8.35 (d, J = 5.4 Hz,




2980, 1771,
C24H30FN2O6,
1H), 7.01 (d, J = 5.5 Hz, 1H),




1733, 1676,
461.2082; found,
6.70 (ddd, J = 17.0, 9.3, 2.7 Hz, 2H),




1507, 1174,
461.2082
5.57 (dq, J = 10.3, 6.1 Hz, 1H),




1130, 1007,

4.82-4.69 (m, 1H), 3.91 (s, 3H), 3.36 (dp, = 10.5,




731 cm−1

6.9 Hz, 1H), 2.40 (d, J = 2.6 Hz,






6H), 2.35 (s, 3H), 1.53 (d, J = 7.2 Hz,






3H), 1.26 (d, J = 7.1 Hz, 3H),






1.02 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.49.



255

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3380,
[M + H]+ calcd for
8.64-8.52 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),




2979, 1770,
C24H31N2O6,
7.07-6.90 (m, 4H), 5.68-5.53 (m,




1733, 1676,
443.2177; found,
1H), 4.86-4.68 (m, 1H), 3.91 (s, 3H),




1506, 1310,
443.2176
3.42 (dp, J = 10.5, 7.1 Hz, 1H),




1195, 1175,

2.39 (m, 6H), 2.38 (s, 3H), 1.56 (dd, J = 14.5,




1006, 907,

7.1 Hz, 3H), 1.28 (d, J = 7.1 Hz,




730 cm−1

3H), 1.04 (dd, J = 6.2, 2.8 Hz, 3H).


256

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3377,
[M + H]+ calcd for
8.68-8.47 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),




2981, 1771,
C24H30FN2O6,
7.01 (d, J = 5.5 Hz, 1H), 6.70 (ddd, J = 14.7,




1734, 1676,
461.2082; found,
9.4, 2.4 Hz, 2H), 5.66-5.48 (m,




1507, 1310,
461.2084
1H), 4.75 (tdd, J = 8.8, 7.2, 5.7 Hz,




1195, 1175,

1H), 3.91 (d, J = 1.6 Hz, 3H), 3.36 (dp,




1007, 908,

J = 10.5, 7.0 Hz, 1H), 2.40 (d, J = 2.8 Hz,




731 cm−1

6H), 2.35 (s, 3H), 1.55 (dd, J = 13.9,






7.2 Hz, 3H), 1.26 (d, J = 7.1 Hz,






3H), 1.03 (dd, J = 6.2, 2.7 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −118.43,







−118.49.


257


HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 8.46 (d,






[M + H]+ calcd for
J = 7.4 Hz, 1H), 8.31 (d, J = 5.5 Hz,





C23H29N2O7,
1H), 7.20-7.10 (m, 2H), 6.98 (d, J = 5.5 Hz,





445.1969; found,
1H), 6.88-6.79 (m, 2H),





445.1949
5.27 (dq, J = 7.7, 6.3 Hz, 1H),






4.61-4.51 (m, 1H), 3.88 (s, 3H), 3.80 (s, 3H),






3.49-3.41 (m, 1H), 2.38 (s, 3H),






1.24 (d, J = 4.7 Hz, 3H), 1.22 (d, J = 3.8 Hz,






3H), 1.11 (d, J = 7.2 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 172.1,







168.9, 162.3, 159.4, 157.2, 146.6,






141.7, 137.5, 131.2, 128.1, 127.3,






120.5, 110.5, 109.7, 74.9, 56.3, 55.4,






48.0, 37.4, 20.7, 18.3, 17.8, 16.6.


258

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.56 (s,





film) 3377,
[M + H]+ calcd for
1H), 8.34 (d, J = 5.5 Hz, 1H),




2980, 2938,
C22H27N2O6,
7.32-7.27 (m, 2H), 7.24-7.16 (m, 3H),




1770, 1732,
415.1864; found,
7.01 (d, J = 5.5 Hz, 1H), 5.09 (dq, J = 7.7,




1674, 1507,
415.1859
6.3 Hz, 1H), 4.77-4.67 (m, 1H),




1310, 1198,

3.91 (s, 3H), 2.96-2.86 (m, 1H), 2.41 (s,




1174, 702 cm−1

3H), 1.49 (d, J = 7.2 Hz, 3H), 1.30 (d, J = 7.0 Hz,






3H), 1.10 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.3,







169.0, 162.4, 159.4, 146.7, 143.0,






141.5, 137.5, 128.4, 127.8, 126.7,






109.7, 76.3, 56.3, 48.1, 45.0, 20.8,






18.7, 18.2, 17.3.


259

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.56 (s,





film) 3380,
[M + H]+ calcd for
1H), 8.34 (d, J = 5.4 Hz, 1H), 7.01 (d, J = 5.5 Hz,




2980, 2938,
C21H27N2O6S,
1H), 6.61 (d, J = 3.5 Hz, 1H),




1770, 1734,
435.1584; found,
6.56 (dq, J = 3.4, 1.1 Hz, 1H),




1674, 1506,
435.1581
5.07-4.98 (m, 1H), 4.77-4.67 (m, 1H),




1193, 1173,

3.91 (s, 3H), 3.20-3.11 (m, 1H), 2.42 (d, J = 1.1 Hz,




1060, 800 cm−1

3H), 2.40 (s, 3H), 1.49 (d, J = 7.2 Hz,






3H), 1.32 (d, J = 7.0 Hz, 3H),






1.17 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.2,







169.0, 162.4, 159.4, 146.7, 143.5,






141.5, 138.0, 137.5, 124.5, 124.1,






109.7, 75.9, 56.3, 48.1, 40.2, 20.8,






18.7, 18.0, 17.3, 15.3.


