RU2777557C2 - Molecules used as pesticides and related intermediate products, compositions and methods - Google Patents

Abstract

FIELD: chemistry; agriculture.

SUBSTANCE: invention relates to a molecule with the formula specified below and its agriculturally acceptable salts of connection to acids or divided stereoisomers, which can be used as pesticide against pests, in particular arthropods. The invention also relates to a method for combating pests, which includes the application to a site of pesticide-effective amount of such a molecule.

EFFECT: obtaining a pesticide.

3 cl, 11 tbl, 105 ex

Description

Cross references to related applications

This application claims benefit and priority under U.S. provisional applications. Nos. 62/407092 and 62/407118; which were both filed on October 12, 2016. The entire contents of the above applications are incorporated herein by reference.

Field of technology to which the invention relates

The present invention relates to the field of molecules used as pesticides against pests of arthropods, molluscs and nematodes, methods for producing such molecules, intermediates used in such methods, pesticide compositions containing such molecules, and methods of using such pesticide compositions for control of such pests. These pesticide compositions can be used, for example, as acaricides, insecticides, miticides, molluscicides and nematicides.

State of the art

“Many of the most dangerous human diseases are transmitted by insect vectors” (Rivero et al.). “Historically, malaria, dengue fever, yellow fever, plague, filariasis, louse-borne typhus, trypanosomiasis, leishmaniasis and other insect-borne diseases were responsible for more illnesses and deaths in the 17th and early 20th centuries than in the sum of all other reasons" (Gubler). Insect-borne diseases are responsible for approximately 17% of parasitic and infectious diseases worldwide. Malaria alone causes more than 800,000 deaths per year, 85% of which occur in children under 5 years of age. There are approximately 50 to approximately 100 million cases of dengue fever each year. In addition, between 250,000 and 500,000 cases of dengue hemorrhagic fever are observed annually (Matthews). Vector control plays a critical role in the prevention and control of infectious diseases. However, insecticide resistance, including resistance to multiple insecticides, has emerged in all insect species that are major vectors of human diseases (Rivero et al.). Recently, more than 550 arthropod pest species have developed resistance to at least one pesticide (Whalon et al.). In addition, the number of cases of insect resistance far exceeds the number of cases of resistance to herbicides and fungicides (Sparks et al.).

Every year, insects, plant pathogens and weeds destroy more than 40% of all food produced. These losses occur despite the use of pesticides and the use of a wide range of non-chemical control techniques such as crop rotation and biological control techniques. If just a portion of this food could be saved, more than 3 billion undernourished people could be fed (Pimental).

Nematodes that parasitize plants are among the most common pests and are often among the most secretive and cause the greatest losses. Estimates of losses attributed to nematodes range from approximately 9% in developed countries to approximately 15% in undeveloped countries. However, in the United States, a survey of 35 states for a variety of crops indicates nematode-related losses of up to 25% (Nicol et al.).

It should be noted that gastropods (slugs and snails) are pests that cause less economic losses than other arthropods or nematodes, but in some areas they can significantly reduce yields, greatly affect the quality of harvested products, and also transmit diseases to people and animals and plants. Although several dozen species of gastropods are regionally significant pests, several species are global pests of concern. In particular, gastropods affect a wide variety of agricultural and fruit crops, such as arable, pasture and fiber crops; vegetables; bush and woody fruit plants; herbaceous plants; and ornamental plants (Speiser).

Termites damage all types of private and public buildings, as well as agricultural and forestry resources. In 2005, it was estimated that termites caused annual losses in excess of US$50 billion worldwide (Korb).

Consequently, for many reasons, including those noted above, there is a continuing need for costly (estimated at approximately $256 billion per pesticide in 2010), time-consuming (average approximately 10 years per pesticide), and labor-intensive development of new pesticides (CropLife America ).

Some literature cited in this application

CropLife America, The Cost of New Agrochemical Product Discovery, Development & Registration and Research & Development predictions for the Future, 2010.

Drewes, M., Tietjen, K., Sparks, T.C., High-Throughput Screening in Agrochemical Research, Modern Methods in Crop Protection Research, Part I, Methods for the Design and Optimization of New Active Ingredients, Edited by Jeschke, P., Kramer, W., Schirmer, U. and Matthias W., p. 1-20, 2012.

Gubler, D., Resurgent Vector-Borne Diseases as a Global Health Problem, Emerging Infectious Diseases, Vol. 4, No. 3, p. 442-450, 1998.

Korb, J., Termites, Current Biology, Vol. 17, No. 23, 2007.

Matthews, G., Integrated Vector Management: Controlling Vectors of Malaria and Other Insect Vector Borne Diseases, Ch. 1, p. 1, 2011.

Nicol, J., Turner S., Coyne, L., den Nijs, L., Hocksland, L., Tahna-Maafi, Z., Current Nematode Threats to World Agriculture, Genomic and Molecular Genetics of Plant - Nematode Interactions, p . 21-43, 2011.

Pimental, D., Pest Control in World Agriculture, Agricultural Sciences - Vol. II, 2009.

Rivero, A., Vezilier, J., Weill, M., Read, A., Gandon, S., Insect Control of Vector-Borne Diseases: When is Insect Resistance a Problem? Public Library of Science Pathogens, Vol. 6, No. 8, p. 1-9, 2010.

Sparks T.C., Nauen R., IRAC: Mode of action classification and insecticide resistance management, Pesticide Biochemistry and Physiology (2014) available online 4 December 2014.

Speiser, B., Molluscicides, Encyclopedia of Pest Management, Ch. 219, p. 506-508, 2002.

Whalon, M., Mota-Sanchez, D., Hollingworth, R., Analysis of Global Pesticide Resistance in Arthropods, Global Pesticide Resistance in Arthropods, Ch. 1, p. 5-33, 2008.

Definitions used in the present invention

The examples given in these definitions are generally not exhaustive and should not be construed as limiting the present invention. It should be understood that the substituent must comply with the rules of chemical bonding and steric compatibility restrictions for the particular molecule to which it is attached. These definitions should be used only for the purposes of the present invention.

"Active ingredient" means a material that has activity useful in pest control and/or is useful in promoting other materials having greater activity in pest control. Examples of such materials include, but are not limited to, acaricides, algaecides, avicides , bactericides, fungicides, herbicides, insecticides, molluscicides, nematicides, rodenticides, viricides, antifeedants, bird repellents, chemosterilizers, herbicide antidotes, insect baits, insect repellents, mammal repellents, mating inhibitors, plant activators , plant growth regulators and synergetics. Specific Examples of such materials include, but are not limited to, those listed on the Alpha Group Active Ingredients List.

"Alpha Active Ingredient" ("AIGA") collectively means the following materials:

(1)(3-ethoxypropyl)mercurobromide, 1,2-dibromoethane, 1,2-dichloroethane, 1,2-dichloropropane, 1,3-dichloropropene, 1-MCP, 1-methylcyclopropene, 1-naphthol, 2-(octylthio )ethanol, 2,3,3-TPA, 2,3,5-triiodobenzoic acid, 2,3,6-TBA, 2,4,5-T, 2,4,5-TB, 2,4,5- TP, 2,4-D, 2,4-DB, 2,4-DEB, 2,4-DEP, 2,4-DES, 2,4-DP, 2,4-MCPA, 2,4-MCPB, 2iP, 2-methoxyethylmercuric chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 3,6-dichloropicolinic acid, 4-aminopyridine, 4-CPA, 4-CPB, 4-CPP , 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-phenylmercuroxyquinoline, abamectin, abamectinaminomethyl, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethione, acetochlor, acetophenate, acetophos, acetoprole, acibenzolar, acifluorfen, aclonifen , ACN, acrep, acrinatrine , acrolein, acrylonitrile, acipetax, afidopyropene, afoxolaner, alachlor, alanap, alanicarb, albendazole, aldicarb, aldicarb sulfone, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, allyl alcohol, allyloxycarb, alorak, alpha- cypermethrin , alpha-endosulfan, alphametrin, altretamine, aluminum phosphide, aluminum phosphide, ametoctradine, ametridione, ametrine, ametrine, ambuzine, amicarbazone, amicartiazole, amidition, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminopyralid, aminotriazole, amiprofos- methyl, amiprofos, amiprofos -methyl, amisulbrom, amitone, amitraz, amitrol, ammonium sulfamate, amobam, amorphous silica gel, amorphous silicon dioxide, ampropylphos, AMS, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, afolate, aramitol, arprocarb, arsenic trioxide, asomat, aspirin, asulam, atidation, atratone, atrazine, aureofungin, avermectin B1, AVG, aviglycin, azaconazole, azadirachtin, azaphenidine, azametifos, azidithione, azimsulfuron, azinfosetil, azinphos-ethyl, azinphosmethyl, azinphos-methyl, aziprotrin, aziprothrin, Azitiram , azobenzene, azocyclotine, azotoate, azoxystrobin, bahmedesh, barban, barbanate, barium hexafluorosilicate, barium polysulfide, barium fluorosilicate, bartrin, basic basic copper carbonate, copper chloride, basic copper sulfate, BCPC, beflubutamide, benalaxyl, benalaxyl-M, benazoline, bencarbazone, benclotiaz, bendakingbingji, bendiocarb, bendioxide, benefin, benfluralin, benfuracarb, benfuresat, benmihuangkaoan, benodanil, benomyl, benoxacor, benoxaphos, benquinox, bensulfuron, bensulide, bensultap, bentaluron, benta zone, bentazone, benthiavalicarb, benthiazole, benthiocarb, bentranil, benzadox, benzalkonium chloride, benzamacryl, benzamidol, benzamorph, benzene hexachloride, benzphendizone, benzimine, benzipram, benzobicyclone, benzoepine, benzophenap, benzofluoro, benzohydroxamic acid, benzomate, benzophosphate, benzothiadiazole, benzovindiflupyr, benzoximate, benzoylprop, benzthiazuron, benzuokaotong, benzyl benzoate, benzyladenine, berberine, beta-cyfluthrin, beta-cypermethrin, betoxazine, BHC, bialaphos, bicyclopyrone, biphenazate, bifenox, bifenthrin, bifujunji, bilanafos, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazole, bismerthiazol- copper, bisphenylmercur methylene di(x-naphthalene-y-sulfonate), bispiribac, bistrifluron, bisultap, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalide, BPPS, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenprox, brofenvalerate, broflanilid, broflutrinate, bromacil, bromadiolone, bromochlorvos, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, brombonil, bromobutide, bromocyclen, bromocyclene, bromo-DDT, bromphenoxime, bromophos, bromomethane, bromophos, bromophos-ethyl, brompro pilate, bromothalonil, bromoxynil, brompyrazone, bromuconazole, bronopol, BRP, BTH, bucaprolate, bufencarb, buminafos, bupirimat, buprofezin, Burgundy liquid, bisulfan, busulfan, butacarb, butachlor, butafenacil, butam, butamifos, butane-fipronil, butatiofos, butenachlor, butene-fipronil , butetrin, butidazole, butiobate, buthiuron, butifos, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butrizol, butroxydim, buturon, butylamine, butylate, butylchlorophos, butylene-fipronil, cacodylic acid, cadusafos, cafenstrol, calciferol, calcium arsenate, chlorine at calcium, calcium cyanamide, calcium cyanide, calcium polysulfide, calvinfos, cambendichlor, camphechlor, camphor, captafol, captan, carbam, carbamorph, carbanolate, carbaryl, carbaryl, carbasulam, carbation, carbendazim, carbendazole, carbetamide, carbophenothione, carbofuran, carbon disulfide, carbon tetrachloride, carbonyl sulfide, carbophenothione, cabofos, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carpropamide, cartap, carvacrol, carvone, CAVP, CDAA, CDEA, CDEC, cellocidin, CEPC, ceralur, cerenox, cevadilla, Cheshunt mixture, quinalphos, quinalphos-methyl, quinomethionate, quinomethionate, chiralaxyl, chitosan, chlorobentiazone, chlomethoxyphene, chloralose, chloramben, chloramine phosphorus, chloramphenicol, chloraniformethane, chloranil, chloranocryl, chlorantraniliprole, chlorazifope, chlorazine, chlorobenzide, chlorobenzuron, chlorobicyclene, chlorbromuron, chlorbufam , chlordane, chlordecone , chlordimeform, chlorampentrine, chloretazate, chlorethefon, chlorethoxyphos, chlorethuron, chlorfenac, chlorfenapyr, chlorphenazole, chlorphenetol, chlorphenidim, chlorfenprop, chlorphenson, chlorphensulfide, chlorfenvinfos, chlorfenvinfos-methyl, chlorfluazuron, chlorflurazol, chlorflurecol, chlorflufen, chlorflurenol, chloridazone, chlorimuron , chlorinate , chlorine-ipc, chlormethos, chlormekvat, chlormeshol, chlormetoxinyl, chlornidine, chlornitrophen, chlorobenzilat, chlorinethonitalin, chlorophenisone, chloroform, chloromeborm, chlorometiurone, chloronebin, chloroforin, chlorofos, chloropicrin, chloroprone, chloroprone, chloroprone, chloroprone, chloroprone, chloride, chloride, chloride, chlorin chloroprillletin, chlorpropylate, chlorotalolin, chlortoluron, chlorxyphenidim, chloroxuron, chloroxynil, chlorphonium, chlorfoxime, chlorprazophos, chlorprocarb, chlorprofam, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthiamide, chlorothiophos, chlortoluron, chlozolinate, chitosan, cholecalciferol, choline chloride, chromafenozide, cycloheximide, cymectacar b, cimetacarb , cinerin I, cinerin II, cinerins, cynidone-ethyl, cinmethylin, cinosulfuron, tsintophen, ciobutide, cisanilide, cismetrin, clacifos, clefoxidim, clenpirin, clenpirin, clethodim, climbazole, cliodinate, clodinafop, cloetocarb, clofencet, clopheno tan, clofentesine, clofenvinfos , clofibric acid, clofop, clomazone, clomeprop, clonitralide, cloprop, cloproxydim, clopyralid, cloquintocet, cloransulam, closantel, clothianidin, clotrimazole, cloxifonac, cloxilacone, closilacone, CMA, CMMP, CMP, CMU, codelur, colecalciferol , colophonate, 8- Copper quinolinolate, copper acetate, copper acetoarsenite, copper arsenate, basic copper carbonate, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, basic copper sulfate, copper-zinc chromate, coumachlor, coumaphene, coumaphos, coumafuryl , coumaphos, coumatetralyl, kumethoxystrobin, cumitoate, cumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, cresylic acid, crimidine, crotamiton, crotoxyphos, crotoxiphos, krufomat, cryolite, ku-lur, kufraneb, cumileron, cumiluron, cuprobam, copper oxide (I), curcumenol, CVMP, cyanamide, cyanathrine, cyanazine, cyanofenphos, cyanogen, cyanophos, cyanoate, cyantraniliprole, cyanuric acid, cyazofamide, cybutrin, cyclofuramide, cyclanilide, cyclaniliprole, cycletrin, cycloate, cycloheximide, cycloprate, cycloprotrin, cyclopyrimorate, cyclo sulfamuron . , cyprodinil, ciprofuram, cypromide, cyprosulfamide, cyromazine , cythioate, citrex, daimuron, dalapon, daminozide, dayoutong, dazomet, DBCP, d-camphor, DCB, DCIP, DCPA (Japan), DCPA (USA), DCPTA, DCU, DDD, DDPP, DDT, DDVP, debacarb, decafentine , decamethrin, decarbofuran, DEET, dehydroacetic acid, deicvat, delachlor, delnav, deltamethrin, demefion, demefion-O, demefion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton- S-methyl, demeton-S-methylsulfone, demeton-S-methylsulfone, DEP, depalletrin, derris, desmedipham, desmethrin, desmethrin, d-fanshilukwebingjuji, diafenthiuron, dialifor, dialifos, diallate, diallate, diamidaphos, dianat, diatomaceous earth, diatomite , diazinon, dibromine, dibutyl phthalate, dibutyl succinate, dicamba, dicaptone, dichlobenil, dichlorobenthiazox, dichlorofenthion, dichlorofluanid, dichlon, dichloralurea, dichlorobenzuron, dichlorphenidim, dichloroflurecop, dichloroflurenol, dichlormate, dichlormide, dichloromethane, dichlorophen, dichlorprop, dichlorprop-P, dichlorvos, dichlorzolin , dichlozolin, diclobutrazol, diclocimet, diclofop, diclomesin, dicloran, dichloromesothiaz, diclosulam, dicofol, dicofan, dicumarol, dicresyl, dicrotophos, dicryl, dicoumarol, dicyclanil, dicyclonone, dieldrin, dienochlor, dietamquat, dietathyl, diethion, diethione, di etofencarb, dietholate , diethylpyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, diphenopentene, difenoxuron, difenzoquat, difethialone, difluvidazine, diflubenzuron, diflufenican, diflufenicanil, diflubenzopyr, diflumetorim, dikegulac, dilor, dimatif, dimefluthrin, dimefox, dimefuron , dimehypo, dimepiperate, dimethachlon, dimethane, dimetacarb, dimethachlon, dimethachlor, dimethamethrin, dimethenamid, dimethenamid-P, dimethipine, dimethyrimol, dimethoate, dimethomorph, dimethrin, dimethylcarbate, dimethyl disulfide, dimethyl phthalate, dimethylvinphos, dimethylane, dimexano, dimidazone, dimoxystrobin, dimpylate, dimuron, dinex, dingjunejuo, diniconazole , diniconazole- M, dinitramine, dinitrophenols, dinobuton, dinocap, dinocap-4, dinocap-6, dinoctone, dinophenate, dinopentone, dinoprop, dinosam, dinoseb, dinosulfone, dinotefuran, dinoterb, dinoterbon, diophenolan, dioxabenzophos, dioxacarb, dioxathion, dioxathion, diphacin, diphacinone, diphenadione, diphenamide, diphenamide, diphenylsulfone, diphenylamine, diphenylsulfide, diprogulic acid, dipropalin, dipropetrin, dipterex, dipimethitrone, dipyrithione, diquat, disodium tetraborate, disosultap, disparlur, disugran, disul, disulfiram, disulfoton, dithalymphos, dithianone, dithicro phos, dithioether, dithiomethone, dithiopyr, diuron, dixanotgen, d-limonene, DMDS, DMPA, DNOC, dodemorph, dodicine, dodine, dophenapine, doguadine, dominicalur, doramectin, DPC, drazoxolone, DSMA, d-trans-allethrin, d-trans -resmethrin, dufulin, dimron, EBEP, EBP, ebuphos, ecdylsterone, echlomesol, EDB, EDC, EDDP, edifenfos, eglinasine, emamectin, EMPC, empentrin, enadenine, endosulfan, endothal, endothall, endothion, endrin, enestroburin, enilconazole, enoxastrobin , ethersulfonate, EPN, epocholeon, epophenonan, epoxiconazole, eprinomectin, epronaz, epsilon-metofluthrin, epsilon-momofluorothrin, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdepalletrin, esfenvalerate, ESP, esprocarb, etacelazil, etaconazole, ethaphos, etam, etaboxam, etachlor , ethalfluralin, etamethsulfuron, ethaprochlor, ethephon, etidimuron, etiophencarb, etiolate, ethion, etiosin, ethiprole, ethirimol, ethoate-methyl, etobenzamide, etofumezate, etohexadiol, ethoprop, etoprofos, ethoxyphene, ethoxyquin, ethoxysulfuron, ethylosate, ethyl formate, ethyl pyrophosphate, ethylane , ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercur-2,3-dihydroxypropyl mercaptide, ethylmercuracetate, ethylmercurbromide, ethylmercurchloride, ethylmercurphosphate, ethinofen, ETM, etnipromide, ethobenzanide, etofenprox, etoxazole, etridiazole, etrimphos, e trimphos, eugenol , EXD, famoxadone, fampur, fenac, fenamidone, fenaminosulf, fenaminstrobin, fenamifos, fenapanil, fenarimol, fenasulam, phenazaflor, phenazakhine, fenbuconazole, fenbutatine oxide, fenchlorazole, fenchlorvos, fenclofos, fenclorim, fenetacarb, fenfluthrin, fenfur am, fenhexamide, phenidine, phenytropan , fenitrothion, phenizone, fenjuntong, fenobucarb, phenol, fenoprop, fenotiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenoxycarb, fenpiclonil, fenpyritrin, fenpropatrine, fenpropidine, fenpropimorph, fenpyrazamine, fenpiroximate, fenchi notrione, fenridazone, fenzone, fensulfothione , fenterakol, fentiaprop, fenthion, fenthion-ethyl, fentiaprop, fentin, fentrazamide, fentrifanil, fenuron, fenuron-TCA, fenvalerate, ferbam, ferimzone, iron(III) phosphate, iron(II) sulfate, fipronil, flamprop, flamprop-M , flazasulfuron, flocumafen, flometoquin, flonicamid, florasulam, florpiraxifen, fluacripyrim, fluazaindolizine, fluazifop, fluazifop-P, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flubrocitrinate, flucarbazone, flucetosulfuron, fluchlora lin, flucofuron, flucycloxuron, flucitrinate, fludioxonil, fluenethyl , fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenoxystrobin, flufenprox, flufenpyr, flufenzin, flufiprol, fluhexaphone, flumethrin, flumetover, flumetralin, flumetsulam, flumesin, flumiclorac, flumioxazin, flumipropin, fl umorph, fluometuron, fluopicolide, fluopyram, fluorobenzide , fluoridamide, fluoroacetamide, fluoroacetic acid, fluorochloridone, fluorodifen, fluoroglycophene, fluorimide, fluoromide, fluormidine, fluornitrophen, fluoroxypyr, fluotiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupyradifuron, flu pirsulfuron, fluquinconazole, fluralaner, flurazol, flurecol, flurenol, fluridone, flurochloridone, fluromidine, fluroxypyr, flurprimidol, flursulamide, flurtamone, flusilazole, flusulfamide, flutensin, flutiacet, flutiamide, flutanil, flutolanil, flutriafol, fluvalinate, fluxamethamide, fluxapyroxad, fluxofenim, folpel, folpet, fomesafen, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formotion, formparanate, fosamine, fosetil, fosmethylane, fospirat, fostiazate, fostietane, frontalin, phthalide, fuberidazole, fukaojing, fukaomi, fuunmanzhi, fulumi, fumarin, funaihekaoling, fufenthiourea, furalan, fur alaxil, furamethrin, furamethpir, furan tebufenozide, furatiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furofanate, furyloxifene, gamma-BHC, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellin A3, gibberellins, glyph torus, glitor , glucochloralose, glufosinate, glufosinate-P, glyodine, glyoxime, glyphosate, glyfosine, gossyplur, grandlur, griseofulvin, guanoctin, guazatin, galacrinate, halauxifen, galfenprox, halofenozide, halosaphen, halosulfuron, haloxidine, haloxyfop, haloxy fop-P, haloxyfop-R . hexafluoramine, hexaflurate, hexalur, hexamide, hexazinone, hexylthiophos, hexythiazox, HHDN, holosulf, homobrassinolide, huankaiwo, huanghongjing, huangkaoling, huangjunjuo, hydramethylnon, hydrargafen, slaked lime, hydrogen cyanamide, hydrogen cyanide, hydroprene, hydroxyisoxazole, hymexazole, x Iquincarb, IAA, IBA, IBP, icaridin , imazalil imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, imibenconazole, imitsiafos, imidacloprid, imidaclotis, iminoctadine, imiprotrin, inabenfide, indanofan, indaziflam, indoxacarb, inesin, infusorial earth, iodobonil, iodo carb, iodofenphos, iodomethane, iodosulfuron , iofensulfuron, ioxynil ipazine, IPC, ipconazole, ipfencarbazone, ipfentrifluconazole, iprobenfos, iprodione, iprovalicarb, iprimidam, ipsdienol, ipsenol, IPSP, IPX, isamidophos, isazofos, isobenzan, isocarbamide, isocarbamide, isocarbofos, isocyl isodrin, isofenphos, isofenphos-methyl isofetamide, isolan, isomethiosine, isonoruron, isopamphos, isopolinate, isoprocarb, isoprocil isopropalin, isopropazole, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isothianil isouron, isovaledione, isoxaben, isoxachlortol, isoxadifen, isoxaflutole, isoxapirifop, isoxathione , isuron, ivermectin, ixoxaben, isopamphos, isopamphos, japonilur, japotrins, jasmoline I, jasmoline II, jasmonic acid, jiahuanghongjong, jiajijengxiaolin, jiaxiangjunji, jiekaowan, jiekaoxygroup, Jinganmycin A, iodfenphos, juvenile hormone I, juvenile hormone II, yu venous hormone III, cadetrin, kappa- bifenthrin, kappa-tefluthrin, carbutylate, caretazan, kasugamycin, kejunlin, kelevan, ketospiradox, kieselguhr, kinetin, kinoprene, kyralaxyl, kresoxim-methyl, cuicaoxygroup, lactofen, lambda-cyhalothrin, lancotrione, latilur, lead arsenate, lenacil, lepimectin, lep tofos , lianbenjingji, lime sulphide, lindane, lineatin, linuron, lyrimphos, litlur, looplur, lufenuron, luxiankaolin, lvdingjunji, lvfumidjivji, lvxinkaolin, lithidathione, M-74, M-81, MAA, magnesium phosphide, malathion, maldison, maleic acid hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandestrobin, mandipropamide, maneb, matrine, mazidox . issil alcohol , melitoxin, MEMC, menasone, MEP, mepanipyrim, meperfluthrin, mephenate, mephospholane, mepiquat, mepronil, meptildinocap, mercaptodimethur, mercaptophos, mercaptophos thiol, mercaptothione, mercuric(II) chloride, mercuric(II) oxide, mercuric(I) chloride, merfos, merfos oxide, mesoprazine, mesosulfuron, mesotrione, mesulfen, mesulfenphos, mesulfen, metacresol, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metham, metamifop, metamitron, metaphos, metaxon, metazachlor, metazosulfuron, metazoxolone, metconazole, metepa, metfluraz he , metabenzthiazuron, metacryphos, metalpropalin, metam, metamidophos, metasulfocarb, metazol, metfuroxam, methibenzuron, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, metocrotophos, metolcarb, metometon, methomyl, methoprene, metoprothrin, metoprothrin, metochin-butyl , methotrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl afolate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methyl parathion, methyl acetophos, methyl chloroform, methyl dithiocarbamic acid, methyl dimron, methylene chloride, methyl isofenphos, methyl mercaptophos, methylmer captophos oxide, methyl mercaptophos thiol, methyl mercurbenzoate, methyl mercurdicyandiamide, methyl mercurpentachlorophenoxide, methylneodecanamide, methylnitrophos, methyltriazothione, methiozolin, metiram, metiram-zinc, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metometuron, metominostrobin, methosulam, methoxadiazone, methoxuron, metrafenone, metriam, metribuzin, metriphonate, metrifonate, metsulfovax, metsulfuron, mevinfos, mexacarbate, miehuvey, mieshuan, mievenjudzhi, milbemectin, milbemycinoxime, milneb, mimanan, mipafox, MIPC, mirex, MNAF, moguchuun, molinate, molosultap, momfluorothrin, monalide, monisuron, monoamitraz, monochloroacetic acid, monocrotophos, monolinuron, monomehypo, monosulf iram, monosulfuron, monosultap . naled, naphthalene, naphthalene acetamide, naphthoic anhydride, naphthalophos, naphthoxyacetic acids, naphthylacetic acids, naphthylindane-1,3-diones, naphthyloxyacetic acids, naproanilide, napropamide, napropamide-M, napthalam, natamycin, NBPOS, neburea, neburon, nendrin, neonicotine , niclofos, niclofen, niclosamide, nicobifen, nicosulfuron, nicotine, nicotine sulfate, nifluridide, nikkomycins, NIP, nipyraclofen, nipyralofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrophen, nitrofluorfen, nitrostyrene, nitrotal-isopropyl, nobormide, nonanol, norbormide, norea, norflurazon, nornicotine, noruron, novaluron, noviflumuron, NPA, nuarimol, nuranon, OCH, octachlorodipropyl ether, octylinone, o-dichlorobenzene, ofurac, omethoate, o-phenylphenol, orbencarb, orfralur, orthobencarb, ortho-dichlorobenzene, orthosulfamuron, o rictalur , orysastrobin, oryzalin, osthole, osthole, ostramon, ovatron, ovex, oxabetrinil, oxadiargyl, oxadiazone, oxadixil, oxamate, oxamyl, oxapyrazone, oxapyrazone, oxasulfuron, oxathiopiproline, oxaziclomefone, oxine-copper, oxine-Cu, oxolinic acid, oxpo conazole, oxycarboxin, oxydemeton-methyl, oxydeprophos, oxydisulfoton, oxyenadenine, oxyfluorphen, oxymatrine, oxytetracycline, oxythioquinox, PAC, paclobutrazol, paichongding, palletrin, PAP, para-dichlorobenzene, parafluron, paraquat, parathion, parathion-methyl, parinol, Paris green, PCNB , PCP, PCP-Na, p-dichlorobenzene, PDJ, pebulate, pedinex, perfurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penphenate, penflufen, penfluron, penoxalin, phenoxsulam, pentachlorophenol, pentachlorophenyl laurate, pentanochlor, penthiopyrad, pentmethrin, pen toxazone, perchlordecone, perfluidone, permethrin, pentoxamide, PHC, phenamacryl, fenamacrylethyl, fenaminosulf, phenazine oxide, fenetacarb, phenizofam, phencapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothiol, phenothrin, phenproxide, phentoate, phenylmercurea, phenylmercuracet t, phenylmercuric chloride, phenylmercuricatechin derivative, phenylmercuric nitrate , phenylmercursalicylate, phorate, fosacetim, fosalone, fosamethine, fosazetim, fosazetin, phoscyclotine, phosdifene, fosetyl, phospholane, phospholanemethyl, fosglycine, phosmet, phosnichlor, phosphamide, phosphamidon, phosphine, phosphinotricin, phosphocarb, phosphorus, fostin, phoxim, phoxim-methyl , phthalide, phthalophos, phthalthrin, picarbutrazox, picaridin, picloram, picolinafen, picoxystrobin, pimaricin, pindon, pinoxaden, piperalin, piperazine, piperonyl butoxide, piperonylcyclonene, piperophos, piproctanil, piproctanil, piprotal, pirimetaphos, pirimicarb, pyriminil, primioxif os, pirimiphos-ethyl , pirimiphos-methyl, pival, pivaldione, plyphenate, PMA, PMP, polybutenes, polycarbamate, polychlorocamphene, polyethoxyquinoline, polyoxin D, polyoxins, polyoxorim, polythialane, potassium arsenite, potassium azide, potassium cyanate, potassium ethyl xanthate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, probenazole, prochloraz, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazole, profluralin, profluthrin, profoxydim, profurit-amine , proglinazine, prohexanedione, prohydrojasmone, promacil, promecarb, prometon, prometrin, prometrin, promurit, pronamide, propachlor, propafos, propamidine, propamocarb, propanil, propafos, propachizafop, propargite, propartrin, propazine, propetamphos, profam, propiconazole, propidine, pro pineb , propisochlor, propoxur, propoxycarbazone, propylysome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, protidation, prothiocarb, prothioconazole, prothiophos, protoate, protrifenbut, proxane, primidophos, prinachlor, psoralen, psoralen, pi danone, pidiflumetofen, piflubumid , pymetrozine, pyracarbolide, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyrafluprol, pyramate, pyrametostrobin, pyraoxystrobin, pyrasulfotol, pyraziflumide, pyrazolate, pyrazolinate, pyrazone, pyrazophos, pyrazosulfuron, pyrazothione, pyrazoxifene, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenes -isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxime, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridafenthion, pyridafenthion, pyridate, pyridinitrile, pyrifenox, pyrifluquinazone, pyriftalide, pyrimethafos, pyrimethanil, pirimicarb, pyrimidifen, pyriminobac, pyrimino strobine, pirimiphos-ethyl , pirimiphos-methyl, pirimisulfan, pyrimitate, pyrinuron, pyriophenone, pyriprole, pyripropanol, pyriproxyfen, pyrizoxazole, pyrithiobac, pyrolan, pyroquilon, pyroxasulfone, pyroxulam, pyroxychlor, piroxifur, kinkaosuan, kingkuling, cassia, quinacetol, quinalphos, quinalphos-methyl, quinazamide , quinclorac, quinconazole, quinmerac, quinoclamine, quinofumeline, quinomethionate, quinonamide, quinothione, quinoxifen, quintiofos, quintocene, hisalofop, hisalofop-P, kuvendzhi, quiingding, rabenzazole, rafoxanide, R-diniconazole, rebemid, Reglon, Renriduron, Rescalur, Resmethrin , rodetanil, rhodojaponin-III, ribavirin, rimsulfuron, rizazole, R-metalaxyl, rodetanil, ronnel, rotenone, riania, sabadilla, saflufenacil, sajunmao, saisentong, salicylanilide, salifluofen, sanguinarine, santonin, S-bioallethrin, shradan, scylliroside , sebutylazine , secbumetone, sedaxane, selamectin, semiamitraz, sesamex, sesamolin, sesone, sethoxydim, sevin, shuangjiankaolin, shuangjianankaolin, S-hydroprene, siduron, sifumijvji, siglur, silafluofen, silatrane, silica airgel, silica gel, silthiopham, silthiopham, silthiophane, silvex , simazine, simeconazole, simeton, symetrine, simetrine, syntofen, S-quinoprene, slaked lime, SMA, S-methoprene, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium cyanide, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate , sodium naphthenate, sodium o-phenylphenoxide, sodium orthophenylphenoxide, sodium pentachlorophenate, sodium pentachlorophenoxide, sodium polysulfide, sodium fluorosilicate, sodium tetrathiocarbonate, sodium thiocyanate, solan, sofamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramate, spiroxamine, styrophos, streptomycin, strychnine, sulcatol, sulcofuron, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramide, sulfodiazole, sulfometuron, sulfosate, sulfosulfuron, sulfotep, sulfotepp, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapine, sulfosate, s ulprofos, sultropen, swep , tau-fluvalinate, tavron, tazimcarb, TBTO, TBZ, TCA, TCBA, TCMTB, TCNB, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquine, tebupirimphos, tebutam, tebuthiuron, tekloftalam, teknazen, tecoram, tedion, teflubenzuron, tefluthrin, tefuril trion , tembotrione, temephos, temephos, tepa, TEPP, tepraloxydim, teproloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumetone, terbutylazine, terbutol, terbutryn, terbutryn, terraclor, terramycin, terramycin, tetcyclacys, tetrachlore tan, tetrachlorvinphos, tetraconazole, tetradiphon , tetradisul, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetraniliprole, tetrapion, tetrasul, thallium sulfate, thallium(I) sulfate, tenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadiazine, thiadifluoro, thiamethoxam, thiameturon, ti apronil, thiazafluron, thiazfluron, thiazone, thiazopyr, ticrofos, thiofen, thidiazimine, thidiazuron, thiencarbazone, thifensulfuron, tifluzamide, thimerosal, thimet, thiobencarb, thiocarboxim, thiochlorfenfim, thiochlorphenprim, thiocyanatodinitrobenzenes, thiocyclam , thiodan, thiodiazole-copper, thiodicarb, thiophanocarb, thiophanox, thiofluoximate, thiohempa, thiomersal, thiometone, thionazine, thiophanate, thiophanate-ethyl, thiophanate-methyl, thiophos, thioquinox, thiosemicarbazide, thiosultap, thiotepa, thioxamil, thiram, thiuram, thuringensin, thiabendazole, tiadinil, tiafenacil, tiaodjiean, TIBA, tifatol, thiocarbazil, thioclorim, thioxazafen, thioximide, tirpate, TMTD, toclofos-methyl, tolfenpyrad, tolprocarb, tolpyralate, tolylfluanid, tolylfluanid, tolylmercuracetate, tomarin, topramesone, toxaphene, TPN, tralkoxydim, tralocitrine, tralomethrine, tralopiril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamon, triallate, tri-allate, triamiphos, triapentenol, triarathene, triarimol, triasulfuron, triazamate, triazbutyl, triaziflam, triazophos, triazothione, triazoxide, tribasic copper chloride, tribasic copper sulfate, tribenuron, tribufos, tributyltin oxide, tricamba, trichlorfon, trichloropyr, trichlorfon, trichlorometaphos-3, trichloronate, trichloronate, trichlorotrinitrobenzenes, trichlorfon, triclopyr, triclopyricarb, tricresol, tricyclazole, tricyclohexyltin hydroxide, tridemorph, tridifan, triethazine, triphenmorph, triphenofos, trifloxystrobin, trifloxysulfuron, trif Ludimoxazine, triflumesopyrim, triflumizole, triflumuron , trifluralin, triflusulfuron, trifop, trifopsime, triforin, trihydroxytriazine, trimedlur, trimetacarb, trimeturon, trinexapac, triphenyltin, triprene, tripropindan, triptolide, tritac, trithialan, triticonazole, tritosulfuron, trunk-kall, tuoyelin, uniconazole, uniconazole-P, urbaci d , uredepa, valerate, validamycin, validamycin A, valifenalate, valon, vamidothion, vangarde, vaniliprole, vernolate, vinclozolin, vitamin D3, warfarin, xiaochongliulin, xinjunan, xivojunan, xivojunji, XMC, xylachlor, xylenols, xylylcarb, ximiazol, iishijin g, zarylamide , zeatin, jengxiaoan, jengxiaolin, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazolate, zinc thiozolate, zinc trichlorophenate, zinc trichlorophenoxide, zineb, ziram, zolaprophos, zoocoumarin, zoxamide, zuoanjunji, zuok aoan, zuojunji, juomihuanglong, α-chlorohydrin , α-ecdysone, α-multistriatin, α-naphthaleneacetic acids and β-ecdysone;

(2) the following molecules

(a) N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide (hereinafter "AI-1")

(b) a molecule known as lotilaner, which has the following structure

; And

(c) the following molecules in table A

Table A - Structure of MNo - active ingredients

When used in the present invention, each of the above is an active ingredient and two or more are active ingredients. For additional information, see the Compendium of Pesticide Common Names, available on the Internet at Alanwood.net, and in various publications, including the online publication The Pesticide Manual, available on the Internet at bcpcdata.com.

Particularly preferred active ingredients selected are 1,3-dichloropropene, chlorpyrifos, hexaflumuron, methoxyfenozide, noviflumuron, spinetoram, spinosad and sulfoxaflor (hereinafter "AIGA-2").

Additionally, other particularly preferred selected active ingredients are acequinocyl, acetamiprid, acetoprol, avermectin, azinphos-methyl, biphenazate, bifenthrin, carbaryl, carbofuran, chlorfenapyr, chlorfluazuron, chromafenozide, clothianidin, cyfluthrin, cypermethrin, deltamethrin, diafenthiuron, emamectin benzoate , endosulfan , esfenvalerate, ethiprole, etoxazole, fipronil, flonicamid, fluacripyrim, gamma-cyhalothrin, halofenoside, indoxacarb, lambda-cyhalothrin, lufenuron, malathion, methomyl, novaluron, permethrin, pyridalyl, pyrimidifen, spirodiclofen, tebufenozide, thiacloprid, thiame toxam, thiodicarb, tolfenpyrad and zeta-cypermethrin (hereinafter "AIGA-3").

The term "alkenyl" means an acyclic unsaturated (containing at least one carbon-carbon double bond), branched or straight-chain substituent consisting of carbon and hydrogen atoms, for example, vinyl, allyl, butenyl, pentenyl and hexenyl.

The term "alkenyloxy group" means alkenyl additionally containing a single carbon-oxygen bond, for example, allyloxy group, butenyloxy group, pentenyloxy group, hexenyloxy group.

The term "alkoxy group" means an alkyl group additionally containing a single carbon-oxygen bond, for example, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group and a tert-butoxy group.

The term "alkyl" means an acyclic, saturated branched or straight-chain substituent consisting of carbon and hydrogen atoms, for example, methyl, ethyl, propyl, isopropyl, butyl and tert-butyl.

The term "alkynyl" means an acyclic unsaturated (containing at least one carbon-carbon triple bond), branched or straight-chain substituent consisting of carbon and hydrogen atoms, for example, ethynyl, propargyl, butynyl and pentynyl.

The term "alkynyloxy group" means an alkynyl group additionally containing a single carbon-oxygen bond, for example, a pentynyloxy group, a hexynyloxy group, a heptynyloxy group and an octinyloxy group.

The term "aryl" means a cyclic aromatic substituent consisting of hydrogen and carbon atoms, for example, phenyl, naphthyl and biphenyl.

"Biopesticide" means a microbiological pest control agent that is typically applied in a manner similar to the application of chemical pesticides. They are usually bacterial, but Examples of fungal control products are also available, including Trichoderma spp. and Ampelomyces quisqualis. One well-known example of a biopesticide is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera and Diptera. Biopesticides include products based on entomopathogenic fungi (eg Metarhizium anisopliae); entomopathogenic nematodes (for example, Steinernema feltiae); and entomopathogenic viruses (for example, Cydia pomonella granulovirus). Other Examples of entomopathogenic microorganisms include, but are not limited to, baculoviruses, protozoa, and microsporidia. To eliminate doubt, biopesticides are considered active ingredients.

The term "cycloalkenyl" means a monocyclic or polycyclic unsaturated (containing at least one carbon-carbon double bond) substituent consisting of carbon and hydrogen atoms, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl and octahydronaphthyl.

The term “cycloalkenyloxy group” means a cycloalkenyl group further containing a carbon-oxygen single bond, for example, a cyclobutenyloxy group, a cyclopentenyloxy group, a norbornenyloxy group and a bicyclo[2.2.2]octenyloxy group.

The term "cycloalkyl" means a monocyclic or polycyclic saturated substituent consisting of carbon and hydrogen atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl and decahydronaphthyl.

The term “cycloalkoxy group” means a cycloalkyl group further containing a carbon-oxygen single bond, for example, a cyclopropyloxy group, a cyclobutyloxy group, a cyclopentyloxy group, a norbornyloxy group and a bicyclo[2.2.2]octyloxy group.

The term "halogen" means fluorine, chlorine, bromine and iodine.

The term “haloalkoxy group” means an alkoxy group further containing from one to a maximum possible number of the same or different halogens, for example, a fluoromethoxy group, a trifluoromethoxy group, a 2,2-difluoropropoxy group, a chloromethoxy group, a trichloromethoxy group, a 1,1,2,2-tetrafluoroethoxy group and a pentafluoroethoxy group.

The term "haloalkyl" means an alkyl further containing from one to a maximum possible number of the same or different halogens, for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl, trichloromethyl and 1,1,2,2-tetrafluoroethyl.

The term “heterocyclyl” means a cyclic substituent which may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon atom and at least one heteroatom, wherein said heteroatom is nitrogen, sulfur or oxygen. Examples are:

(1) aromatic heterocyclyl substituents including, but not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl and triazolyl;

(2) fully saturated heterocyclyl substituents, including, but not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl and tetrahydropyranyl;

(3) partially or fully unsaturated heterocyclyl substituents including, but not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydrooxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydroisoxazolyl and 2,3-dihydro-[1,3,4]-oxadiazolyl; And

(4) Additional examples of heterocyclyls include the following:

thietanyl thietanyl oxide and thietanyl dioxide.

The term "site" means a habitat, breeding site, plant, seed, soil, material or environment in which the pest grows, is likely to grow, or may traverse, for example, the site may include: crops, trees, fruits, grains, fodder species, grapes, turf and/or ornamental plants; where domesticated animals live; interior or exterior surfaces of buildings (such as those in which grain is stored); construction materials used in buildings (such as treated wood); and the soil around buildings.

“MoA Material” means a material having a Type of Impact (“MoA”) specified in IRAC MoA Classification v. 7.3, located on the Internet at irac-online.org, which describes:

(1) Acetylcholinesterase (AChE) inhibitors include the following active ingredients acephate, alanicarb, aldicarb, azametifos, azinphos-ethyl, azinphos-methyl, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, cadusafos, carbaryl, carbofuran, carbosulfan, chlorethoxyphos, chlorfenvinphos, chlorine mephos, chlorpyrifos, chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos/DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, etiophencarb, ethion, ethoprofos, fampur, fenamiphos, fenitrothion, fenobucarb, fenthion, formetanate, fosthiazate, furathiocarb, heptenophos, imitsiaphos, isofenphos, isoprocarb, isopropyl O-(methoxyaminothiophosphoryl) salicylate, isoxathion, malathion, mecarbam, methamidophos, methidathione, methiocarb, methomyl, metolcarb, mevinphos, monocrotophos, naled, omethoate, oxamyl , oxydemeton-methyl, parathion, parathion-methyl, phentoate, phorate, fosalone, phosmet, phosphamidon, phoxim, pirimicarb, pirimiphos-methyl, profenofos, propetamphos, propoxur, prothiophos, pyraclofos, pyridafention, quinalphos, sulfotep, tebupirimphos, temefos, terbufos, tetrachlorvinphos, thiodi carb, thiofanox, thiometone, triazamate, triazophos, trichlorfon, trimetacarb, vamidothione, XMC and xylylcarb.

(2) GABA-regulated chloride channel antagonists include the following active ingredients: chlordane, endosulfan, ethiprole and fipronil.

(3) Sodium channel modulators include the following active ingredients acrinatrine, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin S-cyclopentenyl, bioresmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin , gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin [(1R)-trans-isomers], deltamethrin, empenthrin [(EZ)-(1R)-isomers], esfenvalerate , etofenprox, fenpropathrin, fenvalerate, flucitrinate, flumethrin, tau-fluvalinate, galfenprox, imiprotrin, cadethrin, permethrin, phenothrin [(1R)-trans isomer], prallethrin, pyrethrins (pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin, tetramethrin [(1R)-isomers], tralomethrine and transfluthrin and methoxychlor.

(4) Nicotinic acetylcholine receptor (nAChR) agonists include the following active ingredients

(4A) acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam,

(4B) nicotine,

(4C) sulfoxaflor,

(4D) flupyradifurone,

(4E) triflumesopyrim and dichloromesothiase.

(5) Allosteric activators of the nicotinic acetylcholine receptor (nAChR) include the following active ingredients spinetoram and spinosad.

(6) Chloride channel activators include the following active ingredients abamectin, emamectin benzoate, lepimectin, and milbemectin.

(7) Juvenile hormone mimics include the following active ingredients hydroprene, kinoprene, methoprene, fenoxycarb, and pyriproxyfen.

(8) Various nonspecific (multisite) inhibitors include the following active ingredients methyl bromide, chloropicrin, sulfuryl fluoride, borax, boric acid, disodium octaborate, sodium borate, sodium metaborate, antimonyl potassium tartrate, diazomet, and metham.

(9) Chordotonal organ modulators include the following active ingredients pymetrosine and flonicamid.

(10) Mite growth inhibitors include the following active ingredients clofentesine, hexythiazox, difluvidazine and etoxazole.

(11) Microbiological agents for disrupting insect midgut membranes include the following active ingredients: Bacillus thuringiensis subsp. israelensis, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, Bacillus thuringiensis subsp. tenebrionenis, Bt plant proteins (Cry1Ab, Cry1Ac, Cry1Fa, Cry1A,105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1/Cry35Ab1) and Bacillus sphaericus.

(12) Mitochondrial ATP synthase inhibitors include the following active ingredients tetradiphone, propargite, azocyclotine, cyhexatin, phenbutatin oxide, and diafenthiuron.

(13) Oxidative phosphorylation uncoupling agents that act by disrupting the proton gradient include the active ingredients chlorfenapyr, DNOC, and sulfuramide.

(14) Nicotinic acetylcholine receptor (nAChR) channel blockers include the following active ingredients bensultap, cartap hydrochloride, thiocyclam, and thiosultap sodium.

(15) Chitin biosynthesis inhibitors type 0 include the following active ingredients bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, and triflumuron.

(16) Type 1 chitin biosynthesis inhibitors include the following active ingredient: buprofezin.

(17) Diptera moulting agents include the following active ingredient cyromazine.

(18) Ecdysone receptor agonists include the following active ingredients chromafenozide, halofenozide, methoxyfenozide, and tebufenozide.

(19) Octopamine receptor agonists include the following active ingredient: amitraz.

(20) Mitochondrial complex III electron transfer inhibitors include the following active ingredients hydramethylnon, acequinocyl, and fluacripyrim.

(21) Mitochondrial complex I electron transfer inhibitors include the following active ingredients phenazachine, fenpyroximate, pyrimidifene, pyridabene, tebufenpyrad, tolfenpyrad, and rotenone.

(22) Voltage-gated sodium channel blockers include the following active ingredients indoxacarb and metaflumizone.

(23) Acetyl-CoA carboxylase inhibitors include the following active ingredients: spirodiclofen, spiromesifen, and spirotetramat.

(24) Mitochondrial complex IV electron transfer inhibitors include the following active ingredients, aluminum phosphide, calcium phosphide, phosphine, zinc phosphide, and cyanide.

(25) Mitochondrial complex II electron transfer inhibitors include the following active ingredients cyenopyrafen, cyflumetofen and piflubumide and

(28) Ryandine receptor modulators include the following active ingredients chlorantraniliprole, cyantraniliprole, and flubendiamide.

Groups 26 and 27 are not used in this version of the classification scheme. In addition, there is the UN group, which contains active ingredients of unknown or undetermined effect. This group includes the following active ingredients azadirachtin, benzoximate, biphenazate, bromopropylate, quinomethionate, cryolite, dicofol, pyridalyl and pyrifluquinazone.

The term “pest” means an organism that is harmful to people or human resources (such as crops, foods, livestock, etc.), where the organism is a member of the orders Arthropods, Molluscs, or Nematodes. Specific Examples are ants, aphids, bedbugs, beetles, bristletails, caterpillars, cockroaches, crickets, earwigs, fleas, flies, grasshoppers, grubs, hornets, leafhoppers, grasshoppers, lice, locusts, grubs, feltworms, mites, moths, nematodes , horseflies, cycads, true psyllids, sawflies, homoptera, silverfish, slugs, snails, spiders, forktails, stink bugs, sessile-bellied hymenoptera, termites, thrips, jellies, wasps, whiteflies and wireworms.

Additional Examples are pests:

(1) Subphyla Chelicerates, Myriapods and Hexapods.

(2) Classes Arachnids, Millipedes and Insects.

(3) Order louse. A non-exhaustive list of specific genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp. and Polyplax spp. A non-exhaustive list of specific species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus and Pthirus pubis.

(4) Order Coleoptera. A non-exhaustive list of specific genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp. ., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp. and Tribolium spp. A non-exhaustive list of specific species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis , Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus , Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Oryzae philus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile and Zabrus tenebrioides.

(5) Order Leatheroptera. A non-exhaustive list of specific species includes, but is not limited to, Forficula auricularia.

(6) Order cockroaches. A non-exhaustive list of specific species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis and Supella longipalpa.

(7) Order Diptera. A non-exhaustive list of specific genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp. ., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp. and Tipula spp. A non-exhaustive list of specific species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris , Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana and Stomoxys calcitrans.

(8) Order Hemipteran bugs. A non-exhaustive list of specific genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp. ., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of specific species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pea, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus su turellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum gran arium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata , Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis and Zulia entreriana.

(9) Order Hymenoptera. A non-exhaustive list of specific genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp. ., Vespula spp. and Xylocopa spp. A non-exhaustive list of specific species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni and Tapinoma sessile.

(10) Order termites. A non-exhaustive list of specific genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procornitermes spp. ., Reticulitermes spp., Schedorhinotermes spp. and Zootermopsis spp. A non-exhaustive list of specific species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes ticulitermes speratus, Reticulitermes tibialis and Reticulitermes virginicus.

(11) Order Lepidoptera. A non-exhaustive list of specific genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp. ., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp. and Yponomeuta spp. A non-exhaustive list of specific species includes, but is not limited to, Achaea janata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana , Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, E uxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta , Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rap ae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae and Zeuzera pyrina.

(12) Order lice eaters. A non-exhaustive list of specific genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp. and Trichodectes spp. A non-exhaustive list of specific species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae and Trichodectes canis.

(13) Order Orthoptera. A non-exhaustive list of specific genera includes, but is not limited to, Melanoplus spp. and Pterophylla spp. A non-exhaustive list of specific species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria and Scudderia furcata.

(14) Order hayeaters. A non-exhaustive list of specific species includes, but is not limited to, Liposcelis decolor, Liposcelis entomophila, Lachesilla quercus and Trogium pulsatorium.

(15) flea order. A non-exhaustive list of specific species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis and Pulex irritans.

(16) Order Fringed Pterus. A non-exhaustive list of specific genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp. and Thrips spp. A non-exhaustive list of specific species includes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilos us, Thrips orientalis and Thrips tabaci .

(17) Order bristletail. A non-exhaustive list of specific genera includes, but is not limited to, Lepisma spp. and Thermobia spp.

(18) Order mites. A non-exhaustive list of specific genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp. ., Rhizoglyphus spp. and Tetranychus spp. A non-exhaustive list of specific species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eote tranychus carpini, Notoedres cati , Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae and Varroa destructor.

(19) Arachnida order. A non-exhaustive list of specific genera includes, but is not limited to, Loxosceles spp., Latrodectus spp. and Atrax spp. A non-exhaustive list of specific species includes, but is not limited to, Loxosceles reclusa, Latrodectus mactans and Atrax robustus.

(20) Class symphyl. A non-exhaustive list of specific species includes, but is not limited to, Scutigerella immaculata.

(21) Subclass of forktail. A non-exhaustive list of specific species includes, but is not limited to, Bourletiella hortensis, Onychiurus armatus, Onychiurus fimetarius and Sminthurus viridis.

(22) A type of nematode. A non-exhaustive list of specific genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Globodera spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp. . and Radopholus spp. A non-exhaustive list of specific species includes, but is not limited to, Dirofilaria immitis, Globodera pallida, Heterodera glycines, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Pratylenchus penetrans, Radopholus similis and Rotylenchulus reniformis.

(23) Like clams. A non-exhaustive list of specific species includes, but is not limited to, Arion vulgaris, Cornu aspersum, Deroceras reticulatum, Limax flavus, Milax gagates and Pomacea canaliculata.

A particularly preferred group of pests to control are sucking pests. Sucking pests typically have piercing and/or sucking mouthparts and feed on plant sap and internal tissues. Examples of particularly agriculturally important sucking pests include, but are not limited to, aphids, leafhoppers, moths, homoptera, thrips, psyllids, felt flies, stink bugs, and whiteflies. Specific examples of species that include agriculturally important sucking pests include, but are not limited to, lice and hemipterans. Specific examples of agriculturally important hemiptera include, but are not limited to, Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Coccus spp., Euschistus spp., Lygus spp., Macrosiphum spp., Nezara spp. and Rhopalosiphum spp.

Another particularly preferred group of pests to control are chewing pests. Gnawing pests typically contain mouthparts that allow them to chew on plant tissue, including roots, stems, leaves, buds, and reproductive tissues (including, but not limited to, flowers, fruits, and seeds). Examples of particularly agriculturally important chewing pests include, but are not limited to, caterpillars, beetles, grasshoppers and locusts. Specific examples of species that include agriculturally important chewing pests include, but are not limited to, Coleoptera and Lepidoptera. Specific examples of particularly agriculturally important Coleoptera include, but are not limited to, Anthonomus spp., Cerotoma spp., Chaetocnema spp., Colaspis spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Phyllophaga spp., Phyllotreta spp. ., Sphenophorus spp., Sitophilus spp.

"Pesticidal effective amount" means the amount of a pesticide required to produce an observable effect on a pest, such as causing necrosis, killing, retardation, prevention, removal, destruction or otherwise reducing the presence and/or activity of a pest at a site, which effect may be manifested by when pest populations have been removed from the site, the pests are rendered incapacitated on or near the site and/or the pests are eliminated from or near the site. Of course, a combination of these effects may occur. It is generally desirable that pest populations, activity, or both be reduced by more than 50%, preferably by more than 90%, and most preferably by more than 99%. Generally, the pesticide effective amount for agricultural purposes is from about 0.0001 g/ha to about 5000 g/ha, preferably from about 0.0001 g/ha to about 500 g/ha, and even more preferably from about 0.0001 g/ha up to approximately 50 g/ha.

Detailed Description of the Invention

Disclosed herein are molecules of Formula 1

Formula 1

in which:

(A) R ¹ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(B) R ² is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(C) R ³ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(D) R ⁴ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(E) R ⁵ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(F) R ⁶ means H;

(G) R ⁷ is selected from the group consisting of F, Cl and Br;

(H) R ⁸ is selected from the group consisting of F, Cl and Br;

(I) R ⁹ means H;

(J) Q ¹ selected from the group consisting of O and S;

(K) Q ² selected from the group consisting of O and S;

(L)R ¹⁰ is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )alkynyl, (C ₁ -C ₃ )alkyl-O( C ₁ -C ₃ )alkyl and (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl;

(M) R ¹¹ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(N)R ¹² is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(O)R ¹³ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(P)R ¹⁴ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(Q) X ³ means:

(1) N(R ^15a )(R ^15b ), where

(a) said R ^15a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkylphenyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ -C ₃ )alkyl and

(b) said R ^15b means substituted or unsubstituted phenyl, said substituted phenyl containing one or more substituents selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , NH ₂ , OH, SF ₅ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )haloalkenyl, (C ₁ -C ₃ )alkoxy group, (C=O) O(C ₁ -C ₃ )alkyl, O(C=O)(C ₁ -C ₃ )alkyl, N(R ^15c ) ₂ , N=CHN(R ^15c )(X ⁴ ), N(R ^15c )C (=O)O(X ⁴ ), N(R ^15c )S(=O) ₂ (X ⁴ ), N(S(=O) ₂ (C ₁ -C ₃ )alkyl) ₂ , N(R ^15c ) C(=O)N(R ^15c ) ₂ , N(R ^15c )C(=O)N(R ^15c )X ⁴ , N(R ^15c )C(=S)N(R ^15c ) ₂ , N(R ^15c )C(=S)N(R ^15c )X ⁴ , N(R ^15c )(C ₁ -C ₃ )alkyl-X ⁴ , N(R ^15c )(CH(O(C ₁ -C ₃ )alkyl) ₂ ), N(R ^15c )((C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl), N(R ^15c )((C ₁ -C ₃ )alkyl-C( =O)N(R ^15c ) ₂ ), N(R ^15c )C(=O)(R ^15c ), N(R ^15c )C(=O)X ⁴ , N(R ^15c )(C(=O) ) ₂ X ⁴ , N(R ^15c )(C(=O)) ₂ OX ⁴ , N(R ^15c )(C(=O)) ₂ N(R ^15c )X ⁴ , N(C(=O)O (C ₁ -C ₆ )alkyl) ₂ , N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, N(R ^15c )C(=O)N(R ^15c )C(=O )O(R ^15c ), N(R ^15C )(C(=O)O(C ₁ -C ₆ )alkyl), N(R ^15C )(C(=O)O(C ₁ -C ₆ )haloalkyl) , N((C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₆ )alkyl)(C(=O)(C ₁ -C ₆ )alkyl), N((C ₁ -C ₃ )alkyl-O(C ₁ -C ₆ )alkyl)(C(=O)O(C ₁ -C ₆ )alkyl) and N(R ^15c )C(=S)X ⁴ ,

(1) said R ^15c is each independently selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl , (C ₂ -C ₃ )haloalkenyl, (C ₁ -C ₃ )alkylphenyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(= O)(C ₁ -C ₃ )alkyl, C(=O)(C ₁ -C ₃ )alkyl and phenyl, optionally for N(R ^15c ) ₂ said N(R ^15c ) ₂ means a heterohydrocarbyl ring containing 1 ring atom nitrogen and 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated,

(2) said X ⁴ is selected from the group consisting of (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, O( C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkylphenyl, phenyl, aryl and heterocyclyl, each of which may contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NO ₂ , NH ₂ , oxo group, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ , O(C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )haloalkyl, N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, N (R ^15c )S(=O) ₂ (R ^15c ), S(=O) ₂ (R ^15c ), (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )cycloalkyl,

wherein in (1)(a) and (1)(b) each of said alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, aryl and heterocyclyl may contain one or more substituents selected from the group consisting of F, Cl, Br, I , CN, OH, NO ₂ , NH ₂ , NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ , O(C ₁ -C ₆ )alkyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl and (C ₃ -C ₆ )cycloalkyl;

(2) N(R ^16a )(R ^16b ), where

(a) said R ^16a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(b) said R ^16b means substituted or unsubstituted (C ₁ -C ₈ )alkyl, said substituted (C ₁ -C ₈ )alkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN , NO ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₁ -C ₈ )alkylphenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl , O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkyl, C(=O)O(C ₁ -C ₈ )alkyl, OC(=O)(C ₁ -C ₈ )alkyl, C(=O)N(R ^16a )(C ₁ - C ₈ )alkyl, N(R ^16a )C(=O)(C ₁ -C ₈ )alkyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O ) ₂ (C ₁ -C ₈ )alkyl, S(O) ₂ NH ₂ and N(R ^16a )S(O) ₂ (C ₁ -C ₈ )alkyl,

where in (2)(a) and (2)(b) each alkyl, alkenyl, alkynyl, cycloalkyl and phenyl may contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ -C ₈ )alkyl) ₂ and C(=O )O(C ₁ -C ₈ )alkyl;

(3) N(R ^17a )(N(R ^17b )(R ^17c )), where

(a) said R ^17a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(b) said R ^17b is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(c) said R ^17c is selected from the group consisting of H, substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, substituted or unsubstituted (C ₃ -C ₈ )cycloalkyl, C(= O)X ⁵ and C(=S)X ⁵ ,

(1) said X ⁵ is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, O(C ₁ -C ₈ )alkyl, O(C ₁ -C ₈ )haloalkyl, O(substituted and unsubstituted)phenyl, N(R ^17a )(C ₁ -C ₈ )alkyl, N(R ^17a )(C ₁ -C ₈ )haloalkyl, N(R ^17a )(C ₃ -C ₈ )cycloalkyl, N(R ^17a ) (substituted and unsubstituted phenyl) and (C ₃ -C ₆ )cycloalkyl,

(2) said substituted phenyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group and (C₁-C₃)alkyl,

(3) said substituted heterocyclyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group and (C₁-C₃)alkyl,

(4) said substituted (C ₁ -C ₈ )alkyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NO ₂ , NH ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, phenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S (O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl, O(C ₁ -C ₈ )alkyl( C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, C(=O)NH(C ₁ -C ₈ )alkyl , NHC(=O)(C ₁ -C ₈ )alkyl, S(O) ₂ NH ₂ , NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ ,

(5) said substituted (C ₃ -C ₈ )cycloalkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, (C ₁ -C ₃ )alkoxy and (C ₁ - C ₃ )alkyl,

wherein in (2)(a), (2)(b) and (2)(c), each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl may optionally contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ -C ₈ )alkyl) ₂ and C(=O)O(C ₁ -C ₈ )alkyl, optionally (N(R ^17b )(R ^17c )) means a heterohydrocarbyl ring containing 1 ring nitrogen atom and 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated;

(4) N(R ^18a )(N=C(R ^18b )(R ^18c )

(a) said R ^18a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )alkyl-O (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ -C ₃ )alkyl,

(b) said R ^18b is selected from the group consisting of H and (C ₁ -C ₃ )alkyl,

(c) said R ^18c is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, substituted or unsubstituted (C ₃ -C ₈ )cycloalkyl,

(1) said substituted phenyl in (4)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO ₂ , OH, (C ₁ -C ₃ )alkoxy group, ( C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkoxy group and (C ₁ -C ₃ )haloalkyl,

(2) said substituted heterocyclyl in (4)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group, (C₁-C₃)alkyl, (C₁-C₃)haloalkoxy group and (C₁-C₃)haloalkyl,

(3) said substituted (C ₁ -C ₈ )alkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, phenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, C(=O)NH(C ₁ -C ₈ )alkyl, NHC(=O)(C ₁ -C ₈ )alkyl and S(O) ₂ NH ₂ ,

(4) said substituted (C ₃ -C ₈ )cycloalkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, (C ₁ -C ₃ )alkoxy and (C ₁ - C ₃ )alkyl,

where in (4)(a), (4)(b) and (4)(c) each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl may contain one or more substituents selected from the group consisting of F , Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ - C ₈ )alkyl) ₂ and C(=O)O(C ₁ -C ₈ )alkyl, optionally C(R ^18b )(R ^18c ) means a hydrocarbyl ring containing from 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated, optionally one or more of said ring carbon atoms may be a nitrogen, oxygen or sulfur atom;

and N-oxides, agriculturally acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystalline polymorphs, isotopes, separated stereoisomers, tautomers, pro-insecticides of molecules of formula 1.

In another embodiment, a molecule of Formula 1, wherein said molecule has the following formula

Formula 2.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ¹ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ² is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ³ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ⁴ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ⁵ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

In another embodiment, a molecule of formula 1 and formula 2, wherein at least one of R ² , R ³ and R ⁴ is SF ₅ .

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ⁷ is Cl.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ⁸ is Cl.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R⁷ And R⁸ are not the same.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein Q ¹ is O.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein Q ² is O.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ¹⁰ is H.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ¹¹ is H.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ¹² is selected from the group consisting of H, F, Cl, CH ₃ and CF ₃ .

In another embodiment, a molecule of Formula 1 and Formula 2, wherein R ¹³ is selected from the group consisting of F, Cl, CH ₃ and OCH ₃ .

In another embodiment, a molecule of formula 1 and formula 2, wherein R ¹⁴ is selected from the group consisting of H, F and Cl.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein:

R ¹ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ² is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ³ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ⁴ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ⁵ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ⁷ is Cl;

R ⁸ is Cl;

Q ¹ means O;

Q ² means O;

R ¹⁰ means H;

R ¹¹ means H;

R ¹² is selected from the group consisting of H, F, Cl, CH ₃ and CF ₃ ;

R ¹³ is selected from the group consisting of F, Cl, CH ₃ and OCH ₃ ; And

R ¹⁴ is selected from the group consisting of H, F and Cl.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein X ³ is N(R ^15a )(R ^15b ).

In another embodiment, a molecule of Formula 1 and Formula 2, wherein X ³ is N(R ^15a )(R ^15b ) and said R ^15b is selected from the group consisting of N(R ^15c )C(=O)(R ^15c ) and N (R ^15c )C(=O)X ⁴ , said R ^15c are all independently selected from the group consisting of (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₁ -C ₃ )haloalkyl and ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, indicated by X ⁴ selected from the group consisting of (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl and (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, and each of said alkyl, haloalkyl and alkenyl may contain one or more substituents selected from the group consisting of F, Cl, CN and (C ₃ -C ₆ )cycloalkyl. For the avoidance of doubt, it should be noted that this includes, for example, substitution of haloalkyl, which includes the term "alkyl" with one or more substituents, for example, CN or (C ₃ -C ₆ )cycloalkyl.

In another embodiment, a molecule of Formula 1 and Formula 2, wherein X ³ is N(R ^16a )(R ^16b ).

In another embodiment, a molecule of Formula 1 and Formula 2, wherein X3 is N(R ^17a )(N(R ^17b )(R ^17c )).

In another embodiment, a molecule of Formula 1 and Formula 2, wherein X ³ is N(R ^18a )(N=C(R ^18b )(R ^18c ).

В другом варианте осуществления молекула, выбранная из таблицы 2, предпочтительно молекула, выбранная из группы, включающей F1007, F1079, F1108, F1147, F1185, F1234, F1241, F1246, F1247, F1248, F1250, F1460, F1465, F1593, F1598, F1613 , F1627, F1657, F1694, F1696, F1697, F1702, F1703, F1704, F1708, F1711, F1740, F2016, F2017, F2021, F2027, F2039, F2042, F2078 and F2081.

The molecules of formula I can exist in different geometric or optical isomeric or different tautomeric forms. One or more centers of chirality may be present, in which case the molecules of Formula 1 may be present as pure enantiomers, mixtures of enantiomers, diastereoisomers, or mixtures of diastereoisomers. Those skilled in the art will appreciate that one stereoisomer may be more active than other stereoisomers. The individual stereoisomers can be prepared by known selective synthesis techniques using separated starting materials or by conventional separation techniques. The molecule may contain double bonds, in which case the compounds of formula 1 may exist as a single geometric isomer (cis or trans, E or Z) or mixtures of geometric isomers (cis and trans, E and Z). Tautomerization sites may be present. The present invention includes all such isomers, tautomers and mixtures thereof in all proportions. The structures disclosed in the present invention are depicted in only one geometric form for clarity, but are intended to be representative of all geometric forms of the molecule.

OBTAINING FORMULA 1 MOLECULES

Preparation of cyclopropylcarboxylic acids

Stilbenes 1-1, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁹ are as disclosed above, can be treated with a base such as sodium hydroxide in the presence of a carbene source such as chloroform or bromoform, and a phase transfer catalyst such as N-benzyl-N,N-diethylethanamine chloride, in a polar protic solvent such as water, at temperatures from about 0°C to about 40°C to obtain diarylcyclopropanes 1-2, in of which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are as described above (Scheme 1, step a). Alternatively, stilbenes 1-1, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁹ are as disclosed above, can be treated with a salt, such as sodium iodide, in the presence of a carbene source, such as trimethyl(trifluoromethyl)silane, in a polar aprotic solvent such as tetrahydrofuran, at temperatures from about 80°C to about 120°C under microwave heating to obtain diarylcyclopropanes 1-2, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are as described above (Scheme 1, step a). Treatment of diarylcyclopropanes 1-2 with a transition metal such as ruthenium(III) chloride in the presence of a stoichiometric amount of an oxidizing agent such as sodium periodate in a mixture of solvents, preferably water, ethyl acetate and acetonitrile, at temperatures from about 0°C to about 40°C can give cyclopropylcarboxylic acids 1-3, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are as described above (Scheme 1, step b).

Scheme 1

Preparation of stilbenes

Stilbenes 1-1 can be prepared by several different procedures, shown in Scheme 2. Phenylcarbonyls 2-1, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are as described above, can be treated with alkoxybenzylphosphonates 2-2 in the presence of a base such as sodium methoxide in a polar aprotic solvent such as N,N-dimethylformamide at temperatures from about -10°C to about 30°C and then heated at a temperature from 40°C to about 80 °C and obtain stilbenes 1-1 (scheme 2, step a). Aryl halides 2-3, in which R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as disclosed above, can be treated with vinylbenzenes 2-4, in which R ⁶ and R ⁹ are as disclosed above, in the presence of a transition metal catalyst such as palladium(II) acetate and a bisphosphine ligand such as 1,1′-bis(diphenylphosphino)ferrocene in a basic solvent such as triethylamine at temperatures from about 60° C. to about 100 °C and obtain stilbenes 1-1 (scheme 2, step b).

Scheme 2

In yet another embodiment, stilbenes 1-1 can also be prepared by the Wittig olifination procedure (Chalal, M.; Vervandier-Fasseur, D.; Meunier, P.; Cattey, H.; Hierso, J.-C. Tetrahedron 2012, 68 , 3899-3907), presented in diagram 2.5. Phenylcarbonyls 2-1, in which R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as described above and R ⁶ is H, can be treated with alkoxybenzyltriphenylphosphonium chlorides 2.5-2 in the presence of a base such as n-butyllithium, in a polar aprotic solvent such as tetrahydrofuran at temperatures from about -78°C to ambient temperature to give stilbenes 1-1 (Scheme 2.5, step a).

Scheme 2.5

Preparation of cyclopropylamides

Cyclopropylamides 3-3, in which Q ¹ means O and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R 10, R ¹¹ , R ¹² , ^{R 13} , R ¹⁴ , Q ² and X ³ are as disclosed above, can be prepared by treatment with amines or salts of amines 3-2, in which R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , Q ² and X ³ are as disclosed above, and activated carboxylic acids 3-1, in which A is an activating group and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are such as disclosed above, a base such as triethylamine, diisopropylethylamine, 4-methylmorpholine or 4-dimethylaminopyridine, in an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide, or any combination thereof, at temperatures from about 0° C to about 120°C (Scheme 3, step a).

The carboxylic acids 3-1 in which A is an activating group may be an acid halide such as an acid chloride, an acid bromide or an acid fluoride; a carboxylic acid ester such as para-nitrophenyl ester, pentafluorophenyl ester, ethyl(hydroxyamino)cyanoacetate, methyl ester, ethyl ester, benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester; O-acylisourea; acid anhydride; or thioester. Acid chlorides can be prepared from the corresponding carboxylic acids by treatment with a dehydrating chlorinating agent such as oxalyl chloride or thionyl chloride. Activated carboxylic acid esters 3-1 can be prepared from carboxylic acids in situ using a uronium salt such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- hexafluorophosphate oxide (HATU), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU), or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholinocarbenium hexafluorophosphate (COMU ). Activated carboxylic acid esters 3-1 can also be prepared from carboxylic acids in situ using a phosphonium salt such as benzotriazol-1-yloxytripyrrolidirophosphonium hexafluorophosphate (PyBop). Activated carboxylic acid esters 3-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide, in the presence of a triazole such as hydroxybenzotriazole monohydrate (HOBt) or 1 -hydroxy-7-azabenzotriazole (HOAt). O-acylisoureas can be prepared using a dehydrating carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated carboxylic acid esters 3-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in the presence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt ). Activated carboxylic acid esters 3-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6- trioxide ( ^T3P® ) in the presence of a base such as pyridine.

Cyclopropylamides 3-3, in which R ^15b contains a sulfide and R ^15a is as disclosed above, can be oxidized to the corresponding sulfoxide or sulfone by treatment with About 1 eq. meta-chloroperoxybenzoic acid in a polar aprotic solvent such as dichloromethane (sulfoxide), or about 2 eq. meta-chloroperoxybenzoic acid (sulfone), at temperatures from about 0°C to about 40°C. Alternatively, cyclopropylamides 3-3, in which R ^15b contains a sulfide, can be oxidized to the corresponding sulfoxide or sulfone by treatment with 1 eq. sodium perborate in a protic solvent such as acetic acid (sulfoxide), or 2 eq. sodium perborate (sulfone). Preferably, the oxidation is carried out at temperatures from about 40°C to about 100°C using about 1.5 eq. sodium perborate and obtain chromatographically separated mixtures of sulfoxide and sulfonecyclopropylamides 3-3. Alternatively, sulfide-containing cyclopropylamides 3-3 can be oxidized to the corresponding sulfilimine by treatment with about 1 eq. amine such as cyanamide, about 1 eq. a base such as potassium tert-butoxide, and 1 to 2 eq. an oxidizing agent such as N-bromosuccinimide in a polar protic solvent such as methanol at temperatures from about 0°C to about 40°C. Sulfilimine can be further oxidized to the corresponding sulfoximine by treatment with approximately 1 eq. meta-chloroperoxybenzoic acid and approximately 2 eq. potassium carbonate in a solvent mixture such as 2:1:1 ethanol:dichloromethane:water, at temperatures from about 0°C to about 40°C.

Cyclopropylamides 3-3 in which R ³ is NO ₂ can be reduced to the corresponding NH ₂ by treatment with an acid source such as ammonium chloride and iron in a polar protic solvent such as methanol, water or any combination thereof, at temperatures from about 20°C to about 60°C.

Amines or salts of amines 3-2 in which Q ² is O can be directly treated with a sulfur source such as phosphorus pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (Lavesson's reagent) with or without additives such as 1,1,1,3,3,3-hexamethyldisoloxane, in an aprotic solvent selected from the group consisting of tetrahydrofuran, dichloromethane, chloroform, toluene or pyridine, at temperatures from about 40 °C to about 120°C and obtain amines or amine salts 3-2, in which Q ² is S.

Scheme 3

Cyclopropylamides 4-3, in which Q ² means O and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R 6, R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , ^{R 12} , R ¹³ , R ¹⁴ and X ³ are as disclosed above, can be prepared by treatment with amines or salts of amines 4-2, in which X ³ is as disclosed above, and activated carboxylic acids 4-1, in which A means an activating group and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ and R ¹⁴ are such as disclosed above, a base such as triethylamine, diisopropylethylamine, 4-methylmorpholine, pyridine or 4-dimethylaminopyridine, in an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide, or any combination thereof, at temperatures from about 0°C to approximately 120°C (Scheme 4, step a).

The activated carboxylic acids 4-1 may be an acid halide such as an acid chloride, an acid bromide or an acid fluoride; a carboxylic acid ester such as para-nitrophenyl ester, pentafluorophenyl ester, ethyl(hydroxyamino)cyanoacetate, methyl ester, ethyl ester, benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester; O-acylisourea; acid anhydride; or thioester. Acid chlorides can be prepared from the corresponding carboxylic acids by treatment with a dehydrating chlorinating agent such as oxalyl chloride or thionyl chloride. Activated carboxylic acid esters 4-1 can be prepared from carboxylic acids in situ using a uronium salt such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- hexafluorophosphate oxide (HATU), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU), or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholinocarbenium hexafluorophosphate (COMU ). Activated carboxylic acid esters 4-1 can also be prepared from carboxylic acids in situ using a phosphonium salt such as benzotriazol-1-yloxytripyrrolidirophosphonium hexafluorophosphate (PyBop). Activated carboxylic acid esters 4-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide, in the presence of a triazole such as hydroxybenzotriazole monohydrate (HOBt) or 1 -hydroxy-7-azabenzotriazole (HOAt). O-acylisoureas can be prepared using a dehydrating carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated carboxylic acid esters 4-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in the presence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt ). Activated carboxylic acid esters 4-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6- trioxide ( ^T3P® ) in the presence of a base such as pyridine.

Scheme 4

Cyclopropylamides 5-2 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ in which one of R ^15c is (C ₁ -C ₃ )alkylphenyl; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, can be prepared by treating amines 5-1 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ , in which R ^15c means H; Q ² means O, R ¹ , R ² , R 3, R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , ^{R 14 ,} R ^15a are as disclosed above, an aldehyde such as benzaldehyde, in the presence of a reducing agent such as sodium cyanoborohydride, in a solvent such as methanol, with or without the use of an acid such as acetic acid, at approximately room temperature (Scheme 5, stage a).

Cyclopropylamides 5-4 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ in which one or more of R ^15c means (C ₁ -C ₃ )alkyl; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, can be prepared by treating amines 5-1 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ , in which R ^15c means H; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, using a 5-3 alkylating reagent such as an alkyl halide, in the presence of a base such as triethylamine, diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridine or pyridine, in an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylformamide, or any combination thereof, at temperatures from about 0°C to about 120°C (Scheme 5, step b).

Cyclopropylamides 5-6, in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c )C(=O)X ⁴ ; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, can be prepared by treating amines 5-1 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ , in which R ^15c means H; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, an activated carboxylic acid 5-5, in which A is an activating group, and a base such as triethylamine, diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridine or pyridine, in an anhydrous aprotic solvent such as dichloromethane , tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylformamide, or any combination thereof, at temperatures from about 0°C to about 120°C (Scheme 5, step c).

The activated carboxylic acids 5-5 may be an acid halide such as an acid chloride, an acid chloride, an acid bromide or a chloroformate; a carboxylic acid ester such as para-nitrophenyl ester, pentafluorophenyl ester, ethyl(hydroxyamino)cyanoacetate, methyl ester, ethyl ester, benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester; O-acylisourea; acid anhydride; or thioester. Acid chlorides can be prepared from the corresponding carboxylic acids by treatment with a dehydrating chlorinating agent such as oxalyl chloride or thionyl chloride. Activated carboxylic acid esters 5-5 can be prepared from carboxylic acids in situ using a uronium salt such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- hexafluorophosphate oxide (HATU), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU), or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholinocarbenium hexafluorophosphate (COMU ). Activated carboxylic acid esters 5-5 can also be prepared from carboxylic acids in situ using a phosphonium salt such as benzotriazol-1-yloxytripyrrolidirophosphonium hexafluorophosphate (PyBop). Activated carboxylic acid esters 5-5 can also be prepared from carboxylic acids in situ using a coupling reagent such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide, in the presence of a triazole such as hydroxybenzotriazole monohydrate (HOBt) or 1 -hydroxy-7-azabenzotriazole (HOAt). O-acylisoureas can be prepared using a dehydrating carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated carboxylic acid esters 5-5 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in the presence of a triazolol such as 1-hydroxy-7-azabenzotriazole (HOAt ). Activated carboxylic acid esters 5-5 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6- trioxide ( ^T3P® ) in the presence of a base such as pyridine. In each of the above, 5-5 X ⁴ is as defined above.

Scheme 5

Cyclopropylamides 6-4 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ in which R ^15c is H; Q ² means O, R ¹ , R ² , R ³ , R 4, R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, can be prepared by treating 6-1 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including NO ₂ ; R ¹ , R ² , R 3 , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ^{1 ,} R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ^15a are those as disclosed above, a metal such as palladium on carbon in the presence of a reducing agent such as hydrogen gas in a solvent such as ethyl acetate, or a metal such as iron in the presence of a reducing agent such as ammonium chloride in a mixture of solvents, such as methanol and water, at a temperature of from about 25°C to about 60°C (Scheme 6, step a).

Alternatively, cyclopropylamides 6-4 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ in which R ^15c is H; Q ² means O, R ¹ , R ² , R ³ , R 4, R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, can be prepared by treating 6-2 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, in which R ^15c is H; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as described above, a solution of an anhydrous acid, such as hydrochloric acid in 1,4-dioxane and dichloromethane, at a temperature of about 25°C (Scheme 6, step c).

Alternatively, cyclopropylamides 6-4 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c ) ₂ in which R ^15c is H; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, can be prepared by treating 6-3 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(C( =O)O(C ₁ -C ₆ )alkyl) ₂ ; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as described above, a solution of an anhydrous acid, such as hydrochloric acid in 1,4-dioxane and dichloromethane, at a temperature of about 25°C (Scheme 6, step c).

Cyclopropylamides 6-6 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including NH(R ^15c ) in which R ^15c is (C ₁ -C ₃ )alkyl; Q ² means O, R ¹ , R ² , R ³ , R ^{4, R 5 ,} R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R 10, R ¹¹ , R ¹² , R ¹³ , R ^{14 and} R ^15a are as disclosed above, can be prepared by treating 6-5 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, in which R ^15c is (C ₁ -C ₃ )alkyl; R ¹ , R ² , R 3 , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ^{1 ,} R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ^15a are those as disclosed above, with a solution of an anhydrous acid, such as hydrochloric acid in 1,4-dioxane and dichloromethane, at a temperature of about 25°C (Scheme 6, step d).

Scheme 6

Cyclopropylamides 7-2 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including (C ₂ -C ₃ )alkenyl or (C ₂ -C ₃ ) a haloalkenyl group; Q ² means O; R ¹ , R ² , R 3 , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ^{1 ,} R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ^15a are those as disclosed above, can be prepared by treating aryl halides 7-1 in which X ³ is N(R ^15a )(R ^15b ) and R ^15b is substituted phenyl containing one or more substituents including Br or I; Q ² means O; R ¹ , R ² , R 3 , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ^{1 ,} R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ^15a are those as disclosed above, a stannane such as 7-2, in which R ^15c is a (C ₂ -C ₃ )alkenyl or (C ₂ -C ₃ )haloalkenyl group, in the presence of a metal catalyst such as bis(triphenylphosphine)palladium (II) dichloride in an aprotic solvent such as 1,4-dioxane at a temperature of about 90°C (Scheme 7, step a), by replacing Br or I with (C ₂ -C ₃ )alkenyl or (C ₂ -C ₃ )haloalkenyl group.

Scheme 7

Cyclopropylamides 8-3, in which Q ¹ means O and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R 6, R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , ^{R 13} , R ¹⁴ , Q ² , R ^17a , R ^17b and R ^17c are as disclosed above, can be obtained by treating amines or salts of amines 8-2, in which R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , Q ² , R ^17a , R ^17b and R ^17c are as described above, and the activated carboxylic acids 8-1 in which A is an activating group and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , ^R7 , ^R8 and ^R9 are as defined above, a base such as triethylamine, diisopropylethylamine, 4-methylmorpholine or 4-dimethylaminopyridine, in an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide or any combination thereof, at temperatures from about 0°C to about 120°C (Scheme 8, step a).

The activated carboxylic acids 8-1 may be an acid halide such as an acid chloride, an acid bromide or an acid fluoride; a carboxylic acid ester such as para-nitrophenyl ester, pentafluorophenyl ester, ethyl(hydroxyamino)cyanoacetate, methyl ester, ethyl ester, benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester; O-acylisourea; acid anhydride; or thioester. Acid chlorides can be prepared from the corresponding carboxylic acids by treatment with a dehydrating chlorinating agent such as oxalyl chloride or thionyl chloride. Activated carboxylic acid esters 8-1 can be prepared from carboxylic acids in situ using a uronium salt such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- hexafluorophosphate oxide (HATU), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU), or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholinocarbenium hexafluorophosphate (COMU ). Activated carboxylic acid esters 8-1 can also be prepared from carboxylic acids in situ using a phosphonium salt such as benzotriazol-1-yloxytripyrrolidirophosphonium hexafluorophosphate (PyBop). Activated carboxylic acid esters 8-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, or dicyclohexylcarbodiimide, in the presence of a triazole such as hydroxybenzotriazole monohydrate (HOBt) or 1-Hydroxy-7-azabenzotriazole (HOAt). O-acylisoureas can be prepared using a dehydrating carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated carboxylic acid esters 8-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in the presence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt ). Activated carboxylic acid esters 8-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6- trioxide ( ^T3P® ) in the presence of a base such as pyridine.

Scheme 8

Cyclopropylamides 9-3, in which Q ² means O and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R 6, R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , ^{R 12} , R ¹³ , R ¹⁴ , R ^17a , R ^17b and R ^17c are as disclosed above, can be prepared by treating hydrazines or hydrazine salts 9-2 in which R ^17a , R ^17b and R ^17c are as disclosed above , and activated carboxylic acids 9-1, in which A denotes ^an activating group and R ¹ , R ² , R ³ , R 4, R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ and R ¹⁴ are as disclosed above, a base such as triethylamine, diisopropylethylamine, 4-methylmorpholine or 4-dimethylaminopyridine, in an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide or any combination thereof, at temperatures from about 0°C to about 120°C (Scheme 9, step a).

The activated carboxylic acids 9-1 may be an acid halide such as an acid chloride, an acid bromide or an acid fluoride; a carboxylic acid ester such as para-nitrophenyl ester, pentafluorophenyl ester, ethyl(hydroxyamino)cyanoacetate, methyl ester, ethyl ester, benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester; O-acylisourea; acid anhydride; or thioester. Acid chlorides can be prepared from the corresponding carboxylic acids by treatment with a dehydrating chlorinating agent such as oxalyl chloride or thionyl chloride. Activated carboxylic acid esters 9-1 can be prepared from carboxylic acids in situ using a uronium salt such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- hexafluorophosphate oxide (HATU), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU), or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholinocarbenium hexafluorophosphate (COMU ). Activated carboxylic acid esters 9-1 can also be prepared from carboxylic acids in situ using a phosphonium salt such as benzotriazol-1-yloxytripyrrolidirophosphonium hexafluorophosphate (PyBop). Activated carboxylic acid esters 9-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, or dicyclohexylcarbodiimide, in the presence of a triazole such as hydroxybenzotriazole monohydrate (HOBt) or 1-Hydroxy-7-azabenzotriazole (HOAt). O-acylisoureas can be prepared using a dehydrating carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated carboxylic acid esters 9-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in the presence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt ). Activated carboxylic acid esters 9-1 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6- trioxide ( ^T3P® ) in the presence of a base such as pyridine.

Scheme 9

Cyclopropylamides 10-2, in which Q ² is O, R ^17a and R ^17b are H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₆ )alkenyl, (C ₂ -C ₆ )alkynyl or (C ₁ -C ₆ )haloalkyl and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ^{7 , R 8 ,} R ⁹ , Q ¹ , R ^{10 , R 11} , R ¹² , R ¹³ and ^{R 14} , are as disclosed above, can be obtained by processing 10-1, in which Q ² means O, R ^17a , R ^17b , R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ and R ¹⁴ are as described above, a solution of an anhydrous acid such as hydrochloric acid in 1,4-dioxane and dichloromethane, at a temperature equal to approximately 25°C (scheme 10, stage a).

Cyclopropylamides 10-4, in which Q ² means O and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ^17a and R ^17b are as defined above, and X ⁵ is substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, O(C ₁ - C ₈ )alkyl, O(C ₁ -C ₈ )haloalkyl, (C ₃ -C ₆ )cycloalkyl and O(substituted and unsubstituted)phenyl can be prepared by treating cyclopropylamides 10-2 in which Q ² is O and R ¹ , R ² , R ^{3 , R 4 ,} R 5 , R ^{6 ,} R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R 12 , R ¹³ , ^{R 14 ,} R ^17a and R ^17b are , as disclosed above, and an activated carboxylic acid or chloroformate 10-3, in which A is an activating group and X ⁵ is a base as disclosed above, such as triethylamine, diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridine or pyridine, in an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylformamide, or any combination thereof, at temperatures from about 0°C to about 120°C (Scheme 10, step b).

The activated carboxylic acids 10-3 may be an acid halide such as an acid chloride, an acid bromide or an acid fluoride; a carboxylic acid ester such as para-nitrophenyl ester, pentafluorophenyl ester, ethyl(hydroxyamino)cyanoacetate, methyl ester, ethyl ester, benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester; O-acylisourea; acid anhydride; or thioester. Acid chlorides can be prepared from the corresponding carboxylic acids by treatment with a dehydrating chlorinating agent such as oxalyl chloride or thionyl chloride. Activated carboxylic acid esters 10-3 can be prepared from carboxylic acids in situ using a uronium salt such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- hexafluorophosphate oxide (HATU), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU), or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholinocarbenium hexafluorophosphate (COMU ). Activated carboxylic acid esters 10-3 can also be prepared from carboxylic acids in situ using a phosphonium salt such as benzotriazol-1-yloxytripyrrolidirophosphonium hexafluorophosphate (PyBop). Activated carboxylic acid esters 10-3 can also be prepared from carboxylic acids in situ using a coupling reagent such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide, in the presence of a triazole such as hydroxybenzotriazole monohydrate (HOBt) or 1 -hydroxy-7-azabenzotriazole (HOAt). O-acylisoureas can be prepared using a dehydrating carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated carboxylic acid esters 10-3 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in the presence of a triazolol such as 1-hydroxy-7-azabenzotriazole (HOAt ). Activated carboxylic acid esters 10-3 can also be prepared from carboxylic acids in situ using a coupling reagent such as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6- trioxide ( ^T3P® ) in the presence of a base such as pyridine.

Cyclopropylamides 10-6, in which Q ² means O and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R 6, R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , ^{R 12} , R ¹³ , R ¹⁴ , R ^17a and R ^17b are as disclosed above, and X ⁵ is N(R ^17a )(C ₁ -C ₈ )alkyl, N(R ^17a )(C ₁ -C ₈ )haloalkyl , N(R ^17a )(C ₃ -C ₈ )cycloalkyl and N(R ^17a )(substituted and unsubstituted phenyl), can be prepared by treating cyclopropylamides 10-2 in which Q ² is O and R ¹ , R ² , R ³ , ^{R4 , R5} , ^R6 , R7, ^R8 , ^R9 , ^Q1 , ^R10 , ^R11 , ^R12 , ^R13 , ^R14 , ^R17a and ^R17b are as disclosed above, using isocyanate or isothiocyanate 10-5, in which Q ⁴ is O or S, respectively, and X ⁵ is as disclosed above, in an anhydrous solvent such as tetrahydrofuran or ethanol, at temperatures from about 0°C to about 80°C (Scheme 10, stage c).

Cyclopropylamides 10-7 in which Q ² is O, R ^17b is H, R ^17c is substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl and (C ₃ -C ₆ )cycloalkyl and R ¹ , R ² , ^R3 , R4, ^R5 , ^R6 , ^R7 , ^R8 , ^R9 , ^Q1 , ^R10 , ^R11 , ^R12 , ^R13 , ^R14 and ^{R17a are} as disclosed above, can be prepared by treating cyclopropylamides 10-2 in which Q ² is O, R ^17b is H and R ^{1 , R 2 ,} R ³ , R 4 , R ⁵ , R ⁶ , R ⁷ , R ⁸ , ^{R 9 ,} Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ are as above, an aldehyde or ketone, wherein R ^17c is as above, in the presence of an acid such as acetic acid and a reducing reagent such as as sodium cyanoborohydride, in a polar aprotic solvent such as ethanol, at temperatures from about 0°C to about 80°C (Scheme 10, step b).

Scheme 10

Cyclopropylamides 11-3, in which Q ² means O and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ^18a , R ^18b and R ^18c are as disclosed above, can be prepared by treating hydrazide 11-1 in which Q ² is O and R ¹ , R ² , R ³ , R ⁴ . R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Q ¹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ^18a are as defined above, aldehydes or ketones 11-2, in wherein R ^18b and R ^18c are as disclosed above, with or without the use of an acid such as acetic acid, in a polar aprotic solvent such as ethanol at temperatures from about 0°C to about 80°C (Scheme 18, stage a).

Scheme 11

In some embodiments, 1-3 can be prepared from the α,β-unsaturated aldehyde 12-1, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁹ are as defined above. One skilled in the art will appreciate that compound 12-1 can be synthesized via aldol condensation (see Yoshikawa, M.; Kamei, T. PCT Int. Appl. 2010123006, 2010) of suitably substituted commercially available aldehyde and acetaldehyde. Treatment with 12-1 (C ₁ -C ₆ )alkyl orthoformate in the presence of an acid with a pH value of 0-5, such as hydrobromic acid, N-bromosuccinimide, hydrochloric acid, N-chlorosuccinimide and pyridinium p-toluenesulfonate (PPTS), in solvent (C ₁ -C ₆ )alkanol, at a temperature from 0°C to ambient temperature and at normal pressure gives acetal 12-2, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁹ are as described above, and R ^a is (C ₁ -C ₆ )alkyl or R ^a and R ^a together can form a cyclic acetal (Scheme 12, step a). Acetal 12-2 can be converted to cyclopropylacetal 12-3, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ^a are as described above, by treatment with a carbene source such as a methane trihalide, for example bromoform or chloroform, in the presence of an inorganic base such as sodium or potassium hydroxide or sodium or potassium carbonate, and a phase transfer catalyst such as benzyltriethylammonium chloride, (-)-N-dodecyl- N-methylephedrinium bromide, tetramethylammonium bromide, tetrapropylammonium bromide, tetrabutylammonium tetrafluoroborate, tetramethylammonium chloride or tetrabutylammonium hexafluorophosphate, at a temperature of approximately ambient temperature to a temperature below the boiling point of methane trihalide (Scheme 12, step b). Caution: Step B is an exothermic reaction and heat must be carefully controlled during this reaction. Cyclopropylacetal 12-3 can be converted to aldehyde 12-4 in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are as described above in a polar solvent , selected from the group consisting of acetone, acetonitrile, methanol, ethanol, nitromethane, N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, tetrahydrofuran and 1,4-dioxane, in the presence of an aqueous inorganic acid selected from the group consisting of nitric acid, hydrochloric acid , hydrobromic acid and sulfuric acid (Scheme 12, step c), at ambient temperature. Cyclopropylcarboxylic acid 1-3, in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are as described above, can be prepared by oxidizing the aldehyde 12-4 with oxidizing agents such as sodium permanganate or potassium permanganate, or under Pinnick oxidation conditions in a polar aprotic solvent selected from the group consisting of acetone, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, tetrahydrofuran and 1,4-dioxane, at a temperature from approximately 0°C to approximately ambient temperature (diagram 12, step d). Standard precautions should be taken as this reaction may generate heat.

Scheme 12

Those skilled in the art will appreciate that in some embodiments, the cyclopropylcarboxylic acid 1-3, wherein ^R1 , ^R2 , ^R3 , ^R4 , ^R5 , ^R6 , ^R7 , ^R8 , and ^R9 are as disclosed above, can be separated into its (R,R) and (S,S) enantiomers using a method such as that given in the publication Kovalenko VN, Kulinkovich OG Tetrahedron: Asymmetry 2011, 22, 26 (scheme 13, stage a).

Scheme 13

In another embodiment, the cyclopropylcarboxylic acid R1-3, in which ^R1 , ^R2 , ^R3 , ^R4 , ^R5 , ^R6 , ^R7 , ^R8 and ^R9 are as described above, can be divided into its ( R,R) and (S,S) enantiomers according to the procedure presented in Scheme R1.