260

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.54 (s,





film) 3381,
[M + H]+ calcd for
1H), 8.35 (d, J = 5.4 Hz, 1H),




2980, 2940,
C23H28FN2O7,
7.14-7.06 (m, 1H), 7.01 (d, J = 5.5 Hz, 1H),




1770, 1733,
463.1875; found,
6.62-6.51 (m, 2H), 5.18-5.08 (m,




1675, 1502,
463.1874
1H), 4.72-4.62 (m, 1H), 3.92 (s, 3H),




1193, 1175,

3.79 (s, 3H), 3.42-3.31 (m, 1H),




1150, 731 cm−1

2.41 (s, 3H), 1.46 (d, J = 7.2 Hz, 3H),






1.23 (d, J = 7.1 Hz, 3H), 1.13 (d, J = 6.3 Hz,






3H).







19F NMR (471 MHz, CDCl3) δ







−113.9-−114.0 (m).


261

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.61 (d,





film) 2978,
[M + H]+ calcd for
J = 5.3 Hz, 1H), 7.24-7.17 (m, 2H),




2942, 1769,
C21H23N2O6,
7.17-7.06 (m, 4H), 5.61 (q, J = 7.1 Hz,




1712, 1602,
399.1551; found,
1H), 5.16-5.06 (m, 1H), 4.06 (s,




1501, 1371,
399.1549
3H), 2.93-2.83 (m, 1H), 1.70 (d, J = 7.1 Hz,




1242, 1081,

3H), 1.27 (d, J = 7.1 Hz, 3H),




702 cm−1

1.04 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 168.2,







158.7, 154.2, 149.1, 145.8, 142.5,






141.6, 131.5, 128.2, 128.0, 126.5,






111.2, 76.5, 56.8, 51.6, 44.7, 17.5,






17.2, 14.0.


262

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.60 (d,





film) 2942,
[M + H]+ calcd for
J = 5.2 Hz, 1H), 7.13 (d, J = 5.3 Hz,




1769, 1713,
C22H24FN2O7,
1H), 7.02 (dd, J = 8.5, 6.7 Hz, 1H),




1602, 1501,
447.1562; found,
6.59-6.50 (m, 2H), 5.56 (q, J = 7.1 Hz,




1371, 1242,
447.1566
1H), 5.15-5.06 (m, 1H), 4.05 (s,




1080, 731 cm−1

3H), 3.79 (s, 3H), 3.31-3.20 (m, 1H),






1.68 (d, J = 7.0 Hz, 3H), 1.18 (d, J = 7.0 Hz,






3H), 1.16 (d, J = 6.3 Hz, 3H).







19F NMR (471 MHz, CDCl3) δ −113.9.



263


ESIMS m/z 427.2

1H NMR (400 MHz, CDCl3) δ 8.55 (d,






[(M + H)+]
J = 7.8 Hz, 1H), 8.35 (dd, J = 5.4, 2.9 Hz,






1H), 7.23-7.05 (m, 4H), 7.01 (dd,






J = 5.5, 2.2 Hz, 1H), 5.15 (dq, J = 8.7,






6.2 Hz, 1H), 4.80-4.62 (m, 1H),






3.91 (d, J = 1.7 Hz, 3H), 3.35-3.02 (m,






1H), 2.41 (d, J = 1.8 Hz, 3H), 2.35 (s,






3H), 1.50 (t, J = 6.8 Hz, 3H), 1.25 (dd,






J = 6.9, 4.3 Hz, 3H), 1.11 (t, J = 5.9 Hz,






3H).







13C NMR (101 MHz, CDCl3) δ 172.39,







168.89, 159.49, 146.67, 141.80,






137.54, 135.55, 130.49, 126.39,






126.30, 126.23, 109.75, 56.28, 48.19,






48.09, 39.75, 20.74, 19.96, 18.56,






18.48, 18.25, 17.58, 17.46, −0.01.


264


ESIMS m/z 429.3

1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 7.6 Hz,






[(M + H)+]
1H), 8.34 (d, J = 5.4 Hz, 1H),






7.23-6.93 (m, 5H), 5.14 (dq, J = 8.4,






6.2 Hz, 1H), 4.73 (p, J = 7.2 Hz, 1H),






3.91 (s, 3H), 3.19 (dq, J = 8.4, 6.9 Hz,






1H), 2.40 (s, 3H), 2.35 (s, 3H), 1.51 (d, J = 7.1 Hz,






3H), 1.25 (d, J = 6.9 Hz, 3H),






1.12 (d, J = 6.2 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 172.39,







168.89, 162.39, 159.48, 146.67,






141.81, 141.66, 137.54, 135.51,






130.50, 126.39, 126.27, 126.26,






109.74, 56.27, 48.19, 39.81, 20.74,






19.94, 18.73, 18.48, 17.46.


265


ESIMS m/z 457.5

1H NMR (400 MHz, CDCl3) δ 8.49 (s,






[(M + H)+]
1H), 8.34 (dd, J = 5.4, 2.9 Hz, 1H),






7.22-7.06 (m, 4H), 6.99 (d, J = 5.4 Hz,






1H), 5.24-5.04 (m, 1H),






4.79-4.64 (m, 1H), 3.89 (d, J = 1.7 Hz, 3H),






3.18 (dq, J = 9.2, 6.9 Hz, 1H), 2.96 (p,






J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.49 (dd,






J = 7.2, 5.9 Hz, 3H), 1.37 (dd, J = 7.0,






1.7 Hz, 6H), 1.30-1.18 (m, 3H),






1.11 (t, J = 6.2 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 174.68,







172.48, 162.41, 159.47, 146.56,






142.03, 141.83, 137.71, 135.55,






130.48, 126.40, 126.29, 126.21,






109.59, 56.28, 48.07, 39.77, 33.97,






19.96, 18.81, 18.56, 18.26, 17.60, −0.01.


266


ESIMS m/z 457.4

1H NMR (400 MHz, CDCl3) δ 8.49 (s,






[(M + H)+]
1H), 8.33 (d, J = 5.4 Hz, 1H),






7.23-7.05 (m, 4H), 6.99 (d, J = 5.5 Hz, 1H),






5.12 (dt, J = 8.4, 6.2 Hz, 1H), 4.73 (p, J = 7.2 Hz,






1H), 3.89 (s, 3H),






3.38-3.09 (m, 1H), 2.95 (p, J = 7.0 Hz, 1H),






2.35 (s, 3H), 1.50 (d, J = 7.1 Hz, 3H),






1.36 (dd, J = 7.0, 1.1 Hz, 6H), 1.25 (d, J = 6.9 Hz,






3H), 1.12 (d, J = 6.2 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 172.48,







162.36, 159.46, 146.56, 142.03,






141.84, 137.70, 135.51, 130.49,






126.40, 126.27, 126.24, 109.58, 56.28,






48.17, 39.81, 33.96, 19.94, 18.81,






18.76, 18.48, 17.45.


267

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3087,
[M + H]+ calcd for
12.93 (s, 1H), 10.74 (d, J = 7.6 Hz, 1H),




2984, 1737,
C21H24F3N2O4S,
8.00 (d, J = 5.1 Hz, 1H), 7.73-7.59 (m,




1513, 1484,
457.1403; found,
1H), 7.51 (t, J = 7.7 Hz, 1H), 7.43 (d, J = 7.8 Hz,




1311, 1151,
457.1399
1H), 7.33 (t, J = 7.5 Hz, 1H),




1118, 800,

6.89 (d, J = 5.1 Hz, 1H),




771 cm−1

5.30-5.18 (m, 1H), 5.14 (p, J = 7.2 Hz, 1H),






3.96 (s, 3H), 3.37 (p, J = 6.8 Hz, 1H),






1.69 (dd, J = 7.2, 3.2 Hz, 3H), 1.30 (d, J = 6.8 Hz,






3H), 1.14 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.23.



268

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3086,
[M + H]+ calcd for
12.91 (s, 1H), 10.72 (d, J = 7.7 Hz, 1H),




2984, 1735,
C21H23F4N2O4S,
8.00 (d, J = 5.1 Hz, 1H), 7.41 (dd, J = 8.7,




1512, 1313,
475.1309; found,
5.3 Hz, 1H), 7.36 (dd, J = 9.1, 2.8 Hz,




1279, 1153,
475.1308
1H), 7.22 (td, J = 8.2, 2.8 Hz, 1H),




1120, 909,

6.90 (d, J = 5.1 Hz, 1H), 5.16 (dp, J = 21.6,




730 cm−1

6.9 Hz, 2H), 3.96 (s, 3H), 3.34 (p, J = 7.2 Hz,






1H), 1.68 (d, J = 7.2 Hz, 3H),






1.29 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.3 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −58.77,







−113.84.


269

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 3128,
[M + H]+ calcd for
12.94 (d, J = 1.8 Hz, 1H), 10.76 (d, J = 7.9 Hz,




2947, 1735,
C19H29N2O4S,
1H), 7.98 (dd, J = 5.1, 1.4 Hz, 1H),




1511, 1479,
381.1843; found,
6.88 (d, J = 5.1 Hz, 1H),




1280, 1200,
381.1840
5.19-5.00 (m, 2H), 3.95 (s, 3H), 1.85-1.69 (m,




1151, 985,

2H), 1.68-1.32 (m, 7H),




797 cm−1

1.30-1.20 (m, 4H), 1.20-1.01 (m, 3H), 0.96 (d, J = 6.8 Hz,






3H).







13C NMR (101 MHz, CDCl3) δ 188.94,







171.20, 157.16, 149.30, 138.96,






131.63, 109.05, 75.08, 56.26, 52.28,






43.32, 43.13, 31.22, 30.75, 25.15,






24.98, 17.81, 17.23, 12.49.