Scheme R1

where: X ^R is selected from the group consisting of C ₁ -C ₄ alkyl or benzyl.

In Scheme R1, the (±)-trans racemate of formula R1-1 (i.e., a mixture of (R,R) and (S,S) enantiomers of trans-2,2-dichloro-3-(substituted phenyl)cyclopropanecarboxylic acid) is combined with a resolving reagent that is an enantiomeric amine of formula R2-1 or formula R2-2, in a suitable solvent, to obtain diastereomeric amine salts of formula R3-1A or formula R3-1B,

or formula R3-2A or formula R3-2B,

which selectively crystallize or precipitate from the resulting mixture. The diastereoisomeric amine salt of Formula R3-1A or Formula R3-1B or Formula R3-2A or Formula R3-2B can then be isolated from the mixture and treated with an acid to give (1R,3R)- or (1S,3S)-2,2 -dihalo-3-(substituted phenyl)cyclopropanecarboxylic acid of formula R1-2A or formula R1-2B, respectively.

Examples

These Examples are provided for illustration purposes and should not be construed as limiting the present invention only to the embodiments disclosed in these Examples.

Starting materials, reagents, and solvents, which were obtained from commercial sources, were used without further purification. Anhydrous solvents were purchased as Sure/Seal ^™ from Aldrich and used as received. Melting points were measured using a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt automatic melting point system from Research Systems and are uncorrected. Examples using "room temperature" were carried out in controlled atmosphere laboratories at temperatures ranging from about 20°C to about 24°C. Molecules are represented by their known names, obtained using programs included in ISIS Draw, ChemDraw or ACD Name Pro. If such programs could not generate the name of the molecule, then the name of the molecule was obtained in accordance with the usual rules of nomenclature. All NMR spectral data are reported in ppm (δ) and spectra were recorded at 300, 400, 500, or 600 MHz; ¹³ C NMR spectral data are in ppm (δ) and spectra were recorded at 75, 100, or 150 MHz and ¹⁹ F NMR spectral data are in ppm (δ) and spectra were recorded at 376 MHz unless otherwise noted other.

Example 1: Preparation of trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(2,2,2 -trifluoroacetamido)phenyl)benzamide (F1061)

To a solution of trans-N-(4-amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP1) (0.100 g, 0.179 mmol) and triethylamine (0.037 ml, 0.269 mmol) in dichloromethane (2.0 ml), trifluoroacetic anhydride (0.030 ml, 0.215 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was directly loaded into a ^Celite® cartridge. Purification by flash column chromatography using 0-40% ethyl acetate/hexanes as eluent gave the title compound as a white solid (0.080 g, 68%).

The following compounds were prepared using a procedure similar to that described in example 1:

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2-difluoroacetamido)-2-methylphenyl)benzamide ( F1062)

Isolated as a white solid (0.109 g, 95%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)benzamide (F1064)

Isolated as a light yellow solid (0.103 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 4-difluorophenyl)benzamide (F1065)

Isolated as a white solid (0.088 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoro-4-(2,2,2-trifluoroacetamido )phenyl)benzamide (F1120)

Isolated as an almost white solid (0.096 g, 82%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-(2,2,2-trifluoroacetamido)phenyl )benzamide (F1121)

Isolated as a light yellow solid (0.111 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2-difluoroacetamido)-3,5-difluorophenyl) benzamide (F1122)

Isolated as an almost white solid (0.066 g, 58%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-(2,2-difluoroacetamido)-4-fluorophenyl)benzamide ( F1123)

Isolated as an almost white solid (0.0885 g, 74%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-4-(2,2 ,2-trifluoroacetamido)phenyl)benzamide (F1261)

Isolated as a light yellow foam (0.065 g, 69%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1330)

Isolated as a white powdery substance (0.068 g, 98%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 4-difluorophenyl)-3-fluorobenzamide (F1333)

Isolated as an almost white powdery substance (0.069 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1334)

Isolated as an almost white powdery substance (0.062 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,4-difluorophenyl)-3-fluorobenzamide (F1335)

Isolated as a light yellow powdery substance (0.057 g, 99%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoro-4-(2,2,2-trichloroacetamido )phenyl)benzamide (F1146)

Isolated as an almost white solid (0.046 g, 37%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,4-difluorophenyl)-3-fluorobenzamide (F1256)

Isolated as a light yellowish-brown foam (0.184 g, 56%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 4-difluorophenyl)-3-fluorobenzamide (F1287)

Isolated as a white solid (0.064 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1288)

Isolated as a white solid (0.068 g, 93%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)-cyclopropane-1-carboxamido)-N-(3-(2,2 -difluoroacetamido)-2,4-difluorophenyl)-3-fluorobenzamide (F1289)

Isolated as a white solid (0.065 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1290)

Isolated as a white solid (0.068 g, 93%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1291)

Isolated as a white solid (0.062 g, 95%).

Example 2: Preparation of N-(3-acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1- carboxamido)benzamide (F1083)

To a solution of N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido) benzamide (DP2) (0.06 g, 0.104 mmol) in pyridine (0.30 ml, 3.71 mmol), acetic anhydride (9.77 μl, 0.104 mmol) was added with stirring at room temperature. The reaction mixture was stirred at room temperature for 18 hours, the reaction was quenched with water (3 ml) and extracted with ethyl acetate (10 ml). The organic layer was washed with hydrochloric acid (1N) and brine and then passed through a phase separator. The organic layer was concentrated under reduced pressure to obtain a residue. Purification by column chromatography using 0-30% ethyl acetate/hexanes as eluent gave the title compound as a white solid (0.043 g, 67%).

The following compounds were prepared using a procedure similar to that described in example 2:

2-Chloro-N-(3-(2-chloro-2,2-difluoroacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4- dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1248)

Isolated as a white solid (0.089 g, 74%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,3,3,3-pentafluoropropanamido)phenyl)benzamide (F1251)

Isolated as a white solid (0.072 g, 57%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-dichloroacetamido)-2, 4-difluorophenyl)benzamide (F1252)

Isolated as a white solid (0.068 g, 57%).

N-(4-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1262)

Isolated as a white solid (0.022 g, 26%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2-dichloroacetamido)-2, 6-difluorophenyl)benzamide (F1272)

Isolated as a white solid (0.028 g, 29%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,6-difluorophenyl)benzamide (F1234)

Isolated as a white foamed solid (0.083 g, 66%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,6-difluorophenyl)benzamide (F1238)

Isolated as an off-white foamed solid (0.090 g, 72%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 6-difluorophenyl)benzamide (F1240)

Isolated as a white foamed solid (0.100 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 6-difluorophenyl)benzamide (F1241)

Isolated as a white foamed solid (0.086 g, 68%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2, 4-difluorophenyl)benzamide (F1242)

Isolated as a glassy solid (0.074 g, 59%).

2-Chloro-N-(5-(2-chloro-2,2-difluoroacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4- dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1243)

Isolated as a white foamed solid (0.065 g, 49%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-dichloroacetamido)-2, 4-difluorophenyl)benzamide (F1244)

Isolated as an off-white foamed solid (0.035 g, 28%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2 ,2-trifluoroacetamido)phenyl)benzamide (F1245)

Isolated as a white foamed solid (0.080 g, 65%).

N-(5-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1246)

Isolated as an off-white foamed solid (0.080 g, 71%).

trans-N-(4-Acetamido-3,5-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1124)

Isolated as an almost white solid (0.042 g, 39%).

trans-N-(2-Acetamido-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1125)

Isolated as an almost white solid (0.039 g, 33%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-(2,2,2-trichloroacetamido)phenyl )benzamide (F1126)

Isolated as a light yellow solid (0.078 g, 59%).

Example 3: Preparation of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4 -difluoro-3-(2,2,2-trifluoroacetamido)phenyl)benzamide (F1169)

Trifluoroacetic anhydride (0.035 g, 0.251 mmol) was added dropwise to the solution of N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3 with stirring -(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (DP9) (0.100 g, 168 mmol) and triethylamine (0.051 g, 0.503 mmol) in anhydrous dichloromethane (3 ml). The solution was stirred for 12 hours at 23°C and concentrated. Purification by flash silica gel chromatography provided the title compound as a white foam (0.084 g, 69%).

The following compounds were prepared using a procedure similar to that described in example 3:

2-Chloro-N-(3-(2-chloro-2,2-difluoroacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1170)

Isolated as a white solid (0.089 g, 71%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- dichloroacetamido)-2,4-difluorophenyl)benzamide (F1174)

Isolated as a white foamy substance (0.058 g, 46%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,4-difluorophenyl)benzamide (F1175)

Isolated as a white solid (0.283 g, 70%).

N-(3-Benzamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1179)

Isolated as a white foamy substance (0.015 g, 12%).

N-(3-(2-Bromo-2,2-difluoroacetamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1276)

Isolated as a white solid (0.078 g, 59%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 4-difluorophenyl)benzamide (F1331)

Isolated as a white foamy substance (0.037 g, 62%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)benzamide (F1332)

Isolated as a white solid (0.031 g, 51%).

Example 4: Preparation of tert-butyl-(4-((3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido) benzamido)-2,6-difluorophenyl)amino)-4-oxobutyl)carbamate (F1199)

To a solution of N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido) benzamide (DP2) (0.100 g, 0.173 mmol) in ethyl acetate (2 ml) stirred at room temperature, 4-((tert-butoxycarbonyl)amino)butanoic acid (0.035 g, 0.173 mmol) and pyridine (0.028 ml, 0.345 mmol) were added . 2,4,6-Tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide ( ^T3P® ; 165 mg, 0.259 mmol) was added as a 50% solution in ethyl acetate. The reaction mixture was heated at 50°C for 18 hours then cooled to room temperature and concentrated under a stream of nitrogen. Purification by column chromatography using 0-80% ethyl acetate/hexanes as eluent gave the title compound as a white solid (0.111 g, 84%).

The following compounds were prepared using a procedure similar to that described in example 4:

trans-tert-Butyl-(4-((4-(2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)-cyclopropane-1-carboxamido)benzamido)-3-methylphenyl) amino)-4-oxobutyl)carbamate (F1200)

Isolated as a white solid (0.097 g, 72%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoropropanamido)-2, 4-difluorophenyl)benzamide (F1249)

Isolated as a white solid (0.097 g, 83%).

N-(3-Benzamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1253)

Isolated as a light brown solid (0.076 g, 64%).

Example 5: Preparation of trans-N-(3-acetamido-2-chloro-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1160)

2,4,6-Tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide ( ^T3P® , 50% solution in ethyl acetate; 0.281 g, 0.441 mmol) was added dropwise with stirring to a solution of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (0.100 g, 220 mmol), N-(3- amino-2-chloro-6-fluorophenyl)acetamide (C194) (0.048 g, 0.220 mmol) and pyridine (0.053 g, 0.661 mmol) in anhydrous ethyl acetate (3 ml). The solution was stirred for 12 hours at 23°C and concentrated. Purification by flash silica gel chromatography provided the title compound as a white foam (0.105 g, 71%).

The following compounds were prepared using a procedure similar to that described in example 5:

N-(3-Acetamido-2-chloro-4-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1161)

Isolated as a white foamy substance (0.052 g, 71%).

Example 6: Preparation of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4 -difluoro-3-(4-fluorobenzamido)phenyl)benzamide (F1204)

2,4,6-Tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide ( ^T3P® , 50% solution in ethyl acetate; 0.213 g, 0.335 mmol) was added dropwise with stirring to a solution of N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (DP9) (0.100 g, 0.168 mmol), 4-fluorobenzoic acid (0.028 g, 0.201 mmol) and pyridine (0.040 g, 0.503 mmol) in anhydrous ethyl acetate (3 ml). The solution was stirred for 12 hours at 50°C and concentrated. Purification by flash silica gel chromatography provided the title compound as a white foam (0.029 g, 23%).

The following compounds were prepared using a procedure similar to that described in example 6:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4-methoxybenzamido)phenyl)benzamide (F1205)

Isolated as a white solid (0.020 g, 16%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)nicotinamide (F1206)

Isolated as a white solid (0.041 g, 33%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1231)

Isolated as a white solid (0.029 g, 26%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-6-fluoronicotinamide (F1258)

Isolated as a white solid (0.019 g, 15%).

2-Chloro-N-(3-(1-cyanocyclopropane-1-carboxamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3- (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1263)

Isolated as a white foamy substance (0.078 g, 64%).

2-Chloro-N-(3-(cyclopropanecarboxamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1264)

Isolated as a white foam (0.100 g, 85%).

2-Chloro-N-(3-(2,2-dichloro-1-methylcyclopropane-1-carboxamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-( 4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1273)

Isolated as a white solid (0.078 g, 30%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -pivalamidophenyl)benzamide (F1274)

Isolated as a white solid (0.014 g, 12%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluorocyclopropane-1-carboxamido)-2,4-difluorophenyl)benzamide (F1275)

Isolated as a white solid (0.135 g, 73%).

2-Chloro-N-(3-(cyclohex-3-ene-1-carboxamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1297)

Isolated as a white solid (0.119 g, 96%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-oxo-2-phenylacetamido)phenyl)benzamide (F1298)

Isolated as a clear, colorless oil (0.087 g, 68%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(methylsulfonyl)acetamido)phenyl)benzamide (F1299)

Isolated as a white foamy substance (0.111 g, 88%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)furan-2-carboxamide (F1300)

Isolated as a white solid (0.085 g, 70%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1301)

Isolated as a white foamy substance (0.103 g, 81%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-5-methylthiophene-2-carboxamide (F1302)

Isolated as a white solid (0.035 g, 28%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3-oxocyclobutane-1-carboxamido)phenyl)benzamide (F1303)

Isolated as a white solid (0.093 g, 76%).

Example 7: Preparation of trans-N-(4-Acetamido-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1059)

To a solution of trans-N-(4-amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP1) (0.100 g, 0.179 mmol) and triethylamine (0.037 ml, 0.269 mmol) in dichloromethane (2.0 ml) was added acetyl chloride (0.015 g, 0.197 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with hydrochloric acid (1N; 2×) and brine. ^Celite® was added to the organic layer and the mixture was concentrated under reduced pressure. Purification by flash column chromatography using 0-40% ethyl acetate/hexanes as eluent gave the title compound as an off-white solid (0.079 g, 73%).

The following compounds were prepared using a procedure similar to that described in example 7:

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(2,2,2-trichloroacetamido)phenyl )benzamide (F1060)

Isolated as a white solid (0.060 g, 47%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trichloroacetamido)phenyl)benzamide (F1063)

Isolated as a white solid (0.039 g, 34%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-methoxyacetamido )phenyl)benzamide (F1254)

Isolated as a white solid (0.072 g, 64%).

Example 8: Preparation of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4 -difluoro-3-(N-(methylsulfonyl)methylsulfonamido)phenyl)benzamide (F1277)

Methanesulfonyl chloride (0.029 g, 0.251 mmol) was added dropwise to the solution of N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3- (4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (DP9) (0.100 g, 168 mmol) and triethylamine (0.051 g, 0.503 mmol) in anhydrous dichloromethane (3 ml). The solution was stirred for 12 hours at 23°C and concentrated. Purification by flash silica gel chromatography provided the title compound as a white foam (0.044 g, 33%).

Example 9: Preparation of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4 -difluoro-3-(phenylsulfonamido)phenyl)benzamide (F1295)

Benzenesulfonyl chloride (0.044 g, 0.251 mmol) was added to the solution of N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4) with stirring -fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (DP9) (0.100 g, 168 mmol) in acetonitrile (3 ml). The solution was stirred for 36 hours at 70°C and concentrated. Purification by flash silica gel chromatography provided the title compound as a pink solid (0.112 g, 86%).

Example 10: Preparation of trans-2-chloro-N-(4-((4-chlorobenzyl)amino)-2-methylphenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamido)benzamide (F1010)

4-Chlorobenzaldehyde (0.0252 g, 0.179 mmol) was added to the suspension of trans-N-(4-amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5) with stirring -dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP4) (0.100 g, 0.179 mmol) and sodium acetate (29.4 mg, 0.359 mmol) in methanol (20 ml), water (15 ml) and acetic acid (3 ml ). The resulting heterogeneous mixture was stirred at 25°C for 3 hours. Sodium cyanoborohydride (0.0158 g, 0.251 mmol) was added in one portion. The resulting colorless solution was stirred at ambient temperature for a further 4 hours. The reaction was quenched with water (50 ml) and extracted with diethyl ether (3×50 ml). The organic extracts were washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated in vacuo on a rotary evaporator. Purification by flash silica gel chromatography provided the title compound as a yellow foam (0.087 g, 68%).

The following compounds were prepared using a procedure similar to that described in example 10:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((4-methoxybenzyl)amino)-2-methylphenyl)benzamide (F1035)

Isolated as a yellow foam (0.095 g, 74%).

trans-2-Chloro-N-(4-((4-cyanobenzyl)amino)-2-methylphenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1040)

Isolated as a yellow solid (0.097 g, 76%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-((4-methylbenzyl)amino)phenyl) benzamide (F1041)

Isolated as a yellow solid (0.081 g, 65%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-((4 -methoxybenzyl)amino)phenyl)benzamide (F1096)

Isolated as a white foamy substance (0.059 g, 47%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-((4-(trifluoromethoxy)benzyl)amino )phenyl)benzamide (F1117)

Isolated as a yellow solid (0.113 g, 82%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-((4-nitrobenzyl)amino)phenyl) benzamide (F1166)

Isolated as a yellow oil (0.076 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-((4-(trifluoromethyl)benzyl)amino )phenyl)benzamide (F1165)

Isolated as a pale yellow solid (0.055 g, 54%).

trans-N-(4-(Benzylamino)-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1176)

Isolated as a pale yellow foam (0.039 g, 42%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(phenethylamino)phenyl)benzamide (F1177)

Isolated as a pale yellow foam (0.025 g, 27%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-((2-phenylpropyl)amino)phenyl) benzamide (F1178)

Isolated as a pale yellow foam (0.055 g, 58%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -((4-nitrobenzyl)amino)phenyl)benzamide (F1296)

Isolated as a yellow oil (0.008 g, 4%).

Example 11: Preparation of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-vinylphenyl)benzamide (F1311)

To a solution of trans-N-(3-bromo-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1304) (0 .4 g, 0.64 mmol) in 1,4-dioxane (7 ml), tributylvinyltin degassed with argon (0.26 ml, 0.89 mmol) and bis(triphenylphosphine) palladium(II) dichloride (0.044 g, 0.064 mmol) were added ), and the reaction mixture was irradiated in a microwave oven at 90°C for 1 hour. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (2×10 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography using 15-20% ethyl acetate/petroleum ether as eluent gave the title compound as an off-white solid (0.11 g, 40%).

The following compounds were prepared using a procedure similar to that described in example 11:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-vinylphenyl)benzamide (F1312)

Isolated as an almost white solid (0.12 g, 44%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-vinylphenyl)benzamide (F1313)

Isolated as an almost white solid (0.18 g, 49%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-vinylphenyl)benzamide (F1314)

Isolated as an almost white solid (0.07 g, 26%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-vinylphenyl)benzamide (F1315)

Isolated as an almost white solid (0.13 g, 48%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-6-vinylphenyl)benzamide (F1316)

Isolated as an almost white solid (0.12 g, 44%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,4-difluoro-5-vinylphenyl)benzamide (F1317)

Isolated as an almost white solid (0.10 g, 37%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-(1-fluorovinyl)phenyl)benzamide (F1318 )

Isolated as an almost white solid (0.15 g, 55%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-(1-fluorovinyl)phenyl)benzamide (F1319 )

Isolated as an almost white solid (0.17 g, 70%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-(1-fluorovinyl)phenyl)benzamide (F1320 )

Isolated as an almost white solid (0.15 g, 62%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(1-fluorovinyl)phenyl)benzamide (F1321)

Isolated as an almost white solid (0.12 g, 63%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-6-(1-fluorovinyl)phenyl)benzamide (F1322)

Isolated as an almost white solid (0.09 g, 50%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,4-difluoro-5-(1-fluorovinyl)phenyl)benzamide (F1323)

Isolated as an almost white solid (0.11 g, 58%).

Example 12: Preparation of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((2-hydroxyethyl)amino)-2 -methylphenyl)benzamide (F1130)

4 M Hydrogen chloride in 1,4-dioxane (0.370 ml, 1.479 mmol) was added dropwise to the solution of trans-2-((tert-butoxycarbonyl)(4-(2-chloro-5-(2,2-dichloro)) with stirring -3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)amino)ethyl acetate (F1129) (0.110 g, 0.148 mmol) in dichloromethane (5 ml). The resulting solid suspension was stirred for 12 hours at 23°C and then neutralized with saturated aqueous sodium bicarbonate (5 ml). The aqueous mixture was extracted with ethyl acetate (3×5 ml) and the organic extract was washed with saturated aqueous sodium chloride (5 ml) and concentrated in vacuo on a rotary evaporator. Purification by flash silica gel chromatography provided the title compound as a pale yellow foam (0.050 g, 53%).

The following compounds were prepared using a procedure similar to that described in example 12:

2-((4-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-3 -methylphenyl)amino)ethyl acetate (F1144)

Isolated as a clear, colorless oil (0.043 g, 31%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-((2-hydroxyethyl )amino)-2-methylphenyl)benzamide (F1145)

Isolated as a pale yellow foam (0.040 g, 31%).

trans-N-(4-((3-Amino-3-oxopropyl)amino)-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamido)benzamide (F1158)

Isolated as a gray solid (0.013 g, 16%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((2-methoxyethyl)amino)-2-methylphenyl)benzamide (F1162)

Isolated as a pale yellow foam (0.062 g, 86%).

Example 13: Preparation of N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane 1-carboxamido)-3-fluorobenzamide (F1255)

To a solution of tert-butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl) cyclopropane-carbonyl]amino]-3-fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1239) (0.166 g, 0.21 mmol) in dioxane (1 ml) was added a 4 M solution of hydrogen chloride in dioxane (0. 53 ml, 2.12 mmol) and the colorless solution was stirred at room temperature for 16 hours. The light yellow solution was concentrated and the residue was partitioned between ethyl acetate (5 ml) and saturated aqueous sodium bicarbonate (5 ml). The phases were separated and the aqueous phase was extracted with additional ethyl acetate (2×2.5 ml). The combined organic extracts were washed with brine (3 ml), dried over sodium sulfate, filtered and concentrated to leave an amber residue. The residue was dissolved in a minimal amount of ethyl acetate and adsorbed onto ^Celite® . Purification by automated flash chromatography using a gradient of 0-40% ethyl acetate in hexanes as eluent gave the title compound as a white solid (0.111 g, 88%).

The following compounds were prepared using a procedure similar to that described in example 13:

N-(3-Amino-2,4-difluorophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-3-methylbenzamide (F1151 ):

Isolated as a white solid (0.056 g, 74%).

N-(3-(4-Aminobutanamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1- carboxamido)benzamide (F1201)

Isolated as a white foamy substance (0.077 g, 81%).

trans-N-(4-(4-Aminobutanamido)-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1202)

Isolated as a white solid (0.035 g, 42%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1227)

Isolated as a brown foamed solid (0.225 g, 95%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1228)

Isolated as an almost white foamed substance (0.216 g, 97%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido) benzamide (F1247)

Isolated as a white foamed solid (0.195 g, 92%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1250)

Isolated as a white foamed solid (0.225 g, 97%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N -methylbenzamide (F1056)

Isolated as a beige foam (0.1 g, 85%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(3-(3,5-dichlorophenyl)-2,2-difluorocyclopropane-1-carboxamido)benzamide (F1080)

Isolated as an almost white powdery substance (0.94 g, 94%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1324)

Isolated as a light yellow solid (0.195 g, 75%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-fluorobenzamide (F1325)

Isolated as an almost white solid (0.130 g, 46%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1336)

Isolated as a yellowish-brown powdery substance (0.160 g, 81%).

trans-N-(3-Amino-2,4-difluorophenyl)-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1110)

Isolated as a light yellowish-brown solid (0.034 g, 76%).

trans-N-(3-Amino-2,4-difluorophenyl)-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluorobenzamide (F1111 )

Isolated as a tan solid (0.044 g, 80%).

trans-N-(4-Amino-3,5-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP3)

Isolated as a light brown foam (1.59 g, 93%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-3-methylbenzamide (F1151)

Isolated as a white solid (0.056 g, 74%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzamide (F1156)

Isolated as a tan solid (0.100 g, 86%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-methylbenzamide (F1222)

Isolated as a tan solid (0.054 g, 46%).

trans-N-(3-Amino-2,4-difluorophenyl)-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methylbenzamide (F1223)

Isolated as a yellowish-brown foam (0.052 g, 46%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-( trifluoromethyl)benzamide (F1225)

Isolated as a white solid (0.052 g, 83%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methoxybenzamide (F1226)

Isolated as a white solid (0.053 g, 81%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1284)

Isolated as a white solid (0.193 g, 91%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-fluorobenzamide (F1285)

Isolated as a white solid (0.208 g, 93%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methylbenzamide (F1286)

Isolated as a white solid (0.062 g, 89%).

trans-N-(4-Amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP4)

Isolated as a white solid (0.053 g, 83%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( DP2)

Isolated as a white solid (0.115 g, 89%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( DP5)

Isolated as a white solid (0.107 g, 96%).

Example 14: Preparation of trans-N-(2-amino-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP6)

To a suspension of trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide (DP13) (0.880 g, 1.49 mmol) to a 4:1 mixture of methanol (14 ml) and water (4.7 ml), powdered iron (0.415 g, 7.44 mmol) and ammonium chloride (0.239 g, 4.46 mmol) were added and the mixture was heated at 55°C and stirred for 21 hours. The reaction mixture was filtered through a pad of Celite ^® and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (100 ml) and water (60 ml). The phases were separated and the organic phase was dried over magnesium sulfate, filtered and concentrated to give a dark residue. The residue was dissolved in a minimal amount of ethyl acetate and adsorbed onto ^Celite® . Purification by automated flash chromatography using a gradient of 0-40% ethyl acetate in hexanes as eluent gave the title compound as a yellow foam (0.66 g, 75%).

The following compounds were prepared using a procedure similar to that described in example 14:

N-(2-Amino-3-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1133)

Isolated as a light brown powdery substance (0.030 g, 80%).

N-(2-Amino-4,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido) benzamide (F1134)

Isolated as a light brown film (0.016 g, 34%).

N-(5-Amino-2-fluoro-4-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1- carboxamido)benzamide (F1135)

Isolated as a light blue solid (0.050 g, 59%).

Example 15: Preparation of trans-N-(4-amino-2,3-dimethylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1229)

Powdered iron (325 mesh; 0.065 g, 1.163 mmol) was added to a solution of ethanol (10 mL) and concentrated HCl (0.01 mL, 0.116 mmol) with stirring. The suspension was heated at 65°C for 1 hour and then cooled to 55°C. A solution of ammonium chloride (0.045 g, 0.838 mmol) in water (3 ml) was added, then trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)- N-(2,3-dimethyl-4-nitrophenyl)benzamide (F1180) (0.140 g, 0.233 mmol). The reaction mixture was heated at 60°C for 2 hours, cooled and filtered through a pad ^{of Celite®} . The filtrate was extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure in a rotary evaporator. Purification of the crude product by flash silica gel chromatography gave the title compound as a tan solid (0.032 g, 23%)

The following compounds were prepared using a procedure similar to that described in example 15:

trans-N-(4-Amino-2,5-dimethylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1257)

Isolated as a golden foam (0.047 g, 36%).

Example 16: Preparation of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-hydroxyphenyl)benzamide ( F1203)

trans-3-(2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenylacetate (F1193) (0.067 g, 0.108 mmol ) was dissolved in methanol (2.2 ml) and treated with saturated sodium hydrogen carbonate solution (0.5 ml) with stirring at room temperature. Analysis of the reaction mixture after 1 hour using thin layer chromatography (2:1 hexanes-ethyl acetate) showed that the reaction was complete. The reaction mixture was partitioned between ethyl acetate and 1N. aqueous hydrochloric acid solution, the layers were separated and the organic layer was dried over sodium sulfate. Purification by preparative thin layer chromatography (20 x 20 x 0.2 cm plate, 3:1 hexanes-ethyl acetate) gave the title compound as a tan foam (0.06 g, 96%).

Example 17: Preparation of tert-butyl-N-tert-butoxycarbonyl-N-[3-[2-chloro-[5-[[(1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl) cyclopropanecarbonyl]amino]-3-fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1292)

(1R,3R)-2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid (C91) (0.131 g, 0.436 mmol) suspended in toluene (4 ml) was treated with oxalyl chloride (0.382 ml. 4.36 mmol) and one drop of N,N-dimethylformamide with stirring at room temperature. After the mixture became homogeneous and gas evolution stopped, the solution was concentrated to obtain a clear oil. tert-Butyl-N-tert-butoxycarbonyl-N-(3-(5-amino-2-chloro-3-fluorobenzamido)-2,6-difluorophenyl)carbamate (C108) (0.225 g, 0.436 mmol) and sodium bicarbonate ( 0.110 g, 1.31 mmol) were added to the flask as solids, then ethyl acetate (4 ml) and the cloudy mixture was stirred at room temperature for 18 hours. Analysis of an aliquot by liquid chromatography/mass spectroscopy indicated complete conversion to the desired compound. The reaction mixture was partitioned between ethyl acetate and an aqueous mixture of sodium hydrogen carbonate and sodium chloride. The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated to give an oil. Trituration with hexanes and drying provided the title compound as an off-white solid (0.347 g, 100%).

The following compounds were prepared using a procedure similar to that described in example 17:

tert-Butyl-N-tert-butoxycarbonyl-N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1- carboxamido)-3-fluorobenzamido)-2,6-difluorophenyl)carbamate (F1294)

Isolated as an almost white solid (0.367 g, 100%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzamido)-2, 6-difluorophenyl)carbamate (F1326)

Isolated as a yellow glassy substance (0.257 g, 100%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzamido)- 2,4-difluorophenyl)carbamate (F1327)

Isolated as a yellow glassy substance (0.240 g, 99%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzamido)-2, 4-difluorophenyl)carbamate (F1328)

Isolated as a yellow glassy substance (0.245 g, 100%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-3- fluorobenzamido)-2,4-difluorophenyl)carbamate (F1329)

Isolated as a light yellow glassy substance (0.242 g, 100%).

Example 18: Preparation of trans-5-(3-(3-bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide (F1005)

Dichloromethane (2 ml) was added at room temperature to a 20 ml glass vial containing 5-amino-2-chloro-N-(4-fluorophenyl)benzamide (C98) (0.105 g, 0.396 mmol), 4-dimethylaminopyridine (0.053 g , 0.436 mmol), trans-3-(3-bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C29) (0.150 g, 0.396 mmol) and 1-ethyl-3-(3 -dimethylaminopropyl)carbodiimide hydrochloride (0.114 g, 0.594 mmol). The reaction mixture was stirred at room temperature for 72 hours, concentrated, and purified by flash column chromatography on silica gel using 0-100% ethyl acetate/hexanes as eluent to give the title compound as a yellow foam (0.118 g, 45% ).

The following compounds were prepared using a procedure similar to that described in example 18:

trans-2-Chloro-5-(2,2-dichloro-3-(2-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1004)

Isolated as a white foamy substance (0.056 g, 61%).

trans-5-(3-(3-Bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide (F1005)

Isolated as a yellow foam (0.1182 g, 45%).

trans-5-(3-(4-Bromo-3,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1006)

Isolated as a yellow foam (0.0959 g, 77%).

trans-5-(3-(3-Bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1007)

Isolated as a yellow foam (0.0878 g, 70%).

trans-2-Chloro-5-(2,2-dichloro-3-(perfluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1009)

Isolated as a white foamy substance (0.068 g, 71%).

trans-5-(3-(3-Bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1011)

Isolated as a white foamy substance (0.060 g, 43%).

cis-5-(3-(3-Bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1012)

Isolated as a white foamy substance (0.031 g, 22%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1024)

Isolated as a white foamy substance (0.071 g, 49%).

cis-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1025)

Isolated as a white solid (0.023 g, 16%).

trans-5-(3-(3-Bromo-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1031)

Isolated as a white foamy substance (0.066 g, 52%).

cis-5-(3-(3-Bromo-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1032)

Isolated as a clear, colorless oil (0.031 g, 24%).

cis-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1033)

Isolated as a white foamy substance (0.043 g, 29%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1034)

Isolated as a white foamy substance (0.033 g, 22%).

trans-2-Cyano-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-N-methylbenzamide (F1039)

Isolated as a white foamy substance (0.043 g, 38%).

trans-N-Allyl-2-chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1055)

Isolated as an orange foam (0.144 g, 47%).

trans-2-Chloro-5-(3-(3,5-dichlorophenyl)-2,2-difluorocyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide (F1057)

Isolated as an almost white solid (0.128 g, 84%).

trans-2-Chloro-5-(3-(3,5-dichlorophenyl)-2,2-difluorocyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1058)

Isolated as a white powdery substance (0.127 g, 80%).

trans-tert-Butyl-(3-(2-chloro-5-(3-(3,5-dichlorophenyl)-2,2-difluorocyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate (F1070)

Isolated as a white powdery substance (0.150 g, 83%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(methylamino)phenyl)-N- methylbenzamide (F1071)

Isolated as a beige foam (0.061 g, 95%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(prop-2- in-1-yl)benzamide (F1072)

Isolated as a yellow foam (0.066 g, 50%).

trans-(2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)methyl acetate (F1084)

Isolated as a yellow film (0.026 g, 22%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-iodophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1087)

Isolated as an almost white powdery substance (0.14 g, 72%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-iodophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1088)

Isolated as a brown semi-liquid substance (0.14 g, 68%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1089)

Isolated as a white foam (0.14 g, 72%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1090)

Isolated as a brown semi-liquid substance (0.15 g, 73%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-ethylbenzamide (F1091)

Isolated as a colorless film (0.083 g, 43%).

trans-N-Benzyl-2-chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1099)

Isolated as a yellow foam (0.228 g, 60%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-iodophenyl)cyclopropane-1-carboxamido)benzamide (F1140)

Isolated as an almost white powdery substance (0.087 g, 42%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-iodophenyl)cyclopropane-1-carboxamido)benzamide (F1141)

Isolated as a gray foamy substance (0.081 g, 40%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxamido) benzamide (F1142)

Isolated as a white powdery substance (0.073 g, 36%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxamido) benzamide (F1143)

Isolated as an almost white foamed substance (0.074 g, 36%).

trans-2-chloro-5-(2,2-dichloro-3-(3-iodophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide ( F1281)

Isolated as a yellowish-brown powdery substance (0.078 g, 49%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,4-difluorophenyl)benzamide (F1293)

Isolated as a pale yellow foam (0.046 g, 29%).

tert-butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino] benzoyl]-methylamino]-2,6-difluorophenyl]carbamate (CF1)

Isolated as a white foam (0.149 g, 65%): ¹ H NMR (500 MHz, methanol-d ₄ ) δ 7.92 (s, 0H), 7.84 - 7.59 (m, 2H), 7 .59 - 7.42 (m, 4H), 7.28 (ddd, J = 15.3, 8.4, 2.1 Hz, 1H), 7.22 (d, J = 8.9 Hz, 1H ), 7.00 (t, J = 9.2 Hz, 1H), 3.55 (dd, J = 16.9, 8.3 Hz, 1H), 3.41 (s, 3H), 3.25 - 3.19 (m, 1H), 3.13 (d, J = 8.3 Hz, 1H), 1.41 (s, 8H), 1.34 - 1.22 (m, 9H); ¹⁹ F NMR (471 MHz, methanol- _d4 ) δ -119.20, -120.57, -121.26 (dt, J = 9.4, 4.8 Hz), -124.91, -125, 98; ESIMS m/z 792 ([MH] ^- ).

trans-tert-Butyl-(3-(2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamido)-2,6-difluorophenyl) (methyl)carbamate (CF2)

Isolated as a white foam (0.081 g, 40.6%): ¹ H NMR (500 MHz, methanol-d ₄ ) δ 7.90 (d, J = 24.5 Hz, 1H), 7.71 (d , J = 13.8 Hz, 1H), 7.56 - 7.44 (m, 3H), 7.38 (s, 1H), 7.31 - 7.25 (m, 1H), 7.22 ( dd, J = 8.9, 1.8 Hz, 1H), 6.93 (t, J = 9.1 Hz, 1H), 3.55 (dd, J = 22.7, 8.3 Hz, 1H ), 3.42 (d, J = 1.7 Hz, 3H), 3.22 (q, J = 3.3 Hz, 1H), 3.18 (s, 0H), 3.14 (d, J = 8.1 Hz, 1H), 3.09 (s, 1H), 2.93 (s, 2H), 1.53 - 1.45 (m, 2H), 1.39 - 1.27 (m, 6H), 1.26 - 1.15 (m, 3H); ^19F NMR (471 MHz, methanol- _d4 ) δ -118.58 (d, J = 165.0 Hz), -119.80, -120.43, -124.14 (d, J = 231.2 Hz), -126.04 (d, J = 428.3 Hz); ESIMS m/z 730 ([M+Na] ⁺ ).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane -1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate (DP7)

Isolated as a white solid (0.174 g, 67%).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate (DP14)

Isolated as a white solid (2.75 g, 78%).

(1R,3R)-2,2-Dichloro-N-(4-chloro-3-(1,2-dimethyl-2-phenylhydrazine-1-carbonyl)phenyl)-3-(3,4-dichlorophenyl)cyclopropane- 1-carboxamide (F2544)

Isolated as a pale orange foam (0.266 g, 66%).

Example 19: Preparation of trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-N-methylbenzamide (F1112)

Step 1: tert-Butyl-N-tert-butoxycarbonyl-N-[3-[(2-chloro-5-nitrobenzoyl)-methylamino]-2,6-difluorophenyl]carbamate (C144) (0.138 g, 0.225 mmol), Ammonium chloride (0.0409 g, 0.764 mmol) and powdered iron (0.0711 g, 1.273 mmol) were transferred to methanol (2.4 ml) and water (0.8 ml) to obtain a black suspension. The reaction mixture was heated at 60°C for 5 hours. The reaction mixture was filtered and the filtrate was washed with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate and evaporated to give the crude material as an orange oil which was used without purification.

Step 2: Crude aniline was dissolved in dichloromethane (2422 µl) to obtain an orange solution. 4.0 M hydrogen chloride in 1,4-dioxane (606 μl, 2.422 mmol) was added and the reaction mixture was stirred at room temperature overnight. Volatiles were removed. Trans-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C76) (0.077 g, 0.242 mmol) and N,N-dimethylpyridine-4- amine (0.0592 g, 0.484 mmol) in dichloromethane (2422 µl) to obtain a yellow suspension. N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (69.6 mg, 0.363 mmol) was added and the whole formed a solution and the reaction mixture darkened to a deep blue color. The reaction mixture was stirred at room temperature for 3 hours. Volatile substances were removed. Purification by flash column chromatography using 0-100% ethyl acetate/hexanes as eluent gave the title compound as a pale yellow foam (0.061 g, 39%).

The following compounds were prepared using a procedure similar to that described in example 19:

trans-N-Allyl-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1113)

Isolated as a yellow foam (0.042 g, 49%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)- N-(prop-2-yn-1-yl)benzamide (F1114)

Isolated as a yellow foam (0.054 g, 35%).

Example 20: Preparation of trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide ( F1105):

To a solution of trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid (C40) (0.040 g, 0.14 mmol), 3-amino-2,6-dichloro- A 50% solution of 2,4,6- tripropyl 1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide (0.17 ml, 0.28 mmol) in ethyl acetate. The resulting colorless solution was stirred at 50°C for 16 hours and cooled to room temperature. The reaction mixture was adsorbed onto ^Celite® (~1.5 g) and purified by automated flash chromatography using a 0-55% ethyl acetate in hexanes eluent to give the title compound as a white solid (0.083 g, 100%) .

The following compounds were prepared using a procedure similar to that described in example 20:

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,6-difluorophenyl)carbamate (F1053)

Isolated as a white foam (2.43 g, 89%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1066)

Isolated as a white foamy substance (0.059 g, 31%).

cis-2-Chloro-5-(2,2-dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1067)

Isolated as a white foamy substance (0.050 g, 26%).

trans-tert-Butyl-(3-(5-(3-(3-bromo-5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl) carbamate (F1073)

Isolated as a white solid (0.129 g, 82%).

tert-Butyl-(3-(2-chloro-5-((1S,3S)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,6-difluorophenyl)carbamate (F1074)

Isolated as a white solid (0.542 g, 73%).

trans-tert-Butyl-(3-(2-chloro-5-(2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2,6- difluorophenyl)carbamate (F1077)

Isolated as a white solid (0.143 g, 85%).

trans-tert-Butyl-(3-(2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2,6- difluorophenyl)carbamate (F1078)

Isolated as a white solid (0.984 g, 85%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2,6-difluorobenzamide (F1086)

Isolated as a white solid (0.047 g, 68%).

trans-tert-Butyl-(3-(2-chloro-5-(2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2,6- difluorophenyl)carbamate (F1092)

Isolated as a white solid (0.199 g, 86%).

trans-5-(3-(3-bromo-2,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1093)

Isolated as a white foamy substance (0.033 g, 30%).

cis-5-(3-(3-Bromo-2,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide (F1094)

Isolated as a clear, colorless oil (0.042 g, 38%).

trans-tert-Butyl-(3-(5-(3-(3-bromo-2,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl)carbamate (F1095)

Isolated as a white solid (0.058 g, 26%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro-N-(4-fluorophenyl)benzamide (F1100)

Isolated as a white solid (0.074 g, 91%).

trans-N-(4-Acetamidophenyl)-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluorobenzamide (F1101)

Isolated as a white solid (0.030 g, 90%).

trans-N-(4-Acetamidophenyl)-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1102)

Isolated as a white solid (0.032 g, 71%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide (F1103)

Isolated as a white solid (0.068 g, 88%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-phenylbenzamide (F1104)

Isolated as a white solid (0.075 g, 94%).

trans-N-(4-Aminophenyl)-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamide (F1106)

Isolated as a tan solid (0.038 g, 53%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2,6-dichloro-3-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino] benzoyl]amino]-2,6-difluorophenyl]carbamate (F1107)

Isolated as a white solid (0.086 g, 80%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro-N-phenylbenzamide (F1108)

Isolated as a tan solid (0.082 g, 96%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[3-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-2,6-difluorobenzoyl ]amino]-2,6-difluorophenyl]carbamate (F1109)

Isolated as a tan solid (0.101 g, 73%).

trans-tert-Butyl-(3-(5-(3-(4-bromo-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl) carbamate (F1115)

Isolated as a white foamy substance (0.179 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1118)

Isolated as a white foamy substance (0.078 g, 83%).

trans-tert-Butyl-(3-(2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2,6- difluorophenyl)carbamate (F1119)

Isolated as a white solid (0.197 g, 88%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1147 )

Isolated as a pale yellow foam (0.094 g, 52%).

cis-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1148 )

Isolated as a clear, colorless oil (0.028 g, 15%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-chloro-3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1163)

Isolated as a clear, colorless oil (0.115 g, 62%).

cis-2-Chloro-5-(2,2-dichloro-3-(4-chloro-3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1164)

Isolated as a white foamy substance (0.040 g, 22%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1172)

Isolated as a white foamy substance (0.076 g, 39%).

cis-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1173)

Isolated as a white foamy substance (0.032 g, 17%).

trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl) benzamide (F1232)

Isolated as a white foamy substance (0.088 g, 50%).

cis-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxamido)-I-(2,4-difluorophenyl) benzamide (F1233)

Isolated as a clear, colorless oil (0.035 g, 20%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino] -3-fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1282)

Isolated as a white solid (0.284 g, 80%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]-3-fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1283)

Isolated as a white solid (0.298 g, 83%).

trans-2-Chloro-5-(2,2-dichloro-3-(2-chloro-5-(trifluoromethyl)phenyl)-cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide ( F2001)

Isolated as a white foamy substance (0.047 g, 52%).

trans-2-Chloro-5-(2,2-dichloro-3-(perfluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2002)

Isolated as a white solid (0.069 g, 76%).

trans-5-(3-(3-Bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F2003)

Isolated as a white foamy substance (0.067 g, 51%).

cis-5-(3-(3-Bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F2004)

Isolated as a white foamy substance (0.029 g, 22%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,3,3,3-pentafluoropropyl) benzamide (F2005)

Isolated as a white solid (0.068 g, 93%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2006)

Isolated as a clear, colorless oil (0.077 g, 56%).

cis-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2007)

Isolated as a clear, colorless oil (0.022 g, 16%).

trans-5-(3-(3-Bromo-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,2,2-trifluoroethyl )benzamide (F2008)

Isolated as a white foamy substance (0.065 g, 54%).

cis-5-(3-(3-Bromo-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,2,2-trifluoroethyl )benzamide (F2009)

Isolated as a clear, colorless oil (0.028 g, 23%).

cis-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2010)

Isolated as a white foamy substance (0.039 g, 28%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2011)

Isolated as a clear, colorless oil (0.037 g, 26%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl )benzamide (F2012)

Isolated as a clear, colorless oil (0.041 g, 31%).

cis-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl )benzamide (F2013)

Isolated as a white foamy substance (0.055 g, 42%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl)phenyl)-cyclopropane-1-carboxamido)-N-(2,2,2- trifluoroethyl)benzamide (F2014)

Isolated as a white foamy substance (0.068 g, 38%).

cis-2-Chloro-5-(2,2-dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl)phenyl)-cyclopropane-1-carboxamido)-N-(2,2,2- trifluoroethyl)benzamide (F2015)

Isolated as a golden oil (0.045 g, 25%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-2,6-difluorobenzamide (F2016)

Isolated as a white solid (0.068 g, 91%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro-N-(2,2,2-trifluoroethyl)benzamide (F2017)

Isolated as a white solid (0.081 g, 96%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro-N-(2,2,3,3,3-pentafluoropropyl) benzamide (F2018)

Isolated as a white solid (0.068 g, 94%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethylbenzamide (F2019)

Isolated as a white solid (0.077 g, 88%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2020)

Isolated as a white solid (0.052 g, 66%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro-N-propylbenzamide (F2021)

Isolated as a white foamy substance (0.084 g, 91%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-propylbenzamide (F2022)

Isolated as a white solid (0.077 g, 90%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro-N-(3,3,3-trifluoropropyl)benzamide (F2023)

Isolated as a white solid, 0.067 g, 82%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3,3,3-trifluoropropyl)benzamide (F2024)

Isolated as a white solid (0.071 g, 92%).

trans-2,6-Dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoroethyl)benzamide (F2025)

Isolated as a white solid (0.070 g, 84%).

trans-2,6-Dichloro-N-(3-chloropropyl)-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F2026)

Isolated as a white solid (0.070 g, 88%).

trans-3-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro-N-(2-fluoroethyl)benzamide (F2027)

Isolated as a white solid (0.088 g, 96%).

trans-N-(3-Chloropropyl)-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluorobenzamide (F2028)

Isolated as a white solid (0.083 g, 98%).

Example 21: Preparation of trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (DP8)

Step 1: Preparation of trans-tert-butyl-N-tert-butoxycarbonyl-N-[3-(5-(3-(4-fluoro3-trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2 -chlorobenzamido)-2,6-difluorophenyl]carbamate. Anhydrous ethyl acetate (3 ml) at room temperature was added to a 10 ml glass test tube containing trans-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C76) ( 0.05 g, 0.158 mmol) and tert-butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-amino-2-chlorobenzamido)-2,6-difluorophenyl)carbamate (C135) ( 0.079 g, 0.158 mmol). Pyridine (0.0374 g, 0.473 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide ( ^T3P® , 50) were then added to the resulting solution % solution in ethyl acetate; 0.201 g, 0.315 mmol). The solution was stirred at 24°C for 12 hours, concentrated to dryness, and purified by flash column chromatography on silica gel using 0-50% ethyl acetate/hexanes as eluent to give trans-tert-butyl-N-tert-butoxycarbonyl- N-[3-(5-(4-fluoro-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl]carbamate as a white solid. (0.114 g, 86%).

Step 2: Preparation of trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide. An anhydrous hydrogen chloride solution (4.0 M in dioxane; 0.326 mL, 1.305 mmol) was added to the trans-tert-butyl-N-tert-butoxycarbonyl-N-[3-(5-(3-(4-fluoro3- trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl]carbamate (0.104 g, 0.130 mmol). The suspension was stirred at 24°C for 12 hours. Dichloromethane was then removed under a stream of nitrogen and the sample was dissolved in ethyl acetate (20 ml) and washed with saturated aqueous sodium bicarbonate (5 ml) and saturated aqueous sodium chloride (5 ml). The ethyl acetate solution was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo on a rotary evaporator. Purification of the residue by flash chromatography on silica gel using 0-50% ethyl acetate/hexanes as eluent gave the title compound as a white foam (0.043 g, 53%).

The following compounds were prepared using a procedure similar to that described in example 21:

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromo-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)- 2-chlorobenzamide (F1042)

Isolated as a white foamy substance (0.079 g, 74%).

cis-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromo-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)- 2-chlorobenzamide (F1043)

Isolated as a clear, colorless oil (0.028 g, 56%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1044)

Isolated as a clear, colorless oil (0.062 g, 56%).

cis-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1045)

Isolated as a clear, colorless oil (0.032 g, 53%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1046)

Isolated as a white foamy substance (0.085 g, 65%).

cis-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1047)

Isolated as a clear, colorless oil (0.026 g, 82%).

N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((cis)-2,2-dichloro-3-(3-chloro-2,4-difluorophenyl)cyclopropane-1-carboxamido) benzamide (F1048)

Isolated as a white foamy substance (0.053 g, 60%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1049)

Isolated as a white solid (0.041 g, 63%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1050)

Isolated as a white foamy substance (0.042 g, 30%).

cis-2-Chloro-5-(2,2-dichloro-3-(3-chloro-2-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1051)

Isolated as a white foamy substance (0.063 g, 46%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (DP9)

Isolated as a white solid (1.5 g, 69%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1068)

Isolated as a white foamy substance (0.042 g, 44%).

cis-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((cis)-2,2-dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1069)

Isolated as a white foamy substance (0.032 g, 51%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromo-5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1075 )

Isolated as a clear, colorless oil (0.062 g, 66%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1079)

Isolated as a white foamy substance (0.068 g, 68%).

cis-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromo-2,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1097)

Isolated as a clear, colorless oil (0.019 g, 58%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromo-2,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1098)

Isolated as a clear, colorless oil (0.014 g, 32%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(4-bromo-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1116 )

Isolated as a white foamy substance (0.140 g, 86%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1127)

Isolated as a clear, colorless oil (0.085 g, 61%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido )benzamide (F1149)

Isolated as a white foamy substance (0.083 g, 81%).

cis-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido )benzamide (F1150)

Isolated as a clear, colorless oil (0.037 g, 70%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-chloro-3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1167)

Isolated as a white foamy substance (0.072 g, 64%).

cis-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-chloro-3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1168)

Isolated as a clear, colorless oil (0.024 g, 63%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1181)

Isolated as a white foamy substance (0.099 g, 68%).

cis-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1182)

Isolated as a white foamy substance (0.038 g, 77%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane- 1-Carboxamido)benzamide (F1259)

Isolated as a clear, colorless oil (0.071 g, 70%).

cis-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane- 1-Carboxamido)benzamide (F1260)

Isolated as a clear, colorless oil (0.032 g, 67%).

Example 22: Preparation of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-methoxyphenyl)benzamide ( F1171)

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (0.1 g, 0.22 mmol) suspended in toluene (2 ml) was treated with oxalyl chloride (0.0.097 ml. 1.1 mmol) and one drop of N,N-dimethylformamide with stirring at room temperature. After the mixture became homogeneous and gas evolution had ceased, the solution was concentrated to a clear oil and then cooled in an ice bath under nitrogen. 2,4-Difluoro-3-methoxyaniline (0.035 g, 0.22 mmol) was added as a solution in pyridine (2 ml) with stirring and the reaction mixture was allowed to warm to room temperature and stirred overnight. An aliquot was taken and diluted with dimethyl sulfoxide and examined by liquid chromatography/mass spectroscopy, which showed the presence of a mixture of the desired product and the parent carboxylic acid. The reaction mixture was partitioned between ethyl acetate and aqueous hydrochloric acid (1N), the layers were separated and the organic phase was dried over sodium sulfate. Purification by flash silica gel chromatography (3:1 hexane-ethyl acetate) provided the title compound as a greenish solid (0.075 g, 57%).

The following compounds were prepared using a procedure similar to that described in example 22:

trans-3-(2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenylacetate (F1193)

Isolated as a light yellow foam (0.105 g, 52%).

trans-Methyl 3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorobenzoate (F1265)

Isolated as a white foamy substance (0.060 g, 44%).

Example 23: Preparation of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-hydroxy-2-methylphenyl)benzamide (F1224)

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (0.221 g, 0.487 mmol), 4-amino-3-methylphenol (0.072 g, 0.59 mmol) and 4-dimethylaminopyridine (0.071 g, 0.59 mmol) were weighed into a round bottom flask. N,N-Dimethylformamide (2 ml) was added by syringe and ethyl 3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.19 g, 0.97 mmol) was added with stirring at room temperature. After 64 hours, an aliquot was removed, diluted with dimethyl sulfoxide and analyzed by liquid chromatography/mass spectroscopy, which showed the presence of several products. After 120 hours, the reaction mixture was partitioned between ethyl acetate and brine, the layers were separated and the organic phase was dried over sodium sulfate. Purification by reverse phase chromatography gave, in order of elution, trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-hydroxy -2-methylphenyl)benzamide was isolated as an almost white solid (0.022 g, 8%) and trans-4-amino-3-methylphenyl 2-chloro-5-(2,2-dichloro-3-(3,5 -dichlorophenyl)cyclopropane-1-carboxamido)benzoate, isolated as an almost white solid (0.064 g, 24%): ¹ H NMR (400 MHz, acetone-d ₆ ) δ 10.25 (br s, 1H), 8 .40 (d, J = 2.6 Hz, 1H), 7.96 (dd, J = 8.8, 2.7 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H) , 7.50 (s, 3H), 6.92 (d, J = 2.6 Hz, 1H), 6.87 (dd, J = 8.5, 2.7 Hz, 1H), 6.74 ( d, J = 8.5 Hz, 1H), 4.47 (ad, J = 10.7 Hz, 2H), 3.67 (d, J = 8.3 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H), 2.17 (s, 3H); ¹³ C NMR (101 MHz, acetone-d ₆ ) δ 163.94, 162.59, 144.40, 141.76, 137.93, 137.41, 134.71, 131.46, 130.64, 127 .85, 127.38, 123.60, 122.74, 122.46, 121.84, 119.33, 114.40, 61.91, 39.23, 37.55, 16.70; ESIMS m/z 559 ([M+H] ⁺ ).

Example 24: Preparation of trans-tert-butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate (DP10)

To a solution of tert-butyl-(4-amino-3-methylphenyl)carbamate (C184) (0.052 g, 0.233 mmol) in dichloromethane (2 ml) was added 3-(((ethylimino)methylene)amino)-N,N-dimethylpropane -1-amine hydrochloride (0.045 g, 0.233 mmol), N,N-dimethylpyridin-4-amine (0.021 g, 0.171 mmol) and trans-2-chloro-5-(2,2-dichloro-3-(3.5 -dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (0.075 g, 0.155 mmol). The reaction mixture was stirred at room temperature for 14 hours. The reaction mixture was directly loaded onto a Celite column and purified using a 0-30% ethyl acetate/hexanes gradient flash column chromatography to obtain the title compound as a white solid ( 0.056 g, 55%): ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 9.90 (s, 1H), 9.32 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1H), 7 .60 - 7.51 (m, 3H), 7.38 (s, 1H), 7.25 (q, J = 8.9 Hz, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 2.23 (s, 3H), 1.48 (s, 9H); (thin film) 3277, 2980, 1684, 1655, 1539 cm ^-1 ; ESIMS 656 ([MH] ^- ).

Example 25: Preparation of tert-butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3-chloro-4- fluorophenyl)cyclopropane-carbonyl]amino]-3-fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1239)

To a solution of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzoic acid (C1) (0.360 g, 0.79 mmol) in ethyl acetate (2.5 ml) was added tert-butyl-N-(3-amino-2,6-difluorophenyl)-N-tert-butoxycarbonylcarbamate (C182) (0.327 g, 0.95 mmol) and pyridine (0.188 g, 0.191 ml, 2.37 mmol), then 50% solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide (0. 94 ml, 1.58 mmol) in ethyl acetate and the resulting golden solution was heated at 45°C and stirred for 68 hours. The reaction mixture was concentrated and the viscous amber residue was dissolved in a minimal amount of methylene chloride (~3 ml) and adsorbed onto ^Celite® . The adsorbed material was purified by automated flash chromatography using a 0-25% ethyl acetate in hexanes gradient to give the title compound (0.166 g, 87%) as a white solid.

The following compounds were prepared using a procedure similar to that described in example 25:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-2-nitrophenyl)benzamide ( F1081)

Isolated as a yellow solid (0.056 g, 43%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-methyl-5- nitrophenyl)benzamide (F1082)

Isolated as an almost white foamy substance (0.109 g, 81%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4,5-difluoro-2-nitrophenyl) benzamide (F1085)

Isolated as a yellow film (0.039 g, 28%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 4-difluorophenyl)benzamide (F1268)

Isolated as a white powdery substance (0.049 g, 34%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,4-difluorophenyl)benzamide (F1269)

Isolated as a white solid (0.078 g, 55%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,4-difluorophenyl)benzamide (F1270)

Isolated as a white foamy substance (0.084 g, 58%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro-N-methylacetamido )-2,4-difluorophenyl)benzamide (F1271)

Isolated as a white foamy substance (0.090 g, 61%).

trans-N-(3-Bromo-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1304)

Isolated as an almost white solid (0.18 g, 33%).

trans-N-(2-Bromo-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1305)

Isolated as an almost white solid (0.18 g, 37%).

trans-N-(4-Bromo-2-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1306)

Isolated as an almost white solid (0.18 g, 37%).

trans-N-(3-Bromo-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1307)

Isolated as an almost white solid (0.33 g, 39%).

trans-N-(5-Bromo-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1308)

Isolated as an almost white solid (0.48 g, 34%).

trans-N-(2-Bromo-4,6-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1309)

Isolated as an almost white solid (0.24 g, 28%).

trans-N-(3-Bromo-4,5-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP11)

Isolated as an almost white solid (0.62 g, 44%).

trans-N-(3-Amino-2,4,5,6-tetrafluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1022)

Isolated as a white foamy substance (0.012 g, 8%).

trans-tert-Butyl-(3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4-difluorophenyl)carbamate (F1023 )

Isolated as a white foamy substance (0.088 g, 56%).

trans-N-(3-Acetamido-2,4-dimethylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1128)

Isolated as a white solid (0.094 g, 66%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,3-dimethyl-4-nitrophenyl)benzamide (F1180)

Isolated as a yellow solid (0.246 g, 70%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,5-dimethyl-4-nitrophenyl)benzamide (F1230)

Isolated as a white solid (0.041 g, 12%).

trans-N-(4-Bromo-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1054)

Isolated as a white powdery substance (0.46 g, 84%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(4-fluorophenyl)benzamide (F1152)

Isolated as a pale yellow solid (0.065 g, 88%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-3-fluorobenzamide (F1153)

Isolated as a pale yellow solid (0.071 g, 93%).

trans-N-(4-Acetamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzamide (F1154)

Isolated as a white solid (0.077 g, 97%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-3 -fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1155)

Isolated as a light yellow solid (0.0185 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-methyl-N-phenylbenzamide (F1183)

Isolated as a white solid (0.072 g, 89%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-3-methylbenzamide (F1184)

Isolated as a tan solid (0.071 g, 86%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-3-methylbenzamide (F1185)

Isolated as a white solid (0.070 g, 84%).

trans-N-(4-Acetamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-methylbenzamide (F1186)

Isolated as a light pink solid (0.067 g, 74%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-3 -methylbenzoyl]amino]-2,6-difluorophenyl]carbamate (F1187)

Isolated as a light yellowish-brown solid (0.109 g, 88%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methyl-N-phenylbenzamide (F1188)

Isolated as a white solid (0.073 g, 93%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-methylbenzamide (F1189)

Isolated as a light yellowish-brown solid (0.072 g, 89%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-methylbenzamide (F1190)

Isolated as a light yellowish-brown solid (0.073 g, 90%).

trans-N-(4-Acetamidophenyl)-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methylbenzamide (F1191)

Isolated as a white solid (0.081 g, 93%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[3-chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-2 -methylbenzoyl]amino]-2,6-difluorophenyl]carbamate (F1192)

Isolated as a white solid (0.131 g, 99%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-phenylbenzamide (F1194)

Isolated as an almost white solid (0.043 g, 44%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide (F1195)

Isolated as an almost white solid (0.072 g, 71%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide (F1196)

Isolated as an almost white solid (0.064 g, 61%).

trans-N-(4-Acetamidophenyl)-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1197)

Isolated as a white solid (0.044 g, 40%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[3-chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-2 -fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1198)

Isolated as an almost white solid (0.099 g, 65%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluoro-N-phenylbenzamide (F1207)

Isolated as an almost white solid (0.066 g, 67%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluoro-N-(4-fluorophenyl)benzamide (F1208)

Isolated as a white solid (0.079 g, 77%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2,3-difluorobenzamide (F1209)

Isolated as a white solid (0.089 g, 84%).

trans-N-(4-Acetamidophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzamide (F1210)

Isolated as a white solid (0.086 g, 78%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-2,3-difluorobenzoyl ]amino]-2,6-difluorophenyl]carbamate (F1211)

Isolated as a light yellow solid (0.130 g, 89%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-phenyl-3-(trifluoromethyl)benzamide (F1212)

Isolated as a tan solid (0.060 g, 76%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methoxy-N-phenylbenzamide (F1213)

Isolated as a tan solid (0.067 g, 86%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-3-(trifluoromethyl)benzamide (F1214)

Isolated as a tan solid (0.066 g, 83%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-3-(trifluoromethyl)benzamide ( F1215)

Isolated as a yellowish-brown foam (0.072 g, 88%).

trans-N-(4-Acetamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-(trifluoromethyl)benzamide (F1216)

Isolated as a tan solid (0.072 g, 83%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-3 -(trifluoromethyl)-benzoyl]amino]-2,6-difluorophenyl]carbamate (F1217)

Isolated as a light yellow solid (0.098 g, 86%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(4-fluorophenyl)-2-methoxybenzamide (F1218)

Isolated as a yellowish-brown foam (0.072 g, 89%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-3-fluoro-2-methoxybenzamide (F1219)

Isolated as a white solid (0.065 g, 79%).

trans-N-(4-Acetamidophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)-cyclopropane-1-carboxamido)-3-fluoro-2-methoxybenzamide (F1220)

Isolated as a light yellow solid (0.075 g, 87%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-3-fluoro-2 -methoxybenzoyl]amino]-2,6-difluorophenyl]carbamate (F1221)

Isolated as a light yellow solid (0.109 g, 94%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[4-[[2-chloro-5-[[2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino]benzoyl]amino] -2,6-difluorophenyl]carbamate (F1266)

Isolated as a light brown solid (2.06 g, 79%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane -1-carboxamido)benzamido)-2,4-difluorophenyl)carbamate (DP12)

Isolated as a white solid (0.154 g, 90%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide (DP13)

Isolated as a yellow solid (0.8 g, 42%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(4-fluorophenyl)-2-methylbenzamide (F1278)

Isolated as a light yellowish-brown solid (0.058 g, 85%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-3-fluoro-2-methylbenzamide (F1279):

Isolated as a light yellowish-brown solid (0.059 g, 84%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-3-fluoro-2 -methylbenzoyl]amino]-2,6-difluorophenyl]carbamate (F1280)

Isolated as a white solid (0.099 g, 100%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-2-fluoro-3-methylbenzamide (F2029)

Isolated as a white solid (0.068 g, 83%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-3-methyl-N-(2,2,2-trifluoroethyl)benzamide ( F2030)

Isolated as a white solid (0.077 g, 84%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-3-methyl-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2031)

Isolated as a white solid (0.083 g, 82%).

trans-N-(3-Chloropropyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)-cyclopropane-1-carboxamido)-2-fluoro-3-methylbenzamide (F2032)

Isolated as a white solid (0.069 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-3-fluorobenzamide (F2033)

Isolated as a white solid (0.046 g, 71%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(2,2,2-trifluoroethyl)benzamide ( F2034)

Isolated as a white solid (0.061 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2035)

Isolated as a white solid (0.070 g, 89%).

trans-2-Chloro-N-(3-chloropropyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzamide (F2036)

Isolated as a white solid (0.063 g, 87%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-3-methylbenzamide (F2037)

Isolated as a white solid (0.055 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-methyl-N-(2,2,2-trifluoroethyl)benzamide ( F2038)

Isolated as a tan solid (0.052 g, 66%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-methyl-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2039)

Isolated as a white solid (0.080 g, 93%).

trans-2-Chloro-N-(3-chloropropyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-methylbenzamide (F2040)

Isolated as a white solid (0.054 g, 69%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-2-methylbenzamide (F2041)

Isolated as a white solid (0.031 g, 44%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methyl-N-(2,2,2-trifluoroethyl)benzamide ( F2042)

Isolated as a white solid (0.066 g, 83%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methyl-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2043)

Isolated as a white solid (0.071 g, 82%).

trans-3-Chloro-N-(3-chloropropyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methylbenzamide (F2044)

Isolated as a tan solid (0.050 g, 64%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(2,2,2-trifluoroethyl)benzamide ( F2045)

Isolated as a white solid (0.047 g, 47%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2046)

Isolated as an almost white solid (0.074 g, 68%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-2-fluorobenzamide (F2047)

Isolated as an almost white solid (0.062 g, 70%).

trans-3-Chloro-N-(3-chloropropyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F2048)

Isolated as an almost white solid (0.062 g, 63%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluoro-N-(2,2,2-trifluoroethyl)benzamide (F2049)

Isolated as a white solid (0.079 g, 79%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluoro-N-(2,2,3,3,3-pentafluoropropyl) benzamide (F2050)

Isolated as a white solid (0.092 g, 84%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-2,3-difluorobenzamide (F2051)

Isolated as a white solid (0.073 g, 82%).

trans-N-(3-Chloropropyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzamide (F2052)

Isolated as a white solid (0.075 g, 76%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-3-(trifluoromethyl)benzamide (F2053)

Isolated as a pale yellow solid (0.045 g, 64%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)-3-(trifluoromethyl) benzamide (F2054)

Isolated as a white foamy substance (0.062 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-(trifluoromethyl)-N-(3,3,3-trifluoropropyl) benzamide (F2055)

Isolated as a white solid (0.063 g, 79%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,3,3,3-pentafluoropropyl)-3 -(trifluoromethyl)benzamide (F2056)

Isolated as a white foamy substance (0.053 g, 62%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-3-fluoro-2-methoxybenzamide (F2057)

Isolated as a white foamy substance (0.054 g, 76%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ( F2058)

Isolated as a white foamy substance (0.069 g, 86%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methoxy-N-(3,3,3-trifluoropropyl)benzamide ( F2059)

Isolated as a white foamy substance (0.070 g, 86%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methoxy-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2060)

Isolated as a white foamy substance (0.069 g, 81%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ( F2061)

Isolated as a white solid (0.060 g, 77%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methoxy-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2062)

Isolated as a white solid (0.075 g, 88%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methyl-N-(2,2,2-trifluoroethyl)benzamide ( F2063)

Isolated as a white solid (0.063 g, 96%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methyl-N-(2,2,3,3,3- pentafluoropropyl)benzamide (F2064)

Isolated as a white solid (0.059 g, 81%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)-3-methylbenzamide (F1136)

Isolated as a tan solid (0.078 g, 81%).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluoro-3-methylbenzamide (F1137)

Isolated as a yellowish-brown foam (0.082 g, 87%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-2-fluoro-3 -methylbenzoyl]amino]-2,6-difluorophenyl]carbamate (F1138)

Isolated as a white solid (0.149 g, 83%).

trans-N-(4-Acetamidophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)-cyclopropane-1-carboxamido)-2-fluoro-3-methylbenzamide (F1139)

Isolated as a white solid (0.088 g, 85%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-methoxybenzamide (F1235)

Isolated as a white solid (0.048 g, 60%).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-methoxybenzamide (F1236)

Isolated as a white solid (0.059 g, 72%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[3-chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl]amino]-2 -methoxybenzoyl]amino]-2,6-difluorophenyl]carbamate (F1237)

Isolated as an almost white solid (0.059 g, 52%).

Example 26: Preparation of trans-2-((tert-butoxycarbonyl)(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3 -methylphenyl)amino)ethyl acetate (F1129)

Step 1: Preparation of 2-((tert-butoxycarbonyl)(3-methyl-4-nitrophenyl)amino)ethyl acetate. tert-Butyl-(3-methyl-4-nitrophenyl)carbamate (C223) (1.0 g, 3.96 mmol), dissolved in anhydrous N,N-dimethylformamide (5 ml), was added dropwise to the hydride suspension with stirring sodium (60% oily suspension, 0.206 g, 5.15 mmol) in anhydrous N,N-dimethylformamide (50 ml) at a rate to maintain the temperature below 30°C. After addition was complete, the resulting orange solution was stirred at room temperature for 30 minutes, then 2-bromoethyl acetate (0.662 g, 3.96 mmol) was added dropwise. The resulting solution was stirred at room temperature for 12 hours, then the reaction was carefully stopped with water (100 ml) and extracted with ethyl acetate (3x50 ml). The organic extracts were washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated in vacuo on a rotary evaporator. Purification by flash silica gel chromatography gave the title compound as a yellow oil (0658 g, 47%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 - 7.97 (m, 1H), 7.26 (m, 2H), 4.31 - 4.23 (m, 2H), 3.93 (t, J = 5.6 Hz, 2H), 2.62 (s, 3H), 1.97 (s, 3H), 1.48 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 170.72, 170.58, 153.57, 146.91, 145.94, 134.81, 129.85, 125.53, 124.40, 81.83 , 77.37, 77.05, 76.73, 62.16, 62.08, 48.76, 28.21, 20.86, 20.76, 20.70; ESIMS m/z 339 ([M+H]+).

Step 2: Preparation of 2-((4-amino-3-methylphenyl)(tert-butoxycarbonyl)amino)ethyl acetate. Palladium hydroxide (10% w/w; 0.135 g, 0.096 mmol) was added to a solution of 2-((tert-butoxycarbonyl)(3-methyl-4-nitrophenyl)amino)ethyl acetate (0.650 g, 1.92 mmol) with stirring ) in ethyl acetate (50 ml). The flask was evacuated and filled with hydrogen from a cylinder through a reducer, and the resulting black suspension was stirred for 13 hours at room temperature. The reaction mixture was filtered through a pad of ^Celite® and concentrated in vacuo on a rotary evaporator to give the title compound as a brown solid (0.527 g, 85%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.85 (s, 2H) , 6.61 (d, J = 8.2 Hz, 1H), 4.18 (t, J = 5.8 Hz, 2H), 3.79 (t, J = 5.8 Hz, 2H), 3 .60 (s, 2H), 2.14 (s, 3H), 2.00 (s, 3H), 1.40 (s, 9H); ESIMS m/z 309 ([M+H] ⁺ ).

Step 3: Preparation of trans-2-((tert-butoxycarbonyl)(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3 -methylphenyl)amino)ethyl acetate (F1129). 2,4,6-Tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide ( ^T3P® , 50% solution in ethyl acetate; 0.281 g, 0.441 mmol) was added dropwise with stirring to a solution of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (0.100 g, 220 mmol), 2-((4 -amino-3-methylphenyl)(tert-butoxycarbonyl)amino)ethyl acetate (0.068 g, 0.220 mmol) and pyridine (0.053 g, 0.661 mmol) in anhydrous ethyl acetate (3 ml). The solution was stirred for 12 hours at 23°C and concentrated. Purification by flash silica gel chromatography provided the title compound as a white foam (0.149 g, 86%).

The following compounds were prepared using a procedure similar to that described in example 26:

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)(2-cyanoethyl) carbamate (F1157)

Isolated as a white solid (0.134 g, 81%).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)(2-methoxyethyl) carbamate (F1159)

Isolated as a clear, colorless oil (0.121 g, 73%).

Example 27: Preparation of N-(4-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamido)benzamide (F1027)

To a solution of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C13) (0.100 g, 0.220 mmol) and tert -butyl-N-((tert-butoxy)carbonyl)-N-(4-amino-3,5-difluorophenyl)carbamate (C181) (0.076 g, 0.220 mmol) in ethyl acetate (2 ml) was added pyridine (0.036 ml, 0.441 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide ( ^T3P® ) as a 50% solution in ethyl acetate (0.210 g, 0.331 mmol ). The mixture was heated at 45°C for 48 hours. The reaction mixture was cooled to room temperature and concentrated under a stream of nitrogen. The residue was purified by flash column chromatography using 0-30% ethyl acetate/hexanes as eluent. The product fractions were combined and concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (2 ml) and a 4 M solution of hydrogen chloride in dioxane (0.545 ml, 2.18 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours. The solvent was evaporated under a stream of nitrogen. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The phases were separated, the organic layer was washed with saturated aqueous sodium bicarbonate and brine and then passed through a phase separator to dry and the solvent was removed. Purification by flash column chromatography using 0-30% ethyl acetate/hexanes as eluent gave the title compound as a white solid (0.025 g, 19%).

The following compounds were prepared using a procedure similar to that described in example 27:

N-(4-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1028)

Isolated as a white solid (0.019 g, 15%).

N-(4-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1029)

Isolated as a white solid (0.022 g, 17%).

N-(4-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido) benzamide (F1030)

Isolated as a white solid (0.019 g, 14%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide ( F1036)

Isolated as a white solid (0.080 g, 42%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1037)

Isolated as a white solid (0.086 g, 46%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1038)

Isolated as a light yellow foam (0.079 g, 42%).

trans-N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1026)

Isolated as a white foamy substance (0.037 g, 76%).

trans-N-(4-Amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (DP1)

Isolated as a white foamy substance (0.838 g, 99%).

Example 28: Preparation of trans-2,2-dichloro-N-(4-chloro-3-(2-(pyridin-2-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane -1-carboxamide (F2502)

To a solution of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (0.080 g, 0.176 mmol) and 2-(1- methylhydrazinyl)pyridine (0.033 g, 0.265 mmol) in ethyl acetate (2 ml) at room temperature, diisopropylethylamine (0.123 ml, 0.706 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6- trioxatriphosphinane-2,4,6-trioxide ( ^T3P® ; 0.225 g, 0.353 mmol) as a 50% solution in ethyl acetate. The reaction mixture was stirred for 18 hours at room temperature and then concentrated under a stream of nitrogen. Purification by column chromatography using 0-100% ethyl acetate/hexanes as eluent gave the title compound as a yellow solid (0.019 g, 20%).

The following compounds were prepared using a procedure similar to that described in example 28:

trans-2,2-dichloro-N-(4-chloro-3-(2-(4-chloro-3-(trifluoromethyl)phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) cyclopropane-1-carboxamide (F2501)

Isolated as a light yellow foam (0.058 g, 44%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-(pyridin-2-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane -1-carboxamide (F2503)

Isolated as a yellow solid (0.046 g, 47%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(5-chloropyridin-2-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2504)

Isolated as an almost white solid (0.045 g, 44%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(3-chloropyridin-2-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2505)

Isolated as an almost white solid (0.036 g, 35%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(6-chloropyridazin-3-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2506)

Isolated as a light yellow solid (0.070 g, 69%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-(4-(trifluoromethyl)pyridin-2-yl)hydrazin-1-carbonyl)phenyl)-3-(3, 5-dichlorophenyl)cyclopropane-1-carboxamide (F2507)

Isolated as a white solid (0.096 g, 86%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(pyrimidin-2-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2508)

Isolated as a white solid (0.027 g, 28%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(pyrimidin-4-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2509)

Isolated as a white solid (0.016 g, 17%).

(1R,3R)-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-phenylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamide (F2510)

Isolated as a white solid (0.045 g, 37%).

(1R,3R)-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-phenylhydrazine-1-carbonyl)phenyl)-3-(3,4,5-trichlorophenyl)cyclopropane- 1-carboxamide (F2511)

Isolated as a white solid (0.048 g, 40%).

(1R,3R)-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-phenylhydrazine-1-carbonyl)phenyl)-3-(3-chloro-4-fluorophenyl)cyclopropane- 1-carboxamide (F2512)

Isolated as a white solid (0.041 g, 33%).

(1R,3R)-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-phenylhydrazine-1-carbonyl)phenyl)-3-(3,4-dichlorophenyl)cyclopropane-1- carboxamide (F2513)

Isolated as a white solid (0.057 g, 46%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-fluorophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2553 )

Isolated as a yellow foam (0.036 g, 31%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-cyanophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2554 )

Isolated as a light foamed substance (0.070 g, 63%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-nitrophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2555 )

Isolated as an orange solid (0.146 g, 66%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-phenylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2556)

Isolated as an almost white foamed substance (0.0911 g, 82%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-phenylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2557)

Isolated as an almost white foamed substance (0.094 g, 85%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,5-difluorophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2558)

Isolated as an almost white foamy substance (0.0796 g, 72%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,4-difluorophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2559)

Isolated as an almost white foamed substance (0.089 g, 80%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(3,4-dichlorophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2560)

Isolated as a light brown foam (0.072 g, 60%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,5-dichlorophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2561)

Isolated as a light brown foam (0.095 g, 79%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-fluoro-2-methylphenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2562)

Isolated as a light brown foam (0.080 g, 71%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-methoxyphenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2563 )

Isolated as a light brown foam (0.039 g, 35%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-(trifluoromethoxy)phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamide (F2564)

Isolated as a light brown foam (0.082 g, 63%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-(perfluoroethoxy)phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamide (F2565)

Isolated as a light brown foam (0.105 g, 79%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(4-(trifluoromethyl)phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamide (F2571)

Isolated as an almost white foamy substance (0.048 g, 38%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(3-(trifluoromethyl)phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamide (F2572)

Isolated as a light brown foam (0.054 g, 43%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2-(trifluoromethyl)phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamide (F2573)

Isolated as a light brown foam (0.107 g, 86%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-(m-tolyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2574)

Isolated as an almost white foamed substance (0.103 g, 88%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(p-tolyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2575 )

Isolated as a light brown foam (0.030 g, 26%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2-cyanophenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2576 )

Isolated as a light yellow foam (0.058 g, 50%).

Example 29: Preparation of trans-N-(3-(2-acetylhydrazine-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2514)

To a solution of trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride (F2567) (0.25 g, 0.498 mmol ) in tetrahydrofuran (5 ml), triethylamine (0.15 g, 1.49 mmol) and acetic anhydride (0.061 g, 0.598 mmol) were added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (20 ml) and washed with water (2×10 ml) and brine (5 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography eluting with 40-60% ethyl acetate/petroleum ether gave the title compound as a white solid (0.08 g, 32%).

The following compounds were prepared using a procedure similar to that described in example 29:

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,2,2-trifluoroacetyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2515)

Isolated as a white solid (0.06 g, 21%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoropropanoyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2516)

Isolated as a white solid (0.06 g, 26%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,2-difluorocyclopropane-1-carbonyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane -1-carboxamide (F2517)

Isolated as a white solid (0.07 g, 31%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(1-cyanocyclopropane-1-carbonyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2518)

Isolated as a white solid (0.07 g, 31%).

trans-N-(3-(2-Benzoylhydrazine-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2519)

Isolated as a white solid (0.15 g, 68%).

trans-N-(3-(2-Acetyl-2-methylhydrazine-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2522)

Isolated as an almost white solid (0.02 g, 10%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-(2,2,2-trifluoroacetyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl )cyclopropane-1-carboxamide (F2523)

Isolated as an almost white solid (0.085 g, 38%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2-cyclopropylacetyl)-2-methylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamide (F2524)

Isolated as an almost white solid (0.04 g, 18%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(1-cyanocyclopropane-1-carbonyl)-2-methylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) cyclopropane-1-carboxamide (F2525)

Isolated as an almost white solid (0.11 g, 50%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(dimethylglycyl)-2-methylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide ( F2526)

Isolated as an almost white solid (0.11 g, 50%).

trans-N-(3-(2-Benzoyl-2-methylhydrazine-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2527)

Isolated as an almost white solid (0.12 g, 48%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2-cyclopropylacetyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2528 )

Isolated as a white solid (0.11 g, 50%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2-methoxyacetyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2529 )

Isolated as an almost white solid (0.09 g, 42%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(dimethylglycyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2530)

Isolated as an almost white foamy substance (0.06 g, 25%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-picolinoylhydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2531)

Isolated as an almost white solid (0.055 g, 26%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoro-2-(trifluoromethyl)propanoyl)hydrazine-1-carbonyl)phenyl)-3-(3, 5-dichlorophenyl)cyclopropane-1-carboxamide (F2532)

Isolated as an almost white solid (0.04 g, 16%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-methyl-2-(3,3,3-trifluoropropanoyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl )cyclopropane-1-carboxamide (F2533)

Isolated as an almost white solid (0.085 g, 38%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,2-difluorocyclopropane-1-carbonyl)-2-methylhydrazine-1-carbonyl)phenyl)-3-(3,5- dichlorophenyl)cyclopropane-1-carboxamide (F2534)

Isolated as an almost white solid (0.065 g, 29%).

Example 30: Preparation of trans-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)-N-(2,2,2-trifluoroethyl) )hydrazine-1-carboxamide (F2535)

To a solution of trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride (F2567) (0.175 g, 0.347 mmol) in tetrahydrofuran (4 ml), triethylamine (0.105 g, 1.04 mmol) and 1,1,1-trifluoro-2-isocyanatoethane (0.052 g, 0.417 mmol) were added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (20 ml) and washed with water (2×10 ml) and brine (5 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography eluting with 40-60% ethyl acetate/petroleum ether gave the title compound as an off-white solid (0.10 g, 48%).

The following compounds were prepared using a procedure similar to that described in example 30:

trans-2-(2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)-N-isopropylhydrazine-1-carboxamide (F2536)

Isolated as an almost white solid (0.13 g, 61%).

trans-2-(2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)-N-phenylhydrazine-1-carboxamide (F2537)

Isolated as an almost white solid (0.06 g, 26%).

trans-2-(2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)-N-(cyclopropylmethyl)hydrazine-1-carboxamide (F2538)

Isolated as an almost white solid (0.11 g, 50%).

Example 31: Preparation of trans-2,2-dichloro-N-(4-chloro-3-(2-((2,2,2-trifluoroethyl)carbamothioyl)hydrazine-1-carbonyl)phenyl)-3-(3, 5-dichlorophenyl)cyclopropane-1-carboxamide (F2539)

To a solution of trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride (F2567) (0.190 g, 0.377 mmol) in tetrahydrofuran (4 ml), triethylamine (0.114 g, 1.13 mmol) and 1,1,1-trifluoro-2-isothiocyanatoethane (0.064 g, 0.452 mmol) were added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (20 ml) and washed with water (2×10 ml) and brine (5 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography eluting with 40-60% ethyl acetate/petroleum ether gave the title compound as an off-white solid (0.08 g, 35%).

The following compounds were prepared using a procedure similar to that described in example 31:

trans-2,2-Dichloro-N-(4-chloro-3-(2-(isopropylcarbamothioyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2540)

Isolated as an almost white solid (0.06 g, 27%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(phenylcarbamothioyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2541)

Isolated as an almost white solid (0.07 g, 26%).

Example 32: Preparation of trans-ethyl 2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)hydrazine-1-carboxylate (F2542)

To a solution of trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride (F2567) (0.175 g, 0.347 mmol) in tetrahydrofuran (4 ml) was added triethylamine (0.114 g, 1.13 mmol) and ethyl chloroformate (0.049 g, 0.452 mmol) at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (20 ml) and washed with water (2×10 ml) and brine (5 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography eluting with 40-60% ethyl acetate/petroleum ether gave the title compound as an off-white solid (0.04 g, 19%).

The following compounds were prepared using a procedure similar to that described in Example 32:

trans-Trifluoromethyl-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)hydrazine-1-carboxylate (F2543)

Isolated as an almost white solid (0.05 g, 21%).

Example 33: Preparation of trans-2,2-dichloro-N-(4-chloro-3-(2-(4-fluorobenzyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2570)

Trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2567) (0.10) was added to a 50 ml flask. g, 0.214 mmol), methanol (3 ml) and 4-fluorobenzaldehyde (0.023 ml, 0.214 mmol). The reaction mixture was stirred at room temperature overnight. The solution was concentrated and the residue was purified by column chromatography using a 0-100% ethyl acetate/hexanes gradient to give the imine as a colorless foam. The foam was dissolved in methanol (3 ml) and sodium borohydride (0.081 g, 1.283 mmol) and acetic acid (0.024 ml, 0.428 mmol) were successively added to the solution. The reaction mixture was stirred overnight at room temperature. A saturated aqueous sodium bicarbonate solution (5 ml) was carefully added to the reaction mixture, and the mixture was extracted with ethyl acetate (10 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to give the title compound as a colorless foam (0.065 g, 48%).

The following compounds were prepared using a procedure similar to that described in example 33:

trans-2,2-dichloro-N-(4-chloro-3-(2-(4,4-difluorocyclohexyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2569)

Isolated as an almost white foamed substance (0.030 g, 22%).

Example 34: Preparation of trans-2,2-dichloro-N-(4-chloro-3-(2-(2,4-difluorobenzyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane -1-carboxamide (F2547)

To a solution of trans-2,2-dichloro-N-(4-chloro-3-(2-(2,4-difluorobenzylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F3004) (0.20 g, 0.34 mmol) in ethanol (6 ml) added acetic acid (0.1 ml) and sodium cyanoborohydride (0.107 g, 1.7 mmol) at 0°C and the reaction mixture stirred at room temperature for 16 hours. The reaction mixture was poured into water (10 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography using 20-40% ethyl acetate/petroleum ether as eluent gave the title compound as an off-white solid (0.155 g, 77%).

The following compounds were prepared using a procedure similar to that described in example 34:

trans-2,2-Dichloro-N-(4-chloro-3-(2-(1-phenylethyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2548 )

Isolated as an almost white solid (0.175 g, 70%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(cyclopropylmethyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2549)

Isolated as an almost white solid (0.085 g, 40%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoropropyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2550)

Isolated as an almost white solid (0.080 g, 35%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(1-methoxypropan-2-yl)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F2551)

Isolated as an almost white solid (0.085 g, 33%).

trans-2,2-Dichloro-N-(4-chloro-3-(1-methyl-2-(3,3,3-trifluoropropyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl )cyclopropane-1-carboxamide (F2552)

Isolated as an almost white solid (0.10 g, 55%).

trans-N-(3-(2-Benzylhydrazine-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2545)

Isolated as an almost white solid (0.100 g, 28%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,5-difluorobenzyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2546)

Isolated as an almost white solid (0.04 g, 32%).

Example 35: Preparation of trans-N-(3-(2-Benzylidenehydrazine-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3001)

To a solution of trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride (F2567) (0.300 g, 0.60 mmol ) in ethanol (8.0 ml) at room temperature, sodium acetate trihydrate (0.099 g, 1.2 mmol) was added and the mixture was stirred for 15 min. Benzaldehyde (0.19 g, 1.8 mmol) was added followed by acetic acid (0.1 ml) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water (10 ml) and extracted with ethyl acetate (2× 10 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography using 20-40% ethyl acetate/petroleum ether as eluent gave the title compound as a pale brown solid (0.110 g, 35%).

The following compounds were prepared using a procedure similar to that described in example 35:

trans-2,2-Dichloro-N-(4-chloro-3-(2-(pyridin-2-ylmethylene)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3002)

Isolated as an almost white solid (0.125 g, 33%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,5-difluorobenzylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3003)

Isolated as an almost white solid (0.13 g, 34%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(2,4-difluorobenzylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3004)

Isolated as an almost white solid (0.105 g, 32%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(1-phenylethylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3005 )

Isolated as an almost white solid (0.100 g, 38%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(thiazol-2-ylmethylene)hydrazin-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3006)

Isolated as a pale yellow solid (0.080 g, 30%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(cyclopropylmethylene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3007)

Isolated as a pale yellow solid (0.100 g, 30%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoropropylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -carboxamide (F3008)

Isolated as an almost white solid (0.300 g, 40%).

trans-2,2-Dichloro-N-(4-chloro-3-(2-(propan-2-ylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3010)

Isolated as an almost white foamed substance (0.05 g, 41%).

Example 36: Preparation of trans-2,2-dichloro-N-(4-chloro-3-(1-methyl-2-(3,3,3-trifluoropropylidene)hydrazine-1-carbonyl)phenyl)-3-(3 ,5-dichlorophenyl)cyclopropane-1-carboxamide (F3009)

To a solution of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (0.50 g, 1.10 mmol) in dichloromethane (10 ml), N,N-dimethylformamide (3 drops) and oxalyl chloride (0.14 ml, 1.66 mmol) were added sequentially at 0°C, and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was then concentrated at reduced pressure (the bath temperature was maintained at 30-35°C). The acid chloride was dissolved in dichloromethane (6 ml) and added to a solution of 1-methyl-2-(3,3,3-trifluoropropylidene)hydrazine (C220) (0.600 g (crude)) and triethylamine (0.46 ml, 3.3 mmol) in dichloromethane (10 ml) at 0°C. The reaction mixture was stirred at room temperature for 10 hours. The reaction mixture was diluted with dichloromethane (20 ml) and washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography using 20-40% ethyl acetate/petroleum ether as eluent gave the title compound as a pink solid (0.320 g, 50%).

Example 37: Preparation of trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride (F2567)

To a solution of trans-tert-butyl-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)hydrazine-1-carboxylate (F2566) ( 1.00 g, 1.77 mmol) in dichloromethane (10 ml) was added 4 M HCl in 1,4-dioxane (5 ml) at 0°C and the reaction mixture was stirred at 20°C for 16 hours. The reaction mixture was concentrated at reduced pressure. The residue was triturated with diethyl ether. and the resulting solid was filtered and dried in vacuo. The title compound was isolated as an almost white solid (0.600 g, 68%).

The following compounds were prepared using a procedure similar to that described in example 37:

trans-2,2-Dichloro-N-(4-chloro-3-(2-methylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride (F2521)

Isolated as a white solid (2.6 g, 78%).

Example 38: Preparation of trans-tert-butyl 2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)hydrazine-1-carboxylate (F2566 )

To a solution of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12) (7.60 g, 16.9 mmol) in dichloromethane (200 ml) tert-butylhydrazine carboxylate (2.20 g, 16.9 mmol) and 3-(((ethylimino)methylene) amino)-N,N-dimethylpropan-1-amine hydrochloride (EDC; 3.20 g, 16) were added .9 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was taken into water and extracted with ethyl acetate (2×200 ml). The organic layer was washed with saturated aqueous sodium bicarbonate (50 ml), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography eluting with 10% ethyl acetate in petroleum ether provided the title compound as an off-white solid (1.20 g, 22%).

The following compounds were prepared using a procedure similar to that described in example 38:

trans-tert-Butyl-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)-1-methylhydrazine-1-carboxylate (F2520)

Isolated as an almost white solid (2.6 g, 78%).

Example 39: Preparation of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzoic acid (C1)

Step 1: To a suspension of (1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid (C93) (0.445 g, 1.57 mmol) in 1.2 -dichloroethane (10 ml) was added 2 drops of N,N-dimethylformamide, then oxalyl dichloride (1.992 g, 15.7 mmol) was added dropwise and the resulting light yellow mixture was stirred at room temperature for 16 hours. The solvent and excess oxalyl dichloride were evaporated at under reduced pressure and the resulting golden oil was dissolved in 1,2-dichloroethane (10 ml) and concentrated (repeated twice) to give the acid chloride intermediate as a golden oil which was used without purification.

Step 2: To a mixture of 5-amino-2-chloro-3-fluorobenzoic acid (C196) (0.357 g, 1.88 mmol) and triethylamine (0.334 g, 3.30 mmol) in 1,2-dichloroethane (15 ml) a solution of freshly prepared acid chloride, (1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carbonyl chloride (0.474 g, 1.57 mmol) was added dropwise at 0°C and the resulting green solution was stirred under a nitrogen atmosphere while warming to room temperature for 1 hour and then stirred at room temperature for 3 hours. The reaction mixture was concentrated to give a dark oil and the oil was partitioned between ethyl acetate (100 ml) and 1 N. aqueous solution of hydrogen chloride (25 ml). The phases were separated and the aqueous layer was extracted with additional ethyl acetate (25 ml). The combined organic extracts were washed with brine (50 ml), dried over sodium sulfate, filtered and concentrated to give an amber oil. The oil was dissolved in a minimal amount of ethyl acetate and adsorbed onto ^Celite® . The adsorbed material was purified by automatic reverse phase chromatography using a gradient of 10-100% acetonitrile in water as eluent to give the title compound as a light tan solid (0.398 g, 55%): m.p. 205 - 208°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.78 (s, 1H), 11.12 (s, 1H), 7.92 (d, J = 10.8 Hz, 2H), 7.71 (dd, J = 7.1, 1.8 Hz, 1H), 7.54 - 7.39 (m, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 ( d, J = 8.4 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -111.57, -117.24; HRMS-ESI (m/z) [M ⁺ ] ⁺ calculated for C ₁₇ H ₉ Cl ₄ F ₂ NO ₃ , 452.9305; found, 452.9303.

The following compounds were prepared using a procedure similar to that described in example 39:

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzoic acid (C2)

Isolated as a light yellowish-brown solid (0.740 g, 50%): m.p. 186 - 189°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.78 (s, 1H), 11.12 (s, 1H), 7.92 (d, J = 10.6 Hz, 2H), 7.71 (d, J = 7.1 Hz, 1H), 7.57 - 7.38 (m, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -111.54, -117.23; ESIMS m/z 454 ([MH] ^- ).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-3-methylbenzoic acid (C3)

Isolated as a tan solid (1.229 g, 87%): m.p. 228 - 235°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.25 (s, 1H), 10.76 (s, 1H), 7.99 (dd, J = 6.1, 2.8 Hz, 1H) , 7.75 (dd, J = 6.2, 2.8 Hz, 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.53 - 7.40 (m , 2H), 3.56 (d, J = 8.4 Hz, 1H), 3.39 (d, J = 8.5 Hz, 1H), 2.27 (d, J = 2.1 Hz, 3H ); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.31, -120.17; ESIMS m/z 434 ([MH] ^- ).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-methylbenzoic acid (C4)

Isolated as a light yellowish-brown solid (0.875 g, 69%): m.p. 218 - 222°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.42 (s, 1H), 10.84 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.80 - 7.63 (m, 2H), 7.59 - 7.33 (m, 2H), 3.56 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H), 2.38 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.29; ESIMS m/z 450 ([MH] ^- ).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methylbenzoic acid (C5)

Isolated as a tan solid (0.780 g, 63%): m.p. 219 - 225°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.34 (s, 1H), 10.90 (s, 1H), 8.02 (d, J = 2.3 Hz, 1H), 7.96 (d, J = 2.3 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.52 - 7.40 (m, 2H), 3.57 ( d, J = 8.4 Hz, 1H), 3.40 (d, J = 8.5 Hz, 1H), 2.49 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.29; ESIMS m/z 450 ([MH] ^- ).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-(trifluoromethyl)benzoic acid (C6)

Isolated as an almost white solid (0.800 g, 47%): m.p. 216 - 219°C; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.00 (s, 1H), 11.23 (s, 1H), 8.33 - 8.23 (m, 2H), 7.72 (dd, J = 7.1, 1.9 Hz, 1H), 7.56 - 7.39 (m, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -61.39, -117.21; ESIMS m/z 503 ([M-2H] ^- ).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methoxybenzoic acid (C7)

Isolated as a tan solid (0.760 g, 50%): m.p. 183 - 186°C; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.28 (s, 1H), 10.91 (s, 1H), 7.93 - 7.78 (m, 1H), 7.78 - 7, 66 (m, 2H), 7.47 (d, J = 9.0 Hz, 2H), 3.83 (s, 3H), 3.57 (d, J = 8.4 Hz, 1H), 3, 40 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.29, -128.27; ESIMS m/z 450 ([MH] ^- ).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzoic acid (C8)

Isolated as a tan solid (0.82 g, 48%): m.p. 217 - 224°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.70 (s, 1H), 11.01 (s, 1H), 8.13 (dd, J = 6.1, 2.8 Hz, 1H) , 8.06 (dd, J = 5.8, 2.7 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.54 - 7.38 (m , 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.25, -119.42; ESIMS m/z 453 ([MH] ^- ).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzoic acid (C9)

Isolated as a white solid (0.93 g, 57%): m.p. 222 - 226°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 8.05 - 7.87 (m, 2H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.46 (dd, J = 8.0, 4.1 Hz, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8 .5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.26, -135.55 (d, J = 22.4 Hz), -142.67 (d, J = 22.4 Hz); ESIMS m/z 437 ([MH] ^- ).

trans-3-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-methoxybenzoic acid (C10)

Isolated as a light tan solid (0.380 g, 22%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.38 (s, 1H), 10.91 (s, 1H), 8 .03 (d, J = 2.7 Hz, 1H), 7.90 (d, J = 2.7 Hz, 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H) , 7.54 - 7.38 (m, 2H), 3.81 (s, 3H), 3.57 (d, J = 8.4 Hz, 1H), 3.40 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.28; ESIMS m/z 466 ([MH] ^- ).

trans-5-(2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-3-fluoro-2-methylbenzoic acid (C11)

Isolated as a white solid (0.304 g, 53%): m.p. 210 - 212°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.26 (s, 1H), 10.94 (s, 1H), 7.88 (d, J = 2.2 Hz, 1H), 7.77 (dd, J = 11.8, 2.1 Hz, 1H), 7.70 (dd, J = 7.1, 1.9 Hz, 1H), 7.46 (dd, J = 7.8, 4 .3 Hz, 2H), 3.57 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H), 2.38 (d, J = 2.0 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -114.04, -117.29; HRMS-ESI (m/z) [M ⁺ ] ⁺ calculated for C ₁₈ H ₁₂ Cl ₃ F ₂ NO ₃ , 432.9851; found, 432.9856.

trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C12)

Isolated as a light brown solid (0.421 g, 93%): m.p. 234 - 236°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.47 (s, 1H), 10.90 (s, 1H), 8.16 (d, J = 2.3 Hz, 1H), 7.78 (dd, J = 8.7, 2.4 Hz, 1H), 7.59 (m, 4H), 3.56 (dd, J = 49.8, 8.5 Hz, 2H), 1.09 ( m, 1H); ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 166.26, 165.77, 162.61, 137.57, 137.27, 134.04, 132.18, 131.44, 131.22, 127 .88, 127.66, 126.40, 125.92, 122.88, 121.17, 102.37, 62.11, 38.41, 36.83; ESIMS m/z 454 ([M+H] ⁺ ).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C13)

Isolated as a gray solid (3.80 g, 96%): ^1H NMR (300 MHz, DMSO- _d6 ) δ 13.48 (s, 1H), 10.90 (s, 1H), 8.15 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8, 2.7 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7 .57 - 7.50 (m, 3H), 3.62 (d, J = 8.5 Hz, 1H), 3.49 (d, J = 8.5 Hz, 1H); ESIMS m/z 454 ([M+H] ⁺ ).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C14)

Isolated as a gray solid (3.70 g, 98%): ^1H NMR (300 MHz, DMSO- _d6 ) δ 13.47 (s, 1H), 10.95 (s, 1H), 8.16 (d, J = 2.7 Hz, 1H), 7.82 - 7.73 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.53 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H); ESIMS m/z 454 ([M+H] ⁺ ).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C15)

Isolated as a gray solid (3.60 g, 99%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.44 (s, 1H), 10.91 (s, 1H), 8.16 (d, J = 2.7 Hz, 1H), 7.80 - 7.76 (m, 3H), 7.54 (d, J = 8.7 Hz, 1H), 3.63 (dt, J = 8.5, 0.7 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H); ESIMS m/z 488 ([M+H] ⁺ ).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzoic acid (C16)

Isolated as a gray solid (3.80 g, 99%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.48 (s, 1H), 10.93 (s, 1H), 8.16 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8, 2.7 Hz, 1H), 7.71 (dd, J = 7.2, 2.0 Hz, 1H), 7.53 (d, J = 8.7 Hz, 1H), 7.50 - 7.42 (m, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3, 42 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.29; ESIMS m/z 438 ([M+H] ⁺ ).

Example 40: Preparation of cis/trans-3-(3-bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C17)

Step 1: Preparation of (E/Z)-1-bromo-2,3-difluoro-5-(4-methoxystyryl)benzene. n-butyllithium (2.5 M in hexane) (3.62 ml, 9.05 mmol) was added with stirring to a suspension of (4-methoxybenzyl)triphenylphosphonium chloride (3.79 g, 9.05 mmol) in dry tetrahydrofuran (50 ml ) at -30°C. The resulting heterogeneous dark red mixture was stirred at -25 - -30°C for 30 minutes, then a solution of 3-bromo-4,5-difluorobenzaldehyde (2 g, 9.05 mmol) in anhydrous tetrahydrofuran (5 ml) was added dropwise. . The resulting white solid suspension was stirred at -30°C for a further 2 hours, then allowed to warm to ambient temperature and stirred for a further 12 hours. The reaction was quenched with water (100 ml) and extracted with diethyl ether (3 x 50 ml). The organic extracts were washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated in vacuo on a rotary evaporator. Purification by flash silica gel chromatography provided the title compound as a clear, colorless oil (1.6 g, 54%, approximately 1:1 mixture of E- and Z-stilbenes): EIMS m/z 325.

Step 2: Preparation of 1-bromo-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2,3-difluorobenzene. With stirring, a solution of (E/Z)-1-bromo-2,3-difluoro-5-(4-methoxystyryl)benzene (1.165 g, 3.58 mmol) and tetrabutylammonium hexafluorophosphate(V) (0.139 g, 0.358 mmol) in Powdered sodium hydroxide (1.433 g, 35.8 mmol) and water (200 μL) were added to chloroform (28.7 ml) at 23°C. The resulting mixture was stirred vigorously at 50-55°C for 16 hours. The reaction mixture was diluted with water and extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by silica gel flash column chromatography provided the title compound as a pale yellow oil (1.7 g, 63%, approximately 2:1 cis-:trans-cyclopropanes): EIMS m/z 325

Step 3. Preparation of cis/trans-3-(3-bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid. Ruthenium(III) chloride hydrate (0.047 g, 0.207 mmol) was added to a mixture of crude cis/trans-3-(3-bromo-4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (1, 69 g, 4.14 mmol) with water:ethyl acetate:acetonitrile (2.5:1:1, 90 ml) at 23°C. Sodium periodate (13.29 g, 62.1 mmol) was carefully added in portions at a rate to maintain the temperature below 50°C. The resulting biphasic brown mixture was stirred vigorously at 23°C for 2 hours. The reaction mixture was diluted with water (200 ml) and extracted with ethyl acetate (3×50 ml). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in a minimal amount of acetonitrile and purified by C-18 flash chromatography to give the title compound as a gray solid (0.665 g, 44% Approximately 2:1 trans/cis cyclopropane mixture): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 8.90 (s, 1H), 7.42 - 7.21 (m, 1H), 7.10 (dddd, J = 26.8, 9.3, 6.6, 2.1 Hz, 1H), 3.35 (dd, J = 49.0, 9.6 Hz, 1H), 3.01 - 2.77 (m, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -129.47, -129.53, -130.16, -130.21, -132.59, -132.64, -133.35, -133.41 ; ESIMS m/z 345 ([MH] ^- ).

The following compounds were prepared using a procedure similar to that described in Example 40:

cis/trans-2,2-Dichloro-3-(3,4-dichloro-5-fluorophenyl)cyclopropane-1-carboxylic acid (C18)

Isolated as a gray solid (0.459 g, 44%, approximately 3:1 trans/cis): ^1H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 8.73 (s, 1H), 7.20 (d, J = 1.7 Hz, 1H), 7.14 - 6.91 (m, 1H), 3.36 (dd, J = 51.9, 9.6 Hz, 1H), 2.91 (dd, J = 47.1, 9.6 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -108.55, -109.27; ESIMS m/z 317 ([MH] ^- ).

cis/trans-3-(3-Bromo-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C19)

Isolated as a gray solid (0.260 g, 40%, approximately 2:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 10.43 (s, 1H), 7.88 (dt, J = 13.2, 1.9 Hz, 1H), 7.75 - 7.48 (m, 2H), 3.61 - 3.29 (m, 1H), 2.96 (dd, J = 38, 3, 9.6 Hz, 1H); ESIMS m/z 435 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(3-chloro-2,4-difluorophenyl)cyclopropane-1-carboxylic acid (C20)

Isolated as a gray solid (0.656 g, 35%, approximately 1:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 9.27 (s, 1H), 7.35 (q, J = 7.5 Hz, 1H), 7.11 - 6.90 (m, 1H), 3.33 (dd, J = 104.1, 9.5 Hz, 1H), 3.06 - 2.77 (m, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -111.34, -111.35, -111.40, -111.41, -112.05, -112.06, -113.13, -113.14 ; ESIMS m/z 300 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(3-chloro-2-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C21)

Isolated as a gray solid (0.485 g, 31%, approximately 2:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 9.02 (s, 1H), 7.87 - 7. 61 (m, 1H), 7.39 - 7.23 (m, 1H), 3.60 - 3.19 (m, 1H), 3.14 - 2.85 (m, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.32, -108.88, -110.51; ESIMS m/z 350 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C22)

Isolated as green oil (1.42 g, 66%, approximately 3:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 7.33 (dd, J = 21.3, 6. 3 Hz, 2H), 6.82 (s, 1H), 3.38 (dd, J = 50.6, 9.7 Hz, 1H), 3.04 - 2.82 (m, 1H), 2, 34 (dd, J = 10.0, 2.3 Hz, 3H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -61.53, -118.49, -119.16; ESIMS m/z 330 ([MH] ^- ).

cis/trans-3-(3-Bromo-2,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C23)

Isolated as a gray solid (0.545 g, 51%, approximately 1:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 9.97 (s, 1H), 7.29 (dtt, J = 7.1, 4.4, 2.3 Hz, 1H), 7.00 (dddd, J = 137.6, 8.2, 5.3, 3.5 Hz, 1H), 3.52 - 3.10 (m, 1H), 3.07 - 2.74 (m, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -112.49, -112.53, -114.36, -114.40, -115.73, -115.77, -116.17, -116.21 ; ESIMS m/z 345 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(3,4-dichloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C24)

Isolated as a tan solid (0.295 g, 25%, approximately 2:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 7.71 - 7.45 (m, 2H), 6.48 (s, 1H), 3.38 (dd, J = 62.2, 9.6 Hz, 1H), 2.95 (dd, J = 41.0, 9.6 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -63.01; ESIMS m/z 366 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(4-chloro-3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C25)

Isolated as a gray solid (0.392 g, 33%, approximately 3:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 9.56 (s, 1H), 7.55 - 7, 36 (m, 1H), 7.28 (dd, J = 8.8, 2.0 Hz, 1H), 3.41 (dd, J = 59.6, 9.6 Hz, 1H), 2.95 (dd, J = 46.2, 9.6 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.50, -109.97, -110.78; ESIMS m/z 350 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxylic acid (C26)

Isolated as a gray solid (0.889 g, 48%, approximately 2:1 trans/cis): ¹ H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 9.83 (s, 1H), 7.54 - 6, 93 (m, 2H), 3.34 (dd, J = 50.9, 9.6 Hz, 1H), 2.89 (dd, J = 46.6, 9.6 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -115.34, -115.98; ESIMS m/z 317 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(3-chloro-5-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxylic acid (C27)

Isolated as a gray solid (0.412 g, 35%, approximately 3:1 trans/cis): ^1H NMR (400 MHz, CDCl ₃ CDCl ₃ ) δ 7.81 - 7.69 (m, 1H), 7. 63 - 7.38 (m, 2H), 5.95 (s, 1H), 3.61 - 3.31 (m, 1H), 3.11 - 2.87 (m, 1H); ESIMS m/z 390 ([MH] ^- ).

cis/trans-2,2-Dichloro-3-(perfluorophenyl)cyclopropane-1-carboxylic acid (C28)

Isolated as a white solid (1.44 g, 67%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.19 (s, 1H), 3.30 (d, J = 8.2 Hz, 1H ), 3.09 (d, J = 8.3 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -140.52, -140.54, -140.58, -140.60, -152.14, -152.20, -152.25, -160.82 , -160.84, -160.87, -160.89, -160.93, -160.95; ESIMS m/z 320 ([MH] ^- ).

trans-3-(3-Bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C29)

Isolated as a white foam (1.3 g, 54%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.53 7.42 (m, 1H), 7.35 (d, J = 2.0 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 2.86 (d, J = 8.2 Hz, 1H). ESIMS m/z 376 ([MH] ^- ).

trans-3-(4-Bromo-3,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C30)

Isolated as a white foam (0.6 g, 29%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.29 (d, J = 0.7 Hz, 2H), 3.39 (d, J = 8.2 Hz, 1H), 2.87 (d, J = 8.3 Hz, 1H). ESIMS m/z 376 ([MH] ^- ).

Example 41: Preparation of trans-2,2-dichloro-3-(3-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxylic acid (C31)

Sodium periodate (37.0 g, 0.174 mol) and water (250 ml) were added to a round bottom flask equipped with a magnetic stir bar. Nitrogen was passed through the solution for 15 minutes. (3-((1R,3R)-2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)phenyl)pentafluoro-λ ⁶ -sulfane (C44) (3.7 g, 0.0109 mol) was dissolved in the mixture ethyl acetate (30 ml)/acetonitrile (30 ml) and added to the flask, then ruthenium chloride (0.150 g, 0.00067 mol) was added. The mixture was stirred for 16 hours. The mixture was diluted with dichloromethane (250 ml), filtered through ^Celite® and the filter cake washed with dichloromethane. The filtrate was transferred to a separatory funnel. The organic layer was separated and the aqueous phase was extracted with dichloromethane (4×100 ml). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by reverse phase intermediate performance liquid chromatography (RP-MPLC) using 10-80% acetonitrile/water as eluent gave the title compound (2.0 g, 51%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.76 (d, J = 8.5 Hz, 1H), 7.65 (s, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 3.55 (d, J = 8.3 Hz, 1H), 2.93 (d, J = 8.3 Hz, 1H); ESIMS m/z 358 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 41:

trans-2,2-Dichloro-3-(4-(pentafluoro-λ ⁶ -sulfanyl)phenyl)cyclopropane-1-carboxylic acid (C32)

Isolated as a white powder (2.2 g): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.78 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 8, 4 Hz, 2H), 3.53 (d, J = 8.3 Hz, 1H), 2.93 (d, J = 8.3 Hz, 1H); ESIMS m/z 358 ([M+H] ⁺ ).

trans-2,2-Dichloro-3-(3-iodophenyl)cyclopropane-1-carboxylic acid (C33)

Isolated as a white powder (0.700 g): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.69 (d, J = 7.9 Hz, 1H), 7.62 (s, 1H), 7.29 - 7.21 (m, 1H), 7.12 (t, J = 7.8 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.87 (d, J = 8.3 Hz, 1H); ESIMS m/z 358 ([M+H] ⁺ ).

trans-2,2-Dichloro-3-(4-iodophenyl)cyclopropane-1-carboxylic acid (C34)

Isolated as a white powder (1.2 g): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.72 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8, 2 Hz, 2H), 3.43 (d, J = 8.3 Hz, 1H), 2.85 (d, J = 8.3 Hz, 1H); ESIMS m/z 358 ([M+H] ⁺ ).

trans-3-(3,5-Dichlorophenyl)-2,2-difluorocyclopropane-1-carboxylic acid (C35)

Isolated as an almost white solid (0.640 g, 44%): m.p. 138-142°C; ^1H NMR (400 MHz, CDCl ₃ ) δ 7.34 (t, J = 1.9 Hz, 1H), 7.16 (d, J = 1.8 Hz, 2H), 3.47 (ddd, J = 11.9, 7.8, 4.1 Hz, 1H), 2.75 (ddd, J = 11.1, 7.9, 1.7 Hz, 1H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 170.91, 135.50, 133.88, 128.56, 126.74, 109.91 (dd, J = 295.1, 289.3 Hz), 32 .62 (dd, J = 11.3, 9.2 Hz), 32.07 (t, J = 11.5 Hz); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -132.28 (d, J = 152.7 Hz), -132.84 (d, J = 152.8 Hz); ESIMS m/z 267 ([MH] ^- ).

Example 42: Preparation of trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid (C36)

Ruthenium(III) chloride (0.080 g, 0.39 mmol) was added to a mixture of trans-1,3-dichloro-5-(-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene (C48) with stirring (2.8 g, 7.7 mmol) and sodium periodate (33 g, 160 mmol) with water: ethyl acetate: acetonitrile (8:1:1, 155 ml) at 23°C. The resulting biphasic brown mixture was stirred vigorously at 23°C for 5 hours. The reaction mixture was diluted with water (1000 ml) and extracted with dichloromethane (4×200 ml). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The residue was diluted with sodium hydroxide solution (1 M, 100 ml) and washed with diethyl ether (4 x 50 ml). The pH of the aqueous layer was adjusted to 2 using concentrated hydrochloric acid and extracted with dichloromethane (3×50 ml). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give the title product as a light brown powder (0.78 g, 34%): m.p. 117 - 120°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.38 (br s, 1H), 7.52 - 7.65 (m, 3H), 3.57 (d, J = 8.5 Hz, 1H ), 3.50 (d, J = 8.5 Hz, 1H); IR (thin film) 3083 (s), 3011 (s), 1731 (s), 1590 (w), 1566 (s), 1448 (w), 1431 (m), 1416 (m) cm ^-1 .

The following compounds were prepared using a procedure similar to that described in Example 42:

trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropanecarboxylic acid (C37)

Isolated as a yellow powdery substance (1.5 g, 39%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31 (d, J = 0.7 Hz, 2H), 3.40 (d, J = 8.2 Hz, 1H), 2.86 (d, J = 8.3 Hz, 1H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 171.05, 134.55, 132.44, 131.75, 128.89, 61.18, 39.26, 37.14; ESIMS m/z 333 ([MH] ^- ).

trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropanecarboxylic acid (C38)

Isolated as a pale yellow solid (3.2 g, 51%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.47 (d, J = 8.3 Hz, 1H), 7.37 (d , J = 1.6 Hz, 1H), 7.12 (ddd, J = 8.3, 2.1, 0.6 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H) , 2.86 (d, J = 8.3 Hz, 1H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 171.52, 132.91, 132.76, 132.29, 130.66, 130.62, 128.02, 61.48, 39.65, 37.13 ; ESIMS m/z 298 ([MH] ^- ).

trans-2,2-Dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropanecarboxylic acid (C39)

Isolated as an almost white solid (0.73 g, 28%): m.p. 113 - 115°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.39 (br s, 1H), 7.91 (s, 1H), 7.86 (s, 1H), 7.84 (s, 1H), 3.69 - 3.60 (m, 2H); ESIMS m/z 333 ([MH] ^- ).

trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarboxylic acid (C40)

Isolated as an almost white solid (1.0 g, 53%): m.p. 121 - 123°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.35 (br s, 1H), 7.71 (dd, J = 2.0, 7.2 Hz, 1H), 7.53 - 7.35 (m, 2H), 3.50 - 3.41 (m, 2H); ESIMS m/z 281 ([MH] ^- ).

trans-2, 2-Dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C41)

Isolated as an almost white solid (2.6 g, 63%): ¹ H NMR (300 MHz, CDCl ₃ ) no COOH signal δ 7.49 (s, 1H), 7.38 (s, 1H), 7 .30 (s, 1H), 6.63 (t, J = 56.0 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H), 2.91 (d, J = 8, 0 Hz, 1H); ¹⁹ F NMR (282.2 MHz, CDCl ₃ ) δ -112.04; ESIMS m/z 313 ([MH] ^- ).

trans-2,2-Dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C42)

Isolated as an off-white solid (6.2 g, 69%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.5 (br s, 1H), 7.55 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 6.95 (t, J = 54.8 Hz, 1H), 3.50 (d , J = 8.4 Hz, 1H), 2.91 (d, J = 8.4 Hz, 1H); ¹⁹ F NMR (376.2 MHz, CDCl ₃ ) δ -115.52; ESIMS m/z 313 ([MH] ^- ).

trans-2,2-Dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclopropane-1-carboxylic acid (C43)

Isolated as an almost white solid (6.0 g, 77%): ¹ H NMR (400 MHz, CDCl ₃ ) no COOH signal δ 7.49 (d, J = 6.0 Hz, 1H), 7.40 (br s, 1H), 7.17 (t, J = 9.2 Hz, 1H), 6.90 (t, J = 54.8 Hz, 1H), 3.49 (d, J = 8.0 Hz, 1H), 2.89 (d, J = 8.4 Hz, 1H); ¹⁹ F NMR (376.2 MHz, CDCl ₃ ) δ -114.47, -119.69; ESIMS m/z 297 ([MH] ^- ).

Example 43: Preparation of trans-(3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)phenyl)pentafluoro-λ ⁶ -sulfane (C44)

(E)-pentafluoro(3-(4-methoxystyryl)phenyl)-λ ⁶ -sulfane (C57) (4.13 g, 0.0123 mol) and benzyltriethylammonium chloride (0. 6 g, 0.00264 mol). Chloroform (150 ml) was added, followed by an ice-cold solution of sodium hydroxide (20 g, 0.5 mol) in water (34 ml). The biphasic mixture was stirred at 40°C for 16 hours. The reaction mixture was cooled to 23°C, water (100 ml) was added, and the reaction mixture was transferred to a separatory funnel. The organic layer was separated and the aqueous phase was extracted with chloroform (2×50 ml). The combined organic layers were washed with brine (50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography using 0-15% ethyl acetate/hexane as eluent gave the title compound (3.8 g, 75%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.75 (m, 2H) , 7.58 - 7.46 (m, 2H), 7.30 (d, J = 8.6 Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 3.84 ( s, 3H), 3.20 (s, 2H); ESIMS m/z 419 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 43:

trans-(4-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)phenyl)pentafluoro-λ ⁶ -sulfane (C45)

Isolated as a white powder (4.0 g): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.75 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8, 4 Hz, 2H), 7.30 - 7.23 (m, 2H), 6.91 (d, J = 8.7 Hz, 2H), 3.81 (s, 3H), 3.21 - 3, 08 (m, 2H); ESIMS m/z 419 ([M+H] ⁺ ).

trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-iodobenzene (C46)

Isolated as a white powder (5.7 g): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.73 (s, 1H), 7.68 (d, J = 7.9 Hz, 1H), 7 .35 (d, J = 7.7 Hz, 1H), 7.31 - 7.25 (m, 2H), 7.13 (t, J = 7.8 Hz, 1H), 6.94 (d, J = 8.7 Hz, 2H), 3.84 (s, 3H), 3.13 (m, 2H); ESIMS m/z 419 ([M+H] ⁺ ).

trans-1-(2,2-Dichloro-3-(4-iodophenyl)cyclopropyl)-4-methoxybenzene (C47)

Isolated as a white powder (4.0 g): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.72 (d, J = 8.4 Hz, 2H), 7.29 (m, 2H), 7 .12 (d, J = 8.1 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H), 3.11 (m, 2H); ESIMS m/z 419 ([M+H] ⁺ ).

Example 44: Preparation of trans-1,3-dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene (C48)

An aqueous solution of sodium hydroxide (50%, 6.8 ml, 130 mmol) was added with stirring to a solution of (E)-1,3-dichloro-5-(4-methoxystyryl)benzene (C61) (2.4 g, 8. 6 mmol) and N-benzyl-N,N-diethylethanamine chloride (0.20 g, 0.86 mmol) in chloroform (14 ml, 170 mmol) at 23°C. The resulting biphasic, dark brown mixture was stirred vigorously at 23°C for 24 hours. The reaction mixture was diluted with water (200 ml) and extracted with dichloromethane (2×100 ml). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give the title product as a brown oil (2.8 g, 90%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.34 (t, J = 1, 8 Hz, 1H), 7.21 - 7.30 (m, 4H), 6.93 (m, 2H), 3.83 (s, 3H), 3.14 (d, J = 8.5 Hz, 1H), 3.08 (d, J = 8.5 Hz, 1H); IR (thin film) 3075 (w), 2934 (w), 2836 (w), 1724 (w), 1640 (w), 1609 (m), 1584 (m), 1568 (s), 1513 (s) cm ^-1 .

The following compounds were prepared using a procedure similar to that described in Example 44:

trans-1,2,3-Trichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene (C49)

Isolated as a dark foam (4.7 g, 100%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.40 (d, J = 0.6 Hz, 2H), 7.29 - 7.22 (m, 2H), 6.96 - 6.89 (m, 2H), 3.83 (s, 3H), 3.12 (d, J = 8.8 Hz, 1H), 3.06 (d, J = 8.7 Hz, 1H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 159.46, 135.08, 134.23, 130.91, 129.85, 129.16, 125.42, 114.02, 64.67, 55.32 , 39.62, 38.48.

trans-1,2-Dichloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene (C50)

Isolated as an orange-red oil (7.6 g, 99%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.47 (d, J = 4.9 Hz, 1H), 7.45 (bs, 1H), 7.30 - 7.23 (m, 2H), 7.21 (dd, J = 8.2, 1.9 Hz, 1H), 6.96 - 6.90 (m, 2H), 3 .83 (s, 3H), 3.11 (apparent q, J = 8.8 Hz, 2H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 159.39, 134.90, 132.62, 131.99, 130.90, 130.40, 129.90, 128.33, 125.81, 113.98 , 64.94, 55.33, 39.52, 38.75.

trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-(difluoromethyl)benzene (C51)

Isolated as a yellow liquid (11.5 g, 69%): ¹ H NMR (300 MHz, CDCl ₃ ): δ 7.47 (s, 2H), 7.39 (s, 1H), 7.28 (d , J = 8.7 Hz, 2H), 6.93 (d, J = 8.7 Hz, 2H), 6.64 (t, J = 56.1 Hz, 1H), 3.83 (s, 3H ), 3.16 (q, J = 8.7 Hz, 2H).

trans-1-Chloro-4-(2, 2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-(difluoromethyl)benzene (C52)

Isolated as a pale yellow solid (10.7 g, 83%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.65 (s, 1H), 7.46 - 7.41 (m, 2H) , 7.28 (d, J = 8.4 Hz, 2H), 7.10 - 6.83 (m, 3H), 3.83 (s, 3H), 3.18 - 3.13 (m, 2H ).

trans-4-(2, 2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-(difluoromethyl)-1-fluorobenzene (C53)

Isolated as an off-white solid (10.0 g, 55%): ESIMS m/z 374 ([M+H] ⁺ ).

trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-(trifluoromethyl)benzene (C54)

Isolated as a brown solid (4.0 g, 74%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.64 (s, 1H), 7.45 (s, 1H), 7.42 (s , 1H), 7.26 (d, J = 9.0 Hz, 2H), 6.93 (d, J = 9.0 Hz, 1H), 3.83 (s, 3H), 3.15 - 3 .05 (m, 2H); ESIMS m/z 395 ([M+H] ⁺ ).

trans-2-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-fluorobenzene (C55)

Isolated as a brown liquid (2.0 g, 58%): ESIMS m/z 345 ([M+H] ⁺ ).

Example 45: Preparation of trans-1,3-dichloro-5-(2,2-difluoro-3-(4-methoxyphenyl)cyclopropyl)benzene (C56)

(E)-1,3-Dichloro-5-(4-methoxystyryl)benzene (C61) (1.5 g, 5.4 mmol) was dissolved in tetrahydrofuran (10 ml) in a 25 ml microwave-safe vessel. Trimethyl(trifluoromethyl)silane (3.8 g, 26.9 mmol) and sodium iodide (0.81 g, 5.4 mmol) were added and the sealed vessel was heated in a microwave oven at 85°C for 1 hour. Vessel pressure was dropped using a needle and analysis of an aliquot by ¹ H NMR spectroscopy indicated a conversion of approximately 20%. Additional trimethyl(trifluoromethyl)silane (7.2 g, 54 mmol) and sodium iodide (0.56 g, 3.8 mmol) were added and the mixture was heated in a microwave oven at 110°C for 8 hours. Subsequent analysis of the aliquot using ¹ H NMR spectroscopy indicated complete conversion with little degradation. The reaction mixture was partitioned between ethyl acetate and saturated sodium chloride solution, the layers were separated and the organic phase was dried over sodium sulfate. Filtration and concentration gave the product as a brown oil (1.8 g, 100%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.30 (t, J = 1.9 Hz, 1H), 7.25 - 7.19 (m, 4H), 6.93 - 6.88 (m, 2H), 3.82 (s, 3H), 2.97 (q, J = 7.8 Hz, 1H), 2.88 (q, J = 7.6 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -133.89; EIMS m/z 329.

Example 46: Preparation of (E)-pentafluoro(3-(4-methoxystyryl)phenyl)-λ ⁶ -sulfane (C57)

A flame-dried round-bottom flask equipped with a magnetic stir bar was purged with nitrogen. Potassium tert-butoxide (0.55 g, 0.0049 mol), 18-crown-6 (0.2 g, 0.00076 mol) and tetrahydrofuran (20 ml) were added. The suspension was cooled to 5°C. 3-(Pentafluorothio)benzaldehyde (0.8, 0.00345 mol) and diethyl (4-methoxybenzyl)phosphonate (1.16 g, 0.00449 mol) were dissolved in tetrahydrofuran (4 ml) and added to the above suspension for 15 minutes. During addition, the internal temperature did not exceed 8°C. The reaction mixture was heated at 23°C for 30 minutes and then heated at 50°C for 4 hours. The reaction mixture was concentrated under reduced pressure. Water (100 ml) and methyl tert-butyl ether (MTBE; 100 ml) were added. The organic layer was separated and the aqueous phase was extracted with MTBE (2×75 ml). The combined organic layers were washed with brine (75 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography using 0-15% ethyl acetate/hexane as eluent gave the title compound as an off-white solid (0.85 g, 73%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7. 84 (s, 1H), 7.64 - 7.56 (m, 2H), 7.47 (d, J = 8.7 Hz, 2H), 7.42 (t, J = 8.0 Hz, 1H ), 7.11 (d, J = 16.3 Hz, 1H), 7.02 - 6.86 (m, 3H), 3.84 (s, 3H); ESIMS m/z 337 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 46:

(E)-Pentafluoro(4-(4-methoxystyryl)phenyl)-λ ⁶ -sulfane (C58)

Isolated as a white powdery substance (3.7 g 70%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.71 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 16.3 Hz, 1H), 7.01 - 6.87 (m, 3H), 3.85 (s, 3H); ESIMS m/z 337 ([M+H] ⁺ ).

(E)-1-Iodo-3-(4-methoxystyryl)benzene (C59)

Isolated as a white powder (5.3 g 91%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.85 (s, 1H), 7.55 (d, J = 7.8 Hz, 1H) , 7.45 - 7.41 (m, 3H), 7.09 - 7.02 (m, 2H), 6.91 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 16.3 Hz, 1H), 3.84 (s, 3H); ESIMS m/z 337 ([M+H] ⁺ ).

(E)-1-Iodine-4-(4-methoxystyryl)benzene (C60)

Isolated as a white powdery substance (3.3 g 94%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.66 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.7 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 16.3 Hz, 1H), 6.94 - 6.83 (m, 3H), 3.83 (s, 3H); ESIMS m/z 337 ([M+H] ⁺ ).

Example 47: Preparation of (E)-1,3-dichloro-5-(4-methoxystyryl)benzene (C61)

Powdered sodium methoxide (98%, 0.63 g, 11 mmol) was added with stirring to a solution of 3,5-dichlorobenzaldehyde (2.0 g, 11 mmol) and diethyl 4-methoxybenzylphosphonate (2.0 ml, 11 mmol) in dry N,N-dimethylformamide (38 ml) at 23°C. The resulting heterogeneous dark blue mixture was heated at 80°C to give a dark brown mixture and stirred for 24 hours. The cooled reaction mixture was diluted with water (500 ml) and extracted with diethyl ether (3×100 ml). The combined organic layers were diluted with hexane (150 ml) and washed with water (300 ml). The organic layer was dried over magnesium sulfate, filtered and concentrated to give the title product as a light brown oil (2.4 g, 75%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.44 (m, 2H), 7.34 (d, J = 2 Hz, 2H), 7.20 (t, J = 2 Hz, 1H), 7.06 (d, J = 16.5 Hz, 1H), 6.91 (m, 2H), 6.82 (d, J = 16.5 Hz, 1H), 3.84 (s, 3H); IR (thin film) 2934 (w), 2835 (w), 1724 (w), 1637 (w), 1605 (m), 1581 (m), 1558 (m), 1511 (s) cm ^-1 .

The following compounds were prepared using a procedure similar to that described in Example 47:

(E)-1,2,3-Trichloro-5-(4-methoxystyryl)benzene (C62)

Isolated as an almost white solid (3.7 g, 31%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.49 - 7.46 (m, 2H), 7.47 - 7.39 (m , 2H), 7.04 (d, J = 16.3 Hz, 1H), 6.93 - 6.89 (m, 2H), 6.78 (d, J = 16.3 Hz, 1H), 3 .84 (s, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 159.46, 135.08, 134.23, 130.91, 129.85, 129.16, 125.42, 114.02, 64.67, 55.32 , 39.62, 38.48; EIMS m/z 313 ([M] ⁺ ).

(E)-1,2-Dichloro-4-(4-methoxystyryl)benzene (C63)

Isolated as an almost white solid (6.0 g, 53%): m.p. 91 - 94°C; ^1H NMR (400 MHz, CDCl ₃ ) δ 7.56 (d, J = 2.0 Hz, 1H), 7.46 - 7.42 (m, 2H), 7.39 (d, J = 8, 4 Hz, 1H), 7.29 (dd, J = 8.4, 2.1 Hz, 1H), 7.04 (d, J = 16.2 Hz, 1H), 6.93 - 6.88 ( m, 2H), 6.85 (d, J = 16.3 Hz, 1H), 3.84 (s, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 159.75, 137.86, 132.72, 130.58, 130.49, 130.12, 129.33, 127.96, 127.77, 125.37 , 123.98, 114.24, 55.35; EIMS m/z 279 ([M] ⁺ ).

(E)-1-Chloro-3-(4-methoxystyryl)-5-(trifluoromethyl)benzene (C64)

Isolated as an off-white solid (4.3 g, 58%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.62 (s, 1H), 7.58 (s, 1H), 7.48 - 7.42 (m, 3H), 7.12 (d, J = 16.2 Hz, 1H), 6.95 - 6.85(m, 3H), 3.84 (s, 3H); ESIMS m/z 313 ([M+H] ⁺ ).

(E)-2-Bromo-1,3-dichloro-5-(4-methoxystyryl)benzene (C65)

Isolated as an off-white solid (2.8 g, 40%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.46 (s, 2H), 7.43 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 13.5 Hz, 1H), 6.90 (d, J = 9.0 Hz, 1H), 6.73 (d, J = 13.5 Hz, 1H) , 3.84 (s, 3H); ESIMS m/z 358 ([M+H] ⁺ ).

(E)-2-Chloro-1-fluoro-4-(4-methoxystyryl)benzene (C66)

Isolated as an almost white solid (6.0 g, 72%): ESIMS m/z 263 ([M+H]⁺).

Example 48: Preparation of (E)-1,3-dichloro-2-fluoro-5-(4-methoxystyryl)benzene (C67)

With stirring, a mixture of 5-bromo-1,3-dichloro-2-fluorobenzene (2.00 g, 8.20 mmol), 1-methoxy-4-vinylbenzene (1.32 g, 9.80 mmol) and triethylamine (20 ml) were degassed under argon for 5 min. Palladium(II) acetate (0.0368 g, 0.164 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (0.181 g, 0.328 mmol) were added and the reaction mixture was heated at 90°C for 16 h. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by flash column chromatography gave the title compound as an off-white solid (1.60 g, 67%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.41 (d, J = 8.8 Hz, 2H), 7.31 (s, 1H), 7.37 (s, 1H), 6.96 (d, J = 16.0 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 16.0 Hz, 1H), 3.84 (s, 3H); ESIMS m/z 297 ([M+H] ⁺ ).

Example 49: Preparation of (E)-3-chloro-5-(4-methoxystyryl)benzaldehyde (C68)

With stirring, 1-methoxy-4-vinylbenzene (18.3 g, 136.9 mmol) and triethylamine (50 ml, 273 .96 mmol) and the reaction mixture was degassed with argon for 5 min. Acetate was added palladium(II) (410 mg, 1.83 mmol) and tri-o-tolylphosphine (1.11 g, 3.65 mmol) and the resulting reaction mixture was heated at 100°C for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layer was dried over sodium sulfate and concentrated under reduced pressure. The resulting crude material was purified by flash column chromatography using 5-10% ethyl acetate in petroleum ether as eluent to give the title compound as a yellow solid (13.5 g, 54%):¹H NMR (300 MHz, CDCl₃) δ 9.99 (s, 1H), 7.85 (s, 1H), 7.69 (s, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.16 (d , J = 16.2 Hz, 1H), 6.94 (t, J = 8.4 Hz, 3H), 3.84 (s, 3H); ESIMS m/z 273 ([M+H]⁺).

The following compounds were prepared using a procedure similar to that described in Example 49:

(E)-2-Chloro-5-(4-methoxystyryl)benzaldehyde (C69)

Isolated as a pale yellow solid (11.8 g, 27%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 10.45 (s, 1H), 8.02 (s, 1H), 7.62 (d, J = 6.4 Hz, 1H), 7.46 - 7.40 (m, 3H), 7.12 (d, J = 16.4 Hz, 1H), 6.95 - 6.90 ( m, 3H), 3.95 (s, 3H); ESIMS m/z 273 ([M+H] ⁺ ).

(E)-2-Fluoro-5-(4-methoxystyryl)benzaldehyde (C70)

Isolated as an almost white solid (0.25 g, 20%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.43 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.54 - 7.46 (m, 4H), 7.20 (d, J = 16.0 Hz, 1H), 6.94 - 6.90 (m, 3H), 3.85 (s , 3H); ESIMS m/z 274 ([M+H] ⁺ ).

Example 50: Preparation of (E)-1-chloro-3-(difluoromethyl)-5-(4-methoxy-styryl)benzene (C71)

While stirring, diethylaminosulfur trifluoride (31.5 mL, 238.97 mmol) at -78°C. The resulting solution was stirred for 20 hours at room temperature. The reaction mixture was cooled to 0°C and a saturated aqueous sodium bicarbonate solution was added dropwise. The layers were separated and the aqueous layer was extracted with dichloromethane (3×75 ml). The combined organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The crude material was purified by flash column chromatography using 10-20% ethyl acetate in hexanes as eluent to give the title compound as a pale yellow oil (13.1 g, 94%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.55 (s, 1H), 7.45 (d, J = 8.8 Hz, 3H), 7.34 (s, 1H), 7.10 (d, J = 16 Hz, 1H), 6.90 (t, J = 8.4 Hz, 3H), 6.61 (t, J = 56.4 Hz, 1H), 3.80 (s, 3H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -111.72.

The following compounds were prepared using a procedure similar to that described in Example 50:

(E)-1-Chloro-2-(difluoromethyl)-4-(4-methoxystyryl)benzene (C72)

Isolated as an almost white solid (12 g, 94%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.75 (s, 1H), 7.51 - 7.44 (m, 3H), 7. 37 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 6.6 Hz, 1H), 7.06 (s, 1H), 6.95 - 6.89 (m, 3H ), 3.95(s, 3H); ¹⁹ F NMR (282 MHz, CDCl ₃ ) δ -115.31; ESIMS m/z 295 ([M+H] ⁺ ).

(E)-2-(Difluoromethyl)-1-fluoro-4-(4-methoxystyryl)benzene (C73)

Isolated as an almost white solid (14.0 g, 70%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.69 (d, J = 9.0 Hz, 1H), 7.57 - 7. 53 (m, 1H), 7.45 (d, J = 9.9 Hz, 2H), 7.13 - 7.06 (m, 2H), 7.00 - 6.89 (m, 4H), 3 .85 (s, 3H); ESIMS m/z 279 ([M+H] ⁺ ).

Example 51: Preparation of trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid (C36)

Sodium permanganate (40% aqueous solution) (84 g, 236 mmol) was added dropwise to a mixture of trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde (C79) (58, 7 g, 196 mmol) in acetone (982 ml) at 15°C. The resulting mixture was stirred at 20°C for 2 hours. The reaction mixture was diluted with isopropyl alcohol (20 ml) and concentrated to remove acetone. Celite ^® and aqueous hydrochloric acid (1 N, 295 ml, 295 mmol) were added to the brown residue. The resulting mixture was diluted with ethyl acetate (500 ml) and filtered through ^Celite® . The filtrate was washed with brine (200 ml). The organic layer was dried over sodium sulfate, filtered and concentrated. The resulting suspension was diluted with heptane (~200 ml) and allowed to solidify at 20°C. The solid was collected, washed with heptane and dried to give the title product as a white solid (54.68 g, 91%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.36 (t, J = 1.9 Hz , 1H), 7.17 (dd, J = 1.9, 0.7 Hz, 2H), 3.48 - 3.37 (m, 1H), 2.87 (d, J = 8.3 Hz, 1H); ¹³ C NMR (400 MHz, CDCl ₃ ) δ 135.44, 135.28, 128.66, 127.30, 39.68, 36.88; ESIMS m/z = 298.9 ([MH]) ^- .

The following compounds were prepared using a procedure similar to that described in Example 51:

trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylic acid (C37)

Isolated as a white solid (2.78 g, 95%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.41 (s, 1H), 7.81 (d, J = 0.6 Hz , 2H), 3.62 (d, J = 8.6 Hz, 1H), 3.52 (d, J = 8.6 Hz, 1H); ESIMS m/z 332 ([MH] ^- ).

trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid (C38)

Isolated as a white solid (124 g, 82%): m.p. 133 - 135°C: ^1H NMR (500 MHz, DMSO- _d6 ) δ 13.39 (s, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.4, 2.1 Hz, 1H), 3.49 (s, 2H). ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 166.34, 133.35, 130.47, 130.33, 130.09, 129.77, 128.81, 61.43, 37.00, 36 .06.

trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid (C40)

Isolated as a white solid (165 g, 71%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 11.57 (s, 1H), 7.42 (dd, J = 8.2, 7.6 Hz , 1H), 7.11 - 6.98 (m, 2H), 3.46 (d, J = 8.2 Hz, 1H), 2.85 (d, J = 8.3 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -114.07; ESIMS m/z 282 ([MH] ^- ).

In another synthesis, it was isolated as a white powdery substance (10.385 g, 77%): 119-121°C; ^1H NMR (400 MHz, _CDCl3 ) δ 11.83 (s, 1H), 7.32 (d, J = 6.9 Hz, 1H), 7.16 (d, J = 6.7 Hz, 2H ), 3.45 (d, J = 8.3 Hz, 1H), 2.85 (d, J = 8.3 Hz, 1H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 172.18, 159.26, 156.77, 130.95, 129.26, 129.22, 128.57, 128.50, 121.52, 121.34 , 116.94, 116.73, 61.59, 39.64, 37.30; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -115.16; ESIMS m/z 281 [(MH] ^- ).

trans-3-(4-Bromo-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C74)

Isolated as a white solid (1.21 g, 51%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.87 (s, 1H), 7.74 (d, J = 8.3 Hz, 1H ), 7.58 (d, J = 2.2 Hz, 1H), 7.30 (dd, J = 8.3, 2.2 Hz, 1H), 3.49 (d, J = 8.3 Hz , 1H), 2.91 (d, J = 8.3 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.77, -62.78; ESIMS m/z 377 ([MH] ^- ).

trans-2,2-Dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C75)

Isolated as a white solid (2.02 g, 43%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.96 - 7.51 (m, 3H), 7.39 (dd, J = 8, 3, 2.2 Hz, 1H), 3.50 (d, J = 8.3 Hz, 1H), 2.90 (d, J = 8.3 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.75, -62.75; ESIMS m/z 332 ([MH] ^- ).

trans-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C76)

Isolated as a white solid (3.08 g, 67%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18 (s, 1H), 7.64 - 7.39 (m, 2H), 7 .24 (t, J = 9.3 Hz, 1H), 3.50 (dd, J = 8.4, 1.0 Hz, 1H), 2.89 (d, J = 8.3 Hz, 1H) ; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -61.48, -61.51, -114.23, -114.26, -114.29; ESIMS m/z 316 ([MH] ^- ).

trans-2,2-Dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C77)

Isolated as a white solid (3.7 g, 55%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 11.40 (s, 1H), 7.42 - 7.27 (m, 2H), 7 .20 (dt, J = 8.9, 2.0 Hz, 1H), 3.53 (d, J = 8.3 Hz, 1H), 2.93 (d, J = 8.3 Hz, 1H) ; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.86, -109.49; ESIMS m/z 316 ([MH] ^- ).

trans-3-(3-Bromo-5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C78)

Isolated as a tan solid (0.375 g, 31%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.52 (s, 1H), 7.77 (s, 1H), 7.62 (d , J = 1.8 Hz, 1H), 7.46 (s, 1H), 3.52 (d, J = 8.2 Hz, 1H), 2.93 (d, J = 8.3 Hz, 1H ); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.84; ESIMS m/z 377 ([MH] ^- ).

Example 52: Preparation of trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde (C79)

An aqueous solution of hydrochloric acid (2N, 237 ml) was added with stirring to a solution of 1,3-dichloro-5-((trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene (C83) (85.7 g, 227 mmol) in acetonitrile (1184 ml). The mixture was stirred at 20°C for 16 hours. The resulting mixture was diluted with water (200 ml) and concentrated to remove acetonitrile. The resulting aqueous mixture was extracted with hexanes (600 ml). The organic layer was washed water (300 ml), dried over anhydrous sodium sulfate, filtered and concentrated.The crude product was purified by flash column chromatography using 0-20% ethyl acetate/hexanes as eluent to give the title product as a yellow oil (58.7 g , 86%, 95% purity: ^1H NMR (400 MHz, CDCl ₃ ) δ 9.54 (d, J = 4.0 Hz, 1H), 7.46 - 7.09 (m, 3H), 3 .51 (d, J = 8.0 Hz, 1H), 2.92 (dd, J = 8.0, 4.0 Hz, 1H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 193.41, 135.33, 135.09, 128.78, 127.34, 42.89, 39.31; IR (thin film) 3078, 2847, 1714, 1590, 1566, 1417, 1387.

The following compounds were prepared using a procedure similar to that described in Example 52:

trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carbaldehyde (C80)

Isolated as an orange oil (143 g, 98%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.53 (d, J = 4.1 Hz, 1H), 7.47 (d, J = 8, 3 Hz, 1H), 7.37 (dd, J = 2.2, 0.7 Hz, 1H), 7.12 (ddd, J = 8.3, 2.2, 0.7 Hz, 1H), 3.51 (dd, J = 7.9, 0.8 Hz, 1H), 2.90 (dd, J = 8.0, 4.1 Hz, 1H).

trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carbaldehyde (C81)

Isolated as a yellow solid (2.8 g, 69%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.55 (d, J = 3.9 Hz, 1H), 7.30 (d, J = 0.7 Hz, 2H), 3.48 (dt, J = 8.0, 0.8 Hz, 1H), 2.92 (dd, J = 7.9, 3.9 Hz, 1H).

trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carbaldehyde (C82)

Isolated as an orange oil (230 g, 97%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.52 (d, J = 4.2 Hz, 1H), 7.36 - 7.30 (m, 1H), 7.19 - 7.16 (m, 1H), 7.15 (d, J = 1.2 Hz, 1H), 3.51 (dt, J = 7.9, 0.7 Hz, 1H ), 2.88 (dd, J = 7.9, 4.2 Hz, 1H).

In another synthesis, isolated as a yellow oil (12.496 g, 71%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.52 (d, J = 4.1 Hz, 1H), 7.33 (d, J = 7.2 Hz, 1H), 7.16 (dd, J = 6.8, 1.0 Hz, 2H), 3.53 (d, J = 7.9 Hz, 1H), 2.90 (dd , J = 7.9, 4.1 Hz, 1H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 193.77, 159.27, 156.78, 131.03, 129.04, 129.00, 128.66, 128.59, 121.49, 121.31 , 116.95, 116.74, 61.68, 43.10, 39.25; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -115.01; EIMS m/z 266.

Example 53: Preparation of 1,3-dichloro-5-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene (C83)

(E)-1,3-Dichloro-5-(3,3-diethoxyprop-1-en-1-yl) )benzene (C87) (40 g, 138 mmol) and CHCl ₃ (447 ml). Tetrabutylammonium hexafluorophosphate(V) (1.081 g, 2.76 mmol) was added. The light yellow solution was heated at 45°C. With vigorous stirring (~400 rpm), aqueous sodium hydroxide solution (50%, 182 ml) was added dropwise through a dropping funnel (over 1 h). After 20 hours the mixture was allowed to cool. The mixture was diluted with hexane (200 ml). The organic top layer was decanted (leaving the lower aqueous suspension) through ^Celite® , and the filter cake was washed with hexane (200 ml). The filtrate was washed with brine (~200 ml), dried over sodium sulfate, filtered and concentrated to give the title compound as a brown oil (50.2 g, 97%, 95% purity): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.31 (t, J = 1.9 Hz, 1H), 7.15 (dd, J = 1.9, 0.7 Hz, 2H), 4.59 (d, J = 6.2 Hz, 1H ), 3.80 - 3.57 (m, 4H), 2.77 (d, J = 8.5 Hz, 1H), 2.25 (dd, J = 8.5, 6.2 Hz, 1H) , 1.30 (t, J = 7.0 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H).

The following compounds were prepared using a procedure similar to that described in example 53:

1,2-Dichloro-4-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene (C84)

Isolated as a brown oil (184 g, 99%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.43 (d, J = 8.2 Hz, 1H), 7.36 (dd, J = 2, 2, 0.7 Hz, 1H), 7.10 (ddd, J = 8.3, 2.1, 0.7 Hz, 1H), 4.59 (d, J = 6.2 Hz, 1H), 3.82 - 3.55 (m, 4H), 2.77 (d, J = 8.5 Hz, 1H), 2.24 (dd, J = 8.5, 6.3 Hz, 1H), 1 .30 (t, J = 7.0 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H).

1,2,3-Trichloro-5-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene (C85)

Isolated as a brown oil (146 g, 93%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.29 (d, J = 0.7 Hz, 2H), 4.59 (d, J = 6, 1 Hz, 1H), 3.82 - 3.54 (m, 4H), 2.75 (d, J = 8.5 Hz, 1H), 2.23 (dd, J = 8.5, 6.1 Hz, 1H), 1.30 (t, J = 7.0 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H).

2-Chloro-4-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-1-fluorobenzene (C86)

Isolated as a brown oil (63 g, 96%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.44 (dd, J = 7.0, 2.2 Hz, 1H), 7.29 - 7, 22 (m, 1H), 7.09 (t, J = 8.7 Hz, 1H), 6.62 (dd, J = 16.1, 1.2 Hz, 1H), 6.14 (dd, J = 16.1, 5.0 Hz, 1H), 5.05 (dd, J = 4.9, 1.2 Hz, 1H), 3.70 (dq, J = 9.3, 7.0 Hz, 2H), 3.56 (dq, J = 9.4, 7.1 Hz, 2H), 1.25 (t, J = 7.1 Hz, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 158.91, 156.42, 133.65, 133.62, 130.47, 128.65, 128.07, 128.05, 126.39, 126.32 , 121.26, 121.08, 116.72, 116.51, 100.93, 61.17, 15.24; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -116.36.

In another synthesis, isolated as an amber oil (22.38 g, 88%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31 (m, 1H), 7.13 (m, 2H), 4. 59 (d, J = 6.3 Hz, 1H), 3.69 (m, 4H), 2.78 (d, J = 8.5 Hz, 1H), 2.23 (dd, J = 8.5 , 6.3 Hz, 1H), 1.30 (t, J = 7.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -116.48;; EIMS m/z 295 [M-OEt].

Example 54: Preparation of (E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C87)

Step 1a: Acetaldehyde (120 g, 2688 mmol) was added to a mixture of 3,5-dichlorobenzaldehyde (96 g, 538 mmol) in toluene (400 ml) at 0°C with stirring. A solution of potassium hydroxide (3.35 g, 53.8 mmol) in methyl alcohol (10 ml) was added dropwise through a dropping funnel. The resulting mixture was stirred at 0°C for 4 hours until all 3,5-dichlorobenzaldehyde was consumed by thin layer chromatography. Step 1b: Ethyl acetate (500 ml) and concentrated hydrochloric acid (37% aqueous solution, 44.1 ml, 538 mmol) were added to the reaction mixture. The resulting mixture was heated to 80°C and the colorless liquid (200 ml) was distilled off. The reaction mixture was diluted with water (500 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated to give (E)-3-(3,5-dichlorophenyl)acrylic aldehyde as a light yellow solid (115 g) which was used without further purification: ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.72 (dd, J = 7.4, 0.5 Hz, 1H), 7.43 (q, J = 1.8 Hz, 3H), 7.35 (d , J = 16.0 Hz, 1H), 6.69 (dd, J = 16.0, 7.4 Hz, 1H).

Step 2: Triethoxymethane (31.4 g, 208 mmol) and pyridinium-1-ium-4-methylbenzenesulfonate (0.528 g, 2.079 mmol) were added to the (E)-3-(3,5-dichlorophenyl)acrylic aldehyde solution with stirring (44 g, 208 mmol) in ethanol (416 ml). The resulting mixture was stirred at 20°C for 20 hours. A saturated aqueous solution of sodium carbonate (50 ml) was added to the reaction mixture. The resulting mixture was concentrated at 45°C to remove ethanol. The concentrate was diluted with water and extracted with hexane. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated to give the title product as a light yellow oil (56.13 g, 93%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.25 (dt, J = 10.6, 1.9 Hz, 3H), 6.61 (dd, J = 16.1, 1.1 Hz, 1H), 6.22 (dd, J = 16.1, 4.7 Hz , 1H), 5.17 (s, 1H), 5.14 - 5.00 (m, 1H), 3.78 - 3.49 (m, 4H), 1.24 (q, J = 7.2 Hz, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 139.34, 135.14, 130.27, 129.88, 127.71, 125.08, 100.60, 61.20, 15.25.

The following compounds were prepared using a procedure similar to that described in Example 54:

(E)-1,2-Dichloro-4-(3,3-diethoxyprop-1-en-1-yl)benzene(C88)

Isolated as an orange oil (142 g, 91%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.48 (d, J = 2.0 Hz, 1H), 7.39 (dd, J = 8, 3, 0.8 Hz, 1H), 6.62 (d, J = 16.1 Hz, 1H), 6.20 (ddd, J = 16.1, 4.9, 0.8 Hz, 1H), 5.06 (dt, J = 4.9, 1.0 Hz, 1H), 3.78 - 3.48 (m, 4H), 1.25 (td, J = 7.1, 0.8 Hz, 6H).

(E)-1,2,3-Trichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C89)

Isolated as an orange oil (40 g, 91%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.41 (s, 2H), 6.58 (dd, J = 16.1, 1.2 Hz, 1H), 6.21 (dd, J = 16.1, 4.6 Hz, 1H), 5.06 (dd, J = 4.7, 1.2 Hz, 1H), 3.69 (dq, J = 9.3, 7.1 Hz, 2H), 3.55 (dq, J = 9.5, 7.0 Hz, 2H), 1.25 (t, J = 7.1 Hz, 6H).

(E)-2-Chloro-4-(3,3-diethoxyprop-1-en-1-yl)-1-fluorobenzene (C90)

Isolated as an orange oil (283 g, 84%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.44 (dd, J = 7.0, 2.2 Hz, 1H), 7.29 - 7, 22 (m, 1H), 7.09 (t, J = 8.7 Hz, 1H), 6.62 (dd, J = 16.1, 1.2 Hz, 1H), 6.14 (dd, J = 16.1, 5.0 Hz, 1H), 5.05 (dd, J = 4.9, 1.2 Hz, 1H), 3.70 (dq, J = 9.3, 7.0 Hz, 2H), 3.56 (dq, J = 9.4, 7.1 Hz, 2H), 1.25 (t, J = 7.1 Hz, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 158.91, 156.42, 133.65, 133.62, 130.47, 128.65, 128.07, 128.05, 126.39, 126.32 , 121.26, 121.08, 116.72, 116.51, 100.93, 61.17, 15.24; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -116.36.

In another synthesis, isolated as a colorless oil (16.75 g, 64%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.43 (dd, J = 7.0, 2.2 Hz, 1H), 7 .25 (m, 1H), 7.07 (t, J = 8.7 Hz, 1H), 6.62 (d, J = 16.1 Hz, 1H), 6.13 (dd, J = 16, 1, 4.9 Hz, 1H), 5.05 (dd, J = 4.9, 1.0 Hz, 1H), 3.70 (dq, J = 9.4, 7.1 Hz, 2H), 3.56 (dq, J = 9.4, 7.0 Hz, 2H), 1.25 (t, J = 7.1 Hz, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 158.91, 156.42, 133.65, 133.62, 130.47, 128.65, 128.07, 128.05, 126.39, 126.32 , 121.26, 121.08, 116.72, 116.51, 100.93, 61.17, 15.24; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -116.36; EIMS m/z 258.

Example 55: Preparation of (1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid (C91)

1st separation: (R)-1-Phenylethanamine (6.49 g, 53.0 mmol) was slowly added to the rac-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-carboxylic acid solution with stirring ) (32.45 g, 106 mmol) in acetone (106 ml). The resulting solution was stirred at 45°C. Once the solid began to precipitate, the mixture was kept at 5°C for 4 hours. The solid was collected, washed with a minimal amount of cold acetone and dried. The white solid salt was diluted with ethyl acetate (100 ml) and washed with aqueous hydrochloric acid (1N, 10 ml) and brine (30 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to give the title product as a white solid (10.33 g, 88% enantiomeric excess "EI").

2nd separation: (R)-1-Phenylethanamine (3.4 g, 28 mmol) was slowly added to the rac-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-carboxylic acid solution with stirring ( 10.33 g, 88% EI) in acetone (100 ml). After 2 h, the solid was collected, washed with a minimal amount of cold acetone and dried. The solid was treated with aqueous hydrochloric acid to obtain the title compound as a white solid (7.84 g, 97% EI, 24.2%): Specific rotation: +47.4 (10 mg/ml in acetonitrile, 589 nm, 25.2°C); ^1H NMR (300 MHz, CDCl ₃ ) δ 7.36 (t, J = 1.9 Hz, 1H), 7.17 (dd, J = 1.9, 0.7 Hz, 2H), 3.48 - 3.37 (m, 1H), 2.87 (d, J = 8.3 Hz, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 166.28, 136.40, 133.39, 127.27, 127.04, 61.36, 37.10, 35.98; ESIMS m/z 298.9 ([MH] ^- ).

Enantiomeric excesses (EI%) were determined using chiral HPLC technique as follows: Column: CHIRALPAK ^@ ZWIX(+), particle size 3 (m, size 3 mm×150 mm, DAIC 511584; Mobile phase is a mixture of 500 ml acetonitrile, 500 ml methanol, 20 ml water, 1.9 ml formic acid and 2.6 ml diethylamine; Flow rate: 0.5 ml/min; Time: 9 min; Temperature: 25°C.

The following compounds were prepared using a procedure similar to that described in Example 55:

(1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid (C92)

Isolated as a white solid (6.7 g, 30%, 96% EI). The assay data were consistent with racemic acid C38.

(1R,3R)-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid (C93)

Isolated as a white solid (0.5 g, 13%, 99% EI). The analytical data were consistent with racemic acid C40.

(1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylic acid (C94)

Isolated as a white solid (2 g, 29%, 99% EI). The assay data were consistent with racemic acid C37.

(1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C95)

Isolated as a clear, colorless oil (0.11 g, 14%, 80% EI). The assay data were consistent with racemic acid C76.

Example 56: Preparation of 3,4,5-trichlorobenzaldehyde (C96)

In an oven-dried, nitrogen-purged 500 mL round bottom flask equipped with a pressure equalizing addition funnel, 5-bromo-1,2,3-trichlorobenzene (10.0 g, 38.4 mmol) was dissolved in tetrahydrofuran (100 mL), and the resulting solution was cooled in an ice bath under a nitrogen atmosphere. Magnesium isopropyl chloride (2 M solution in tetrahydrofuran, 21.1 mL, 42.3 mmol) was added dropwise through a dropping funnel with vigorous stirring for 15 min. After 0.5 h, N,N-dimethylformamide (3.72 mL, 48.0 mmol) was added to the dark solution with stirring. After another 0.5 h, hydrochloric acid (1 N, 100 ml) was added with stirring. The layers were separated and the organic layer was washed with brine. The combined aqueous layers were extracted with ether and the combined organics were dried over sodium sulfate, filtered and concentrated to give the title compound as a white solid (10:1 mixture of title compound with 1,2,3-trichlorobenzene, 7.96 g, 99% ): ^1H NMR (CDCl ₃ ) δ 9.91 (s, 1H), 7.88 (s, 2H); EIMS m/z 209 ([M] ⁺ ).

Example 57: Preparation of 5-amino-2-cyano-N-(2,4-difluorophenyl)-N-methylbenzamide (C97)

To a solution of 2-cyano-N-(2,4-difluorophenyl)-N-methyl-5-nitrobenzamide (C138) (0.051 g, 0.16 mmol) in methanol (1.5 ml) and water (0.5 ml ) powdered iron (0.045 g, 0.80 mmol) and ammonium chloride (0.026 g, 0.48 mmol) were added. The reaction mixture was heated at 60°C for 2 hours. The reaction mixture was filtered through ^Celite® and the filtrate was diluted with ethyl acetate and washed with water. The combined organic phases were dried over magnesium sulfate, filtered and concentrated to give the title compound as a colorless oil (0.054 g, 99%): Major isomer - ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.37 (td, J = 8 ,8, 5.8 Hz, 1H), 7.22 (d, J = 8.5 Hz, 1H), 6.82 - 6.70 (m, 2H), 6.53 (t, J = 1, 9 Hz, 1H), 6.47 (dd, J = 8.5, 2.4 Hz, 1H), 4.27 (s, 2H), 3.41 (s, 3H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -107.99 (p, J = 7.8 Hz), -115.44 (q, J = 8.8 Hz); ESIMS m/z 288 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in example 57:

Preparation of 5-amino-2-chloro-N-(4-fluorophenyl)benzamide (C98)

Isolated as a white solid (1.75 g, 54%).

5-Amino-2-chloro-N-(2,4-difluorophenyl)benzamide (C99)

Isolated as a purple solid (0.37 g, 28%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.42 (tdd, J = 9.7, 6.0, 3.6 Hz, 1H) , 8.25 (s, 1H), 7.21 (d, J = 8.5 Hz, 1H), 7.13 (d, J = 2.9 Hz, 1H), 6.97 - 6.88 ( m, 2H), 6.73 (dd, J = 8.5, 2.9 Hz, 1H), 3.84 (s, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -114.57 (d, J = 4.6 Hz), -125.78 (d, J = 4.6 Hz); ESIMS m/z 283 ([M+H] ⁺ ).

N-Allyl-5-amino-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide (C100)

A mixture of rotary amide isomers was isolated as a golden oil (0.156 g, quantitative yield): Main isomer - ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.53 - 7.34 (m, 2H), 7.27 - 7, 11 (m, 2H), 6.90 (d, J = 8.6 Hz, 1H), 6.44 (dd, J = 8.6, 2.8 Hz, 1H), 5.97 (ddq, J = 16.9, 10.1, 6.8 Hz, 1H), 5.29 - 5.04 (m, 1H), 4.94 (dq, J = 16.6, 1.2 Hz, 1H), 4.37 - 4.16 (m, 2H), 3.88 (s, 2H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -110.82 (q, J = 7.5 Hz); ESIMS m/z 330 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2-cyano-4-fluorophenyl)-N-(prop-2-yn-1-yl)benzamide (C101)

A mixture of amide rotary isomers was isolated as a colorless oil (0.067 g, 62%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.70 - 7.40 (m, 2H), 7.26 - 7.15 (m , 1H), 7.01 - 6.64 (m, 2H), 6.46 (dd, J = 8.6, 2.8 Hz, 1H), 5.20 - 4.29 (m, 3H), 3.81 (d, J = 80.7 Hz, 1H), 2.29 (dt, J = 11.8, 2.4 Hz, 1H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -110.08 (q, J = 7.2 Hz); ESIMS m/z 328 ([M+H] ⁺ ).

(5-Amino-2-chloro-N-(2-cyano-4-fluorophenyl)benzamido)methyl acetate (C102)

A mixture of amide rotary isomers was isolated as a colorless oil (0.063 g, 97%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.58 - 7.34 (m, 2H), 7.31 - 7.14 (m , 2H), 6.94 - 6.62 (m, 2H), 6.49 - 6.37 (m, 1H), 4.98 - 4.45 (m, 1H), 4.24 (s, 1H ), 3.80 (d, J = 77.8 Hz, 2H), 1.26 (td, J = 7.2, 1.9 Hz, 3H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -109.28 - -109.86 (m); ESIMS m/z 383 ([M+H] ⁺ ).

2-Chloro-N-(2-cyano-4-fluorophenyl)-N-ethyl-5-nitrobenzamide (C103)

A mixture of rotary amide isomers was isolated as a white solid (0.110 g, 64%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.58 - 7.34 (m, 2H), 7.31 - 7.14 ( m, 2H), 6.94 - 6.62 (m, 2H), 6.49 - 6.37 (m, 1H), 4.98 - 4.45 (m, 1H), 4.24 (s, 1H), 3.80 (m, 2H), 1.26 (td, J = 7.2, 1.9 Hz, 3H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -108.27 (s), -109.81 (q, J = 6.7 Hz); ESIMS m/z 348 ([M+H] ⁺ ).

5-Amino-N-benzyl-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide (C104)

A mixture of amide rotary isomers was isolated as a white foam (0.206 g, 98%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.38 - 7.17 (m, 7H), 7.15 - 6.92 ( m, 2H), 6.92 - 6.84 (m, 1H), 6.68 (dd, J = 8.8, 2.8 Hz, 1H), 6.41 (dd, J = 8.6, 2.8 Hz, 1H), 5.76 (d, J = 14.5 Hz, 1H), 4.69 - 4.41 (m, 1H), 3.85 (m, 2H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -108.73 - -110.02 (m); ESIMS m/z 380 ([M+H] ⁺ ).

tert-Butyl-N-[3-[(5-amino-2-chlorobenzoyl)-methylamino]-2,6-difluorophenyl]-N-tert-butoxycarbonylcarbamate (C105)

A mixture of rotary amide isomers was isolated as a colorless oil (0.140 g, 63%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.23 - 7.09 (m, 1H), 7.04 - 6.86 (m , 1H), 6.79 - 6.64 (m, 1H), 6.50 - 6.34 (m, 2H), 3.77 (s, 2H), 3.39 (s, 3H), 1, 43 (d, J = 13.3 Hz, 18H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -116.85 - -118.50 (m), -123.55 (s); ESIMS m/z 534 ([M+Na] ⁺ ).

tert-Butyl-N-[3-[(5-amino-2-chlorobenzoyl)-methylamino]-2,6-difluorophenyl]-N-methylcarbamate (C106)

A mixture of amide rotary isomers was isolated as a pale yellow foam (0.114 g, 92%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.25 - 6.86 (m, 2H), 6.85 - 6, 28 (m, 3H), 4.50 (dd, J = 72.3, 40.3 Hz, 1H), 3.41 (s, 3H), 3.23 - 2.99 (m, 3H), 1 .56 (s, 1H), 1.55 - 1.30 (m, 9H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -118.27 (dt, J = 10.7, 5.6 Hz), -122.00 - -124.47 (m); ESIMS m/z 448 ([M+Na] ⁺ ).

5-Amino-2-chloro-N,N'-dimethyl-N'-phenylbenzohydrazide (C107)

Isolated as a yellow solid (0.203 g, 80%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 7.32 - 7.22 (m, 2H), 6.99 (d, J = 8, 4 Hz, 1H), 6.87 (t, J = 7.1 Hz, 1H), 6.83 - 6.75 (m, 2H), 6.48 (q, J = 2.6 Hz, 2H) , 5.24 (s, 2H), 3.04 (s, 3H), 2.98 (s, 3H); ESIMS m/z 273 ([M+H] ⁺ ).

tert-Butyl-N-[3-[(5-amino-2-chloro-3-fluorobenzoyl)amino]-2,6-difluorophenyl]-N-tert-butoxycarbonylcarbamate (C108)

Isolated as a light yellowish-brown solid (0.864 g, 71%): m.p. 150 - 153°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.39 (s, 1H), 7.68 (td, J = 8.8, 5.8 Hz, 1H), 7.25 (td, J = 9.2, 1.7 Hz, 1H), 6.59 (ddd, J = 7.0, 5.5, 2.5 Hz, 2H), 5.82 (s, 2H), 1.40 (s , 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -115.54, -123.59, -126.30; HRMS-ESI (m/z) [M ⁺ ] ⁺ calculated for C ₂₃ H ₂₅ ClF ₃ N ₃ O ₅ , 515.1435; found, 515.1431.

3-Amino-2,6-dichloro-N-(2,2,3,3,3-pentafluoropropyl)benzamide (C109)

Isolated as a tan solid (0.057 g, 82%): m.p. 116 - 128°C; ^1H NMR (400 MHz, CDCl ₃ ) δ 7.10 (d, J = 8.7 Hz, 1H), 6.74 (d, J = 8.7 Hz, 1H), 6.04 (s, 1H ), 4.18 (td, J = 15.1, 6.5 Hz, 3H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -84.15, -121.50; EIMS m/z 336.

3-Amino-N-ethyl-2,6-difluorobenzamide (C110)

Isolated as a cream solid (0.036 g, 44%): m.p. 123 - 126°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.56 (t, J = 5.6 Hz, 1H), 6.92 - 6.69 (m, 2H), 5.09 (s, 2H) , 3.23 (qd, J = 7.2, 5.5 Hz, 2H), 1.08 (t, J = 7.2 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -131.96, -131.96, -135.48, -135.49; ESIMS m/z 201 ([M+H] ⁺ ).

3-Amino-2,6-difluoro-N-(2,2,2-trifluoroethyl)benzamide (C111)

Isolated as a yellow solid (0.106 g, 68%): m.p. 133 - 136°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.30 (t, J = 6.3 Hz, 1H), 6.93 - 6.74 (m, 2H), 5.17 (s, 2H) , 4.07 (qd, J = 9.7, 6.3 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -70.67, -131.95, -131.95, -135.20, -135.21; ESIMS m/z 255 ([M+H] ⁺ ).

3-Amino-2,6-difluoro-N-(2,2,3,3,3-pentafluoropropyl)benzamide (C112)

Isolated as a light brown solid (0.090 g, 59%): m.p. 82 - 85°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.31 (t, J = 6.3 Hz, 1H), 6.93 - 6.72 (m, 2H), 5.17 (s, 2H) , 4.12 (td, J = 15.5, 6.4 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -83.42, -120.11, -131.86, -135.12; ESIMS m/z 305 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-ethylbenzamide (C113)

Isolated as a peach solid (0.058 g, 68%): m.p. 179 - 182°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.45 (t, J = 5.7 Hz, 1H), 7.10 (d, J = 8.7 Hz, 1H), 6.77 (d , J = 8.8 Hz, 1H), 5.61 (s, 2H), 3.22 (qd, J = 7.2, 5.6 Hz, 2H), 1.09 (t, J = 7, 3 Hz, 3H); ESIMS m/z 233 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-(2,2,2-trifluoroethyl)benzamide (C114)

Isolated as an orange solid (0.125 g, 77%): m.p. 178 - 181°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.23 (t, J = 6.4 Hz, 1H), 7.13 (d, J = 8.8 Hz, 1H), 6.81 (d , J = 8.8 Hz, 1H), 5.68 (s, 2H), 4.05 (qd, J = 9.7, 6.3 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -70.05; ESIMS m/z 287 ([M+H] ⁺ ).

3-Amino-2,6-difluoro-N-propylbenzamide (C115)

Isolated as a light orange oil (0.080 g, 62%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.54 (t, J = 5.7 Hz, 1H), 6.90 - 6 .65 (m, 2H), 5.09 (s, 2H), 3.17 (td, J = 6.8, 5.7 Hz, 2H), 1.48 (h, J = 7.2 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -131.92,

-131.93, -135.41, -135.41; ESIMS m/z 215 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-propylbenzamide (C116)

Isolated as a tan solid (0.089 g, 72%): m.p. 165 - 168°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.47 (t, J = 5.7 Hz, 1H), 7.10 (d, J = 8.8 Hz, 1H), 6.77 (d , J = 8.7 Hz, 1H), 3.16 (td, J = 6.8, 5.6 Hz, 2H), 1.50 (h, J = 7.2 Hz, 2H), 0.91 (t, J = 7.4 Hz, 3H); ESIMS m/z 247 ([M+H] ⁺ ).

3-Amino-2,6-difluoro-N-(3,3,3-trifluoropropyl)benzamide (C117)

Isolated as an orange solid (0.104 g, 67%): m.p. 71 - 74°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.81 (t, J = 5.7 Hz, 1H), 6.92 - 6.69 (m, 2H), 5.13 (s, 2H) , 3.45 (q, J = 6.5 Hz, 2H), 2.57 - 2.43 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -63.90, -131.90, -135.35; ESIMS m/z 269 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-(3,3,3-trifluoropropyl)benzamide (C118)

Isolated as a peach solid (0.129 g, 80%): m.p. 144 - 147°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.77 (t, J = 5.7 Hz, 1H), 7.11 (d, J = 8.7 Hz, 1H), 6.79 (d , J = 8.8 Hz, 1H), 5.65 (s, 2H), 3.43 (td, J = 6.9, 5.7 Hz, 2H), 2.58 - 2.44 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -64.00; ESIMS m/z 301 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-(2-fluoroethyl)benzamide (C119)

Isolated as a peach solid (0.092 g, 74%): m.p. 170 - 172°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.78 (t, J = 5.6 Hz, 1H), 7.11 (d, J = 8.7 Hz, 1H), 6.78 (d , J = 8.8 Hz, 1H), 5.63 (s, 2H), 4.50 (dt, J = 47.4, 5.1 Hz, 2H), 3.51 (dq, J = 26, 6, 5.3 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ 16.09; ESIMS m/z 251 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-(3-chloropropyl)benzamide (C120)

Isolated as a peach solid (0.128 g, 84%): m.p. 124 - 127°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.59 (t, J = 5.7 Hz, 1H), 7.11 (d, J = 8.7 Hz, 1H), 6.78 (d , J = 8.8 Hz, 1H), 5.64 (s, 2H), 3.71 (t, J = 6.6 Hz, 2H), 3.33 (d, J = 5.8 Hz, 5H ), 1.95 (p, J = 6.7 Hz, 2H); ESIMS m/z 281 ([M+H] ⁺ ).

3-Amino-2,6-difluoro-N-(2-fluoroethyl)benzamide (C121)

Isolated as a purple solid (0.079 g, 74%): m.p. 97 - 99°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.83 (t, J = 5.6 Hz, 1H), 6.89 - 6.71 (m, 2H), 5.11 (s, 2H) , 4.49 (dt, J = 47.5, 5.0 Hz, 2H), 3.52 (dq, J = 27.0, 5.2 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ 15.42, -131.81, -131.82, -135.24, -135.25; ESIMS m/z 219 ([M+H] ⁺ ).

3-Amino-N-(3-chloropropyl)-2,6-difluorobenzamide (C122)

Isolated as an amber oil (0.083 g, 73%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.67 (t, J = 5.7 Hz, 1H), 6.93 - 6.66 (m, 2H), 5.12 (s, 2H), 3.68 (t, J = 6.6 Hz, 2H), 3.34 (q, J = 6.4 Hz, 2H), 1.93 (p, J = 6.6 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -132.00, -132.00, -135.48, -135.48; ESIMS m/z 249 ([M+H] ⁺ ).

3-Amino-N-(2,4-difluorophenyl)-2,6-difluorobenzamide (C123)

Isolated as a peach solid (0.077 g, 46%): m.p. 147 - 150°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.51 (s, 1H), 7.75 (td, J = 8.9, 6.1 Hz, 1H), 7.37 (ddd, J = 11.4, 9.2, 2.8 Hz, 1H), 7.12 (tt, J = 8.7, 1.9 Hz, 1H), 6.95 - 6.77 (m, 2H), 5 ,20 (s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -113.26, -113.28, -117.37, -117.39, -131.64, -131.65, -134.94, -134 .95; ESIMS m/z 285 ([M+H] ⁺ ).

3-Amino-2,6-difluoro-N-(4-fluorophenyl)benzamide (C124)

Isolated as a light orange solid (0.114 g, 77%): m.p. 164 - 167°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.74 (s, 1H), 7.82 - 7.62 (m, 2H), 7.20 (t, J = 8.9 Hz, 2H) , 7.04 - 6.68 (m, 2H), 5.22 (s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -118.34, -118.36, -131.90, -131.90, -135.32, -135.33; ESIMS m/z 267 ([M+H] ⁺ ).

N-(4-Acetamidophenyl)-3-amino-2,6-difluorobenzamide (C125)

Isolated as a white solid (0.017 g, 54%): m.p. 210 - 213°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.59 (s, 1H), 9.92 (s, 1H), 7.60 (d, J = 9.0 Hz, 2H), 7.54 (d, J = 9.0 Hz, 2H), 6.94 - 6.77 (m, 2H), 5.19 (s, 2H), 2.03 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -131.84, -131.85, -135.29, -135.30; ESIMS m/z 306 ([M+H] ⁺ ).

N-(4-Acetamidophenyl)-3-amino-2,6-dichlorobenzamide (C126)

Isolated as a gray solid (0.029 g, 25%): m.p. 215 - 278°C; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.50 (s, 1H), 9.91 (s, 1H), 7.62 - 7.56 (m, 2H), 7.56 - 7, 50 (m, 2H), 7.17 (d, J = 8.8 Hz, 1H), 6.84 (d, J = 8.8 Hz, 1H), 5.70 (s, 2H), 2, 02 (s, 3H); ESIMS m/z 338 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-(4-fluorophenyl)benzamide (C127)

Isolated as a white solid (0.093 g, 81%): m.p. 204 - 207°C; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.65 (s, 1H), 7.75 - 7.66 (m, 2H), 7.24 - 7.14 (m, 3H), 6, 85 (d, J = 8.8 Hz, 1H), 5.73 (s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -118.56; ESIMS m/z 299 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-phenylbenzamide (C128)

Isolated as a white solid (0.129 g, 91%): m.p. 172 - 175; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.58 (s, 1H), 7.73 - 7.63 (m, 2H), 7.41 - 7.27 (m, 2H), 7, 18 (d, J = 8.8 Hz, 1H), 7.14 - 7.06 (m, 1H), 6.85 (d, J = 8.8 Hz, 1H), 5.72 (s, 2H ), ESIMS m/z 281 ([M+H] ⁺ ).

3-Amino-2,6-dichloro-N-(2,4-difluorophenyl)benzamide (C129)

Isolated as a white solid (0.127 g, 87%): m.p. 187 - 189°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.47 (s, 1H), 7.76 (td, J = 8.9, 6.2 Hz, 1H), 7.35 (ddd, J = 10.7, 9.1, 2.9 Hz, 1H), 7.23 - 7.08 (m, 2H), 6.84 (d, J = 8.8 Hz, 1H), 5.71 (s , 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -113.48, -113.50, -117.40, -117.41; ESIMS m/z 317 ([M+H] ⁺ ).

3-Amino-N-(4-aminophenyl)-2,6-dichloro-N-methylbenzamide (C130)

Isolated as a waxy gray solid (0.052 g, 80%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.03 - 6.89 (m, 3H), 6.58 (d, J = 8 .7 Hz, 1H), 6.38 - 6.31 (m, 2H), 5.47 (s, 2H), 5.10 (s, 2H), 3.24 (s, 3H); ESIMS m/z 310 ([M+H] ⁺ ).

tert-Butyl-N-[3-[(3-amino-2,6-dichlorobenzoyl)amino]-2,6-difluorophenyl]-N-tert-butoxycarbonylcarbamate (C131)

Isolated as a white waxy solid (0.166 g, 61%): m.p. 84 - 89°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.58 (s, 1H), 7.76 (td, J = 8.8, 5.8 Hz, 1H), 7.26 (td, J = 9.2, 1.7 Hz, 1H), 7.18 (d, J = 8.7 Hz, 1H), 6.85 (d, J = 8.8 Hz, 1H), 5.73 (s, 2H), 1.40 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -123.71, -126.64; ESIMS m/z 530 ([MH] ^- ).

3-Amino-2,6-difluoro-N-phenylbenzamide (C132)

Isolated as a tan solid (0.109 g, 85%): m.p. 173 - 176°C; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.67 (s, 1H), 7.75 - 7.64 (m, 2H), 7.41 - 7.30 (m, 2H), 7, 19 - 7.07 (m, 1H), 6.98 - 6.77 (m, 2H), 5.21 (s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -131.91, -131.92, -135.34, -135.35; ESIMS m/z 249 ([M+H] ⁺ ).

tert-Butyl-N-[3-[(3-amino-2,6-difluorobenzoyl)amino]-2,6-difluorophenyl]-N-tert-butoxycarbonylcarbamate (C133)

Isolated as an orange solid (0.086 g, 61%): m.p. 148 - 151°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.62 (s, 1H), 7.75 (td, J = 8.8, 5.8 Hz, 1H), 7.26 (td, J = 9.3, 1.7 Hz, 1H), 6.99 - 6.78 (m, 2H), 5.22 (s, 2H), 1.40 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -123.58, -126.68, -131.69, -131.70, -134.99, -135.00; ESIMS m/z 498 ([MH] ^- ).

Example 58: Preparation of tert-butyl-(4-(5-amino-2-chlorobenzamido)-3-methylphenyl)carbamate (C134)

To a solution of tert-butyl-(4-(2-chloro-5-nitrobenzamido)-3-methylphenyl)carbamate (C153) (2.2 g, 5.42 mmol) in ethyl acetate (54 ml) under N ₂ was added Pd /C (0.95 g, 0.445 mmol). The reaction mixture was placed in a hydrogen atmosphere under a pressure of approximately 1 atm. (from the bottle) and stirred overnight at room temperature. The reaction mixture was filtered through a pad of ^Celite® and concentrated under reduced pressure to give the title compound as a brown foam (2.09 g, 92%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 9.68 (s, 1H), 9.28 (s, 1H), 7.35 (d, J = 2.2 Hz, 1H), 7.26 (dd, J = 8.6, 2.4 Hz, 1H), 7, 18 (d, J = 8.6 Hz, 1H), 7.12 (d, J = 8.6 Hz, 1H), 6.75 (d, J = 2.7 Hz, 1H), 6.64 ( dd, J = 8.6, 2.7 Hz, 1H), 5.64 (s, 2H), 2.21 (s, 3H), 1.48 (s, 9H); ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 165.69, 152.77, 147.30, 137.32, 137.27, 133.57, 130.14, 129.79, 126.41, 119 .77, 115.93, 115.55, 113.84, 78.91, 54.86, 28.13, 18.21; ESIMS m/z 374 ([MH] ^- ).

The following compounds were prepared using a procedure similar to that described in Example 58:

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-amino-2-chlorobenzamido)-2,6-difluorophenyl)carbamate (C135)

Isolated as a white solid (2.89 g, 59%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.28 (s, 1H), 7.67 (td, J = 8.8, 5.8 Hz, 1H), 7.24 (td, J = 9.3, 1.7 Hz, 1H), 7.13 (d, J = 8.6 Hz, 1H), 6.73 (d, J = 2.7 Hz, 1H), 6.65 (dd, J = 8.6, 2.8 Hz, 1H), 5.48 (s, 2H), 1.40 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -123.86, -126.24; ESIMS m/z 496 ([MH] ^- ).

5-Amino-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide (C136)

Isolated as a brown foam (0.485 g, 97%): ESIMS m/z 376 ([M+H]+). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.77 (s, 1H), 10.28 (s, 1H), 7.73 - 7.54 (m, 1H), 7.31 - 7, 18 (m, 1H), 7.13 (d, J = 8.6 Hz, 1H), 6.73 (d, J = 2.8 Hz, 1H), 6.70 - 6.27 (m, 2H ), 5.49 (s, 2H). ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -120.94 (d, J = 2.6 Hz), -124.00 (d, J = 2.7 Hz), -125.80.

Example 59: Preparation of tert-butyl-N-((tert-butoxyl)carbonyl)-N-(5-(5-amino-2-chlorobenzamido)-2,4-difluorophenyl)carbamate (C137)

2 -chloro-5-nitrobenzoic acid (0.23 g, 1.16 mmol), 4-dimethylaminopyridine (0.15 g, 1.28 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.33 g, 1.74 mmol) and dichloromethane (6 ml). The reaction mixture was stirred at room temperature for 18 hours, then directly loaded into a prefilled Celite ^® cartridge and passed through a silica gel ethyl acetate/hexanes column. The resulting yellow foam was dissolved in ethyl acetate (2 ml) and 10% palladium on carbon (10 mg, 0.009 mmol) was added. The suspension was stirred under a hydrogen atmosphere (from a balloon) for 7 hours. The suspension was filtered through a pad of ^Celite® , eluting with ethyl acetate, and concentrated. Purification by flash column chromatography gave the title compound as a white foam (0.1479 g, 25%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.27 (s, 1H), 7.67 (t, J = 8.1 Hz, 1H), 7.50 (t, J = 10.1 Hz, 1H), 7.12 (d, J = 8.6 Hz, 1H), 6.73 (d , J = 2.7 Hz, 1H), 6.65 (dd, J = 8.6, 2.7 Hz, 1H), 5.48 (s, 2H), 1.40 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.30 (d, J = 6.4 Hz), -122.18 (d, J = 6.4 Hz); ESIMS m/z 495.6 [(MH] ^- ).

Example 60: Preparation of 2-cyano-N-(2,4-difluorophenyl)-N-methyl-5-nitrobenzamide (C138)

To a solution of 2-bromo-N-(2,4-difluorophenyl)-N-methyl-5-nitrobenzamide (0.120 g, 0.323 mmol) (C149) in N,N-dimethylformamide (1.6 ml) was added copper(I) cyanide ) (0.145 g, 1.62 mmol). The reaction mixture was degassed in vacuo, refilled with nitrogen, sealed in a 2 ml microwave vial and heated at 160°C for 20 min in a Biotage Initiator ^® microwave reactor with an external IR temperature sensor measured from the side of the vial. The reaction mixture was diluted with vigorous stirring with ethyl acetate and then filtered through ^Celite® , washing with ethyl acetate. The filtrate was washed with brine. The organic phase was dried over magnesium sulfate, filtered and concentrated. Purification by flash column chromatography using 0-25% ethyl acetate/hexanes as eluent gave the title compound as a mixture of amide rotatable isomers as a beige solid (0.051 g, 47%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.20 (d, J = 8.1 Hz, 2H), 7.81 - 7.72 (m, 1H), 7.39 (td, J = 8.8, 5.7 Hz, 1H) , 6.86 (dddd, J = 8.9, 7.5, 2.8, 1.5 Hz, 1H), 6.76 (ddd, J = 10.6, 8.3, 2.8 Hz, 1H), 3.50 (s, 3H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -106.15 (h, J = 8.1 Hz), -115.12 (q, J = 8.9 Hz); ESIMS m/z 318 ([M+H] ⁺ ).

Example 61: Preparation of N-allyl-2-chloro-N-(2-cyano-4-fluorophenyl)-5-nitrobenzamide (C139)

Sodium hydride (60 % oil suspension, 0.030 g, 0.75 mmol). The slurry was stirred for 30 min and allyl bromide (0.081 ml, 0.94 mmol) was added. The reaction mixture was stirred for 18 hours. The reaction was stopped by slowly adding water (10 ml) and diluted with ethyl acetate (10 ml). The organic layer was dried over magnesium sulfate, filtered and concentrated. Purification by flash column chromatography using 0-25% ethyl acetate/hexanes as eluent gave the title compound as a mixture of amide rotary isomers as an off-white solid (0.162 g, 68%): Major isomer - ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.31 (d, J = 2.7 Hz, 1H), 8.05 (dd, J = 8.8, 2.7 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 7.40 (s, 1H), 7.30 (dd, J = 7.4, 2.9 Hz, 1H), 7.20 (ddd, J = 8.9, 7 ,5, 3.0 Hz, 1H), 5.99 (ddt, J = 17.0, 10.1, 6.7 Hz, 1H), 5.30 - 5.17 (m, 2H), 4, 89 (dd, J = 14.6, 6.0 Hz, 1H), 4.29 (dd, J = 14.6, 7.5 Hz, 1H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -108.13 (q, J = 6.9 Hz); ESIMS m/z 360 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in example 61:

2-Chloro-N-(2-cyano-4-fluorophenyl)-5-nitro-N-(prop-2-yn-1-yl)benzamide (C140)

A mixture of rotary amide isomers was isolated as a white foam (0.128 g, quantitative yield): Main isomer - ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.30 (d, J = 2.6 Hz, 1H), 8. 07 (dd, J = 8.8, 2.6 Hz, 1H), 7.54 (dt, J = 6.7, 3.4 Hz, 1H), 7.43 (d, J = 8.8 Hz , 1H), 7.33 (dd, J = 7.3, 2.9 Hz, 1H), 7.23 (ddd, J = 8.9, 7.5, 3.0 Hz, 1H), 5, 21 (dd, J = 17.4, 2.5 Hz, 1H), 4.41 (m, 1H), 2.34 (t, J = 2.5 Hz, 1H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -107.37 (q, J = 6.8 Hz); ESIMS m/z 358 ([M+H] ⁺ ).

(2-Chloro-N-(2-cyano-4-fluorophenyl)-5-nitrobenzamido)methyl acetate (C141)

A mixture of rotary amide isomers was isolated as a yellow oil (0.067 g, 52%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.50 - 8.34 (m, 1H), 8.35 - 8.04 (m , 1H), 7.73 - 7.39 (m, 3H), 7.34 - 7.19 (m, 1H), 5.99 - 5.80 (m, 1H), 5.56 - 5.28 (m, 1H), 2.14 (d, J = 4.0 Hz, 3H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -108.78 (q, J = 7.0 Hz); ESIMS m/z 392 ([M+H] ⁺ ).

2-Chloro-N-(2-cyano-4-fluorophenyl)-N-ethyl-5-nitrobenzamide (C142)

A mixture of rotary amide isomers was isolated as a white solid (0.110 g, 64%): Main isomer - ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.32 - 8.28 (m, 1H), 8.04 (dd , J = 8.8, 2.7 Hz, 1H), 7.40 (dd, J = 8.9, 5.2 Hz, 2H), 7.32 (dd, J = 7.4, 2.9 Hz, 1H), 7.22 (ddd, J = 8.9, 7.4, 2.9 Hz, 1H), 4.27 (dq, J = 14.2, 7.2 Hz, 1H), 3 .84 (dq, J = 14.1, 7.1 Hz, 1H), 1.31 (t, J = 7.2 Hz, 3H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -108.27 (s); ESIMS m/z 348 ([M+H] ⁺ ).

N-Benzyl-2-chloro-N-(2-cyano-4-fluorophenyl)-5-nitrobenzamide (C143)

A mixture of amide rotary isomers was isolated as a white foam (0.216 g, 80%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.32 - 8.27 (m, 1H), 8.03 (dd, J = 8.8, 2.6 Hz, 1H), 7.40 (d, J = 8.8 Hz, 1H), 7.33 - 7.24 (m, 6H), 7.02 - 6.92 (m , 2H), 5.77 (m, 1H), 4.60 (m, 1H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -107.79 - -108.26 (m); ESIMS m/z 410 ([M+H] ⁺ ).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[(2-chloro-5-nitrobenzoyl)-methylamino]-2,6-difluorophenyl]carbamate (C144)

A mixture of amide rotary isomers was isolated as a pale yellow oil (0.179 g, 55%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.15 (dd, J = 2.6, 1.5 Hz, 1H), 8.03 (dd, J = 8.8, 2.7 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 7.29 - 7.23 (m, 1H), 6 .81 (td, J = 8.8, 1.9 Hz, 1H), 3.45 (s, 3H), 1.41 (dd, J = 39.8, 7.5 Hz, 18H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -115.52 (s), -120.91 - -123.25 (m); ESIMS m/z 541 ([M+H] ⁺ ).

tert-Butyl-N-[3-[allyl-(2-chloro-5-nitrobenzoyl)amino]-2,6-difluorophenyl]-N-tert-butoxycarbonylcarbamate (C145)

A mixture of rotary amide isomers was isolated as a colorless oil (0.068 g, 38%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.16 (t, J = 2.2 Hz, 1H), 8.03 (dd, J = 8.8, 2.7 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 7.31 - 7.22 (m, 1H), 6.81 (td, J = 8.8, 1.8 Hz, 1H), 5.95 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.26 - 5.16 (m, 2H), 4.61 (dd, J = 14.9, 6.3 Hz, 1H), 4.34 (dd, J = 14.7, 6.9 Hz, 1H), 1.46 - 1.32 (m, 18H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -114.18 - -116.23 (m), -121.37 (s); ESIMS m/z 590 ([M+Na] ⁺ ).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[(2-chloro-5-nitrobenzoyl)-prop-2-ynylamino]-2,6-difluorophenyl]carbamate (C146)

A mixture of amide rotary isomers was isolated as a beige sticky solid (0.144 g, 85%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.17 (t, J = 2.2 Hz, 1H), 8.04 ( dd, J = 8.8, 2.7 Hz, 1H), 7.47 - 7.40 (m, 1H), 7.37 (d, J = 8.8 Hz, 1H), 6.84 (td , J = 8.8, 1.8 Hz, 1H), 4.99 (d, J = 17.4 Hz, 1H), 4.43 - 4.31 (m, 1H), 2.29 (t, J = 2.5 Hz, 1H), 1.40 (dd, J = 31.4, 3.8 Hz, 18H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -114.79 (s), -121.53 (s); ESIMS m/z 588 ([M+Na] ⁺ ).

tert-Butyl-(3-(2-chloro-N-methyl-5-nitrobenzamido)-2,6-difluorophenyl)(methyl)carbamate (C147)

A mixture of amide rotary isomers was isolated as a colorless oil (0.071 g, 26%): ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.16 (d, J = 51.3 Hz, 1H), 8.03 (ddd, J = 9.6, 6.8, 2.6 Hz, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.21 - 6.98 (m, 1H), 6.86 - 6.57 (m, 1H), 3.65 - 3.43 (m, 3H), 3.22 - 2.92 (m, 3H), 1.40 (m, 9H); ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ -115.40 (s), -122.10 (s); ESIMS m/z 455 ([M+H] ⁺ ).

Example 62: Preparation of N-(2,6-difluoro-3-nitrophenyl)-2,2-difluoro-N-methylacetamide (C148)

To a solution of N-(2,6-difluoro-3-nitrophenyl)-2,2-difluoroacetamide (C193) (0.400 g, 1.59 mmol) in dry N,N-dimethylformamide (12 ml) with cooling in an ice bath sodium hydride (60% oil suspension, 0.076 g, 1.90 mmol) was added. The slurry was stirred for 5 min in an ice bath. The bath was removed and the reaction mixture was stirred for another 40 minutes. Iodomethane (0.099 mL, 1.59 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction was stopped with water (15 ml) and diluted with ethyl acetate (40 ml). The phases were separated and the organic layer was washed with 1:1 brine/water (4×20 ml). The organic layer was passed through a phase separator to dry and then concentrated under reduced pressure to give the title compound as a yellow oil (0.30 g, 71%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ rotary isomers 8.45 (ddd, J = 9.5, 8.5, 5.7 Hz, 0.65H), 8.36 (ddd, J = 9.5, 8.4, 5.5 Hz, 0.35H), 7 .69 - 7.52 (m, 1H), 7.05 (t, J = 52.1 Hz, 0.35H), 6.43 (t, J = 51.6 Hz, 0.65H), 3, 43 (d, J = 1.2 Hz, 1H), 3.25 (s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ rotary isomers -106.63 (d, J = 10.3 Hz), -106.82 - -107.10 (m),

-120.60 - -120.78 (m), -120.98 (d, J = 10.4 Hz), -124.26 - -124.99 (m), -124.80 -

-125.41 (m), -126.78 (d, J = 3.4 Hz); EIMS m/z 266.