270


HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 9.96 (d,






[M + H]+ calcd for
J = 7.3 Hz, 1H), 8.34 (d, J = 5.5 Hz,





C23H26F3N2O5S,
1H), 7.71-7.59 (m, 1H),





499.1509; found,
7.59-7.47 (m, 1H), 7.44 (d, J = 7.8 Hz, 1H),





499.1508
7.39-7.28 (m, 1H), 7.00 (d, J = 5.5 Hz,






1H), 5.28-5.15 (m, 2H), 3.91 (s, 3H),






3.42-3.29 (m, 1H), 2.37 (s, 3H),






1.64 (d, J = 7.2 Hz, 3H), 1.30 (d, J = 6.8 Hz,






3H), 1.12 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.23.



271


HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ 9.95 (d,






[M + H]+ calcd for
J = 7.3 Hz, 1H), 8.34 (d, J = 5.4 Hz,





C23H25F4N2O5S,
1H), 7.42 (dd, J = 8.8, 5.3 Hz, 1H),





517.1415; found,
7.35 (dd, J = 9.2, 2.8 Hz, 1H), 7.22 (td,





517.1410
J = 8.2, 2.8 Hz, 1H), 7.00 (d, J = 5.5 Hz,






1H), 5.35-5.03 (m, 2H), 3.91 (s,






3H), 3.41-3.21 (m, 1H), 2.37 (s, 3H),






1.64 (d, J = 7.1 Hz, 3H), 1.29 (d, J = 6.8 Hz,






3H), 1.13 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.78,







−113.98.


272


HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ






[M + H]+ calcd for
10.00 (d, J = 7.3 Hz, 1H), 8.33 (d, J = 5.4 Hz,





C21H31N2O5S,
1H), 6.99 (d, J = 5.4 Hz, 1H),





423.1948; found,
5.24-5.06 (m, 2H), 3.91 (s, 3H), 2.36 (s,





423.1944
3H), 1.83-1.71 (m, 3H),






1.71-1.54 (m, 6H), 1.50 (dtd, J = 14.3, 8.0, 3.3 Hz,






1H), 1.39 (dqd, J = 9.7, 6.9, 3.0 Hz,






1H), 1.25 (d, J = 6.5 Hz, 3H),






1.20-1.02 (m, 2H), 0.96 (dd, J = 6.9, 1.7 Hz,






3H).







13C NMR (101 MHz, CDCl3) δ 189.09,







171.67, 168.57, 159.84, 146.29,






145.12, 136.88, 109.21, 74.86, 56.41,






53.04, 43.36, 43.13, 31.22, 30.75,






25.17, 24.99, 21.27, 17.86, 17.08,






12.46.


273

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 2984,
[M + H]+ calcd for
14.35 (s, 1H), 12.85 (d, J = 6.8 Hz, 1H),




1739, 1571,
C21H24F3N2O6,
7.91 (d, J = 7.1 Hz, 1H), 7.64 (dd, J = 7.9,




1480, 1310,
457.1581; found,
1.4 Hz, 1H), 7.51 (td, J = 7.6, 1.3 Hz,




1150, 1117,
457.1583
1H), 7.44 (d, J = 7.8 Hz, 1H), 7.32 (t, J = 7.6 Hz,




759 cm−1

1H), 6.79 (d, J = 7.2 Hz, 1H),






5.28-5.14 (m, 1H), 4.73 (p, J = 7.1 Hz,






1H), 3.97 (s, 3H), 3.35 (tt, J = 7.5,






3.8 Hz, 1H), 1.62 (d, J = 7.2 Hz, 3H),






1.29 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 6.2 Hz,






3H).







19F NMR (376 MHz, CDCl3) δ −58.22.



274

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 2985,
[M + H]+ calcd for
14.33 (s, 1H), 12.85 (d, J = 6.9 Hz, 1H),




1739, 1480,
C21H23F4N2O6,
7.91 (d, J = 7.2 Hz, 1H), 7.44 (dd, J = 8.8,




1313, 1153,
475.1487; found,
5.4 Hz, 1H), 7.35 (dd, J = 9.2, 2.8 Hz,




1123, 909,
475.1492
1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H),




738 cm−1

6.80 (d, J = 7.2 Hz, 1H), 5.23-5.09 (m,






1H), 4.73 (p, J = 7.2 Hz, 1H), 3.98 (s,






3H), 3.41-3.25 (m, 1H), 1.61 (d, J = 7.2 Hz,






3H), 1.27 (d, J = 6.8 Hz, 3H),






1.11 (d, J = 6.3 Hz, 3H).







19F NMR (376 MHz, CDCl3) δ −58.77,







−114.03.


275

IR (thin
HRMS-ESI (m/z)

1H NMR (400 MHz, CDCl3) δ





film) 2945,
[M + H]+ calcd for
14.40 (s, 1H), 12.75 (d, J = 7.1 Hz, 1H),




1733, 1569,
C19H29N2O6,
7.91 (d, J = 7.2 Hz, 1H), 6.79 (d, J = 7.2 Hz,




1479, 1300,
381.2020; found,
1H), 5.10 (qd, J = 6.4, 3.0 Hz, 1H),




1212, 1152,
381.2016
4.78-4.63 (m, 1H), 3.97 (s, 3H),




1029, 757 cm−1

1.85-1.68 (m, 2H), 1.68-1.51 (m, 7H),






1.51-1.44 (m, 1H), 1.44-1.33 (m,






1H), 1.24 (d, J = 6.4 Hz, 3H),






1.18-0.99 (m, 2H), 0.94 (d, J = 6.9 Hz, 3H).