Example 63: Preparation of 2-bromo-N-(2,4-difluorophenyl)-N-methyl-5-nitrobenzamide (C149)

2-Bromo-5-nitrobenzoic acid (0.500 g, 2.03 mmol) and 4-dimethylaminopyridine (0.273 g, 2.24 mmol) were added sequentially with stirring to a mixture of 2,4-difluoro-N-methylaniline (0.349 ml, 2 .44 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.584 g, 3.05 mmol) in dichloromethane (13.5 ml) at room temperature. The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate, then with hydrochloric acid (1 N). The organic phase was dried over magnesium sulfate, filtered and concentrated. Purification by flash column chromatography using 0-25% ethyl acetate/hexanes as eluent gave the title compound as a beige solid (0.149 g, 19%): ¹ HNMR (500 MHz, CDCl ₃ ) δ 8.29 (d , J = 2.7 Hz, 0H), 8.21 - 8.14 (m, 0H), 8.07 (dd, J = 2.7, 1.4 Hz, 1H), 7.93 (dd, J = 8.8, 2.7 Hz, 1H), 7.86 (dd, J = 8.7, 6.2 Hz, 0H), 7.61 (d, J = 8.8 Hz, 1H), 7.47 - 7.39 (m, 0H), 7.30 (dt, J = 9.0, 4.5 Hz, 1H), 7.04 - 6.97 (m, 0H), 6.83 - 6.72 (m, 2H), 3.45 (s, 4H), 3.19 (s, 1H); 19F NMR (471 MHz, CDCl ₃ ) δ -106.76, -108.81 (dt, J = 14.9, 7.9 Hz), -114.38, -115.36 (q, J = 8, 6 Hz); ESIMS m/z 373 ([M+H] ⁺ ).

Example 64: Preparation of 2-chloro-N-(4-fluorophenyl)-5-nitrobenzamide (C150)

2-Chloro-5-nitrobenzoic acid (0.250 g, 1.24 mmol) and 4-dimethylaminopyridine (0.197 g, 1.61 mmol) were added sequentially with stirring to a mixture of 4-fluoroaniline (0.141 ml, 1.49 mmol) and 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.357 g, 1.86 mmol) in 1,2-dichloroethane (12.4 ml) at room temperature. The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate, then hydrochloric acid (1 N) to obtain the title compound as a light brown solid (0.188 g, 49%): ^1H NMR (400 MHz, CDCl ₃ ) δ 8.59 (d, J = 2.7 Hz, 1H), 8.26 (dd, J = 8.8, 2.8 Hz, 1H), 7.90 (s, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.64 - 7.57 (m, 2H), 7.15 - 7.05 (m, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -116.03; ESIMS m/z 295 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 64:

2-Chloro-N-(2,4-difluorophenyl)-5-nitrobenzamide (C151)

Isolated as a light purple solid (1.48 g, 64%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.68 (d, J = 2.7 Hz, 1H), 8.40 (td , J = 9.1, 6.7 Hz, 1H), 8.30 (dd, J = 8.8, 2.7 Hz, 1H), 8.09 (s, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.04 - 6.89 (m, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -113.04 (d, J = 5.0 Hz), -125.45 (d, J = 5.1 Hz); ESIMS m/z 313 ([M+H] ⁺ ).

2-Chloro-N-(2-cyano-4-fluorophenyl)-5-nitrobenzamide (C152)

Isolated as a white solid (0.439 g, 55%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.06 (s, 1H), 8.52 (d, J = 2.8 Hz, 1H ), 8.38 (dd, J = 8.8, 2.8 Hz, 1H), 8.02 - 7.86 (m, 2H), 7.83 - 7.61 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -113.90; ESIMS m/z 320 ([M+H] ⁺ ).

tert-Butyl-(4-(2-chloro-5-nitrobenzamido)-3-methylphenyl)carbamate (C153)

Isolated as a yellow solid (2.19 g, 67%): m.p. 195 - 200°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.06 (s, 1H), 9.34 (s, 1H), 8.45 (d, J = 2.7 Hz, 1H), 8.33 (dd, J = 8.8, 2.8 Hz, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.43 - 7.24 (m, 3H), 2.24 ( s, 3H), 1.48 (s, 9H); ESIMS m/z 404 ([MH] ^- ).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-nitrobenzamido)-2,4-difluorophenyl)carbamate (C154)

Isolated as a yellow oil (5.2 g, 66%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.69 (s, 1H), 8.51 (d, J = 2.7 Hz, 1H), 8.35 (dd, J = 8.8, 2.8 Hz, 1H), 7.97 - 7.79 (m, 2H), 7.30 (td, J = 9.3, 1, 7 Hz, 1H), 1.41 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -123.43, -127.02 (d, J = 2.0 Hz); ESIMS m/z 526 ([MH] ^- ).

Example 65: Preparation of tert-butyl-N-tert-butoxycarbonyl-N-[3-[(2-chloro-3-fluoro-5-nitrobenzoyl)amino]-2,6-difluorophenyl]carbamate (C155)

To a solution of 2-chloro-3-fluoro-5-nitrobenzoic acid (C206) (1.81 g, 8.25 mmol) and tert-butyl-N-(5-amino-2,6-difluorophenyl)-N-tert -butoxycarbonylcarbamate (C182) (2.84 g, 8.25 mmol) in ethyl acetate (41 ml) was added pyridine (1.96 g, 24.7 mmol), then a 50% solution of 2,4,6-tripropyl-1, 3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide (9.82 ml, 16.5 mmol) in ethyl acetate and the resulting golden solution was heated at 48°C and stirred for 12 hours. The reaction mixture concentrated under reduced pressure to give a viscous golden oil. The oil was dissolved in a minimal amount of dichloromethane (~8 ml) and adsorbed onto Celite ^® . The adsorbed material was purified by automated flash chromatography using a 0-40% ethyl acetate in hexanes gradient to give the title compound as a white solid (2.095 g, 83%): m.p. 167 - 169°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.76 (s, 1H), 8.52 (dd, J = 8.8, 2.6 Hz, 1H), 8.43 (dd, J = 2.6, 1.4 Hz, 1H), 7.89 (td, J = 8.9, 5.8 Hz, 1H), 7.31 (td, J = 9.3, 1.8 Hz, 1H ), 1.41 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -109.64, -123.26, -127.07, -127.08; HRMS-ESI (m/z) [M ⁺ ] ⁺ calculated for C ₂₃ H ₂₃ ClF ₃ N ₃ O ₇ , 545.1177; found, 545.1172.

Example 66: Preparation of 2,6-dichloro-N-(2,4-difluorophenyl)-3-nitrobenzamide (C156)

Step 1: To a suspension of 2,6-dichloro-3-nitrobenzoic acid (0.15 g, 0.64 mmol) in 1,2-dichloroethane (10 ml) add 2 drops of N,N-dimethylformamide, then add oxalyl dichloride dropwise (0.40 g, 0.27 ml, 3.2 mmol) and the resulting light yellow solution was stirred at room temperature for 16 hours. The solvent and excess oxalyl dichloride were evaporated under reduced pressure and the resulting golden oil was dissolved in 1,2-dichloroethane (10 ml) and concentrated (repeated twice) to obtain the acid chloride intermediate as a golden oil, which was used without purification.

Step 2: To a solution of 2,4-difluoroaniline (0.082 g, 0.64 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.17 g, 1.34 mmol) in 1,2-dichloroethane (1 ml) a solution of freshly prepared acid chloride, 2,6-dichloro-3-nitrobenzoyl chloride (0.162 g, 0.64 mmol) in 1,2-dichloroethane (1 ml) was added dropwise at 0°C. The resulting light orange solution was heated at 50°C and stirred for 8 hours. The reaction mixture was adsorbed onto Celite ^® and purified using automated flash chromatography in a gradient mode of 0-60% ethyl acetate in hexanes as eluent to obtain the desired compound as tan solid (0.171 g, 75%): m.p. 199 - 202°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.83 (s, 1H), 8.21 (d, J = 8.8 Hz, 1H), 7.94 (td, J = 8.9, 6.1 Hz, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.41 (ddd, J = 10.9, 9.0, 2.9 Hz, 1H), 7, 17 (dddd, J = 9.5, 8.4, 2.9, 1.4 Hz, 1H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -112.94,

-112.95, -112.96, -112.96, -112.97, -112.97, -112.98, -112.99, -113.00, -118.60, -118.62, -118.62, -118.64, -118.64, -118.66; ESIMS m/z 347 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 66:

N-(4-Acetamidophenyl)-2,6-dichloro-3-nitrobenzamide (C157)

Isolated as a light yellow solid (0.153 g, 63%): m.p. 268 - 270°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.82 (s, 1H), 9.97 (s, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.58 (s, 4H), 2.04 (s, 3H); IR (thin film) 3640, 3250, 3054, 1656, 1527, 1310, 827, 706 cm ^-1 ; ESIMS m/z 366([M-2H] ^- ).

2,6-Dichloro-N-(4-fluorophenyl)-3-nitrobenzamide (C158)

Isolated as a light orange solid (0.148 g, 70%): m.p. 211 - 214°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 8.22 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 8.8 Hz , 1H), 7.77 - 7.63 (m, 2H), 7.34 - 7.11 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -117.60; ESIMS m/z 329 ([M+H] ⁺ ).

2,6-Dichloro-3-nitro-N-phenylbenzamide (C159)

Isolated as a light orange solid (0.173 g, 86%): m.p. 180 - 183°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 8.22 (d, J = 8.7 Hz, 1H), 7.90 (d, J = 8.7 Hz , 1H), 7.70 - 7.64 (m, 2H), 7.42 - 7.34 (m, 2H), 7.22 - 7.08 (m, 1H); ESIMS m/z 311 ([M+H] ⁺ ).

N-(4-Aminophenyl)-2,6-dichloro-N-methyl-3-nitrobenzamide (C160)

Isolated as a green solid (0.085 g, 36%): m.p. 176 - 180°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 7.93 (d, J = 8.8 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.02 - 6 .97 (m, 2H), 6.41 - 6.35 (m, 2H), 5.23 (s, 2H), 3.30 (s, 3H); ESIMS m/z 340 ([M+H] ⁺ ).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[(2,6-dichloro-3-nitrobenzoyl)amino]-2,6-difluorophenyl]carbamate (C161)

Isolated as a light orange solid (0.302 g, 78%): m.p. 164 - 167°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 8.23 (d, J = 8.8 Hz, 1H), 7.97 - 7.84 (m, 2H) , 7.31 (td, J = 9.3, 1.7 Hz, 1H), 1.40 (s, 18H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -123.11, -123.12,

-123.14, -127.55, -127.57; ESIMS m/z 560 ([MH] ^- ).

2,6-Difluoro-3-nitro-N-phenylbenzamide (C162)

Isolated as a yellow solid (0.161 g, 90%): m.p. 161 - 163°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 8.42 (td, J = 9.0, 5.6 Hz, 1H), 7.71 - 7.63 ( m, 2H), 7.56 (ddd, J = 9.4, 7.9, 1.5 Hz, 1H), 7.44 - 7.35 (m, 2H), 7.24 - 7.14 ( m, 1H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -102.54, -102.56, -102.56, -102.57, -102.58, -102.60, -117.46, -117 .48, -117.51; ESIMS m/z 279 ([M+H] ⁺ ).

2,6-Difluoro-N-(4-fluorophenyl)-3-nitrobenzamide (C163)

Isolated as a light orange solid (0.178 g, 93%): m.p. 158 - 160°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 11.05 (s, 1H), 8.43 (td, J = 9.0, 5.6 Hz, 1H), 7.76 - 7.65 ( m, 2H), 7.56 (ddd, J = 9.5, 8.0, 1.5 Hz, 1H), 7.25 (t, J = 8.9 Hz, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -102.47, -102.48, -102.49, -102.50, -102.50, -102.52, -117.37, -117 .39, -117.40, -117.41, -117.42, -117.43, -117.44; ESIMS m/z 297 ([M+H] ⁺ ).

N-(4-Acetamidophenyl)-2,6-difluoro-3-nitrobenzamide (C164)

Isolated as a white solid (0.041 g, 19%): m.p. 251 - 255°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 9.97 (s, 1H), 8.41 (td, J = 9.0, 5.6 Hz, 1H) , 7.59 (s, 4H), 7.54 (ddd, J = 9.3, 7.9, 1.4 Hz, 1H), 2.04 (s, 3H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -102.50, -102.52, -102.54, -102.55, -117.45, -117.47, -117.49; ESIMS m/z 336 ([M+H] ⁺ ).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[(2,6-difluoro-3-nitrobenzoyl)amino]-2,6-difluorophenyl]carbamate (C165)

Isolated as a pale yellow solid (0.165 g, 48%): m.p. 163 - 165°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 8.43 (td, J = 9.0, 5.6 Hz, 1H), 7.87 (td, J = 8.8, 5.7 Hz, 1H), 7.55 (ddd, J = 9.4, 8.0, 1.4 Hz, 1H), 7.31 (td, J = 9.2, 1, 7 Hz, 1H), 1.40 (s, 18H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -102.41, -102.43, -102.45, -102.46, -117.12, -117.14, -117.16, -122 .89, -122.91, -122.93, -127.37, -127.39; ESIMS m/z 528 ([MH] ^- ).

2,6-Dichloro-3-nitro-N-(2,2,3,3,3-pentafluoropropyl)benzamide (C166)

Isolated as a white solid (0.095 g, 64%): m.p. 139 - 142°C; ^1H NMR (400 MHz, _CDCl3 ) δ 7.85 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H), 6.29 (s, 1H ), 4.18 (td, J = 14.9, 6.4 Hz, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -84.17, -121.45; ESIMS m/z 367 ([M+H] ⁺ ).

2,6-Dichloro-N-ethyl-3-nitrobenzamide (C167)

Isolated as a yellow solid (0.108 g, 61%): m.p. 104 - 108°C; ^1H NMR (400 MHz, _CDCl3 ) δ 7.80 (d, J = 8.7 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 5.91 (s, 1H ), 3.54 (qd, J = 7.3, 5.8 Hz, 2H), 1.29 (t, J = 7.3 Hz, 3H); IR (thin film) 3253, 3086, 2980, 1819, 1645, 1564, 1518, 1344, 928, 698 cm ^-1 ; ESIMS m/z 261 ([MH] ^- ).

N-Ethyl-2,6-difluoro-3-nitrobenzamide (C168):

Isolated as a yellow solid (0.108 g, 62%): m.p. 104 - 108°C; ^1H NMR (400 MHz, CDCl ₃ ) δ 8.16 (ddd, J = 9.3, 8.2, 5.5 Hz, 1H), 7.10 (ddd, J = 9.4, 7.7 , 1.8 Hz, 1H), 6.08 (s, 1H), 3.52 (qd, J = 7.3, 5.7 Hz, 2H), 1.27 (t, J = 7.3 Hz , 3H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -100.08, -100.10, -114.72, -114.75; IR (thin film) 3240, 3087, 2996, 1713, 1620, 1531, 1347, 1298, 1028, 843 cm ^-1 ; ESIMS m/z 231 ([M+H] ⁺ ).

2,6-Dichloro-3-nitro-N-propylbenzamide (C169):

Isolated as a yellow solid (0.158 g, 88%): m.p. 126 - 129°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.82 (t, J = 5.8 Hz, 1H), 8.12 (d, J = 8.8 Hz, 1H), 7.81 (d , J = 8.8 Hz, 1H), 3.23 (td, J = 6.9, 5.7 Hz, 2H), 1.54 (h, J = 7.2 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H); ESIMS m/z 277 ([M+H] ⁺ ).

2,6-Dichloro-N-(2-fluoroethyl)-3-nitrobenzamide (C170)

Isolated as a cream solid (0.154 g, 84%): m.p. 148 - 150°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.14 (t, J = 5.7 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 7.82 (d , J = 8.7 Hz, 1H), 4.55 (dt, J = 47.4, 4.9 Hz, 2H), 3.65 - 3.53 (m, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ 20.28, 20.23, 20.18, 20.12, 20.07, 20.06, 20.02, 19.96; ESIMS m/z 281 ([M+H] ⁺ ).

2,6-Dichloro-3-nitro-N-(2,2,2-trifluoroethyl)benzamide (C171)

Isolated as a pale yellow solid (0.182 g, 88%): m.p. 182 - 184°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.57 (t, J = 6.3 Hz, 1H), 8.18 (d, J = 8.7 Hz, 1H), 7.85 (d , J = 8.8 Hz, 1H), 4.17 (qd, J = 9.7, 6.3 Hz, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -70.07, -70.09, -70.11; ESIMS m/z 315 ([MH] ^- ).

2,6-Dichloro-3-nitro-N-(3,3,3-trifluoropropyl)benzamide (C172)

Isolated as a pale yellow solid (0.186 g, 86%): m.p. 128 - 130°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.14 (t, J = 5.8 Hz, 1H), 8.15 (d, J = 8.7 Hz, 1H), 7.82 (d , J = 8.8 Hz, 1H), 3.51 (td, J = 6.8, 5.7 Hz, 2H), 2.61 - 2.52 (m, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -63.89, -63.91, -63.94; ESIMS m/z 331 ([M+H] ⁺ ).

2,6-Dichloro-N-(3-chloropropyl)-3-nitrobenzamide (C173)

Isolated as a yellow solid (0.180 g, 89%): m.p. 116 - 120°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 8.94 (t, J = 5.7 Hz, 1H), 8.14 (d, J = 8.7 Hz, 1H), 7.82 (d , J = 8.7 Hz, 1H), 3.72 (t, J = 6.5 Hz, 2H), 3.40 (q, J = 6.4 Hz, 2H), 1.98 (p, J = 6.6 Hz, 2H); ESIMS m/z 311 ([M+H] ⁺ ).

2,6-Difluoro-3-nitro-N-propylbenzamide (C174)

Isolated as a light yellow solid (0.149 g, 95%): m.p. 85 - 88°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 8.93 - 8.83 (m, 1H), 8.33 (td, J = 9.0, 5.6 Hz, 1H), 7.46 ( ddd, J = 9.4, 8.0, 1.5 Hz, 1H), 3.24 (td, J = 6.8, 5.6 Hz, 2H), 1.52 (h, J = 7, 2 Hz, 2H), 0.91 (t, J = 7.4 Hz, 3H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -102.84, -102.85, -102.87, -102.88, -102.89, -117.84, -117.86, -117 .88; ESIMS m/z 245 ([M+H] ⁺ ).

2,6-Difluoro-N-(2-fluoroethyl)-3-nitrobenzamide (C175)

Isolated as a yellow solid (0.135 g, 82%): m.p. 95 - 99°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.20 (t, J = 5.6 Hz, 1H), 8.35 (td, J = 9.0, 5.6 Hz, 1H), 7 .47 (ddd, J = 9.4, 8.0, 1.6 Hz, 1H), 4.54 (dt, J = 47.5, 4.9 Hz, 2H), 3.66 - 3.54 (m, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ 19.65, 19.59, 19.55, 19.53, 19.49, 19.45, 19.43, 19.39, 19.33, - 102.68, -102.70, -102.71, -102.71, -102.72, -102.74, -117.56, -117.58, -117.60; ESIMS m/z 249 ([M+H] ⁺ ).

2,6-Difluoro-3-nitro-N-(2,2,2-trifluoroethyl)benzamide (C176)

Isolated as a white solid (0.175 g, 97%): m.p. 137 - 139°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.64 (t, J = 6.3 Hz, 1H), 8.39 (td, J = 9.0, 5.6 Hz, 1H), 7 .50 (ddd, J = 9.5, 8.0, 1.5 Hz, 1H), 4.19 (qd, J = 9.6, 6.3 Hz, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -70.70, -70.72, -70.74, -102.73, -102.74, -102.75, -102.75, -102 .76, -102.76, -102.77, -102.78, -117.46, -117.48, -117.50; ESIMS m/z 283 ([MH] ^- ).

2,6-Difluoro-3-nitro-N-(3,3,3-trifluoropropyl)benzamide (C177)

Isolated as a pale yellow solid (0.167 g, 87%): m.p. 108 - 110°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.18 (t, J = 5.8 Hz, 1H), 8.35 (td, J = 9.0, 5.6 Hz, 1H), 7 .47 (ddd, J = 9.5, 8.1, 1.5 Hz, 1H), 3.53 (td, J = 6.6, 5.6 Hz, 2H), 2.60 - 2.51 (m, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -63.83, -63.86, -63.88, -102.67, -102.69, -102.70, -102.72, -117 .59, -117.61, -117.63; ESIMS m/z 299 ([M+H] ⁺ ).

2,6-Difluoro-3-nitro-N-(2,2,3,3,3-pentafluoropropyl)benzamide (C178)

Isolated as a white solid (0.177 g, 83%): m.p. 143-145°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.66 (t, J = 6.3 Hz, 1H), 8.39 (td, J = 9.0, 5.6 Hz, 1H), 7 .50 (ddd, J = 9.5, 8.1, 1.6 Hz, 1H), 4.24 (td, J = 15.2, 6.3 Hz, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -83.41, -102.65, -102.66, -102.68, -102.70, -117.38, -117.40, -117 .42, -120.07, -120.10, -120.14; IR (thin film) 3282, 3100, 2973, 1677, 1541, 1224, 1033, 730 cm ^-1 ; ESIMS m/z 333 ([MH] ^- ).

N-(3-Chloropropyl)-2,6-difluoro-3-nitrobenzamide (C179)

Isolated as a yellow solid (0.137 g, 77%): m.p. 84 - 87°C; ^1H NMR (500 MHz, DMSO- _d6 ) δ 9.00 (t, J = 5.7 Hz, 1H), 8.35 (td, J = 9.0, 5.6 Hz, 1H), 7 .47 (ddd, J = 9.5, 8.0, 1.5 Hz, 1H), 3.70 (t, J = 6.5 Hz, 2H), 3.41 (td, J = 6.7 , 5.5 Hz, 2H), 1.97 (p, J = 6.6 Hz, 2H); ¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ -102.82, -102.82, -102.83, -102.84, -102.85, -117.76, -117.78, -117 .81; ESIMS m/z 279 ([M+H] ⁺ ).

tert-Butyl-(3-(2-chloro-3-fluoro-5-nitrobenzamido)-2,4-difluorophenyl)carbamate (C180)

Isolated as an almost white solid (0.590 g, 100%): m.p. = 202-204°C (dec); ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.63 (s, 1H), 9.06 (s, 1H), 8.51 (dd, J = 8.8, 2.6 Hz, 1H) , 8.40 (dd, J = 2.6, 1.4 Hz, 1H), 8.07 (t, J = 8.3 Hz, 1H), 7.42 (t, J = 10.4 Hz, 1H), 1.46 (s, 9H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -109.72, -122.28, -123.56; ESIMS m/z 544 ([MH] ^- ).

Example 67: Preparation of tert-butyl-N-((tert-butoxy)carbonyl)-N-(4-amino-3,5-difluorophenyl)carbamate (C181)

To a solution of tert-butyl-N-((tert-butoxy)carbonyl)-(3,5-difluoro-4-nitrophenyl)carbamate (C189) (1.75 g, 4.67 mmol) in ethyl acetate (30 ml) was added 5% palladium on carbon (0.498 g, 0.234 mmol). The reaction mixture was stirred vigorously overnight at room temperature under a hydrogen atmosphere from a balloon. The reaction mixture was filtered through a pad of ^Celite® and washed with ethyl acetate. The filtrates were concentrated under reduced pressure to give the title compound as an off-white solid (1.57 g, 98%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.07 (ddd, J = 11.4, 8.9, 2.8 Hz, 1H), 6.79 (dd, J = 9.3, 2.4 Hz, 1H), 4.87 (s, 2H), 1.36 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -128.55, -129.75.

The following compounds were prepared using a procedure similar to that described in Example 67:

tert-Butyl-N-(3-amino-2,6-difluorophenyl)-N-tert-butoxycarbonylcarbamate (C182)

Isolated as a white solid (5.06 g, 100%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 6.87 (td, J = 9.3, 1.7 Hz, 1H), 6 .74 (td, J = 9.4, 5.7 Hz, 1H), 5.12 (s, 2H), 1.39 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -137.96 (d, J = 3.7 Hz), -141.10 (d, J = 3.7 Hz); ESIMS m/z 244 ([M-BOC] ^- ).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-amino-2,4-difluorophenyl)carbamate (C183)

Isolated as a cream solid (1.05 g, 88%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.82 (dd, J = 10.5, 9.3 Hz, 1H), 6.60 (dd, J = 9.1, 7.5 Hz, 1H), 3.59 (s, 2H), 1.43 (s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -131.04 (t, J = 2.2 Hz), -131.38 (d, J = 2.0 Hz); ESIMS m/z 245 ([MC ₅ H ₉ O ₂ +H] ⁺ ).

tert-Butyl-(4-amino-3-methylphenyl)carbamate (C184)

Isolated as a light pink solid (12.4 g, 87%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.72 (s, 1H), 7.01 (s, 1H), 6 .93 (d, J = 8.5 Hz, 1H), 6.49 (d, J = 8.4 Hz, 1H), 4.49 (s, 2H), 2.00 (s, 3H), 1 .44 (s, 9H); ESIMS m/z 223 ([M+H] ⁺ ).

tert-Butyl-N-((tert-butoxy)carbonyl-(4-amino-2,6-difluorophenyl)carbamate (C185)

Isolated as an almost white solid (1.5 g, 73%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 6.28 - 6.18 (m, 2H), 5.83 (s, 2H ), 1.37 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -122.91; ESIMS m/z 345 ([M+H] ⁺ ).

N-(3-Amino-2,6-difluorophenyl)-2,2-difluoroacetamide (C186)

Isolated as a light brown solid (0.91 g, 98%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.50 (s, 1H), 6.88 (td, J = 9, 3, 1.9 Hz, 1H), 6.72 (td, J = 9.3, 5.5 Hz, 1H), 6.49 (t, J = 53.2 Hz, 1H), 5.58 ( s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -125.61, -135.65 (d, J = 3.4 Hz), -138.69 (d, J = 3.5 Hz); EIMS m/z 222.

N-(3-Amino-2,6-difluorophenyl)-2,2-difluoro-N-methylacetamide (C187)

Isolated as a light yellow oil (0.26 g, 96%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ rotary isomers 7.00 (td, J = 9.3, 1.7 Hz, 1H ), 6.85 (td, J = 9.4, 5.7 Hz, 1H), 6.24 (t, J = 52.1 Hz, 1H), 5.32 (s, 2H), 3.33 (d, J = 2.7 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ rotary isomers -124.15 (dd, J = 16.1, 2.9 Hz), -137.89 - -138.92 (m), -140, 84 - -141.99 (m); EIMS m/z 236.

tert-Butyl-(3-(5-amino-2-chloro-3-fluorobenzamido)-2,4-difluorophenyl)carbamate (C188)

Isolated as a yellowish-brown powdery substance (0.563 g, 100%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.99 (t, J = 8.5 Hz, 1H), 8.08 (br s, 1H), 6.97 - 6.89 (m, 2H), 6.59 (dd, J = 10.4, 2.7 Hz, 1H), 6.55 (br s, 1H), 3.98 ( br s, 2H), 1.54 (s, 9H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -112.06, -131.58, -132.13; ESIMS m/z 414 ([MH] ^- ).

Example 68: Preparation of tert-butyl-N-((tert-butoxy)carbonyl)-(3,5-difluoro-4-nitrophenyl)carbamate (C189)

To a solution of 3,5-difluoro-4-nitroaniline (1.0 g, 5.74 mmol) in dichloromethane (25.0 ml) was added di-tert-butyl dicarbonate (2.63 g, 12.1 mmol), then 4 -dimethylaminopyridine (0.070 g, 0.574 mmol). The reaction mixture was stirred for 48 hours at room temperature. The reaction was stopped with water and passed through a phase separator. The organic layer was concentrated. Purification by flash column chromatography using 0-20% ethyl acetate/hexanes as eluent gave the title compound as a yellow solid (1.79 g, 83%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7. 04 (ddd, J = 9.7, 8.0, 2.7 Hz, 1H), 6.90 (ddd, J = 8.2, 2.7, 1.9 Hz, 1H), 1.43 ( s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -133.35 (d, J = 23.5 Hz), -137.44 (d, J = 23.4 Hz); ESIMS m/z 375 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 68:

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2,6-difluoro-3-nitrophenyl)carbamate (C190)

Isolated as a white foam (5.2 g, 69%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.14 (ddd, J = 9.2, 8.1, 5.5 Hz, 1H) , 7.10 (ddd, J = 9.7, 8.0, 2.0 Hz, 1H), 1.45 (s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -105.95 (dd, J = 10.9, 2.7 Hz), -119.53 (d, J = 10.6 Hz); ESIMS m/z 397 ([M+Na] ⁺ ).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2,4-difluoro-5-nitrophenyl)carbamate (C191)

Isolated as a white solid (1.2 g, 56%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (t, J = 7.7 Hz, 1H), 7.11 (dd, J = 10.2, 8.9 Hz, 1H), 1.46 (s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -105.08 (dd, J = 14.8, 2.2 Hz), -111.35 (dd, J = 14.6, 2.3 Hz); ESIMS m/z 397 ([M+Na] ⁺ ).

tert-Butyl-N-((tert-butoxy)carbonyl)-(2,6-difluoro-4-nitrophenyl)carbamate (C192)

Isolated as a light yellow solid (2.0 g, 84%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.33 - 8.24 (m, 2H), 1.40 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -115.68; ESIMS m/z 374 ([MH] ^- ).

Example 69: Preparation of N-(2,6-difluoro-3-nitrophenyl)-2,2-difluoroacetamide (C193)

To a solution of 2,6-difluoro-3-nitroaniline (1.00 g, 5.74 mmol) in dichloromethane (2.0 ml) was added triethylamine (1.20 ml, 8.62 mmol) and 2, 2-difluoroacetic anhydride (1.30 g, 7.47 mmol). The reaction mixture was stirred at room temperature for 18 hours. The mixture was then loaded into a ^Celite® cartridge and purified by column chromatography using 0-40% ethyl acetate/hexanes as eluent to give the title compound as a white solid (1.50 d, 100% yield): ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.07 (s, 1H), 8.29 (ddd, J = 9.5, 8.4, 5.5 Hz, 1H), 7.53 (td, J = 9.2, 1.9 Hz, 1H), 6.59 (t, J = 53.0 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -105.42 (d, J = 10.7 Hz), -120.10 (d, J = 10.6 Hz), -125.98; EIMS m/z 252.

Example 70: Preparation of N-(3-amino-2-chloro-6-fluorophenyl)acetamide (C194)

Step 1: Preparation of N-(2-chloro-6-fluorophenyl)acetamide. Acetic anhydride (10 g, 99 mmol) was added dropwise with stirring to a solution of 2-chloro-6-fluoroaniline (12.5 g, 86 mmol) in glacial acetic acid (50 ml). The resulting golden solution was heated at 90°C for 2 hours, then cooled and the reaction was stopped with water (500 ml). The resulting solid was collected by vacuum filtration, washed with water (100 ml) and hexanes (100 ml) and dried in vacuum at 40°C to constant weight to obtain the title compound as a tan solid (14.87 g, 88 %): ^1H NMR (400 MHz, CDCl ₃ ) δ 7.86 (s, 1H), 7.05 (dt, J = 63.2, 8.4 Hz, 3H), 2.13 (s, 3H ); ESIMS m/z 188 ([M+H] ⁺ ).

Step 2: Preparation of N-(2-chloro-6-fluoro-3-nitrophenyl)acetamide. Sodium nitrate (4.53 g, 53.3 mmol) dissolved in water (5 ml) was added dropwise to the N-(2-chloro-6-fluorophenyl)acetamide solution (5 g, 26.7 mmol) with stirring. in concentrated sulfuric acid (10 ml) at -10°C. After addition was complete, the resulting yellow solution was stirred at 0°C for 30 min, then heated at and stirred at room temperature for another 12 h. The reaction mixture was poured into water (~250 ml) and the resulting solid was collected by vacuum filtration. Recrystallization from acetonitrile gave the title compound as a light tan solid (3.2 g, 49%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.07 (s, 1H), 8.12 (dd, J = 9.2, 5.0 Hz, 1H), 7.70 - 7.55 (m, 1H), 2.12 (s, 3H); ESIMS m/z 233 ([M+H] ⁺ ).

Step 3: Preparation of N-(3-amino-2-chloro-6-fluorophenyl)acetamide.

Powdered iron (325 mesh; 2.16 g, 38.7 mmol) was added to a solution of ethanol (50 mL) and concentrated hydrochloric acid (0.37 mL, 3.87 mmol) with stirring. The suspension was heated at 65°C for 1 hour and then cooled to 55°C. A solution of ammonium chloride (1.49 g, 27.0 mmol) in water (5 ml) was added, then N-(2-chloro-6-fluoro-3-nitrophenyl)acetamide (1.8 g, 7.74 mmol) was added. . The reaction mixture was heated at 60°C for 8 hours, cooled and filtered through a pad ^{of Celite®} . The filtrate was extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure in a rotary evaporator. Purification by flash silica gel chromatography gave the title compound as a tan solid (1.2 g, 72%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.51 (s, 1H), 6.96 (t, J = 9.2 Hz, 1H), 6.71 (dd, J = 9.0, 5.1 Hz, 1H), 5.23 (s, 2H), 2.03 (s , 3H); ESIMS m/z 203 ([M+H] ⁺ ).

Example 71: Preparation of 3-amino-2,6-difluorophenylacetate (C195)

3-Amino-2,6-difluorophenol (0.074 g, 0.51 mmol) and 4-dimethylaminopyridine (0.005 g, 0.042 mmol) were dissolved in methylene chloride (2 ml) and the resulting solution was cooled in an ice bath under a nitrogen atmosphere. Acetic anhydride (0.042 ml, 0.446 mmol) and triethylamine (0.062 ml, 0.446 mmol) were added by syringe while stirring. After 3 hours, analysis by thin layer chromatography (1:1 hexanes-ethyl acetate) indicated complete conversion. The reaction mixture was concentrated, loaded directly onto a silica gel flash column and eluted with 4:1 hexanes-ethyl acetate to give the title compound as an orange sticky solid (0.071 g, 89%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.78 (td, J = 9.2, 2.2 Hz, 1H), 6.58 (td, J = 9.1, 5.0 Hz, 1H), 3.63 (br s, 2H) , 2.37 (s, 3H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -140.23 (d, J = 1.6 Hz), -146.77 (d, J = 1.9 Hz); EIMS m/z 187.

Example 72: Preparation of 5-amino-2-chloro-3-fluorobenzoic acid (C196)

To a solution of 2-chloro-3-fluoro-5-nitrobenzoic acid (C206) (5 g, 22.8 mmol) in ethyl acetate (150 ml) was added 5% platinum on carbon (0.5 g, 10% w/w .) and the reaction mixture was stirred under a hydrogen atmosphere (15 psi) for 24 ^hours . The reaction mixture was carefully filtered through a pad ^{of Celite®} , the layer was washed with 50% ethyl acetate in methanol and the filtrate was concentrated under reduced pressure. The crude product was triturated with diethyl ether to give the title compound as a pale yellow solid (2.1 g, 50%): m.p. 187 - 189°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.28 (br s, 1H), 6.81 (dd, J = 1.2, 2.4 Hz, 1H), 6.61 (dd, J = 2.4, 12.0 Hz, 1H), 5.77 (br s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -114.65; ESIMS m/z 190 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 72:

5-Amino-2-chloro-3-(trifluoromethyl)benzoic acid (C197)

Isolated as a brown solid (3.2 g, 68%): m.p. 195 - 197°C; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.18 - 7.08 (m, 1H), 7.06 - 7.02 (m, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -61.21; ESIMS m/z 240 ([M+H] ⁺ ).

5-Amino-2-chloro-3-methylbenzoic acid (C198)

Isolated as a brown solid (3.2 g, 72%): m.p. 190 - 192°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 12.82 (br s, 1H), 6.76 (d, J = 2.4 Hz, 1H), 6.67 (d, J = 2.4 , 1H), 2.22 (s, 3H); ESIMS m/z 186 ([M+H] ⁺ ).

5-Amino-2,3-difluorobenzoic acid (C199)

Isolated as a brown solid (2.5 g, 60%): m.p. 211 - 213°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.20 (br s, 1H), 6.84 - 6.78 (m, 1H), 6.74 - 6.64 (m, 1H), 5 .46 (br s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -138.22, -155.42; ESIMS m/z 174 ([M+H] ⁺ ).

5-Amino-3-chloro-2-fluorobenzoic acid (C200)

Isolated as a brown solid (4.0 g, 66%): m.p. 205 - 207°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 13.40 (br s, 1H), 7.02 - 6.94 (m, 1H), 6.92 - 6.84 (m, 1H), 5 .48 (br s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -132.31; ESIMS m/z 190 ([M+H] ⁺ ).

5-Amino-2-fluoro-3-methylbenzoic acid (C201)

Isolated as a brown solid (5.2 g, 76%): m.p. 206 - 208°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 12.82 (br s, 1H), 6.88 - 6.80 (m, 1H), 6.68 - 6.58 (m, 1H), 5 .28 (br s, 2H), 2.12 (s, 3H); ¹⁹ F NMR (282 MHz, DMSO-d ₆ ) δ -132.24; ESIMS m/z 170 ([M+H] ⁺ ).

5-Amino-3-chloro-2-methylbenzoic acid (C202)

Isolated as an almost white solid (1.3 g, 65%): m.p. 192 - 194°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 12.82 (br s, 1H), 6.93 (d, J = 2.1 Hz, 1H), 6.78 (d, J = 2.4 Hz, 1H), 5.37 (br s, 2H), 2.31 (s, 3H); ESIMS m/z 186 ([M+H] ⁺ ).

5-Amino-3-fluoro-2-methylbenzoic acid (C203)

Isolated as a brown solid (0.3 g, 55%): m.p. 164 - 166°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 12.82 (br s, 1H), 6.87 (d, J = 2.0 Hz, 1H), 6.48 (dd, J = 2.0 , 8.0 Hz, 1H), 5.36 (br s, 2H), 2.19 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -116.94; ESIMS m/z 170 ([M+H] ⁺ ).

5-Amino-3-chloro-2-methoxybenzoic acid (C204)

Isolated as a brown solid (2.5 g, 75%): m.p. 173 - 175°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 12.8 (br s, 1H), 6.84 (d, J = 2.8 Hz, 1H), 6.79 (d, J = 2.8 Hz, 1H), 5.62 (br s, 2H), 3.68 (s, 3H); ESIMS m/z 202 ([M+H] ⁺ ).

5-Amino-3-fluoro-2-methoxybenzoic acid (C205)

Isolated as a pale yellow solid (6.01 g, 85%): m.p. 148 - 150°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 12.82 (br s, 1H), 6.72 - 6.66 (m, 1H), 6.55 (dd, J = 2.0, 13, 6 Hz, 1H), 5.40 (br s, 2H), 3.69 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -131.02; ESIMS m/z 186 ([M+H] ⁺ ).

Example 73: Preparation of 2-chloro-3-fluoro-5-nitrobenzoic acid (C206)

To a suspension of 2-chloro-3-fluorobenzoic acid (10 g, 57.5 mmol) in concentrated sulfuric acid (62 mL, 1149.5 mmol), concentrated nitric acid (4 mL, 86.2 mmol) was added dropwise at -10°C and the reaction mixture was stirred at -10°C to 0°C for 3 hours. the mixture was slowly poured into a glass with crushed ice (~1 L) and the resulting solid was filtered and washed with water (100 ml). The crude product was recrystallized from hot water to give the title compound as an off-white solid (7.5 g, 60%): m.p. 163 - 165°C;¹H NMR (400 MHz, DMSO-d₆) δ 14.60 - 13.92 (br s, 1H), 8.53 (dd, J = 2.8, 8.8 Hz, 1H), 8.44 - 8.41 (m, 1H);¹⁹F NMR (376 MHz, DMSO-d₆) δ -108.50; ESIMS m/z 218 ([M-H]^-).

The following compounds were prepared using a procedure similar to that described in Example 73:

2-Chloro-5-nitro-3-(trifluoromethyl)benzoic acid (C207)

The title compound was recrystallized from hot water to give a brown solid (9 g, 80%): m.p. 165 - 167°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.77 (d, J = 2.8 Hz, 1H), 8.61 (d, J = 2.8 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -61.72; ESIMS m/z 268 ([MH] ^- ).

2-Chloro-3-methyl-5-nitrobenzoic acid (C208)

The title compound was precipitated from diethyl ether solution with n-pentane to give an almost white solid (8.2 g, 65%): m.p. 205 - 207°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 8.41 (d, J = 2.4 Hz, 1H), 8.34 (d, J = 3.0 Hz, 1H), 2.24 (s , 3H); ESIMS m/z 214 ([MH] ^- ).

2,3-Difluoro-5-nitrobenzoic acid (C209)

The title compound was recrystallized from hot water to give an almost white solid (5.2 g, 40%): m.p. 132 - 134°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 14.60 - 13.80 (br s, 1H), 8.74 - 8.62 (m, 1H), 8.52 - 8.40 (m, 1H); ¹⁹ F NMR (282 MHz, DMSO-d ₆ ) δ -125.36, -132.16; ESIMS m/z 202 ([MH] ^- ).

3-Chloro-2-fluoro-5-nitrobenzoic acid (C210)

The title compound was recrystallized from hot water to give an almost white solid (6.9 g, 55%): m.p. 186 - 188°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 14.40 - 13.80 (br s, 1H), 8.78 - 8.70 (m, 1H), 8.58 - 8.48 (m, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -102.78; ESIMS m/z 218 ([MH] ^- ).

2-Fluoro-3-methyl-5-nitrobenzoic acid (C211)

The title compound was precipitated with water from the methanol solution to give a pale brown solid (7.5 g, 58%): m.p. 168 - 170°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 13.88 (br s, 1H) 8.48 - 8.40 (m, 2H), 2.41 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -106.64; ESIMS m/z 198 ([MH] ^- ).

3-Chloro-2-methoxy-5-nitrobenzoic acid (C212)

Note: The reaction solvent was a mixture of sulfuric acid and acetic acid (1:1) and the title compound was recrystallized from hot water and isolated as an almost white solid (9.3 g, 75%): m.p. 155 - 157°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 8.54 (d, J = 2.4 Hz, 1H), 8.42 (d, J = 2.4 Hz, 1H), 3.96 (s , 3H); ESIMS m/z 232 ([MH] ^- ).

3-Fluoro-2-methoxy-5-nitrobenzoic acid (C213)

Note: The reaction solvent was a mixture of sulfuric acid and acetic acid (1:1) and the title compound was recrystallized from hot water and isolated as an almost white solid (9.1 g, 70%): m.p. 106 - 108°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.62 (br s, 1H), 8.40 (dd, J = 2.8, 10.8 Hz, 1H), 8.32 - 8.28 (m, 1H), 4.04 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -125.26; ESIMS m/z 216 ([M+H] ⁺ ).

Example 74: Preparation of methyl 3-chloro-2-methyl-5-nitrobenzoate (C214)

Step 1: Preparation of 3-chloro-2-methyl-5-nitrobenzoic acid. To a suspension of 3-chloro-2-methylbenzoic acid (10 g, 57.5 mmol) in concentrated sulfuric acid (48 ml, 867 mmol), concentrated nitric acid (2.5 ml, 68.4 mmol) was added dropwise at -10°C and the reaction mixture was stirred at -10°C to 0°C for 3 hours. the mixture was slowly poured into a beaker filled with crushed ice (~1 L) and the precipitated solid was collected by filtration and washed with water (100 ml). The crude product was recrystallized from hot water to give a mixture of 3-chloro-2-methyl-5/6-nitrobenzoic acid as a brown solid (7.5 g) which was used without purification: ESIMS m/z 214 ([M-H]^-).

Step 2: Preparation of methyl 3-chloro-2-methyl-5-nitrobenzoate. While stirring, thionyl chloride was added to a solution of 3-chloro-2-methyl-5/6-nitrobenzoic acid (6 g, 28 mmol) in methanol (100 ml) at ambient temperature and the reaction mixture was stirred at 80 °C for 4 h. The reaction mixture was concentrated under reduced pressure. Purification by silica gel column chromatography using 20-30% ethyl acetate in petroleum ether as eluent gave the title compound (1.5 g; 12% yield in 2 steps) as a pale yellow solid: ¹ H NMR (400 MHz , CDCl ₃ ) δ 8.58 (d, J = 2.4 Hz, 1H), 8.37 (d, J = 2.4 Hz, 1H), 3.97 (s, 3H), 2.72 ( s, 3H); ESIMS m/z 228 ([MH] ^- ).

The following compounds were prepared using a procedure similar to that described in Example 74:

Methyl 3-fluoro-2-methyl-5-nitrobenzoate (C215)

Isolated as a pale yellow solid (1 g, 10% yield in 2 steps): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.58 (s, 1H), 8.04 (dd, J = 2, 4, 9.0 Hz, 1H), 3.97 (s, 3H), 2.61 (d, J = 2.4, 3H); ESIMS m/z 214 ([M+H] ⁺ ).

Example 75: Preparation of 3-chloro-2-methyl-5-nitrobenzoic acid (C216)

With stirring, to a solution of methyl 3-chloro-2-methyl-5-nitrobenzoate (C214) (1.5 g, 6.5 mmol) in a mixture of tetrahydrofuran, methanol and water (2:1:2; 20 ml total) lithium hydroxide monohydrate (0.820 g, 19.5 mmol) and the reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in water (20 ml) and acidified with 2N. hydrochloric acid (10 ml; pH = 1-2). The resulting solid was collected by filtration, washed with water (50 ml) and dried in vacuo to give the title compound (1 g, 71%) as an off-white solid: m.p. 176 - 178°C; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.9 (br s, 1H), 8.43 (s, 2H), 2.64 (s, 3H); ESIMS m/z 214 ([MH] ^- ).

The following compounds were prepared using a procedure similar to that described in Example 75:

3-Fluoro-2-methyl-5-nitrobenzoic acid (C217)

Isolated as an almost white solid (0.800 g, 86%): m.p. 146 - 148°C; ^1H NMR (300 MHz, DMSO- _d6 ) δ 13.92 (br s, 1H), 8.37 (s, 1H), 8.25 (dd, J = 2.4, 9.3 Hz, 1H ), 2.50 (d, J = 2.1 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -110.64; ESIMS m/z 198 ([MH] ^- ).

Example 76: Preparation of 2-chloro-N,N'-dimethyl-5-nitro-N'-phenylbenzohydrazide (C218)

To a solution of 2-chloro-N'-methyl-5-nitro-N'-phenylbenzohydrazide (C219) (0.273 g, 0.893 mmol) in N,N-dimethylformamide (8.5 ml), cooled to 0°C, was added the hydride sodium (60% dispersion in oil, 0.045 g, 1.116 mmol). The reaction mixture was stirred at 0°C for 15 min and then methyl iodide (0.070 ml, 1.116 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 3 hours. The reaction was stopped with water (10 ml) and extracted with ethyl acetate (25 ml). The organic layer was washed with water (3×15 ml) and brine (15 ml) and then concentrated under reduced pressure to give the title compound as a yellow solid (0.283 g, 98%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.13 (d, J = 2.6 Hz, 1H), 8.08 (dd, J = 8.8, 2.6 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H ), 7.32 (dd, J = 8.9, 7.3 Hz, 2H), 6.95 (tt, J = 7.3, 1.1 Hz, 1H), 6.75 (dt, J = 7.9, 1.1 Hz, 2H), 3.20 (s, 3H), 3.11 (s, 3H); IR (thin film) 3074, 2925, 1662, 1524, 1494, 1345, 869, 741 cm ^-1 ; ESIMS m/z 320 ([M+H] ⁺ ).

Example 77: Preparation of 2-chloro-N'-methyl-5-nitro-N'-phenylbenzohydrazide (C219)

To a solution of 2-chloro-5-nitrobenzoic acid (0.300 g, 1.49 mmol) and 1-methyl-1-phenylhydrazine (0.282 g, 2.31 mmol) in ethyl acetate (5.0 ml) was added with stirring at room temperature pyridine (0.235 g, 2.98 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide ( ^T3P® ) as a 50% solution in ethyl acetate (1.421 g, 2.23 mmol). The reaction mixture was stirred at room temperature for 48 hours. The reaction mixture was diluted with ethyl acetate (20 ml). The organic phase was washed with 1 M aqueous hydrochloric acid (15 ml), water (2 x 10 ml) and brine (10 ml) and concentrated under reduced pressure. Purification by column chromatography using 0-35% ethyl acetate/hexanes as eluent gave the title compound as a pale yellow solid (0.273 g, 60%): ¹ H NMR (400 MHz, CDCl ₃ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.71 (s, 1H), 8.47 (d, J = 2.8 Hz, 1H), 8.34 (dd, J = 8.8, 2.8 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.41 - 7.17 (m, 2H), 6.94 (dt, J = 7.7, 1.0 Hz, 2H ), 6.87 - 6.52 (m, 1H), 3.24 (s, 3H); IR (thin film) 3207, 3064, 2967, 2807, 1670, 1538, 1351, 737 cm ^-1 ; ESIMS m/z 306 ([M+H] ⁺ ).

Example 78: Preparation of 1-methyl-2-(3,3,3-trifluoropropylidene)hydrazine (C220)

To a solution of 3,3,3-trifluoropropanal (0.600 g, 5.4 mmol) in ethanol (12 ml) was added methylhydrazine (0.493 g, 10.8 mmol) and acetic acid (0.1 ml) at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water (20 ml) and extracted with diethyl ether (2×20 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (crude) as a brown liquid (0.600 g): ¹ H NMR (300 MHz, CDCl ₃ ) δ 6.67 (t, J = 5 .6 Hz, 1H), 5.34 - 5.30 (m, 1H), 3.10 - 2.96 (m, 2H), 2.83 (s, 3H).

Example 79: Preparation of 5-amino-N-(3-amino-2,4-difluorophenyl)-2-chlorobenzamide hydrochloride (C221)

A 4 M solution of hydrochloric acid in 1,4-dioxane (4.5 ml, 18 mmol) was added with stirring to a solution of tert-butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-amino- 2-chlorobenzamido)-2,6-difluorophenyl)carbamate (C135) in dichloromethane (18 ml) at 23°C. The resulting thick, off-white mixture was stirred at 23°C for 18 hours. The reaction mixture was concentrated by rotary evaporation to give the title compound as an off-white powder (0.660 g, 99% crude yield): 1H NMR (400 MHz, DMSO-d6) δ 10.16 (s, 1H), 7.47 (d, J = 8.5 Hz, 1H), 7.23 (br s, 1H), 7.17 (br d, J = 8 .5 Hz, 1H), 6.90 (td, J = 10, 1.2 Hz, 1H), 6.80 (m, 1H); ESIMS m/z 298 ([M+H]+).

Example 80: Preparation of 2-chloro-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)-5-nitrobenzamide (C222)

To a solution of N-(3-amino-2,6-difluorophenyl)-2,2-difluoroacetamide (C186) (0.455 g, 2.05 mmol) in ethyl acetate (7 ml) was added sodium bicarbonate (0.344 g, 4.10 mmol ) and 2-chloro-5-nitrobenzoyl chloride (0.451 mg, 2.05 mmol). The reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was diluted with ethyl acetate and washed with water (15 ml). The organic layer was passed through a phase separator to dry and concentrated to give the title compound as a white solid (0.55 g, 66%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.80 (s, 1H), 10.69 (s, 1H), 8.50 (d, J = 2.7 Hz, 1H), 8.35 (dd, J = 8.8, 2.8 Hz, 1H), 7, 94 - 7.80 (m, 2H), 7.31 (td, J = 9.3, 1.8 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -120.61 (d, J = 2.6 Hz), -124.72 (d, J = 2.7 Hz), -125.81; ESIMS m/z 406 ([M+H] ⁺ ).

Example 81: Preparation of tert-butyl-(3-methyl-4-nitrophenyl)carbamate (C223)

N,N-Dimethylpyridin-4-amine (2.41 g, 19.72 mmol) was added portionwise with stirring to a solution of 3-methyl-4-nitroaniline (15 g, 99 mmol) and di-tert-butyl dicarbonate (25.8 g, 118 mmol) in dichloromethane (200 ml). The resulting yellow solution was stirred at 24°C for 18 hours and concentrated in vacuo on a rotary evaporator. Purification by flash silica gel chromatography with a gradient of ethyl acetate in hexanes gave the title compound as a pale yellow solid (11.5 g, 44%), 1H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 9.0 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.30 (dd, J = 9.0, 2.5 Hz, 1H), 6.80 ( s, 1H), 2.62 (s, 3H), 1.53 (s, 9H); ¹³ C NMR (101 MHz, CDCl3) δ 151.96, 142.97, 136.22, 126.70, 120.79, 115.55, 81.75, 28.22, 21.45; ESIMS m/z 253 ([M+H] ⁺ ).

Example R1: Resolution of racemic trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid with (L)-leucinamide to give (1R,3R)-2,2-dichloro-3 -(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid

Mixture of (L)-leucinamide (163 mg, 1.25 mmol) and racemic trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-carboxylic acid) (750 mg, 2.5 mmol) in acetonitrile (20 ml) was stirred at 60°C for 0.5 h. Once the solid began to precipitate, the mixture was kept at room temperature for 4 h. The white solid was collected, washed with a minimum amount of acetonitrile and dried: ¹ H NMR (400 MHz, DMSO-d ⁶ ) δ 7.81 (s, 1H), 7.53 (t, J = 1.9 Hz, 1H), 7.43 (d, J = 1.9 Hz, 2H), 7.31 (s, 1H), 3.58 - 3.44 (m, 1H), 3.27 (d, J = 8.6 Hz, 1H), 3.08 (d, J = 8.6 Hz, 1H) , 1.68 (dt, J = 13.3, 6.6 Hz, 1H), 1.49 (dt, J = 10.1, 6.8 Hz, 2H), 0.89 (t, J = 6 .7 Hz, 6H).

The white solid salt was diluted with EtOAc and washed with 1N. HCl and brine. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated to give the title product as a white solid: (0.202 g, 91% EI, 27% yield); ^1H NMR (300 MHz, CDCl ₃ ) δ 7.36 (t, J = 1.9 Hz, 1H), 7.17 (dd, J = 1.9, 0.7 Hz, 2H), 3.48 - 3.37 (m, 1H), 2.87 (d, J = 8.3 Hz, 1H). ¹³ C NMR (400 MHz, DMSO-d ⁶ ) δ 166.28, 136.40, 133.39, 127.27, 127.04, 61.36, 37.10, 35.98. LCMS m/z = 298.9 [M+H].

Example R2: Resolution of racemic trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid with (L)-leucinamide to give (R,R)-trans-2,2 -dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid

Mixture of (L)-leucinamide (0.45 g, 3.5 mmol) and racemic trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-carboxylic acid) (1.41 g, 5 mmol) in acetonitrile (20 ml) was stirred at 60°C for 0.5 h. Once the solid began to precipitate, the mixture was kept at room temperature for 4 h. The white solid was collected, washed with a minimum amount of acetonitrile and dried: 1H NMR ( 400 MHz, DMSO-d6) δ 7.81 (s, 1H), 7.53 (t, J = 1.9 Hz, 1H), 7.43 (d, J = 1.9 Hz, 2H), 7 .31 (s, 1H), 3.58 - 3.44 (m, 1H), 3.27 (d, J = 8.6 Hz, 1H), 3.08 (d, J = 8.6 Hz, 1H), 1.68 (dt, J = 13.3, 6.6 Hz, 1H), 1.49 (dt, J = 10.1, 6.8 Hz, 2H), 0.89 (t, J = 6.7 Hz, 6H).

The white solid salt was diluted with EtOAc and washed with 1N. HCl and brine. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated to give the title product as a white solid: (0.64 g, 91% EI, 45% yield); 1H NMR (400 MHz, DMSO-d6) δ 13.29 (s, 1H), 7.72 (dd, J = 7.1, 2.1 Hz, 1H), 7.56 - 7.32 (m, 2H), 3.46 (d, J = 1.0 Hz, 2H); 19F NMR (376 MHz, DMSO-d6) δ -117.35.

Example R3: Resolution of racemic trans-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid with (L)-leucinamide to give (R,R)-trans-2,2-dichloro -3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid

Mixture of (L)-leucinamide (326 mg, 2.5 mmol) and racemic trans-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarboxylic acid) (1.5 g, 5 mmol) in acetonitrile (20 ml) was stirred at 60°C for 0.5 h. Once the solid began to precipitate, the mixture was kept at room temperature for 4 h. The solid was collected, washed with a minimum amount of acetonitrile and dried: ¹ H NMR (400 MHz, DMSO -d ⁶ ) δ 7.72 (s, 1H), 7.64 (d, J = 2.1 Hz, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.34 ( dd, J = 8.4, 2.1 Hz, 1H), 7.31 - 7.26 (m, 1H), 3.48 (dd, J = 8.2, 6.2 Hz, 1H), 3 .26 (d, J = 8.6 Hz, 1H), 3.03 (d, J = 8.7 Hz, 1H), 1.74 - 1.57 (m, 1H), 1.47 (ddd, J = 14.6, 7.7, 6.1 Hz, 2H), 0.89 (t, J = 6.9 Hz, 6H).

The white solid salt was diluted with EtOAc and washed with 1N. HCl and brine. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated to give the title product as a white solid: (0.56 g, 96% EI, 36% yield); ^1H NMR (500 MHz, DMSO- ^d6 ) δ 13.39 (s, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.64 (d, J = 8.3 Hz , 1H), 7.44 (dd, J = 8.4, 2.1 Hz, 1H), 3.49 (s, 2H). ¹³ C NMR (126 MHz, DMSO) δ 166.34, 133.35, 130.47, 130.33, 130.09, 129.77, 128.81, 61.43, 37.00, 36.06. LCMS m/z = 298.9 [M+H].

Example R4: Resolution of racemic trans-2,2-dichloro-3-(3-trifluoromethyl-4-fluorophenyl)cyclopropane-1-carboxylic acid with (L)-leucinamide to give (1R,3R)-2,2-dichloro -3-(3-trifluoromethyl-4-fluorophenyl)cyclopropane-1-carboxylic acid

Mixture of (L)-leucinamide (15.6 g, 120 mmol) and racemic trans-2,2-dichloro-3-(3-trifluoromethyl-4-fluorophenyl)cyclopropane-1-carboxylic acid (63.4 g, 200 mmol ) in acetonitrile (800 ml) was stirred at 60°C for 1 hour. Once the solid began to precipitate, the mixture was kept at room temperature for 4 hours. The solid was collected, washed with a minimal amount of acetonitrile and dried to give the (L)-leucinamide salt and trans-(1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylate as a white solid: (38.9 g, 95% EI, 43%); ^1H NMR (400 MHz, DMSO- ^d6 ) δ 7.80 (s, 1H), 7.73 (m, Hz, 2H), 7.49 (dd, J = 10.7, 8.6 Hz, 1H), 7.31 (s, 1H), 3.53 (dd, J = 7.9, 6.4 Hz, 1H), 3.34 (d, J = 8.6 Hz, 1H), 3, 07 (d, J = 8.6 Hz, 1H), 1.77 - 1.60 (m, 1H), 1.60 - 1.40 (m, 2H), 0.89 (t, J = 6, 7 Hz, 6H); ¹⁹ F NMR (376 MHz, DMSO) δ -59.88, -117.93.

The white solid salt was diluted with EtOAc and washed with 1.5N. HCl and water. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated to give the title product as a white solid (27.3 g, 95% EI, 43% yield). ^1H NMR (400 MHz, DMSO- ^d6 ) δ 13.24 (s, 1H), 8.03 - 7.71 (m, 2H), 7.54 (dd, J = 10.6, 8.7 Hz, 1H), 3.65 - 3.51 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ⁶ ) δ -59.93, -117.06; LCMS m/z = 316 [MH].

Example R5: Resolution of racemic trans-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid with (R)-2-amino-3-phenylpropanamide-((D )-phenylalanine) and obtaining (R)-2-amino-3-phenylpropanamide-(1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylate

In a flask with a magnetic stirrer, a mixture of 2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (1.58 g, 5.0 mmol) and (R)-2- amino-3-phenylpropanamide (411 mg, 2.5 mmol) in acetonitrile (20 ml) was heated at 60°C. The resulting suspension was stirred at 60°C for 10 min, then cooled to RT. The mixture was stirred overnight. The product was filtered and washed with acetonitrile, then dried in air and at 35°C in a vacuum oven to obtain (R)-2-amino-3-phenylpropanamide (1R,3R)-2,2-dichloro-3-(4-fluoro -3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylate (710 mg, 1.475 mmol, 29.5% yield) as a white solid. Chiral HPLC analysis showed that the SS/RR ratio was 6/93 (86% EI).

Example R6: Resolution of racemic trans-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid with (S)-2-amino-3-phenylpropanamide to obtain (S )-2-amino-3-phenylpropanamide-(1S,3S)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylate

In a flask with a magnetic stirrer, a mixture of racemic 2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (1.58 g, 5.0 mmol) and (S)-2 -amino-3-phenylpropanamide (411 mg, 2.5 mmol) in acetonitrile (ACN, 20 ml) was heated at 60°C. The resulting suspension was stirred at 60°C for 10 min, then cooled to RT. The mixture was stirred overnight. The product was filtered and washed with ACN, then dried in air and at 35°C in a vacuum oven to give (S)-2-amino-3-phenylpropanamide-(1S,3S)-2,2-dichloro-3-( 4-Fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylate (0.669 g, 1.390 mmol, 27.8% yield) as a white solid. Chiral HPLC analysis showed that the SS/RR ratio was 96/3 (93%EI).

The following compounds were prepared using a procedure similar to that described in example 1:

trans-5-(3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(2,2,2- trifluoroacetamido)phenyl)benzamide (F1358)

Isolated as a white solid (0.140 g, 63%).

trans-5-(3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl )benzamide (F1359)

Isolated as a white solid (0.098 g, 56%).

trans-2-Chloro-N-(4-chloro-3-(2,2,2-trifluoroacetamido)phenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1 -carboxamido)benzamide (F1366)

Isolated as a white solid (0.076 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3,5-dichloro-4-(2,2,2 -trifluoroacetamido)phenyl)benzamide (F1368)

Isolated as a white solid (0.069 g, 76%).

trans-2-Chloro-N-(3-chloro-4-(2,2,2-trifluoroacetamido)phenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1 -carboxamido)benzamide (F1384)

Isolated as a white solid (0.093 g, 70%).

trans-2-Chloro-N-(3-cyano-4-(2,2,2-trifluoroacetamido)phenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1 -carboxamido)benzamide (F1388)

Isolated as a yellow foam (0.039 g, 72%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,3-dimethyl-4 -(2,2,2-trifluoroacetamido)phenyl)benzamide (F1392)

Isolated as a white foamy substance (0.055 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2,2-trifluoroacetamido)-3- (trifluoromethyl)phenyl)benzamide (F1393)

Isolated as a white foamy substance (0.078 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,6-difluorophenyl)benzamide (F1394)

Isolated as a white foamy substance (0.078 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2-methyl-3-( 2,2,2-trifluoroacetamido)phenyl)benzamide (F1451)

Isolated as a white solid (0.087 g, 75%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl) -2-fluorobenzamide (F1491)

Isolated as a white solid (0.086 g, 76%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2,2-trifluoroacetamido )phenyl)-2-fluorobenzamide (F1492)

Isolated as a white solid (0.102 g, 87%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2,4-difluorophenyl) -2-fluorobenzamide (F1509)

Isolated as a white foamy substance (0.059 g, 51.9%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2,2-trifluoroacetamido )phenyl)-2-fluorobenzamide (F1510)

Isolated as a tan solid (0.119 g, 85%).

trans-5-(3-(4-Bromophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide (F1597 )

Isolated as a clear, colorless oil (0.050 g, 86%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide ( F1598)

Isolated as a clear, colorless oil (0.052 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-chlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide ( F1599)

Isolated as a white foamy substance (0.101 g, 87%).

trans-5-(3-(3-Bromophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide (F1600 )

Isolated as a clear, colorless oil (0.057 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide ( F1601)

Isolated as a white foamy substance (0.076 g, 75%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide ( F1602)

Isolated as a white foamy substance (0.103 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoro-N-methylacetamido)phenyl)benzamide (F1614)

Isolated as a white foamy substance (0.109 g, 93%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,3,3,3-pentafluoro-N-methylpropanamido)phenyl)benzamide (F1615)

Isolated as a white foamy substance (0.123 g, 98%).

trans-5-(3-(3-Bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4 -difluorophenyl)benzamide (F1623)

Isolated as a white foamy substance (0.061 g, 68%). The desired compound was obtained from N-(3-amino-2,4-difluorophenyl)-5-(3-(3-bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide, which was obtained according to the methods described in the publication of the U.S. patent application. US20160304522A1 (F621).

trans-2-Chloro-5-(2,2-dichloro-3-(4-fluoro-3-iodophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4- difluorophenyl)benzamide (F1624)

Isolated as a white solid (0.066 g, 74%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)benzamide (F1656)

Isolated as a white foamy substance (0.077 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,4-difluorophenyl)benzamide (F1657)

Isolated as a white foamy substance (0.082 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2 ,4-difluorophenyl)benzamide (F1675)

Isolated as a white solid (0.077 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(5-(2,2- difluoroacetamido)-2,4-difluoro-3-methylphenyl)benzamide (F1680)

Isolated as a white foamy substance (0.048 g, 71%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)benzamide (F1695)

Isolated as a yellow foam (0.094 g, 80%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,3,3,3-pentafluoropropanamido)phenyl)benzamide (F1696)

Isolated as a white foamy substance (0.089 g, 71%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,4-difluorophenyl)benzamide (F1711)

Isolated as a white solid (0.075 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(5-(2,2- difluoroacetamido)-2,3,4-trifluorophenyl)benzamide (F1744)

Isolated as a clear, colorless oil (0.117 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-N-methylbenzamide (F1792)

Isolated as a white foamy substance (0.082 g, 70%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)-N-methylbenzamide (F1795)

Isolated as a light yellow oil (0.091 g, 79%).

trans-5-(3-(3,5-bis(Trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(2,2, 2-trifluoroacetamido)phenyl)benzamide (F1801)

Isolated as a white solid (0.098 g, 86%).

trans-5-(3-(3,5-bis(Trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4 -difluorophenyl)benzamide (F1802)

Isolated as a white solid (0.096 g, 86%).

The following compounds were prepared using a procedure similar to that described in example 2:

N-(3-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1493 )

Isolated as a tan solid (0.100 g, 66%).

N-(5-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1511 )

Isolated as a white foam (0.108 g, 84%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1658)

Isolated as a white solid (0.061 g, 72%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido) benzamide (F1694)

Isolated as a white foamy substance (0.094 g, 88%). The desired compound was obtained from N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane- 1-carboxamido)benzamide, which was prepared according to the methods described in the publication of the U.S. patent application. US20160304522A1 (F317).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-N-methylbenzamide (F1799)

Isolated as a white foamy substance (0.070 g, 65%).

trans-N-(3-Acetamido-2,4-difluorophenyl)-5-(3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1803)

Isolated as a white foamy substance (0.062 g, 58%).

The following compounds were prepared using a procedure similar to that described in example 3:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1340)

Isolated as a white solid (0.050 g, 96%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 6-difluorophenyl)-3-fluorobenzamide (F1341)

Isolated as a yellow solid (0.052 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1342)

Isolated as a white solid (0.051 g, 98%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,6-difluorophenyl)-3-fluorobenzamide (F1343)

Isolated as an almost white solid (0.050 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1344)

Isolated as a white solid (0.049 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 6-difluorophenyl)-3-fluorobenzamide (F1345)

Isolated as a white solid (0.047 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1346)

Isolated as a white solid (0.046 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,6-difluorophenyl)-3-fluorobenzamide (F1347)

Isolated as an almost white solid (0.045 g, 100%).

N-(3-(2-Bromo-2,2-difluoroacetamido)-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-3-fluorobenzamide (F1356)

Isolated as an almost white solid (0.048 g, 96%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)- 2,4-difluorophenyl)-3-fluorobenzamide (F1400)

Isolated as a tan solid (0.086 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2 ,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1401)

Isolated as a white solid (0.087 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2, 4-difluorophenyl)-3-fluorobenzamide (F1402)

Isolated as a tan solid (0.078 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1403)

Isolated as a light yellowish-brown solid (0.090 g, 93%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)- 2,4-difluorophenyl)-3-fluorobenzamide (F1404)

Isolated as a light yellowish-brown solid (0.085 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2 ,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1405)

Isolated as a white solid (0.085 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(5-(2,2- difluoroacetamido)-2,4-difluorophenyl)-3-fluorobenzamide (F1406)

Isolated as a light yellowish-brown solid (0.087 g, 94%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5 -(2,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1407)

Isolated as a white solid (0.086 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2, 4-difluorophenyl)-3-fluorobenzamide (F1408)

Isolated as a light yellowish-brown solid (0.084 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1409)

Isolated as a white solid (0.087 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 6-difluorophenyl)-3-methylbenzamide (F1429)

Isolated as a white solid (0.056 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1430)

Isolated as a tan solid (0.057 g, 98%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,6-difluorophenyl)-3-methylbenzamide (F1431)

Isolated as a tan solid (0.058 g, 94%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1432)

Isolated as a white solid (0.060 g, 95%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,6-difluorophenyl)-3-methylbenzamide (F1468)

Isolated as a white solid (0.056 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1469)

Isolated as a white solid (0.058 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2, 4-difluorophenyl)-3-methylbenzamide (F1484)

Isolated as a yellowish-brown powdery substance (0.057 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1485)

Isolated as a yellowish-brown powdery substance (0.058 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- 2,4-difluorophenyl)-3-methylbenzamide (F1486)

Isolated as a yellowish-brown powdery substance (0.062 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1487)

Isolated as a yellowish-brown powdery substance (0.060 g, 95%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,4-difluorophenyl)-3-methylbenzamide (F1494)

Isolated as a yellowish-brown powdery substance (0.047 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1495)

Isolated as a yellowish-brown powdery substance (0.049 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2, 4-difluorophenyl)-3-methylbenzamide (F1496)

Isolated as a yellowish-brown powdery substance (0.055 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2 ,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1497)

Isolated as a yellowish-brown powdery substance (0.063 g, 100%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)- 2,4-difluorophenyl)-3-methylbenzamide (F1498)

Isolated as a yellowish-brown powdery substance (0.067 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2 ,2,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1499)

Isolated as a yellowish-brown powdery substance (0.066 g, 95%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(5-(2,2- difluoroacetamido)-2,4-difluorophenyl)-3-methylbenzamide (F1500)

Isolated as a yellowish-brown powdery substance (0.056 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5 -(2,2,2-trifluoroacetamido)phenyl)-3-methylbenzamide (F1501)

Isolated as a yellowish-brown powdery substance (0.057 g, 99%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1502)

Isolated as a yellowish-brown powdery substance (0.039 g, 52%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-fluorobenzamide (F1504)

Isolated as a yellowish-brown powdery substance (0.071 g, 44%).

The following compounds were prepared using a procedure similar to that described in example 4:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,3,3-tetrafluoropropanamido)phenyl)benzamide (F1414)

Isolated as a white foam (0.104 g, 85%).

2-Chloro-N-(2,4-dichloro-3-(2-cyanoacetamido)phenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1 -carboxamido)benzamide (F1415)

Isolated as a white solid (0.110 g, 98%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)furan -2-carboxamide (F1416)

Isolated as a white solid (0.089 g, 76%).

2-Chloro-N-(3-(2-cyclopropylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1- carboxamido)benzamide (F1417)

Isolated as a white solid (0.104 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(3,3 ,3-trifluoropropanamido)phenyl)benzamide (F1418)

Isolated as a white solid (0.103 g, 87%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(3-ethoxypropanamido)-2,4- difluorophenyl)benzamide (F1419)

Isolated as a white foamy substance (0.098 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,3,3,4,4,4-heptafluorobutanamido)phenyl)benzamide (F1463)

Isolated as a white foamy substance (0.087 g, 65%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro-2-phenylacetamido )-2,4-difluorophenyl)benzamide (F1471)

Isolated as a light yellow foam (0.086 g, 68%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-propionamidophenyl)benzamide ( F1472)

Isolated as a white solid (0.074 g, 67%).

N-(3-Butyramido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1473)

Isolated as a white solid (0.088 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-pentanamidophenyl)benzamide ( F1474)

Isolated as a white solid (0.092 g, 80%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(3-oxocyclobutane -1-carboxamido)phenyl)benzamide (F1475)

Isolated as a white foamy substance (0.106 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2 ,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1534)

Isolated as a white solid (0.037 g, 65%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2 ,3,3-tetrafluoropropanamido)phenyl)benzamide (F1535)

Isolated as a white solid (0.039 g, 67%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3 -(2,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1564)

Isolated as a white solid (0.104 g, 76%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2 ,3,3-tetrafluoropropanamido)phenyl)benzamide (F1565)

Isolated as a white solid (0.043 g, 58%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1567)

Isolated as a white solid (0.107 g, 87%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2 ,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1568)

Isolated as a white solid (0.096 g, 78%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5 -(2,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1569)

Isolated as a white solid (0.099 g, 80%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido)-2,4- difluorophenyl)benzamide (F1604)

Isolated as a white solid (0.093 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxy-2-methylpropanamido)- 2,4-difluorophenyl)benzamide (F1605)

Isolated as a white foamy substance (0.097 g, 81%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-isobutyramidophenyl)benzamide ( F1606)

Isolated as a white solid (0.084 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(3,3 ,3-trifluoro-2-(trifluoromethyl)propanamido)phenyl)benzamide (F1607)

Isolated as a white solid (0.115 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluorocyclopropane-1-carboxamido )-2,4-difluorophenyl)benzamide (F1608)

Isolated as a white solid (0.102 g, 87%).

2-Chloro-N-(3-(1-cyanocyclopropane-1-carboxamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl) cyclopropane-1-carboxamido)benzamide (F1609)

Isolated as a white foamy substance (0.090 g, 77%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)tetrahydrofuran -3-carboxamide (F1610)

Isolated as a white foam (0.111 g, 95%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)tetrahydrofuran -2-carboxamide (F1611)

Isolated as a white foamy substance (0.066 g, 56%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxy-N-methylpropanamido)- 2,4-difluorophenyl)benzamide (F1616)

Isolated as a white foamy substance (0.093 g, 79%).

2-Chloro-N-(3-(2-cyano-N-methylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl) cyclopropane-1-carboxamido)benzamide (F1617)

Isolated as a white foamy substance (0.096 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-methoxy -N-methylacetamido)phenyl)benzamide (F1630)

Isolated as a white foamy substance (0.082 g, 92%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido)-2, 4-difluorophenyl)benzamide (F1645)

Isolated as a white solid (0.079 g, 68%). The desired compound was obtained from N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane- 1-carboxamido)benzamide, which was prepared according to the methods described in the publication of the U.S. patent application. US20160304522A1 (F315).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 -methoxyacetamido)phenyl)benzamide (F1646)

Isolated as a white solid (0.087 g, 78%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl )tetrahydrofuran-2-carboxamide (F1647)

Isolated as a white foamy substance (0.071 g, 77%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl )furan-2-carboxamide (F1648)

Isolated as a white foamy substance (0.072 g, 62%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(3 -oxocyclobutane-1-carboxamido)phenyl)benzamide (F1649)

Isolated as a white foamy substance (0.040 g, 35%).

2-Chloro-N-(3-(2-cyanoacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane- 1-Carboxamido)benzamide (F1650)

Isolated as a yellow foam (0.062 g, 56%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(3 ,3,3-trifluoropropanamido)phenyl)benzamide (F1651)

Isolated as a white foamy substance (0.074 g, 63%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,3,3,4,4,4-heptafluorobutanamido)phenyl)benzamide (F1652)

Isolated as a white foamy substance (0.052 g, 39%).

2-Chloro-N-(3-(2-cyclopropylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane- 1-Carboxamido)benzamide (F1653)

Isolated as a white foamy substance (0.099 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-propionamidophenyl) benzamide (F1654)

Isolated as a white foamy substance (0.099 g, 90%).

N-(3-Butyramido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1655)

Isolated as a white foamy substance (0.095 g, 85%).

N-(3-Butyramido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1659)

Isolated as a white foamy substance (0.067 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido) -2,4-difluorophenyl)benzamide (F1660)

Isolated as a white solid (0.071 g, 77%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)tetrahydrofuran-2-carboxamide (F1661)

Isolated as a white solid (0.069 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(1-( trifluoromethyl)cyclopropane-1-carboxamido)phenyl)benzamide (F1662)

Isolated as a white foamy substance (0.033, 27%).

(R)-N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6 -difluorophenyl)pyrrolidine-2-carboxamide (F1663)

Isolated as a white foamy substance (0.044 g, 38%).

(S)-N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6 -difluorophenyl)pyrrolidine-2-carboxamide (F1664)

Isolated as a white foamy substance (0.039 g, 33%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)isoxazole -5-carboxamide (F1671)

Isolated as a white foamy substance (0.069 g, 70%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)isothiazole -5-carboxamide (F1672)

Isolated as a white foamy substance (0.059 g, 58%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-phenylacetamido )phenyl)benzamide (F1673)

Isolated as a white foamy substance (0.073 g, 72%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-dichloroacetamido)- 2,4-difluorophenyl)benzamide (F1685)

Isolated as a white foamy substance (0.104 g, 88%).

2-Chloro-N-(3-(2-chloro-2,2-difluoroacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4, 5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1686)

Isolated as a white foamy substance (0.097 g, 82%).

2-Chloro-N-(3-(2-chloro-2,2-difluoroacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3-chloro- 4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1697)

Isolated as a white foam (0.104 g, 87%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido)-2, 4-difluorophenyl)benzamide (F1698)

Isolated as a white solid (0.098 g, 83%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl )tetrahydrofuran-2-carboxamide (F1699)

Isolated as a white foamy substance (0.107 g, 91%).

2-Chloro-N-(3-(2-cyanoacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane- 1-Carboxamido)benzamide (F1700)

Isolated as a white foamy substance (0.089 g, 80%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(3 ,3,3-trifluoropropanamido)phenyl)benzamide (F1701)

Isolated as a white foamy substance (0.098 g, 82%).

2-Chloro-N-(3-(2-cyclopropylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane- 1-Carboxamido)benzamide (F1702)

Isolated as a white solid (0.094 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1703)

Isolated as a white foam (0.110 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-propionamidophenyl) benzamide (F1704)

Isolated as a white foamy substance (0.103 g, 94%).

N-(3-Butyramido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido) benzamide (F1705)

Isolated as a white solid (0.99 g, 88%).

2-Chloro-N-(3-(2-chloro-2,2-difluoroacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-chloro- 3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1719)

Isolated as a white foam (0.54 g, 76%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-((S)- 2-ethoxypropanamido)-2,4-difluorophenyl)benzamide (F1731)

Isolated as a white foamy substance (0.080 g, 69%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-((R)- 2-ethoxypropanamido)-2,4-difluorophenyl)benzamide (F1732)

Isolated as a white foamy substance (0.097 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-((S)-2-ethoxypropanamido)- 2,4-difluorophenyl)benzamide (F1733)

Isolated as a white foamy substance (0.068 g, 58%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-((R)-2-ethoxypropanamido)- 2,4-difluorophenyl)benzamide (F1734)

Isolated as a white foamy substance (0.081 g, 69%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,3,3,4,4,4-heptafluorobutanamido)phenyl)benzamide (F1741)

Isolated as a white solid (0.051 g, 38%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(trifluoromethoxy)acetamido)phenyl)benzamide (F1742)

Isolated as a white solid (0.104 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-oxopropanamido)phenyl)benzamide (F1754)

Isolated as a white solid (0.035 g, 40%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,4,4-trifluoro-3-methylbutanamido)phenyl)benzamide (F1760)

Isolated as a white foamy substance (0.101 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-( trifluoromethoxy)acetamido)phenyl)benzamide (F1766)

Isolated as a white foam (0.100 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-( trifluoromethoxy)propanamido)phenyl)benzamide (F1767)

Isolated as a white foamy substance (0.096 g, 78%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 -(trifluoromethoxy)acetamido)phenyl)benzamide (F1768)

Isolated as a white foamy substance (0.101 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 -(trifluoromethoxy)propanamido)phenyl)benzamide (F1769)

Isolated as a white foamy substance (0.109 g, 87%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2-(trifluoromethoxy) acetamido)phenyl)-2,3-difluorobenzamide (F1777)

Isolated as a white foamy substance (0.058 g, 83%).

N-(3-(5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzamido)-2,4- difluorophenyl)tetrahydrofuran-2-carboxamide (F1778)

Isolated as a white foamy substance (0.046 g, 68%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2,3 ,3,4,4,4-heptafluorobutanamido)phenyl)-2,3-difluorobenzamide (F1779)

Isolated as a white foamy substance (0.053 g, 70%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-( trifluoromethoxy)acetamido)phenyl)-N-methylbenzamide (F1793)

Isolated as a white foamy substance (0.107 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido)-2,4- difluorophenyl)-N-methylbenzamide (F1794)

Isolated as a white foamy substance (0.088 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(trifluoromethoxy)acetamido)phenyl)-N-methylbenzamide (F1796)

Isolated as a white foamy substance (0.095 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido) -2,4-difluorophenyl)-N-methylbenzamide (F1797)

Isolated as a white foamy substance (0.092 g, 79%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-methylbenzamido) -2,6-difluorophenyl)tetrahydrofuran-2-carboxamide (F1798)

Isolated as a white foamy substance (0.098 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,4,4-trifluorobutanamido)phenyl)benzamide (F1800)

Isolated as a white foam (0.11 g, 92%).

trans-5-(3-(3,5-bis(Trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(2-(trifluoromethoxy )acetamido)phenyl)benzamide (F1804)

Isolated as a white foamy substance (0.106 g, 89%).

trans-N-(3-(5-(3-(3,5-bis(Trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl)tetrahydrofuran-2 -carboxamide (F1805)

Isolated as a white foamy substance (0.105 g, 91%).

trans-5-(3-(3,5-bis(Trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-N-(3-butyramido-2,4-difluorophenyl)-2-chlorobenzamide (F1806)

Isolated as a white foam (0.098 g, 89%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)isoxazole-5-carboxamide (F1816)

Isolated as a white foamy substance (0.078 g, 84%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)isothiazole-5-carboxamide (F1817)

Isolated as a white foamy substance (0.036 g, 38%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)isoxazole-3-carboxamide (F1818)

Isolated as a white foamy substance (0.067 g, 72%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-carboxamide (F1819)

Isolated as a white foamy substance (0.070 g, 67%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-1,2,3-thiadiazole-5-carboxamide (F1820)

Isolated as a white foamy substance (0.040 g, 42%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-3-(trifluoromethyl)isoxazole-5-carboxamide (F1824)

Isolated as a white foamy substance (0.024 g, 24%).

trans-5-(3-(3,5-bis(Trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(2,2, 3,3,4,4,4-heptafluorobutanamido)phenyl)benzamide (F1825)

Isolated as a white foamy substance (0.105 g, 80%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,4,4-trifluoro-3-(trifluoromethyl)butanamido)phenyl)benzamide (F1833)

Isolated as a white foamy substance (0.114 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(4,4- difluoropentanamido)-2,4-difluorophenyl)benzamide (F1843)

Isolated as a white foam (0.100 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,4,5,5,5-pentafluoropentanamido)phenyl)benzamide (F1844)

Isolated as a white foamy substance (0.113 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3-methylbutanamido)phenyl)benzamide (F1845)

Isolated as a white foamy substance (0.101 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(2,2,2-trifluoroethoxy)acetamido)phenyl)benzamide (F1846)

Isolated as a white foamy substance (0.119 g, 80%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(4,4 ,4-trifluorobutanamido)phenyl)benzamide (F1847)

Isolated as a white foamy substance (0.105 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(4 ,4,4-trifluorobutanamido)phenyl)benzamide (F1848)

Isolated as a white foamy substance (0.101 g, 83%).

N-(3-(1-Acetylcyclopropane-1-carboxamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3- (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1850)

Isolated as a white solid (0.044 g, 42%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(4,4-difluoropentanamido)-2, 4-difluorophenyl)benzamide (F1860)

Isolated as a white solid (0.103 g, 85%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(4,4 ,5,5,5-pentafluoropentanamido)phenyl)benzamide (F1861)

Isolated as a white foamy substance (0.119 g, 92%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(4,4 ,4-trifluoro-2-methylbutanamido)phenyl)benzamide (F1862)

Isolated as a white foamy substance (0.047 g, 38%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-( 2,2,2-trifluoroethoxy)acetamido)phenyl)benzamide (F1863)

Isolated as a white foamy substance (0.109 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(4,4-difluoropentanamido)- 2,4-difluorophenyl)benzamide (F1864)

Isolated as a white foam (0.100 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(4 ,4,5,5,5-pentafluoropentanamido)phenyl)benzamide (F1865)

Isolated as a white foamy substance (0.113 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(4 ,4,4-trifluoro-2-methylbutanamido)phenyl)benzamide (F1866)

Isolated as a white foamy substance (0.094 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 -(2,2,2-trifluoroethoxy)acetamido)phenyl)benzamide (F1867)

Isolated as a white foamy substance (0.115 g, 92%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2-fluoroacrylamido )phenyl)benzamide (F1871)

Isolated as a white foamy substance (0.047 mg, 42%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 -fluoroacrylamido)phenyl)benzamide (F1872)

Isolated as an almost white foamed substance (0.053 g, 47%).

N-(3-(But-3-enamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane- 1-Carboxamido)benzamide (F1873)

Isolated as a white foamy substance (0.065 g, 69%).

N-(3-(But-3-enamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl )phenyl)cyclopropane-1-carboxamido)benzamide (F1874)

Isolated as a white foamy substance (0.097 g, 87%).

N-(3-(But-3-enamido)-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1- carboxamido)-2,3-difluorobenzamide (F1875)

Isolated as a white foam (0.054 g, 84%).

N-(3-(But-3-enamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl) cyclopropane-1-carboxamido)benzamide (F1876)

Isolated as a white foamy substance (0.074 g, 66%).

N-(3-Acrylamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1877)

Isolated as a white solid (0.041 g, 21%).

The following compounds were prepared using a procedure similar to that described in example 5:

N-(3-Acetamido-2,4-dichlorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1412)

Isolated as a white solid (0.043 g, 29%).

N-(3-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2,3 -difluorobenzamide (F1433)

The title compound was synthesized by reacting for 24-48 hours and isolated as a clear oil (0.086 g, 76%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4-difluorophenyl )carbamate (F1434)

The title compound was synthesized by reacting for 24-48 hours and isolated as a white solid (0.330 g, 88%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4-difluorophenyl )carbamate (F1435)

The title compound was synthesized by reacting for 24-48 hours and isolated as a white solid (0.270 g, 76%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4 -difluorophenyl)carbamate (F1436)

The desired compound was synthesized by reacting for 24-48 hours and isolated as a white foam (0.320 g, 81%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4- difluorophenyl)-2,3-difluorobenzamide (F1437)

The desired compound was synthesized by reacting for 24-48 hours and isolated as a brown powder (0.050 g, 38%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2,2 -trifluoroacetamido)phenyl)-2,3-difluorobenzamide (F1438)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.058 g, 48%).

N-(3-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzamide (F1439)

The title compound was synthesized by reacting for 24-48 hours and isolated as a clear oil (0.024 g, 21%).

5-((1R,3R)-2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl) -2,3-difluorobenzamide (F1440)

The desired compound was synthesized by reacting for 24-48 hours and isolated as a glassy oil (0.040 g, 32%).

5-((1R,3R)-2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2,2-trifluoroacetamido )phenyl)-2,3-difluorobenzamide (F1441)

The title compound was synthesized by reacting for 24-48 hours and isolated as a clear oil (0.028 g, 22%).

N-(3-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzamide (F1442)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.100 g, 84%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl) -2,3-difluorobenzamide (F1443)

The title compound was synthesized by reacting for 24-48 hours and isolated as a clear oil (0.085 g, 67%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2,2-trifluoroacetamido )phenyl)-2,3-difluorobenzamide (F1444)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.058 g, 45%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4 -difluorophenyl)carbamate (F1445)

The title compound was synthesized by reacting for 24-48 hours and isolated as a foamed solid (0.325 g, 98%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(N-ethyl- 2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide (F1452)

Isolated as a white foam (0.148 g, 94%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-[3-[[5-[[(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino ]-2-fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1453)

Isolated as a colorless oil (0.661 g, 76%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro-N -methylacetamido)-2,4-difluorophenyl)benzamide (F1460)

Isolated as a white foamy substance (0.117 g, 78%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro-N -methylacetamido)-2,4-difluorophenyl)benzamide (F1461)

Isolated as a white foamy substance (0.119 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro-N-methylacetamido )-2,4-difluorophenyl)benzamide (F1462)

Isolated as a white foamy substance (0.111 g, 75%).

N-(3-(N-Allyl-2,2-difluoroacetamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1482)

Isolated as a clear, colorless oil (0.052 g, 33%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(N-methylacetamido)phenyl)benzamide (F1506)

Isolated as a white foamy substance (0.057 g, 39%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,6-difluorophenyl) -2-fluorobenzamide (F1512)

Isolated as a white solid (0.068 g, 46%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2,2-trifluoroacetamido )phenyl)-2-fluorobenzamide (F1513)

Isolated as a white solid (0.064 g, 42%).

N-(3-Acetamido-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1514 )

Isolated as a white foamy substance (0.031 g, 24%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2,2 -trifluoroacetamido)phenyl)-2-fluorobenzamide (F1526)

Isolated as a white solid (0.083 g, 56%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4- difluorophenyl)-2-fluorobenzamide (F1527)

Isolated as a white solid (0.065 g, 46%).

N-(3-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1528)

Isolated as a brown solid (0.088 g, 65%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2, 2,2-Trifluoroacetamido)phenyl)-2-fluorobenzamide (F1529)

Isolated as a white solid (0.100 g, 67%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2 ,4-difluorophenyl)-2-fluorobenzamide (F1530)

Isolated as a white solid (0.095 g, 66%).

N-(3-acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)- 2-fluorobenzamide (F1531)

Isolated as a brown solid (0.117 g, 85%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl )(methyl)carbamate (F1549)

Isolated as a colorless glassy substance (1.05 g, 98%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2,2 -trifluoroacetamido)phenyl)-2-fluorobenzamide (F1551)

Isolated as a yellow foam (0.087 g, 59%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2,4- difluorophenyl)-2-fluorobenzamide (F1552)

Isolated as a yellow foam (0.073 g, 51%).

N-(5-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1553)

Isolated as a white foamy substance (0.081 g, 60%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2,2 -trifluoroacetamido)phenyl)-2-fluorobenzamide (F1554)

Isolated as a white foamy substance (0.092 g, 63%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,6- difluorophenyl)-2-fluorobenzamide (F1555)

Isolated as a white foamy substance (0.073 g, 51%).

N-(3-Acetamido-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1556)

Isolated as a white solid (0.083 g, 61%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2, 2,2-trifluoroacetamido)phenyl)-2-fluorobenzamide (F1557)

Isolated as a white foam (0.114 g, 76%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2 ,4-difluorophenyl)-2-fluorobenzamide (F1558)

Isolated as a yellow foam (0.112 g, 77%).

N-(5-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)- 2-fluorobenzamide (F1559)

Isolated as a white foam (0.122 g, 89%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2, 2,2-trifluoroacetamido)phenyl)-2-fluorobenzamide (F1560)

Isolated as a white foamy substance (0.128 g, 86%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2 ,6-difluorophenyl)-2-fluorobenzamide (F1561)

Isolated as a white foamy substance (0.101 g, 70%).

N-(3-Acetamido-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)- 2-fluorobenzamide (F1562)

Isolated as a white solid (0.108 g, 79%).

N-(3-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)- 2,3-difluorobenzamide (F1570)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.046 g, 61%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2 ,4-difluorophenyl)-2,3-difluorobenzamide (F1571)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy white solid (0.054 g, 68%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2, 2,2-trifluoroacetamido)phenyl)-2,3-difluorobenzamide (F1572)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.057 g, 70%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2 ,6-difluorophenyl)-2,3-difluorobenzamide (F1573)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.024 g, 29%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2, 2,2-trifluoroacetamido)phenyl)-2,3-difluorobenzamide (F1574)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.060 g, 73%).

N-(3-Acetamido-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzamide (F1575)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.062 g, 91%).

N-(3-Acetamido-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)- 2,3-difluorobenzamide (F1576)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.055 g, 73%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,6-difluorophenyl) -2,3-difluorobenzamide (F1577)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.058 g, 72%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2,2-trifluoroacetamido )phenyl)-2,3-difluorobenzamide (F1578)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.048 g, 65%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2,2 -trifluoroacetamido)phenyl)-2,3-difluorobenzamide (F1579)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.055 g, 68%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2,4- difluorophenyl)-2,3-difluorobenzamide (F1580)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.061 g, 82%).

N-(5-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2,3 -difluorobenzamide (F1581)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.055 g, 70%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2,2-trifluoroacetamido )phenyl)-2,3-difluorobenzamide (F1582)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.053 g, 68%).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2,4-difluorophenyl) -2,3-difluorobenzamide (F1583)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.052 g, 61%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2, 2,2-trifluoroacetamido)phenyl)-2,3-difluorobenzamide (F1584)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.057 g, 74%).

N-(5-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzamide (F1585)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy brown solid (0.060 g, 79%).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)-2 ,4-difluorophenyl)-2,3-difluorobenzamide (F1586)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.054 g, 72%).

N-(5-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)- 2,3-difluorobenzamide (F1587)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.055 g, 69%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2,2 -trifluoroacetamido)phenyl)-2,3-difluorobenzamide (F1588)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.060 g, 83%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,6- difluorophenyl)-2,3-difluorobenzamide (F1589)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.046 g, 58%).

N-(3-Acetamido-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2,3 -difluorobenzamide (F1590)

The title compound was synthesized by reacting for 24-48 hours and isolated as a glassy solid (0.066 g, 98%).

N-(3-Acetamido-2,4,6-trifluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1613)

Isolated as a white solid (0.076 g, 52%).

N-(3-Acetamido-2,4,6-trifluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1- carboxamido)benzamide (F1627)

Isolated as a white solid (0.083 g, 55%).

N-(3-Acetamido-2,4,6-trifluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1628)

Isolated as a white solid (0.081 g, 55%).

N-(3-Acetamido-2,4,6-trifluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1629)

Isolated as a white solid (0.095 g, 64%).

trans-N-(2-Acetamido-3,5-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1632)

The title compound was synthesized by reacting for 24-48 hours and isolated as a waxy solid (0.038 g, 50%).

trans-N-(2-Acetamido-4,6-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1633)

The title compound was synthesized by reacting for 24-48 hours and isolated as a waxy fawn solid (0.035 g, 46%).

trans-N-(2-Acetamido-4,5-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1634)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.061 g, 80%).

trans-N-(5-Acetamido-2-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1635)

The title compound was synthesized by reacting for 24-48 hours and isolated as a waxy, pale yellow solid (0.042 g, 54%).

trans-N-(2-Acetamido-6-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1636)

The title compound was synthesized by reacting for 24-48 hours and isolated as a waxy, fawn solid (0.041 g, 55%).

trans-N-(2-Acetamido-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1637)

The desired compound was synthesized by carrying out the reaction for 24-48 hours and isolated in the form of a pale-colored semi-liquid substance (0.020 g, 24%).

trans-N-(3-Acetamido-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1638)

The desired compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.007 g, 10%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-5-(2,2,2-trifluoroacetamido)phenyl )benzamide (F1639)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.011 g, 13%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-5-(2,2,2-trifluoroacetamido)phenyl )benzamide (F1640)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.020 g, 23%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-(2,2,2-trifluoroacetamido)phenyl )benzamide (F1641)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.015 g, 21%).