276

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ





film) 2978,
[M + H]+ calcd for
14.39 (s, 1H), 12.82 (d, J = 6.9 Hz, 1H),




2937, 1735,
C20H25N2O6,
7.89 (d, J = 7.2 Hz, 1H), 7.32-7.25 (m,




1643, 1569,
389.1707; found,
2H), 7.25-7.15 (m, 3H), 6.78 (d, J = 7.2 Hz,




1479, 1452,
389.1703
1H), 5.10 (dq, J = 8.1, 6.3 Hz,




1211, 1154,

1H), 4.75-4.64 (m, 1H), 3.97 (s, 3H),




729, 702 cm−1

2.96-2.86 (m, 1H), 1.56 (d, J = 7.2 Hz,






3H), 1.30 (d, J = 6.9 Hz, 3H),






1.12 (d, J = 6.2 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 171.1,







165.5, 152.5, 149.3, 143.0, 131.0,






128.4, 127.8, 126.7, 123.7, 107.6, 76.5,






56.5, 48.9, 45.0, 18.2, 17.9, 17.4.


277

IR (thin
HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ





film) 2978,
[M + H]+ calcd for
14.42 (s, 1H), 12.80 (d, J = 7.1 Hz, 1H),




2939, 1735,
C21H26FN2O7,
7.89 (d, J = 7.2 Hz, 1H), 7.11 (dd, J = 8.4,




1570, 1502
437.1719; found,
6.7 Hz, 1H), 6.78 (d, J = 7.1 Hz, 1H),




1453, 1213,
437.1727
6.63-6.55 (m, 2H), 5.22-5.13 (m,




1152, 1031,

1H), 4.72-4.61 (m, 1H), 3.98 (s, 3H),




952, 731 cm−1

3.80 (s, 3H), 3.38-3.29 (m, 1H),






1.51 (d, J = 7.2 Hz, 3H), 1.25 (d, J = 7.1 Hz,






3H), 1.13 (d, J = 6.3 Hz, 3H).







19F NMR (471 MHz, CDCl3) δ







−113.9 (dt, J = 11.2, 7.3 Hz).


278
87-88

HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.53 (d, J = 7.1 Hz,






[M + H]+ calcd for
1H), 8.34 (d, J = 5.4 Hz, 1H),





C24H30N2O6,
7.22-7.06 (m, 4H), 7.00 (d, J = 5.5 Hz,





443.2177; found,
1H), 5.14 (dq, J = 8.4, 6.3 Hz, 1H),





443.2186
4.78-4.68 (m, 1H), 3.90 (s, 3H), 3.18 (dt, J = 8.4,






6.9 Hz, 1H), 2.74 (q, J = 7.5 Hz,






2H), 2.35 (s, 3H), 1.51 (d, J = 7.1 Hz,






3H), 1.28 (t, J = 7.5 Hz, 3H), 1.25 (d, J = 6.9 Hz,






3H), 1.12 (d, J = 6.3 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.43,







172.35, 162.39, 159.50, 146.60, 141.81,






141.71, 137.61, 135.51, 130.49, 126.38,






126.27, 109.70, 76.30, 56.28, 48.16,






39.78, 30.93, 27.28, 19.97, 18.77, 18.49,






17.47, 8.81.


279
88-91

HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.52 (d, J = 6.1 Hz,






[M + H]+ calcd for
1H), 8.33 (d, J = 5.4 Hz, 1H),





C25H32N2O6,
7.21-7.06 (m, 4H), 6.99 (d, J = 5.5 Hz,





457.2333; found,
1H), 5.14 (dq, J = 8.4, 6.2 Hz, 1H),





457.2343
4.77-4.69 (m, 1H), 3.89 (s, 3H), 3.18 (dq, J = 8.4,






6.9 Hz, 1H), 2.68 (t, J = 7.5 Hz,






2H), 2.35 (s, 3H), 1.82 (h, J = 7.4 Hz,






2H), 1.50 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 6.8 Hz,






3H), 1.12 (d, J = 6.2 Hz, 3H),






1.05 (t, J = 7.4 Hz, 3H).







13C NMR (126 MHz, CDCl3) δ 172.43,







171.45, 162.37, 159.46, 146.60, 141.81,






141.76, 137.58, 135.51, 130.49, 126.38,






126.27, 109.67, 76.28, 56.25, 48.15,






39.77, 35.79, 19.96, 18.77, 18.48, 18.15,






17.46, 13.60.


280


ESIMS m/z 471

1H NMR (400 MHz, CDCl3) δ 8.53 (s,






([M + H]+)
1H), 8.34 (d, J = 5.4 Hz, 1H),






7.22-7.06 (m, 4H), 7.00 (d, J = 5.5 Hz, 1H),






5.13 (dq, J = 8.3, 6.2 Hz, 1H),






4.85-4.67 (m, 1H), 3.90 (s, 3H), 3.18 (dq, J = 8.4,






6.9 Hz, 1H), 2.80-2.67 (m, 2H),






2.35 (s, 3H), 1.77 (p, J = 7.6 Hz, 2H),






1.48 (dd, J = 17.8, 7.4 Hz, 5H), 1.25 (d,






J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz,






3H), 0.96 (t, J = 7.4 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 172.46,







171.62, 162.40, 159.50, 146.61, 141.84,






141.82, 137.63, 135.53, 130.51, 126.41,






126.29, 126.27, 109.68, 56.26, 48.17,






39.80, 33.67, 26.64, 22.22, 19.96, 18.77,






18.49, 17.47, 13.77.


281


ESIMS m/z 455.4

1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.0 Hz,






([M + H]+)
1H), 8.33 (d, J = 5.4 Hz, 1H),






7.22-7.05 (m, 4H), 6.99 (d, J = 5.5 Hz,






1H), 5.13 (dq, J = 8.3, 6.2 Hz, 1H),






4.82-4.68 (m, 1H), 3.90 (s, 3H), 3.19 (dq, J = 8.4,






6.9 Hz, 1H), 2.35 (s, 3H), 1.97 (tt,






J = 8.0, 4.6 Hz, 1H), 1.51 (d, J = 7.2 Hz,






3H), 1.32-1.21 (m, 5H), 1.12 (d, J = 6.3 Hz,






3H), 1.07 (dq, J = 7.5, 4.0 Hz,






2H).







13C NMR (101 MHz, CDCl3) δ 172.49,







172.45, 162.36, 159.53, 146.61, 142.00,






141.84, 137.50, 135.52, 130.51, 126.41,






126.29, 126.26, 109.67, 60.39, 56.31,






48.13, 39.80, 21.04, 19.96, 18.83, 18.49,






17.47, 14.21, 13.03, 9.26.


282


ESIMS m/z 491.4

1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 7.9 Hz,






([M + H]+)
1H), 8.40 (d, J = 5.5 Hz, 1H),






8.32-8.17 (m, 2H), 7.67-7.57 (m,






1H), 7.50 (dd, J = 8.3, 7.0 Hz, 2H),






7.20-7.08 (m, 4H), 7.06 (d, J = 5.5 Hz, 1H),






5.11 (dq, J = 8.2, 6.2 Hz, 1H),






4.89-4.55 (m, 1H), 3.90 (s, 3H),






3.23-3.03 (m, 1H), 2.34 (s, 3H), 1.47 (d, J = 7.2 Hz,






3H), 1.23 (d, J = 6.9 Hz, 3H),






1.08 (d, J = 6.2 Hz, 3H).







13C NMR (101 MHz, CDCl3) δ 172.51,







164.53, 162.25, 159.68, 146.82, 141.85,






135.53, 133.47, 130.60, 130.50, 129.20,






128.55, 126.40, 126.28, 126.25, 109.77,






56.33, 48.08, 39.79, 19.95, 18.84, 18.47,






17.46.


284


HRMS-ESI (m/z)

1H NMR (500 MHz, CDCl3) δ 8.43 (d, J = 7.8 Hz,






[M + H]+ calcd for
1H), 8.28 (d, J = 5.3 Hz, 1H),





C26H34N2O7,
7.22-7.05 (m, 4H), 6.94 (d, J = 5.4 Hz,





487.2439; found,
1H), 5.78 (q, J = 6.4 Hz, 2H), 5.15 (dq, J = 8.5,





487.2450
6.3 Hz, 1H), 4.75 (p, J = 7.2 Hz,






1H), 3.89 (s, 3H), 3.25-3.15 (m, 1H),






2.55 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H),






1.53 (d, J = 7.2 Hz, 3H), 1.26 (dd, J = 7.1,






5.9 Hz, 3H), 1.14 (dd, J = 8.7, 6.6 Hz,






9H).







13C NMR (126 MHz, CDCl3) δ 176.26,







172.52, 162.94, 160.27, 145.58, 144.25,






142.19, 141.80, 135.51, 130.50, 126.37,






126.26, 109.50, 89.96, 76.30, 56.13,






48.38, 39.79, 33.86, 19.96, 18.69, 18.62,






18.51, 17.51.


285


ESIMS m/z 413

1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 5.3 Hz,






([M + H]+)
1H), 7.18 (d, J = 5.4 Hz, 1H),






7.14 (dd, J = 3.8, 1.4 Hz, 2H),






7.08-6.99 (m, 2H), 5.60 (q, J = 7.1 Hz, 1H),






5.18 (dq, J = 8.2, 6.2 Hz, 1H), 4.06 (s,






3H), 3.14 (dq, J = 8.3, 6.9 Hz, 1H),






2.29 (s, 3H), 1.71 (d, J = 7.0 Hz, 3H), 1.22 (d,






J = 6.9 Hz, 3H), 1.07 (d, J = 6.3 Hz,






3H).







13C NMR (101 MHz, CDCl3) δ 168.34,







158.73, 154.19, 149.12, 145.79, 141.65,






141.53, 135.54, 131.44, 130.30, 126.41,






126.23, 126.11, 111.45, 56.84, 51.51,






39.55, 20.00, 17.74, 17.71, 14.03.