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]benzoyl]amino]-2,4-difluoro-3-methylphenyl]carbamate (F1670)

Isolated as a white solid (0.240 g, 88%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[3-fluoro-5-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]benzoyl]amino]-2,6-difluorophenyl]carbamate (F1681)

Isolated as a white foam (1.14 g, 86%).

N-(4-Bromo-2-methyl-3-nitrophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1688)

Isolated as a yellow foam (0.140 g, 92%).

tert-Butyl-(5-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,3,4-trifluorophenyl)carbamate (F1736)

Isolated as a white foamy substance (0.288 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -iodophenyl)benzamide (F1758)

Isolated as a white foamy substance (0.338 g, 71%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,6-difluorophenyl)(ethyl)carbamate (F1761)

Isolated as a white foam (0.540 g, 54%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-(2,2,2 -trifluoroacetamido)phenyl)benzamide (F1812)

The title compound was synthesized by reacting for 24-48 hours and isolated as a foamed solid (0.140 g, 92%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-(2,2,2 -trifluoroacetamido)phenyl)benzamide (F1813)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.142 g, 93%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)benzamide (F1814)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.133 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-( 2,2,2-trifluoroacetamido)phenyl)benzamide (F1815)

The title compound was synthesized by reacting for 24-48 hours and isolated as a pale yellow solid (0.136 g, 87%).

The following compounds were prepared using a procedure similar to that described in example 6:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- dichloropropanamido)-2,4-difluorophenyl)benzamide (F1351)

Isolated as a white solid (0.062 g, 49%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoropropanamido)-2,4-difluorophenyl)benzamide (F1352)

Isolated as a white solid (0.134 g, 74%).

N-(3-(2-Bromo-2-methylpropanamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3- (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1354)

Isolated as a white solid (0.038 g, 29%).

2-Chloro-N-(3-(2,2-dibromoacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl )phenyl)cyclopropane-1-carboxamido)benzamide (F1355)

Isolated as a white solid (0.111 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluorobutanamido)-2,4-difluorophenyl)benzamide (F1357)

Isolated as a white solid (0.165 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(1-methylcyclopropane-1-carboxamido)phenyl)benzamide (F1362)

Isolated as a white solid (0.107 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxyacetamido) -2,4-difluorophenyl)benzamide (F1363)

Isolated as a white foamy substance (0.106 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido) -2,4-difluorophenyl)benzamide (F1364)

Isolated as a white solid (0.101 g, 82%).

2-Chloro-N-(3-(2-cyanoacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1369)

Isolated as a yellow foam (0.112 g, 96%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -propionamidophenyl)benzamide (F1371)

Isolated as a white solid (0.180 g, 78%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -pentanamidophenyl)benzamide (F1372)

Isolated as a white foamy substance (0.191 g, 80%).

N-(3-Butyramido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1385)

Isolated as a white solid (0.103 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,3,3,4,4,4-heptafluorobutanamido)phenyl)benzamide (F1450)

Isolated as a white foamy substance (0.119 g, 85%).

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1454)

Isolated as a white foamy substance (0.168 g, 65%).

N-(3-(2-Bromopropanamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1479)

Isolated as a white solid (0.120 g, 93%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)tetrahydrofuran-3-carboxamide (F1480)

Isolated as a white foam (0.104 g, 85%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,3,3-tetrafluorocyclobutane-1-carboxamido)phenyl)benzamide (F1481)

Isolated as a white foamy substance (0.114 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -isobutyramidophenyl)benzamide (F1483)

Isolated as a white solid (0.108 g, 92%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3-oxocyclopentane-1-carboxamido)phenyl)benzamide (F1488)

Isolated as a golden foam (0.113 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3-methoxypropanamido)phenyl)benzamide (F1489)

Isolated as a white foamy substance (0.094 g, 78%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)oxetane-2-carboxamide (F1503)

Isolated as a white solid (0.036 g, 30%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- dimethyl-3-oxocyclobutane-1-carboxamido)-2,4-difluorophenyl)benzamide (F1507)

Isolated as a white solid (0.090 g, 71%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)tetrahydrofuran-2-carboxamide (F1521)

Isolated as a white foamy substance (0.054 g, 44%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxy- 2-methylpropanamido)-2,4-difluorophenyl)benzamide (F1603)

Isolated as a clear, colorless oil (0.047 g, 38%).

(2S,5S)-N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido )benzamido)-2,6-difluorophenyl)-5-methyltetrahydrofuran-2-carboxamide (F1612)

Isolated as a white foamy substance (0.100 g, 80%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-5-oxotetrahydrofuran-2-carboxamide (F1625)

Isolated as a white solid (0.110 g, 88%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-5-ethyltetrahydrofuran-2-carboxamide (F1626)

Isolated as a clear, colorless oil (0.105 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-methylbutanamido)phenyl)benzamide (F1642)

Isolated as a white solid (0.092 g, 77%).

2-Chloro-N-(3-(cyclopentanecarboxamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1643)

Isolated as a white solid (0.086 g, 70%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(3,3- difluorocyclobutane-1-carboxamido)-2,4-difluorophenyl)benzamide (F1644)

Isolated as a white solid (0.100 g, 79%).

2-Chloro-N-(3-(2-chloropropanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1667)

Isolated as a white solid (0.112 g, 92%).

2-Chloro-N-(3-(2-chlorobutanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1668)

Isolated as a white solid (0.097 g, 78%).

2-Chloro-N-(3-(3-chlorobutanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1669)

Isolated as a white solid (0.097 g, 78%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl) tetrahydrofuran-2-carboxamide (F1676)

Isolated as a white solid (0.076 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2, 2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1677)

Isolated as a clear, colorless oil (0.061 g, 63%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1678)

Isolated as a white solid (0.069 g, 81%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-propionamidophenyl)benzamide (F1679)

Isolated as a white solid (0.070 g, 81%).

2-Chloro-N-(3-(2-cyclopropylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1682)

Isolated as a white foam (0.113 g, 94%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3,3,3-trifluoropropanamido)phenyl)benzamide (F1683)

Isolated as a white foam (0.114 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -((R)-2-methoxypropanamido)phenyl)benzamide (F1689)

Isolated as a white foamy substance (0.082 g, 68%).

(R)-N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido )-2,6-difluorophenyl)tetrahydrofuran-2-carboxamide (F1691)

Isolated as a white foamy substance (0.103 g, 84%).

(S)-N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido )-2,6-difluorophenyl)tetrahydrofuran-2-carboxamide (F1692)

Isolated as a white foamy substance (0.088 g, 72%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)tetrahydrofuran-2-carboxamide (F1706)

Isolated as a white solid (0.060 g, 65%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1707)

Isolated as a clear, colorless oil (0.066 g, 69%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1708)

Isolated as a white solid (0.057 g, 67%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -propionamidophenyl)benzamide (F1709)

Isolated as a white solid (0.063 g, 73%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3,3,3-trifluoropropanamido)phenyl)benzamide (F1710)

Isolated as a white solid (0.068 g, 73%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-methoxypropanamido)phenyl)benzamide (F1712)

Isolated as a white solid (0.110 g, 91%).

N-(3-(5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl)tetrahydrofuran -2-carboxamide (F1714)

Isolated as a white solid (0.036 g, 59%).

5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(2, 2,3,3-tetrafluoropropanamido)phenyl)benzamide (F1715)

Isolated as a white solid (0.030 g, 47%).

N-(3-Acetamido-2,4-difluorophenyl)-5-((1R,3R)-3-(3-bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide ( F1716)

Isolated as a white solid (0.037 g, 66%).

5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-propionamidophenyl)benzamide (F1717)

Isolated as a white solid (0.042 g, 73%).

5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(3, 3,3-trifluoropropanamido)phenyl)benzamide (F1718)

Isolated as a white solid (0.031 g, 50%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -((S)-2-methoxypropanamido)phenyl)benzamide (F1720)

Isolated as a white solid (0.101 g, 84%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)tetrahydrothiophen-2-carboxamide (F1721)

Isolated as a white solid (0.110 g, 88%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)tetrahydro-2H-pyran-3-carboxamide (F1722)

Isolated as a white solid (0.102 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-methoxyacetamido)phenyl)benzamide (F1724)

Isolated as a white solid (0.098 g, 83%).

2-Chloro-N-(3-(2-chloroacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1726)

Isolated as a white foamy substance (0.090 g, 76%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,3- dichloropropanamido)-2,4-difluorophenyl)benzamide (F1728)

Isolated as a white foamy substance (0.060 g, 47%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3-fluoropropanamido)phenyl)benzamide (F1735)

Isolated as a white solid (0.100 g, 85%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypropanamido)-2,4 -difluorophenyl)benzamide (F1737)

Isolated as a white solid (0.077 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(3, 3,3-trifluoropropanamido)phenyl)benzamide (F1738)

Isolated as a white solid (0.078 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-propoxypropanamido)phenyl)benzamide (F1739)

Isolated as a white solid (0.101 g, 81%).

N-(5-Acetamido-2,3,4-trifluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1743)

Isolated as a white foamy substance (0.078 g, 92%).

2-Chloro-N-(3-(2-(cyclopropylmethoxy)propanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-( trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1745)

Isolated as a white solid (0.081 g, 85%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-isobutoxypropanamido)phenyl)benzamide (F1746)

Isolated as a white foamy substance (0.067 g, 70%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(2,2,2-trifluoroethoxy)propanamido)phenyl)benzamide (F1747)

Isolated as a white foamy substance (0.081 g, 82%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-3-methyloxirane-2-carboxamide (F1748)

Isolated as a white solid (0.028 g, 31%).

2-Chloro-N-(3-(2-cyano-N-methylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3- (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1752)

Isolated as a white foamy substance (0.062 g, 72%).

2-Chloro-N-(3-(2-cyanopropanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1755)

Isolated as a white solid (0.067 g, 75%).

2-Chloro-N-(3-(2-cyanobutanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1756)

Isolated as a white solid (0.033 g, 36%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxybutanamido) -2,4-difluorophenyl)benzamide (F1757)

Isolated as a white solid (0.026 g, 28%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxypentanamido) -2,4-difluorophenyl)benzamide (F1759)

Isolated as a white solid (0.096 g, 75%).

2-Chloro-N-(3-(2-cyano-N-ethylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3- (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1763)

Isolated as a white foamy substance (0.071 g, 81%).

2-Chloro-N-(3-(2-cyano-N-ethylpropanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3- (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1764)

Isolated as a white foamy substance (0.061 g, 68%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(trifluoromethoxy)propanamido)phenyl)benzamide (F1771)

Isolated as a yellowish-brown foam (0.080 g, 82%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(trifluoromethoxy)acetamido)phenyl)benzamide (F1772)

Isolated as a white foamy substance (0.032 g, 36%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(trifluoromethoxy)propanamido)phenyl)benzamide (F1773)

Isolated as a white foamy substance (0.043 g, 47%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2- (trifluoromethoxy)acetamido)phenyl)benzamide (F1774)

Isolated as a yellowish-brown foam (0.071 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2- (trifluoromethoxy)propanamido)phenyl)benzamide (F1775)

Isolated as a white solid (0.073 g, 80%).

5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(2- (trifluoromethoxy)acetamido)phenyl)benzamide (F1780)

Isolated as a white solid (0.070 g, 79%).

5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluoro-3-(2- (trifluoromethoxy)propanamido)phenyl)benzamide (F1781)

Isolated as a white solid (0.074 g, 82%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-2,3,3,4,4,5,5-tetrafluorotetrahydrofuran-2-carboxamide (F1782)

Isolated as a white solid (0.079 g, 73%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-2,3,3,4,4,5,5,6,6-nonafluorotetrahydro-2H-pyran-2-carboxamide (F1783)

Isolated as a white solid (0.033 g, 29%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(N-ethyl- 2-(trifluoromethoxy)acetamido)-2,4-difluorophenyl)benzamide (F1789)

Isolated as a white solid (0.058 g, 61%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-(difluoromethoxy )acetamido)-2,4-difluorophenyl)benzamide (F1790)

Isolated as a white foamy substance (0.078 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(perfluoroethoxy)acetamido)phenyl)benzamide (F1808)

Isolated as a white solid (0.078 g, 76%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-2-methyltetrahydrofuran-2-carboxamide (F1809)

Isolated as a white solid (0.061 g, 65%).

2-Chloro-N-(3-(2-cyano-N-(prop-2-yn-1-yl)acetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2- Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1810)

Isolated as a white foam (0.144 g, 99%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(N-(prop-2-yn-1-yl)-2-(trifluoromethoxy)acetamido)phenyl)benzamide (F1811)

Isolated as a clear, colorless oil (0.027 g, 20%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(1-((trifluoromethoxy)methyl)cyclopropane-1-carboxamido)phenyl)benzamide (F1821)

Isolated as a white solid (0.024 g, 24%).

Ethyl 3-((3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido) -2,6-difluorophenyl)amino)-2-fluoro-3-oxopropanoate (F1822)

Isolated as a white foamy substance (0.097 g, 100%).

2-Chloro-N-(3-(2-cyano-N-(2-fluoroethyl)acetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4 -fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1823)

Isolated as a white foamy substance (0.053 g, 68%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxy- N-ethylpropanamido)-2,4-difluorophenyl)benzamide (F1827)

Isolated as a golden oil (0.065 g, 71%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-(difluoromethoxy )propanamido)-2,4-difluorophenyl)benzamide (F1828)

Isolated as a white foamy substance (0.037 g, 39%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,5,5,5-tetrafluoro-4-(trifluoromethyl)pentanamido)phenyl)benzamide (F1829)

Isolated as a white foamy substance (0.081 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(5,5,5-trifluoropentanamido)phenyl)benzamide (F1830)

Isolated as a white solid (0.070 g, 72%).

N-(3-(2-Bromo-4,4,4-trifluorobutanamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4- fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1831)

Isolated as a white foamy substance (0.073 g, 69%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(3,3,3-trifluoro-2-methylpropanamido)phenyl)benzamide (F1832)

Isolated as a white foamy substance (0.032 g, 34%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,3,3-tetrafluoro-3-(trifluoromethoxy)propanamido)phenyl)benzamide (F1834)

Isolated as a clear, colorless oil (0.014 g, 13%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,4,4-trifluoro-2-methylbutanamido)phenyl)benzamide (F1835)

Isolated as a white solid (0.044 g, 45%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-(1-(trifluoromethyl)cyclopropyl)acetamido)phenyl)benzamide (F1836)

Isolated as a white solid (0.060 g, 61%).

N-(3-(2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2, 6-difluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-carboxamide (F1837)

Isolated as a white solid (0.042 g, 42%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,3,4,4,4-hexafluorobutanamido)phenyl)benzamide (F1839)

Isolated as a white solid (0.043 g, 42%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,4,4-trifluoro-3-oxobutanamido)phenyl)benzamide (F1840)

Isolated as a golden solid (0.029 g, 30%).

2-Chloro-N-(3-(2-cyano-N-propylacetamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3- (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1841)

Isolated as a white solid (0.096 g, 64%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2-ethoxy- N-propylpropanamido)-2,4-difluorophenyl)benzamide (F1842)

Isolated as a white solid (0.056 g, 29%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(1-(trifluoromethyl)cyclobutane-1-carboxamido)phenyl)benzamide (F1849)

Isolated as a white solid (0.006 g, 6%).

N-(3-(3-Bromopropanamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1851)

Isolated as a white solid (0.043 g, 44%).

N-(3-(3-Bromobutanamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1853)

Isolated as a white solid (0.054 g, 55%).

2-Chloro-N-(3-(3-cyclopropylpropanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1854)

Isolated as a white solid (0.061 g, 67%).

2-Chloro-N-(3-(3-cyanopropanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1855)

Isolated as a white solid (0.007 g, 8%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(5,5- dimethylhexanamido)-2,4-difluorophenyl)benzamide (F1856)

Isolated as a white solid (0.074 g, 77%).

2-Chloro-N-(3-(4-cyanobutanamido)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1857)

Isolated as a white solid (0.060 g, 66%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(4,5,5,5-tetrafluoro-4-(trifluoromethoxy)pentanamido)phenyl)benzamide (F1858)

Isolated as a white solid (0.082 g, 74%).

N-(3-((E)-but-2-enamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1868)

Isolated as a white solid (0.055 g, 47%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -((E)-4,4,4-trifluorobut-2-enamido)phenyl)benzamide (F1869)

Isolated as a white solid (0.096 g, 76%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2-fluoroacrylamido)phenyl)benzamide (F1870)

Isolated as a white solid (0.064 g, 54%).

N-(3-(But-3-enamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1878)

Isolated as a white solid (0.076 g, 86%).

N-(3-(But-3-enamido)-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl )phenyl)cyclopropane-1-carboxamido)benzamide (F1879)

Isolated as a white solid (0.076 g, 86%).

5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-N-(3-(but-3-enamido)-2,4-difluorophenyl )-2-chlorobenzamide (F1880)

Isolated as a white solid (0.089 g, 100%).

The following compounds were prepared using a procedure similar to that described in example 7:

Methyl-2-((3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido) -2,6-difluorophenyl)amino)-2-oxoacetate (F1753)

Isolated as a white solid (0.064 g, 72%).

The following compounds were prepared using a procedure similar to that described in example 9:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -((3,3,3-trifluoropropyl)sulfonamido)phenyl)benzamide (F1350)

Isolated as a clear, colorless oil (0.019 g, 14%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(((2, 2-dichlorocyclopropyl)methyl)sulfonamido)-2,4-difluorophenyl)benzamide (F1361)

Isolated as a white foamy substance (0.028 g, 20%).

The following compounds were prepared using a procedure similar to that described in example 10:

trans-tert-Butyl-(4-(((4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl) amino)methyl)phenyl)carbamate (F1348)

Isolated as a yellow oil (0.109 g, 76%).

The following compounds were prepared using a procedure similar to that described in example 12:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((4-hydroxybenzyl)amino)-2-methylphenyl)benzamide (F1353)

Isolated as a pale yellow foam (0.057 g, 69%).

The following compounds were prepared using a procedure similar to that described in example 13:

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-fluorobenzamide (F1337)

Isolated as a white solid (0.166 g, 80%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1338)

Isolated as an almost white powdery substance (0.154 g, 73%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-fluorobenzamide (F1339)

Isolated as a light yellow solid (0.153 g, 74%).

trans-N-(4-((4-Aminobenzyl)amino)-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F1349)

Isolated as a yellow solid (0.018 g, 26%).

trans-N-(3-Amino-4-chlorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1365)

Isolated as a white solid (0.143 g, 84%).

trans-N-(4-Amino-3,5-dichlorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1367)

Isolated as a tan solid (0.154 g, 61%).

trans-N-(4-Amino-3-chlorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1370)

Isolated as a white foamy substance (0.170 g, 70%).

trans-N-(4-Amino-3-cyanophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1387)

Isolated as a white foamy substance (0.106 g, 34%).

N-(4-Amino-2,3-dimethylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1389)

Isolated as a white solid (0.111 g, 64%).

trans-N-(4-Amino-3-(trifluoromethyl)phenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1390 )

Isolated as a white foamy substance (0.191 g, 67%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1391)

Isolated as a tan solid (0.600 g, 98%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido) -3-fluorobenzamide (F1395)

Isolated as a light yellowish-brown solid (0.276 g, 83%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1396)

Isolated as a tan solid (0.319 g, 95%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-fluorobenzamide (F1397)

Isolated as a light yellowish-brown solid (0.302 g, 92%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-fluorobenzamide (F1398)

Isolated as a tan solid (0.311 g, 92%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1399)

Isolated as a light yellowish-brown solid (0.301 g, 95%).

N-(3-Amino-4-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido )benzamide (F1413)

Isolated as a white solid (0.143 g, 65%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -methylbenzamide (F1426)

Isolated as a white powdery substance (0.176 g, 76%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-methylbenzamide (F1427)

Isolated as an almost white solid (0.194 g, 82%).

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-methylbenzamide (F1428)

Isolated as a yellowish-brown powdery substance (0.163 g, 70%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -methylbenzamide (F1446)

Isolated as an almost white solid (0.167 g, 66%).

N-(3-Amino-2-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido )benzamide (F1448)

Isolated as a white solid (0.146 g, 80%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-methylbenzamide (F1449)

Isolated as an almost white solid (0.193 g, 78%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-methylbenzamide (F1458)

Isolated as an almost white powdery substance (0.154 g, 64%).

N-(3-Amino-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1459 )

Isolated as a light yellow foam (0.382 g, 80%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -methylbenzamide (F1470)

Isolated as an almost white powdery substance (0.194 g, 85%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-methylbenzamide (F1477)

Isolated as an almost white powdery substance (0.155 g, 61%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-methylbenzamide (F1478)

Isolated as an almost white powdery substance (0.185 g, 70%).

N-(5-Amino-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F1490 )

Isolated as a light brown foam (0.387 g, 89%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(methylamino)phenyl )benzamide (F1550)

Isolated as a yellow foam (0.870 g, 97%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1566)

Isolated as a tan solid (0.210 g, 89%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-iodophenyl)cyclopropane-1-carboxamido)benzamide (F1622)

Isolated as a yellowish-brown foam (0.108 g, 94%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1631)

Isolated as a tan solid (0.64 g, 98%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide (F1666)

Isolated as a white solid (0.860 g, 85%).

N-(5-Amino-2,4-difluoro-3-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl )cyclopropane-1-carboxamido)benzamide (F1674)

Isolated as a white solid (0.151 g, 79%).

N-(3-Amino-6-bromo-2-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1684)

Isolated as a white solid (0.039 g, 75%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1687)

Isolated as a white solid (0.784 g, 87%).

N-(3-Amino-2,4-difluorophenyl)-5-((1R,3R)-3-(3-bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide ( F1713)

Isolated as a white solid (0.308 g, 85%).

N-(5-Amino-2,3,4-trifluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1740)

Isolated as a white foamy substance (0.188 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(ethylamino)-2 ,4-difluorophenyl)benzamide (F1762)

Isolated as a white foam (0.424 g, 87%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-N-methylbenzamide (F1785)

Isolated as a brown foam (0.565 g, 98%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1791)

Isolated as a white foam (1.27 g, 98%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(prop-2-yn-1-ylamino)phenyl)benzamide (F1807)

Isolated as an amber oil (0.215 g, 72%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -((2-fluoroethyl)amino)phenyl)benzamide (F1826)

Isolated as a golden oil (0.147 g, 68%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(propylamino)phenyl)benzamide (F1838)

Isolated as a clear, colorless oil (0.331 g, 66%).

The following compounds were prepared using a procedure similar to that described in example 14:

N-(3-Amino-2,6-difluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2,3 -difluorobenzamide (F1770)

Isolated as a white foam (0.274 g, 81%).

The following compounds were prepared using a procedure similar to that described in example 15:

N-(3-Amino-4-bromo-2-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane -1-carboxamido)benzamide (F1690)

Isolated as a white foamy substance (0.090 g, 69%).

The following compounds were prepared using a procedure similar to that described in example 18:

5-((1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2 ,4-difluorophenyl)benzamide (F1410)

Isolated as a white solid (0.059 g, 35%).

5-((1R,3R)-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2 ,4-difluorophenyl)benzamide (F1411)

Isolated as a white solid (0.053 g, 32%).

The following compounds were prepared using a procedure similar to that described in example 20:

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonyl] amino]-3-fluorobenzoyl]amino]-2,4-difluorophenyl]carbamate (F1379)

Isolated as a white solid (0.429 g, 79%).

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino] -3-fluorobenzoyl]amino]-2,4-difluorophenyl]carbamate (F1380)

Isolated as a white solid (0.402 g, 69%).

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropanecarbonyl] amino]-3-fluorobenzoyl]amino]-2,4-difluorophenyl]carbamate (F1381)

Isolated as a white solid (0.425 g, 70%).

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]-3-fluorobenzoyl]amino]-2,4-difluorophenyl]carbamate (F1382)

Isolated as a white solid (0.355 g, 62%).

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarbonyl]amino] -3-fluorobenzoyl]amino]-2,4-difluorophenyl]carbamate (F1383)

Isolated as a white solid (0.266 g, 47%).

3-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl) benzamide (F1447)

Isolated as a white foamy substance (0.123 g, 56%).

trans-5-(3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl )benzamide (F1618)

Isolated as a white foamy substance (0.077 g, 76%). The title compound was prepared from trans-3-(3-bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid, which was prepared according to the methods described in the U.S. patent application publication. US20160304522A1 (C215).

trans-tert-Butyl-N-[3-[[5-[[3-(3-bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropanecarbonyl]amino]-2-chlorobenzoyl]amino]-2,6 -difluorophenyl]-N-tert-butoxycarbonylcarbamate (F1619)

Isolated as a white solid (0.139 g, 88%).

trans-tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[2,2-dichloro-3-(4-fluoro-3-iodophenyl)cyclopropanecarbonyl]amino]benzoyl] amino]-2,6-difluorophenyl]carbamate (F1620)

Isolated as a white solid (0.155 g, 97%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-chloro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]benzoyl]amino]-2,6-difluorophenyl]carbamate (F1621)

Isolated as a colorless glassy substance (0.87 g, 99%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[3-(trifluoromethyl)phenyl]cyclopropanecarbonyl]amino ]benzoyl]amino]-2,6-difluorophenyl]carbamate (F1665)

Isolated as a white foam (1.35 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1693)

Isolated as an almost white solid (0.500 g, 35%), 2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxamido )-N-(2,4-difluorophenyl)benzamide (F1749)

Isolated as an almost white solid (0.360 g, 46%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1750)

Isolated as an almost white solid (0.500 g, 50%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1751)

Isolated as a pale yellow solid (0.500 g, 50%).

tert-Butyl-N-[3-[[5-[[(1R,3R)-3-(3-bromo-4-fluorophenyl)-2,2-dichlorocyclopropanecarbonyl]amino]-2-chlorobenzoyl]amino]-2 ,6-difluorophenyl]-N-tert-butoxycarbonylcarbamate (F1776)

Isolated as a white solid (1.2 g, 93%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]benzoyl]-methylamino]-2,6-difluorophenyl)carbamate (F1784)

Isolated as a white foamy substance (0.730 g, 82%).

trans-tert-Butyl-N-[3-[[5-[[3-[3,5-bis(trifluoromethyl)phenyl]-2,2-dichlorocyclopropanecarbonyl]amino]-2-chlorobenzoyl]amino]-2,6 -difluorophenyl]-N-tert-butoxycarbonylcarbamate (F1786)

Isolated as a white foam (1.7 g, 92%). The title compound was prepared from trans-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropanecarboxylic acid, which was prepared according to the methods described in the U.S. patent application publication. US20160304522A1 (C8).

trans-tert-Butyl-N-[3-[[5-[[3-[3-bromo-5-(trifluoromethyl)phenyl]-2,2-dichlorocyclopropanecarbonyl]amino]-2-chlorobenzoyl]amino]-2, 6-difluorophenyl]-N-tert-butoxycarbonylcarbamate (F1787)

Isolated as a white foam (1.7 g, 94%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]benzoyl]amino]-2,6-difluorophenyl]carbamate (F1788)

Isolated as a white foam (1.9 g, 94%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-(2,2,2-trifluoroacetamido)ethyl)benzamide (F2066 )

Isolated as a white solid (0.075 g, 24%).

trans-N-(3-Acetamidopropyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F2067)

Isolated as a white solid (0.100 g, 34%).

trans-N-(4-Acetamidobutyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F2068)

Isolated as a white solid (0.140 g, 47%).

trans-N-(5-Acetamidopentyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide (F2069)

Isolated as a white solid (0.100 g, 33%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(methylamino)-3-oxopropyl)benzamide (F2070)

Isolated as a white solid (0.090 g, 32%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,2-difluoropropyl)benzamide (F2075)

Isolated as an almost white solid (0.150 g, 60%).

trans-Ethyl-3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,2-difluoropropanoate (F2076)

Isolated as a pale yellow solid (0.120 g, 46%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,2-difluoro-2-phenylethyl)benzamide (F2077)

Isolated as an almost white solid (0.150 g, 57%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl )benzamide (F2078)

Isolated as an almost white solid (0.063 g, 19%).

trans-2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-oxo-3-(2,2 ,2-trifluoroethylamino)propyl)benzamide (F2079)

Isolated as an almost white solid (0.140 g, 39%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-oxo-4-(2,2,2-trifluoroethylamino)butyl )benzamide (F2080)

Isolated as an almost white solid (0.089 g, 26%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-oxo-2-(3,3,3-trifluoropropylamino)ethyl )benzamide (F2081)

Isolated as an almost white solid (0.075 g, 19%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-(2,2,2-trifluoroacetamido)ethyl)benzamide (F2082 )

Isolated as an almost white solid (0.060 g, 32%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,2-difluorobutyl)benzamide (F2086)

Isolated as an almost white solid (0.050 g, 28%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,2-difluoropropyl)benzamide (F2087)

Isolated as an almost white solid (0.100 g, 60%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,2-difluorobutyl)-3-fluorobenzamide (F2088)

Isolated as an almost white solid (0.150 g, 30%).

trans-Ethyl-3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzamido)-2,2-difluoropropanoate (F2089)

Isolated as an almost white solid (0.100 g, 21%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(2-oxopropyl)benzamide (F2090)

Isolated as an almost white solid (0.100 g, 18%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,2-difluoro-2-phenylethyl)-3-fluorobenzamide (F2091 )

Isolated as an almost white solid (0.090 g, 13%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-oxo-3-(3,3,3-trifluoropropylamino)propyl )benzamide (F2092)

Isolated as an almost white solid (0.125 g, 31%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)-N-(4-oxo-4-(3,3,3-trifluoropropylamino)butyl)benzamide (F2093 )

Isolated as a pale pink solid (0.130 g, 31%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2,2-trifluoroacetamido)propyl)benzamide (F2094 )

Isolated as an almost white solid (0.075 g, 19%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2,2-trifluoroacetamido)butyl)benzamide (F2095 )

Isolated as an almost white solid (0.171 g, 42%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-(2,2,3,3,3-pentafluoropropanamido)ethyl )benzamide (F2096)

Isolated as an almost white solid (0.170 g, 40%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2,3,3,3-pentafluoropropanamido)propyl )benzamide (F2097)

Isolated as a pale blue solid (0.131 g, 30%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2,3,3,3-pentafluoropropanamido)butyl )benzamide (F2098)

Isolated as an almost white solid (0.151 g, 34%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2099)

Isolated as an almost white solid (0.450 g, 48%). The title compound was prepared from 5-amino-2-chloro-N-(2,2,2-trifluoroethyl)benzamide, which was prepared according to the methods described in the U.S. patent application publication. 20160302418A1 (C70).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F2100)

Isolated as an almost white solid (0.450 g, 48%). The title compound was prepared from 5-amino-2-chloro-N-(2,2,2-trifluoroethyl)benzamide, which was prepared according to the methods described in the U.S. patent application publication. 20160302418A1 (C70).

The following compounds were prepared using a procedure similar to that described in example 21:

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(4-bromophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1591)

Isolated as a white foamy substance (0.108 g, 36%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1592)

Isolated as a white foamy substance (0.092 g, 27%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(4-chlorophenyl)cyclopropane-1-carboxamido)benzamide (F1593)

Isolated as a white foamy substance (0.162 g, 50%).

trans-N-(3-Amino-2,4-difluorophenyl)-5-(3-(3-bromophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide (F1594)

Isolated as a white foamy substance (0.103 g, 34%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chlorophenyl)cyclopropane-1-carboxamido)benzamide (F1595)

Isolated as a white foamy substance (0.152 g, 47%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-fluorophenyl)cyclopropane-1-carboxamido)benzamide (F1596)

Isolated as a white foamy substance (0.199 g, 59%).

The following compounds were prepared using a procedure similar to that described in example 22:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-dichloro-4-hydroxyphenyl)benzamide (F1360)

Isolated as a yellowish-brown foam (0.096 g, 93%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3-methylbenzamido)-2, 4-difluorophenyl)carbamate (F1420)

Isolated as a yellowish-brown foam (0.270 g, 91%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-3-methylbenzamido)- 2,4-difluorophenyl)carbamate (F1421)

Isolated as an almost white solid (0.274 g, 94%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-3- methylbenzamido)-2,4-difluorophenyl)carbamate (F1422)

Isolated as an almost white solid (0.271 g, 100%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino] -3-methylbenzoyl]amino]-2,6-difluorophenyl]carbamate (F1423)

Isolated as an almost white solid (0.320 g, 100%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropanecarbonyl] amino]-3-methylbenzoyl]amino]-2,6-difluorophenyl]carbamate (F1424)

Isolated as an almost white solid (0.325 g, 98%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]-3-methylbenzoyl]amino]-2,6-difluorophenyl]carbamate (F1425)

Isolated as an almost white solid (0.315 g, 100%).

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino] -3-methylbenzoyl]amino]-2,4-difluorophenyl]carbamate (F1455)

Isolated as an almost white solid (0.305 g, 100%)

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropanecarbonyl] amino]-3-methylbenzoyl]amino]-2,4-difluorophenyl]carbamate (F1456)

Isolated as an almost white solid (0.335 g, 100%)

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]-3-methylbenzoyl]amino]-2,4-difluorophenyl]carbamate (F1457)

Isolated as an almost white solid (0.352 g, 100%).

The following compounds were prepared using a procedure similar to that described in example 25:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoro-N-methylacetamido)-2,4-difluorophenyl)benzamide (F1386)

Isolated as a white foamy substance (0.122 g, 79%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-[5-[[5-[[(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropanecarbonyl]amino ]-2-fluorobenzoyl]amino]-2,4-difluorophenyl]carbamate (F1467)

Isolated as a white solid (0.590 g, 68%).

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1515)

Isolated as a white solid (0.100 g, 73%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)benzamide (F1516)

Isolated as a white solid (0.118 g, 79%).

N-(5-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1517)

Isolated as a white solid (0.116 g, 85%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)- 2,4-difluorophenyl)benzamide (F1518)

Isolated as a tan solid (0.114 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2 ,2,2-trifluoroacetamido)phenyl)benzamide (F1519)

Isolated as a white solid (0.118 g, 79%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) benzamide (F1532)

Isolated as a white solid (0.119 g, 87%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2 ,2,2-trifluoroacetamido)phenyl)benzamide (F1533)

Isolated as a white solid (0.121 g, 79%).

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide ( F1536)

Isolated as a white solid (0.131 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)benzamide (F1537)

Isolated as a white solid (0.141 g, 91%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)benzamide (F1538)

Isolated as a white solid (0.138 g, 90%).

N-(5-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)benzamide (F1539)

Isolated as a white solid (0.127 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(5-(2,2- difluoroacetamido)-2,4-difluorophenyl)benzamide (F1540)

Isolated as a tan solid (0.137 g, 94%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-5 -(2,2,2-trifluoroacetamido)phenyl)benzamide (F1541)

Isolated as a white solid (0.133 g, 89%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,4-difluorophenyl)carbamate (F1542)

Isolated as a white solid (0.712 g, 93%).

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]benzoyl]amino]-2,4-difluorophenyl]carbamate (F1563)

Isolated as a white solid (0.310 g, 90%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-4-fluoro-N-phenylbenzamide (F1723)

Isolated as a light yellowish-brown solid (0.070 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-4-fluoro-N-(4-fluorophenyl )benzamide (F1725)

Isolated as a light yellowish-brown solid (0.091 g, 97%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)- 4-fluorobenzamide (F1727)

Isolated as a white solid (0.085 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2- difluoroacetamido)-2,4-difluorophenyl)-4-fluorobenzamide (F1729)

Isolated as a white solid (0.093 g, 83%).

tert-Butyl-N-tert-butoxycarbonyl-N-[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-[4-fluoro-3-(trifluoromethyl)phenyl ]cyclopropanecarbonyl]amino]-4-fluorobenzoyl]amino]-2,6-difluorophenyl]carbamate (F1730)

Isolated as a white solid (0.102 g, 79%).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluoro-3-nitrophenyl)-2,3 -difluorobenzamide (F1765)

Isolated as a white foam (0.425 g, 44%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,6-difluorophenyl)(prop-2-yn-1-yl)carbamate (F1881)

Isolated as a yellow oil (0.33 g, 80%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,6-difluorophenyl)(2-fluoroethyl)carbamate (F1882)

Isolated as an amber oil (0.24 g, 63%).

tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)- 2,6-difluorophenyl)(propyl)carbamate (F1883)

Isolated as a white foamy substance (0.55 g, 65%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-ethyl-4-fluorobenzamide (F2083)

Isolated as a white solid (0.051 g, 63%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-4-fluoro-N-(2,2 ,2-trifluoroethyl)benzamide (F2084)

Isolated as a white solid (0.070 g, 78%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-4-fluoro-N-(2,2 ,3,3,3-pentafluoropropyl)benzamide (F2085)

Isolated as a white solid (0.078 g, 80%).

The following compounds were prepared using a procedure similar to that described in Example 32:

Ethyl (3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate (F1476)

Isolated as a yellowish-brown foam (0.034 g, 30%).

The following compounds were prepared using a procedure similar to that described in example 39:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3-methylbenzoic acid (C224)

Isolated as a white solid (0.60 g, 77%): m.p. 212 - 215°C; ^1H NMR (400 MHz, acetone- _d6 ) δ 11.30 (br s, 1H), 10.09 (s, 1H), 8.07 (d, J = 2.7 Hz, 1H), 7, 83 (d, J = 2.7 Hz, 1H), 7.68 (d, J = 1.9 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.45 ( dd, J = 8.3, 1.7 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H), 2, 42 (s, 3H); ¹³ C NMR (101 MHz, acetone-d ₆ ) δ 166.20, 162.50, 138.25, 137.21, 134.35, 132.38, 131.88, 131.48, 130.99, 130 .54, 129.20, 126.66, 123.79, 119.06, 62.01, 39.28, 37.38, 19.94; ESIMS m/z 468 ([M+H] ⁺ ).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-3-methylbenzoic acid (C225)

Isolated as a white solid (0.635 g, 85%): m.p. 195 - 200°C; ^1H NMR (400 MHz, acetone- _d6 ) δ 10.09 (s, 1H), 8.06 (d, J = 2.6 Hz, 1H), 7.83 (d, J = 2.5 Hz , 1H), 7.71 (d, J = 0.8 Hz, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H ), 2.42 (s, 3H); ¹³ C NMR (101 MHz, acetone-d ₆ ) δ 166.18, 162.30, 138.26, 137.18, 134.90, 133.64, 132.39, 130.22, 129.76, 126 .70, 123.79, 119.07, 61.79, 39.34, 37.08, 19.94; ESIMS m/z 501 ([M+H] ⁺ ).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-3-methylbenzoic acid (C226)

Isolated as a white solid (0.570 g, 75%): m.p. 190 - 193°C; ^1H NMR (400 MHz, acetone- _d6 ) δ 11.39 (br s, 1H), 10.08 (s, 1H), 8.07 (d, J = 2.6 Hz, 1H), 7, 87 - 7.81 (m, 3H), 7.48 (t, J = 9.9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.42 (s, 3H); ¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87 (d, J = 12.8 Hz), -117.65 (q, J = 12.8 Hz); ESIMS m/z 484 ([M+H] ⁺ ).

5-((1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzoic acid (C227)

Isolated as a gray foam (1.6 g, 93%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.32 (s, 1H), 10.86 (s, 1H), 8.21 (dd, J = 6.6, 2.8 Hz, 1H), 7.85 (ddd, J = 9.0, 4.1, 2.8 Hz, 1H), 7.75 (d, J = 2 ,1 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.42 (dd, J = 8.4, 2.2 Hz, 1H), 7.31 (dd, J = 10.5, 8.9 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -116.06; ESIMS m/z 438 ([M+H] ⁺ ).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzoic acid (C228)

Isolated as a brown foam (1.15 g, 80%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.34 (s, 1H), 10.83 (s, 1H), 8.21 (dd, J = 6.6, 2.8 Hz, 1H), 7.85 (ddd, J = 9.0, 4.2, 2.9 Hz, 1H), 7.80 (s, 2H), 7.32 (dd, J = 10.5, 8.9 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H ); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -116.06; ESIMS m/z 472 ([M+H] ⁺ ).

5-((1R,3R)-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-2-fluorobenzoic acid (C229)

Isolated as a cream solid (1.01 g, 88%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.34 (s, 1H), 10.86 (s, 1H), 8.22 (dd, J = 6.6, 2.9 Hz, 1H), 7.90 - 7.78 (m, 3H), 7.59 (dd, J = 10.7, 8.6 Hz, 1H), 7.32 (dd, J = 10.5, 8.9 Hz, 1H), 3.68 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H ); ¹⁹ F NMR (376 MHz, DMSO-d6) δ -59.92 (d, J = 12.9 Hz), -116.06, -116.98 (q, J = 13.0 Hz); ESIMS m/z 454 ([M+H] ⁺ ).

5-((1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2,3-difluorobenzoic acid (C230)

Isolated as a brown foam (0.73 g, 88%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.69 (s, 1H), 11.02 (s, 1H), 8.00 (ddd, J = 12.2, 6.6, 2.7 Hz, 1H), 7.93 (dt, J = 4.7, 2.0 Hz, 1H), 7.81 (d, J = 0 .7 Hz, 2H), 3.66 - 3.61 (m, 1H), 3.53 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -135.50 (d, J = 22.7 Hz), -142.58 (d, J = 22.6 Hz); ESIMS m/z 488 ([M+H] ⁺ ).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)-cyclopropane-1-carboxamido)-4-fluorobenzoic acid (C231)

Isolated as a cream solid (1.23 g, 68%): m.p. 188 - 191°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.54 (s, 1H), 10.73 (s, 1H), 8.60 (d, J = 8.4 Hz, 1H), 7.82 (ddd, J = 11.1, 6.0, 2.4 Hz, 2H), 7.68 (d, J = 10.7 Hz, 1H), 7.60 (dd, J = 10.7, 8 .5 Hz, 1H), 3.73 (d, J = 8.5 Hz, 1H), 3.68 (d, J = 8.6 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -59.94 (d, J = 12.4 Hz), -116.92 (q, J = 12.4 Hz), -118.01; HRMS _- ESI ₍ m/z _{) [} M+] ⁺ calculated for _{C18H9Cl3F5NO3} , 486.9568; found, 486.9579.

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)-cyclopropane-1-carboxamido)benzoic acid (C232)

Isolated as a tan solid (5.8 g, 93%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.48 (s, 1H), 10.94 (s, 1H), 8 .17 (d, J = 2.7 Hz, 1H), 7.94 - 7.72 (m, 3H), 7.68 - 7.44 (m, 2H), 3.68 (d, J = 8 .4 Hz, 1H), 3.49 (d, J = 8.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -59.93 (d, J = 12.6 Hz), -116.95 (q, J = 12.5 Hz); ESIMS m/z 472 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 40:

trans-2,2-Dichloro-3-(3-fluorophenyl)cyclopropane-1-carboxylic acid (C233)

Isolated as a pale yellow solid (2.8 g, 52%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.39 (s, 1H), δ 7.46 - 7.39 (m , 1H), 7.29 (t, J = 8.0 Hz, 2H), 7.21 - 7.15 (m, 1H), 3.45 (d, J = 8.0 Hz, 1H), 3 .41 (d, J = 8.8 Hz, 1H); ESIMS m/z 247.11 ([MH ] ^- ).

trans-2,2-Dichloro-3-(3-chlorophenyl)cyclopropane-1-carboxylic acid (C234)

Isolated as a white solid (1.1 g, 23%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.39 (s, 1H), 7.52 (s, 1H), 7.42 - 7.38 (m, 3H), 3.45 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H); ESIMS m/z 262.73 ([MH] ^- ).

trans-3-(3-Bromophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C235)

Isolated as a white solid (1.25 g, 26%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.41 (s, 1H), 7.66 (s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 7.6 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 3.45 (d , J = 8.8 Hz, 1H), 3.42 (d, J = 8.4 Hz, 1H); ESIMS m/z 307.05 ([MH] ^- )

trans-2,2-Dichloro-3-(3-(trifluoromethoxy)phenyl)cyclopropane-1-carboxylic acid (C236)

Isolated as a pale yellow solid (1.8 g, 38%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.39 (s, 1H), 7.54 - 7.43 (m, 3H), 7.34 (d, J = 8.0 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H), 3.44 (d, J = 8.8 Hz, 1H) ; ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -56.76; ESIMS m/z 312.77 ([MH] ^- ).

trans-2,2-Dichloro-3-(4-fluorophenyl)cyclopropane-1-carboxylic acid (C237)

Isolated as a white solid (2.5 g, 43%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.39 (s, 1H), 7.46 - 7.42 (m, 2H) , 7.23 - 7.17 (m, 2H), 3.41 (d, J = 8.4 Hz, 1H), 3.30 (d, J = 8.4 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -114.31; ESIMS m/z 246.78 ([MH] ^- ).

trans-2,2-Dichloro-3-(4-chlorophenyl)cyclopropane-1-carboxylic acid (C238)

Isolated as a pale yellow solid (2.4 g, 44%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.29 (s, 1H), 7.48 - 7.42 (m, 4H), 3.43 (d, J = 8.8 Hz, 1H), 3.33 (d, J = 8.8 Hz, 1H); ESIMS m/z 262.73 ([MH] ^- ).

trans-3-(4-Bromophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C239)

Isolated as a white solid (0.45 g, 9%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.56 (d, J = 8.8 Hz, 2H), 7.36 (d , J = 8.0 Hz, 2H), 3.38 (d, J = 8.4 Hz, 1H), 3.28 (d, J = 8.4Hz, 1H); ESIMS m/z 306.72 ([MH] ^- ).

The following compounds were prepared using a procedure similar to that described in example 51:

trans-2,2-Dichloro-3-(4-fluoro-3-iodophenyl)cyclopropane-1-carboxylic acid (C240)

Isolated as a white solid (1.35 g, 80%): m.p. 147 - 149°C; ^1H NMR (400 MHz, CDCl ₃ ) δ 7.67 -7.62 (m, 1H), 7.62 (dd, J = 6.4, 2.4 Hz, 1H), 6.93 - 6 .88 (m, 1H), 3.45 (d, J = 4.4 Hz, 1H), 2.88 (d, J = 4.4 Hz, 1H); ESIMS m/z 374.98 ([M+H] ⁺ ).

trans-2,2-Dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C241)

Isolated as a white solid (24 g, 43%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.55 (s, 1H), 7.66 - 7.59 (m, 1H), 7.57 - 7.44 (m, 3H), 3.55 (d, J = 8.3 Hz, 1H), 2.94 (d, J = 8.3 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.70; ESIMS m/z 298 ([MH] ^- ).

The following compounds were prepared using a procedure similar to that described in Example 55:

(1R,3R)-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C242)

Isolated as a white solid (1.05 g, 42%, 93% EI): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.53 (d, J = 2.1 Hz, 1H), 7.47 (d, J = 8.3 Hz, 1H), 7.17 (dd, J = 8.4, 2.1 Hz, 1H), 3.43 (d, J = 8.2 Hz, 1H), 2 .86 (d, J = 8.3 Hz, 1H); ESIMS m/z 343 ([MH] ^- ). Racemic trans-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid can be prepared by the methods described in US patent application publication US20160304522A1 (C422). The title compound was prepared from the racemate using (S)-1-phenylethan-1-amine and the conditions in Example 55.

The following compounds were prepared using a procedure similar to that described in Example 57:

tert-Butyl-N-[5-[(5-amino-2-chloro-3-fluorobenzoyl)amino]-2,4-difluorophenyl]-N-tert-butoxycarbonylcarbamate (C245)

Isolated as a light orange solid (3.125 g, 79%): 143 - 152°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.38 (s, 1H), 7.69 (t, J = 8.1 Hz, 1H), 7.52 (t, J = 10.1 Hz , 1H), 6.59 (ddd, J = 7.7, 5.5, 2.5 Hz, 2H), 5.81 (s, 2H), 1.40 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -115.57, -117.36, -117.38, -121.88, -121.90; HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₃ H ₂₅ ClF ₃ N ₃ O ₅ , 515.1435; found, 515.1438.

The following compounds were prepared using a procedure similar to that described in example 61:

N-(2,6-Difluoro-3-nitrophenyl)-N-ethyl-2,2-difluoroacetamide (C246)

Isolated as a golden oil (0.45 g, 25%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.39 - 8.15 (m, 1H), 7.21 (dddd, J = 11.9 , 9.7, 7.9, 2.0 Hz, 1H), 6.08 (dt, J = 154.5, 53.3 Hz, 1H), 4.01 - 3.69 (m, 2H), 1.21 (tt, J = 7.3, 1.2 Hz, 3H); ESIMS m/z 280 ([M+H] ⁺ ).

N-Allyl-N-(2,6-difluoro-3-nitrophenyl)-2,2-difluoroacetamide (C247)

Isolated as a golden oil (0.21 g, 12%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.23 (dddd, J = 15.3, 9.5, 8.1, 5.5 Hz , 1H), 7.35 - 7.09 (m, 1H), 6.54 - 5.71 (m, 2H), 5.30 - 5.09 (m, 2H), 4.52 - 4.25 (m, 2H); ESIMS m/z 293 ([M+H] ⁺ ).

N-(2,6-Difluoro-3-nitrophenyl)-N-methylacetamide (C248)

Isolated as a tan solid (1.02 g, 61%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.15 (dddd, J = 31.6, 9.4, 8.1, 5 .5 Hz, 1H), 7.32 - 7.05 (m, 1H), 3.31 (d, J = 53.3 Hz, 3H), 2.13 (d, J = 164.4 Hz, 3H ); ESIMS m/z 231 ([M+H] ⁺ ).

tert-Butyl-(2,6-difluoro-3-nitrophenyl)(ethyl)carbamate (C249)

Isolated as a yellow oil (0.4 g, 69%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 - 8.00 (m, 1H), 7.10 (ddd, J = 9.8 , 8.2, 2.0 Hz, 1H), 3.62 (dq, J = 25.2, 7.3 Hz, 2H), 1.37 (s, 9H), 1.15 (dt, J = 17.2, 7.2 Hz, 3H); ESIMS m/z 303 ([M+H] ⁺ ).

tert-Butyl-(2,6-difluoro-3-nitrophenyl)(prop-2-yn-1-yl)carbamate (C250)

Isolated as a yellow oil (0.40 g, 67%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.20 - 8.03 (m, 1H), 7.12 (ddd, J = 9.7 , 8.2, 2.0 Hz, 1H), 4.53 - 4.28 (m, 2H), 2.21 (dt, J = 20.9, 2.6 Hz, 1H), 1.56 ( d, J = 3.4 Hz, 9H); ESIMS m/z 313 ([M+H] ⁺ ).

tert-Butyl-(2,6-difluoro-3-nitrophenyl)(2-fluoroethyl)carbamate (C251)

Isolated as a yellow oil (0.198 g, 32%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.19 - 7.99 (m, 1H), 7.21 - 7.01 (m, 1H), 4.76 - 4.45 (m, 2H), 4.07 - 3.77 (m, 2H), 1.39 (s, 9H); ESIMS m/z 321 ([M+H] ⁺ ).

tert-Butyl-(2,6-difluoro-3-nitrophenyl)(propyl)carbamate (C252)

Isolated as a yellow oil (0.350 g, 58%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.09 (m, 1H), 7.10 (tt, J = 9.5, 4.8 Hz, 1H), 3.64 - 3.48 (m, 2H), 1.56 (d, J =6.1 Hz, 4H), 1.38 (d, J = 7.2 Hz, 7H), 0, 92 (p, J = 7.6 Hz, 3H); ESIMS m/z 317 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 62:

tert-Butyl-(2,6-difluoro-3-nitrophenyl)(methyl)carbamate (C253)

Isolated as a yellow oil (0.56 g, 76%): ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 8.32 - 8.19 (m, 1H), 7.49 (td, J = 9.2, 1.9 Hz, 1H), 3.15 (s, 1H), 3.11 (s, 2H), 1.48 (s, 3H), 1.31 (s, 6H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -106.79 (d, J = 11.4 Hz),

-107.54 (d, J = 11.3 Hz), -121.48 (d, J = 11.4 Hz), -122.14 (d, J = 11.4 Hz).

The following compounds were prepared using a procedure similar to that described in Example 65:

tert-Butyl-N-tert-butoxycarbonyl-N-[5-[(2-chloro-3-fluoro-5-nitrobenzoyl)amino]-2,4-difluorophenyl]carbamate (C254)

Isolated as a yellow solid (3.943 g, 85%): m.p. 172 - 175°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.74 (s, 1H), 8.52 (dd, J = 8.8, 2.6 Hz, 1H), 8.44 (dd, J = 2.6, 1.4 Hz, 1H), 7.90 (t, J = 8.1 Hz, 1H), 7.57 (t, J = 10.2 Hz, 1H), 1.42 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -109.73, -118.21, -118.22, -121.44, -121.46; HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₃ H ₂₃ ClF ₃ N ₃ O ₇ , 545.1177; found, 545.1179.

The following compounds were prepared using a procedure similar to that described in Example 67:

tert-Butyl-(3-amino-2,6-difluorophenyl)(methyl)carbamate (C255)

Isolated as a white solid (0.45 g, 89%): ¹ H NMR (400 MHz, CDCl ₃ ) rotary isomers δ 6.72 (td, J = 9.1, 1.9 Hz, 1H), 6 .68 - 6.58 (m, 1H), 3.59 (s, 2H), 3.16 (s, 3H), 1.53 (s, 2H), 1.37 (s, 7H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) rotary isomers δ -132.31, -132.53, -138.84,

-139.43; EIMS m/z 258.

tert-Butyl-N-(5-amino-2-chlorophenyl)-N-tert-butoxycarbonylcarbamate (C256)

Isolated as a gray solid (1.7 g, 78%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.15 (d, J = 8.5 Hz, 1H), 6.62 - 6.51 (m, 2H), 3.74 (s, 2H), 1.42 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 150.87, 145.76, 137.39, 129.65, 121.50, 116.14, 115.67, 82.71, 27.85; ESIMS m/z 341 ([MH] ^- ).

tert-Butyl-N-(4-amino-2,6-dichlorophenyl)-N-tert-butoxycarbonylcarbamate (C257)

Isolated as a tan solid (1.88 g, 85%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.64 (s, 2H), 3.95 (s, 2H), 1.41 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 150.32, 147.10, 134.34, 125.31, 113.81, 82.64, 27.77; ESIMS m/z 376 ([MH] ^- ).

tert-Butyl-N-(4-amino-2-chlorophenyl)-N-tert-butoxycarbonylcarbamate (C258)

Isolated as a tan solid (1.96 g, 93%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.93 (d, J = 8.5 Hz, 1H), 6.71 (d , J = 2.6 Hz, 1H), 6.52 (dd, J = 8.5, 2.6 Hz, 1H), 3.80 (s, 2H), 1.41 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 151.33, 146.96, 132.95, 130.03, 127.62, 115.23, 113.59, 82.43, 27.86; ESIMS m/z 341 ([MH] ^- ).

tert-Butyl-N-(4-amino-2-cyanophenyl)-N-tert-butoxycarbonylcarbamate (C259)

Isolated as a white solid (2.45 g, 85%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 7.01 (dd, J = 8.6, 0.4 Hz, 1H), 6.94 - 6.76 (m, 2H), 4.10 (d, J = 7.1 Hz, 2H), 1.43 (s, 18H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 150.99, 146.11, 132.35, 130.02, 119.18, 117.76, 116.21, 113.30, 83.42, 27.85 ; ESIMS m/z 332 ([MH] ^- ).

tert-Butyl-N-(4-amino-2,3-dimethylphenyl)-N-tert-butoxycarbonylcarbamate (C260)

Isolated as a white solid (0.19 g, 38%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.76 (d, J = 8.3 Hz, 1H), 6.53 (d, J = 8.4 Hz, 1H), 3.18 (s, 2H), 2.08 (d, J = 1.9 Hz, 6H), 1.42 (s, 18H); ESIMS m/z 335 ([MH] ^- ).

tert-Butyl-N-[4-amino-2-(trifluoromethyl)phenyl]-N-tert-butoxycarbonylcarbamate (C261)

Isolated as a white solid (0.19 g, 38%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.99 - 6.88 (m, 2H), 6.78 (dd, J = 8, 5, 2.7 Hz, 1H), 3.99 (s, 2H), 1.38 (s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -61.98; ESIMS m/z 375 ([MH] ^- ).

tert-Butyl-(5-amino-2-methylphenyl)carbamate (C262)

Isolated as a brown foam (1.33 g, 91%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.96 (d, J = 8.1 Hz, 1H), 6.70 (s, 1H ), 6.56 (dd, J = 8.1, 2.5 Hz, 1H), 6.44 (s, 1H), 3.48 (s, 2H), 2.06 (s, 3H), 1 .43 (s, 9H); ESIMS m/z 221 ([MH] ^- ).

tert-Butyl-N-(3-amino-2-methylphenyl)-N-tert-butoxycarbonylcarbamate (C263)

Isolated as a white solid (0.98 g, 89%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.98 (t, J = 7.9 Hz, 1H), 6.63 (dd, J = 8.0, 1.1 Hz, 1H), 6.55 (dd, J = 7.8, 1.1 Hz, 1H), 3.61 (s, 2H), 1.99 (s, 3H) , 1.41 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 151.83, 145.13, 138.90, 126.28, 120.32, 118.63, 114.63, 82.19, 27.92, 11.37 ; ESIMS m/z 323 ([M+H] ⁺ ).

tert-Butyl-N-(5-amino-2,4-difluoro-3-methylphenyl)-N-tert-butoxycarbonylcarbamate (C264)

Isolated as a tan solid (0.71 g, 83%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.49 - 6.40 (m, 1H), 3.56 (s, 2H) , 2.19 (t, J = 2.1 Hz, 3H), 1.44 (s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ

-135.31, -135.93; ESIMS m/z 359 ([M+H] ⁺ ).

N-(3-Amino-2,6-difluorophenyl)-N-ethyl-2,2-difluoroacetamide (C265)

Isolated as a golden oil (0.36 g, 86%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.94 - 6.75 (m, 2H), 5.80 (t, J = 53.5 Hz, 1H), 3.92 - 3.66 (m, 2H), 1.17 (tt, J = 7.2, 1.1 Hz, 3H); ESIMS m/z 251 ([M+H] ⁺ ).

N-(3-Amino-2,6-difluorophenyl)-N-methylacetamide (C266)

Isolated as a brown oil (0.74 g, 76%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.96 - 6.67 (m, 2H), 3.94 (d, J = 47.1 Hz, 2H), 3.20 (s, 3H), 1.91 (s, 3H); ESIMS m/z 231 ([M+H] ⁺ ).

tert-Butyl-(3-amino-2,6-difluorophenyl)(ethyl)carbamate (C267)

Isolated as a pink solid (0.36 g, 92%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.87 - 6.58 (m, 2H), 3.60 (dtt, J = 18, 7, 11.8, 5.8 Hz, 4H), 1.36 (s, 9H), 1.11 (dt, J = 14.6, 7.1 Hz, 3H); ESIMS m/z 273 ([M+H] ⁺ ).

tert-Butyl-(3-amino-2,6-difluorophenyl)(2-fluoroethyl)carbamate (C268)

Isolated as a golden oil (0.153 g, 81%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.86 - 6.55 (m, 2H), 4.68 - 4.43 (m, 2H), 3.85 (ddt, J = 26.3, 11.8, 5.8 Hz, 2H), 3.67 (s, 2H), 1.37 (s, 9H); ESIMS m/z 291 ([M+H] ⁺ ).

tert-Butyl-(3-amino-2,6-difluorophenyl)(propyl)carbamate (C269)

Isolated as a tan solid (0.310 g, 93%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.85 - 6.55 (m, 2H), 3.94 - 2.96 (m, 4H), 1.36 (s, 11H), 0.89 (q, J = 7.8 Hz, 3H); ESIMS m/z 287 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 68:

tert-Butyl-N-tert-butoxycarbonyl-N-(2-chloro-5-nitrophenyl)carbamate (C270)

Isolated as a white solid (2.26 g, 66%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.20 - 8.10 (m, 2H), 7.63 (d, J = 8, 8 Hz, 1H), 1.42 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 149.83, 146.69, 140.24, 138.31, 130.25, 125.29, 123.68, 84.04, 27.80; ESIMS m/z 373 ([MH] ^- ).

tert-Butyl-N-tert-butoxycarbonyl-N-(2,6-dichloro-4-nitrophenyl)carbamate (C271)

Isolated as a golden oil (2.26 g, 73%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.25 (s, 2H), 1.41 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 152.16, 148.46, 146.81, 141.22, 135.61, 123.13, 84.25, 27.69; ESIMS m/z 408 ([MH] ^- ).

tert-Butyl-N-tert-butoxycarbonyl-N-(2-chloro-4-nitrophenyl)carbamate (C272)

Isolated as a white solid (3.3 g, 97%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 2.6 Hz, 1H), 8.17 (dd, J = 8.7, 2.5 Hz, 1H), 7.43 (d, J = 8.7 Hz, 1H), 1.41 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 149.57, 147.24, 143.02, 134.09, 130.62, 124.92, 122.33, 83.99, 27.76; ESIMS m/z 371 ([MH] ^- ).

tert-Butyl-N-tert-butoxycarbonyl-N-(2-cyano-4-nitrophenyl)carbamate (C273)

Isolated as a yellow solid (3.0 g, 86%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.56 (d, J = 2.6 Hz, 1H), 8.47 (dd, J = 8.8, 2.6 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 1.47 (s, 18H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 149.52, 147.35, 146.52, 130.85, 128.04, 128.01, 114.68, 114.00, 85.19, 27.81 ; ESIMS m/z 362 ([MH] ^- ).

tert-Butyl-N-tert-butoxycarbonyl-N-(2,3-dimethyl-4-nitrophenyl)carbamate (C274)

Isolated as a white solid (0.52 g, 25%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.63 (d, J = 8.6 Hz, 1H), 7.09 (d, J = 8.6 Hz, 1H), 2.42 (s, 3H), 2.20 (s, 3H), 1.42 (s, 18H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 150.90, 150.17, 141.64, 137.39, 131.88, 126.47, 121.86, 83.36, 27.89, 15.94 , 14.65; ESIMS m/z 365 ([MH] ^- ).

tert-Butyl-N-tert-butoxycarbonyl-N-[4-nitro-2-(trifluoromethyl)phenyl]carbamate (C275)

Isolated as a yellow solid (2.93 g, 94%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.58 (d, J = 2.6 Hz, 1H), 8.45 (dd, J = 8.7, 2.6 Hz, 1H), 7.50 (d, J = 8.7 Hz, 1H), 1.39 (s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.25; ESIMS m/z 405 ([MH] ^- ).

tert-Butyl-(2-methyl-5-nitrophenyl)carbamate (C276)

Isolated as a white solid (1.58 g, 63%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 (s, 1H), 8.14 (dd, J = 8.5, 2, 3 Hz, 2H), 7.43 (d, J = 8.4 Hz, 1H), 2.40 (s, 3H), 1.45 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 151.02, 146.64, 138.69, 131.30, 123.88, 123.38, 84.52, 27.86, 18.10; ESIMS m/z 253 ([M+H] ⁺ ).

tert-Butyl-N-tert-butoxycarbonyl-N-(2-methyl-3-nitrophenyl)carbamate (C277)

Isolated as a white solid (1.15 g, 31%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.91 - 7.81 (m, 1H), 7.41 - 7.25 (m, 2H), 2.37 (s, 3H), 1.41 (s, 18H); ESIMS m/z 353 ([M+H]+).

tert-Butyl-N-tert-butoxycarbonyl-N-(2,4-difluoro-3-methyl-5-nitrophenyl)carbamate (C278)

Isolated as a golden solid (0.87 g, 40%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.88 (t, J = 7.7 Hz, 1H), 2.32 (t, J = 2.2 Hz, 3H), 1.46 (s, 18H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ

-108.86, -108.91, -115.35, -115.39; ESIMS m/z 389 ([M+H]⁺).

The following compounds were prepared using a procedure similar to that described in Example 70:

N-(3-Amino-2,4,6-trifluorophenyl)acetamide (C279)

Isolated as a tan solid (2.8 g, 37% in 3 steps from 2,4,6-trifluoroaniline): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.50 (s, 1H) , 7.11 - 7.00 (m, 1H), 5.07 (s, 2H), 2.04 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -131.69, -131.69, -131.72, -131.73, -134.98, -135.69, -135.70, -135 .72, -135.73; ESIMS m/z 205 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example R4:

(1R,3R)-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid (C243)

Isolated as a white solid (4.0 g, 40%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.53 (d, J = 2.1 Hz, 1H), 7.47 (d, J = 8.3 Hz, 1H), 7.17 (dd, J = 8.4, 2.1 Hz, 1H), 3.43 (d, J = 8.2 Hz, 1H), 2.86 (d , J = 8.3 Hz, 1H); ESIMS m/z 343 ([MH] ^- ). Racemic trans-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic acid can be prepared by the methods described in US patent application publication US20160304522A1 (C430).

(1R,3R)-2,2-Dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C244)

Isolated as a white solid (0.37 g, 25%, 97% EI): ^1H NMR (400 MHz, DMSO- _d6 ) δ 13.41 (s, 1H), 7.96 (d, J= 1.6 Hz, 1H), 7.79 - 7.71 (m, 2H), 3.69 - 3.50 (m, 2H).

(1R,3R)-2,2-Dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C280)

Isolated as a white solid (3.4 g, 95% EI, 26% yield): ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.38 (s, 1H), 7.66 - 7.59 (m , 1H), 7.57 - 7.44 (m, 3H), 3.55 (d, J = 8.3 Hz, 1H), 2.94 (d, J = 8.3 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.70; ESIMS m/z 298 ([MH] ^- ).

(1R,3R)-2,2-Dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C281)

Isolated as a white solid (2.5 g, 95% EI, 24% yield): ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.93 (s, 1H), 7.34 (dd, J = 7 ,1, 1.9 Hz, 2H), 7.20 (dt, J = 8.8, 2.0 Hz, 1H), 3.54 (d, J = 8.3 Hz, 1H), 2.93 (d, J = 8.3 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -62.86,

-109.50; ESIMS m/z 316 ([MH] ^- ).

Example 82: Preparation of N-(3-acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamido)-3-fluorobenzamide (F1505)

N-(3-Amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3 α-fluorobenzamide (F1336) (0.041 g, 0.069 mmol) and sodium bicarbonate (0.029 g, 0.343 mmol) were weighed into a 1-neck vessel containing a magnetic stir bar. Ethyl acetate (0.7 mL) was added and acetyl chloride (6 μL, 0.084 mmol) was added by syringe. The heterogeneous mixture was stirred for 3 hours at room temperature. The reaction mixture was diluted with ethyl acetate and saturated aqueous sodium bicarbonate; the layers were separated; and the organic layer was dried over sodium sulfate. Filtration and concentration provided the title compound as a white powder (0.044 g, 100%).

The following compounds were prepared using a procedure similar to that described in Example 82:

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-fluorobenzamide (F1520)

Isolated as a white powdery substance (0.047 g, 98%).

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -fluorobenzamide (F1522)

Isolated as a yellowish-brown powdery substance (0.044 g, 98%).

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -methylbenzamide (F1523)

Isolated as a yellowish-brown powdery substance (0.052 g, 100%).

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-methylbenzamide (F1524)

Isolated as a tan solid (0.053 g, 92%).

N-(3-Acetamido-2,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-methylbenzamide (F1525)

Isolated as a yellowish-brown powdery substance (0.036 g, 91%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -methylbenzamide (F1543)

Isolated as a yellowish-brown powdery substance (0.029 g, 97%).

N-(3-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido) -3-methylbenzamide (F1544)

Isolated as a yellowish-brown powdery substance (0.052 g, 94%).

N-(3-acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-methylbenzamide (F1545)

Isolated as a yellowish-brown powdery substance (0.039 g, 99%).

N-(5-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-3 -methylbenzamide (F1546)

Isolated as a peach-colored powder (0.044 g, 98%).

N-(5-Acetamido-2,4-difluorophenyl)-3-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-5-methylbenzamide (F1547)

Isolated as an almost white solid (0.048 g, 78%).

N-(5-Acetamido-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1 -carboxamido)-3-methylbenzamide (F1548)

Isolated as an almost white solid (0.037 g, 94%).

Example 83: Preparation of 6-chloro-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4- fluorophenyl)benzamide (F1465)

Step 1: To a solution of tert-butyl-(4-chloro-2-fluoro-3-((4-fluorophenyl)carbamoyl)phenyl)carbamate (C310; 0.066 g, 0.172 mmol) in dichloromethane (1 ml) was added hydrogen chloride ( 0.431 ml, 1.724 mmol) as a 4 M solution in dioxane and the resulting cloudy mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was suspended in dichloromethane and concentrated under a stream of nitrogen to give the intermediate hydrochloride, which was immediately used in next stage.

Step 2: To a mixture of (1R,3R)-2,2-dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-carboxylic acid (C93; 0.049 g, 0.172 mmol) and freshly prepared aniling hydrochloride intermediate in ethyl acetate ( 1 ml) pyridine (0.074 ml, 0.69 mmol) was added, then a 50% solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide (0.103 ml, 0.345 mmol) in ethyl acetate and the resulting light orange solution was heated at 50°C and stirred for 16 hours. The reaction mixture was concentrated under a stream of nitrogen and the resulting red viscous oil was purified by automatic flash chromatography (silica gel; 0→50% ethyl acetate in hexanes). The resulting glassy oil was dissolved/suspended in diethyl ether (1 ml) and treated with hexanes until the turbidity disappeared (a few drops). The solvents were evaporated under a stream of nitrogen to give the title compound as a light tan solid (0.081 mg, 85%).

The following compounds were prepared using a procedure similar to that described in Example 83:

6-Chloro-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide (F1464)

Isolated as a white solid (0.036 g, 61%).

6-Chloro-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-phenylbenzamide (F1466)

Isolated as a white solid (0.076 g, 77%).

N-(3-Amino-2,4-difluorophenyl)-6-chloro-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido) -2-fluorobenzamide (F1508)

Isolated as a white solid (0.028 g, 41%).

6-Chloro-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-ethyl-2-fluorobenzamide (F2071)

Isolated as a white solid (0.024 g, 55%).

6-Chloro-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(2,2,2- trifluoroethyl)benzamide (F2072)

Isolated as a white solid (0.030 g, 70%).

6-Chloro-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(2,2,3, 3,3-pentafluoropropyl)benzamide (F2073)

Isolated as a white solid (0.038 g, 77%).

6-Chloro-N-(3-chloropropyl)-3-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide (F2074 )

Isolated as a white solid (0.028 g, 76%).

Example 84: Preparation of trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzoic acid (C282):

With stirring, to a solution of trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid (C1 in US patent application publication US20160304522A1; 0.25 g, 0.83 mmol) in ethyl acetate ( 15 ml) 5-amino-2-chloro-3-fluorobenzoic acid (C196; 0.15 g, 0.83 mmol), 2,4,6-tripropyl-1,3,5,2,4,6- trioxatriphosphinane-2,4,6-trioxide (50% solution in ethyl acetate; 1 ml, 3.34 mmol) and pyridine (0.8 ml, 4.18 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered through a pad of ^Celite® and the layer was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The title compound was isolated as a pale yellow liquid (0.4 g), which was used in the next step without further purification: ESIMS m/z 468.90 ([MH] ^- ).

Example 85: Supercritical Liquid Chromatography (SFC) for the Purification of (1R,3R)-2,2-Dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxylic acid (C283) and (1S,3S)- 2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxylic acid (C284)

Racemic (trans)-2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxylic acid (US Patent Application Publication US20160304522A1 (C228); 2.29 g) was separated using preparative SFC on a column Chiralpak IE (30x250 mm, 5 µm) using 90:10 CO ₂ /0.5% isopropylamine in isopropanol and 100.0 bar back pressure gave the desired compounds: (C283) (0.9 g, peak 2) ; (C284) (0.9 g, peak 1).

The following compounds were prepared using a procedure similar to that described in Example 85:

(1R,3R)-2,2-Dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxylic acid (C285)

(1.5 g, peak 2): ^1H NMR (300 MHz, DMSO- _d6 ) δ 13.36 (br s, 1H), 7.58 (ddd, J = 2.0, 7.7, 11 ,9 Hz, 1H), 7.45 (td, J = 8.6, 10.6 Hz, 1H), 7.32 (br d, J = 1.8 Hz, 1H), 3.50 - 3, 40 (m, 2H); ESIMS m/z 264.81 ([MH] ^- ). The title compound was obtained by resolution of racemic trans-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxylic acid (US Patent Application Publication US20160304522A1 (C421)).

(1S,3S)-2,2-Dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxylic acid (C286)

(1.5 g, peak 1): ^1H NMR (300 MHz, DMSO- _d6 ) δ 13.36 (br s, 1H), 7.58 (ddd, J = 2.0, 7.8, 11 .8 Hz, 1H), 7.45 (td, J = 8.4, 10.6 Hz, 1H), 7.36 - 7.26 (m, 1H), 3.52 - 3.42 (m, 2H); ESIMS m/z 264.81 ([MH] ^- ). The title compound was obtained by resolution of racemic trans-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxylic acid (US Patent Application Publication US20160304522A1 (C421)).

Example 86: Preparation of N-(5-amino-2,4-difluorophenyl)-2,2-difluoroacetamide (C287)

2,2-Difluoroacetic anhydride (2 mL, 2.87 mmol) was added to 2,4-difluoro-5-nitroaniline (0.5 g, 2.87 mmol) in a 40 mL glass vessel with a magnetic stir bar. The reaction mixture was stirred overnight. The mixture was dried and the crude product was dissolved in ethyl acetate (10 ml). Palladium (5% on carbon, 500 mg) was added to the vessel and the mixture was stirred overnight with hydrogen supplied from a cylinder. The mixture was filtered through a pad of ^Celite® , washed with ethyl acetate and the solvent was removed under reduced pressure. The title compound was isolated as a brown solid (0.354 g, 50%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.98 (s, 1H), 7.79 (dd, J = 9.2, 7. 7 Hz, 1H), 6.87 (t, J = 10.3 Hz, 1H), 6.02 (t, J = 54.2 Hz, 1H), 3.71 (s, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -125.72,

-134.01, -140.54, -140.54; ESIMS m/z 223 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 86:

N-(5-Amino-2,4-difluorophenyl)-2,2,2-trifluoroacetamide (C288)

Isolated as a gray solid (0.383 g, 50%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.93 (s, 1H), 7.74 (dd, J = 9.0, 7.7 Hz , 1H), 6.89 (t, J = 10.3 Hz, 1H), 3.35 (s, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -75.74, -133.08, -140.33; ESIMS m/z 241 ([M+H] ⁺ ).

N-(5-Amino-2,4-difluorophenyl)acetamide (C289)

Isolated as a brown solid (1.06 g, 90%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.82 (dd, J = 9.4, 7.9 Hz, 1H), 7.20 (s, 1H), 6.80 (t, J = 10.5 Hz, 1H), 3.63 (s, 2H), 2.19 (s, 3H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -136.64, -141.55; ESIMS m/z 187 ([M+H] ⁺ ).

N-(2-Amino-3-fluorophenyl)acetamide (C290)

Isolated as a tan solid (1.07 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.26 (s, 1H), 7.07 (dt, J = 8.0, 1.3 Hz, 1H), 6.87 (ddd, J = 11.0, 8.2, 1.4 Hz, 1H), 6.52 (td, J = 8.1, 5.9 Hz, 1H ), 4.84 (s, 2H), 2.05 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -133.10.

N-(2-amino-5-fluorophenyl)acetamide (C291)

Isolated as a brown solid (1.06 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.13 (s, 1H), 7.22 (dd, J = 10.7, 2.8 Hz, 1H), 6.82 - 6.60 (m, 2H), 4.79 (s, 2H), 2.05 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -127.99.

N-(5-Amino-2-fluorophenyl)acetamide (C292)

Isolated as a fawn solid (1.07 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.40 (s, 1H), 7.13 (dd, J = 6.9, 2.8 Hz, 1H), 6.84 (dd, J = 10.9, 8.7 Hz, 1H), 6.33 - 6.17 (m, 1H), 4.93 (s, 2H), 2.04(s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -141.63.

N-(3-Amino-4-fluorophenyl)acetamide (C293)

Isolated as a fawn solid (1.08 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.66 (s, 1H), 7.11 (dd, J = 8.5, 2.6 Hz, 1H), 6.85 (dd, J = 11.3, 8.7 Hz, 1H), 6.63 (ddd, J = 8.7, 4.0, 2.6 Hz, 1H ), 5.11 (s, 2H), 1.98 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -141.04.

N-(2-Amino-4,6-difluorophenyl)acetamide (C294)

Isolated as a brown solid (1.06 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.89 (s, 1H), 6.35 - 6.20 (m, 2H) , 5.51 (s, 2H), 2.00 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ

-113.54, -113.56, -117.69, -117.71.

N-(2-Amino-3,5-difluorophenyl)acetamide (C295)

Isolated as a black solid (1.1 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.31 (s, 1H), 7.19 (dt, J = 10.8, 2.3 Hz, 1H), 6.90 (ddd, J = 11.5, 8.8, 2.9 Hz, 1H), 4.78 (s, 2H), 2.07 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -126.81, -129.59.71.

N-(2-Amino-4,5-difluorophenyl)acetamide (C296)

Isolated as a gray solid (1.06 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.11 (s, 1H), 7.31 (dd, J = 12.5, 8.8 Hz, 1H), 6.65 (dd, J = 13.0, 8.1 Hz, 1H), 5.07 (s, 2H), 2.03 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -142.62 (d, J = 24.2 Hz), -153.98 (d, J = 23.7 Hz).

N-(2-Amino-4,6-difluorophenyl)-2,2,2-trifluoroacetamide (C297)

Isolated as a brown solid (1.06 g, 90%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 14.52 (s, 1H), 7.67 - 7.18 (m, 2H) ; ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -63.00, -113.06, -123.55.

N-(6-Amino-2,3-difluorophenyl)-2,2,2-trifluoroacetamide (C298)

Isolated as a brown solid (0.34 g, 50%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 14.51 (s, 1H), 7.51 (ddt, J = 19.3, 13.2, 7.1 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -63.06,

-147.20, -153.46 (d, J = 21.0 Hz).

N-(2-Amino-4,5-difluorophenyl)-2,2,2-trifluoroacetamide (C299)

Isolated as a brown solid (0.38 g, 50%): ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.30 (s, 1H), 7.84 (s, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -62.94, -62.95, -139.23, -142.16.

N-(2-Amino-3,5-difluorophenyl)-2,2,2-trifluoroacetamide (C300)

Isolated as a gray solid (0.38 g, 50%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 14.54 (s, 1H), 7.40 (d, J = 8.2 Hz , 1H), 7.31 (t, J = 10.6 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ

-63.00, -113.06, -123.56.

N-(2-Amino-5-fluorophenyl)-2,2,2-trifluoroacetamide (C301)

Isolated as a fawn solid (0.39 g, 50%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 12.89 (s, 1H), 7.68 (ddd, J = 12.2, 9.2, 3.5 Hz, 2H), 7.40 (td, J = 9.3, 2.4 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -62.70, -118.54.

N-(5-Amino-2-fluorophenyl)-2,2,2-trifluoroacetamide (C302)

Isolated as a black solid (0.4 g, 50%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (s, 1H), 7.66 (dd, J = 6.5, 2. 8 Hz, 1H), 6.94 (dd, J = 10.5, 8.8 Hz, 1H), 6.45 (ddd, J = 8.8, 4.2, 2.8 Hz, 1H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -75.79, -144.06.

N-(3-Amino-4-fluorophenyl)-2,2,2-trifluoroacetamide (C303)

Isolated as a gray solid (0.42 g, 50%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.72 (s, 1H), 7.22 (dd, J = 7.8, 2, 6 Hz, 1H), 6.97 (dd, J = 10.5, 8.7 Hz, 1H), 6.69 (ddd, J = 8.7, 3.9, 2.7 Hz, 1H), 3.86(s, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -75.74, -136.95.

N-(3-Amino-5-fluorophenyl)-2,2,2-trifluoroacetamide (C304)

Isolated as a gray solid (0.40 g, 50%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.71 (s, 1H), 6.80 (td, J = 2.0, 0, 7 Hz, 1H), 6.63 (dt, J = 9.9, 2.1 Hz, 1H), 6.25 (dt, J = 10.3, 2.1 Hz, 1H), 3.90 ( s, 2H); ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -75.79, -110.83.

N-(2-Amino-3-fluorophenyl)-2,2,2-trifluoroacetamide (C305)

Isolated as a brown solid (0.39 g, 50%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 14.36 (s, 1H), 7.51 (s, 1H), 7.40 (td, J = 8.1, 4.8 Hz, 1H), 7.20 (t, J = 9.5 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -62.86, -127.62.

N-(2-Amino-6-fluorophenyl)-2,2,2-trifluoroacetamide (C306)

Isolated as a gray solid (0.4 g, 50%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 14.33 (s, 1H), 7.60 - 7.43 (m, 1H) , 7.44 - 7.32 (m, 1H), 7.20 (d, J = 9.0 Hz, 1H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -62.74, -62.75, -62.87, -127.60.

Example 87: Preparation of N-(3-amino-2,4-difluorophenyl)-2,2-difluoroacetamide hydrochloride (C307)

2,2- difluoroacetic anhydride (2.5 ml, 3.59 mmol). The reaction mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The crude product was dissolved in dichloromethane (30 ml). Hydrochloric acid (4 M in dioxane, 7.25 ml) was added to the solution and the reaction mixture was stirred at room temperature for 6 hours. The resulting precipitate was filtered and washed with cold dichloromethane. The title compound was isolated as a white solid (0.74 g, 98%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.47 (s, 1H), 6.91 (ddd, J = 10, 7, 8.9, 1.9 Hz, 1H), 6.76 (td, J = 8.5, 5.5 Hz, 1H), 6.44 (t, J = 53.5 Hz, 1H), 5.09(s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -125.40, -133.15 (d, J = 14.3 Hz), -138.66 (d, J = 14.4 Hz).

The following compounds were prepared using a procedure similar to that described in Example 87:

N-(3-Amino-2,4-difluorophenyl)-2,2,2-trifluoroacetamide hydrochloride (C308)

Isolated as a brown solid (0.80 g, 99%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.09 (s, 1H), 6.95 (ddd, J = 10.7, 8.8, 1.9 Hz, 1H), 6.57 (td, J = 8.4, 5.4 Hz, 1H), 5.56 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -73.91, -131.57 (d, J = 15.6 Hz), -137.08 (d, J = 15.6 Hz).

N-(3-Amino-2,4-difluorophenyl)acetamide hydrochloride (C309)

Isolated as a brown solid (0.60 g, 93%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.55 (s, 1H), 6.91 (td, J = 8.5, 5.7 Hz, 1H), 6.83 (ddd, J = 10.7, 8.9, 1.8 Hz, 1H), 5.94 (s, 3H), 2.04 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -135.33 (d, J = 12.4 Hz), -140.18 (d, J = 12.3 Hz).

Example 88: Preparation of tert-butyl (4-chloro-2-fluoro-3-((4-fluorophenyl)carbamoyl)phenyl)carbamate (C310)

To a solution of 3-((tert-butoxycarbonyl)amino)-6-chloro-2-fluorobenzoic acid (C318; 85.0 mg, 0.293 mmol) and 4-fluoroaniline (34.2 mg, 0.308 mmol) in ethyl acetate (2, 5 ml) pyridine (0.094 ml, 0.880 mmol) was added, then 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide (0.35 ml, 0.587 mmol) and the resulting light yellow solution was heated at 50°C and stirred for 8 hours. The reaction mixture was concentrated under a stream of nitrogen and the resulting red-orange oil was purified by automated flash chromatography (silica gel; 0→65% ethyl acetate in hexanes ). The title compound was isolated as a white solid (0.075 g, 66%): m.p. 145 - 148°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.83 (s, 1H), 9.32 (s, 1H), 7.80 - 7.64 (m, 3H), 7.36 (dd, J = 8.8, 1.4 Hz, 1H), 7.27 - 7.16 (m, 2H), 1.47 (s, 9H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -118.08, -124.58; ESIMS m/z 381 ([MH] ^- ).

The following compounds were prepared using a procedure similar to that described in Example 88:

tert-Butyl-(4-chloro-2-fluoro-3-(phenylcarbamoyl)phenyl)carbamate (C311)

Isolated as a white solid (0.085 g, 79%): m.p. 91 - 94°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.76 (s, 1H), 9.31 (s, 1H), 7.74 (t, J = 8.7 Hz, 1H), 7.71 - 7.66 (m, 2H), 7.42 - 7.29 (m, 3H), 7.21 - 7.06 (m, 1H), 1.47 (s, 9H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -124.64; ESIMS m/z 363 ([MH] ^- ).

tert-Butyl-(4-chloro-3-((2,4-difluorophenyl)carbamoyl)-2-fluorophenyl)carbamate (C312)

Isolated as a white solid (0.048 g, 40%): m.p. 136 - 139°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.66 (s, 1H), 9.31 (s, 1H), 7.81 (td, J = 8.9, 6.1 Hz, 1H) , 7.74 (t, J = 8.6 Hz, 1H), 7.43 - 7.32 (m, 2H), 7.18 - 7.10 (m, 1H), 1.47 (s, 9H ); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -113.14, -113.16, -117.72, -117.74, -124.47; ESIMS m/z 399 ([MH] ^- ).

tert-Butyl-(tert-butoxycarbonyl)(3-(3-((tert-butoxycarbonyl)amino)-6-chloro-2-fluorobenzamido)-2,6-difluorophenyl)carbamate (C313)

Isolated as a white solid (0.076 g, 34%): m.p. 83 - 88°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.75 (s, 1H), 9.30 (s, 1H), 7.88 - 7.68 (m, 2H), 7.35 (dd, J = 8.8, 1.4 Hz, 1H), 7.32 - 7.23 (m, 1H), 1.47 (s, 9H), 1.40 (s, 18H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -123.39, -124.42, -126.90; ESIMS m/z 614 ([M-2H] ^- ).

tert-Butyl-(4-chloro-3-(ethylcarbamoyl)-2-fluorophenyl)carbamate (C314)

Isolated as a white solid (0.032 g, 34%): m.p. 145 - 147°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.21 (s, 1H), 8.66 (t, J = 5.6 Hz, 1H), 7.65 (t, J = 8.6 Hz , 1H), 7.26 (dd, J = 8.8, 1.5 Hz, 1H), 3.25 (qd, J = 7.2, 5.5 Hz, 2H), 1.46 (s, 9H), 1.10 (t, J = 7.2 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -124.90; ESIMS m/z 315 ([MH] ^- ).

tert-Butyl-(4-chloro-2-fluoro-3-((2,2,2-trifluoroethyl)carbamoyl)phenyl)-carbamate (C315)

Isolated as a white solid (0.035 g, 32%): m.p. 177 - 180°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.42 (t, J = 6.2 Hz, 1H), 9.27 (s, 1H), 7.70 (t, J = 8.6 Hz , 1H), 7.31 (dd, J = 8.8, 1.4 Hz, 1H), 4.19 - 4.00 (m, 2H), 1.46 (s, 9H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -70.42, -124.62; ESIMS m/z 369 ([MH] ^- ).

tert-Butyl-(4-chloro-2-fluoro-3-((2,2,3,3,3-pentafluoropropyl)carbamoyl)phenyl)-carbamate (C316)

Isolated as a white solid (0.047 g, 38%): m.p. 152 - 155°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.44 (t, J = 6.3 Hz, 1H), 9.26 (s, 1H), 7.70 (t, J = 8.6 Hz , 1H), 7.31 (dd, J = 8.9, 1.4 Hz, 1H), 4.15 (td, J = 15.7, 5.7 Hz, 2H), 1.46 (s, 9H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -83.41, -120.04, -124.47; ESIMS m/z 419 ([MH] ^- ).

tert-Butyl-(4-chloro-3-((3-chloropropyl)carbamoyl)-2-fluorophenyl)carbamate (C317)

Isolated as a white solid (0.032 g, 30%): m.p. 126 - 128°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.23 (s, 1H), 8.77 (t, J = 5.6 Hz, 1H), 7.66 (t, J = 8.6 Hz , 1H), 7.28 (dd, J = 8.8, 1.4 Hz, 1H), 3.70 (t, J = 6.6 Hz, 2H), 3.40 - 3.36 (m, 2H), 1.95 (p, J = 6.6 Hz, 2H), 1.46 (s, 9H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -124.88; ESIMS m/z 363 ([M-2H] ^- ).

Example 89: Preparation of 3-((tert-butoxycarbonyl)amino)-6-chloro-2-fluorobenzoic acid (C318)

To a suspension of ethyl 3-[bis(tert-butoxycarbonyl)amino]-6-chloro-2-fluorobenzoate (C319; 7.57 g, 18.1 mmol) in a 2:1 mixture of tetrahydrofuran (48 ml) and water (24 ml) lithium hydroxide monohydrate (2.28 g, 54.3 mmol) was added and the resulting cloudy mixture was stirred vigorously for 16 hours at room temperature, then LC-MS analysis indicated the presence of only the starting material and the starting material containing one of the groups Boc, split. The reaction mixture was diluted with methanol (25 ml) and the mixture was stirred at room temperature for 16 hours, then LC-MS indicated complete consumption of the starting ester. The organics were evaporated under reduced pressure and the remaining aqueous mixture (cream-colored precipitate) was diluted with ethyl acetate (~200 ml) and stirred vigorously while adjusting the pH (6 - 7) by dropwise addition of 1 N. aqueous solution of hydrogen chloride (~35 ml). The phases were separated and the aqueous phase was extracted with additional ethyl acetate (2×50 ml). The combined organic extracts were washed successively with water (100 ml) and brine (2×75 ml), dried over sodium sulfate, filtered and concentrated. The title compound was isolated as a colorless glassy solid (1.465 g, 27%): m.p. 79 - 84°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.12 (s, 1H), 7.58 (t, J = 8.6 Hz, 1H), 7.21 (dd, J = 8.8, 1.4 Hz, 1H), 1.46 (s, 9H); ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 170.20, 163.68, 152.78, 151.13, 148.66, 125.75, 125.63, 124.53, 124.50, 123 .63, 79.62, 59.64, 27.90, 20.65, 13.99; ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ

-124.86; ESIMS m/z 288 ([MH] ^- ).

Example 90: Preparation of ethyl 3-[bis(tert-butoxycarbonyl)amino]-6-chloro-2-fluorobenzoate (C319)

To a solution of ethyl 3-amino-6-chloro-2-fluorobenzoate (C320; 8.5 g, 39.1 mmol) in N,N-dimethylformamide (32.5 ml), N,N-dimethylpyridin-4- amine (0.239 g, 1.95 mmol), N-ethyl-N-isopropylpropan-2-amine (20.4 ml, 117 mmol) and di-tert-butyl dicarbonate (25.6 g, 117 mmol; added in portions) and the resulting light yellow solution was stirred at room temperature for about 16 hours. The reaction mixture was treated with additional di-tert-butyl dicarbonate (3.00 g, 13.7 mmol), stirred for 3 hours at room temperature and partitioned between ethyl acetate (200 ml) and 5% aqueous sodium bicarbonate solution (600 ml). The phases were separated and the aqueous phase was extracted with diethyl ether (150 ml). All organic extracts were washed with water (ethyl acetate: 3×200 ml; diethyl ether: 2×100 ml). The extracts were combined, dried over sodium sulfate, filtered and concentrated to give a viscous red oil. The crude oil was purified by automated flash chromatography (silica gel; 0→30% ethyl acetate in hexanes) to give the title compound as a viscous golden oil that solidified slowly on standing (12.55 g, 77%): m.p. 91 - 95°C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.25 - 7.13 (m, 2H), 4.45 (q, J = 7.2 Hz, 2H), 1.45 - 1.36 (m, 21H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 162.51, 156.15, 153.60, 150.19, 131.43, 131.38, 131.19, 131.17, 126.73, 126.60 , 125.14, 125.10, 123.16, 122.97, 83.74, 62.41, 27.81, 14.11; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -119.43.

Example 91: Preparation of ethyl 3-amino-6-chloro-2-fluorobenzoate (C320)

To a solution of 4-chloro-2-fluoroaniline (11 g, 76 mmol) in anhydrous tetrahydrofuran (151 ml), cooled to -76°C, was added butyllithium (31.7 ml, 79 mmol) as a 2.5 M solution in hexanes at a rate to maintain the temperature below -68°C and the resulting greenish-brown solution was stirred at -75°C for 45 minutes. The heterogeneous brown reaction mixture was treated with a solution of 1,2-bis(chlorodimethylsilyl)ethane (17.24 g, 80 mmol) in tetrahydrofuran (50 ml) at a rate to maintain the temperature at -68 to -75°C. After addition, the resulting brown solution was stirred at -75°C for 75 minutes.

The resulting brown solution was treated with butyllithium (31.7 mL, 79 mmol) at a rate to maintain the temperature below -70°C, and the resulting solution was stirred at -74°C for 30 minutes. The cooling bath was removed and the reaction mixture solution was allowed to warm slowly to 15°C over approximately 2 hours.

The solution was cooled to -72°C and treated dropwise with butyllithium (31.7 ml, 79 mmol) at a rate to maintain the temperature below -70°C. After stirring for 60 min at -74°C, the resulting amber brown solution was treated dropwise with ethyl chloroformate (10.66 g, 98 mmol) at a rate to maintain the temperature below -70°C and the resulting dark solution was allowed to warm slowly to room temperature. temperatures as solid carbon dioxide is consumed.

The resulting heterogeneous mixture (yellowish-brown precipitate) was cooled to 0°C and the reaction was stopped by carefully adding 3N. aqueous hydrogen chloride solution (140 ml, 0.42 mmol). The ice bath was removed and the resulting dark solution was stirred at room temperature for 60 minutes. The pH was adjusted to ~8 by careful addition of solid sodium carbonate (~28 g) and the mixture was extracted with ethyl acetate (3×150 ml). The combined extracts were washed with brine (3 x 100 ml), dried over sodium sulfate, filtered and concentrated to give a dark oil. The crude oil was purified by automated flash chromatography (silica gel; 0→30% ethyl acetate in hexanes) to give the title compound as a light orange oil (8.96 g, 54%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.97 (dd, J = 8.6, 1.5 Hz, 1H), 6.73 (t, J = 8.9 Hz, 1H), 4.43 (q, J = 7.1 Hz , 2H), 3.84 (s, 2H), 1.40 (t, J = 7.2 Hz, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 163.49, 149.38, 146.94, 133.85, 133.73, 125.36, 125.32, 122.35, 122.18, 119.48 , 119.44, 117.95, 117.90, 62.19, 14.14; ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -134.47; EIMS m/z 217.

Example 92: Preparation of N-(3-amino-2,6-dichlorophenyl)acetamide (C321)

Step 1: Preparation of tert-butyl (3-acetamido-2,4-dichlorophenyl)carbamate. 3-Acetamido-2,4-dichlorobenzoic acid (1 g, 4.03 mmol) was added portionwise to a solution of diphenylphosphoryl azide (1.47 g, 5.34 mmol) and triethylamine (0.54 g, 5.34 mmol) with stirring. in anhydrous tert-butanol (25 ml). The resulting golden solution was heated at 80°C for 1 hour, then cooled and the reaction was stopped with water (20 ml). The resulting aqueous mixture was extracted with ethyl acetate (2×50 ml) and washed with saturated aqueous sodium bicarbonate (50 ml) and saturated aqueous sodium chloride (50 ml). Organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo on a rotary evaporator. Purification by silica gel flash column chromatography using 0-30% ethyl acetate in hexanes as eluent gave the title compound as a white solid (0.72 g, 44%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (d, J = 9.1 Hz, 1H), 7.32 - 7.25 (m, 2H), 6.96 (s, 1H), 2.23 (s, 3H), 1.54 (s, 9H); ESIMS m/z 320 ([M+H] ⁺ ).

Step 2: Preparation of N-(3-amino-2,6-dichlorophenyl)acetamide. 4 M Hydrogen chloride in 1,4-dioxane (2.8 ml, 11.3 mmol) was added dropwise to a solution of tert-butyl (3-acetamido-2,4-dichlorophenyl)carbamate (0.72 g, 2.25 mmol) in dichloromethane (5 ml). The resulting solid suspension was stirred for 11 hours at 23°C and then concentrated in vacuo on a rotary evaporator. The resulting crude product was dispersed in dichloromethane (2 ml) and treated with triethylamine to form a solution (~0.3 ml). Purification by flash silica gel chromatography using 0-100% ethyl acetate in hexanes as eluent gave the title compound as a white solid. (0.45 g, 87%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.60 (s, 1H), 7.13 (d, J = 8.8 Hz, 1H), 6, 73 (d, J = 8.8 Hz, 1H), 5.54 (s, 2H), 2.02 (s, 3H); ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 168.34, 145.19, 133.52, 127.82, 119.20, 117.75, 114.48, 22.92; ESIMS m/z 220 ([M+H] ⁺ ).

Example 93: Preparation of 5-amino-2-chloro-N-(2,2-difluoropropyl)benzamide (C322)

To a solution of 2-chloro-N-(2,2-difluoropropyl)-5-nitrobenzamide (C386; 0.45 g, 1.61 mmol) in tetrahydrofuran-ethanol-water (3:2:1, 12 ml) powdered iron (0.54 g, 9.71 mmol) and ammonium chloride (0.86 g, 16.18 mmol) and the reaction mixture was stirred at 80°C for 8 hours. The reaction mixture was filtered through a pad of Celite ^® and washed with ethyl acetate (50 ml) and methanol (30 ml). The filtrate was concentrated under reduced pressure and the residue was taken up in water and made basic with sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate (3×20 ml) and the organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. Purification by preparative high performance liquid chromatography (HPLC) provided the title compound as an off-white solid (0.24 g, 63%): m.p. 99 - 101°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.68 (t, J = 6.4 Hz, 1H), 7.06 (d, J = 1.6, 7.2 Hz, 1H), 6 .62 - 6.55 (m, 2H), 5.39 (s, 2H), 3.68 - 3.58 (m, 2H), 1.63 (t, J = 19.1 Hz, 3H); ESIMS m/z 249.10 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 93:

5-Amino-2-chloro-N-(2,2-difluorobutyl)benzamide (C323)

Isolated as an almost white solid (0.21 g, 52%): m.p. 82 - 84°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.64 (t, J = 6.4 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.62 - 6 .54 (m, 2H), 5.39 (s, 2H), 3.66 - 3.61 (m, 2H), 2.04 - 1.83 (m, 2H), 0.98 (t, J = 7.6 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -102.95; ESIMS m/z 263.12 ([M+H] ⁺ ).

Ethyl 3-(5-amino-2-chlorobenzamido)-2,2-difluoropropanoate (C324)

Isolated as a yellow solid (0.095 g, 18%): m.p. 100 - 102°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.78 (t, J = 6.4 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.59 (dd , J = 2.4, 8.8 Hz, 1H), 6.55 (d, J = 2.8 Hz, 1H), 5.42 (s, 2H), 4.28 (q, J = 6, 8 Hz, 2H), 3.93 - 3.84 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -109.55; ESIMS m/z 307.12 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2,2-difluoro-2-phenylethyl)benzamide (C325)

Isolated as a brown solid (0.22 g, 37%): m.p. 109 - 111°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.71 (t, J = 6.4 Hz, 1H), 7.61 - 7.46 (m, 5H), 7.03 (d, J = 8.8 Hz, 1H), 6.57 (dd, J = 2.8, 8.4 Hz, 1H), 6.50 (d, J = 2.8 Hz, 1H), 5.38 (s, 2H), 4.00 - 3.90 (m, 2H); ESIMS m/z 311.16 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2-oxopropyl)benzamide (C326)

Isolated as an almost white solid (0.2 g, 57%): m.p. 118 - 120°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.54 (t, J = 5.6 Hz, 1H), 7.06 (d, J = 8.8 Hz, 1H), 6.66 (d , J = 2.4 Hz, 1H), 6.59 (dd, J = 2.4, 8.4 Hz, 1H), 5.42 (s, 2H), 3.98 (d, J = 5, 6 Hz, 2H), 2.12 (s, 3H); ESIMS m/z 227.30 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2-oxobutyl)benzamide (C327)

Isolated as an almost white solid (0.25 g, 26%): m.p. 91 - 93°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.52 (t, J = 5.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.66 (d , J = 2.8 Hz, 1H), 6.59 (d, J = 2.4, 8.8 Hz, 1H), 5.42 (s, 2H), 3.99 (d, J = 5, 8 Hz, 2H), 2.49 - 2.41 (m, 2H), 0.96 (t, J =7.2 Hz, 3H); ESIMS m/z 241.06 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(4-methyl-2-oxopentyl)benzamide (C328)

Isolated as an almost white solid (0.2 g, 23%): m.p. 115 - 117°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.50 (t, J = 5.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.66 (d , J = 2.8 Hz, 1H), 6.59 (dd, J = 2.4, 8.8 Hz, 1H), 5.43 (s, 2H), 3.97 (d, J = 6, 0 Hz, 2H), 2.36 (d, J = 6.8 Hz, 2H), 2.13 - 1.99 (m, 1H), 0.88 (d, J = 6.4 Hz, 6H) ; ESIMS m/z 269.06 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2-oxo-2-phenylethyl)benzamide (C329)

Isolated as an almost white solid (0.06 g, 17%): m.p. 132 - 134°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.54 (t, J = 5.6 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.70 - 7 .66 (m, 1H), 7.59 - 7.54 (m, 2H), 7.07 (d, J = 8.4 Hz, 1H), 6.73 (d, J = 2.8 Hz, 1H), 6.60 (dd, J = 2.8, 8.4 Hz, 1H), 5.42 (s, 2H), 4.71 (d, J = 6.0 Hz, 2H); ESIMS m/z 289.14 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2,2-difluoropropyl)-3-fluorobenzamide (C330)

Isolated as an almost white solid (0.2 g, 63%): m.p. 107 - 109°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.80 (t, J = 6.4 Hz, 1H), 6.53 (dd, J = 2.8, 12.0 Hz, 1H), 6 .43 (d, J = 1.6 Hz, 1H), 5.73 (br s, 2H), 3.69 - 3.60 (m, 2H), 1.63 (t, J = 18.8 Hz , 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -93.66, -115.77; ESIMS m/z 267.08 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2,2-difluorobutyl)-3-fluorobenzamide (C331)

Isolated as an almost white solid (0.19 g, 53%): m.p. 79 - 81°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.81 (t, J = 6.0 Hz, 1H), 6.56 (dd, J = 2.8, 12.4 Hz, 1H), 6 .45 - 6.42 (m, 1H), 5.72 (br s, 2H), 3.70 - 3.60 (m, 2H), 1.97 - 1.86 (m, 2H), 0. 98 (t, J = 8.0 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -103.09, -115.77; ESIMS m/z 281.14 ([M+H] ⁺ ).

Ethyl 3-(5-amino-2-chloro-3-fluorobenzamido)-2,2-difluoropropanoate (C332)

Isolated as an almost white solid (0.12 g, 19%): m.p. 83 - 85°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.92 (t, J = 6.4 Hz, 1H), 6.54 (dd, J = 2.4, 11.6 Hz, 1H), 6 .42 - 6.40 (m, 1H), 5.76 (br s, 2H), 4.28 (q, J = 7.2 Hz, 2H), 3.95 - 3.85 (m, 2H) , 1.28 (t, J = 6.8 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -109.59, -115.63; ESIMS m/z 325.17 ([M+H] ⁺ ).

5-Amino-2-chloro-3-fluoro-N-(2-oxobutyl)benzamide (C333)

Isolated as an almost white solid (0.14 g, 40%): m.p. 96 - 98°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.65 (t, J = 6.0 Hz, 1H), 6.55 - 6.50 (m, 2H), 5.76 (br s, 2H ), 4.01 (d, J = 5.6, Hz, 2H), 2.49 - 2.46 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -115.66; ESIMS m/z 259.12 ([M+H] ⁺ ).

5-Amino-2-chloro-3-fluoro-N-(4-methyl-2-oxopentyl)benzamide (C334)

Isolated as an almost white solid (0.32 g, 58%): m.p. 99 - 101°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.58 (t, J = 6.0 Hz, 1H), 6.54 - 6.51 (m, 2H), 5.74 (br s, 2H ), 3.98 (d, J = 6.0 Hz, 2H), 2.35 (d, J = 6.8 Hz, 2H) 2.08 - 2.01 (m, 1H), 0.88 ( d, J = 6.8 Hz, 6H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -115.68; ESIMS m/z 287.15 ([M+H] ⁺ ).

5-Amino-2-chloro-3-fluoro-N-(2-oxo-2-phenylethyl)benzamide (C335)

Isolated as an almost white solid (0.21 g, 57%): m.p. 147 - 149°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.67 (t, J = 5.6 Hz, 1H), 8.04 - 8.01 (m, 2H), 7.70 - 7.66 ( m, 1H), 7.56 (t, J = 8.0 Hz, 2H), 6.58 - 6.52 (m, 2H), 5.76 (br s, 2H), 4.72 (d, J = 5.6 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -115.29; ESIMS m/z 307.19 ([M+H] ⁺ ).

5-Amino-2-chloro-3-fluoro-N-(2-oxopropyl)benzamide (C336)

Isolated as an almost white solid (0.075 g, 30%): m.p. 126 - 128°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.65 (t, J = 5.6 Hz, 1H), 6.55 - 6.50 (m, 2H), 5.76 (br s, 2H ), 4.01 (d, J = 6.0 Hz, 2H), 2.13 (s, 3H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -115.66; ESIMS m/z 245.03 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2,2-difluoro-2-phenylethyl)-3-fluorobenzamide (C337)

Isolated as an almost white solid (0.25 g, 60%): m.p. 136 - 138°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.83 (t, J = 6.4 Hz, 1H), 7.58 - 7.49 (m, 5H), 6.51 (dd, J = 2.4, 11.6 Hz, 1H), 6.36 - 6.31 (m, 1H), 5.72 (br s, 2H), 4.01 - 3.91 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -98.49, -115.60; ESIMS m/z 329.17 ([M+H] ⁺ ).

Example 94: Preparation of 5-amino-2-chloro-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide (C338)

To a solution of 5-amino-2-chlorobenzoic acid (0.6 g, 3.49 mmol) in dichloromethane (10 ml) 2-amino-N-(2,2,2-trifluoroethyl)acetamide (C350; 0. 8 g, 4.20 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2 g, 10.5 mmol), diisopropylethylamine (1.73 ml, 10.5 mmol) and 4-(dimethylamino)pyridine (catalyst) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure. Purification by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% ethyl acetate in methanol gave the title compound as an off-white solid (0.28 g, 26%): m.p. 109 - 111°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.47 (t, J = 5.6 Hz, 1H), 8.42 (t, J = 6.0 Hz, 1H), 7.05 (d , J = 8.4 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 6.58 (dd, J = 2.4, 8.8 Hz, 1H), 5.38 (m, 2H), 3.98 - 3.89 (m, 2H), 3.87 (d, J = 6.0 Hz, 2H); ESIMS m/z 310.15 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 94:

5-Amino-2-chloro-N-(3-oxo-3-((2,2,2-trifluoroethyl)amino)propyl)benzamide (C339)

Isolated as an almost white solid (0.17 g, 15%): m.p. 148 - 150°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.56 (t, J = 6.4 Hz, 1H), 8.22 (t, J = 5.2 Hz, 1H), 7.04 (d , J = 8.4 Hz, 1H), 6.58 - 6.54 (m, 2H), 5.33 (s, 2H), 3.92 - 3.84 (m, 2H), 3.41 - 3.35 (m, 2H), 2.44 (t, J = 7.2 Hz, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -70.71; ESIMS m/z 324.20 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(4-oxo-4-((2,2,2-trifluoroethyl)amino)butyl)benzamide (C340)

Isolated as an almost white solid (0.59 g, 25%): m.p. 136 - 138°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.46 (t, J = 6.4 Hz, 1H), 8.22 (t, J = 5.2 Hz, 1H), 7.05 - 7 .02 (m, 1H), 6.58 - 6.55 (m, 2H), 5.34 (s, 2H), 3.93 - 3.84 (m, 2H), 3.28 - 3.14 (m, 2H), 2.23 (t, J = 7.2 Hz, 2H), 1.75 - 1.68 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -70.85; ESIMS m/z 338.18 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2-oxo-2-((3,3,3-trifluoropropyl)amino)ethyl)benzamide (C341)

Isolated as an almost white solid (0.98 g, 33%): m.p. 110 - 112°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.39 (t, J = 6.0 Hz, 1H), 8.04 (t, J = 5.6, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.68 (d, J = 3.2 Hz, 1H), 6.58 (dd, J = 2.4, 8.4 Hz, 1H), 5.39 ( s, 2H), 3.78 (d, J = 6.0 Hz, 2H), 3.35 - 3.30 (m, 2H), 2.49 - 2.39 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -63.98; ESIMS m/z 324.13 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(3-oxo-3-((3,3,3-trifluoropropyl)amino)propyl)benzamide (C342)

Isolated as an almost white solid (0.83 g, 28%): m.p. 109 - 111°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.23 (t, J = 5.6 Hz, 1H), 8.13 (t, J = 5.6 Hz, 1H), 7.04 (d , J = 8.4 Hz, 1H), 6.57 (d, J = 3.2 Hz, 1H), 6.56 - 6.54 (m, 1H), 5.36 (s, 2H), 3 .39 - 3.34 (m, 2H), 3.30 - 3.25 (m, 2H), 2.50 - 2.31(m, 4H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -63.98; ESIMS m/z 338.15 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(4-oxo-4-((3,3,3-trifluoropropyl)amino)butyl)benzamide (C343)

Isolated as an almost white solid (0.51 g, 17%): m.p. 121 - 123°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 8.24 (t, J = 6.0 Hz, 1H), 8.02 (t, J = 5.2 Hz, 1H), 7.04 (d , J = 8.8 Hz, 1H), 6.57 - 6.55 (m, 2H), 5.36 (s, 2H), 3.30 - 3.24 (m, 2H), 3.18 - 3.13 (m, 2H), 2.50 - 2.35 (m, 2H), 2.13 (t, J = 7.2 Hz, 2H), 1.73 - 1.65 (m, 2H) ; ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -63.91; ESIMS m/z 352.41 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(2-(2,2,2-trifluoroacetamido)ethyl)benzamide (C344)

Isolated as an almost white solid (0.32 g, 18%): m.p. 157 - 159°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.38 - 9.35 (m, 1H), 8.38 - 8.36 (m, 1H), 7.06 - 7.03 (m, 1H ), 6.60 - 6.56 (m, 2H), 5.34 (s, 2H), 3.37 - 3.28 (m, 4H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -74.47; ESIMS m/z 310.15 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(3-(2,2,2-trifluoroacetamido)propyl)benzamide (C345)

Isolated as an almost white solid (0.80 g, 28%): m.p. 105 - 107°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.38 - 9.36 (m, 1H), 8.25 (t, J = 5.6 Hz, 1H), 7.04 (dd, J = 2.0, 7.2 Hz, 1H), 6.59 - 6.56 (m, 2H), 5.35 (s, 2H), 3.29 - 3.17 (m, 4H), 1.74 - 1.67 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -74.42; ESIMS m/z 324.24 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(4-(2,2,2-trifluoroacetamido)butyl)benzamide (C346)

Isolated as a pale yellow resinous substance (0.98 g, 34%):¹H NMR (400 MHz, DMSO-d₆) δ 9.44 (t, J = 5.6 Hz, 1H), 8.25 (t, J = 5.6 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.57 (d, J = 2.8 Hz, 1H), 6.55 - 6.54 (m, 1H), 5.37 (s, 2H), 3.22 - 3.15 (m, 4H) , 1.57 - 1.45 (m, 4H);¹⁹F NMR (376 MHz, DMSO-d₆) δ -74.36; IR 749.91 cm^-1 (C-Cl stretching vibration); ESIMS m/z 338.37 ([M+H]⁺).

5-Amino-2-chloro-N-(2-(2,2,3,3,3-pentafluoropropanamido)ethyl)benzamide (C347)

Isolated as an almost white solid (0.97 g, 46%): m.p. 150 - 152°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.48 (t, J = 5.6 Hz, 1H), 8.32 (t, J = 5.2 Hz, 1H), 7.05 (d , J = 9.2 Hz, 1H), 6.59 - 6.57 (m, 2H), 5.34 (s, 2H), 3.38 - 3.29 (m, 4H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -82.30, -121.85; ESIMS m/z 360.36 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(3-(2,2,3,3,3-pentafluoropropanamido)propyl)benzamide (C348)

Isolated as an almost white solid (0.70 g, 21%): m.p. 118 - 120°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 9.50 (t, J = 5.6 Hz, 1H), 8.27 (t, J = 6.0 Hz, 1H), 7.05 (dd , J = 2.0, 7.6 Hz, 1H), 6.59 - 6.56 (m, 2H), 5.37 (s, 2H), 3.32 - 3.25 (m, 2H), 3.22 - 3.16 (m, 2H), 1.74 - 1.67 (m, 2H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -82.37, -121.89; ESIMS m/z 374.33 ([M+H] ⁺ ).

5-Amino-2-chloro-N-(4-(2,2,3,3,3-pentafluoropropanamido)butyl)benzamide (C349)

Isolated as a brown tarry solid (0.36 g, 11%): IR 749.81 (C-Cl stretching vibration) cm^-1;¹H NMR (400 MHz, DMSO-d₆) δ 9.47 - 9.46 (m, 1H), 8.21 (t, J = 5.2 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.58 - 6.55 (m, 2H), 5.33 (s, 2H), 3.29 - 3.15 (m, 4H), 1.57 - 1.44 (m, 4H);¹⁹F NMR (376 MHz, DMSO-d₆) δ -82.35, -121.76; ESIMS m/z 388 ([M+H]⁺).

Example 95: Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (C350)

With stirring, a solution of tert-butyl-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)carbamate (C362; 3 g, 15.6 mmol) in dioxane (20 ml) dropwise at At 0°C, 4 M HCl in dioxane (23 mL, 93.8 mmol) was added and the reaction mixture was stirred at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure. The title compound was isolated as an almost white solid (2.4 g), which was used without purification: ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 9.17 - 9.13 (m, 1H), 8.21 (br s, 3H), 4.07 - 3.95 (m, 2H), 3.67 - 3.64 (m, 2H).

The following compounds were prepared using a procedure similar to that described in Example 95:

3-Amino-N-(2,2,2-trifluoroethyl)propanamide hydrochloride (C351)

Isolated as an almost white solid (2.3 g), which was used without purification: ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 8.93 (br s, 1H), 8.21 (br s, 3H ), 3.97 - 3.85 (m, 2H), 2.98 - 2.94 (m, 2H), 2.65 - 2.60 (m, 2H).

4-Amino-N-(2,2,2-trifluoroethyl)butanamide hydrochloride (C352)

Isolated as an almost white solid (2 g). The product was used in the next step without purification or analysis.

2-Amino-N-(3,3,3-trifluoropropyl)acetamide hydrochloride (C353)

Isolated as an almost white solid (2.4 g). The product was used in the next step without purification or analysis.

3-Amino-N-(3,3,3-trifluoropropyl)propanamide hydrochloride (C354)

Isolated as an almost white solid (2.7 g). The product was used in the next step without purification or analysis.

4-Amino-N-(3,3,3-trifluoropropyl)butanamide hydrochloride (C355)

Isolated as an almost white solid (2.7 g), which was used without purification: ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 8.26 (br s, 1H), 8.01 (br s, 3H ), 3.31 - 3.24 (m, 2H), 2.78 - 2.72 (m, 2H), 2.51 - 2.36 (m, 2H), 2.18 (t, J = 7 .5 Hz, 2H), 1.82 - 1.72 (m, 2H).

N-(2-Aminoethyl)-2,2,2-trifluoroacetamide hydrochloride (C356)

Isolated as an off-white solid (2.1 g) which was used without purification: ^1H NMR (300 MHz, DMSO- _d6 ) δ 9.67 (br s, 1H), 8.24 (br s, 3H ), 3.50 - 3.44 (m, 2H), 2.98 - 2.93 (m, 2H).

N-(3-Aminopropyl)-2,2,2-trifluoroacetamide hydrochloride (C357)

Isolated as an almost white solid (1.7 g). The product was used in the next step without purification or analysis.

N-(4-Aminobutyl)-2,2,2-trifluoroacetamide hydrochloride (C358)

Isolated as an almost white solid (3.2 g). The product was used in the next step without purification or analysis.

N-(2-Aminoethyl)-2,2,3,3,3-pentafluoropropanamide hydrochloride (C359)

Isolated as an off-white solid (2.9 g) which was used without purification: ^1H NMR (300 MHz, DMSO- _d6 ) δ 9.78 (br s, 1H), 8.23 (br s, 3H ), 3.56 - 3.38 (m, 2H), 2.96 - 2.94 (m, 2H).

N-(3-Aminopropyl)-2,2,3,3,3-pentafluoropropanamide hydrochloride (C360)

Isolated as an off-white solid (2.9 g): The product was used in the next step without purification or analysis.

N-(4-Aminobutyl)-2,2,3,3,3-pentafluoropropanamide hydrochloride (C361)

Isolated as an almost white solid (3.1 g), which was used without purification: ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 9.65 (br s, 1H), 8.10 (br s, 3H ), 3.23 - 3.21 (m, 2H), 2.78 - 2.76 (m, 2H), 1.55 - 1.54 (m, 4H).

Example 96: Preparation of tert-butyl-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)carbamate (C362)

To a solution of (tert-butoxycarbonyl)glycine (3 g, 17.1 mmol) in ethyl acetate (25 ml) 2,2,2-trifluoroethane-1-amine (2.55 g, 18.8 mmol) was added successively, 2. 4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide (50% solution in ethyl acetate; 22 ml, 68.5 mmol) and pyridine (4.4 ml, 54.8 mmol). The reaction mixture was stirred at room temperature for 16 hours, then poured into water and extracted with ethyl acetate (2×50 ml). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give the title compound as an off-white solid (3 g), which was used in the next step without purification or analysis.

The following compounds were prepared using a procedure similar to that described in Example 96:

tert-Butyl-(3-oxo-3-((2,2,2-trifluoroethyl)amino)propyl)carbamate (C363)

Isolated as an almost white solid (2.9 g). The product was used in the next step without purification or analysis.

tert-Butyl-(4-oxo-4-((2,2,2-trifluoroethyl)amino)butyl)carbamate (C364)

Isolated as an almost white solid (2.9 g). The product was used in the next step without purification: ^1H NMR (300 MHz, DMSO- _d6 ) δ 8.49 - 8.45 (m, 1H), 6.83 - 6.79 (m, 1H), 3.93 - 3.81 (m, 2H), 2.89 (dd, J = 6.0, 13.2 Hz, 2H), 2.16 - 2.11 (m, 2H), 1.64 - 1.54 (m, 2H), 1.37 (s, 9H).

tert-Butyl-(2-oxo-2-((3,3,3-trifluoropropyl)amino)ethyl)carbamate (C365)

Isolated as an almost white solid (2.8 g). The product was used in the next step without purification: ^1H NMR (300 MHz, DMSO- _d6 ) δ 8.00 - 7.98 (m, 1H), 7.00 - 6.96 (m, 1H), 3.50 - 3.25 (m, 4H), 2.50 - 2.34 (m, 2H), 1.38 (s, 9H).

tert-Butyl-(3-oxo-3-((3,3,3-trifluoropropyl)amino)propyl)carbamate (C366)

Isolated as an almost white solid (3.2 g). The product was used in the next step without purification: ^1H NMR (300 MHz, DMSO- _d6 ) δ 8.11 - 8.07 (m, 1H), 6.78 - 6.74 (m, 1H), 3.29 - 3.22 (m, 2H), 3.14 - 3.08 (m, 2H), 2.51 - 2.19 (m, 4H), 1.37 (s, 9H).

tert-Butyl-(4-oxo-4-((3,3,3-trifluoropropyl)amino)butyl)carbamate (C367)

Isolated as an off-white solid (3.8 g, crude). The product was used in the next step without purification: ^1H NMR (300 MHz, DMSO- _d6 ) δ 8.05 - 8.01 (m, 1H), 6.83 - 6.79 (m, 1H), 3.29 - 3.22 (m, 2H), 2.91 - 2.85 (m, 2H), 2.45 - 2.33 (m, 2H), 2.06 - 1.99 (m, 2H), 1 .62 - 1.52 (m, 2H), 1.37 (s, 9H).

Example 97: Preparation of tert-butyl (2-(2,2,2-trifluoroacetamido)ethyl)carbamate (C368)

To a solution of tert-butyl (2-aminoethyl)carbamate (3 g, 18.8 mmol) in tetrahydrofuran (25 ml) was added ethyl trifluoroacetate (2.7 g, 18.8 mmol) and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure. The title compound was isolated as an off-white solid (2.8 g) which was used in the next step without purification: ESIMS m/z 257.40 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 97:

tert-Butyl-(3-(2,2,2-trifluoroacetamido)propyl)carbamate (C369)

Isolated as an almost white solid (3.0 g). The product was used in the next step without purification: ESIMS m/z 271.40 ([M+H] ⁺ ).

tert-Butyl-(4-(2,2,2-trifluoroacetamido)butyl)carbamate (C370)

Isolated as an almost white solid (2.8 g). The product was used in the next step without purification: ESIMS m/z 285.41 ([M+H] ⁺ ).

tert-Butyl-(2-(2,2,3,3,3-pentafluoropropanamido)ethyl)carbamate (C371)

Isolated as an almost white solid (3.8 g). The product was used in the next step without purification: ESIMS m/z 307.37 ([M+H] ⁺ ).

tert-Butyl-(3-(2,2,3,3,3-pentafluoropropanamido)propyl)carbamate (C372)

Isolated as an almost white solid (4.3 g). The product was used in the next step without purification or analysis.

tert-Butyl-(4-(2,2,3,3,3-pentafluoropropanamido)butyl)carbamate (C373)

Isolated as an almost white solid (2.7 g). The product was used in the next step without purification or analysis.

Example 98: Preparation of 5-amino-2-chloro-3-fluorobenzoic acid (C196)

To a solution of 2-chloro-3-fluoro-5-nitrobenzoic acid (C206; 0.25 g, 1.14 mmol) in ethyl acetate (20 ml) was added 10% palladium on carbon (0.07 g) and the reaction mixture was stirred in hydrogen atmosphere (20 pounds per square inch (lbf/in ² )) for 16 hours. The reaction mixture was filtered through a pad of ^Celite® and washed with ethyl acetate and the filtrate was concentrated under reduced pressure. The crude product was triturated with n-pentane. The desired compound was isolated as an almost white solid (0.18 g, 82%): ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.24 (br s, 1H), 6.82 - 6.81 ( m, 1H), 6.61 (dd, J = 2.7, 12.0 Hz, 1H), 5.80 (br s, 2H); ESIMS m/z 189.95 ([M+H] ⁺ ).

Example 99: Preparation of N-allyl-N-(3-amino-2,6-difluorophenyl)-2,2-difluoroacetamide (C375)

Anhydrous tin chloride (0.62 g, 3.25 mmol) was added in portions with stirring to a solution of N-allyl-N-(2,6-difluoro-3-nitrophenyl)-2,2-difluoroacetamide (C247; 0.19 g , 0.65 mmol) in 1:1 methanol-dichloromethane (10 ml) at 5°C. The resulting yellow solution was stirred at 0-5°C for 2 hours and for 13 hours at 24°C. The reaction mixture was concentrated in vacuo on a rotary evaporator. Purification by flash chromatography on silica gel using 0-60% ethyl acetate in hexanes as eluent gave the title compound as a golden oil (0.15 g, 83%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 6. 96 - 6.82 (m, 2H), 6.06 - 5.62 (m, 2H), 5.23 - 5.07 (m, 2H), 4.33 (h, J = 7.6, 7 .0 Hz, 2H), 3.61 (s, 2H); ESIMS m/z 263 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 99:

tert-Butyl-(3-amino-2,6-difluorophenyl)(prop-2-yn-1-yl)carbamate (C376)

Isolated as a tan solid (0.151 g, 42%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.86 - 6.59 (m, 2H), 4.47 - 4.26 (m, 2H), 3.62 (s, 2H), 2.17 (dt, J = 18.7, 2.5 Hz, 1H), 1.55 (s, 9H); ESIMS m/z 283 ([M+H] ⁺ ).

Example 100: Preparation of tert-butyl (2,6-difluoro-3-nitrophenyl)carbamate (C377)

To a solution of tert-butyl-N-((tert-butoxy)carbonyl)-N-(2,6-difluoro-3-nitrophenyl)carbamate (C190) (2.60 g, 6.60 mmol) in ethyl acetate (66 ml ) trifluoroacetic acid (7.60 g, 66.0 mmol) was added. The reaction mixture was stirred at room temperature for 5 days. Additional trifluoroacetic acid (6.02 g, 52.3 mmol) was added and the reaction mixture was stirred for an additional 5 days. The reaction mixture was transferred to a separatory funnel and washed successively with saturated aqueous sodium bicarbonate until the pH of the organic layer was >3. The organic layer was then washed with brine, passed through a phase separator to dry and concentrated. Purification by column chromatography using 0 to 20% ethyl acetate/hexanes as eluent gave the title compound as a light yellow solid (1.32 g, 73%): ¹ H NMR (400 MHz, DMSO- _d6 ) δ 9.28 (s, 1H), 8.15 (ddd, J = 9.5, 8.3, 5.5 Hz, 1H), 7.43 (td, J = 9.2, 1.9 Hz , 1H), 1.45 (s, 9H); ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -106.41, -121.41; ESIMS m/z 273 ([MH] ^- ).

Example 101: Preparation of 2-chloro-N-(2,2-difluoropropyl)-3-fluoro-5-nitrobenzamide (C378):

To a solution of 2-chloro-3-fluoro-5-nitrobenzoic acid (C206; 0.5 g, 2.28 mmol) in ethyl acetate (15 ml) was added 2,2-difluoropropan-1-amine (0.3 g, 2 .28 mmol), 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinan-2,4,6-trioxide [50% solution in ethyl acetate] (2.7 ml, 9.13 mmol), pyridine (0.92 ml, 11.41 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (2×20 ml). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. Purification by column chromatography (silica gel 100 - 200 mesh) eluting with 15 - 20% ethyl acetate in petroleum ether gave the title compound as an off-white solid (0.35 g, 60%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.35 - 8.33 (m, 1H), 8.13 (dd, J = 2.7, 7.8 Hz, 1H), 6.44 - 6.41 (m, 1H), 3.97 - 3.85 (m, 2H), 1.74 (t, J = 18.6 Hz, 3H); ESIMS m/z 294.91 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 101:

2-Chloro-N-(2,2-difluorobutyl)-3-fluoro-5-nitrobenzamide (C379)

Isolated as an almost white solid (0.4 g, 56%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.35 - 8.33 (m, 1H), 8.12 (dd, J = 2 ,4, 8.1 Hz, 1H), 6.48 - 6.42 (m, 1H), 3.97 - 3.85 (m, 2H), 2.07 - 1.91 (m, 2H), 1.12 (t, J = 7.8 Hz, 3H); ESIMS m/z 310.94 ([M+H] ⁺ ).

Ethyl 3-(2-chloro-3-fluoro-5-nitrobenzamido)-2,2-difluoropropanoate (C380)

Isolated as a brown liquid (0.7 g). The product was used in the next step without purification: ESIMS m/z 355.15 ([M+H] ⁺ ).

2-Chloro-N-(2,2-difluoro-2-phenylethyl)-3-fluoro-5-nitrobenzamide (C381)

Isolated as an almost white solid (0.4 g, 56%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.26 - 8.23 (m, 1H), 8.10 (dd, J = 2 ,4, 7.8 Hz, 1H), 7.62 - 7.48 (m, 5H), 6.48 - 6.41 (m, 1H), 4.23 - 4.11 (m, 2H); ESIMS m/z 359.15 ([M+H] ⁺ ).

2-Chloro-3-fluoro-5-nitro-N-(2-oxopropyl)benzamide (C382)

Isolated as an almost white solid (0.21 g, 32%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 - 8.34 (m, 1H), 8.11 (dd, J = 2 ,4, 8.4 Hz, 1H), 7.05 - 7.01 (m, 1H), 4.40 (d, J = 4.4 Hz, 2H), 2.31 (s, 3H); ESIMS m/z 274.94 ([M+H] ⁺ ).

2-Chloro-3-fluoro-5-nitro-N-(2-oxobutyl)benzamide (C383)

Isolated as a brown liquid (0.35 g). The product was used in the next step without purification: ESIMS m/z 289.15 ([M+H] ⁺ ).

2-Chloro-3-fluoro-N-(4-methyl-2-oxopentyl)-5-nitrobenzamide (C384)

Isolated as an almost white solid (0.4 g, 58%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.39 - 8.36 (m, 1H), 8.12 (dd, J = 2 ,4, 7.8 Hz, 1H), 7.09 - 7.06 (m, 1H), 4.35 (d, J = 4.2 Hz, 2H), 2.42 (d, J = 6, 9 Hz, 2H), 2.27 - 2.18 (m, 1H), 0.98 (d, J = 6.6 Hz, 6H); ESIMS m/z 317.05 ([M+H] ⁺ ).

2-Chloro-3-fluoro-5-nitro-N-(2-oxo-2-phenylethyl)benzamide (C385)

Isolated as an almost white solid (0.4 g, 56%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.43 - 8.43 (m, 1H), 8.13 (dd, J = 2 ,4, 7.8 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.71 - 7.65 (m, 1H), 7.58 - 7.53 (m, 2H), 7.44 -7.41 (m, 1H), 5.01 (d, J = 4.2 Hz, 2H); ESIMS m/z 337.17 ([M+H] ⁺ ).

Example 102: Preparation of 2-chloro-N-(2,2-difluoropropyl)-5-nitrobenzamide (C386):

To a solution of 2-chloro-5-nitrobenzoic acid (0.7 g, 3.5 mmol) in dichloromethane (10 ml), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[ hexafluorophosphate was added successively 4,5-b]pyridinium 3-oxide (HATU; 4.0 g, 10.4 mmol), diisopropylethylamine (3 ml, 17.36 mmol) and 2,2-difluoropropan-1-amine (0.5 g, 3.8 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with dichloromethane (2×20 ml). The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated under reduced pressure. Purification by column chromatography (silica gel 100-200 mesh) eluting with 40-50% ethyl acetate in petroleum ether gave the title compound as an off-white solid (0.9 g, 93%): ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.53 (d, J = 2.4 Hz, 1H), 8.24 (dd, J = 2.4, 8.8 Hz, 1H), 7.63 (d, J = 8, 8 Hz, 1H), 6.46 - 6.41 (m, 1H), 3.94 - 3.86 (m, 2H), 1.73 (t, J = 18.8 Hz, 3H); ESIMS m/z 279.12 ([M+H] ⁺ ).

The following compounds were prepared using a procedure similar to that described in Example 102:

2-Chloro-N-(2,2-difluorobutyl)-5-nitrobenzamide (C387)

Isolated as an almost white solid (0.4 g, 54%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.53 (d, J = 3.0 Hz, 1H), 8.24 (dd, J = 3.3, 8.7 Hz, 1H), 7.62 (d, J = 8.7 Hz, 1H), 6.47-6.44 (m, 1H), 3.97 - 3.72 (m, 2H), 2.05 - 1.91 (m, 2H), 1.11 (t, J = 7.5 Hz, 3H).

Ethyl 3-(2-chloro-5-nitrobenzamido)-2,2-difluoropropanoate (C388)

Isolated as an almost white solid (0.7 g, 85%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.52 (d, J = 2.4 Hz, 1H), 8.25 (dd, J = 2.7, 8.7 Hz, 1H), 7.63 (d, J = 9.2 Hz, 1H), 6.54 - 6.52 (m, 1H), 4.38 (q, J = 6.9 Hz, 2H), 4.22 - 4.11 (m, 2H), 1.39 (t, J = 7.2 Hz, 3H); ESIMS m/z 336.98 ([M+H] ⁺ ).

2-Chloro-N-(2,2-difluoro-2-phenylethyl)-5-nitrobenzamide (C389)

Isolated as an almost white solid (0.68 g, 80%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.42 (d, J = 1.2 Hz, 1H), 8.22 (dd, J = 1.5, 9.3 Hz, 1H), 7.61 - 7.47 (m, 6H), 6.54 - 6.51 (m, 1H), 4.32 - 4.10 (m, 2H); ESIMS m/z 341.14 ([M+H] ⁺ ).

2-Chloro-5-nitro-N-(2-oxopropyl)benzamide (C390)

Isolated as a yellow solid (0.6 g, 50%): ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.53 (d, J = 2.4 Hz, 1H), 8.22 (dd, J = 2.1, 8.4 Hz, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.09 - 7.06 (m, 1H), 4.39 (d, J = 4.5 Hz, 2H), 2.28 (s, 3H); ESIMS m/z 257.01 ([M+H] ⁺ ).

2-Chloro-5-nitro-N-(2-oxobutyl)benzamide (C391)

Isolated as an off-white solid (0.6 g, 38%): ESIMS m/z 271.01 ([M+H] ⁺ ).

2-Chloro-N-(4-methyl-2-oxopentyl)-5-nitrobenzamide (C392)

Isolated as a yellow solid (1.2 g, 81%): ^1H NMR (400 MHz, DMSO- _d6 ) δ 7.06 (d, J = 8.4 Hz, 1H), 6.66 (d , J = 2.4 Hz, 1H), 6.50 (dd, J = 2.8, 8.4 Hz, 1H), 3.97 (d, J = 6.0 Hz, 2H), 2.36 (d, J = 6.8 Hz, 2H) 2.09 - 2.00 (m, 1H), 0.88 (d, J = 6.9 Hz, 6H).

2-Chloro-5-nitro-N-(2-oxo-2-phenylethyl)benzamide (C393)

Isolated as an off-white solid (0.6 g, 50%): ESIMS m/z 319.21 ([M+H] ⁺ ).

Example 103: Resolution of 5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide (F1373) and 5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide using preparative SFC (F1374 )

Racemic 5-((trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide (US Patent Application Publication US20160304522A1 (F129 )) were separated by preparative SFC using the following conditions: IC column (20 mm×250 mm), 5 μm; 35/65 MeOH (0.2% diethylamine)/CO ₂ , 40 g/min and obtained 5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido )-2-fluoro-N-(4-fluorophenyl)benzamide (F1373) (2nd eluting enantiomer, 100% EI) and 5-((1R,3R)-2,2-dichloro-3-(3,5 -dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide (F1374) (1st eluting enantiomer, 98.5% EI).

Example 104: Resolution of 5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide (F1375 ) and 5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide by preparative HPLC (F1376)

Racemic 5-((trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide (U.S. Patent Application Publication US20160304522A1 ( F61)) were separated by preparative HPLC using the following conditions: OJ - H column (20 mm×250 mm), 5 μm; 50/50 isopropanol (0.2% diethylamine)/hexane, 4.0 ml/min to obtain 5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1- carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide (F1375) (1st eluting enantiomer, 96.2% EI) and 5-((1S,3S)-2,2-dichloro-3- (3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide (F1376) (2nd eluting enantiomer, 96.0% EI).

Example 105: Separation of 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4,6-trifluorophenyl) benzamide (F1377) and 2-chloro-5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4,6-trifluorophenyl )benzamide using preparative SFC (F1378)

Racemic 2-Chloro-5-((trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4,6-trifluorophenyl)benzamide (US Patent Application Publication US20160304522A1 (F24)) were separated by preparative SFC using the following conditions: IC column (20 mm×250 mm), 5 μm; 35/65 MeOH (0.2% diethylamine)/CO ₂ , 40 g/min to obtain 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane -1-carboxamido)-N-(2,4,6-trifluorophenyl)benzamide (F1377) (1st eluting enantiomer, 100% EI) and 2-chloro-5-((1S,3S)-2,2- dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4,6-trifluorophenyl)benzamide (F1378) (2nd eluting enantiomer, 100% EI).

It should be understood that some reagents and reaction conditions may be incompatible with some functional groups that may be contained in some molecules of Formula 1 or some molecules used to prepare some molecules of Formula 1. In such cases, it may be necessary to use standard deprotection and deprotection techniques. groups described in detail in the literature and well known to one skilled in the art. In addition, in some cases it may be necessary to carry out additional standard synthetic steps not described in the present invention to complete the synthesis of the desired molecules. One skilled in the art will also understand that it is possible to synthesize the desired molecules by performing a series of steps not in the order described. One skilled in the art will also understand that standard functional group interconversions or substitution reactions can be performed on the molecules of interest to introduce or change substituents.

BIOLOGICAL RESEARCH

The following biological studies using the armyworm (Spodoptera exigua), armyworm (Trichoplusia ni) and yellow fever mosquito (Aedes aegypti) are included in the present invention due to the damage they cause. Additionally, the cutworm and armyworm are three good indicator species for a wide range of chewing pests. In addition, the green peach aphid is a good indicator species for a wide range of plant sap-feeding pests. Results for these four indicator species and the yellow fever mosquito indicate the broad applicability of the molecules of Formula 1 to control arthropod, mollusc and nematode pests (Drewes et al.).

Example A: Biological studies using the armyworm (Spodoptera exigua, LAPHEG) ("BAW") and the armyworm (Trichoplusia ni, TRIPNI) ("CL")

The armyworm is a pest that causes economic damage, along with other crops, to alfalfa, asparagus, beets, citrus fruits, corn, cotton, onions, peas, peppers, potatoes, soybeans, sugar beets, sunflowers, tobacco, and tomatoes. It is native to Southeast Asia but is now found in Africa, Australia, Japan, North America and Southern Europe. The larvae can feed in large aggregations, causing devastating crop losses. It is known to be resistant to various pesticides.

Armyworm is a dangerous pest found throughout the world. Along with other agricultural crops, it affects alfalfa, beans, beets, broccoli, Brussels sprouts, cabbage, cantaloupe, cauliflower, celery, brauncol, cotton, cucumbers, eggplant, cabbage, lettuce, melons, mustard, parsley, peas, peppers, potatoes, soybeans, spinach, pumpkin, tomatoes, turnips and watermelons. This species has a very destructive effect on plants due to its insatiable appetite. The larvae daily consume an amount of food that is three times their weight. Feeding sites are marked by large accumulations of sticky, wet fecal material. It is known to be resistant to various pesticides.

Therefore, due to these factors, controlling these pests is important. In addition, the molecules that provide control of these pests (BAW and CL), which are known as chewing pests, are useful for controlling other pests that chew plants.

Certain molecules disclosed herein have been studied to combat BAW and CL using the procedures described in the Examples below. When describing the results, we used the “Table of indicators for BAW and CL” (see Tables section).

Biological research using BAW

Biological studies using BAW were performed through a 128-well tray feeding assay. From 1 to 5 BAW larvae of the second larval stage were placed in each well of a feeding test tray (3 ml), into which 1 ml of artificial nutrient medium was previously placed, to which 50 μg/cm ² of the test molecules (dissolved in 50 μl of a mixture of 90: 10 acetone-water) (into each of the 8 wells) and then allowed to dry. The trays were covered with transparent self-adhesive film and kept at 25°C for 5 - 7 days in a light:dark cycle of 14:10. The percentage of larval mortality was recorded for each well; then the activity data for the 8 wells were averaged. The results are shown in the table entitled "Table ABC: Biological Results" (See tables section).

Biological research using CL

Biological studies using CL were performed through a 128-well tray feeding assay. From 1 to 5 CL larvae of the second larval stage were placed in each well of the feeding test tray (3 ml), into which 1 ml of artificial nutrient medium was previously placed, to which 50 μg/cm ² of the test molecules (dissolved in 50 μl of a mixture of 90: 10 acetone-water) (into each of the 8 wells) and then allowed to dry. The trays were covered with transparent self-adhesive film and kept at 25°C for 5 - 7 days in a light:dark cycle of 14:10. The percentage of larval mortality was recorded for each well; then the activity data for the 8 wells were averaged. The results are shown in the table entitled "Table ABC: Biological Results" (See tables section).

Example B: Biological studies using the green peach aphid (Myzus persicae, MYZUPE) (“GPA”).

GPA is the most significant aphid pest of peach trees, causing reduced growth, leaf wilting, and death of various tissues. They are also dangerous because they act as vectors for the transfer of plant viruses such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA affects plants such as broccoli, burdock, cabbage, carrots, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress and zucchini, among other plants. GPA also affects many ornamental crops such as carnations, chrysanthemums, flowering cabbages, poinsettias and roses. GPA has developed resistance to many pesticides. Therefore, due to these factors, control of this pest is important. In addition, the molecules that provide control of this pest (GPA), which is known as a sap-feeding pest, are useful in the control of other plant sap-feeding pests.

Certain molecules disclosed herein have been studied to combat GPA using the procedures described in the Example below. When describing the results, we used the “Table of Indicators for GPA and YFM” (see Tables section).

The study used cabbage seedlings grown in 3-inch pots with 2-3 small (3-5 cm) true leaves. 1 day before chemical application, seedlings were infested with 20-50 GPA (wingless adults and pupal stage insects). For each treatment, 4 pots containing one seedling were used. The test molecules (2 mg) were dissolved in 2 ml of acetone/MeOH (1:1) solvent to obtain stock solutions containing 1000 ppm of the test molecules. Stock solutions were diluted 5× with 0.025% Tween 20 in water to obtain a solution containing 200 ppm of the test molecules. A manual aspirator-type spraying device was used to spray the solution on both sides of the cabbage leaves until they drained. Control plants (solvent test) were sprayed only with a diluent containing 20 vol.% acetone/methanol solvent (1:1). Before examination, the treated plants were kept in a storage chamber for 3 days at approximately 25°C and ambient relative humidity (RH). The survey was carried out by counting the number of live aphids on one plant using a microscope. The percentage kill rate was calculated using the adjusted Abbott formula (W.S. Abbott, "A Method of Computing the Effectiveness of an Insecticide" J. Econ. Entomol. 18 (1925), pp. 265-267) as follows. Adjusted % kill rate = 100 * (X - Y)/X where X = number of live aphids on solvent-only control plants and Y = number of live aphids on treated plants. The results are shown in a table entitled "Table ABC: Biological Results" (See tables section).

Example C: Biological studies using the yellow fever mosquito (Aedes aegypti, AEDSAE) (“YFM”).

YFM prefers to feed on people during the daytime and is most often found near human habitation. YFM is a carrier of several diseases. It is a mosquito that can expand the spread of dengue and yellow fever viruses. Yellow fever is the second most dangerous mosquito-borne disease after malaria. Yellow fever is an acute viral hemorrhagic disease and, if left untreated, up to 50% of severely ill subjects die from yellow fever. There are an estimated 200,000 cases of yellow fever worldwide each year, resulting in 30,000 deaths. Dengue fever is a dangerous viral disease; it is sometimes called "bonebreaker fever" or "heartbreak fever" because it can cause severe pain. Dengue fever kills approximately 20,000 people every year. Due to the above factors, it is important to control this pest. In addition, the molecules that provide control of this pest (YFM), which is known as the sucking pest, are useful in the control of other pests that affect humans and animals.

Certain molecules disclosed herein have been studied to combat YFM using the procedures described in the Example below. When describing the results, we used the “Table of indicators for GPA and YFM” (See Tables section).

Standard plates containing 400 μg of molecules dissolved in 100 μl of dimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) were used. The reference plate contained the collected molecules at a concentration of 15 μl/well. 135 μl of a 90:10 water:acetone mixture was added to each well of this plate. The robot (Biomek ^® NXP Laboratory Automation Workstation) was programmed to transfer 15 μl of liquid from the reference plate into an empty shallow 96-well plate ("child" plate). For each reference plate, 6 replicate plates (“daughter” plates) were prepared. The prepared daughter plates were immediately infected with YFM larvae.

1 day before plate treatment, mosquito eggs were placed in Millipore water containing liver powder to hatch larvae (4 g in 400 ml). After preparing the daughter plates using the robot, they were infected with 220 μl of liver powder/mosquito larvae mixture (Approximately one day old larvae). After plates were infested with mosquito larvae, the plate was covered with an anti-evaporation lid to reduce drying out. Before examination, the plates were kept at room temperature for 3 days. After 3 days, each well was examined and mortality assessed. The results are shown in the table entitled "Table ABC: Biological Results" (See tables section).

Agriculturally acceptable acid addition salts, salt derivatives, solvates, ester derivatives, polymorphs, isotopes and radionuclides

The molecules of Formula 1 can be prepared as addition salts with agriculturally acceptable acids. As non-limiting Examples, it may be noted that amines can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic , benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic and hydroxyethanesulfonic acids. Additionally, by way of non-limiting example, acids can form salts, including alkali or alkaline earth metal salts and salts with ammonia and amines. Examples of preferred cations include sodium, potassium and magnesium cations.

The molecules of formula I can be prepared as derivative salts. By way of non-limiting example, a salt derivative can be prepared by reacting the free base with a sufficient amount of the desired acid to produce the salt. The free base can be regenerated by treating the salt with a dilute aqueous solution of a suitable base, such as a dilute aqueous solution of sodium hydroxide, potassium carbonate, ammonia and sodium bicarbonate. For example, in many cases a pesticide such as 2,4-D is more soluble in water when it is converted to a salt with dimethylamine.

The molecules of formula I can be prepared in the form of stable complexes with a solvent such that the complex does not change after removal of the uncomplexed solvent. These complexes are often called "solvates". However, it is particularly preferred to prepare stable hydrates with water as solvent.

The molecules of formula I can be prepared as ester derivatives. These ester derivatives can then be used in the same manner as the molecules disclosed herein.

The molecules of formula I can be prepared in various polymorphic crystalline forms. Polymorphism is important for the development of agricultural chemicals because different polymorphic crystalline forms or structures of the same molecule can have widely different physical characteristics and biological activities.

The molecules of formula I can be prepared with various isotopes. Particularly important are molecules containing ^2H (also known as deuterium) or ^3H (also known as tritium) instead of 1H. Formula 1 molecules can be prepared with various radionuclides. Molecules containing ¹⁴ C are especially important. Molecules of Formula 1 containing deuterium, tritium or ¹⁴ C can be used in biological research, allowing the study of chemical and physiological processes and half-lives, as well as the study of MoA.

Combinations

In another embodiment of the present invention, molecules of Formula 1 can be used in combination (such as a compositional mixture, or by simultaneous or sequential application) with one or more active ingredients.

In another embodiment of the present invention, molecules of Formula 1 can be used in combination (such as a compositional mixture, or by simultaneous or sequential administration) with one or more active ingredients, each of which has a MoA that is the same, similar, but, more likely different from the MoA of molecules of formula 1.

In another embodiment, the molecules of Formula 1 can be used in combination (such as a compositional mixture, or by simultaneous or sequential application) with one or more molecules having acaricidal, algaecidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal and/or virocidal ability.

In another embodiment, the molecules of Formula 1 can be used in combination (such as a compositional mixture, or by simultaneous or sequential application) with one or more molecules that are antifeedants, bird deterrents, chemosterilants, herbicide antidotes, insect decoys, insect repellents, mammal repellents, mating inhibitors, plant activators, plant growth regulators and/or synergists.

In another embodiment, molecules of Formula 1 can also be used in combination (such as a compositional mixture, or by simultaneous or sequential application) with one or more biopesticides.

In another embodiment, combinations of a molecule of Formula 1 and an active ingredient can be used in a pesticide composition over a wide range of weight ratios. For example, in a two-component mixture, the weight ratios of the molecule of Formula 1 to the weight of the active ingredient can be used using the weight ratios shown in Table B. Generally, however, weight ratios of less than about 10:1 to about 1:10 are preferred. It is also sometimes preferable to use a mixture containing 3, 4, 5, 6, 7 or more components and a molecule of Formula 1 and one or more active ingredients.

The ratio of the mass of the molecule of formula 1 to the mass of the active ingredient can also be represented as X:Y; where X means the content in parts by weight. molecules of formula 1 and Y means the content in parts by weight. active ingredient. Numerical range of content in parts by weight. for X is 0 < X ≤ 100 and the range is in parts by weight. for Y is 0 < Y ≤ 100, as shown in Table C. As a non-limiting example, the ratio of the weight of the molecule of Formula 1 to the weight of the active ingredient may be 20:1.

Ranges of ratios of the mass of the molecule of formula 1 to the mass of the active ingredient can be represented as from X ₁ :Y ₁ to X ₂ :Y ₂ , where X and Y are as defined above.

In one embodiment, the range of mass ratios may be from X ₁ :Y ₁ to X ₂ :Y ₂ , where X ₁ > Y ₁ and X ₂ < Y ₂ . As a non-limiting example, the range of the ratio of the weight of the molecule of Formula 1 to the weight of the active ingredient may be from 3:1 to 1:3, including cutoff points.

In another embodiment, the range of mass ratios may be from X ₁ :Y ₁ to X ₂ :Y ₂ , where X ₁ > Y ₁ and X ₂ > Y ₂ . As a non-limiting example, the range of the ratio of the weight of the molecule of Formula 1 to the weight of the active ingredient can be from 15:1 to 3:1, including cutoff points.

In another embodiment, the range of mass ratios may be from X ₁ :Y ₁ to X ₂ :Y ₂ , where X ₁ < Y ₁ and X ₂ < Y ₂ . As a non-limiting example, the range of ratios of the weight of the molecule of Formula 1 to the weight of the active ingredient can be from about 1:3 to about 1:20, including cutoff points.

Drugs

A pesticide is rarely suitable for use in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in a suitable form for easy application, handling, transportation, storage and maximum activity of the pesticide. Thus, pesticides are formulated, for example, as baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulated preparations, seed treatments, suspension concentrates, suspoemulsions, tablets, water-soluble liquids, water-dispersible granules or dry bulk mixtures, wettable powders and ultra-low volume solutions.

Pesticides are most often used in the form of aqueous suspensions or emulsions prepared from concentrated preparations of such pesticides. Such water-soluble, water-suspendable or water-emulsifiable preparations are solids, commonly known as wettable powders or water-dispersible granules, or liquids, commonly known as emulsifiable concentrates, or aqueous suspensions. Wettable powders, which can be compressed into water-dispersible granules, are a homogeneous mixture of pesticide, carrier and surfactants. The pesticide concentration is typically from about 10% to about 90% by weight. The carrier is typically selected from the group consisting of attapulgite clays, montmorillonite clays, diatomaceous earths or purified silicates. Effective surfactants containing from about 0.5% to about 10% wettable powder include sulfonated lignins, condensed naphthalene sulfonates, naphthalene sulfonates, alkyl benzene sulfonates, alkyl sulfates, and nonionic surfactants such as ethylene oxide adducts with alkyl phenols.

Emulsifiable pesticide concentrates contain the pesticide at a typical concentration, such as about 50 to about 500 g/L of liquid, dissolved in a vehicle, which is a water-miscible solvent or a mixture of a water-immiscible organic solvent and emulsifiers. Suitable organic solvents include aromatics, especially xylenes and petroleum fractions, especially high boiling naphthalene and olefinic petroleum fractions such as heavy aromatic naphtha. Other organic solvents may also be used, such as terpene solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are selected from conventional anionic and nonionic surfactants.

Aqueous suspensions include suspensions of water-insoluble pesticides dispersed in an aqueous vehicle at a concentration ranging from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mixing it with a carrier containing water and surfactants. Ingredients such as inorganic salts and synthetic or natural gums can also be added to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide simultaneously by preparing the aqueous mixture and homogenizing it in an apparatus such as a sand mill, ball mill, or piston-type homogenizer.

Oil dispersions (OD) include suspensions of organic solvent-insoluble pesticides finely dispersed in a mixture of organic solvent and emulsifiers at a concentration ranging from about 2% to about 50% by weight. One or more pesticides may be dissolved in the organic solvent. Useful organic solvents include aromatics, particularly xylenes, and petroleum fractions, particularly the high boiling naphthalene and olefin portions of petroleum such as heavy aromatic naphtha. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils. Suitable emulsifiers for the oil dispersion are selected from conventional anionic and nonionic surfactants. Thickeners or gelling agents are added to an oil dispersion preparation to alter the rheological characteristics or flow of the liquid and to prevent the separation and settling of dispersed particles or droplets.

Pesticides can also be used in the form of granular compositions, which are particularly suitable for application to soil. Granular compositions typically contain from about 0.5% to about 10% by weight of pesticide dispersed in a carrier that includes clay or the like. Such compositions are typically prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier that has been preformed into particles of a suitable size, ranging from about 0.5 to about 3 mm. Such compositions can also be prepared by preparing a dough or paste from the carrier and combining and grinding and drying to obtain granules of the required size. Another form of granules is water-emulsifying granules. They are a preparation containing granules applied as a conventional oil-in-water emulsion of the active ingredient(s), solubilized or diluted in an organic solvent after being dispersed and dissolved in water. Water-emulsifying granules comprise one or more active ingredients solubilized or diluted in a suitable organic solvent and adsorbed into a water-soluble polymer shell or other type of soluble or insoluble matrix.

Pesticide-containing dusts are prepared by thoroughly mixing the pesticide in powder form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, etc. Dusts may preferably contain from about 1% to about 10% pesticide. They can be used as a seed dressing or for foliar application with a pollinator.

It is equally advisable to use the pesticide in the form of a solution in a suitable organic solvent, usually petroleum oil, such as the insecticidal oils that are widely used in agrochemicals.

Pesticides can also be used in aerosol formulation. In such compositions, the pesticide is dissolved or dispersed in a carrier, which is a pressurized mixture of propellants. The aerosol composition is packaged in a container from which the mixture is dispensed through a spray valve.

Pesticide baits are produced when a pesticide is mixed with a feed or attractant, or both. When pests eat the bait, they also consume the pesticide. Baits may be in the form of granules, gels, loose powders, liquids or solids. They can be used in places where pests hide.

Fumigants are pesticides that have a relatively high vapor pressure and can therefore be present as a gas in concentrations sufficient to kill pests in soil or confined spaces. The toxicity of a fumigant is proportional to its concentration and duration of exposure. They are characterized by good diffusion ability and act by penetrating the pest's respiratory system or being absorbed through the pest's cuticle. Fumigants are used to control pests of stored products using sheet material that protects against gas escape in sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending pesticide particles or droplets in different types of polymers. By changing the chemical structure of the polymer or changing the processing characteristics, microcapsules of different sizes, solubilities, wall thicknesses and degrees of penetration can be formed. These factors determine the rate at which the active ingredient present is released, which in turn affects the residual effect, speed of action, and odor of the product. Microcapsules can be prepared as suspension concentrates or water-dispersible granules.

Oil solution concentrates are made by dissolving the pesticide in a solvent, which holds the pesticide in solution. Oil solutions of a pesticide generally provide faster breakdown and control of pests than other formulations because the solvents themselves are pesticidal and dissolution of the waxy coating of the outer coat increases the rate of release of the pesticide. Other benefits of oil-based solutions include better storage stability, better crack penetration, and better adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, where the emulsion contains oil beads that are coated with a layered liquid crystal coating and dispersed in an aqueous phase, wherein each bead contains at least one compound that is agriculturally active and is individually coated with a monolamellar or an oligolamellar layer comprising: (1) at least one nonionic lipophilic surfactant, (2) at least one nonionic hydrophilic surfactant, and (3) at least one ionic surfactant, wherein the beads have with an average diameter of less than 800 nm.

Other drug components

Typically, when the molecules disclosed in Formula I are used in a formulation, the formulation may also contain other components. These components include, but are not limited to (this list is not exhaustive or mutually exclusive), wetting agents, distributing agents, adhesives, permeation agents, buffers, complexing agents, drift reducing agents, compatibilizers, antifoaming agents, cleaning agents agents and emulsifiers. Some components are described below.

A wetting agent is a substance that, when added to a liquid, enhances the spreading or penetrating ability of the liquid by reducing the interfacial tension between the liquid and the surface over which it is spreading. Wetting agents are used in agrochemical preparations for two main purposes: during processing and manufacturing to increase the degree of wetting of powders in water in the preparation of dissolving liquid concentrates or suspension concentrates; and during mixing of the product with water in the spray tank to reduce the wetting time of wettable powders and to improve water penetration into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate and water-dispersible granule formulations include: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkylphenol ethoxylates and aliphatic alcohol ethoxylates.

A dispersing agent is a substance that is adsorbed on the surface of particles and helps to maintain the particles in a dispersed state and prevents their re-aggregation. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture and to enable redispersal into the water in the spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants, which are used as dispersing agents, have the ability to strongly adsorb onto the surface of a particle and create a charge or steric barrier to re-aggregation of the particles. The most commonly used surfactants are anionic, nonionic, or mixtures of the two. For wettable powder preparations, the most commonly used dispersing agents are sodium lignosulfonates. For suspension concentrates, very good adsorption and stabilization are achieved by using polyelectrolytes, such as the condensation products of sodium naphthalene sulfonate with formaldehyde. Tristyrylphenol ethoxylate phosphates are also used. Nonionic compounds, such as the condensation products of alkylaryl ethylene oxide with EO-PO (ethylene oxide-propylene oxide) block copolymers, are sometimes combined with anionic compounds as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed for use as dispersants. They have very long hydrophobic backbones and a large number of ethylene oxide chains forming the "teeth" of the surfactant "comb". These very high molecular weight polymers can impart very long-term stability to suspension concentrates because the hydrophobic backbones are able to attach at multiple positions on particle surfaces. Examples of dispersing agents used in agrochemical preparations are: sodium lignosulfonates; condensation products of sodium naphthalene sulfonate with formaldehyde; tristyrylphenol ethoxylate phosphates; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.

An emulsifying agent is a substance that stabilizes a suspension of droplets of a liquid phase in another liquid phase. Without an emulsifying agent, the two liquids separate into two immiscible liquid phases. The most commonly used emulsifier mixtures contain an alkylphenol or aliphatic alcohol containing 12 or more ethylene oxide units and an oil-soluble calcium salt of dodecylbenzenesulfonic acid. The Lipophilic-Hydrophilic Balance ("LHB") range of 8 to 18 typically produces emulsions that have good stability. Emulsion stability can sometimes be improved by adding a small amount of block copolymer surfactant EO-PO.

A solubilizing agent is a surfactant that forms micelles in water at concentrations above the critical micelle concentration. The micelles can then dissolve or solubilize water-insoluble substances within the hydrophobic portion of the micelle. The types of surfactants commonly used for solubilization are nonionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleates.

Surfactants are sometimes used alone or together with other additives such as mineral or vegetable oils as adjuvants in tank spray mixtures to improve the biological effect of the pesticide on the target. The types of surfactants used to enhance biological effects generally depend on the nature and type of exposure of the pesticide. However, they are often nonionic, such as: alkyl ethoxylates; ethoxylates of linear aliphatic alcohols; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural product is a substance added to a pesticide to produce the product at the required concentration. Carriers are usually substances having a high absorption capacity, and diluents are usually substances having a low absorption capacity. Carriers and diluents are used to prepare dusts, wettable powders, granules and water-dispersible granules.

Organic solvents are used primarily for the preparation of emulsifiable concentrates, oil-in-water emulsions, suspoemulsions and ultra-low-volume preparations, and to a lesser extent in granular preparations. Sometimes mixtures of solvents are used. The first major groups of solvents are aliphatic paraffin oils such as kerosene or refined paraffins. The second major group (and most common) includes aromatic solvents such as xylene and the higher molecular weight fractions of _C9 and _C10 aromatic solvents. Chlorinated hydrocarbons are useful as co-solvents to prevent crystallization of pesticides when the drug is emulsified in water. Alcohols are sometimes used as co-solvents to increase solubility. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used primarily in the preparation of suspension concentrates, emulsions, and suspoemulsions to alter the rheological or flow characteristics of a liquid and to prevent the separation and settling of dispersed particles or droplets. Thickening, gelling and anti-settling agents are generally divided into two categories, namely water-insoluble particulates and water-soluble polymers. Suspension concentrate preparations can be prepared using clays and silicon dioxides. Examples of these types of materials include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate and attapulgite. Water-soluble polysaccharides have been used for many years as thickening-gelling agents. These most commonly used types of polysaccharides are natural seed and seaweed extracts or synthetic cellulose derivatives. Examples of these types of materials include, but are not limited to, guar gum; carob gum; carrageenan; alginates; methylcellulose; sodium carboxymethylcellulose (SCMC); hydroxyethylcellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can spoil finished products. Therefore, preservative agents are used to eliminate or reduce their influence. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; sodium salt of p-hydroxybenzoic acid; methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often results in foaming of water-based formulations during formulation and spray tank application operations. To reduce the tendency to foam, antifoam agents are often added at the manufacturing stage or before packaging into bottles. There are generally two types of antifoams available, namely silicones and non-silicones. Silicones are usually aqueous emulsions of dimethylpolysiloxane, non-silicone antifoams are water-insoluble oils such as octanol and nonanol, or silica. In both cases, the purpose of the antifoam is to dislodge the surfactant from the air-water interface.

Green agents (eg excipients, surfactants, solvents) can reduce the overall environmental impact of crop protection products. Green agents are biodegradable and are typically obtained from natural and/or sustainable sources, such as plant and animal sources. Specific Examples are: vegetable oils, plant seed oils and their esters, and alkoxylated alkyl polyglucosides.

Application

Formula 1 molecules can be used on any site. Specific crop sites for application of such molecules include alfalfa, almonds, apples, barley, beans, canola, corn, cotton, brassicas, flowers, forages (perennial ryegrass, sudangrass, tall fescue, bluegrass and clover), fruit crops, lettuce, oats, oilseeds, oranges, peanuts, pears, peppers, potatoes, rice, sorghum, soybeans, strawberries, sugar cane, sugar beets, sunflowers, tobacco, tomatoes, wheat (e.g. durum red grain winter wheat, soft red grain winter wheat, white grain winter wheat, hard red grain spring wheat and durum spring wheat) and other valuable agricultural crops grow or on which their seeds will be sown.

The molecules of Formula 1 can also be used where plants, such as crops, grow and where there are few (or even no) pests that can cause large-scale damage to such plants. The use of such molecules in such an area is also beneficial for the plants growing in such area. Such beneficial factors may include, but are not limited to: promoting the growth of a better root system in the plant: promoting better tolerance of the plant to difficult growing conditions; improving the condition of the plant; increasing plant productivity (for example, increasing biomass and/or increasing the content of valuable components); improving plant vigor (eg, improving plant growth and/or producing greener leaves); improving the quality of the plant (for example, increasing the content or improving the composition of certain components); and improving plant resistance to abiotic and/or biotic stress.

Formula 1 molecules can be used in conjunction with ammonium sulfate when growing a variety of plants as this may provide additional benefits.

Molecules of formula I can be used on, in or around plants genetically modified to express special traits, such as Bacillus thuringiensis (for example, Cry1Ab, Cry1Ac, Cry1Fa, Cry1A,105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1/ Cry35Ab1) or other insecticidal toxins, or development of herbicide resistance, or possessing a foreign gene sequence expressing insecticidal toxins conferring herbicide resistance, enhanced nutrition, or any other favorable traits.

The molecule of formula I can be used to control pests on foliage and fruiting parts of plants. Such molecules either come into direct contact with the pest, or the pest consumes the pesticide by eating the plant or by sucking sap or other nutrients from the plant.

The Formula I molecule can also be applied to the soil and, when used in this manner, control can be provided by roots and stems eaten by pests. Roots can absorb such molecules, transferring them to the leafy parts of the plant to combat these soil-gnawing and sap-sucking pests.

Systemic movement of pesticides in plants can be used to control pests in one part of the plant by applying (eg, by spraying an area) molecules of formula I to different parts of the plant. For example, control of leaf-eating insects can be achieved by drip or furrow application, by soil treatment, such as by irrigating the soil before or after planting, or by treating the plant's seed before planting.

Formula 1 molecules can be used with baits. Typically when baits are used they are placed on the ground where, for example, termites may come into contact with the bait and/or be attracted to the bait. Baits can also be applied to a building surface (horizontal, vertical or sloped surface) where, for example, ants, termites, cockroaches and flies may come into contact with the bait and/or be attracted to the bait.

The molecules of Formula I can be encapsulated within a capsule or placed on the surface of a capsule. Capsule sizes can range from nanometer (approximately 100-900 nm in diameter) to micrometer (approximately 10-900 µm in diameter).

Formula 1 molecules can be used for pest eggs. Due to the specific resistance of some pest eggs to certain pesticides, repeated applications of Formula I molecules may be desirable to control emerging larvae.

Formula 1 molecules can be used as a seed treatment. Seed treatments can be used on all types of seeds, including those that grow into plants that have been genetically modified to express special traits. Typical Examples include seeds expressing proteins that are toxic to invertebrate pests such as Bacillus thuringiensis or other insecticidal toxins, conferring resistance to a herbicide such as "Roundup Ready" seed, or having foreign gene sequences expressing insecticidal toxins conferring resistance to herbicide, increased nutrition, drought tolerance or any other favorable traits. In addition, such seed treatments with molecules of Formula I may further enhance the plant's ability to better tolerate difficult growing conditions. This results in healthier, stronger plants, which can lead to higher yields at harvest time. In general, about 1 gram of molecules of Formula I to about 500 g per 100,000 seeds is expected to produce favorable results, amounts of about 10 g to about 100 g per 100,000 seeds are expected to produce better results and amounts of about 25 g to approximately 75 g per 100,000 seeds is believed to lead to even better results.

Formula 1 molecules can be used together with one or more active ingredients to improve soil.

The molecules of formula I can be used to control endoparasites and ectoparasites in veterinary or non-human animal husbandry. Such molecules can be used, for example, by oral administration in the form of, for example, tablets, capsules, drinks, granules, by application to the skin by, for example, dipping, spraying, pouring, patching and dusting, and by parenteral administration, e.g. using an injection.

The molecules of Formula I can also be used effectively in the management of livestock such as cattle, sheep, pigs, chickens and geese. They can also be used effectively on pets such as horses, dogs and cats. It is especially important to combat pests such as fleas and ticks that bother such animals. Suitable drugs are administered to animals orally through drinking water or food. Dosages and which drugs are appropriate depend on the species.

The molecules of formula I can also be used to control parasitic worms, especially in the intestines of the animals listed above.

The molecules of Formula I can also be used in human therapeutic applications. Such techniques include, but are not limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules and by application to the skin.

Formula 1 molecules can also be used against invasive pests. All over the world, pests migrate to new (for that pest) territories and then develop into new invasive species in that new territory. Such molecules could also be used to control such new invasive species in such new territory.

Therefore, in view of the above and the tables below in the tables section, the present invention relates to the following objects.

1. Molecule with the following formula

Formula 1

wherein:

(A) R ¹ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(B) R ² is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(C) R ³ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(D) R ⁴ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(E) R ⁵ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(F) R ⁶ means H;

(G) R ⁷ is selected from the group consisting of F, Cl and Br;

(H) R ⁸ is selected from the group consisting of F, Cl and Br;

(I) R ⁹ means H;

(J) Q ¹ selected from the group consisting of O and S;

(K) Q ² selected from the group consisting of O and S;

(L)R ¹⁰ is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )alkynyl, (C ₁ -C ₃ )alkyl-O( C ₁ -C ₃ )alkyl and (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl;

(M) R ¹¹ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(N)R ¹² is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(O)R ¹³ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(P)R ¹⁴ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(Q) X ³ means:

(1) N(R ^15a )(R ^15b ), where

(a) said R ^15a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkylphenyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ -C ₃ )alkyl and

(b) said R ^15b means substituted or unsubstituted phenyl, said substituted phenyl containing one or more substituents selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , NH ₂ , OH, SF ₅ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )haloalkenyl, (C ₁ -C ₃ )alkoxy group, (C=O) O(C ₁ -C ₃ )alkyl, O(C=O)(C ₁ -C ₃ )alkyl, N(R ^15c ) ₂ , N=CHN(R ^15c )(X ⁴ ), N(R ^15c )C (=O)O(X ⁴ ), N(R ^15c )S(=O) ₂ (X ⁴ ), N(S(=O) ₂ (C ₁ -C ₃ )alkyl) ₂ , N(R ^15c ) C(=O)N(R ^15c ) ₂ , N(R ^15c )C(=O)N(R ^15c )X ⁴ , N(R ^15c )C(=S)N(R ^15c ) ₂ , N(R ^15c )C(=S)N(R ^15c )X ⁴ , N(R ^15c )(C ₁ -C ₃ )alkyl-X ⁴ , N(R ^15c )(CH(O(C ₁ -C ₃ )alkyl) ₂ ), N(R ^15c )((C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl), N(R ^15c )((C ₁ -C ₃ )alkyl-C( =O)N(R ^15c ) ₂ ), N(R ^15c )C(=O)(R ^15c ), N(R ^15c )C(=O)X ⁴ , N(R ^15c )(C(=O) ) ₂ X ⁴ , N(R ^15c )(C(=O)) ₂ OX ⁴ , N(R ^15c )(C(=O)) ₂ N(R ^15c )X ⁴ , N(C(=O)O (C ₁ -C ₆ )alkyl) ₂ , N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, N(R ^15c )C(=O)N(R ^15c )C(=O )O(R ^15c ), N(R ^15C )(C(=O)O(C ₁ -C ₆ )alkyl), N(R ^15C )(C(=O)O(C ₁ -C ₆ )haloalkyl) , N((C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₆ )alkyl)(C(=O)(C ₁ -C ₆ )alkyl), N((C ₁ -C ₃ )alkyl-O(C ₁ -C ₆ )alkyl)(C(=O)O(C ₁ -C ₆ )alkyl) and N(R ^15c )C(=S)X ⁴ ,

(1) said R ^15c is each independently selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl , (C ₂ -C ₃ )haloalkenyl, (C ₁ -C ₃ )alkylphenyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(= O)(C ₁ -C ₃ )alkyl, C(=O)(C ₁ -C ₃ )alkyl and phenyl, optionally for N(R ^15c ) ₂ said N(R ^15c ) ₂ means a heterohydrocarbyl ring containing 1 ring atom nitrogen and 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated,

(2) said X ⁴ is selected from the group consisting of (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, O( C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkylphenyl, phenyl, aryl and heterocyclyl, each of which may contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NO ₂ , NH ₂ , oxo group, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ , O(C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )haloalkyl, N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, N (R ^15c )S(=O) ₂ (R ^15c ), S(=O) ₂ (R ^15c ), (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )cycloalkyl,

wherein in (1)(a) and (1)(b) each of said alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, aryl and heterocyclyl may contain one or more substituents selected from the group consisting of F, Cl, Br, I , CN, OH, NO ₂ , NH ₂ , NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ , O(C ₁ -C ₆ )alkyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl and (C ₃ -C ₆ )cycloalkyl;

(2) N(R ^16a )(R ^16b ), where

(a) said R ^16a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(b) said R ^16b means substituted or unsubstituted (C ₁ -C ₈ )alkyl, said substituted (C ₁ -C ₈ )alkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN , NO ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₁ -C ₈ )alkylphenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl , O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkyl, C(=O)O(C ₁ -C ₈ )alkyl, OC(=O)(C ₁ -C ₈ )alkyl, C(=O)N(R ^16a )(C ₁ - C ₈ )alkyl, N(R ^16a )C(=O)(C ₁ -C ₈ )alkyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O ) ₂ (C ₁ -C ₈ )alkyl, S(O) ₂ NH ₂ and N(R ^16a )S(O) ₂ (C ₁ -C ₈ )alkyl,

where in (2)(a) and (2)(b) each alkyl, alkenyl, alkynyl, cycloalkyl and phenyl may contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ -C ₈ )alkyl) ₂ and C(=O )O(C ₁ -C ₈ )alkyl;

(3) N(R ^17a )(N(R ^17b )(R ^17c )), where

(a) said R ^17a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(b) said R ^17b is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(c) said R ^17c is selected from the group consisting of H, substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, substituted or unsubstituted (C ₃ -C ₈ )cycloalkyl, C(= O)X ⁵ and C(=S)X ⁵ ,

(1) said X ⁵ is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, O(C ₁ -C ₈ )alkyl, O(C ₁ -C ₈ )haloalkyl, O(substituted and unsubstituted)phenyl, N(R ^17a )(C ₁ -C ₈ )alkyl, N(R ^17a )(C ₁ -C ₈ )haloalkyl, N(R ^17a )(C ₃ -C ₈ )cycloalkyl, N(R ^17a ) (substituted and unsubstituted phenyl) and (C ₃ -C ₆ )cycloalkyl,

(2) said substituted phenyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group and (C₁-C₃)alkyl,

(3) said substituted heterocyclyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group and (C₁-C₃)alkyl,

(4) said substituted (C ₁ -C ₈ )alkyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NO ₂ , NH ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, phenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S (O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl, O(C ₁ -C ₈ )alkyl( C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, C(=O)NH(C ₁ -C ₈ )alkyl , NHC(=O)(C ₁ -C ₈ )alkyl, S(O) ₂ NH ₂ , NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ ,

(5) said substituted (C ₃ -C ₈ )cycloalkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, (C ₁ -C ₃ )alkoxy and (C ₁ - C ₃ )alkyl,

wherein in (2)(a), (2)(b) and (2)(c), each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl may optionally contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ -C ₈ )alkyl) ₂ and C(=O)O(C ₁ -C ₈ )alkyl, optionally (N(R ^17b )(R ^17c )) means a heterohydrocarbyl ring containing 1 ring nitrogen atom and 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated;

(4) N(R ^18a )(N=C(R ^18b )(R ^18c )

(a) said R ^18a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )alkyl-O (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ -C ₃ )alkyl,

(b) said R ^18b is selected from the group consisting of H and (C ₁ -C ₃ )alkyl,

(c) said R ^18c is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, substituted or unsubstituted (C ₃ -C ₈ )cycloalkyl,

(1) said substituted phenyl in (4)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group, (C₁-C₃)alkyl, (C₁-C₃)haloalkoxy group and (C₁-C₃)haloalkyl,

(2) said substituted heterocyclyl in (4)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group, (C₁-C₃)alkyl, (C₁-C₃)haloalkoxy group and (C₁-C₃)haloalkyl,

(3) said substituted (C ₁ -C ₈ )alkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, phenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, C(=O)NH(C ₁ -C ₈ )alkyl, NHC(=O)(C ₁ -C ₈ )alkyl and S(O) ₂ NH ₂ ,

(4) said substituted (C ₃ -C ₈ )cycloalkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, (C ₁ -C ₃ )alkoxy and (C ₁ - C ₃ )alkyl,

where in (4)(a), (4)(b) and (4)(c) each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl may contain one or more substituents selected from the group consisting of F , Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ - C ₈ )alkyl) ₂ and C(=O)O(C ₁ -C ₈ )alkyl, optionally C(R ^18b )(R ^18c ) means a hydrocarbyl ring containing from 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated, optionally one or more of said ring carbon atoms may be a nitrogen, oxygen or sulfur atom;

and N-oxides, agriculturally acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystalline polymorphs, isotopes, separated stereoisomers, tautomers, pro-insecticides of molecules of formula 1.

2. The molecule according to paragraph 1, in which:

(A) R ¹ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(B) R ² is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(C) R ³ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(D) R ⁴ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(E) R ⁵ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , SF ₅ and (C ₁ -C ₃ )haloalkyl;

(F) R ⁶ means H;

(G) R ⁷ is selected from the group consisting of F, Cl and Br;

(H) R ⁸ is selected from the group consisting of F, Cl and Br;

(I) R ⁹ means H;

(J) Q ¹ selected from the group consisting of O and S;

(K) Q ² selected from the group consisting of O and S;

(L)R ¹⁰ is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )alkynyl, (C ₁ -C ₃ )alkyl-O( C ₁ -C ₃ )alkyl and (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl;

(M) R ¹¹ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(N)R ¹² is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(O)R ¹³ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(P)R ¹⁴ is selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ ) alkoxy group;

(Q) X ³ means:

(1) N(R ^15a )(R ^15b ), where

(a) said R ^15a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkylphenyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ -C ₃ )alkyl and

(b) said R ^15b means substituted or unsubstituted phenyl, said substituted phenyl containing one or more substituents selected from the group consisting of H, F, Cl, Br, I, CN, NO ₂ , NH ₂ , OH, SF ₅ , (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )haloalkenyl, (C ₁ -C ₃ )alkoxy group, (C=O) O(C ₁ -C ₃ )alkyl, O(C=O)(C ₁ -C ₃ )alkyl, N(R ^15c ) ₂ , N=CHN(R ^15c )(X ⁴ ), N(R ^15c )C (=O)O(X ⁴ ), N(R ^15c )S(=O) ₂ (X ⁴ ), N(S(=O) ₂ (C ₁ -C ₃ )alkyl) ₂ , N(R ^15c ) C(=O)N(R ^15c ) ₂ , N(R ^15c )C(=O)N(R ^15c )X ⁴ , N(R ^15c )C(=S)N(R ^15c ) ₂ , N(R ^15c )C(=S)N(R ^15c )X ⁴ , N(R ^15c )(C ₁ -C ₃ )alkyl-X ⁴ , N(R ^15c )(CH(O(C ₁ -C ₃ )alkyl) ₂ ), N(R ^15c )((C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl), N(R ^15c )((C ₁ -C ₃ )alkyl-C( =O)N(R ^15c ) ₂ ), N(R ^15c )C(=O)(R ^15c ), N(R ^15c )C(=O)X ⁴ , N(R ^15c )(C(=O) ) ₂ X ⁴ , N(R ^15c )(C(=O)) ₂ OX ⁴ , N(R ^15c )(C(=O)) ₂ N(R ^15c )X ⁴ , N(C(=O)O (C ₁ -C ₆ )alkyl) ₂ , N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, N(R ^15c )C(=O)N(R ^15c )C(=O )O(R ^15c ), N(R ^15C )(C(=O)O(C ₁ -C ₆ )alkyl), N(R ^15C )(C(=O)O(C ₁ -C ₆ )haloalkyl) , N((C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₆ )alkyl)(C(=O)(C ₁ -C ₆ )alkyl), N((C ₁ -C ₃ )alkyl-O(C ₁ -C ₆ )alkyl)(C(=O)O(C ₁ -C ₆ )alkyl) and N(R ^15c )C(=S)X ⁴ ,

(1) said R ^15c is each independently selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl , (C ₂ -C ₃ )haloalkenyl, (C ₁ -C ₃ )alkylphenyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(= O)(C ₁ -C ₃ )alkyl, C(=O)(C ₁ -C ₃ )alkyl and phenyl, optionally for N(R ^15c ) ₂ said N(R ^15c ) ₂ means a heterohydrocarbyl ring containing 1 ring atom nitrogen and 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated,

(2) said X ⁴ is selected from the group consisting of (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, O( C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkylphenyl, phenyl, aryl and heterocyclyl, each of which may contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NO ₂ , NH ₂ , oxo group, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ , O(C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )haloalkyl, N(R ^15c )C(=O)O(C ₁ -C ₆ )alkyl, N (R ^15c )S(=O) ₂ (R ^15c ), S(=O) ₂ (R ^15c ), (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )cycloalkyl,

wherein in (1)(a) and (1)(b) each of said alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, aryl and heterocyclyl may contain one or more substituents selected from the group consisting of F, Cl, Br, I , CN, OH, NO ₂ , NH ₂ , NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ , O(C ₁ -C ₆ )alkyl, (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl and (C ₃ -C ₆ )cycloalkyl;

(2) N(R ^16a )(R ^16b ), where

(a) said R ^16a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(b) said R ^16b means substituted or unsubstituted (C ₁ -C ₈ )alkyl, said substituted (C ₁ -C ₈ )alkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN , NO ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₁ -C ₈ )alkylphenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl , O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkyl, C(=O)O(C ₁ -C ₈ )alkyl, OC(=O)(C ₁ -C ₈ )alkyl, C(=O)N(R ^16a )(C ₁ - C ₈ )alkyl, N(R ^16a )C(=O)(C ₁ -C ₈ )alkyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O ) ₂ (C ₁ -C ₈ )alkyl, S(O) ₂ NH ₂ and N(R ^16a )S(O) ₂ (C ₁ -C ₈ )alkyl,

where in (2)(a) and (2)(b) each alkyl, alkenyl, alkynyl, cycloalkyl and phenyl may contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ -C ₈ )alkyl) ₂ and C(=O )O(C ₁ -C ₈ )alkyl;

(3) N(R ^17a )(N(R ^17b )(R ^17c )), where

(a) said R ^17a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(b) said R ^17b is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )haloalkyl, ( C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ - C ₃ )alkyl,

(c) said R ^17c is selected from the group consisting of H, substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, substituted or unsubstituted (C ₃ -C ₈ )cycloalkyl, C(= O)X ⁵ and C(=S)X ⁵ ,

(1) said X ⁵ is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, O(C ₁ -C ₈ )alkyl, O(C ₁ -C ₈ )haloalkyl, O(substituted and unsubstituted)phenyl, N(R ^17a )(C ₁ -C ₈ )alkyl, N(R ^17a )(C ₁ -C ₈ )haloalkyl, N(R ^17a )(C ₃ -C ₈ )cycloalkyl, N(R ^17a ) (substituted and unsubstituted phenyl) and (C ₃ -C ₆ )cycloalkyl,

(2) said substituted phenyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group and (C₁-C₃)alkyl,

(3) said substituted heterocyclyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group and (C₁-C₃)alkyl,

(4) said substituted (C ₁ -C ₈ )alkyl in (3)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NO ₂ , NH ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, phenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S (O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl, O(C ₁ -C ₈ )alkyl( C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, C(=O)NH(C ₁ -C ₈ )alkyl , NHC(=O)(C ₁ -C ₈ )alkyl, S(O) ₂ NH ₂ , NH(C ₁ -C ₃ )alkyl, N((C ₁ -C ₃ )alkyl) ₂ ,

(5) said substituted (C ₃ -C ₈ )cycloalkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, (C ₁ -C ₃ )alkoxy and (C ₁ - C ₃ )alkyl,

wherein in (2)(a), (2)(b) and (2)(c), each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl may optionally contain one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ -C ₈ )alkyl) ₂ and C(=O)O(C ₁ -C ₈ )alkyl, optionally (N(R ^17b )(R ^17c )) means a heterohydrocarbyl ring containing 1 ring nitrogen atom and 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated; And

(4) N(R ^18a )(N=C(R ^18b )(R ^18c ))

(a) said R ^18a is selected from the group consisting of H, (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₂ -C ₃ )kynyl, (C ₁ -C ₃ )alkyl-O (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkyl-OC(=O)(C ₁ -C ₃ )alkyl and C(=O)(C ₁ -C ₃ )alkyl,

(b) said R ^18b is selected from the group consisting of H and (C ₁ -C ₃ )alkyl,

(c) said R ^18c is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C ₁ -C ₈ )alkyl, substituted or unsubstituted (C ₃ -C ₈ )cycloalkyl,

(1) said substituted phenyl in (4)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group, (C₁-C₃)alkyl, (C₁-C₃)haloalkoxy group and (C₁-C₃)haloalkyl,

(2) said substituted heterocyclyl in (4)(c) contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO₂, OH, (C₁-C₃)alkoxy group, (C₁-C₃)alkyl, (C₁-C₃)haloalkoxy group and (C₁-C₃)haloalkyl,

(3) said substituted (C ₁ -C ₈ )alkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, NO ₂ , O(C ₁ -C ₈ )alkyl, (C ₃ -C ₈ )cycloalkyl, phenyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, S(C ₁ -C ₈ )alkyl, S(O)(C ₁ -C ₈ )alkyl, S(O) ₂ (C ₁ -C ₈ )alkyl, O-phenyl, O(C ₂ -C ₈ )alkenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, O(C ₁ -C ₈ )alkylphenyl, O(C ₁ -C ₈ )alkyl(C ₃ -C ₈ )cycloalkyl, C(=O)NH(C ₁ -C ₈ )alkyl, NHC(=O)(C ₁ -C ₈ )alkyl and S(O) ₂ NH ₂ ,

(4) said substituted (C ₃ -C ₈ )cycloalkyl contains one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, (C ₁ -C ₃ )alkoxy and (C ₁ - C ₃ )alkyl,

where in (4)(a), (4)(b) and (4)(c) each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl may contain one or more substituents selected from the group consisting of F , Cl, Br, I, CN, OH, NH ₂ , NO ₂ , (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )alkoxy group, (C ₁ -C ₈ )haloalkyl, N((C ₁ - C ₈ )alkyl) ₂ and C(=O)O(C ₁ -C ₈ )alkyl, optionally C(R ^18b )(R ^18c ) means a hydrocarbyl ring containing from 3 to 5 ring carbon atoms, where said ring may be saturated or unsaturated, optionally one or more of said ring carbon atoms may be a nitrogen, oxygen or sulfur atom.

3. The molecule according to the previous paragraphs 1 and 2, where the specified molecule has the following formula

Formula 2.

4. A molecule as defined in any of the preceding paragraphs, wherein R ¹ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

5. A molecule as defined in any of the preceding paragraphs, wherein R ² is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

6. A molecule as defined in any of the preceding paragraphs, wherein R ³ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

7. A molecule as defined in any of the preceding paragraphs, wherein R ⁴ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

8. A molecule as defined in any of the preceding paragraphs, wherein R ⁵ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ .

9. A molecule as defined in any of the preceding paragraphs, wherein at least one of R ² , R ³ and R ⁴ is SF ₅ .

10. A molecule as defined in any of the preceding paragraphs, wherein R ⁷ is Cl.

11. A molecule as defined in any of the preceding paragraphs, wherein R ⁸ is Cl.

12. A molecule according to any of the previous paragraphs, in which R ⁷ and R ⁸ are not the same.

13. A molecule according to any of the previous paragraphs, in which Q ¹ means O.

14. A molecule according to any of the previous paragraphs in which Q ² is O.

15. A molecule as defined in any of the preceding paragraphs, wherein R ¹⁰ is H.

16. A molecule as defined in any of the preceding paragraphs, in which R ¹¹ is H.

17. A molecule as defined in any of the preceding paragraphs, wherein R ¹² is selected from the group consisting of H, F, Cl, CH ₃ and CF ₃ .

18. A molecule as defined in any of the preceding paragraphs, wherein R ¹³ is selected from the group consisting of F, Cl, CH ₃ and OCH ₃ .

19. A molecule as defined in any of the preceding paragraphs, wherein R ¹⁴ is selected from the group consisting of H, F and Cl.

20. A molecule according to any of the previous paragraphs, in which:

R ¹ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ² is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ³ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ⁴ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ⁵ is selected from the group consisting of H, F, Cl, Br, SF ₅ and CF ₃ ;

R ⁷ is Cl;

R ⁸ is Cl;

Q ¹ means O;

Q ² means O;

R ¹⁰ means H;

R ¹¹ means H;

R ¹² is selected from the group consisting of H, F, Cl, CH ₃ and CF ₃ ;

R ¹³ is selected from the group consisting of F, Cl, CH ₃ and OCH ₃ ; And

R ¹⁴ is selected from the group consisting of H, F and Cl.

21. A molecule according to any of the previous paragraphs 1-20 inclusive, in which X ³ means N(R ^15a )(R ^15b ),

said R ^15b is selected from the group consisting of N(R ^15c )C(=O)(R ^15c ) and N(R ^15c )C(=O)X ⁴ ,

said R ^15c are all independently selected from the group consisting of (C ₁ -C ₃ )alkyl, (C ₂ -C ₃ )alkenyl, (C ₁ -C ₃ )haloalkyl and (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl,

said X ⁴ is selected from the group consisting of (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl and (C ₁ -C ₃ )alkyl-O(C ₁ -C ₃ )alkyl,

wherein each of said alkyl, haloalkyl and alkenyl may contain one or more substituents selected from the group consisting of F, Cl, CN and (C ₃ -C ₆ )cycloalkyl.

22. A molecule as defined in any of the preceding paragraphs 1 to 20, inclusive, wherein X ³ is N(R ^15a )(R ^15b ) and R ^15b is N(R ^15c )C(C=O)X ⁴ ).

23. A molecule as defined in any of the preceding paragraphs 1 to 20, inclusive, wherein X ³ is N(R ^16a )(R ^16b ).

24. A molecule as defined in any of the preceding paragraphs 1 to 20, inclusive, wherein X3 is N(R ^17a )(N(R ^17b )(R ^17c )).

25. A molecule as defined in any of the preceding paragraphs 1 to 20, inclusive, wherein X ³ is N(R ^18a )(N=C(R ^18b )(R ^18c ).

26. A molecule selected from Table 2, preferably a molecule selected from the group consisting of F1007, F1079, F1108, F1147, F1185, F1234, F1241, F1246, F1247, F1248, F1250, F1460, F1465, F1593, F1598, F1613 , F1627 , F1657, F1694, F1696, F1697, F1702, F1703, F1704, F1708, F1711, F1740, F2016, F2017, F2021, F2027, F2039, F2042, F2078 and F2081.

27. A composition comprising a molecule according to any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient.

28. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26 inclusive, further comprising an active ingredient selected from the group consisting of acaricides, algaecides, antifeedants, avicides, bactericides, bird repellents, chemosterilants, fungicides, herbicide antidotes, herbicides, insect attractants, insect repellents, insecticides, mammal repellents, mating inhibitors, molluscicides, nematicides, plant activators, plant growth regulators, rodenticides, synergists and viricides.

29. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising an active ingredient selected from the group AIGA.

30. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising AI-1.

31. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising lotilaner.

32. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising a molecule selected from Table A.

33. A composition comprising a molecule according to any of the preceding paragraphs 1 to 26 inclusive, further comprising an active ingredient selected from the group AIGA-2.

34. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising chlorpyrifos.

35. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising hexaflumuron.

36. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising methoxyfenozide.

37. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising noviflumuron.

38. A composition comprising the molecule of any of the preceding paragraphs 1-26 inclusive, further comprising spinatoram.

39. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising spinosad.

40. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising sulfoxaflor.

41. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising an active ingredient selected from the group AIGA-2.

42. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising acequinocyl.

43. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising acetamiprid.

44. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising acetoprol.

45. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising avermectin.

46. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising azinphos-methyl.

47. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising biphenazate.

48. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising bifenthrin.

49. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising carbaryl.

50. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising carbofuran.

51. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising chlorfenapyr.

52. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising chlorfluazuron.

53. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising chromafenozide.

54. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising clothianidin.

55. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising cyfluthrin.

56. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising cypermethrin.

57. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising deltamethrin.

58. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising diafenthiuron.

59. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising emamectin benzoate.

60. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising endosulfan.

61. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising esfenvalerate.

62. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising ethiprole.

63. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising ethoxazole.

64. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising fipronil.

65. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising flonicamid.

66. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising fluacripyrim.

67. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising gamma-cyhalothrin.

68. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising a halofenozide.

69. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising indoxacarb.

70. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising lambda-cyhalothrin.

71. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising lufenuron.

72. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising malathion.

73. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising methomyl.

74. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising novaluron.

75. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising permethrin.

76. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising pyridalyl.

77. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising pyrimidifene.

78. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising spirodiclofen.

79. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising tebufenozide.

80. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising thiacloprid.

81. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising thiamethoxam.

82. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising thiodicarb.

83. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising tolfenpyrad.

84. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising zeta-cypermethrin.

85. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising a biopesticide.

86. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an acetylcholinesterase (AChE) inhibitor active ingredient.

87. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a GABA-regulated chloride channel antagonist.

88. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising a sodium channel modulator active ingredient.

89. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising a nicotinic acetylcholine receptor (nAChR) agonist active ingredient.

90. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient among allosteric activators of the nicotinic acetylcholine receptor (nAChR).

91. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising a chloride channel activator active ingredient.

92. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a juvenile hormone mimic.

93. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising an active ingredient from among various non-specific (multisite) inhibitors.

94. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising a chordotonal organ modulator active ingredient.

95. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising a mite growth inhibitor active ingredient.

96. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a microbiological agent for disrupting insect midgut membranes.

97. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a mitochondrial ATP synthase inhibitor.

98. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of oxidative phosphorylation uncoupling agents that act by disrupting the proton gradient.

99. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a nicotinic acetylcholine receptor (nAChR) channel blocker.

100. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of chitin biosynthesis inhibitors, type 0.

101. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of chitin biosynthesis inhibitors, type 1.

102. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a dipteran moulting agent.

103. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an ecdysone receptor agonist active ingredient.

104. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an octopamine receptor agonist active ingredient.

105. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a mitochondrial complex III electron transfer inhibitor.

106. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient from among mitochondrial complex I electron transfer inhibitors.

107. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising a voltage-gated sodium channel blocker active ingredient.

108. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an acetyl-CoA carboxylase inhibitor active ingredient.

109. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a mitochondrial complex IV electron transfer inhibitor.

110. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising an active ingredient of a mitochondrial complex II electron transfer inhibitor.

111. A composition comprising a molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, further comprising a ryanodine receptor modulator active ingredient.

112. A composition comprising a molecule according to any of the preceding paragraphs 1-26 inclusive, further comprising an active ingredient of group UN.

113. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is from 100:1 to 1:100.

114. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is from 50:1 to 1:50.

115. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is from 20:1 to 1:20.

116. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is from 10:1 to 1:10.

117. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is from 5:1 to 1:5.

118. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is from 3:1 to 1:3.

119. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is from 2:1 to 1:2.

120. A composition comprising a molecule as defined in any of the preceding paragraphs 27 to 112, inclusive, wherein the ratio of the weight of the molecule of Formula 1 or Formula 2 to the weight of the active ingredient is 1:1.

121. A composition comprising a molecule according to any of the preceding paragraphs 27-112 inclusive, in which the ratio of the weight of the molecule of formula 1 or formula 2 to the weight of the active ingredient is X:Y; where X means the content in parts by weight. molecules of formula 1 or formula 2 and Y means the content in parts by weight. active ingredient; in addition, where is the numerical range of mass.frequency. for X is 0 < X ≤ 100 and wt.part. for Y is 0 < Y ≤ 100; and furthermore where X and Y are selected from Table C.

122. The composition according to paragraph 121, in which the range of mass ratios in parts by weight. molecules of formula 1 or formula 2 to the mass of the active ingredient is from X ₁ :Y ₁ to X ₂ :Y ₂ ; in addition, where X ₁ > Y ₁ and X ₂ < Y ₂ .

123. The composition according to paragraph 121, in which the range of mass ratios in parts by weight. molecules of formula 1 or formula 2 to the mass of the active ingredient is from X ₁ :Y ₁ to X ₂ :Y ₂ ; in addition, where X ₁ > Y ₁ and X ₂ > Y ₂ .

124. The composition according to paragraph 121, in which the range of mass ratios in parts by weight. molecules of formula 1 or formula 2 to the mass of the active ingredient is from X ₁ :Y ₁ to X ₂ :Y ₂ ; in addition, where X ₁ < Y ₁ and X ₂ < Y ₂ .

125. A method of preparing a composition, said method comprising mixing the molecule of any of the preceding paragraphs 1 to 26, inclusive, with one or more active ingredients.

126. Semanas treated with a molecule according to any of the preceding paragraphs 1-26 inclusive.

127. The molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule is in the form of an agriculturally acceptable acid addition salt.

128. A molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule is in the form of a salt derivative.

129. A molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule is in the form of a solvate.

130. A molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule is in the form of an ester derivative.

131. A molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule is in a crystalline polymorphic form.

132. A molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule contains deuterium, tritium, radiocarbon, or a combination thereof.

133. A molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule is in the form of one or more stereoisomers.

134. A molecule as defined in any of the preceding paragraphs 1 to 26, inclusive, wherein said molecule is in the form of a separated stereoisomer.

135. A method of pest control, said method comprising applying to the area a pesticidal effective amount of a molecule according to any of the preceding paragraphs 1-26 inclusive.

136. A method of pest control, said method includes applying to the area a pesticide effective amount of the composition according to any of the previous paragraphs 27-112 inclusive.

137. The method of paragraphs 135 and 136, wherein said pest is selected from the group consisting of the following: ants, aphids, bedbugs, beetles, bristletails, caterpillars, cockroaches, crickets, earwigs, fleas, flies, grasshoppers, grubs, leafhoppers, lice , locusts, larvae, mites, nematodes, cycads, psyllids, sawflies, homoptera, silverfish, slugs, snails, spiders, forktails, stink bugs, sessile hymenoptera, termites, thrips, jigs, wasps, whiteflies and wireworms.

138. The method of paragraphs 135 and 136, wherein said pest is selected from the subtypes Cheliceraceae, Myriapods or Hexapods.

139. The method of paragraphs 135 and 136, wherein said pest is selected from the class arachnids, symphila or insects.

140. The method of paragraphs 135 and 136, wherein said pest is selected from the order louse.

141. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Coleoptera.

142. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Leatheroptera.

143. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order cockroaches.

144. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Diptera.

145. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Hemiptera.

146. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Hymenoptera.

147. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order termites.

148. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Lepidoptera.

149. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order of lice beetles.

150. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Orthoptera.

151. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order of hay beetles.

152. The method of paragraphs 135 and 136, wherein said pest is selected from the order flea.

153. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Fringed Ptera.

154. The method of paragraphs 135 and 136, wherein said pest is selected from the order Bristletail.

155. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order mites.

156. The method according to paragraphs 135 and 136, in which the specified pest is selected from the order Spiders.

157. The method of paragraphs 135 and 136, wherein said pest is selected from the class Symphyla.

159. The method of paragraphs 135 and 136, wherein said pest is selected from the subclass of forktail.

160. The method of paragraphs 135 and 136, wherein said pest is selected from a type of nematode.

161. The method of paragraphs 135 and 136, wherein said pest is selected from a type of mollusc.

162. The method of paragraphs 135 and 136, wherein said pest is a sucking pest.

163. The method of paragraphs 135 and 136, wherein said pest is selected from the group consisting of aphids, leafhoppers, moths, homoptera, thrips, psyllids, felt flies, stink bugs and whiteflies.

164. The method according to paragraphs 135 and 136, in which the specified pest is selected from the orders Lice and Hemiptera.

165. The method of paragraphs 135 and 136, wherein said pest is selected from the group consisting of Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Coccus spp., Euschistus spp., Lygus spp., Macrosiphum spp., Nezara spp. and Rhopalosiphum spp.

166. The method of paragraphs 135 and 136, wherein said pest is a chewing pest.

167. The method of paragraphs 135 and 136, wherein said pest is selected from the group consisting of caterpillars, beetles, grasshoppers and locusts.

168. The method of paragraphs 135 and 136, wherein said pest is selected from the group consisting of Coleoptera and Lepidoptera.

169. The method of paragraphs 135 and 136, wherein said pest is selected from the group consisting of Anthonomus spp., Cerotoma spp., Chaetocnema spp., Colaspis spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Phyllophaga spp., Phyllotreta spp., Sphenophorus spp., Sitophilus spp.

170. The method of paragraphs 135 and 136, wherein said area is an area containing alfalfa, almonds, apples, barley, beans, canola, corn, cotton, brassicas, lettuce, oats, oranges, pears, peppers, potatoes, rice, sorghum, soybeans, strawberries, sugar cane, sugar beets, sunflowers, tobacco, tomatoes, wheat and other valuable agricultural crops grow or on which their seeds are sown.

171. The method of paragraphs 135 and 136, wherein said area is an area in which plants genetically modified to express special traits are sown.

172. The method according to paragraphs 135 and 136, in which said application is carried out on the leaves and/or fruiting parts of plants.

173. The method according to paragraphs 135 and 136, in which the specified application is carried out on the soil.

174. The method of paragraphs 135 and 136, wherein said application is carried out by drip irrigation, furrow application or watering of the soil before or after sowing.

175. The method according to paragraphs 135 and 136, in which said application is carried out on the leaves and/or fruiting parts of plants, or by treating the seeds of the plant before sowing.

176. A method comprising applying a molecule according to any of the preceding paragraphs 1-26, inclusive, to a site that includes a non-human animal to control endoparasites, ectoparasites, or both.

The headings in this document are for convenience only and should not be used to interpret any part of this document.

TABLES

TABLE B

Mass relations
Formula 1 molecule: active ingredient from 100:1 to 1:100 from 50:1 to 1:50 from 20:1 to 1:20 from 10:1 to 1:10 from 5:1 to 1:5 from 3:1 to 1:3 from 2:1 to 1:2 1:1

TABLE C

Active ingredient (Y) parts by weight 100 X,Y X,Y X,Y 50 X,Y X,Y X,Y X,Y X,Y 20 X,Y X,Y X,Y X,Y X,Y 15 X,Y X,Y X,Y X,Y X,Y 10 X,Y X,Y 5 X,Y X,Y X,Y X,Y 3 X,Y X,Y X,Y X,Y X,Y X,Y X,Y 2 X,Y X,Y X,Y X,Y X,Y 1 X,Y X,Y X,Y X,Y X,Y X,Y X,Y X,Y X,Y 1 2 3 5 10 15 20 50 100 Formula 1 molecule
(X) wt.part.

Table 2. Structure and method of obtaining molecules of group F

*obtained in accordance with Example No.

Table 3. Structure and method of obtaining molecules of the DP group

*obtained in accordance with Example No.

Table 4. Structure and method of obtaining molecules of groups C and CF

*obtained in accordance with Example No.