*Cmpd. No.—Compound Number













TABLE 3







Biological Testing Rating Scale


Rating Table for Fungal Pathogens










% Control
Rating







 >80
A



≤80
B



Not Tested
C



 ≤0
D

















TABLE 4







Biological Activity - PUCCRT and SEPTTR


Disease Control in High Volume Applications










HV activity at 100 ppm*












*Cmpd.
*PUCCRT

*SEPTTR












No.
1DP*
3DC*
1DP*
3DC*





116
A
A
B
A


117
B
B
B
B


118
A
A
D
B


119
A
B
D
B


120
B
B
D
B


121
A
A
D
B


122
A
A
B
B


123
A
B
D
B


124
B
D
D
B


125
B
D
D
B


126
A
B
D
B


127
B
B
D
B


128
A
A
A
A


129
A
B
B
B


130
A
A
B
B


131
A
A
B
B


132
A
A
A
B


133
A
B
B
B


134
B
B
B
B


135
B
B
B
B


136
A
B
B
B


137
A
B
B
B


138
A
A
A
B


139
B
D
B
B


140
A
B
B
B


141
A
B
A
B


142
A
A
A
B


143
A
D
B
B


144
D
B
B
B


145
B
B
B
B


146
A
B
A
B


147
A
B
A
B


148
A
B
A
B


149
D
D
B
B


150
D
B
B
B


151
B
D
B
B


152
A
B
B
B


153
B
B
B
B


154
D
D
B
B


155
B
B
B
B


156
D
B
B
B


157
B
D
B
B


158
A
A
A
B


159
A
A
A
A


160
B
A
B
B


161
D
D
B
B


162
D
D
B
B


163
B
B
B
B


164
A
A
B
A


165
A
A
A
A


166
A
A
A
A


167
A
A
A
A


168
A
A
B
A


169
A
A
A
A


170
A
A
B
B


171
A
A
B
B


172
B
A
B
B


173
A
B
B
B


175
A
A
B
B


176
A
B
D
B


258
A
A
B
B


259
A
A
B
D


260
A
B
B
B


267
A
B
B
B


268
A
B
B
B


269
B
A
B
B


276
A
B
B
B


277
B
D
B
B





*Cmpd. No.—Compound Number


*PUCCRT - Wheat Brown Rust (Puccinia triticina)


*SEPTTR - Wheat Leaf Blotch (Zymoseptoria tritici)


*1DP—1 Day Protectant


*3DC—3 Day Curative


*ppm—Parts Per Million













TABLE 5







Biological Activity - PUCCRT and SEPTTR


Disease Control in Low Volume Applications










LV activity at 121.5 g/ha*












*Cmpd
*PUCCRT

*SEPTTR












No.
1DP*
3DC*
1DP*
3DC*





177
A
A
A
A


178
B
B
B
B


179
A
A
B
B


180
B
B
B
B


234
B
B
B
B


235
B
B
A
A


236
B
B
B
D


237
B
B
B
B


238
A
B
A
A


239
D
D
B
B


240
D
D
B
B


241
D
D
B
D


242
A
B
A
A


243
B
B
B
B


244
A
B
A
A


245
A
B
A
A


246
A
A
A
A


247
B
B
B
B


248
A
B
B
A


249
A
A
A
A


250
D
B
B
B


251
B
B
B
B


252
D
B
D
B


253
A
B
B
B


254
A
A
A
A


255
A
B
B
A


256
A
A
A
A


257
B
B
B
B


258
B
A
B
A


259
B
D
B
D


260
D
D
B
D


261
B
D
B
D


262
D
D
B
B


263
B
B
B
B


264
A
A
B
B


265
B
B
B
B


266
B
B
B
B


275
B
D
D
D


231
A
B
B
B


232
A
B
D
B


233
A
B
B
B


270
B
B
B
B


271
B
B
B
B


272
B
B
B
B


273
B
B
B
B


274
B
B
B
B


276
B
B
B
B


277
D
B
B
B





*Cmpd. No.—Compound Number


*PUCCRT - Wheat Brown Rust (Puccinia triticina)


*SEPTTR - Wheat Leaf Blotch (Zymoseptoria tritici)


*1DP—1 Day Protectant


*3DC—3 Day Curative


*g/ha—grams per hectare













TABLE 6







Biological Activity - High Volume Disease Control at 25 ppm









*Cmpd.
PHAKPA*










No.
1DP*
3DC*





128
C
A


158
C
B


159
C
A


175
A
A


177
A
A


178
A
B


179
A
A


180
A
B


181
B
D


182
B
B


183
A
B


184
A
A


185
D
D


186
B
B


187
A
D


188
A
B


189
A
B


190
D
D


191
B
B


192
B
D


193
B
D


194
D
D


195
B
D


196
A
B


197
D
D


198
D
D


199
D
D


200
B
B


201
B
B


202
B
D


203
A
B


204
A
A


205
A
B


206
B
D


207
B
D


208
A
D


209
A
A


210
D
D


211
B
D


212
B
B


213
A
B


214
B
B


215
B
B


216
B
D


217
B
D


218
D
B


219
D
D


220
B
B


221
D
D


222
D
D


223
D
D


224
B
D


225
D
D


226
D
B


227
B
D


228
D
D


229
D
D


230
D
D


231
B
D


232
B
D


233
A
B


234
A
A


235
A
A


236
A
D


237
A
A


238
A
A


239
B
B


240
B
B


241
D
D


242
A
A


243
A
A


244
A
A


245
A
A


246
A
A


247
A
B


248
A
A


249
A
A


250
B
B


251
A
B


252
B
B


253
A
A


254
A
A


255
A
A


256
A
A


257
B
D


258
A
A


259
B
B


260
A
B


261
B
B


262
B
B


263
A
B


264
A
A


265
A
A


266
A
A


270
A
B


271
A
A


272
A
B


273
B
B


274
B
B


275
B
B


276
D
B


277
B
B


284
A
A


278
A
A


279
A
A


280
A
A


281
A
A


282
A
A


285
A
A





*Cmpd. No.—Compound Number


*PHAKPA - Asian Soybean Rust (Phakopsora pachyrhizi)


*1DP—1 Day Protectant


*3DC—3 Day Curative













TABLE 7







Biological Activity - Disease Control in 1DP* test at 100 ppm











Cmpd. No.*
ALTESO*
CERCBE*
COLLLA*
LEPTNO*





263
B
B
D
B


264
B
A
B
A


266
B
B
D
A





*Cmpd. No.—Compound Number


*ALTESO - Tomato Early Blight (Alternaria solani)


*CERCBE - Leaf Spot of Sugar Beets (Cercospora beticola)


*COLLLA - Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotricum lagenarium)


*LEPTNO - Wheat Glume Blotch (Parastagonospora nodorum)













TABLE 8







Biological Activity - Disease Control in 1DP* Test at 100 ppm











Cmpd. No.*
PSPECU*
PYRIOR*
RHYNSE*
UNCINE*





263
B
B
B
A


264
B
A
B
A


266
D
A
B
A





*Cmpd. No.—Compound Number


*PSPECU - Cucumber Downy Mildew (Pseudoperonospora cubensis)


*PYRIOR - Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae)


*RHYNSE - Barley Scald (Rhyncosporium secalis)


*UNCINE - Grape Powdery Mildew (Uncinula necator)


*1DP—1 Day Protectant





Claims
  • 1. A compound according to the formula:
  • 2. An antifungal composition comprising the compound, or an enantiomer or diastereomer of the compound, of claim 1.
  • 3. The composition of claim 2 wherein the composition further comprises one or more fungicides, insecticides, nematocides, miticides, arthropodicides, bactericides and combinations thereof.
  • 4. A method for the control of fungal attack on a plant, the method including the step of: applying a fungicidally effective amount of the compound, or an enantiomer or diastereomer of the compound, of claim 1 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, and foliage of the plant.
  • 5. A method for the control of fungal attack on a plant, the method including the step of: applying a fungicidally effective amount of the composition of claim 2 or 3 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, and foliage of the plant.
  • 6. The method of claim 5, wherein the fungal attack on the plant is an attack by a fungal pathogen selected from Leaf Blotch of Wheat (Zymoseptoria tritici), Wheat Brown Rust (Puccinia triticina), Stripe Rust (Puccinia striiformis), Scab of Apple (Venturia inaequalis), Blister Smut of Maize (Ustilago maydis), Powdery Mildew of Grapevine (Uncinula necator), Barley Scald (Rhynchosporium secalis), Blast of Rice (Pyricularia oryzae), Rust of Soybean (Phakopsora pachyrhizi), Glume Blotch of Wheat (Parastagonospora nodorum), Powdery Mildew of Wheat (Blumeria graminis f. sp. tritici), Powdery Mildew of Barley (Blumeria graminis f. sp. hordei), Powdery Mildew of Cucurbits (Erysiphe cichoracearum), Anthracnose of Cucurbits (Colletotrichum lagenarium), Leaf Spot of Beet (Cercospora beticola), Early Blight of Tomato (Alternaria solani), Cucumber Downy Mildew (Pseudoperonospora cubensis), and Net Blotch of Barley (Pyrenophora teres).
  • 7. The method of claim 5, wherein the fungal attack on the plant is an attack by a fungal pathogen selected from Leaf Blotch of Wheat (Zymoseptoria tritici), Wheat Brown Rust (Puccinia triticina), Barley Scald (Rhynchosporium secalis), Blast of Rice (Pyricularia oryzae), Rust of Soybean (Phakopsora pachyrhizi), Glume Blotch of Wheat (Parastagonospora nodorum), Anthracnose of Cucurbits (Colletotrichum lagenarium), Leaf Spot of Beet (Cercospora beticola), Powdery Mildew of Grapevine (Uncinula necator), Cucumber Downy Mildew (Pseudoperonospora cubensis), and Early Blight of Tomato (Alternaria solani).
CROSS REFERENCE TO RELATED APPLICATION

The present application claims priority to the benefit of U.S. Provisional Patent Application Ser. No. 62/640,424 filed Mar. 8, 2018 and U.S. Provisional Patent Application Ser. No. 62/640,434 filed Mar. 8, 2018 the disclosure of which is hereby incorporated by reference in its entirety.

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Related Publications (1)
Number Date Country
20190276404 A1 Sep 2019 US
Provisional Applications (2)
Number Date Country
62640424 Mar 2018 US
62640434 Mar 2018 US