Table 5: Analytical data for molecules in Table 2

Connection No. m.p. (°C) IR (cm ^-1 ) Mass spectrum NMR ( ^1H , ^13C , ^19F ) F1004 ESIMS m/z 599 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.46 (s, 1H), 8.19 (td, J = 9.0, 6.0 Hz, 1H) , 8.05 (d, J = 2.6 Hz, 1H), 7.87 - 7.74 (m, 4H), 7.49 (d, J = 8.8 Hz, 1H), 7.15 ( ddd, J = 11.2, 8.7, 2.9 Hz, 1H), 7.08 (tt, J = 8.6, 2.0 Hz, 1H), 3.68 (d, J = 8, 4 Hz, 1H), 3.54 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.91, -115.67, -122.06, -122.18 F1005 ESIMS m/z 624.6 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.15 (s, 1H), 9.63 (s, 1H), 7.98 (dd, J = 2.6, 1.1 Hz, 1H) , 7.88 - 7.81 (m, 3H), 7.81 - 7.76 (m, 1H), 7.74 (dd, J = 2.1, 0.8 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H), 7.21 - 7.09 (m, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-120.03 F1006 ESIMS m/z 640.6 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.44 (s, 1H), 8.27 - 8.14 (m, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.7, 2.6 Hz, 1H), 7.69 (d, J = 0.7 Hz, 2H), 7.49 ( d, J = 8.8 Hz, 1H), 7.16 (ddd, J = 11.2, 8.8, 2.9 Hz, 1H), 7.08 (t, J = 8.9 Hz, 1H ), 3.65 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.78 (dd, J = 12.2, 5.1 Hz),
-122.25 (dd, J = 45.8, 5.1 Hz) F1007 ESIMS m/z 642.6 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.44 (s, 1H), 8.29 - 8.15 (m, 1H), 8.03 (d, J = 2.5 Hz, 1H), 7.85 (dd, J = 2.1, 0.7 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.75 (dd, J = 2.0, 0.8 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.16 (ddd, J = 11.2, 8, 8, 2.9 Hz, 1H), 7.08 (t, J = 8.9 Hz, 1H), 3.67 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.78 (dd, J = 12.3, 5.1 Hz),
-122.24 (dd, J = 45.9, 5.1 Hz) F1009 ESIMS m/z 586 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.32 (s, 1H), 9.47 (s, 1H), 8.20 (tt, J = 8.8, 5.8 Hz, 1H) , 8.03 (d, J = 2.5 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.50 (d, J = 8.7 Hz, 1H), 7.21 - 7.03 (m, 2H), 3.51 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.69, -122.09, -122.21,
-142.47, -142.52, -155.96,
-164.11, -164.16 F1010 ESIMS m/z 683 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.90 (s, 1H), 7.95 - 7.87 (m, 2H), 7.42 (d, J = 2.6 Hz, 1H), 7 .34 - 7.18 (m, 7H), 7.11 (d, J = 2.0 Hz, 2H), 6.41 - 6.30 (m, 2H), 4.21 (s, 2H), 3.44 (d, J = 8.2 Hz, 1H), 2.85 (d, J = 8.2 Hz, 1H), 2.18 (s, 3H);
¹³ C NMR (101 MHz, CDCl ₃ ) δ 166.24, 163.16, 146.84, 137.64, 137.09, 136.38, 135.12, 134.97, 133.96, 132.98 , 131.46, 130.80, 128.80, 128.60, 128.25, 127.45, 126.65, 125.30, 124.54, 123.72, 121.28, 114.60, 110 .75, 77.35, 77.24, 77.03, 76.71, 60.43, 47.50, 39.09, 38.09, 18.53 F1011 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.45 (s, 1H), 8.19 (td, J = 8.9, 5.9 Hz, 1H) , 8.02 (d, J = 2.5 Hz, 1H), 7.81 (dd, J = 8.7, 2.6 Hz, 1H), 7.65 - 7.58 (m, 1H), 7.59 - 7.45 (m, 2H), 7.21 - 7.03 (m, 2H), 3.69 - 3.62 (m, 1H), 3.41 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.68, -122.09, -122.22,
-133.27, -133.33, -135.71,
-135.77 F1012 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 9.43 (s, 1H), 8.17 (td, J = 8.9, 6.0 Hz, 1H) , 7.89 (d, J = 2.6 Hz, 1H), 7.71 (dd, J = 8.8, 2.6 Hz, 1H), 7.56 (dtd, J = 5.5, 2 ,0, 1.0 Hz, 1H), 7.53 - 7.39 (m, 2H), 7.19 - 7.01 (m, 2H), 3.55 (dd, J = 11.2, 1 .5 Hz, 1H), 3.26 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.71, -122.04, -134.36,
-134.42, -136.87, -136.93 F1022 ESIMS m/z 616 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.34 (s, 1H), 8.06 (d, J = 2.6 Hz, 1H), 7.84 (dd, J = 9.0, 2.6 Hz, 1H), 7.51 (s, 4H), 5.01 (d, J = 7.6 Hz, 2H), 3.67 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-144.47, -158.67, -159.65
-169.17, -169.22 F1023 ESIMS m/z 680 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.43 (s, 1H), 8.68 (q, J = 8.3, 7.5 Hz, 1H) , 8.10 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 8.7, 2.6 Hz, 1H), 7.49 ( s, 3H), 7.17 (t, J = 10.4 Hz, 1H), 3.66 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.50 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-128.34 F1024 ESIMS m/z 583 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.47 (s, 1H), 8.20 (tt, J = 9.0, 5.9 Hz, 1H) , 8.03 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.58 (s, 1H), 7.51 - 7.42 (m, 2H), 7.20 - 7.02 (m, 2H), 3.67 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz , 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-111.23, -115.58, -122.01,
-122.13 F1025 ESIMS m/z 583 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.12 (s, 1H), 9.43 (s, 1H), 8.18 (tt, J = 8.9, 5.8 Hz, 1H) , 7.89 (d, J = 2.6 Hz, 1H), 7.71 (dd, J = 8.8, 2.6 Hz, 1H), 7.53 (q, J = 1.5 Hz, 1H), 7.48 - 7.38 (m, 2H), 7.14 (ddd, J = 11.2, 8.7, 2.9 Hz, 1H), 7.06 (tt, J = 8, 9, 2.0 Hz, 1H), 3.58 (d, J = 11.3 Hz, 1H), 3.29 (d, J = 11.3 Hz, 1H).
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-112.52, -115.73, -122.08,
-122.20 F1026 ESIMS m/z 580 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.23 (s, 1H), 7.99 (d, J = 2.5 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.73 (ddd, J = 9.5, 7.9, 5.7 Hz, 1H), 7.52 - 7.43 (m , 4H), 6.97 (t, J = 10.7 Hz, 1H), 4.69 (d, J = 9.4 Hz, 2H), 3.66 (d, J = 8.3 Hz, 1H ), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-137.27, -139.71, -139.73 F1027 ESIMS m/z 580 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 9.65 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.58 - 7.52 (m, 3H), 6.45 - 6.34 (m, 2H), 5.46 (s, 2H), 3.63 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.67 (d, J = 7.5 Hz), -116.74 (d, J = 7.4 Hz) F1028 ESIMS m/z 580 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 9.65 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7 .55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 6.49 - 6.33 (m, 2H), 5, 46 (s, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.67 (d, J = 7.4 Hz), -116.75 (d, J = 7.4 Hz) F1029 ESIMS m/z 614 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 9.65 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.83 - 7.77 (m, 3H), 7.55 (d, J = 8.8 Hz, 1H), 6.52 - 6.24 (m, 2H), 5.46 (s, 2H), 3, 64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.66 (d, J = 7.3 Hz), -116.75 (d, J = 7.4 Hz) F1030 ESIMS m/z 564 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 9.65 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 2.0 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.51 - 7.42 (m, 2H), 6.46 - 6.34 (m, 2H), 5.46 (s, 2H), 3.59 (d, J = 8.5 Hz , 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.67 (d, J = 7.4 Hz), -116.74 (d, J = 7.4 Hz), -117.29 F1031 ESIMS m/z 701 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.46 (s, 1H), 8.20 (tt, J = 8.9, 5.9 Hz, 1H) , 8.11 - 7.97 (m, 4H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.20 - 7.02 (m, 2H), 3.81 (d, J = 8.3 Hz, 1H), 3.54 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.61, -122.05, -122.18 F1032 ESIMS m/z 701 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 9.42 (s, 1H), 8.18 (tt, J = 9.0, 5.9 Hz, 1H) , 8.02 - 7.90 (m, 3H), 7.85 (d, J = 2.6 Hz, 1H), 7.72 (dd, J = 8.8, 2.6 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.19 - 7.01 (m, 2H), 3.69 (dd, J = 11.2, 1.1 Hz, 1H), 3 .34 (d, J = 11.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.73, -115.76, -122.07,
-122.21 F1033 ESIMS m/z 567 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.43 (s, 1H), 8.18 (tt, J = 9.0, 6.0 Hz, 1H) , 7.90 (d, J = 2.5 Hz, 1H), 7.69 (dd, J = 8.8, 2.6 Hz, 1H), 7.61 - 7.45 (m, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.29 - 7.08 (m, 2H), 7.06 (tt, J = 8.6, 2.1 Hz, 1H), 3 .45 (dd, J = 11.0, 1.7 Hz, 1H), 3.28 (d, J = 11.0 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -112.61, -115.66, -115.79, -122.01, -122.02 F1034 ESIMS m/z 567 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.27 (s, 1H), 9.47 (s, 1H), 8.19 (td, J = 9.0, 5.9 Hz, 1H) , 8.03 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.53 - 7.39 (m, 2H), 7.25 (td, J = 8.7, 1.8 Hz, 1H), 7.15 (ddd, J = 11.2, 8.8, 2.9 Hz, 1H), 7.13 - 7, 03 (m, 1H), 3.59 (d, J = 8.2 Hz, 1H), 3.37 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-114.47, -115.16, -115.66,
-122.03, -122.17 F1035 ESIMS m/z 678 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 8.83 (s, 1H), 7.96 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.55 - 7.38 (m, 4H), 7.36 - 7.21 (m, 3H), 6.94 - 6.80 (m, 2H), 6.64 - 6.46 (m, 2H), 5.32 (s, 1H), 4.26 (s, 2H), 3.76 (s, 3H), 3.64 ( d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H), 2.25 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 165.04, 164.94, 162.42, 162.33, 158.78, 147.41, 137.81, 137.71, 137.40, 134 .70, 133.85, 133.80, 132.06, 130.20, 128.46, 127.98, 127.84, 127.82, 126.79, 126.73, 125.15, 124.94 , 121.43, 121.34, 119.82, 119.73, 114.18, 113.72, 110.27, 61.96, 54.61, 46.90, 39.19, 37.53, 17 .91 F1036 ESIMS m/z 580 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.17 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 (d, J = 6.2 Hz, 2H), 7.54 (d, J = 8.7 Hz, 1H), 7 .44 (t, J = 9.5 Hz, 1H), 7.24 (t, J = 54.2 Hz, 1H), 6.91 (ddd, J = 10.6, 9.0, 1.7 Hz, 1H), 6.80 (td, J = 8.4, 5.6 Hz, 1H), 5.30 (s, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.34 (dd, J = 7.3, 4.7 Hz),
-119.51 (t, J = 4.7 Hz), -133.96 (d, J = 14.0 Hz), -138.07 (d, J = 13.8 Hz) F1037 ESIMS m/z 596 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.17 (s, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7.77 - 7.71 (m, 2H), 7.70 - 7.61 (m, 2H), 7.54 (d, J = 8.8 Hz, 1H), 7.24 (t, J = 54.2 Hz, 1H), 6.91 (ddd, J = 10.6, 8.8, 1.7 Hz, 1H), 6.80 (td, J = 8.4, 5.6 Hz, 1H), 5 .30 (s, 2H), 3.67 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-114.86 (d, J = 5.3 Hz), -133.96 (d, J = 13.8 Hz), -138.07 (d, J = 13.8 Hz) F1038 ESIMS m/z 596 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.17 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.74 (dd, J = 8.7, 2.4 Hz, 2H), 7.65 (d, J = 14.3 Hz, 2H), 7.54 (d, J = 8.8 Hz, 1H), 7 .08 (t, J = 55.6 Hz, 1H), 6.94 - 6.86 (m, 1H), 6.80 (td, J = 8.5, 5.6 Hz, 1H), 5, 30 (s, 2H), 3.69 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-110.56 (d, J = 34.1 Hz), -133.96 (d, J = 13.8 Hz), -138.07 (d, J = 13.9 Hz) F1039 ESIMS m/z 570 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 7.86 - 7.79 (m, 1H), 7.69 - 7.57 (m, 2H), 7.43 (t, J = 1.9 Hz, 2H), 7.34 (d, J = 2.1 Hz, 2H), 7.00 - 6.86 (m, 2H), 3.56 (d, J = 8.3 Hz, 1H), 3.44 (s, 3H), 3.20 (d, J = 8.3 Hz, 1H), 2.15 (s, 1H);
¹⁹ F NMR (471 MHz, methanol-d ₄ ) δ -109.58 - -110.01 (m), -117.20 (d, J = 128.4 Hz) F1040 ESIMS m/z 673 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 8.83 (s, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.83 - 7.67 (m, 3H), 7.67 - 7.57 (m, 2H), 7.55 - 7.39 (m, 4H), 7.27 (d, J = 8.5 Hz, 1H ), 6.61 - 6.43 (m, 2H), 5.69 (t, J = 6.1 Hz, 1H), 4.49 (d, J = 4.6 Hz, 2H), 3.64 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H), 2.24 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.95, 162.42, 162.33, 146.78, 146.63, 137.82, 137.72, 137.40, 134.70, 133 .99, 132.33, 132.14, 130.20, 127.96, 127.83, 126.85, 125.63, 124.92, 121.41, 121.32, 119.79, 119.70 , 118.58, 114.22, 110.37, 110.22, 61.94, 46.92, 39.19, 39.15, 37.50, 17.86 F1041 ESIMS m/z 662 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 8.82 (s, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.7, 2.6 Hz, 1H), 7.26 (dd, J = 8.1, 5.7 Hz, 3H), 7.12 (d, J = 7.8 Hz, 2H), 6.63 - 6.41 (m, 2H), 5.43 (s, 1H), 4.29 (s, 2H), 3.63 (d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H), 2.27 (d, J = 12.9 Hz, 6H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 165.01, 164.92, 162.42, 162.33, 147.40, 137.82, 137.80, 137.71, 137.40, 137 ,23, 136.03, 134.70, 133.85, 133.79, 130.19, 128.93, 127.84, 127.82, 127.24, 126.78, 126.73, 125.16 , 125.06, 124.93, 121.42, 121.33, 119.81, 119.73, 114.16, 110.25, 61.96, 47.17, 39.19, 39.15, 37 .52, 20.21, 17.90 F1042 ESIMS m/z 716 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.27 (s, 1H), 8.15 - 7.91 (m, 4H), 7.81 (dd, J = 8.7, 2.6 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.38 (td, J = 8.6, 5.6 Hz, 1H), 6.89 (ddd, J = 10.8, 9.0, 2.0 Hz, 1H), 4.78 (s, 2H), 3.81 (d, J = 8.3 Hz, 1H), 3 .53 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-137.22, -144.24 F1043 ESIMS m/z 716 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.23 (s, 1H), 8.05 - 7.91 (m, 3H), 7.82 (d, J = 2.6 Hz, 1H), 7.73 (dd, J = 8.8, 2.6 Hz, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.35 ( td, J = 8.6, 5.6 Hz, 1H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz, 1H), 4.75 (d, J = 8, 4 Hz, 2H), 3.77 - 3.63 (m, 1H), 3.33 (d, J = 11.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-137.33, -144.22 F1044 ESIMS m/z 626 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.27 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 - 7.57 (m, 1H), 7.55 - 7.44 (m, 2H), 7.37 (td, J = 8.6, 5.6 Hz, 1H), 6.89 (ddd, J = 10.8, 9.1, 2.0 Hz, 1H), 4.77 (d, J = 8.4 Hz, 2H), 3.72 - 3.57 (m, 1H), 3.40 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-133.23, -133.28, -135.65,
-135.70, -137.17, -137.20,
-144.18, -144.21 F1045 ESIMS m/z 626 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.09 (s, 1H), 9.24 (s, 1H), 7.87 (d, J = 2.6 Hz, 1H), 7.71 (dd, J = 8.8, 2.6 Hz, 1H), 7.56 (dtd, J = 5.4, 2.0, 1.0 Hz, 1H), 7.51 - 7.29 (m , 3H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz, 1H), 4.77 (s, 2H), 3.60 - 3.48 (m, 1H), 3.26 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-134.35, -134.41, -136.85,
-136.91, -137.23, -137.26,
-144.15, -144.18 F1046 ESIMS m/z 598 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.28 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.79 (dd, J = 8.8, 2.6 Hz, 1H), 7.57 (s, 1H), 7.50 - 7.32 (m, 3H), 6.88 (ddd, J = 10.9 , 9.1, 2.0 Hz, 1H), 4.77 (s, 2H), 3.67 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz , 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-111.17, -137.06, -137.10,
-144.10 F1047 ESIMS m/z 598 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 9.23 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.72 (dd, J = 8.8, 2.6 Hz, 1H), 7.53 (dt, J = 2.6, 1.2 Hz, 1H), 7.50 - 7.38 (m, 2H), 7.35 (td, J = 8.6, 5.6 Hz, 1H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz, 1H), 4.77 (s, 2H), 3.57 (d, J = 11.3 Hz, 1H), 3.29 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-112.50, -137.27, -137.30,
-144.22 F1048 ESIMS m/z 582 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.12 (s, 1H), 9.26 (d, J = 13.0 Hz, 1H), 7.90 - 7.77 (m, 1H) , 7.69 (dd, J = 8.8, 2.6 Hz, 1H), 7.61 - 7.30 (m, 3H), 7.21 (dtd, J = 21.8, 8.8, 1.8 Hz, 1H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz, 1H), 4.76 (s, 2H), 3.45 (dp, J = 11 ,0, 1.1 Hz, 1H), 3.28 (d, J = 11.0 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-112.63, -115.79, -137.22,
-137.26, -144.17, -144.32 F1049 ESIMS m/z 582 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.27 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.51 - 7.39 (m, 2H), 7.37 (td, J = 8.6, 5.6 Hz, 1H), 7.25 (td, J = 8.7, 1.8 Hz, 1H), 6.89 (ddd, J = 10.8, 9.0, 2.0 Hz, 1H), 4.77 (d, J = 8.4 Hz, 2H), 3.63 - 3.53 (m, 1H), 3.36 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-114.46, -115.15, -137.24,
-144.22, -144.37 F1050 ESIMS m/z 617 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.27 (s, 1H), 9.47 (s, 1H), 8.19 (td, J = 8.9, 5.9 Hz, 1H) , 8.07 - 7.95 (m, 2H), 7.86 - 7.78 (m, 2H), 7.49 (d, J = 8.8 Hz, 1H), 7.15 (ddd, J = 11.2, 8.7, 2.8 Hz, 1H), 7.13 - 7.02 (m, 1H), 3.70 (d, J = 8.2 Hz, 1H), 3.56 ( d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.63, -111.91, -115.66, -122.03 F1051 ESIMS m/z 617 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.44 (s, 1H), 8.18 (tt, J = 8.9, 5.8 Hz, 1H) , 7.92 - 7.84 (m, 3H), 7.70 (dd, J = 8.8, 2.6 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.19 - 7.01 (m, 2H), 3.61 - 3.53 (m, 1H), 3.37 (d, J = 10.9 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.66, -109.41, -115.71,
-122.09, -122.22 F1053 ESIMS m/z 697 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.46 (s, 1H), 8.13 - 7.99 (m, 2H), 7.93 (s, 1H), 7.84 (dd, J = 7.7, 5.0 Hz, 3H), 7.53 - 7.43 (m, 2H), 7.11 (td, J = 9.4, 2, 0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.88, -117.60, -124.18,
-129.98, -130.09 F1054 225-228 (thin film) 3215 (w), 3051 (w), 1665 (s), 1653 (s), 1586 (s), 1564 (s), 1516 (s), 1481 (s), 1471 (s), 1403 (s), 1327 (s), 1314 (s) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₄ H ₁₇ BrCl ₅ N ₂ O ₂ , 622.8860; found, 622.8858 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (br s, 1H), 10.10 (br s, 1H), 7.92 (d, J = 2.5 Hz, 1H), 7 .73 (dd, J = 9, 2.5 Hz, 1H), 7.63 (t, J = 1.7 Hz, 1H), 7.58 - 7.53 (m, 3H), 7.51 ( br s, 1H), 7.45 - 7.37 (m, 2H), 3.63 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) , 2.29 (s, 3H) F1055 ESIMS m/z 612 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 8.04 - 7.44 (m, 5H), 7.44 - 7.19 (m, 4H), 6.07 - 5.79 (m, 1H ), 5.28 - 4.88 (m, 3H), 4.50 - 4.13 (m, 2H), 3.56 (m, 1H), 3.22 (m, 1H);
¹⁹ F NMR (471 MHz, methanol-d ₄ ) δ -110.76, -111.52 (d, J = 38.1 Hz), -112.39 (q, J = 7.1 Hz),
-112.68 (q, J = 7.1 Hz) F1056 ESIMS m/z 594 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 7.69 (s, 1H), 7.56 - 7.39 (m, 4H), 7.31 - 7.17 (m, 2H), 6, 95 - 6.59 (m, 1H), 6.55 (t, J = 7.5 Hz, 1H), 3.77 - 3.50 (m, 2H), 3.38 (s, 3H), 3 .25 - 3.11 (m, 2H);
^19F NMR (471 MHz, methanol- _d4 ) δ -132.10, -133.36 (ddd, J = 15.6, 10.4, 5.3 Hz), -139.44, -139.92 F1057 ESIMS m/z 513 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 9.96 (bs, 1H), 9.65 (bs, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7.84 (ddd, J = 10.4, 5.2, 2.8 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.49 - 7.42 (m , 4H), 7.19 - 7.11 (m, 2H), 3.72 (ddd, J = 12.1, 7.9, 3.1 Hz, 1H), 3.33 (dd, J = 13 ,1, 8.0 Hz, 1H);
¹³ C NMR (101 MHz, acetone- _d6 ) δ 164.49, 162.01, 159.14 (d, J = 241.2 Hz), 137.79, 137.23, 135.84, 135.31 (d, J = 2.7 Hz), 134.87, 130.30, 127.63, 127.16, 124.98, 121.76, 121.54 (d, J = 8.2 Hz), 119 .64, 115.26 (d, J = 22.5 Hz), 110.88 (dd, J = 294.3, 286.7 Hz), 33.68 (t, J = 9.9 Hz), 30 .61 (dd, J = 11.6, 8.8 Hz);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-119.95, -134.25 (d, J = 150.9 Hz), -135.00 (d, J = 150.9 Hz) F1058 ESIMS m/z 523 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 9.95 (s, 1H), 9.44 (s, 1H), 8.19 (tt, J = 8.9, 5.9 Hz, 1H) , 8.00 (d, J = 2.6 Hz, 1H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.48 - 7.45 (m, 2H), 7.44 (d, J = 1.8 Hz, 2H), 7.15 (ddd, J = 11.2, 8.8, 2.9 Hz, 1H), 7.07 (ddt, J = 11, 0, 8.8, 2.2 Hz, 1H), 3.73 (ddd, J = 12.2, 7.9, 3.1 Hz, 1H), 3.33 (dd, J = 13.9, 7.9 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.60 (d, J = 5.3 Hz), -115.63 (d, J = 5.1 Hz), -121.99 (d, J = 5.3 Hz), -122.11 ( d, J = 5.3 Hz),
-134.23 (d, J = 150.7 Hz), -135.00 (d, J = 150.8 Hz) F1059 (thin film) 3258, 3068, 1658, 1612, 1514 ESIMS m/z 600 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 9.93 (s, 1H), 9.91 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.5, 2.4 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 2.3 Hz, 1H), 7.42 (td, J = 8.8, 2.3 Hz, 2H), 7.28 (d, J = 8.5 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.25 (s, 3H) , 2.04 (s, 3H) F1060 (thin film) 3272, 1658, 1587, 1505, 1472 ESIMS m/z 704 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.81 (s, 1H), 10.06 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.70 (d, J = 8.3 Hz, 1H), 7.58 - 7.53 (m, 2H), 7, 49 (dd, J = 8.5, 2.4 Hz, 1H), 7.46 - 7.40 (m, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.30 (s, 3H) F1061 ESIMS m/z 653
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.24 (s, 1H), 10.95 (s, 1H), 10.07 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.79 - 7.73 (m, 2H), 7.70 (d, J = 8.4 Hz, 1H), 7.59 - 7.54 (m, 2H), 7, 51 (dd, J = 8.6, 2.4 Hz, 1H), 7.47 - 7.41 (m, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.30 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.85 F1062 ESIMS m/z 636 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.72 (s, 1H), 10.03 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.78 - 7.73 (m, 2H), 7.70 (d, J = 8.4 Hz, 1H), 7.59 - 7.53 (m, 2H), 7, 50 (dd, J = 8.6, 2.4 Hz, 1H), 7.44 (dd, J = 8.5, 2.1 Hz, 1H), 7.39 (d, J = 8.6 Hz , 1H), 6.38 (t, J = 53.7 Hz, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H ), 2.29 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-125.15 F1063 ESIMS m/z 724
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (d, J = 8.8 Hz, 2H), 10.52 (s, 1H), 7.94 (d, J = 2.5 Hz , 1H), 7.75 (dd, J = 6.3, 2.4 Hz, 3H), 7.69 (d, J = 8.3 Hz, 1H), 7.56 (d, J = 8, 8 Hz, 1H), 7.47 - 7.40 (m, 1H), 7.30 (s, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.40, -124.61, -133.96 (d, J = 14.0 Hz), -138.07 (d, J = 13.8 Hz) F1064 ESIMS m/z 674
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.56 (s, 1H), 10.96 (s, 1H), 10.55 (s, 1H), 7.94 (d, J = 2, 5 Hz, 1H), 7.81 - 7.72 (m, 3H), 7.69 (d, J = 8.3 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H) , 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.37 - 7.29 (m, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.83, -121.07, -124.40 F1065 ESIMS m/z 656
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.79 (s, 1H), 10.51 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.81 - 7.65 (m, 4H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.28 (td, J = 9.2, 1.8 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3.61 (d, J = 8 .4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.66 (d, J = 2.6 Hz), -124.22 (d, J = 2.7 Hz), -125.80 F1066 ESIMS m/z 596 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.46 (s, 1H), 8.20 (tt, J = 8.9, 5.9 Hz, 1H) , 8.03 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.70 (dd, J = 6.8, 2 .2 Hz, 1H), 7.61 (dd, J = 6.3, 2.2 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.20 - 7.02 (m, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 2.38 (d, J = 2.3 Hz , 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.86, -115.64, -121.64,
-122.05, -122.06 F1067 ESIMS m/z 596 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.07 (s, 1H), 9.41 (s, 1H), 8.18 (tt, J = 9.0, 5.9 Hz, 1H) , 7.87 (d, J = 2.6 Hz, 1H), 7.71 (dd, J = 8.8, 2.6 Hz, 1H), 7.62 (ddd, J = 13.3, 6 ,9, 2.2 Hz, 2H), 7.44 (d, J = 8.7 Hz, 1H), 7.14 (ddd, J = 11.2, 8.8, 2.9 Hz, 1H) , 7.06 (tt, J = 8.9, 1.7 Hz, 1H), 3.55 (d, J = 11.3 Hz, 1H), 3.26 (d, J = 11.3 Hz, 1H), 2.33 (d, J = 2.2 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.82, -115.75, -122.12,
-122.13, -122.76 F1068 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.26 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.7, 2.6 Hz, 1H), 7.71 (dd, J = 6.7, 2.2 Hz, 1H), 7.61 (dd, J = 6.4, 2 ,2 Hz, 1H), 7.58 - 7.44 (m, 1H), 7.38 (td, J = 8.6, 5.7 Hz, 1H), 6.89 (ddd, J = 10, 9, 9.0, 2.1 Hz, 1H), 4.77 (d, J = 8.6 Hz, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.42 ( d, J = 8.3 Hz, 1H), 2.38 (d, J = 2.3 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -121.69, -137.32,
-144.30, -144.45 F1069 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.06 (s, 1H), 9.22 (s, 1H), 7.84 (d, J = 2.6 Hz, 1H), 7.72 (dd, J = 8.7, 2.6 Hz, 1H), 7.66 - 7.56 (m, 2H), 7.46 - 7.30 (m, 2H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz, 1H), 4.76 (d, J = 8.2 Hz, 2H), 3.55 (d, J = 11.4 Hz, 1H), 3 .26 (d, J = 11.3 Hz, 1H), 2.33 (d, J = 2.3 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.81, -122.76, -137.34,
-144.27, -144.45 F1070 ESIMS m/z 645
([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 9.93 (s, 1H), 9.44 (s, 1H), 8.06 (td, J = 8.8, 4.4 Hz, 1H) , 7.99 (d, J = 2.6 Hz, 1H), 7.92 (s, 1H), 7.79 (dd, J = 8.8, 2.6 Hz, 1H), 7.50 - 7.46 (m, 2H), 7.45 (d, J = 1.9 Hz, 2H), 7.11 (td, J = 9.4, 2.0 Hz, 1H), 3.73 (ddd , J = 12.2, 7.9, 3.1 Hz, 1H), 3.33 (dd, J = 13.4, 8.5 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-124.19, -124.23, -129.97,
-130.09, -134.27 (d, J = 150.8 Hz), -135.04 (d, J = 150.7 Hz) F1071 ESIMS m/z 608 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 7.94 - 7.64 (m, 1H), 7.58 - 7.49 (m, 2H), 7.49 - 7.35 (m, 1H ), 7.32 - 7.18 (m, 2H), 6.76 - 6.52 (m, 2H), 3.61 - 3.47 (m, 1H), 3.38 (s, 3H), 3.25 - 3.12 (m, 2H), 2.94 (m, 4H);
¹⁹ F NMR (471 MHz, methanol-d ₄ ) δ -129.75 (d, J = 118.5 Hz), -130.59 (t, J = 14.1 Hz), -136.84, -138 .15 (d, J = 196.9 Hz) F1072 ESIMS m/z 610 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 7.91 (d, J=16.0 Hz, 1H), 7.83 - 7.59 (m, 2H), 7.54 (qd, J= 7.9, 7.4, 2.8 Hz, 2H), 7.46 - 7.21 (m, 5H), 5.09 (m, 1H), 4.58 - 4.31 (m, 1H) , 3.57 (m, 1H), 3.23 (m, 1H), 2.79 (m, 1H);
^19F NMR (471 MHz, methanol- _d4 ) δ -111.10 (d, J = 35.0 Hz), -112.31 (t, J = 7.1 Hz) F1073 ESIMS m/z 758 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.47 (s, 1H), 8.12 - 7.87 (m, 5H), 7.84 (s, 1H), 7.87 - 7.77 (m, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.09 (td, J = 9.3, 1.9 Hz, 1H ), 3.77 (d, J = 8.3 Hz, 1H), 3.51 (d, J = 8.3 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.18, -124.01, -129.87 F1074 ESIMS m/z 697 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.46 (s, 1H), 8.14 - 7.97 (m, 2H), 7.93 (s, 1H), 7.87 - 7.74 (m, 3H), 7.58 - 7.39 (m, 2H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 3 .72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -117.61, -124.13, -129.94 F1075 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.27 (s, 1H), 8.04 - 7.95 (m, 2H), 7.91 (s, 1H), 7.87 - 7.77 (m, 2H), 7.47 (d, J = 8.7 Hz, 1H), 7.38 (td, J = 8.6, 5.6 Hz, 1H ), 6.89 (ddd, J = 10.8, 9.0, 2.1 Hz, 1H), 4.77 (d, J = 8.5 Hz, 2H), 3.77 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.22, -137.23, -144.24, -144.39 F1077 ESIMS m/z 714 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.47 (s, 1H), 8.12 - 7.99 (m, 2H), 7.96 - 7, 88 (m, 2H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.79 - 7.69 (m, 2H), 7.48 (d, J = 8, 8 Hz, 1H), 7.10 (td, J = 9.4, 2.0 Hz, 1H), 3.73 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.96, -124.04, -129.87 F1078 ESIMS m/z 697 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.46 (s, 1H), 8.13 - 7.99 (m, 2H), 7.93 (s, 1H), 7.87 - 7.78 (m, 3H), 7.53 - 7.43 (m, 2H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 3 .72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.86, -117.61, -124.19, -129.96 F1079 ESIMS m/z 614 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.27 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.85 - 7.69 (m, 3H), 7.47 (d, J = 8.7 Hz, 1H), 7.37 (td, J = 8.6, 5.6 Hz, 1H), 6.89 (ddd, J = 10.9, 9.0, 2.0 Hz, 1H), 4.78 (s, 2H), 3.73 (d , J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.99, -137.24, -144.24 F1080 215-217 ESIMS m/z 546 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.11 (s, 1H), 8.29 (s, 1H), 7.94 (dd, J = 8.8, 2.6 Hz, 1H), 7 .65 (d, J = 2.6 Hz, 1H), 7.43 (td, J = 8.7, 5.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H) , 7.30 (t, J = 1.9 Hz, 1H), 7.10 (d, J = 1.8 Hz, 2H), 6.77 (td, J = 9.6, 2.0 Hz, 1H), 3.79 (s, 2H), 3.53 (ddd, J = 12.1, 7.9, 3.0 Hz, 1H), 2.76 (dd, J = 12.6, 7, 8 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-132.65 (d, J = 152.6 Hz), -133.45 (d, J = 152.5 Hz), -134.38 (d, J = 11.7 Hz), -145.24 ( d, J = 11.7 Hz) F1081 ESIMS m/z 574
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 11.00 (s, 1H), 7.87 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 8.7, 2.6 Hz, 1H), 7.78 - 7.68 (m, 2H), 7.58 (d, J = 8.7 Hz, 1H), 7.52 - 7.43 (m, 3H), 7.38 (d, J = 8.2 Hz, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8 .5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -122.49 F1082 ESIMS m/z 590 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.78 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.56 (dd, J = 9.9, 5.7 Hz, 2H), 7.51 - 7.42 (m, 2H), 3.59 (d, J = 8.4 Hz, 1H ), 3.45 (d, J = 8.5 Hz, 1H), 2.55 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-114.58, -117.28 F1083 ESIMS m/z 620
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.77 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.2, 2.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.65 - 7.57 ( m, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.23 - 7.13 (m , 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.46 (d, J = 3.9 Hz), -124.55 (d, J = 3.8 Hz) F1084 ESIMS m/z 642 ([MH] ^- ) ^1H NMR (500 MHz, methanol- _d4 ) δ 7.99 (m, 1H), 7.86 - 7.71 (m, 1H), 7.71 - 7.58 (m, 2H), 7, 56 - 7.41 (m, 2H), 7.26 (dd, J = 8.8, 3.2 Hz, 3H), 5.99 - 5.80 (m, 1H), 5.64 - 5, 38 (m, 1H), 5.35 - 5.00 (m, 1H), 3.57 (m, 1H), 3.23 (m, 1H), 2.11 - 2.01 (m, 3H) ;
¹⁹ F NMR (471 MHz, methanol- _d4 ) δ -111.20 (d, J = 24.2 Hz), -111.38, -112.29 (q, J = 7.2 Hz), -112 .45 - -112.55 (m) F1085 ESIMS m/z 592 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.07 (s, 1H), 11.01 (s, 1H), 8.36 - 8.27 (m, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.76 (dd, J = 11.4, 7.4 Hz, 1H), 7.71 (d, J = 6.5 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.46 (dd, J = 7.9, 4.3 Hz, 2H ), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -127.77, -138.33 F1086 101-105 ESIMS m/z 549 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.73 (s, 1H), 10.63 (s, 1H), 8.03 (td, J = 8.9, 5.9 Hz, 1H) , 7.84 (td, J = 8.9, 6.1 Hz, 1H), 7.68 (dd, J = 7.0, 2.1 Hz, 1H), 7.57 - 7.35 (m , 3H), 7.26 (t, J = 8.8 Hz, 1H), 7.20 - 7.10 (m, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3 .59 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.97, -112.98, -117.28,
-117.88, -117.90, -118.24,
-123.42 F1087 206-208 (thin film) 3195 (w), 3029 (w), 1682 (w), 1651 (m), 1635 (m), 1612 (m), 1522 (s), 1507 (s), 1485 (m), 1472 (m) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H ₁₅ Cl ₃ F ₂ IN ₂ O ₂ , 622.9180; found, 622.9186 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (br s, 1H), 10.39 (br s, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7 .69-7.80 (m, 4H), 7.55 (d, J = 8.6 Hz, 1H), 7.37 (m, 1H), 7.18-7.24 (m, 2H), 7.13 (m, 1H), 3.51 (d, J = 8.5 Hz, 1H), 3.35 (d, J = 8.5 Hz, 1H) F1088 (thin film) 3268 (w), 3062 (w), 1660 (m), 1610 (m), 1588 (m), 1526 (s), 1472 (s) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H ₁₅ Cl ₃ F ₂ IN ₂ O ₂ , 622.9180; found, 622.9184 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (br s, 1H), 10.39 (br s, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7 .80 (br s, 1H), 7.70-7.78 (m, 3H), 7.55 (d, J = 8.7 Hz, 1H), 7.43 (br d, J = 7.8 Hz, 1H), 7.37 (m, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.13 (m, 1H), 3.54 (d, J = 8.5 Hz, 1H), 3.40 (d, J = 8.5 Hz, 1H) F1089 (thin film) 3277 (w), 1661 (m), 1611 (m), 1588 (m), 1525 (m), 1473 (m), 1432 (m), 1403 (m) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H ₁₅ Cl ₃ F ₇ N ₂ O ₂ S, 622.9776; found, 622.9777 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.02 (br s, 1H), 10.40 (br s, 1H), 7.94-8.00 (m, 2H), 7.91 ( d, J = 2.5 Hz, 1H), 7.70-7.79 (m, 2H), 7.63-7.69 (m, 2H), 7.56 (d, J = 8.9 Hz , 1H), 7.37 (m, 1H), 7.13 (m, 1H), 3.69 (d, J = 8.5 Hz, 1H), 3.48 (d, J = 8.5 Hz , 1H) F1090 (thin film) 3277 (w), 1663 (m), 1610 (m), 1589 (m), 1529 (m), 1473 (m), 1432 (m), 1405 (m) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H ₁₅ Cl ₃ F ₇ N ₂ O ₂ S, 622.9776; found, 622.9784 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (br s, 1H), 10.40 (br s, 1H), 7.99 (br s, 1H), 7.89-7.94 (m, 2H), 7.64-7.79 (m, 4H), 7.55 (d, J = 8.6 Hz, 1H), 7.37 (m, 1H), 7.13 (m, 1H), 3.74 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F1091 ESIMS m/z 600 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 7.97 - 7.69 (m, 2H), 7.67 - 7.40 (m, 4H), 7.39 - 7.20 (m, 3H ), 4.27 (tq, J = 14.2, 7.2 Hz, 1H), 3.83 - 3.61 (m, 1H), 3.56 (m, 1H), 3.22 (m, 1H), 2.16 (d, J = 12.4 Hz, 1H), 1.28 (t, J = 7.2 Hz, 2H), 1.10 (t, J = 7.2 Hz, 1H) ;
^19F NMR (471 MHz, methanol- _d4 ) δ -111.69 (d, J = 37.4 Hz), -112.69 (q, J = 7.0 Hz) F1092 ESIMS m/z 697 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.46 (s, 1H), 8.13 - 8.00 (m, 2H), 7.93 (s, 1H), 7.83 (dd, J = 8.9, 2.6 Hz, 1H), 7.70 (s, 1H), 7.62 (dd, J = 9.4, 2.3 Hz, 1H ), 7.59 - 7.46 (m, 2H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 3.78 (d, J = 8.3 Hz, 1H) , 3.50 (d, J = 8.3 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.21, -111.85, -124.22, -130.01 F1093 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.45 (d, J = 11.4 Hz, 1H), 8.19 (td, J = 8.9, 5.9 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.57 (ddd, J = 8.0, 5.2, 3.0 Hz, 1H), 7.53 - 7.34 (m, 1H), 7.35 - 7.25 (m, 1H), 7.21 - 7, 12 (m, 1H), 7.09 (ddt, J = 17.4, 8.4, 2.5 Hz, 2H), 3.67 - 3.60 (m, 1H), 3.40 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.63, -115.65, -115.83,
-115.87, -117.44, -117.48,
-122.04, -122.05 F1094 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.44 (s, 1H), 8.18 (td, J = 9.0, 5.9 Hz, 1H) , 7.89 (d, J = 2.6 Hz, 1H), 7.70 (dd, J = 8.8, 2.6 Hz, 1H), 7.53 - 7.34 (m, 3H), 7.19 - 7.01 (m, 2H), 3.51 (d, J = 11.0 Hz, 1H), 3.31 (d, J = 11.0 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-113.36, -113.40, -115.73,
-115.74, -118.58, -118.62,
-122.06, -122.07 F1095 ESIMS m/z 726 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.47 (s, 1H), 8.12 - 7.99 (m, 2H), 7.90 (d, J = 19.1 Hz, 1H), 7.83 (dd, J = 8.7, 2.6 Hz, 1H), 7.57 (ddd, J = 8.0, 5.2, 3.0 Hz , 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.35 - 7.25 (m, 1H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 3.67 - 3.59 (m, 1H), 3.40 (d, J = 8.3 Hz, 1H), 1.47 (d, J = 1.9 Hz, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.81, -115.85, -117.41,
-117.45, -124.09, -129.93,
-130.04 F1096 ESIMS m/z 717 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.26 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.82 (dq, J = 11.3, 2.7 Hz, 3H), 7.47 (t, J = 9.0 Hz, 3H), 7.29 (d, J = 8.5 Hz, 2H), 6 .93 - 6.80 (m, 3H), 5.07 - 5.00 (m, 1H), 4.45 (d, J = 7.1 Hz, 2H), 3.74 (s, 3H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -117.53, -117.57,
-132.66, -140.47, -140.67 F1097 ESIMS m/z 626 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.24 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.71 (dd, J = 8.7, 2.7 Hz, 1H), 7.54 - 7.31 (m, 4H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz , 1H), 4.76 (s, 2H), 3.51 (d, J = 11.1 Hz, 1H), 3.35 - 3.28 (m, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-113.42, -118.62, -137.34,
-137.38, -144.27 F1098 ESIMS m/z 626 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.26 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.58 (ddd, J = 8.0, 5.2, 3.1 Hz, 1H), 7.49 (d, J = 8 .7 Hz, 1H), 7.45 - 7.26 (m, 2H), 6.89 (ddd, J = 10.8, 9.0, 2.1 Hz, 1H), 4.77 (d, J = 8.4 Hz, 2H), 3.63 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.86, -115.90, -117.49,
-117.53, -137.30, -137.33,
-144.27, -144.31, -144.46 F1099 ESIMS m/z 662 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 8.11 - 7.73 (m, 1H), 7.58 - 7.36 (m, 3H), 7.36 - 7.25 (m, 6H ), 7.25 - 7.17 (m, 1H), 7.17 - 7.03 (m, 2H), 5.69 (m, 1H), 4.91 - 4.60 (m, 3H), 3.56 (m, 1H), 3.29 - 3.13 (m, 1H);
¹⁹ F NMR (471 MHz, methanol-d ₄ ) δ -111.42, -112.68 - -113.02 (m) F1100 159-162 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₃ F ₄ N ₂ O ₂ , 529.9979; found, 529.9979 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.63 (s, 1H), 8.02 (td, J = 8.9, 5.9 Hz, 1H) , 7.80 - 7.63 (m, 3H), 7.57 - 7.39 (m, 2H), 7.34 - 7.17 (m, 3H), 3.62 (d, J = 8, 6 Hz, 1H), 3.58 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -117.91, -118.34,
-118.35, -123.65, -123.65 F1101 142-146 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₅ H ₁₇ Cl ₃ F ₃ N ₃ O ₃ , 569.0288; found, 569.0292 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.78 (s, 1H), 10.62 (s, 1H), 9.95 (s, 1H), 8.01 (td, J = 8, 9, 5.9 Hz, 1H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.61 (d, J = 9.1 Hz, 2H), 7.57 ( d, J = 9.1 Hz, 2H), 7.47 - 7.40 (m, 2H), 7.30 - 7.22 (m, 1H), 3.62 (d, J = 8.6 Hz , 1H), 3.58 (d, J = 8.6 Hz, 1H), 2.04 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -118.36, -118.37,
-123.72, -123.73 F1102 142-147 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₅ H ₁₇ Cl ₅ FN ₃ O ₃ , 600.9697; found, 600.9696 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.71 (s, 1H), 10.42 (s, 1H), 9.94 (s, 1H), 7.90 (d, J = 8, 8 Hz, 1H), 7.68 (dd, J = 7.2, 2.2 Hz, 1H), 7.64 - 7.54 (m, 5H), 7.53 - 7.41 (m, 2H ), 3.74 (d, J = 8.5 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H), 2.03 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27 F1103 126-129 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₅ F ₂ N ₂ O ₂ , 561.9388; found, 561.9387 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.86 (s, 1H), 10.44 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.76 - 7.65 (m, 3H), 7.61 (d, J = 8.8 Hz, 1H), 7.53 - 7.41 (m, 2H), 7.22 (t, J = 8.9 Hz, 2H), 3.74 (d, J = 8.5 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.26, -118.12 F1104 155-161 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₄ Cl ₅ FN ₂ O ₂ , 543.9482; found, 543.9483 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.79 (s, 1H), 10.43 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.69 (td, J = 8.3, 1.7 Hz, 3H), 7.60 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.38 ( dd, J = 8.5, 7.4 Hz, 2H), 7.18 - 7.11 (m, 1H), 3.74 (d, J = 8.5 Hz, 1H), 3.60 (d , J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.26 F1105 112-116 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₂ Cl ₅ F ₃ N ₂ O ₂ , 579.9294; found, 579.9294 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.71 (s, 1H), 10.43 (s, 1H), 7.96 - 7.83 (m, 2H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.54 - 7.34 (m, 3H), 7.16 (tdd, J = 8.5, 2.9, 1.4 Hz, 1H), 3.74 (d, J = 8.5 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.26, -113.27, -117.26,
-118.00, -118.01 F1106 150-157 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₇ Cl ₅ FN ₃ O ₂ , 572.9747; found, 572.9747 ¹ H NMR (400 MHz, DMSO-d ₆ ) ~4:1 mixture of rotary isomers d 10.77 (s, 0.2H), 10.65 (s, 0.8H), 7.76 - 7.69 ( m, 0.61H), 7.66 (dd, J = 7.0, 2.1 Hz, 0.83H), 7.54 - 7.50 (m, 1.55H), 7.49 - 7, 38 (m, 2.06H), 7.32 - 7.26 (m, 1.58H), 7.23 (d, J = 8.8 Hz, 0.16H), 6.94 (d, J = 8.8 Hz, 0.73H), 6.85 (d, J = 8.8 Hz, 0.18H), 6.60 (d, J = 8.7 Hz, 0.77H), 5.80 ( s, 0.35H), 5.54 (s, 1.54H), 3.59 (d, J = 8.5 Hz, 0.2H), 3.53 (d, J = 8.4 Hz, 0 ,84H), 3.44 (d, J = 8.5 Hz, 0.17H), 3.41 - 3.35 (m, 0.93H), 3.34 (m, J = 4.5 Hz, 3.2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.34, -117.36 F1107 138-143 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₃ H ₂₉ Cl ₅ F ₃ N ₃ O ₆ , 795.0451; found, 795.0445 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.82 (s, 1H), 10.44 (s, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.86 (td, J = 8.8, 5.7 Hz, 1H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.53 - 7.41 (m, 2H), 7.30 (td, J = 9.3, 1.7 Hz, 1H), 3.74 (d, J = 8.5 Hz, 1H ), 3.60 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -123.43, -127.12 F1108 175-180 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₄ Cl ₃ F ₃ N ₂ O ₂ , 512.0073; found, 512.0075 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.86 (s, 1H), 10.63 (s, 1H), 8.02 (td, J = 9.0, 6.0 Hz, 1H) , 7.74 - 7.65 (m, 3H), 7.55 - 7.35 (m, 4H), 7.27 (td, J = 8.9, 1.5 Hz, 1H), 7.20 - 7.12 (m, 1H), 3.63 (d, J = 8.6 Hz, 1H), 3.59 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -118.42, -118.42,
-123.75, -123.76 F1109 103-112 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₃ H ₂₉ Cl ₃ F ₅ N ₃ O ₆ , 763.1042; found, 763,1035 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 10.63 (s, 1H), 8.03 (td, J = 9.0, 5.9 Hz, 1H) , 7.83 (td, J = 8.8, 5.7 Hz, 1H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.55 - 7.39 (m , 2H), 7.35 - 7.22 (m, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H), 1 .40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -118.21, -123.24,
-123.39, -127.10 F1110 120-125 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₅ F ₃ N ₃ O ₂ , 594.9402; found, 594.9400 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.47 (s, 1H), 10.41 (s, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.53 - 7.41 (m, 2H), 6.96 - 6.88 (m, 2H), 5.32 (s, 2H), 3.74 (d, J = 8.5 Hz, 1H), 3.59 (d, J = 15.9 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -134.03, -134.06,
-138.68, -138.72 F1111 81-90 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₃ F ₅ N ₃ O ₂ , 562.9994; found, 562.9990 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.61 (s, 1H), 10.50 (s, 1H), 8.01 (td, J = 8.9, 5.9 Hz, 1H) , 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.57 - 7.39 (m, 2H), 7.24 (td, J = 8.8, 1.5 Hz , 1H), 7.04 - 6.80 (m, 2H), 5.34 (s, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.59 (d, J = 8.8 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -118.34, -118.35,
-123.59, -123.60, -133.76,
-133.80, -138.80, -138.83 F1112 ESIMS m/z 612 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 7.95 - 7.59 (m, 4H), 7.56 - 7.31 (m, 2H), 7.23 (d, J = 8.8 Hz, 1H), 6.99 - 6.60 (m, 2H), 6.54 (d, J = 7.7 Hz, 1H), 3.68 - 3.56 (m, 1H), 3.39 (s, 3H), 3.28 - 3.16 (m, 2H);
¹⁹ F NMR (471 MHz, methanol- _d4 ) δ -62.87 (d, J = 12.5 Hz), -117.85 (pq, J = 12.6, 5.7 Hz), -132, 21,
-133.45 (ddd, J = 15.5, 10.3, 5.5 Hz), -139.42, -139.99 F1113 ESIMS m/z 638 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 8.00 - 7.63 (m, 3H), 7.48 (m, 1H), 7.41 - 7.32 (m, 1H), 7, 23 (d, J = 8.8 Hz, 1H), 6.94 - 6.60 (m, 1H), 6.55 (s, 1H), 6.04 - 5.72 (m, 1H), 5 .27 - 5.15 (m, 2H), 4.71 - 4.54 (m, 1H), 4.31 - 4.05 (m, 1H), 3.68 - 3.55 (m, 1H) , 3.23 (m, 1H);
^19F NMR (471 MHz, methanol- _d4 ) δ -62.87 (d, J = 12.8 Hz), -117.84 (ddt, J = 22.0, 16.1, 7.7 Hz) ,
-131.98, -133.29 (ddd, J = 15.6, 10.3, 5.6 Hz), -137.67, -138.47 F1114 ESIMS m/z 636 ([M+H] ⁺ ) ^1H NMR (500 MHz, methanol- _d4 ) δ 8.02 - 7.62 (m, 3H), 7.49 (m, 1H), 7.41 - 7.32 (m, 1H), 7, 24 (d, J = 8.8 Hz, 1H), 6.99 - 6.60 (m, 2H), 4.90 (s, 1H), 4.60 - 4.25 (m, 1H), 3 .70 - 3.55 (m, 1H), 3.29 - 3.14 (m, 1H), 2.74 - 2.60 (m, 1H), 2.15 (s, 3H);
^19F NMR (471 MHz, methanol- _d4 ) δ -62.88 (d, J = 12.5 Hz), -117.85 (ddp, J = 19.1, 12.9, 7.0, 6 ,0 Hz), -131.59, -132.87 (ddd, J = 15.8, 10.4, 5.6 Hz), -137.76, -138.48 F1115 ESIMS m/z 758 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.46 (s, 1H), 8.16 - 7.99 (m, 2H), 7.92 (d, J = 8.1 Hz, 3H), 7.83 (dd, J = 8.8, 2.6 Hz, 1H), 7.67 (dd, J = 8.2, 2.2 Hz, 1H), 7.49 (d, J = 8.7 Hz, 1H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H ), 3.45 (d, J = 8.4 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.00, -124.20, -129.99 F1116 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.27 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.94 - 7.87 (m, 2H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 (dd, J = 8.3, 2.1 Hz, 1H), 7.47 (d, J = 8.7 Hz, 1H), 7.37 (td, J = 8.6, 5.5 Hz, 1H), 6.91-6.87 (dd, J = 19, 6, 2.1 Hz, 1H), 4.77 (d, J = 8.5 Hz, 2H), 3.72 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.97, -137.14, -144.17 F1117 ESIMS m/z 732 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 8.82 (s, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.77 (dt, J = 8.7, 1.9 Hz, 1H), 7.57 - 7.40 (m, 6H), 7.28 (dd, J = 8.5, 1.7 Hz, 3H), 6.57 (d, J = 2.6 Hz, 1H), 6.51 (dd, J = 8.5, 2.7 Hz, 1H), 5.57 (t, J = 6.2 Hz, 1H ), 4.41 (d, J = 4.9 Hz, 2H), 3.64 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H), 2.25(s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-58.56. F1118 ESIMS m/z 599 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.46 (s, 1H), 8.19 (td, J = 9.0, 6.0 Hz, 1H) , 8.03 (d, J = 2.6 Hz, 1H), 7.87 - 7.74 (m, 4H), 7.49 (d, J = 8.7 Hz, 1H), 7.20 - 7.02 (m, 2H), 3.77 (d, J = 8.3 Hz, 1H), 3.52 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.25, -115.64, -122.08 F1119 ESIMS m/z 714 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.47 (s, 1H), 8.12 - 7.99 (m, 2H), 7.93 (s, 1H), 7.86 - 7.74 (m, 4H), 7.48 (d, J = 8.8 Hz, 1H), 7.10 (td, J = 9.3, 1.9 Hz, 1H ), 3.77 (d, J = 8.3 Hz, 1H), 3.52 (d, J = 8.3 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.22, -124.05, -129.90 F1120 125-148 ESIMS m/z 676.1 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.39 (s, 1H), 11.03 (d, J = 30.8 Hz, 2H), 7.92 (d, J = 2.5 Hz , 1H), 7.84 - 7.52 (m, 6H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.81, -117.36 F1121 118-130 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.73 (s, 1H), 10.37 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.80 - 7.53 (m, 5H), 7.44 (dt, J = 8.4, 2.9 Hz, 2H), 7.28 (t, J = 8.8 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-74.01, -115.31 F1122 138-150 ESIMS m/z 674.9 ([M+H ₂ O] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.00 (d, J = 13.2 Hz, 2H), 10.62 (s, 1H), 7.92 (d, J = 2.6 Hz , 1H), 7.77 (dd, J = 9.0, 2.5 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.57 (dd, J = 16, 3, 9.3 Hz, 3H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 6.65 (s, 0H), 6.52 (s, 0H), 6, 39 (s, 0H), 3.60 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.01, -125.75 F1123 152-178 ESIMS m/z 640 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.29 (s, 1H), 10.07 (s, 1H), 7.96 (d, J = 2, 6 Hz, 1H), 7.81 - 7.47 (m, 6H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.21 (td, J = 8.5 , 2.9 Hz, 1H), 6.57 (s, 0H), 6.43 (s, 1H), 6.30 (s, 0H), 3.61 (d, J = 8.5 Hz, 1H ), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-115.21, -126.15 F1124 235-238 ESIMS m/z 622 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (d, J = 20.1 Hz, 2H), 9.61 (s, 1H), 7.90 (d, J = 2.6 Hz , 1H), 7.77 (dd, J = 8.7, 2.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8, 8 Hz, 1H), 7.54 - 7.38 (m, 3H), 3.60 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H) , 2.05 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.03 F1125 137-159 ESIMS m/z 604 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 9.91 (s, 1H), 9.40 (s, 1H), 8.00 (d, J = 2, 6 Hz, 1H), 7.84 - 7.37 (m, 6H), 7.07 (td, J = 8.4, 3.0 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-115.50 F1126 127-144 ESIMS m/z 730 ([M+Na] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.70 (s, 1H), 10.23 (s, 1H), 8.01 (d, J = 2, 5 Hz, 1H), 7.80 - 7.65 (m, 3H), 7.59 (d, J = 8.7 Hz, 1H), 7.55 - 7.39 (m, 3H), 7, 27 (td, J = 8.5, 2.9 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-114.56 F1127 ESIMS m/z 614 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.27 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.87 - 7.74 (m, 4H), 7.47 (d, J = 8.7 Hz, 1H), 7.38 (td, J = 8.6, 5.6 Hz, 1H), 6.89 ( ddd, J = 10.9, 9.1, 2.0 Hz, 1H), 4.77 (d, J = 8.4 Hz, 2H), 3.77 (d, J = 8.3 Hz, 1H ), 3.52 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.24, -137.23, -144.24 F1128 ESIMS m/z 614 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.15 (s, 1H), 8.68 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.74 (dd, J = 8.7, 2.6 Hz, 1H), 7.52 - 7.38 (m, 5H), 7.07 (d, J = 8.2 Hz, 1H), 3.64 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H),
2.22 - 2.08 (m, 9H) F1129 ESIMS m/z 744 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.10 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.84 - 7.69 (m, 2H), 7.55 - 7.37 (m, 4H), 7.26 - 7.09 (m, 2H), 4.20 (t, J = 5.6 Hz, 2H ), 3.88 (t, J = 5.6 Hz, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 2.37 (s, 3H), 1.96 (s, 3H), 1.44 (s, 9H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 170.03, 164.76, 162.45, 162.37, 154.19, 140.15, 137.86, 137.76, 137.38, 137 .36, 134.72, 133.92, 133.82, 132.20, 132.09, 130.28, 129.07, 127.87, 127.84, 126.35, 124.98, 124.92 , 124.84, 124.73, 121.69, 121.60, 119.88, 79.72, 61.95, 61.65, 48.81, 39.20, 39.17, 37.52, 27 .64, 19.98, 17.54 F1130 ESIMS m/z 602 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 8.84 (s, 1H), 7.98 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.52 - 7.41 (m, 4H), 7.28 (d, J = 8.4 Hz, 1H), 6.58 - 6.47 (m, 2H), 4.82 (s, 1H), 3.85 (s, 1H), 3.73 (q, J = 5.6, 5.0 Hz, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 3.22 (t, J = 5.7 Hz, 2H), 2.28 (s , 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 165.00, 162.43, 162.34, 147.59, 137.87, 137.81, 137.72, 137.41, 134.70, 133 .92, 130.19, 127.83, 126.84, 126.78, 125.15, 124.93, 121.39, 119.80, 114.03, 110.16, 61.95, 60.37 , 59.66, 46.10, 39.19, 37.51, 17.85 F1133 ESIMS m/z 546 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 9.99 (s, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.40 (m, 2H), 7.21 (d, J = 8.0 Hz, 1H), 6.97 (ddd, J = 11.0, 8.2, 1, 4 Hz, 1H), 6.62 (td, J = 8.1, 5.9 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -132.67 F1134 ESIMS m/z 564 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 9.84 (s, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7.84 - 7.65 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.51 - 7.39 (m, 3H), 6.74 (dd, J = 12.9 , 8.0 Hz, 1H), 5.12 (s, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -141.37 (d, J = 24.4 Hz), -153.51 (d, J = 24.4 Hz) F1135 ESIMS m/z 560 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.08 (s, 1H), 7.87 (d, J = 2.6 Hz, 1H), 7.73 (ddd, J = 12.1, 7.8, 2.2 Hz, 2H), 7.60 - 7.40 (m, 3H), 7.09 (d, J = 7.1 Hz, 1H), 6.90 (d, J = 11.1 Hz, 1H), 5.39 (s, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8 .5 Hz, 1H), 2.07 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28 F1136 138-143 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₃ F ₃ N ₂ O ₂ , 526.0029; found, 526.0233 F1137 90-96 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₅ Cl ₃ F ₄ N ₂ O ₂ , 544.0135; found, 544.0136 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.79 (s, 1H), 10.15 (s, 1H), 7.88 - 7.66 (m, 4H), 7.53 - 7, 43 (m, 2H), 7.37 (ddd, J = 11.1, 9.1, 2.8 Hz, 1H), 7.17 - 7.09 (m, 1H), 3.57 (d, J = 8.5 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 2.31 (d, J = 1.9 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.33, -113.35, -117.30,
-117.32, -123.52 F1138 151-154 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₄ H ₃₂ Cl ₃ F ₄ N ₃ O ₆ , 759.1293; found, 759,1282 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.79 (s, 1H), 10.30 (s, 1H), 7.80 (dd, J = 5.8, 2.7 Hz, 1H) , 7.72 (ddd, J = 12.9, 6.7, 2.4 Hz, 3H), 7.53 - 7.41 (m, 2H), 7.35 - 7.20 (m, 1H) , 3.57 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 2.35 - 2.28 (m, 3H), 1.40 ( s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.30, -123.52, -123.67,
-126.46 F1139 152-157 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₆ H ₂₀ Cl ₃ F ₂ N ₃ O ₃ , 565.0538; found, 565.0538 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.77 (s, 1H), 10.35 (s, 1H), 9.92 (s, 1H), 7.74 - 7.68 (m, 3H), 7.63 (d, J = 9.1 Hz, 2H), 7.58 - 7.52 (m, 2H), 7.51 - 7.41 (m, 2H), 3.57 (d , J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 2.35 - 2.27 (m, 3H), 2.03 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.31, -124.42 F1140 170-173 (thin film) 3266 (w), 1642 (m), 1588 (m), 1538 (m), 1505 (s), 1466 (s) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H ₁₆ Cl ₃ F ₂ IN ₃ O ₂ , 637.9289; found, 637.9290 ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.96 (br s, 1H), 10.16 (br s, 1H), 7.88 (d, J = 2.5 Hz, 1H), 7 .76-7.80 (m, 2H), 7.74 (dd, J = 8.5, 2.5 Hz, 1H), 7.53 (d, J = 8.5 Hz, 1H), 7. 19-7.23 (m, 2H), 6.90 (m, 1H), 6.79 (m, 1H), 5.30 (br s, 2H), 3.51 (d, J = 8.5 Hz, 1H), 3.35 (d, J = 8.5 Hz, 1H) F1141 (thin film) 3267 (w), 3060 (w), 1643 (m), 1588 (m), 1540 (s), 1504 (s), 1468 (s) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H1 ₆ Cl ₃ F ₂ IN ₃ O ₂ , 637.9289; found, 637.9291 ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.92 (br s, 1H), 10.16 (br s, 1H), 7.89 (d, J = 2.5 Hz, 1H), 7 .80 (br s, 1H), 7.71-7.75 (m, 2H), 7.54 (d, J = 8.5 Hz, 1H), 7.44 (br d, J = 7.9 Hz, 1H), 7.22 (t, J = 7.9 Hz, 1H), 6.90 (m, 1H), 6.80 (m, 1H), 5.30 (br s, 2H), 3 .54 (d, J = 8.5 Hz, 1H), 3.40 (d, J = 8.5 Hz, 1H) F1142 171-173 (thin film) 3260 (w), 1714 (m), 1648 (m), 1605 (w), 1549 (m), 1505 (m), 1474 (m) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H ₁₆ Cl ₃ F ₇ N ₃ O ₂ S, 637.9885; found, 637.9886 ^1H NMR (500 MHz, DMSO- _d6 ) δ 11.00 (br s, 1H), 10.17 (br s, 1H), 7.94-7.99 (m, 2H), 7.89 ( d, J = 2.5 Hz, 1H), 7.75 (dd, J = 8.8, 2.5 Hz, 1H), 7.64-7.69 (m, 2H), 7.54 (d , J = 8.8 Hz, 1H), 6.90 (m, 1H), 6.80 (m, 1H), 5.30 (br s, 2H), 3.69 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.4 Hz, 1H) F1143 (thin film) 3270 (w), 1644 (m), 1606 (m), 1588 (m), 1542 (m), 1505 (m), 1468 (m) HRMS-ESI (m/z)[M+H] ⁺ calculated for C ₂₃ H ₁₆ Cl ₃ F ₇ N ₃ O ₂ S, 637.9885; found, 637.9888 ^1H NMR (500 MHz, DMSO- _d6 ) δ 10.96 (br s, 1H), 10.17 (br s, 1H), 7.99 (br s, 1H), 7.88-7.93 (m, 2H), 7.72-7.77 (m, 2H), 7.68 (br t, J = 8 Hz, 1H), 7.54 (d, J = 8.7 Hz, 1H), 6.90 (m, 1H), 6.80 (m, 1H), 5.30 (br s, 2H), 3.74 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F1144 ESIMS m/z 661 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 8.82 (s, 1H), 7.98 (d, J = 2.6 Hz, 1H), 7.88 - 7.74 (m, 3H), 7.53 - 7.42 (m, 2H), 7.31 (d, J = 8.5 Hz, 1H), 6.61 - 6.50 (m, 2H ), 5.02 (s, 1H), 4.22 (t, J = 5.8 Hz, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.46 - 3.36 (m, 3H), 2.29 (s, 3H), 2.01 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.86, -117.62 F1145 ESIMS m/z 619 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 8.85 (s, 1H), 7.99 (d, J = 2.6 Hz, 1H), 7.87 - 7.72 (m, 3H), 7.54 - 7.41 (m, 2H), 7.28 (d, J = 8.4 Hz, 1H), 6.58 - 6.48 (m, 2H ), 4.82 (s, 1H), 3.85 (s, 1H), 3.77 - 3.61 (m, 3H), 3.42 (d, J = 8.3 Hz, 1H), 3 .22 (t, J = 5.7 Hz, 2H), 2.28 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.81, -117.63 F1146 152-172 ESIMS m/z 685 ([M-Cl] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.01 (d, J = 22.2 Hz, 2H), 10.76 (s, 1H), 7.92 (d, J = 2.6 Hz , 1H), 7.77 (dd, J = 9.0, 2.5 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.64 - 7.52 (m, 3H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.66 F1147 ESIMS m/z 633 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.05 (s, 1H), 9.32 (s, 1H), 8.04 (td, J = 8.9, 6.0 Hz, 1H) , 7.88 (t, J = 2.5 Hz, 2H), 7.79 (d, J = 2.0 Hz, 1H), 7.66 (dd, J = 8.8, 2.6 Hz, 1H), 7.33 (d, J = 8.7 Hz, 1H), 7.00 (ddd, J = 11.2, 8.8, 2.8 Hz, 1H), 6.92 (tt, J = 8.8, 2.2 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.27, -115.53, -122.00 F1148 ESIMS m/z 633 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.15 (s, 1H), 9.42 (s, 1H), 8.17 (td, J = 8.9, 6.0 Hz, 1H) , 8.00 - 7.95 (m, 1H), 7.87 (dd, J = 13.9, 2.3 Hz, 2H), 7.71 (dd, J = 8.8, 2.6 Hz , 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.19 - 7.01 (m, 2H), 3.65 (dd, J = 11.2, 1.1 Hz, 1H), 3.34 (d, J = 11.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.24, -115.71, -122.10 F1149 ESIMS m/z 648 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.27 (s, 1H), 8.01 (dd, J = 6.3, 2.3 Hz, 2H) , 7.93 (d, J = 2.0 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.47 (d, J = 8.7 Hz, 1H), 7.37 (td, J = 8.6, 5.6 Hz, 1H), 6.88 (ddd, J = 10.9, 9.1, 2.0 Hz, 1H), 4.77 (s, 2H), 3.77 (d, J = 8.3 Hz, 1H), 3.53 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.27, -137.15, -144.15 F1150 ESIMS m/z 648 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 9.23 (s, 1H), 8.05 - 7.95 (m, 1H), 7.89 (d, J = 2.0 Hz, 1H), 7.82 (d, J = 2.6 Hz, 1H), 7.72 (dd, J = 8.8, 2.6 Hz, 1H), 7.43 ( d, J = 8.8 Hz, 1H), 7.35 (td, J = 8.6, 5.6 Hz, 1H), 6.88 (td, J = 9.8, 9.0, 2, 1 Hz, 1H), 4.75 (d, J = 8.5 Hz, 2H), 3.69 - 3.63 (m, 1H), 3.33 (d, J = 11.2 Hz, 1H) ;
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.23, -137.28, -144.27 F1151 110-116 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₃ F ₄ N ₃ O ₂ , 559.0244; found, 559.0245 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.78 (s, 1H), 9.94 (d, J = 1.9 Hz, 1H), 7.77 (d, J = 5.4 Hz , 1H), 7.71 (td, J = 6.8, 2.3 Hz, 2H), 7.52 - 7.42 (m, 2H), 6.90 (t, J = 9.6 Hz, 1H), 6.82 (q, J = 8.1, 7.6 Hz, 1H), 5.29 (s, 2H), 3.57 (d, J = 8.4 Hz, 1H), 3, 41 (d, J = 8.5 Hz, 1H), 2.38 - 2.23 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.31, -123.71, -134.08,
-134.11, -138.53, -138.56 F1152 248-251 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₄ F ₃ N ₂ O ₂ , 545.9683; found, 545.9684 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.14 (s, 1H), 10.71 (s, 1H), 7.88 (dd, J = 11.3, 2.4 Hz, 1H) , 7.77 - 7.67 (m, 3H), 7.63 (dd, J = 2.3, 1.2 Hz, 1H), 7.47 (dd, J = 8.2, 3.2 Hz , 2H), 7.28 - 7.17 (m, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.55, -117.22, -118.17 F1153 236-239 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₂ Cl ₄ F ₄ N ₂ O ₂ , 563.9589; found, 563.9582 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.14 (s, 1H), 10.51 (s, 1H), 7.89 (dd, J = 11.3, 2.4 Hz, 1H) , 7.82 - 7.70 (m, 2H), 7.65 (dd, J = 2.5, 1.2 Hz, 1H), 7.53 - 7.44 (m, 2H), 7.39 (ddd, J = 10.9, 9.1, 2.9 Hz, 1H), 7.20 - 7.08 (m, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.64, -112.96, -112.98,
-117.23, -117.36, -117.37 F1154 152-156 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₅ H ₁₇ Cl ₄ F ₂ N ₃ O ₃ , 584.9992; found, 584.9987 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.57 (s, 1H), 9.94 (s, 1H), 7.87 (dd, J = 11, 3, 2.4 Hz, 1H), 7.75 - 7.69 (m, 1H), 7.64 - 7.59 (m, 3H), 7.56 (d, J = 9.1 Hz, 2H ), 7.51 - 7.43 (m, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H), 2.03 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.63, -117.23 F1155 236-239 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₃ H ₂₉ Cl ₄ F ₄ N ₃ O ₆ , 779.0747; found, 779.0738 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.14 (s, 1H), 10.61 (s, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H) , 7.80 - 7.69 (m, 2H), 7.67 (dd, J = 2.4, 1.2 Hz, 1H), 7.52 - 7.44 (m, 2H), 7.29 (td, J = 9.2, 1.7 Hz, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H), 1 .41(s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.56, -117.22, -123.24,
-126.64 F1156 231-241 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₄ F ₄ N ₃ O ₂ , 578.9698; found, 578.9695 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.28 (s, 1H), 7.88 (dd, J = 11.3, 2.4 Hz, 1H) , 7.77 - 7.69 (m, 1H), 7.63 (dd, J = 2.4, 1.2 Hz, 1H), 7.52 - 7.45 (m, 2H), 6.92 (ddd, J = 10.6, 8.9, 1.7 Hz, 1H), 6.82 (td, J = 8.4, 5.6 Hz, 1H), 5.33 (s, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.72, -117.23, -133.72,
-133.76, -138.28, -138.31 F1157 ESIMS m/z 711 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.11 (s, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.86 - 7.69 (m, 2H), 7.56 - 7.41 (m, 4H), 7.26 - 7.15 (m, 2H), 3.96 (t, J = 6.7 Hz, 2H ), 3.66 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.76 (t, J = 6.7 Hz, 2H), 2.38(s, 3H), 1.45(s, 9H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.69, 162.46, 153.92, 139.06, 137.88, 137.79, 137.39, 134.71, 134.38, 132 .29, 130.30, 129.17, 127.86, 127.84, 125.08, 124.91, 124.85, 124.75, 121.68, 119.86, 119.77, 118.02 , 80.20, 61.93, 45.85, 39.21, 37.50, 17.52, 16.57 F1158 ESIMS m/z 629 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetonitrile- _d3 ) δ 9.23 (s, 1H), 8.12 (s, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7.72 (dd, J = 8.7, 2.6 Hz, 1H), 7.57 - 7.38 (m, 4H), 7.23 (d, J = 8.5 Hz, 1H), 6.66 - 6.47 (m, 2H), 6.21 (s, 1H), 5.67 (s, 1H), 4.87 (s, 1H), 3.60 (d, J = 8.3 Hz, 1H ), 3.36 (t, J = 6.6 Hz, 2H), 3.19 (d, J = 8.3 Hz, 1H), 2.45 (t, J = 6.6 Hz, 2H), 2.25 (s, 3H) F1159 ESIMS m/z 716 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.07 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.85 - 7.67 (m, 2H), 7.56 - 7.41 (m, 4H), 7.26 - 7.09 (m, 2H), 3.78 (t, J = 6.0 Hz, 2H ), 3.66 (d, J = 8.4 Hz, 1H), 3.50 (t, J = 6.0 Hz, 2H), 3.42 (d, J = 8.3 Hz, 1H), 3.29 (s, 3H), 2.37 (s, 3H), 1.43 (s, 9H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.66, 162.44, 162.35, 154.15, 140.33, 137.87, 137.78, 137.45, 137.40, 134 .71, 133.75, 133.65, 131.96, 131.85, 130.28, 129.03, 127.84, 124.95, 124.90, 124.64, 124.54, 121.65 , 119.86, 119.78, 79.41, 69.82, 61.93, 57.74, 49.34, 39.21, 37.50, 17.53, F1160 ESIMS m/z 639 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.28 (s, 1H), 8.94 (s, 1H), 8.05 (d, J = 2, 6 Hz, 2H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.49 (s, 4H), 7.26 (t, J = 9.1 Hz, 1H) , 3.66 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-119.75 F1161 ESIMS m/z 656 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.27 (s, 1H), 8.92 (s, 1H), 8.08 (d, J = 11, 8 Hz, 1H), 8.07 (s, 1H), 7.83 (dd, J = 7.5, 4.5 Hz, 3H), 7.48 (t, J = 9.3 Hz, 2H) , 7.27 (t, J = 9.1 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2 ,17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -117.60, -119.88 F1162 ESIMS m/z 616 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 10.17 (s, 1H), 8.82 (s, 1H), 7.97 (d, J = 2.5 Hz, 1H), 7.81 - 7 .72 (m, 1H), 7.52 - 7.40 (m, 4H), 7.34 - 7.26 (m, 1H), 6.59 - 6.48 (m, 2H), 4.79 (s, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.55 (t, J = 5.6 Hz, 2H), 3.41 (d, J = 8.4 Hz , 1H), 3.32 (s, 5H), 2.28 (s, 3H);
¹³ C NMR (101 MHz, CDCl ₃ ) δ 167.62, 152.59, 143.11, 143.02, 142.62, 139.90, 139.09, 135.40, 133.05, 132.01 , 130.48, 130.13, 126.58, 125.04, 119.20, 115.32, 76.12, 67.15, 63.01, 48.43, 44.39, 42.70, 23 .05 F1163 ESIMS m/z 617 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.46 (s, 1H), 8.20 (tt, J = 9.0, 5.9 Hz, 1H) , 8.03 (d, J = 2.6 Hz, 1H), 7.80 (dt, J = 9.6, 2.2 Hz, 3H), 7.48 (d, J = 8.8 Hz, 1H), 7.20 - 7.02 (m, 2H), 3.78 (d, J = 8.3 Hz, 1H), 3.51 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.76, -112.79, -115.56, -122.02 F1164 ESIMS m/z 617 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.15 (s, 1H), 9.42 (s, 1H), 8.18 (tt, J = 8.9, 5.9 Hz, 1H) , 7.87 (d, J = 2.5 Hz, 1H), 7.77 (s, 1H), 7.80 - 7.67 (m, 2H), 7.44 (d, J = 8.8 Hz, 1H), 7.19 - 7.01 (m, 2H), 3.66 (d, J = 11.2 Hz, 1H), 3.34 (d, J = 11.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.73, -114.13, -115.73, -122.13 F1165 ESIMS m/z 716 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 8.83 (s, 1H), 7.96 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.7, 2.6 Hz, 1H), 7.64 (q, J = 8.3 Hz, 4H), 7.58 - 7.40 (m, 4H), 7.28 ( dd, J = 8.5, 4.2 Hz, 1H), 6.57 (d, J = 2.6 Hz, 1H), 6.50 (dd, J = 8.5, 2.7 Hz, 1H ), 5.66 (s, 1H), 4.48 (s, 2H), 3.64 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.4 Hz, 1H ), 2.25 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.72 F1166 ESIMS m/z 693 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 8.86 (s, 1H), 8.24 - 8.11 (m, 2H), 8.00 - 7, 92 (m, 1H), 7.79 - 7.71 (m, 1H), 7.70 - 7.59 (m, 2H), 7.51 - 7.39 (m, 4H), 7.28 ( dd, J = 8.5, 4.1 Hz, 1H), 6.55 (d, J = 2.6 Hz, 1H), 6.48 (dd, J = 8.5, 2.7 Hz, 1H ), 5.75 (t, J = 6.3 Hz, 1H), 4.54 (d, J = 5.6 Hz, 2H), 3.63 (d, J = 8.4 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H), 2.25 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 162.43, 162.34, 148.88, 147.00, 146.73, 146.69, 137.81, 137.74, 137.71, 137 .38, 134.70, 134.04, 133.98, 130.20, 127.98, 127.84, 127.81, 126.94, 126.89, 126.84, 125.64, 125.54 , 124.92, 123.41, 123.20, 121.44, 121.36, 119.80, 119.71, 114.26, 110.27, 62.77, 61.94, 46.75, 39 .18, 39.14, 37.51, 17.87 F1167 ESIMS m/z 632 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.27 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.85 - 7.75 (m, 3H), 7.47 (d, J = 8.8 Hz, 1H), 7.37 (td, J = 8.6, 5.6 Hz, 1H), 6.89 ( ddd, J = 10.9, 9.0, 2.0 Hz, 1H), 4.77 (d, J = 8.5 Hz, 2H), 3.77 (d, J = 8.3 Hz, 1H ), 3.51 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.76, -112.80, -137.13, -144.17 F1168 ESIMS m/z 632 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 9.23 (s, 1H), 7.84 (d, J = 2.6 Hz, 1H), 7.77 (s, 1H), 7.80 - 7.68 (m, 2H), 7.43 (d, J = 8.8 Hz, 1H), 7.35 (td, J = 8.6, 5.6 Hz, 1H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz, 1H), 4.76 (d, J = 8.5 Hz, 2H), 3.70 - 3 .52 (m, 1H), 3.34 (d, J = 11.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.72, -114.12, -137.32, -144.27 F1169 ESIMS m/z 693 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.37 (s, 1H), 10.20 (s, 1H), 9.61 (s, 1H), 8.22 (td, J = 8, 8, 5.7 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (t, J = 9.3 Hz, 2H), 7.25 (td, J = 9.3, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8 ,3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.88, -75.84, -117.57, -123.34, -128.52 F1170 ESIMS m/z 710 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (d, J = 3.1 Hz, 2H), 9.59 (s, 1H), 8.21 (td, J = 8.8, 5.6 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (t, J = 9.4 Hz, 2H), 7.25 (td, J = 9.2, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.84, -64.49, -117.60, -123.43, -128.63 F1171 ESIMS m/z 595 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.46 (s, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.89 - 7.83 (m, 1H), 7.81 (dd, J = 8.8, 2.7 Hz, 1H), 7.52 - 7.44 (m, 4H), 7.09 (ddd, J = 11.1, 9.4, 2.3 Hz, 1H), 4.00 (s, 3H), 3.66 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-134.04 (d, J = 6.3 Hz), -140.51 (d, J = 6.2 Hz) F1172 ESIMS m/z 583 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.46 (s, 1H), 8.19 (td, J = 8.9, 6.0 Hz, 1H) , 8.03 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 - 7.59 (m, 2H), 7.48 (d, J = 8.8 Hz, 1H), 7.15 (ddd, J = 11.2, 8.7, 2.9 Hz, 1H), 7.12 - 7.02 (m, 1H), 3.69 - 3.61 (m, 1H), 3.42 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.56, -118.83, -122.01,
-122.13 F1173 ESIMS m/z 583 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.11 (s, 1H), 9.42 (s, 1H), 8.18 (tt, J = 9.0, 5.9 Hz, 1H) , 7.89 (d, J = 2.4 Hz, 1H), 7.71 (dd, J = 8.8, 2.6 Hz, 1H), 7.58 (dd, J = 6.4, 1 .0 Hz, 2H), 7.44 (d, J = 8.7 Hz, 1H), 7.10 (dddd, J = 30.1, 10.8, 8.7, 2.7 Hz, 2H) , 3.55 (dd, J = 11.4, 1.4 Hz, 1H), 3.27 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.71, -120.00, -122.07,
-122.19 F1174 ESIMS m/z 708 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.61 (s, 1H), 9.54 (s, 1H), 8.15 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.87 - 7.75 (m, 3H), 7.48 (t, J = 8.7 Hz, 2H), 7.19 (td, J = 9.2, 2.0 Hz, 1H), 6.66 (s, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.86, -117.59, -123.30, -128.58 F1175 118-127 ESIMS m/z 675 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.76 (s, 1H), 9.55 (s, 1H), 8.18 (tt, J = 8, 7, 4.4 Hz, 1H), 8.04 (d, J = 2.5 Hz, 1H), 7.82 (td, J = 8.4, 4.3 Hz, 3H), 7.48 ( t, J = 8.7 Hz, 2H), 7.21 (td, J = 9.3, 1.9 Hz, 1H), 6.39 (d, J = 53.5 Hz, 1H), 3, 72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.88, -117.60, -123.17,
-127.10, -128.48 F1176 ESIMS m/z 648 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 8.78 (s, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.79 (dt, J = 8.7, 1.8 Hz, 1H), 7.49 (s, 3H), 7.48 - 7.37 (m, 3H), 7.36 - 7.23 (m, 3H ), 7.27 - 7.18 (m, 1H), 6.61 - 6.45 (m, 2H), 5.45 (s, 1H), 4.36 (s, 2H), 3.65 ( d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.25 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.76, 162.40, 147.29, 140.39, 137.96, 137.82, 137.43, 134.70, 133.81, 130 ,19, 128.29, 127.85, 127.22, 126.73, 126.68, 126.66, 125.33, 124.91, 121.33, 119.79, 119.71, 114.13 , 110.20, 61.93, 47.37, 39.20, 37.48, 17.85 F1177 ESIMS m/z 662 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 8.78 (d, J = 6.5 Hz, 1H), 7.98 (d, J = 2.6 Hz , 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.52 - 7.37 (m, 5H), 7.30 (s, 2H), 7.38 - 7.15 (m, 3H), 6.55 (ddt, J = 11.8, 6.3, 3.0 Hz, 2H), 4.89 (s, 1H), 3.66 (d, J = 8.3 Hz, 1H), 3.47 - 3.33 (m, 3H), 2.92 (dd, J = 8.3, 6.5 Hz, 2H), 2.29 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.74, 162.40, 147.23, 140.02, 138.01, 137.84, 137.44, 134.70, 133.87, 130 ,19, 128.72, 128.32, 128.29, 127.84, 127.21, 126.79, 126.02, 125.23, 124.91, 121.32, 119.80, 113.90 , 110.04, 61.94, 45.22, 39.20, 37.49, 35.40, 17.84 F1178 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 8.80 (s, 1H), 8.13 (s, 1H), 7.98 (d, J = 2, 6 Hz, 1H), 7.79 (dd, J = 8.7, 2.7 Hz, 1H), 7.51 - 7.37 (m, 4H), 7.30 (s, 2H), 7, 38 - 7.14 (m, 4H), 6.56 - 6.37 (m, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8, 3 Hz, 1H), 3.29 (dd, J = 7.2, 1.7 Hz, 2H), 3.09 (h, J = 7.0 Hz, 1H), 2.27 (s, 3H) , 1.33 (d, J = 6.9 Hz, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.84, 162.43, 161.65, 147.29, 145.36, 137.95, 137.85, 137.75, 137.44, 134 .70, 133.87, 130.19, 128.40, 127.84, 127.18, 126.79, 126.74, 126.21, 125.09, 124.91, 121.36, 121.27 , 119.81, 119.73, 113.88, 109.99, 61.96, 50.85, 39.18, 39.12, 37.50, 19.03, 17.84 F1179 ESIMS m/z 701 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.53 (s, 1H), 9.41 (s, 1H), 8.20 - 7.98 (m, 4H), 7.91 - 7.76 (m, 3H), 7.68 - 7.58 (m, 1H), 7.63 - 7.34 (m, 5H), 7.18 (td, J = 9.2, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H). ¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.65, -123.13, -128.69. F1180 ESIMS m/z 602 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.44 (s, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.81 - 7.71 (m, 2H), 7.63 (t, J = 1.9 Hz, 1H), 7.61 - 7.48 (m, 4H), 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H), 2.33 (d, J = 28.4 Hz, 6H);
¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 163.15, 139.68, 138.23, 137.76, 134.73, 134.56, 131.78, 130.78, 128.38, 124 .53, 124.49, 122.02, 121.89, 119.64, 62.64, 37.32, 16.00, 15.43 F1181 ESIMS m/z 598 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.27 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.79 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 - 7.59 (m, 2H), 7.46 (d, J = 8.7 Hz, 1H), 7.37 ( td, J = 8.6, 5.6 Hz, 1H), 6.88 (ddd, J = 10.9, 9.0, 2.0 Hz, 1H), 4.76 (d, J = 8, 5 Hz, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-118.82, -137.10, -144.13 F1182 ESIMS m/z 598 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.11 (s, 1H), 9.23 (s, 1H), 7.88 (dd, J = 10.1, 2.6 Hz, 1H) , 7.75 - 7.66 (m, 1H), 7.58 (dd, J = 6.3, 1.0 Hz, 2H), 7.43 (dd, J = 8.8, 2.0 Hz , 1H), 7.35 (td, J = 8.6, 5.5 Hz, 1H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz, 1H), 4, 72 (s, 2H), 3.58 - 3.50 (m, 1H), 3.27 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-119.99, -137.27, -144.16,
-144.34 F1183 228-231 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₇ Cl ₄ FN ₂ O ₂ , 524.0028; found, 524.0027 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.85 (s, 1H), 10.52 (s, 1H), 7.77 - 7.65 (m, 5H), 7.51 - 7, 42 (m, 2H), 7.35 (t, J = 7.9 Hz, 2H), 7.11 (t, J = 7.3 Hz, 1H), 3.57 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28 F1184 205-208 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₄ F ₂ N ₂ O ₂ , 541.9934; found, 541.9933 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.86 (s, 1H), 10.59 (s, 1H), 7.72 (dtd, J = 9.1, 4.6, 4.1 , 1.8 Hz, 5H), 7.53 - 7.40 (m, 2H), 7.27 - 7.11 (m, 2H), 3.57 (d, J = 8.4 Hz, 1H) , 3.43 (d, J = 8.4 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -118.57 F1185 194-197 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₅ Cl ₄ F ₃ N ₂ O ₂ , 559.9840; found, 559.9838 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.86 (s, 1H), 10.36 (s, 1H), 7.82 - 7.65 (m, 4H), 7.56 - 7, 42 (m, 2H), 7.42 - 7.34 (m, 1H), 7.20 - 7.07 (m, 1H), 3.57 (d, J = 8.5 Hz, 1H), 3 .43 (d, J = 8.5 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.29, -113.31, -117.22,
-117.23, -117.28 F1186 167-173 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₆ H ₂₀ Cl ₄ FN ₃ O ₃ , 581.0243; found, 581.0240 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.85 (s, 1H), 10.45 (s, 1H), 9.92 (s, 1H), 7.76 - 7.67 (m, 3H), 7.62 (d, J = 9.0 Hz, 2H), 7.54 (d, J = 9.0 Hz, 2H), 7.46 (dd, J = 7.8, 5.4 Hz, 2H), 3.57 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.39 (s, 3H), 2.03 ( s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29 F1187 121-127 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₄ H ₃₂ Cl ₄ F ₃ N ₃ O ₆ , 775.0997; found, 775.0988 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.87 (s, 1H), 10.48 (s, 1H), 7.80 - 7.67 (m, 4H), 7.46 (dd, J = 8.0, 5.4 Hz, 2H), 7.34 - 7.22 (m, 1H), 3.57 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.40 (s, 3H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -123.57, -126.57 F1188 120-125 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₇ Cl ₄ FN ₂ O ₂ , 524.0028; found, 524.0026 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.49 (s, 1H), 7.97 (d, J = 2.2 Hz, 1H), 7.72 (tt, J = 5.3, 4.2, 1.6 Hz, 3H), 7.61 (d, J = 2.2 Hz, 1H), 7.53 - 7.39 (m, 2H), 7.36 (t, J = 7.9 Hz, 2H), 7.12 (t, J = 7.5 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H), 3, 43 (d, J = 8.5 Hz, 1H), 2.34 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27 F1189 123-127 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₄ F ₂ N ₂ O ₂ , 541.9934; found, 541.9933 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.56 (s, 1H), 7.96 (d, J = 2.1 Hz, 1H), 7.81 - 7.67 (m, 3H), 7.61 (d, J = 2.2 Hz, 1H), 7.55 - 7.39 (m, 2H), 7.21 (t, J = 8.9 Hz, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.33 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -118.52 F1190 108-112 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₅ Cl ₄ F ₃ N ₂ O ₂ , 559.9840; found, 559.9838 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.32 (s, 1H), 7.97 (d, J = 2.2 Hz, 1H), 7.80 - 7.60 (m, 3H), 7.53 - 7.43 (m, 2H), 7.38 (ddd, J = 11.0, 9.0, 2.8 Hz, 1H), 7.19 - 7.09 (m, 1H), 3.58 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.36 (s, 3H) ;
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.00, -113.01, -116.89,
-116.91, -117.27 F1191 162-170 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₆ H ₂₀ Cl ₄ FN ₃ O ₃ , 581.0243; found, 581.0244 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.42 (s, 1H), 9.92 (s, 1H), 7.96 (d, J = 2, 1 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.66 - 7.58 (m, 3H), 7.55 (d, J = 9.0 Hz, 2H), 7.51 - 7.42 (m, 2H), 3.58 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.33(s, 3H), 2.03(s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27 F1192 108-114 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₄ H ₃₂ Cl ₄ F ₃ N ₃ O ₆ , 775.0997; found, 775.0990 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.43 (s, 1H), 7.97 (d, J = 2.2 Hz, 1H), 7.80 - 7.62 (m, 3H), 7.53 - 7.42 (m, 2H), 7.28 (t, J = 9.2 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.37 (s, 3H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -123.26, -123.27,
-126.31, -126.31 F1193 ESIMS m/z 623 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.55 (s, 1H), 7.92 (d, J = 2.5 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 - 7.60 (m, 2H), 7.59 - 7.53 (m, 3H), 7.32 (t, J = 9.5 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 2.43 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-129.69 (d, J = 3.1 Hz), -132.69 (d, J = 3.2 Hz) F1194 212-217 ESIMS m/z 531 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.02 (s, 1H), 10.60 (s, 1H), 8.09 (dd, J = 6.4, 2.7 Hz, 1H) , 7.83 - 7.66 (m, 4H), 7.54 - 7.31 (m, 4H), 7.19 - 7.10 (m, 1H), 3.59 (d, J = 8, 4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.24, -123.09 F1195 207-209 ESIMS m/z 546 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 10.66 (s, 1H), 8.09 (dd, J = 6.4, 2.6 Hz, 1H) , 7.88 - 7.63 (m, 4H), 7.56 - 7.37 (m, 2H), 7.22 (t, J = 8.9 Hz, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.23, -118.10, -123.04 F1196 169-173 ESIMS m/z 661 ([M+OH+DMSO-d ₆ ] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 10.39 (s, 1H), 8.10 (dd, J = 6.3, 2.7 Hz, 1H) , 7.91 - 7.66 (m, 3H), 7.54 - 7.33 (m, 3H), 7.14 (td, J = 8.5, 2.3 Hz, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.01 (d, J = 6.0 Hz), -117.24,
-117.42 (d, J = 6.1 Hz), -122.36 F1197 154-170 ESIMS m/z 586 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.02 (s, 1H), 10.52 (s, 1H), 9.94 (s, 1H), 8.08 (dd, J = 6, 4, 2.6 Hz, 1H), 7.77 (dd, J = 5.3, 2.6 Hz, 1H), 7.74 - 7.67 (m, 1H), 7.66 - 7.52 (m, 4H), 7.51 - 7.41 (m, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H) , 2.03 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.25, -123.06 F1198 132-149 ESIMS m/z 780 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 10.52 (s, 1H), 8.10 (dd, J = 6.3, 2.6 Hz, 1H) , 7.93 - 7.62 (m, 3H), 7.58 - 7.40 (m, 2H), 7.37 - 7.22 (m, 1H), 6.94 - 6.66 (m, 1H), 5.12 (s, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 1.41 (s, 19H), 1.39 (s, 7H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.24, -122.32, -123.33,
-126.62, -137.98 (d, J = 3.7 Hz),
-141.11 (d, J = 3.9 Hz) F1199 ESIMS m/z 763 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.43 (s, 1H), 9.73 (s, 1H), 7.91 (d, J = 2, 5 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.66 - 7.57 (m, 1H), 7, 55 (d, J = 8.7 Hz, 1H), 7.47 - 7.40 (m, 1H), 7.18 (t, J = 9.3 Hz, 1H), 6.86 (s, 1H ), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.97 (q, J = 6.6 Hz, 2H), 2.39 - 2.28 (m, 2H), 1.69 (t, J = 7.4 Hz, 2H), 1.38 (s, 9H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.50, -124.51 F1200 ESIMS m/z 741 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 9.93 (s, 1H), 9.86 (s, 1H), 7.90 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.7 Hz, 1H), 7.51 (s, 1H), 7.46 - 7.39 (m, 2H), 7.28 (d, J = 8.6 Hz, 1H), 6.88 - 6.80 (m, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.96 (q, J = 6 .6 Hz, 2H), 2.29 (t, J = 7.6 Hz, 2H), 2.25 (s, 3H), 1.73 - 1.63 (m, 2H), 1.38 (s , 9H) F1201 ESIMS m/z 665 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.42 (s, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.2, 2.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.65 - 7.51 (m, 2H), 7.43 ( dd, J = 8.5, 2.1 Hz, 1H), 7.24 - 7.13 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d , J = 8.5 Hz, 1H), 2.61 (t, J = 6.9 Hz, 2H), 2.39 (t, J = 7.4 Hz, 2H), 1.68 (p, J = 7.3 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.50, -124.47 F1202 (thin film) 3258, 2926, 1651, 1588, 1503 ESIMS m/z 643 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 9.94 (s, 1H), 9.91 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.4, 2.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.58 - 7.48 ( m, 2H), 7.43 (ddd, J = 6.9, 4.2, 2.1 Hz, 2H), 7.28 (d, J = 8.6 Hz, 1H), 3.62 (d , J = 8.5 Hz, 1H), 3.48 (d, J = 8.5 Hz, 1H), 2.58 (t, J = 6.9 Hz, 2H), 2.33 (t, J = 7.4 Hz, 2H), 2.25 (s, 3H), 1.66 (p, J = 7.1 Hz, 2H) F1203 ESIMS m/z 581 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.32 (bs, 1H), 10.30 (s, 1H), 7.89 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.58 - 7.52 ( m, 3H), 7.15 - 6.99 (m, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-135.11 (d, J = 10.9 Hz), -138.91 (d, J = 10.1 Hz) F1204 ESIMS m/z 719 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.53 (s, 1H), 9.45 (s, 1H), 8.21 - 8.07 (m, 3H), 8.04 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.48 (t, J = 8.5 Hz, 2H), 7, 32 (t, J = 8.8 Hz, 2H), 7.18 (td, J = 9.2, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.88, -109.41, -117.65,
-123.14, -128.67 F1205 ESIMS m/z 731 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.52 (s, 1H), 9.27 (s, 1H), 8.17 - 8.02 (m, 3H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.48 (dd, J = 8.7, 3.2 Hz, 2H ), 7.15 (td, J = 9.3, 2.0 Hz, 1H), 7.11 - 7.02 (m, 2H), 3.89 (s, 3H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -117.64, -123.07, -128.67 F1206 ESIMS m/z 702 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.66 (s, 1H), 9.59 (s, 1H), 9.25 (d, J = 2, 3 Hz, 1H), 9.17 (d, J = 2.1 Hz, 1H), 8.80 (dt, J = 4.9, 1.6 Hz, 1H), 8.37 (ddt, J = 21.4, 7.9, 2.0 Hz, 2H), 8.14 (td, J = 8.8, 5.6 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H ), 7.87 - 7.77 (m, 2H), 7.62 - 7.43 (m, 2H), 7.20 (td, J = 9.2, 2.0 Hz, 1H), 3, 72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -117.59, -122.96, -128.41 F1207 232-234 ESIMS m/z 513 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.05 (s, 1H), 10.59 (s, 1H), 7.95 (ddd, J = 12.6, 6.8, 2.5 Hz, 1H), 7.77 - 7.60 (m, 4H), 7.53 - 7.34 (m, 4H), 7.20 - 7.10 (m, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.24, -135.59 (d, J = 24.0 Hz), -145.33 (d, J = 23.8 Hz) F1208 204-210 ESIMS m/z 530 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.05 (s, 1H), 10.65 (s, 1H), 7.95 (ddd, J = 12.4, 6.8, 2.6 Hz, 1H), 7.72 (ddt, J = 8.6, 6.1, 3.4 Hz, 3H), 7.68 - 7.62 (m, 1H), 7.52 - 7.40 ( m, 2H), 7.22 (t, J = 8.9 Hz, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.24, -118.10, -135.56 (d, J = 23.9 Hz), -145.31 (d, J = 24.0 Hz) F1209 184-188 ESIMS m/z 551 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.05 (s, 1H), 10.37 (s, 1H), 8.01 - 7.90 (m, 1H), 7.81 - 7, 66 (m, 3H), 7.54 - 7.33 (m, 3H), 7.20 - 7.09 (m, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3 .43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.96 (d, J = 6.1 Hz), -117.25,
-117.31 (d, J = 6.1 Hz), -135.66 (d, J = 23.8 Hz), -144.76 (d, J = 23.9 Hz) F1210 153-159 ESIMS m/z 570 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.04 (s, 1H), 10.51 (s, 1H), 9.94 (s, 1H), 7.94 (ddd, J = 12, 4, 6.9, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.67 - 7.53 (m, 5H), 7.51 - 7.41 (m, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.4 Hz, 1H), 2.03 (s, 3H) ;
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.25, -135.65 (d, J = 24.2 Hz), -145.33 (d, J = 24.1 Hz) F1211 130-140 ESIMS m/z 764 ([MH] ^- ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.05 (s, 1H), 10.49 (s, 1H), 8.04 - 7.90 (m, 1H), 7.82 - 7, 67 (m, 3H), 7.54 - 7.41 (m, 2H), 7.28 (t, J = 9.0 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H ), 3.43 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.25, -123.29, -126.49,
-135.59 (d, J = 23.9 Hz), -137.99 (d, J = 3.7 Hz), -141.11 (d, J = 3.9 Hz), -144.71 ( d, J = 23.7 Hz) F1212 233-235 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₄ Cl ₄ F ₄ N ₂ O ₂ , 577.9746; found, 577.9745 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.24 (s, 1H), 10.72 (s, 1H), 8.28 (d, J = 2.5 Hz, 1H), 8.08 (d, J = 2.5 Hz, 1H), 7.82 - 7.67 (m, 3H), 7.53 - 7.44 (m, 2H), 7.42 - 7.35 (m, 2H ), 7.15 (tt, J = 7.5, 1.2 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.4 Hz , 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.39, -117.19 F1213 227-229 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₇ Cl ₃ F ₂ N ₂ O ₃ , 524.0273; found, 524.0275 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.38 (s, 1H), 7.81 (dd, J = 13.4, 2.5 Hz, 1H) , 7.76 - 7.68 (m, 3H), 7.56 (dd, J = 2.6, 1.4 Hz, 1H), 7.51 - 7.42 (m, 2H), 7.40 - 7.33 (m, 2H), 7.12 (tt, J = 7.4, 1.2 Hz, 1H), 3.89 (d, J = 1.1 Hz, 3H), 3.58 ( d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -128.01 F1214 244-247 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₃ Cl ₄ F ₅ N ₂ O ₂ , 595.9651; found, 595.9649 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.24 (s, 1H), 10.78 (s, 1H), 8.28 (d, J = 2.5 Hz, 1H), 8.09 (d, J = 2.5 Hz, 1H), 7.79 - 7.65 (m, 3H), 7.56 - 7.41 (m, 2H), 7.23 (t, J = 8.9 Hz, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.41, -117.19, -118.05 F1215 219-222 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₂ Cl ₄ F ₆ N ₂ O ₂ , 613.9557; found, 613.9563 d 11.24 (s, 1H), 10.60 (s, 1H), 8.29 (d, J = 2.5 Hz, 1H), 8.10 (d, J = 2.5 Hz, 1H) , 7.82 (td, J = 8.9, 6.1 Hz, 1H), 7.77 - 7.68 (m, 1H), 7.54 - 7.46 (m, 2H), 7.40 (ddd, J = 10.8, 9.0, 2.8 Hz, 1H), 7.22 - 7.11 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.41, -112.96, -112.98,
-117.20, -117.74, -117.75 F1216 163-168 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₆ H ₁₇ Cl ₄ F ₄ N ₃ O ₃ , 634.9960; found, 634.9956 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.23 (s, 1H), 10.64 (s, 1H), 9.95 (s, 1H), 8.27 (d, J = 2, 5 Hz, 1H), 8.06 (d, J = 2.5 Hz, 1H), 7.72 (dd, J = 7.5, 1.8 Hz, 1H), 7.59 (q, J = 9.0 Hz, 4H), 7.54 - 7.40 (m, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.03 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.39, -117.20 F1217 138-143 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₄ H ₂₉ Cl ₄ F ₆ N ₃ O ₆ , 829.0715; found, 829.0706 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.24 (s, 1H), 10.70 (s, 1H), 8.29 (d, J = 2.4 Hz, 1H), 8.12 (d, J = 2.4 Hz, 1H), 7.81 (q, J = 8.5 Hz, 1H), 7.75 - 7.69 (m, 1H), 7.52 - 7.44 ( m, 2H), 7.34 - 7.26 (m, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 1.40(s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.42, -117.20, -123.22, -126.96 F1218 216-218 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₃ F ₃ N ₂ O ₃ , 542.0179; found, 542.0182 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.43 (s, 1H), 7.88 - 7.64 (m, 4H), 7.57 (dd, J = 2.6, 1.4 Hz, 1H), 7.51 - 7.40 (m, 2H), 7.26 - 7.15 (m, 2H), 3.89 (d, J = 1, 1 Hz, 3H), 3.58 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -118.52, -127.98 F1219 210-214 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₅ Cl ₃ F ₄ N ₂ O ₃ , 560.0084; found, 560.0086 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 10.25 (s, 1H), 7.98 (td, J = 9.0, 6.2 Hz, 1H) , 7.89 (dd, J = 13.3, 2.6 Hz, 1H), 7.77 (dd, J = 2.7, 1.4 Hz, 1H), 7.71 (dd, J = 7 ,2, 1.9 Hz, 1H), 7.52 - 7.37 (m, 3H), 7.15 (ddt, J = 10.7, 8.5, 1.9 Hz, 1H), 3, 97 (d, J = 1.3 Hz, 3H), 3.59 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.91, -113.92, -117.28,
-120.18, -120.19, -120.20,
-127.74 F1220 126-134 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₆ H ₂₀ Cl ₃ F ₂ N ₃ O ₄ , 581.0487; found, 581.0488 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.30 (s, 1H), 9.93 (s, 1H), 7.80 (dd, J = 13, 3, 2.5 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.65 - 7.60 (m, 2H), 7.59 - 7.52 (m, 3H), 7.51 - 7.42 (m, 2H), 3.89 (d, J = 1.1 Hz, 3H), 3.58 (d, J = 8.4 Hz, 1H) , 3.42 (d, J = 8.5 Hz, 1H), 2.03 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -128.06 F1221 100-106 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₄ H ₃₂ Cl ₃ F ₄ N ₃ O ₇ , 775.1242; found, 775,1234 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.31 (s, 1H), 7.89 (ddd, J = 15.8, 11.0, 4.2 Hz, 2H), 7.71 (dd, J = 7.3, 1.9 Hz, 2H), 7.52 - 7.43 (m, 2H), 7.33 - 7.22 (m, 1H) , 3.95 (d, J = 1.3 Hz, 3H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 1 .41(s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -124.07, -127.77,
-128.65 F1222 105-113 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₄ F ₃ N ₃ O ₂ , 574.9949; found, 574.9947 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.85 (s, 1H), 10.14 (s, 1H), 7.75 - 7.66 (m, 3H), 7.53 - 7, 44 (m, 2H), 6.95 - 6.86 (m, 1H), 6.79 (td, J = 8.4, 5.6 Hz, 1H), 5.29 (s, 2H), 3 .57 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.39 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -134.01, -134.04,
-138.07, -138.11 F1223 114-125 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₄ F ₃ N ₃ O ₂ , 574.9949; found, 574.9944 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.11 (s, 1H), 7.96 (d, J = 2.1 Hz, 1H), 7.76 - 7.68 (m, 1H), 7.62 (d, J = 2.2 Hz, 1H), 7.55 - 7.42 (m, 2H), 6.97 - 6.86 (m, 1H ), 6.73 (td, J = 8.5, 5.6 Hz, 1H), 5.31 (s, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.4 Hz, 1H), 2.36 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -133.68, -133.72,
-137.74, -137.77 F1224 ESIMS m/z 559 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (bs, 1H), 8.90 (bs, 1H), 8.32 (bs, 1H), 7.99 (d, J = 2, 6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.50 (s, 3H), 7.47 (d, J = 8.7 Hz, 1H) , 7.39 (dd, J = 8.5, 4.4 Hz, 1H), 6.75 (d, J = 2.8 Hz, 1H), 6.70 (dd, J = 8.5, 2 .8 Hz, 1H), 3.66 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.4 Hz, 1H), 2.30 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.81, 162.46, 155.55, 137.87, 137.77, 137.43, 134.70, 134.43, 130.22, 127 .84, 126.91, 124.91, 121.45, 119.80, 116.85, 112.76, 61.94, 39.18, 37.50, 17.64 F1225 108-115 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₃ Cl ₄ F ₆ N ₃ O ₂ , 628.9666; found, 628.9665 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.23 (s, 1H), 10.38 (s, 1H), 8.28 (d, J = 2.4 Hz, 1H), 8.07 (d, J = 2.4 Hz, 1H), 7.72 (d, J = 6.7 Hz, 1H), 7.55 - 7.41 (m, 2H), 6.99 - 6.80 ( m, 2H), 5.33 (s, 2H), 3.62 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.39, -117.20, -133.71,
-133.75, -138.62, -138.65 F1226 218-222 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₃ F ₄ N ₃ O ₃ , 575.0193; found, 575.0191 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 10.10 (s, 1H), 7.89 (dd, J = 13.3, 2.6 Hz, 1H) , 7.76 (s, 1H), 7.74 - 7.68 (m, 1H), 7.53 - 7.41 (m, 2H), 7.11 (q, J = 8.3 Hz, 1H ), 6.92 (t, J = 9.8 Hz, 1H), 5.33 (s, 2H), 3.96 (s, 3H), 3.59 (d, J = 8.4 Hz, 1H ), 3.42 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -127.79, -134.67,
-134.70, -142.07, -142.10 F1227 ESIMS m/z 580.1 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.14 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.55 (dd, J = 1.9, 0.6 Hz, 2H), 7.53 (d, J = 8.7 Hz, 1H), 7.25 - 7.06 (m, 2H), 5.11 (s, 2H), 3.62 (d, J = 8 .5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-134.18, -135.43 (d, J = 8.1 Hz) F1228 ESIMS m/z 614.1 (M+) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.14 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.80 (d, J = 0.6 Hz, 2H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.54 (d, J = 8.7 Hz, 1H), 7 .13 (q, J = 10.9, 9.9 Hz, 2H), 5.11 (s, 2H), 3.63 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-134.18, -135.44 (d, J = 8.2 Hz) F1229 ESIMS m/z 572 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 8.86 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.78 (dt, J = 8.7, 1.8 Hz, 1H), 7.52 - 7.42 (m, 4H), 7.06 (d, J = 8.4 Hz, 1H), 6.60 ( d, J = 8.4 Hz, 1H), 4.48 (s, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.24 (s, 3H), 2.09 (s, 3H) F1230 ESIMS m/z 602 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.34 (s, 1H), 8.61 (d, J = 2.7 Hz, 1H), 8.05 - 7.95 (m, 2H) , 7.63 (d, J = 8.8 Hz, 1H), 7.50 (s, 3H), 7.41 (s, 1H), 3.68 (d, J = 8.3 Hz, 1H) , 3.47 (d, J = 8.3 Hz, 1H), 2.59 (s, 3H), 2.35 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 163.40, 162.98, 152.99, 147.63, 138.79, 138.03, 135.40, 133.45, 132.55, 130 .57, 129.49, 128.64, 128.55, 128.53, 127.96, 126.79, 125.11, 122.98, 62.59, 39.91, 39.87, 38.25 , 19.65, 15.79 F1231 ESIMS m/z 639 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.49 (s, 1H), 8.91 (s, 1H), 8.13 - 7.99 (m, 2H), 7.90 - 7.77 (m, 3H), 7.53 - 7.43 (m, 2H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 3 .72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.88, -117.61, -123.33, -128.80 F1232 ESIMS m/z 657 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.46 (s, 1H), 8.19 (td, J = 8.9, 5.9 Hz, 1H) , 8.10 - 7.95 (m, 3H), 7.89 - 7.74 (m, 2H), 7.48 (d, J = 8.7 Hz, 1H), 7.21 - 7.02 (m, 2H), 3.81 (d, J = 8.3 Hz, 1H), 3.54 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.59, -115.62, -122.03, -122.15 F1233 ESIMS m/z 657 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 9.42 (s, 1H), 8.17 (td, J = 8.9, 5.9 Hz, 1H) , 7.95 - 7.83 (m, 3H), 7.78 (s, 1H), 7.72 (dd, J = 8.7, 2.6 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.14 (ddd, J = 11.2, 8.8, 2.8 Hz, 1H), 7.06 (ddd, J = 10.6, 8.7, 2 .2 Hz, 1H), 3.69 (d, J = 11.2 Hz, 1H), 3.34 (d, J = 11.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-115.72, -115.74, -122.07, -122.21 F1234 ESIMS m/z 640.1 (M+) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.72 (s, 1H), 10.50 (s, 1H), 8.04 (t, J = 8, 1 Hz, 1H), 7.91 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.61 - 7.37 (m, 4H), 6.46 (t, J = 53.5 Hz, 1H), 3.59 (d, J = 8 .4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.16 - -117.62 (m), -119.86,
-120.76 (d, J = 12.7 Hz), -125.38 - -126.07 (m) F1235 242-245 ESIMS m/z 561 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.50 (s, 1H), 8.00 (d, J = 2.5 Hz, 1H), 7.81 - 7.66 (m, 4H), 7.53 - 7.40 (m, 2H), 7.21 (t, J = 8.8 Hz, 2H), 3.81 (s, 3H), 3, 58 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.26, -118.46 F1236 216-218 ESIMS m/z 574 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.29 (s, 1H), 8.06 (d, J = 2.6 Hz, 1H), 7.95 - 7.80 (m, 2H), 7.71 (dd, J = 7.4, 1.8 Hz, 1H), 7.54 - 7.33 (m, 3H), 7.20 - 7.10 (m, 1H), 3.87 (s, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.58 (d, J = 5.6 Hz), -117.27,
-119.04 (d, J = 5.7 Hz) F1237 208-210 ESIMS m/z 791 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.38 (s, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.88 - 7.76 (m, 2H), 7.75 - 7.67 (m, 1H), 7.55 - 7.39 (m, 2H), 7.34 - 7.23 (m, 1H), 3 .86 (s, 3H), 3.58 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 1.41 (s, 17H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -123.73, -127.72 F1238 ESIMS m/z 711.1 ([M+Na] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.72 (s, 1H), 10.50 (s, 1H), 8.04 (t, J = 8, 1 Hz, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.80 (s, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H) , 7.55 (t, J = 9.9 Hz, 2H), 6.47 (t, J = 53.5 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3 .55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.80 (td, J = 9.9, 9.0, 5.3 Hz), -120.75 (ddd, J = 10.3, 8.1, 5.2 Hz), -125.61 , -125.75 F1239 134-138 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₃ H ₂₉ Cl ₄ F ₄ N ₃ O ₆ , 779.0747; found, 779.0744 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.14 (s, 1H), 10.61 (s, 1H), 7.89 (dd, J = 11.3, 2.4 Hz, 1H) , 7.81 - 7.69 (m, 2H), 7.67 (dd, J = 2.4, 1.2 Hz, 1H), 7.51 - 7.43 (m, 2H), 7.29 (td, J = 9.2, 1.7 Hz, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.4 Hz, 1H), 1 .41(s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.56, -117.22, -123.24, -126.64 F1240 ESIMS m/z 656.2 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.72 (s, 1H), 10.49 (s, 1H), 8.04 (t, J = 8, 1 Hz, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.79 - 7.74 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H) , 7.54 (dd, J = 12.7, 9.5 Hz, 2H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 6.46 (t, J = 53 .5 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.86, -120.78, -125.62 (d, J = 53.5 Hz) F1241 ESIMS m/z 770.0 ([M+DMSO+Cl] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.72 (s, 1H), 10.51 (s, 1H), 8.04 (t, J = 8, 0 Hz, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.7, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.59 - 7.50 (m, 4H), 6.47 (t, J = 53.5 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.78 (dd, J = 8.2, 5.4 Hz),
-120.74 (dt, J = 10.5, 5.3 Hz),
-125.68 (d, J = 53.5 Hz) F1242 ESIMS m/z 769.6 ([M+Cl+DMSO-d ₆ ] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.72 (s, 1H), 10.49 (s, 1H), 8.04 (t, J = 8, 1 Hz, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.76 (dt, J = 4.8, 2.6 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.54 (dd, J = 13.1, 9.5 Hz, 2H), 7.46 - 7.36 (m, 1H), 6.46 (t, J = 53 .5 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.89, -120.79, -125.61 (d, J = 53.4 Hz) F1243 ESIMS m/z 690.2 ([M] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.20 (s, 1H), 10.95 (s, 1H), 10.53 (s, 1H), 7.96 - 7.87 (m, 2H), 7.76 (dt, J = 6.2, 3.2 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8 .5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-62.85, -118.49, -119.27 F1244 ESIMS m/z 709.1 ([M+Na] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.57 (s, 1H), 10.50 (s, 1H), 8.16 (t, J = 8, 0 Hz, 1H), 7.91 (d, J = 2.6 Hz, 1H), 7.80 - 7.74 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H) , 7.56 (d, J = 8.7 Hz, 2H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 6.76 (s, 1H), 3.61 ( d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.17, -122.11 F1245 ESIMS m/z 693.1 ([M+H ₃ O] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.36 (s, 1H), 10.95 (s, 1H), 10.54 (s, 1H), 7.96 - 7.83 (m, 2H), 7.76 (td, J = 4.6, 2.5 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.65 - 7.50 (m, 2H ), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz , 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.86, -118.45, -119.27 F1246 ESIMS m/z 639.2 ([M+H ₃ O] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.40 (s, 1H), 9.79 (s, 1H), 8.13 (t, J = 8, 2 Hz, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7.76 (d, J = 2.1 Hz, 2H), 7.69 (d, J = 8.3 Hz , 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.48 - 7.37 (m, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3 .46 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.10 - -122.34 (m), -122.80 (q, J = 8.3, 6.2 Hz) F1247 ESIMS m/z 564.1 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.14 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.81 - 7.68 (m, 2H), 7.53 (d, J = 8.8 Hz, 1H), 7.51 - 7.40 (m, 1H), 7.13 (q, J = 11.2 , 10.0 Hz, 2H), 5.11 (s, 2H), 3.59 (d, J = 8.5 Hz, 1H), 3.57 (s, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -134.18, -135.43 (d, J = 8.2 Hz) F1248 ESIMS m/z 690 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.96 (s, 1H), 10.54 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 6.1, 2.4 Hz, 3H), 7.69 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.32 (t, J = 9.4 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.03, -121.26, -124.53 F1249 ESIMS m/z 670 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.63 (s, 1H), 10.49 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.79 - 7.66 (m, 4H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.5, 2.0 Hz, 1H), 7.27 (t, J = 9.2 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 1.88 (t, J = 19.6 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-97.13, -121.01, -124.48 F1250 ESIMS m/z 580.1 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.14 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 9.5, 2.3 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7 .43 (dd, J = 8.7, 2.1 Hz, 1H), 7.18 - 7.07 (m, 2H), 3.60 (d, J = 8.5 Hz, 1H), 3, 57 (s, 1H), 3.46 (d, J = 8.5 Hz, 1H), 3.30 (d, J = 2.1 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-134.18 (t, J = 10.4 Hz), -135.45 (dd, J = 10.3, 7.9 Hz) F1251 ESIMS m/z 724 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.61 (s, 1H), 10.96 (s, 1H), 10.55 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.76 (dt, J = 5.3, 3.2 Hz, 3H), 7.69 (d, J = 8.3 Hz, 1H), 7.56 (d, J = 8.9 Hz, 1H), 7.43 (dd, J = 8.5, 2.0 Hz, 1H), 7.33 (t, J = 9.2 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-82.43, -121.41, -121.68, -124.67 F1252 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.59 (s, 1H), 10.50 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 - 7.64 (m, 4H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.26 (t, J = 9.2 Hz, 1H), 6.77 (s, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 ( d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.96, -124.43 F1253 ESIMS m/z 684 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.49 (s, 1H), 10.24 (s, 1H), 8.02 (d, J = 7, 6 Hz, 2H), 7.94 (d, J = 2.5 Hz, 1H), 7.79 - 7.61 (m, 6H), 7.56 (dt, J = 7.6, 3.2 Hz, 3H), 7.43 (dd, J = 8.4, 2.0 Hz, 1H), 7.26 (t, J = 9.2 Hz, 1H), 3.61 (d, J = 8 .4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.48 (d, J = 3.4 Hz), - F1254 ESIMS m/z 650 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.71 (s, 1H), 7.92 (d, J = 2, 5 Hz, 1H), 7.75 (dd, J = 8.2, 2.3 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.64 (dd, J = 8.7, 5.8 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.5, 2.0 Hz, 1H), 7, 20 (t, J = 9.1 Hz, 1H), 4.07 (s, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 3.40 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.58 (d, J = 3.4 Hz), -124.46 (d, J = 3.5 Hz) F1255 196-200 HRMS-ESI (m/z)[M+H] ⁺
calculated for C ₂₃ H ₁₃ Cl ₄ F ₄ N ₃ O ₂ , 578.9698; found, 578.9695 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.28 (s, 1H), 7.88 (dd, J = 11.3, 2.3 Hz, 1H) , 7.72 (dd, J = 7.3, 1.7 Hz, 1H), 7.67 - 7.59 (m, 1H), 7.54 - 7.40 (m, 2H), 6.96 - 6.88 (m, 1H), 6.82 (td, J = 8.4, 5.6 Hz, 1H), 5.32 (s, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.72, -117.23, -133.72,
-133.76, -138.28, -138.31 F1256 135-140 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₅ H ₁₃ Cl ₄ F ₆ N ₃ O ₃ , 656.9615; found, 656.9614 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.80 (s, 1H), 10.62 (s, 1H), 7.89 (dd, J = 11, 2, 2.3 Hz, 1H), 7.74 (ddt, J = 9.1, 7.0, 3.6 Hz, 2H), 7.68 (d, J = 2.2 Hz, 1H), 7.51 - 7.43 (m, 2H), 7.29 (t, J = 9.2 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3.61 (d , J = 8.4 Hz, 1H), 3.45 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.59, -117.22, -120.43,
-120.44, -124.34, -124.34,
-125.81 F1257 ESIMS m/z 572 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 8.44 (d, J = 2.6 Hz, 1H), 7.97 (dd, J = 8.8, 2.7 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 3.2 Hz, 4H), 6.81 (s, 1H), 6 .61 (s, 1H), 4.38 (s, 2H), 3.68 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.4 Hz, 1H), 2 .12 (d, J = 7.5 Hz, 6H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 163.70, 162.60, 144.34, 140.32, 137.95, 137.39, 134.71, 131.52, 130.59, 127 .85, 127.45, 127.36, 123.60, 122.95, 121.80, 120.17, 116.15, 61.91, 39.26, 37.54, 16.26, 15.37 F1258 ESIMS m/z 720 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.95 (s, 1H), 9.57 (s, 1H), 9.00 (dd, J = 9, 6, 4.9 Hz, 2H), 8.30 - 8.14 (m, 2H), 8.06 (d, J = 2.5 Hz, 1H), 7.91 - 7.76 (m, 3H ), 7.48 (t, J = 9.3 Hz, 2H), 7.23 (td, J = 9.3, 1.9 Hz, 1H), 3.72 (d, J = 8.3 Hz , 1H), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.86, -68.57, -117.64, -122.86, -128.20 F1259 ESIMS m/z 672 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.27 (s, 1H), 7.98 (dt, J = 21.8, 1.6 Hz, 3H) , 7.87 - 7.77 (m, 2H), 7.47 (d, J = 8.7 Hz, 1H), 7.37 (td, J = 8.6, 5.6 Hz, 1H), 6.89 (td, J = 10.3, 9.8, 2.0 Hz, 1H), 4.77 (d, J = 8.5 Hz, 2H), 3.81 (d, J = 8, 3 Hz, 1H), 3.53 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-137.20, -144.21. F1260 ESIMS m/z 672 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 9.23 (s, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.90 - 7.76 (m, 3H), 7.73 (dd, J = 8.8, 2.6 Hz, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.35 ( td, J = 8.6, 5.8 Hz, 1H), 6.93 - 6.83 (m, 1H), 4.75 (d, J = 8.6 Hz, 2H), 3.69 - 3 .65 (m, 1H), 3.34 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-137.32, -144.22 F1261 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.99 (s, 1H), 10.94 (s, 1H), 10.15 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.76 (td, J = 4.7, 2.7 Hz, 2H), 7.70 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.4, 2.2 Hz, 2H), 7.35 (d, J = 9.5 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.85, -111.18, -112.79 F1262 ESIMS m/z 622 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 9.74 (s, 1H), 9.43 (s, 1H), 8.00 (d, J = 2, 6 Hz, 1H), 7.82 - 7.74 (m, 2H), 7.70 (d, J = 8.3 Hz, 1H), 7.58 (t, J = 9.4 Hz, 2H) , 7.47 - 7.40 (m, 1H), 7.16 (t, J = 9.3 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.48 ( d, J = 8.5 Hz, 1H), 2.11 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-111.33, -113.53 F1263 ESIMS m/z 690 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.52 (s, 1H), 9.24 (s, 1H), 8.14 (td, J = 8, 8, 5.7 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.82 (ddd, J = 11.6, 6.6, 1.7 Hz, 3H), 7.53 - 7.43 (m, 2H), 7.15 (td, J = 9.3, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3 .43 (d, J = 8.3 Hz, 1H), 1.71 - 1.59 (m, 4H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -117.58, -123.21, -128.83 F1264 ESIMS m/z 665 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.49 (s, 1H), 9.16 (s, 1H), 8.10 - 7.97 (m, 2H), 7.87 - 7.75 (m, 3H), 7.48 (dd, J = 10.3, 8.5 Hz, 2H), 7.09 (td, J = 9.3, 1, 9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 1.92 (dt, J = 8.8, 4.0 Hz, 1H), 0.96 - 0.79 (m, 4H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.80, -117.52, -123.12, -128.66 F1265 ESIMS m/z 623 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.72 (s, 1H), 8.51 - 8.41 (m, 2H), 7.89 - 7.83 (m, 2H), 7.41 ( d, J = 8.5 Hz, 1H), 7.34 (t, J = 1.9 Hz, 1H), 7.16 (d, J = 1.2 Hz, 2H), 7.00 (td, J = 9.1, 1.7 Hz, 1H), 3.97 (s, 3H), 3.53 (d, J = 8.1 Hz, 1H), 2.87 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-113.75, -125.08 F1266 ESIMS m/z 680 ([MC ₅ O ₂ H ₉ +H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.06 (s, 1H), 10.99 (s, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.77 (dd, J = 8.9, 2.5 Hz, 2H), 7.70 (d, J = 8.3 Hz, 1H), 7.58 (dd, J = 15.1, 9.4 Hz, 3H), 7.44 (dd, J = 8.6, 2.1 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.48 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H). F1268 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.79 (s, 1H), 10.50 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.79 - 7.66 (m, 2H), 7.63 (t, J = 1.9 Hz, 1H), 7.59 - 7.52 (m, 3H), 7, 27 (t, J = 9.3 Hz, 1H), 6.53 (t, J = 53.3 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.52 ( d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.71, -124.30, -125.70 F1269 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.79 (s, 1H), 10.51 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.82 - 7.66 (m, 3H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7, 28 (td, J = 9.2, 1.8 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.66 (d, J = 2.7 Hz), -124.22 (d, J = 2.8 Hz), -125.80 F1270 ESIMS m/z 642 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.79 (s, 1H), 10.51 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.82 - 7.66 (m, 3H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7, 28 (td, J = 9.2, 1.8 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -120.66 (d, J = 2.6 Hz),
-124.22 (d, J = 2.7 Hz), -125.80 F1271 ESIMS m/z 672 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ rotary isomers 10.97 (s, 1H), 10.64 (s, 0.65H), 10.55 (s, 0.35H), 7.95 ( q, J = 4.4, 3.1 Hz, 2H), 7.86 - 7.71 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.56 (d , J = 8.8 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.41 - 7.28 (m, 1H), 7.04 (t, J = 52.2 Hz, 0.35H), 6.34 (t, J = 51.9 Hz, 0.65H), 3.65 - 3.55 (m, 1H), 3.50 - 3.44 (m, 1H), 3.41 (s, 1H), 3.24 (s, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.12 (d, J = 7.3 Hz), -123.13 (d, J = 3.4 Hz), -124.26 (dq, J = 5.8, 2.8 Hz), - 125.56 (d, J = 9.0 Hz), -126.21 (d, J = 3.5 Hz),
-126.48 F1272 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.05 (d, J = 17.2 Hz, 2H), 8.04 (d, J = 2.6 Hz , 1H), 7.80 - 7.72 (m, 2H), 7.70 (d, J = 8.3 Hz, 1H), 7.57 (d, J = 8.8 Hz, 3H), 7 .43 (dd, J = 8.6, 2.1 Hz, 1H), 7.32 (s, 1H), 6.78 (s, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-110.53, -113.38 F1273 ESIMS m/z 748 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.48 (s, 1H), 9.26 (s, 1H), 8.09 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 9.8 , 5.2 Hz, 2H), 7.13 (td, J = 9.3, 1.9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d , J = 8.3 Hz, 1H), 2.24 (d, J = 7.6 Hz, 1H), 1.77 (s, 3H), 1.63 - 1.56 (m, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -117.58, -122.69, -128.21 F1274 ESIMS m/z 681 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.42 (s, 1H), 8.48 (s, 1H), 8.11 - 7.99 (m, 2H), 7.83 (td, J = 8.8, 7.6, 2.5 Hz, 3H), 7.54 - 7.44 (m, 2H), 7.10 (td, J = 9, 2, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 1.33 (s, 9H) ;
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.89, -117.63, -123.54, -129.11 F1275 ESIMS m/z 701 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.54 (s, 1H), 9.42 (s, 1H), 8.12 - 7.99 (m, 2H), 7.81 (ddd, J = 13.9, 7.9, 2.4 Hz, 3H), 7.51 - 7.41 (m, 2H), 7.12 (t, J = 9, 3 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.93 (ddd, J = 13.5, 10.9, 7.8 Hz, 1H), 2.11 (dq, J = 13.8, 7.5 Hz, 1H), 1.92 (dq, J = 18.5, 11.4, 8, 3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.80, -117.43, -122.83,
-126.20, -126.60, -128.28,
-141.53, -141.93 F1276 ESIMS m/z 754 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (d, J = 19.8 Hz, 2H), 9.57 (s, 1H), 8.27 - 8.16 (m, 1H) , 8.05 (d, J = 2.6 Hz, 1H), 7.83 (td, J = 8.7, 8.0, 2.7 Hz, 3H), 7.49 (t, J = 9 .7 Hz, 2H), 7.25 (td, J = 9.3, 2.0 Hz, 1H), 3.76 - 3.68 (m, 1H), 3.44 (d, J = 8, 3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.90, -117.65, -123.50, -128.67 F1277 ESIMS m/z 753 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.67 (s, 1H), 8.38 (td, J = 9.0, 5.6 Hz, 1H) , 8.06 (d, J = 2.6 Hz, 1H), 7.83 (ddd, J = 8.7, 5.2, 2.6 Hz, 3H), 7.54 - 7.43 (m , 2H), 7.33 (td, J = 9.2, 2.0 Hz, 1H), 3.76 - 3.68 (m, 1H), 3.55 (s, 6H), 3.43 ( d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -117.54, -117.61,
-121.02, -126.00, -126.11 F1278 135-141 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₃ F ₃ N ₂ O ₂ , 526.0229; found, 526.0229 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.95 (s, 1H), 10.53 (s, 1H), 7.81 - 7.65 (m, 4H), 7.57 - 7, 38 (m, 3H), 7.21 (t, J = 8.9 Hz, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.09 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-114.07, -117.27, -118.58 F1279 104-112 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₅ Cl ₃ F ₄ N ₂ O ₂ , 544.0135; found, 544.0129 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.96 (s, 1H), 10.28 (s, 1H), 7.82 - 7.62 (m, 3H), 7.58 - 7, 42 (m, 3H), 7.38 (ddd, J = 10.6, 9.1, 2.8 Hz, 1H), 7.19 - 7.07 (m, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.4 Hz, 1H), 2.26 (d, J = 2.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.03, -113.05, -114.10,
-116.77, -116.79, -117.28 F1280 171-175 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₄ H ₃₂ Cl ₃ F ₄ N ₃ O ₆ , 759.1280; found, 759,1293 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.96 (s, 1H), 10.39 (s, 1H), 7.79 - 7.63 (m, 3H), 7.59 - 7, 53 (m, 1H), 7.53 - 7.41 (m, 2H), 7.27 (td, J = 9.2, 1.7 Hz, 1H), 3.58 (d, J = 8, 4 Hz, 1H), 3.43 (d, J = 8.4 Hz, 1H), 2.26 (d, J = 2.0 Hz, 3H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-114.03, -117.28, -123.31,
-126.21, -126.21 F1281 120-130 dets (thin film) 3262 (w), 1711 (m), 1672 (s), 1611 (w), 1587 (m), 1535 (s), 1507 (s), 1454 (m), 1408 (m) HRMS-ESI (m/z)[M+H] ⁺
calculated for C ₂₅ H ₁₆ Cl ₃ F ₄ IN ₃ O ₃ , 715.9207; found, 715.9192 ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.81 (br s, 1H), 10.50 (s, 1H), 7.93 (d, J = 2 .5 Hz, 1H), 7.64-7.82 (m, 4H), 7.56 (d, J = 8.8 Hz, 1H), 7.44 (br d, J = 7.8 Hz, 1H), 7.18-7.31 (m, 2H), 6.53 (t, J = 53 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 3.40 ( d, J = 8.5 Hz, 1H) F1282 132-138 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₃ H ₂₉ Cl ₅ F ₃ N ₃ O ₆ , 779.0452; found, 779.0450 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.61 (s, 1H), 7.89 (dd, J = 11.3, 2.4 Hz, 1H) , 7.80 - 7.73 (m, 2H), 7.70 (d, J = 8.4 Hz, 1H), 7.67 (dd, J = 2.4, 1.2 Hz, 1H), 7.44 (dd, J = 8.7, 2.1 Hz, 1H), 7.29 (td, J = 9.2, 1.7 Hz, 1H), 3.62 (d, J = 8, 4 Hz, 1H), 3.48 (d, J = 8.5 Hz, 1H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.56, -123.24, -126.64 F1283 129-135 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₃₄ H ₂₉ Cl ₃ F ₇ N ₃ O ₆ , 813.1010; found, 813,1002 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.16 (s, 1H), 10.61 (s, 1H), 7.94 - 7.72 (m, 4H), 7.67 (dd, J = 2.4, 1.2 Hz, 1H), 7.59 (dd, J = 10.6, 8.7 Hz, 1H), 7.29 (td, J = 9.3, 1.8 Hz , 1H), 3.71 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -112.55, -116.83, -116.86, -116.89, -116.93,
-123.24, -126.65 F1284 126-131 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₅ F ₃ N ₃ O ₂ , 594.9402; found, 594.9399 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.28 (s, 1H), 7.87 (dd, J = 11.3, 2.4 Hz, 1H) , 7.76 (d, J = 2.1 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.63 (dd, J = 2.4, 1.2 Hz, 1H), 7.44 (dd, J = 8.4, 2.1 Hz, 1H), 6.92 (ddd, J = 10.6, 9.0, 1.8 Hz, 1H), 6.82 (td, J = 8.4, 5.5 Hz, 1H), 5.32 (s, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.71, -133.72, -133.76,
-138.28, -138.32 F1285 113-121 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₃ Cl ₃ F ₇ N ₃ O ₂ , 612.9962; found, 612.9962 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.14 (s, 1H), 10.28 (s, 1H), 7.91 - 7.81 (m, 3H), 7.67 - 7, 54 (m, 2H), 6.92 (ddd, J = 10.6, 8.9, 1.7 Hz, 1H), 6.82 (td, J = 8.4, 5.6 Hz, 1H) , 5.32 (s, 2H), 3.71 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -112.71, -116.83, -116.86, -116.90, -116.93,
-133.72, -133.76, -138.29,
-138.32 F1286 110-120 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₄ H ₁₆ Cl ₃ F ₄ N ₃ O ₂ , 559.0244; found, 559.0243 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.95 (s, 1H), 10.08 (s, 1H), 7.77 - 7.64 (m, 2H), 7.56 - 7, 41 (m, 3H), 6.91 (ddd, J = 10.6, 8.8, 1.9 Hz, 1H), 6.73 (td, J = 8.5, 5.6 Hz, 1H) , 5.31 (s, 2H), 3.59 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 2.26 (d, J = 1.9 Hz, 3H);
d -114.21, -117.29, -133.73, -133.77, -137.66, -137.70 F1287 137-145 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₅ H ₁₃ Cl ₅ F ₅ N ₃ O ₃ , 672.9320; found, 672.9315 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.81 (s, 1H), 10.62 (s, 1H), 7.89 (dd, J = 11, 3, 2.4 Hz, 1H), 7.81 - 7.66 (m, 4H), 7.44 (dd, J = 8.5, 2.1 Hz, 1H), 7.30 (td, J = 9.2, 1.8 Hz, 1H), 6.56 (t, J = 53.2 Hz, 1H), 3.63 (d, J = 8.4 Hz, 1H), 3.48 (d , J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.58, -120.43, -120.44,
-124.34, -124.35, -125.81 F1288 134-141 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₅ H ₁₂ Cl ₅ F ₆ N ₃ O ₃ , 690.9225; found, 690.9217 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.58 (s, 1H), 11.16 (s, 1H), 10.67 (s, 1H), 7.89 (dd, J = 11, 3, 2.4 Hz, 1H), 7.85 - 7.75 (m, 2H), 7.74 - 7.66 (m, 2H), 7.44 (dd, J = 8.4, 2, 1 Hz, 1H), 7.35 (td, J = 9.2, 1.8 Hz, 1H), 3.63 (d, J = 8.4 Hz, 1H), 3.49 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.83, -112.55, -120.82,
-120.82, -124.53 F1289 116-123 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₆ H ₁₃ Cl ₃ F ₉ N ₃ O ₃ , 680.9879; found, 680.9874 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.16 (s, 1H), 10.81 (s, 1H), 10.63 (s, 1H), 7.94 - 7.81 (m, 3H), 7.76 (td, J = 8.8, 5.7 Hz, 1H), 7.69 (dd, J = 2.4, 1.3 Hz, 1H), 7.60 (dd, J = 10.6, 8.7 Hz, 1H), 7.30 (td, J = 9.3, 1.8 Hz, 1H), 6.56 (t, J = 53.1 Hz, 1H), 3 .72 (d, J = 8.4 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -112.59, -116.83, -116.87, -116.90, -116.93,
-120.44, -120.44, -124.34,
-124.35, -125.81 F1290 132-138 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₆ H ₁₂ Cl ₃ F ₁₀ N ₃ O ₃ , 708.9785; found, 708.9782 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.58 (s, 1H), 11.16 (s, 1H), 10.67 (s, 1H), 7.96 - 7.76 (m, 4H), 7.69 (dd, J = 2.4, 1.2 Hz, 1H), 7.60 (dd, J = 10.7, 8.6 Hz, 1H), 7.35 (td, J = 9.2, 1.8 Hz, 1H), 3.71 (d, J = 8.4 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.94, -73.83, -112.55,
-116.83, -116.87, -116.90,
-116.93, -120.82, -120.83,
-124.53, -124.54 F1291 131-137 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₅ H ₁₂ Cl ₄ F ₇ N ₃ O ₃ , 674.9521; found, 674.9516 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.58 (s, 1H), 11.15 (s, 1H), 10.67 (s, 1H), 7.89 (dd, J = 11, 3, 2.4 Hz, 1H), 7.80 (td, J = 8.7, 5.7 Hz, 1H), 7.75 - 7.67 (m, 2H), 7.52 - 7.44 (m, 2H), 7.35 (td, J = 9.3, 1.8 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.83, -112.56, -117.23,
-120.82, -124.53 F1292 ESIMS m/z 796 ([MH] ^- ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.99 (bs, 1H), 8.37 - 8.25 (m, 2H), 7.93 (dd, J = 10.4, 2.5 Hz, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.35 (d, J = 2.1 Hz, 1H), 7.17 (d, J = 1.9 Hz, 2H) , 7.05 - 6.95 (m, 1H), 3.54 (d, J = 8.1 Hz, 1H), 2.86 (d, J = 8.1 Hz, 1H), 1.45 ( s, 18H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.95, -122.51, -132.96 F1293 (thin film) 3272 (w), 1669 (m), 1608 (w), 1589 (w), 1540 (m), 1507 (m), 1474 (m) HRMS-ESI (m/z)[M+H] ⁺
calculated for C ₂₅ H ₁₆ Cl ₃ F ₉ N ₃ O ₃ S, 715.9803; found, 715.9804 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.78 (br s, 1H), 10.50 (s, 1H), 7.88-8.02 (m , 3H), 7.64-7.80 (m, 4H), 7.56 (d, J = 8.8 Hz, 1H), 7.27 (t, J = 8.8 Hz, 1H), 6 .53 (t, J = 53 Hz, 1H), 3.74 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F1294 ESIMS m/z 830 ([MH] ^- ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.97 (s, 1H), 8.36 - 8.28 (m, 2H), 7.93 (dd, J = 10.4, 2.5 Hz, 1H), 7.64 (d, J = 2.5 Hz, 1H), 7.31 (d, J = 0.8 Hz, 2H), 7.06 - 6.96 (m, 1H), 3, 52 (d, J = 8.2 Hz, 1H), 2.86 (d, J = 8.1 Hz, 1H), 1.45 (s, 9H), 1.45 (s, 9H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.89, -122.52, -132.94 F1295 ESIMS m/z 737 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.47 (s, 1H), 8.76 (s, 1H), 8.26 - 8.10 (m, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.92 - 7.77 (m, 5H), 7.74 - 7.64 (m, 1H), 7.62 - 7 .53 (m, 2H), 7.49 (dd, J = 9.5, 7.5 Hz, 2H), 7.08 (td, J = 9.2, 2.0 Hz, 1H), 3, 72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.89, -117.63, -123.01, -128.45 F1296 ESIMS m/z 732 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.26 (s, 1H), 8.30 - 8.12 (m, 2H), 8.00 (d, J = 2.6 Hz, 1H), 7.82 (ddd, J = 16.9, 7.7, 2.5 Hz, 3H), 7.68 (d, J = 8.4 Hz, 2H), 7.48 (t, J = 10.1 Hz, 3H), 6.90 (ddd, J = 11.5, 9.1, 2.1 Hz, 1H), 5.56 (s, 1H), 4 .71 (d, J = 7.3 Hz, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.89, -117.64, -133.36, -140.76 F1297 ESIMS m/z 705 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.48 (s, 1H), 8.89 (s, 1H), 8.09 - 7.97 (m, 2H), 7.81 (ddd, J = 11.5, 7.3, 2.4 Hz, 3H), 7.47 (t, J = 9.3 Hz, 2H), 7.08 (td, J = 9.2, 1.9 Hz, 1H), 5.69 (s, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz , 1H), 2.83 - 2.70 (m, 1H), 2.41 - 2.17 (m, 2H), 2.19 - 1.94 (m, 4H), 1.81 - 1.65 (m, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.82, -117.52, -123.10, -128.61 F1298 ESIMS m/z 729 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.90 (s, 1H), 9.60 (s, 1H), 8.28 - 8.14 (m, 3H), 8.06 (d, J = 2.7 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.80 - 7.71 (m, 1H), 7.66 - 7 .56 (m, 2H), 7.47 (dd, J = 11.0, 8.4 Hz, 2H), 7.23 (td, J = 9.2, 1.9 Hz, 1H), 3, 72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.83, -117.52, -122.50, -128.11 F1299 ESIMS m/z 717 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.52 (s, 1H), 9.40 (s, 1H), 8.11 (td, J = 8, 7, 5.5 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.48 (dd, J = 8.7 , 3.4 Hz, 2H), 7.15 (td, J = 9.2, 1.9 Hz, 1H), 4.35 (s, 2H), 3.75 - 3.68 (m, 1H) , 3.43 (d, J = 8.3 Hz, 1H), 3.18 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.82, -117.55, -122.52, -127.87 F1300 ESIMS m/z 691 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.56 (s, 1H), 9.35 (s, 1H), 8.13 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.76 (m, 4H), 7.47 (dt, J = 8.4 , 5.1 Hz, 2H), 7.32 - 7.20 (m, 1H), 7.25 - 7.11 (m, 1H), 6.65 (ddd, J = 20.0, 3.5 , 1.8 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.83, -117.53, -122.76, -128.41 F1301 ESIMS m/z 724 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (d, J = 13.2 Hz, 2H), 9.60 (s, 1H), 8.20 (td, J = 8.8, 5.7 Hz, 1H), 8.03 (dd, J = 14.9, 2.6 Hz, 1H), 7.91 - 7.75 (m, 3H), 7.47 (td, J = 8 .7, 1.7 Hz, 2H), 7.23 (td, J = 9.3, 2.0 Hz, 1H), 6.65 (tt, J = 52.1, 5.4 Hz, 1H) , 3.72 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -117.50, -123.15,
-125.60, -128.43, -140.20 F1302 ESIMS m/z 721 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.53 (s, 1H), 9.29 (s, 1H), 8.10 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.76 (m, 4H), 7.48 (dt, J = 10.1 , 5.2 Hz, 2H), 7.15 (td, J = 9.2, 2.0 Hz, 1H), 6.94 - 6.87 (m, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.54 (d, J = 1.1 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.86, -117.62, -122.97, -128.51 F1303 ESIMS m/z 693 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.53 (s, 1H), 9.25 (s, 1H), 8.11 - 8.00 (m, 2H), 7.87 - 7.75 (m, 3H), 7.47 (dt, J = 8.4, 5.1 Hz, 2H), 7.12 (td, J = 9.2, 1, 9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.58 (td, J = 8.4, 4.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 3.43 - 3.26 (m, 4H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.81, -117.51, -123.05, -128.51 F1304 243-245 ESIMS m/z 623 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.76 (s, 1H), 8.15 (dd, J = 3.2.6.4 Hz, 1H) , 7.89 (d, J = 2.8 Hz, 1H), 7.74 (dd, J = 2.4, 8.8 Hz, 1H), 7.66 - 7.62 (m, 2H), 7.58 - 7.55 (m, 3H), 7.42 - 7.37 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H F1305 165-167 ESIMS m/z 621 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.27 (s, 1H), 7.94 (d, J = 2.4 Hz, 1H), 7.78 (dd, J = 2.4, 8.8 Hz, 1H), 7.70 (dd, J = 2.8, 8.4 Hz, 1H), 7.64 - 7.62 (m, 1H), 7.59 - 7.54 (m, 4H), 7.36 - 7.32 (m, 1H), 3.63 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H F1306 201-203 ESIMS m/z 621 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.49 (s, 1H), 7.90 (d, J = 1.6 Hz, 1H), 7.82 - 7.73 (m, 2H), 7.67 - 7.62 (m, 2H), 7.58 - 7.53 (m, 3H), 7.45 (d, J = 8.8 Hz, 1H ), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H) F1307 248-250 ESIMS m/z 640 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.56 (s, 1H), 7.93 (d, J = 2.4 Hz, 1H), 7.75 (dd, J = 2.4, 8.8 Hz, 2H), 7.64 - 7.55 (m, 4H), 7.38 - 7.33 (m, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F1308 165-167 ESIMS m/z 641 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.58 (s, 1H), 8.16 - 8.12 (m, 1H), 7.91 (d, J = 2.4 Hz, 1H), 7.74 (dd, J = 2.8, 8.8 Hz, 1H), 7.67 - 7.62 (m, 2H), 7.56 -7.55 (m, 3H), 3.62 (d, J = 8.8 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F1309 211-213 ESIMS m/z 641 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.35 (s, 1H), 7.94 (d, J = 2.4 Hz, 1H), 7.81 (dd, J = 2.4, 8.8 Hz, 1H), 7.78 - 7.46 (m, 6H), 3.64 (d, J = 8.4 Hz, 1H), 3.51 ( d, J = 8.8 Hz, 1H) F1311 128-130 ESIMS m/z 571 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.61 (s, 1H), 7.97 (dd, J = 2.4, 6.8 Hz, 1H) , 7.89 (d, J = 2.4 Hz, 1H), 7.74 (dd, J = 2.4, 8.8 Hz, 1H), 7.66 - 7.60 (m, 2H), 7.58 - 7.55 (m, 3H), 7.26 - 7.19 (m, 1H), 6.84 (dd, J = 11.2, 17.6 Hz, 1H), 5.82 ( d, J = 17.6 Hz, 1H), 5.46 (d, J = 11.2 Hz, 1H), 3.62 (d, J = 8.8 Hz, 1H), 3.52 (d, J = 8.0 Hz, 1H) F1312 191-193 ESIMS m/z 571 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.23 (s, 1H), 7.89 (d, J = 2.8 Hz, 1H), 7.76 (dd, J = 2.4, 8.8 Hz, 1H), 7.64 - 7.62 (m, 1H), 7.58 - 7.54 (m, 4H), 7.42 (dd, J = 6.4, 8.8 Hz, 1H), 7.21 - 7.18 (m, 1H), 6.98 - 6.90 (m, 1H), 5.94 (d, J = 17.6 Hz, 1H), 5.41 (d, J = 11.6 Hz, 1H), 3.63 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.4 Hz, 1H) F1313 102-104 ESIMS m/z 571 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.41 (s, 1H), 7.90 (d, J = 2.0 Hz, 1H), 7.84 - 7.73 (m, 2H), 7.66 - 7.60 (d, J = 2.0 Hz, 1H), 7.58 - 7.53 (m, 3H), 7.47 (d, J = 12.0 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 6.72 (dd, J = 10.8, 18.0 Hz, 1H), 5.90 (d , J = 17.6 Hz, 1H), 5.31 (d, J = 10.8 Hz, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F1314 107-109 ESIMS m/z 589 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.40 (s, 1H), 7.92 (d, J = 2.4 Hz, 1H), 7.74 (dd, J = 2.8, 8.8 Hz, 1H), 7.65 - 7.62 (m, 2H), 7.56 - 7.54 (m, 3H), 7.19 - 7.15 (m, 1H), 6.73 (dd, J = 11.6, 17.6 Hz, 1H), 6.00 (d, J = 18.0 Hz, 1H), 5.70 (d, J = 12.0 Hz, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F1315 99-101 ESIMS m/z 587 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.41 (s, 1H), 7.94 - 7.90 (m, 2H), 7.73 (dd, J = 8.4, 2.4 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.56 - 7.54 (m, 3H), 7.43 - 7.37 (m, 1H), 6.81 (dd, J = 11.2, 17.6 Hz, 1H), 5.87 (d, J = 17.6 Hz, 1H), 5.46 (d, J = 11.2 Hz, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H) F1316 199-201 ESIMS m/z 589 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.20 (s, 1H), 7.89 (dd, J = 2.4 Hz, 1H), 7.81 (dd, J = 2.4, 8.8 Hz, 1H), 7.64 - 7.62 (m, 1H), 7.60 - 7.56 (m, 3H), 7.50 (d, J = 10.0 Hz, 1H), 7.36 - 7.30 (m, 1H), 6.92 (dd, J = 11.2, 17.6 Hz, 1H), 6.04 (d, J = 17.6 Hz, 1H), 5.51 (d, J = 11.2 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8, 4 Hz, 1H) F1317 125-127 ESIMS m/z 589 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.78 (s, 1H), 7.91 (d, J = 2.4 Hz, 1H), 7.77 - 7.72 (m, 2H), 7.69 - 7.64 (m, 1H), 7.63 - 7.54 (m, 4H), 6.85 (dd, J = 11.2, 17, 6 Hz, 1H), 5.87 (d, J = 17.6 Hz, 1H), 5.56 (d, J = 11.2 Hz, 1H), 3.61 (d, J = 8.4 Hz , 1H), 3.51 (d, J = 8.4 Hz, 1H) F1318 114-116 ESIMS m/z 589 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.74 (s, 1H), 7.99 (dd, J = 2.4, 6.8 Hz, 1H) , 7.90 (d, J = 2.4 Hz, 1H), 7.82 - 7.72 (m, 2H), 7.64 - 7.54 (m, 4H), 7.38 - 7.33 (m, 1H), 5.36 - 5.22 (m, 2H), 3.61 (d, J = 8.8 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H) F1319 109-111 ESIMS m/z 589 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.30 (s, 1H), 7.86 (d, J = 2.4 Hz, 1H), 7.77 (dd, J = 2.4, 8.8 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.55 - 7.50 (m, 3H), 7.50-7.47 (m, 1H), 7.44 - 7.41 (m, 1H), 7.39 - 7.34 (m, 1H), 5.26 - 5.08 (m, 2H), 3.63 (d , J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F1320 153-155 ESIMS m/z 589 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.56 (s, 1H), 7.97 - 7.90 (m, 2H), 7.75 (dd, J = 2.4, 8.8 Hz, 1H), 7.62 - 7.60 (m, 2H), 7.57 - 7.54 (m, 3H), 7.49 (d, J = 7, 6 Hz, 1H), 5.47 (dd, J = 4.0, 62.0 Hz, 1H), 5.01 (dd, J = 4.0, 18.8 Hz, 1H), 3.62 ( d, J = 9.2 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F1321 189-191 ESIMS m/z 607 ([M+H] ⁺ ) ^1H NMR (400 MHz, CD3OD) δ 8.00 - 7.94 (m, 2H), 7.74 (dd, J = 2.4, 8.8 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.45 - 7.44 (m, 1H), 7.38 - 7.30 (m, 2H), 7.14 - 7.10 (m, 1H), 5, 29 (dd, J = 3.6, 16.8 Hz, 1H), 5.00 (dd, J = 3.6, 44.4 Hz, 1H), 3.58 (d, J = 8.4 Hz , 1H), 3.24 (d, J = 8.4 Hz, 1H) F1322 133-135 ESIMS m/z 607 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.24 (s, 1H), 7.88 (d, J = 2.4 Hz, 1H), 7.80 (dd, J = 2.8, 8.8 Hz, 1H), 7.64 - 7.62 (m, 1H), 7.57 - 7.52 (m, 4H), 7.36 (d, J = 9.6 Hz, 1H), 5.35 - 5.19 (m, 2H), 3.64 (d, J = 8.8 Hz, 1H), 3.51 (d, J = 8.8 Hz , 1H) F1323 120-122 ESIMS m/z 607 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.92 (s, 1H), 10.90 (s, 1H), 7.94 - 7.89 (m, 2H), 7.76 - 7, 69 (m, 2H), 7.63 - 7.62 (m, 1H), 7.59 - 7.54 (m, 3H), 5.42 - 5.28 (m, 2H), 3.61 ( d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F1324 170-175 ESIMS m/z 598 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.37 (s, 1H), 9.35 (s, 1H), 7.94 (dd, J = 11.3, 2.4 Hz, 1H) , 7.69 (s, 1H), 7.51 (s, 3H), 7.36 (dt, J = 14.5, 6.8 Hz, 1H), 6.90 (t, J = 9.4 Hz, 1H), 4.81 (bs, 2H), 3.68 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-113.67, -113.69, -137.04,
-137.07, -137.10, -144.20,
-144.23, -144.34, -144.37 F1325 ESIMS m/z 632 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.41 (s, 1H), 9.34 (s, 1H), 7.93 (dd, J = 11.3, 2.5 Hz, 1H) , 7.72 (s, 2H), 7.70 (s, 1H), 7.36 (ddd, J = 14.4, 8.5, 5.7 Hz, 1H), 6.94 - 6.84 (m, 1H), 4.81 (bs, 2H), 3.68 (d, J = 8.3 Hz, 1H), 3.49 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-113.66, -113.67, -137.04,
-137.08, -137.11, -144.23,
-144.26, -144.37, -144.40 F1326 ESIMS m/z 696 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.48 (s, 1H), 9.52 (s, 1H), 8.71 - 8.61 (m, 1H), 8.13 (s, 1H), 7.96 (dd, J = 11.3, 2.5 Hz, 1H), 7.73 (s, 1H), 7.51 (s, 3H), 7.20 (t, J = 10 .4 Hz, 1H), 3.68 (d, J = 8.3 Hz, 1H), 3.47 (dd, J = 8.3, 1.4 Hz, 1H), 1.50 (s, 9H );
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-113.60, -113.62, -128.20,
-128.41, -128.46, -128.55,
-128.59 F1327 ESIMS m/z 730 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.55 (s, 1H), 9.51 (s, 1H), 8.71 - 8.61 (m, 1H), 8.13 (s, 1H), 7.96 (dd, J = 11.3, 2.4 Hz, 1H), 7.76 - 7.69 (m, 3H), 7.19 (t, J = 10.4 Hz, 1H ), 3.68 (d, J = 8.3 Hz, 1H), 3.51 (dd, J = 8.3, 2.3 Hz, 1H), 1.50 (s, 9H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-113.59, -113.61, -128.18,
-128.40, -128.44, -128.53,
-128.57 F1328 ESIMS m/z 696 ([MH] ^- ) ^1H NMR (400 MHz, _CDCl3 ) δ 9.58 (s, 1H), 9.10 (t, J = 8.2 Hz, 1H), 8.44 (s, 1H), 8.22 (d , J = 10.4 Hz, 1H), 7.63 (d, J = 2.2 Hz, 1H), 7.37 (d, J = 8.3 Hz, 1H), 7.26 (s, 1H ), 7.03 (dd, J = 8.2, 2.1 Hz, 1H), 6.93 (t, J = 10.1 Hz, 1H), 6.65 (d, J = 2.5 Hz , 1H), 3.47 (d, J = 8.2 Hz, 1H), 2.97 (d, J = 8.1 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.91, -130.61, -131.25 F1329 ESIMS m/z 712 ([MH] ^- ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.46 (s, 1H), 9.08 (t, J = 8.4 Hz, 1H), 8.40 (s, 1H), 8.20 (dd , J = 10.6, 2.4 Hz, 1H), 7.65 - 7.61 (m, 1H), 7.48 - 7.43 (m, 1H), 7.36 (m, 1H), 7.14 (t, J = 9.2 Hz, 1H), 6.92 (t, J = 10.2 Hz, 1H), 6.62 (d, J = 2.7 Hz, 1H), 3, 53 (d, J = 8.1 Hz, 1H), 3.00 (d, J = 8.1 Hz, 1H), 1.47 (s, 9H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-61.47 (d, J = 12.8 Hz), -108.86,
-114.94 (q, J = 12.6 Hz), -130.67, -131.25 F1330 ESIMS m/z 692 ([MH] ^- ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.43 (s, 1H), 8.39 - 8.28 (m, 2H), 7.94 (d, J = 10.2 Hz, 1H), 7 .83 (s, 1H), 7.57 (s, 1H), 7.36 (t, J = 1.9 Hz, 1H), 7.18 (d, J = 1.8 Hz, 2H), 7 .09 (t, J = 9.1 Hz, 1H), 3.56 (d, J = 8.1 Hz, 1H), 2.83 (d, J = 8.1 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-74.97, -108.42, -121.65, -129.33 F1331 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.79 (s, 1H), 9.57 (s, 1H), 8.17 (td, J = 8, 8, 5.5 Hz, 1H), 8.03 (d, J = 2.7 Hz, 1H), 7.81 (dd, J = 8.8, 2.7 Hz, 1H), 7.64 ( d, J = 6.3 Hz, 2H), 7.49 (d, J = 8.7 Hz, 1H), 7.20 (td, J = 9.3, 2.1 Hz, 1H), 6, 46 (t, J = 53.5 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-118.90, -123.11, -127.07,
-128.43. F1332 ESIMS m/z 694 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.40 (s, 1H), 10.21 (s, 1H), 9.61 (s, 1H), 8.21 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.64 ( d, J = 6.3 Hz, 2H), 7.49 (d, J = 8.8 Hz, 1H), 7.25 (td, J = 9.3, 2.0 Hz, 1H), 3, 65 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-75.82, -118.89, -123.31, -128.50 F1333 ESIMS m/z 674 ([MH] ^- ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.09 (s, 1H), 8.55 (s, 1H), 8.15 (td, J = 8.8, 5.7 Hz, 1H), 8 .04 (s, 1H), 7.82 (dd, J = 10.4, 2.5 Hz, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.34 (t, J = 1.9 Hz, 1H), 7.15 (dd, J = 1.9, 0.7 Hz, 2H), 7.02 (t, J = 9.0 Hz, 1H), 6.16 ( t, J = 53.8 Hz, 1H), 3.53 (d, J = 8.1 Hz, 1H), 2.87 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.67, -121.24, -125.66, -128.24 F1334 ESIMS m/z 726 ([MH] ^- ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.40 - 8.26 (m, 3H), 7.94 (d, J = 10.4 Hz, 1H), 7.76 (bs, 1H), 7 .61 (s, 1H), 7.32 (s, 2H), 7.10 (t, J = 9.0 Hz, 1H), 3.55 (d, J = 7.9 Hz, 1H), 2 .81 (d, J = 8.0 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-74.98, -108.36, -121.81, -129.55 F1335 ESIMS m/z 708 ([MH] ^- ) ^1H NMR (400 MHz, _CDCl3 ) δ 8.66 (s, 1H), 8.42 (s, 1H), 8.33 - 8.23 (m, 1H), 7.88 (dd, J= 10.3, 2.5 Hz, 1H), 7.81 (s, 1H), 7.55 (s, 1H), 7.31 (d, J = 0.7 Hz, 2H), 7.06 ( t, J = 9.0 Hz, 1H), 6.15 (t, J = 53.8 Hz, 1H), 3.53 (d, J = 8.0 Hz, 1H), 2.83 (d, J = 8.1 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.53, -121.83, -125.58,
-129.09 F1336 ESIMS m/z 598 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.44 (s, 1H), 9.31 (s, 1H), 7.94 (dd, J = 11.2, 2.4 Hz, 1H) , 7.76 - 7.66 (m, 2H), 7.51 (s, 3H), 6.99 (t, J = 10.7 Hz, 1H), 4.71 (bs, 2H), 3, 67 (d, J = 8.3 Hz, 1H), 3.48 (dd, J = 8.3, 2.0 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-113.74, -113.76, -137.08,
-137.11, -139.74, -139.76,
-139.77, -139.86, -139.89,
-139.90 F1337 ESIMS m/z 632 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.64 (s, 1H), 8.15 (s, 1H), 8.02 (dd, J = 10.4, 2.6 Hz, 1H), 7 .88 (dd, J = 9.2, 7.7 Hz, 1H), 7.57 (dd, J = 2.5, 1.4 Hz, 1H), 7.30 (s, 2H), 6, 87 (t, J = 10.3 Hz, 1H), 3.71 (s, 2H), 3.53 (d, J = 8.1 Hz, 1H), 2.82 (d, J = 8.1 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.49, -134.30, -139.55 F1338 ESIMS m/z 598 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.33 (s, 1H), 9.31 (s, 1H), 7.93 (dd, J = 11.3, 2.4 Hz, 1H) , 7.76 - 7.60 (m, 4H), 7.46 (ddd, J = 8.3, 2.1, 0.7 Hz, 1H), 6.99 (t, J = 10.7 Hz , 1H), 4.72 (ad, J = 9.3 Hz, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H );
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.51, -134.24, -139.43 F1339 ESIMS m/z 615 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.35 (s, 1H), 9.31 (s, 1H), 7.93 (dd, J = 11.3, 2.4 Hz, 1H) , 7.84 (dd, J = 7.0, 3.9 Hz, 2H), 7.75 - 7.66 (m, 2H), 7.49 (t, J = 9.9 Hz, 1H), 6.99 (t, J = 10.7 Hz, 1H), 4.72 (d, J = 9.4 Hz, 2H), 3.73 (d, J = 8.2 Hz, 1H), 3, 45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -61.45 (d, J = 12.8 Hz), -108.53, -114.43 (q, J = 12.7 Hz), -134.40 , -139.61 F1340 ESIMS m/z 694 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.48 (s, 1H), 10.26 (br s, 1H), 9.68 (s, 1H), 8.53 (td, J = 8 ,0, 5.0 Hz, 1H), 7.95 (dd, J = 11.2, 2.5 Hz, 1H), 7.74 (dd, J = 2.4, 1.4 Hz, 1H) , 7.51 (d, J = 0.7 Hz, 3H), 7.36 (t, J = 10.3 Hz, 1H), 3.67 (d, J = 8.3 Hz, 1H), 3 .48 (dd, J = 8.3, 1.2 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -75.53, -108.40, -125.82, -127.37 F1341 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.46 (s, 1H), 9.71 (s, 1H), 9.63 (s, 1H), 8.66 (q, J = 8, 0 Hz, 1H), 7.96 (dd, J = 11.3, 2.5 Hz, 1H), 7.75 - 7.72 (m, 1H), 7.51 (d, J = 0.7 Hz, 3H), 7.32 (t, J = 10.3 Hz, 1H), 6.42 (t, J = 53.7 Hz, 1H), 3.67 (d, J = 8.3 Hz, 1H), 3.48 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-108.45, -125.74, -126.86,
-127.99 F1342 ESIMS m/z 726
([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.45 (s, 1H), 10.25 (br s, 1H), 9.67 (s, 1H), 8.59 - 8.48 (m , 1H), 7.94 (dd, J = 11.3, 2.5 Hz, 1H), 7.76 - 7.68 (m, 3H), 7.36 (t, J = 10.2 Hz, 1H), 3.68 (d, J = 8.3 Hz, 1H), 3.50 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -75.51, -108.33, -125.78, -127.41 F1343 ESIMS m/z 708
([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.38 (s, 1H), 9.71 (s, 1H), 9.62 (s, 1H), 8.67 (s, 1H), 7 .95 (dd, J = 11.2, 2.5 Hz, 1H), 7.75 - 7.67 (m, 3H), 7.32 (t, J = 10.3 Hz, 1H), 6, 42 (t, J = 53.7 Hz, 1H), 3.68 (d, J = 8.3 Hz, 1H), 3.47 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone) δ
-113.53, -113.55, -124.28, -124.30, -124.31, -124.40, -124.41, -124.43, -124.56, -124.57, -124.68, -124.69, -127.21, -127.26 F1344 ESIMS m/z 694 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.37 (s, 1H), 11.15 (s, 1H), 10.65 (s, 1H), 7.95 (t, J = 8, 0 Hz, 1H), 7.89 (dd, J = 11.2, 2.4 Hz, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.66 (br s, 1H), 7.61 (t, J = 10.3 Hz, 1H), 7.44 (dd, J = 8.6, 2.1 Hz , 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.48 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO) δ -73.86, -112.62, -118.62, -119.01 F1345 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.74 (s, 1H), 10.61 (s, 1H), 8.07 (t, J = 8, 1 Hz, 1H), 7.89 (dd, J = 11.3, 2.3 Hz, 1H), 7.76 (d, J = 2.2 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 7.56 (t, J = 10.3 Hz, 1H), 7.44 (dd, J = 8.4, 2.0 Hz, 1H), 6.47 (t, J = 53.4 Hz, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.48 (d, J = 8.5 Hz, 1H) ;
¹⁹ F NMR (376 MHz, DMSO) δ
-112.61, -120.01, -120.53, -125.66 F1346 ESIMS m/z 710 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.38 (s, 1H), 11.16 (s, 1H), 10.65 (s, 1H), 7.95 (t, J = 8, 0 Hz, 1H), 7.94 - 7.84 (m, 2H), 7.88 - 7.79 (m, 1H), 7.66 (s, 1H), 7.59 (t, J = 9 .6 Hz, 2H), 3.71 (d, J = 8.2 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.7 Hz), -73.85,
-112.62, -116.88 (q, J = 12.6 Hz),
-118.61, -119.03 F1347 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.16 (s, 1H), 10.74 (s, 1H), 10.62 (s, 1H), 8.08 (t, J = 8, 1 Hz, 1H), 7.93 - 7.86 (m, 2H), 7.88 - 7.79 (m, 1H), 7.68 - 7.62 (m, 1H), 7.58 (aq , J = 10.4 Hz, 2H), 6.47 (t, J = 53.5 Hz, 1H), 3.71 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.5 Hz), -112.60,
-116.88 (q, J = 12.4 Hz), -120.03,
-120.54 (d, J = 5.2 Hz), -125.66 F1348 ESIMS m/z 764 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 8.81 (s, 1H), 8.35 (s, 1H), 8.05 - 7.87 (m, 1H), 7.84 - 7.71 (m, 1H), 7.56 - 7.37 (m, 6H), 7.37 - 7.21 (m, 3H), 6.61 - 6.42 ( m, 2H), 4.28 (s, 2H), 3.64 (d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H), 2.25 ( s, 3H), 1.48 (d, J = 1.6 Hz, 9H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.96, 162.42, 152.90, 147.39, 138.50, 138.44, 137.85, 137.80, 137.41, 136 .34, 134.70, 134.00, 133.83, 133.77, 130.19, 127.83, 127.66, 127.12, 126.76, 126.71, 125.18, 124.94 , 121.40, 119.82, 118.30, 118.03, 114.16, 110.28, 78.96, 63.58, 59.67, 47.06, 39.19, 37.51, 29 .55, 29.36, 29.17, 28.98, 28.79, 28.59, 28.40, 27.69, 19.63, 17.89 F1349 ESIMS m/z 663 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.88 (s, 1H), 8.05 - 7.83 (m, 2H), 7.44 (d, J = 2.6 Hz, 1H), 7 .36 - 7.20 (m, 4H), 7.18 - 7.03 (m, 3H), 6.73 - 6.53 (m, 2H), 6.51 - 6.31 (m, 2H) , 4.12 (dd, J = 14.4, 7.3 Hz, 3H), 3.90 - 3.54 (m, 2H), 3.53 - 3.37 (m, 1H), 2.86 (d, J = 8.3 Hz, 1H), 2.19 (s, 3H);
¹³ C NMR (101 MHz, CDCl ₃ ) δ 166.16, 163.11, 147.31, 145.64, 137.15, 136.41, 135.19, 134.97, 133.83, 130.81 , 128.88, 128.78, 128.25, 127.47, 126.58, 125.26, 124.13, 123.68, 121.31, 115.30, 114.50, 110.69, 77 .34, 77.02, 76.71, 61.67, 47.89, 39.15, 38.09, 18.52 F1350 ESIMS m/z 757 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.77 (s, 1H), 8.44 (s, 1H), 8.07 (q, J = 8.3 Hz, 1H), 7.82 (dd , J = 8.8, 2.6 Hz, 1H), 7.71 (d, J = 2.6 Hz, 1H), 7.52 - 7.44 (m, 2H), 7.36 (d, J = 8.7 Hz, 1H), 7.21 (t, J = 9.5 Hz, 1H), 7.09 - 6.94 (m, 1H), 6.82 (s, 1H), 3, 58 (d, J = 8.1 Hz, 1H), 3.52 - 3.43 (m, 2H), 2.93 (d, J = 8.1 Hz, 1H), 2.83 - 2.67 (m, 2H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-61.39, -65.97, -114.52, -122.09, -130.00 F1351 ESIMS m/z 722 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.61 (s, 1H), 9.53 (s, 1H), 8.15 (td, J = 8, 7, 5.6 Hz, 1H), 8.04 (d, J = 2.5 Hz, 1H), 7.83 (dd, J = 8.9, 6.3 Hz, 3H), 7.48 ( t, J = 9.0 Hz, 2H), 7.19 (td, J = 9.2, 2.0 Hz, 1H), 3.72 (d, J = 8.2 Hz, 1H), 3, 44 (d, J = 8.3 Hz, 1H), 2.37 (s, 3H) F1352 ESIMS m/z 689 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.69 (s, 1H), 9.57 (s, 1H), 8.16 (td, J = 8, 7, 5.5 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.87 - 7.76 (m, 3H), 7.52 - 7.42 (m, 2H ), 7.19 (td, J = 9.2, 2.0 Hz, 1H), 3.75 - 3.68 (m, 1H), 3.43 (d, J = 8.3 Hz, 1H) , 1.99 - 1.89 (m, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.83, -117.57, -123.31, -128.75 F1353 ESIMS m/z 664 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 8.82 (s, 1H), 8.24 (s, 1H), 8.08 - 7.91 (m, 1H), 7.77 (ddd, J = 8.7, 2.6, 1.1 Hz, 1H), 7.59 - 7.36 (m, 4H), 7.33 - 7.16 (m, 2H), 6.89 - 6.71 (m, 2H), 6.65 - 6.47 (m, 2H), 5.36 - 5.14 (m, 1H), 4.23 (d, J = 4.8 Hz, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H), 2.26 (s, 3H);
¹³ C NMR (101 MHz, acetone-d ₆ ) δ 164.95, 162.42, 156.35, 147.48, 137.87, 137.84, 137.81, 137.71, 137.41, 134 .70, 133.82, 133.76, 130.80, 130.19, 128.56, 128.14, 127.83, 126.75, 126.70, 125.12, 124.93, 121.39 , 119.80, 115.14, 115.05, 114.11, 110.22, 59.66, 47.05, 39.20, 37.51, 29.54, 29.35, 29.16, 28 .96, 28.77, 28.58, 28.39, 26.92, 17.88 F1354 ESIMS m/z 746 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.48 (s, 1H), 9.08 (s, 1H), 8.09 (td, J = 8, 8, 5.7 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.53 - 7.43 (m, 2H ), 7.14 (td, J = 9.2, 2.0 Hz, 1H), 3.75 - 3.68 (m, 1H), 3.44 (d, J = 8.3 Hz, 1H) ;
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.86, -117.62, -123.24, -128.77 F1355 ESIMS m/z 797 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.55 (d, J = 7.3 Hz, 2H), 8.14 (td, J = 8.7, 5.5 Hz, 1H), 8.04 (d, J = 2.7 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.53 - 7.43 (m, 2H), 7.18 (td, J = 9.3, 2.0 Hz, 1H), 6.54 (s, 1H), 3.72 (d, J = 8.5 Hz, 1H), 3.43 (d , J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.80, -61.84, -117.53, -123.25,
-128.54 F1356 ESIMS m/z 770
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.16 (s, 1H), 11.14 (s, 1H), 10.65 (s, 1H), 7.94 - 7.84 (m, 3H), 7.88 - 7.79 (m, 1H), 7.66 (br s, 1H), 7.65 - 7.55 (m, 2H), 3.71 (d, J = 8.1 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.8 Hz), -60.71,
-112.62, -116.88 (q, J = 12.5 Hz),
-118.75, -119.02 F1357 ESIMS m/z 703 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.70 (s, 1H), 9.57 (s, 1H), 8.16 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.86 - 7.76 (m, 3H), 7.52 - 7.42 (m, 2H ), 7.19 (td, J = 9.2, 2.0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz , 1H), 2.22 (tq, J = 16.8, 7.5 Hz, 2H), 1.09 (t, J = 7.5 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.82, -107.73, -117.45, -123.01,
-128.53 F1358 ESIMS m/z 721 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.36 (s, 1H), 10.18 (s, 1H), 9.60 (s, 1H), 8.22 (td, J = 8, 8, 5.7 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.0, 2.5 Hz, 2H), 7.63 ( d, J = 8.3 Hz, 1H), 7.53 - 7.45 (m, 2H), 7.26 (td, J = 9.3, 2.1 Hz, 1H), 3.64 (d , J = 8.3 Hz, 1H), 3.38 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-75.87, -123.40, -128.53 F1359 ESIMS m/z 703 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.75 (s, 1H), 9.55 (s, 1H), 8.18 (tt, J = 8, 6, 4.3 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.88 - 7.74 (m, 2H), 7.62 (d, J = 8.3 Hz, 1H), 7.57 - 7.41 (m, 2H), 7.21 (td, J = 9.2, 2.0 Hz, 1H), 6.45 (t, J = 53.5 Hz , 1H), 3.64 (d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-123.19, -127.10, -128.50 F1360 (thin film) 3276, 1659, 1588, 1569, 1534, 1488, 1404, 1292, 1220, 1189, 1047, 798, 709 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.99 (s, 1H), 10.58 (s, 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.70 (s, 2H), 7.63 (t, J = 2.0 Hz, 1H), 7.58 - 7.53 ( m, 3H), 3.62 (d, J = 8.4 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H) F1361 ESIMS m/z 784 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.57 (s, 1H), 8.68 (s, 1H), 8.18 (tt, J = 8, 7, 5.6 Hz, 1H), 8.04 (d, J = 2.5 Hz, 1H), 7.88 - 7.78 (m, 3H), 7.48 (t, J = 9.0 Hz, 2H), 7.21 (td, J = 9.3, 2.1 Hz, 1H), 3.82 (dd, J = 14.5, 5.9 Hz, 1H), 3.72 (d , J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 3.30 (dd, J = 14.5, 8.3 Hz, 1H), 2.23 (dtd, J = 10.6, 8.1, 5.9 Hz, 1H), 1.93 (dd, J = 10.6, 7.7 Hz, 1H), 1.65 (t, J = 7 ,8 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.88, -117.60, -123.18,
-128.63 F1362 ESIMS m/z 679 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.49 (s, 1H), 9.10 (s, 1H), 8.07 - 7.88 (m, 2H), 7.88 - 7.72 (m, 3H), 7.58 - 7.38 (m, 2H), 7.07 (td, J = 9.2, 1.9 Hz, 1H), 3 .70 (d, J = 8.2 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H), 1.65 (dt, J = 8.5, 4.2 Hz, 1H) , 1.42 - 1.25 (m, 1H), 1.25 - 1.00 (m, 4H), 0.68 (ddd, J = 8.0, 6.2, 3.6 Hz, 1H) ;
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.81, -117.48, -122.94,
-128.48 F1363 ESIMS m/z 683 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.52 (s, 1H), 8.92 (s, 1H), 8.07 (td, J = 8, 8, 5.6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.86 - 7.75 (m, 3H), 7.47 (t, J = 8.9 Hz, 2H), 7.11 (td, J = 9.2, 1.9 Hz, 1H), 4.13 (s, 2H), 3.74 - 3.63 (m, 3H), 3.42 (d, J = 8.3 Hz, 1H), 1.24 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.81, -117.48, -122.89, -128.53 F1364 ESIMS m/z 697 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.48 (s, 1H), 8.91 (s, 1H), 8.07 (td, J = 8, 8, 5.6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.87 - 7.76 (m, 3H), 7.52 - 7.43 (m, 2H ), 7.11 (td, J = 9.2, 1.9 Hz, 1H), 4.04 (q, J = 6.7 Hz, 1H), 3.76 - 3.57 (m, 3H) , 3.42 (d, J = 8.3 Hz, 1H), 1.42 (d, J = 6.7 Hz, 3H), 1.25 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.83, -117.51, -123.18,
-128.81 F1365 ESIMS m/z 562 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.52 (s, 1H), 7.94 (d, J = 2.7 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.61 - 7.48 (m, 2H), 7.46 - 7.36 (m, 2H), 7.32 (t, J = 8.8 Hz, 1H), 7.17 (d, J = 8.6 Hz, 1H), 6.98 (dd, J = 8.6, 2.4 Hz, 1H), 5.01 (s , 2H), 3.65 - 3.58 (m, 1H), 3.33 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-117.92 F1366 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.98 (s, 1H), 9.88 (s, 1H), 8.28 (d, J = 2, 6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.81 (ddd, J = 13.7, 8.8, 2.6 Hz, 2H), 7.64 - 7.52 (m, 2H), 7.51 - 7.41 (m, 2H), 7.35 (t, J = 8.9 Hz, 1H), 3.65 - 3.58 (m, 1H) , 3.35 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-76.16, -118.19 F1367 ESIMS m/z 597 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.54 (s, 1H), 7.96 (d, J = 2.6 Hz, 1H), 7.81 - 7.73 (m, 3H), 7.63 - 7.56 (m, 1H), 7.48 - 7.39 (m, 2H), 7.34 (t, J = 8.9 Hz, 1H ), 5.05 (s, 2H), 3.65 - 3.58 (m, 1H), 3.34 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-118.08 F1368 ESIMS m/z 693 ([M+H] ⁺ ) ^1H NMR (300 MHz, acetone- _d6 ) δ 10.36 (s, 1H), 10.22 (s, 1H), 10.02 (s, 1H), 8.09 - 7.99 (m, 3H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.61 (ddd, J = 7.0, 2.2, 0.7 Hz, 1H), 7.55 - 7.40 (m, 2H), 7.36 (t, J = 8.8 Hz, 1H), 3.62 (dt, J = 8.3, 0.8 Hz, 1H), 3.36 ( d, J = 8.3 Hz, 1H) F1369 ESIMS m/z 664 ([M+H] ⁺ ) ^1H NMR (300 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.54 (s, 1H), 9.31 (s, 1H), 8.18 - 8.00 (m, 2H), 7.88 - 7.75 (m, 3H), 7.55 - 7.41 (m, 2H), 7.15 (td, J = 9.3, 2.0 Hz, 1H), 4 .05 - 3.94 (m, 2H), 3.72 (dd, J = 8.3, 0.9 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -117.57, -123.13, -128.37 F1370 ESIMS m/z 562 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.54 (s, 1H), 7.96 (d, J = 2.6 Hz, 1H), 7.81 - 7.73 (m, 3H), 7.63 - 7.56 (m, 1H), 7.48 - 7.39 (m, 2H), 7.34 (t, J = 8.9 Hz, 1H ), 5.05 (s, 2H), 3.65 - 3.58 (m, 1H), 3.34 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-118.08 F1371 ESIMS m/z 653 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.48 (s, 1H), 8.82 (s, 1H), 8.09 - 7.98 (m, 2H), 7.81 (ddd, J = 11.5, 7.0, 2.7 Hz, 3H), 7.48 (dd, J = 10.0, 8.0 Hz, 2H), 7.09 (td, J = 9.2, 2.0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2 .48 (q, J = 7.6 Hz, 2H), 1.18 (t, J = 7.6 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -117.57, -123.19,
-128.71 F1372 ESIMS m/z 681 ([M+H] ⁺ ) ^1H NMR (300 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.49 (s, 1H), 8.88 (s, 1H), 8.11 - 7.96 (m, 2H), 7.88 - 7.74 (m, 3H), 7.48 (t, J = 9.0 Hz, 2H), 7.09 (td, J = 9.3, 2.0 Hz, 1H ), 3.71 (dd, J = 8.3, 0.9 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.47 (t, J = 7.4 Hz , 2H), 1.76 - 1.60 (m, 2H), 1.41 (dq, J = 14.5, 7.3 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H), -3.92 (s, 1H) F1373 ESIMS m/z 531 ([M+H] ⁺ ) F1374 ESIMS m/z 531 ([M+H] ⁺ ) F1375 ESIMS m/z 549 ([M+H] ⁺ ) F1376 ESIMS m/z 549 ([M+H] ⁺ ) F1377 ESIMS m/z 583 ([M+H] ⁺ ) F1378 ESIMS m/z 583 ([M+H] ⁺ ) F1379 130-134 ESIMS m/z 780
([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.61 (s, 1H), 7.89 (dd, J = 11.3, 2.4 Hz, 1H) , 7.79 (t, J = 8.1 Hz, 1H), 7.72 (dd, J = 7.2, 1.8 Hz, 1H), 7.66 (dd, J = 2.4, 1 .3 Hz, 1H), 7.56 (t, J = 10.1 Hz, 1H), 7.51 - 7.43 (m, 2H), 3.60 (d, J = 8.4 Hz, 1H ), 3.46 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.63, -117.22, -117.74,
-117.76, -121.51, -121.53 F1380 166-169 ESIMS m/z 796
([M-2H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.61 (s, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H) , 7.83 - 7.75 (m, 2H), 7.70 (d, J = 8.3 Hz, 1H), 7.67 (dd, J = 2.4, 1.2 Hz, 1H), 7.56 (t, J = 10.1 Hz, 1H), 7.44 (dd, J = 8.4, 2.2 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H ), 3.48 (d, J = 8.5 Hz, 1H), 1.42 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.62, -117.74, -117.76,
-121.51, -121.53 F1381 152-154 ESIMS m/z 830 ([M-2H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.61 (s, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H) , 7.81 (d, J = 7.8 Hz, 3H), 7.67 (dd, J = 2.4, 1.2 Hz, 1H), 7.57 (t, J = 10.1 Hz, 1H), 3.66 (d, J = 8.5 Hz, 1H), 3.57 (d, J = 8.5 Hz, 1H), 1.42 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -112.60, -117.75, -117.77, -121.51, -121.52 F1382 129-132 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₃₄ H ₂₉ Cl ₃ F ₇ N ₃ O ₆ , 813.1010; found, 813,1005 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.61 (s, 1H), 7.96 - 7.75 (m, 4H), 7.67 (dd, J = 2.5, 1.2 Hz, 1H), 7.63 - 7.53 (m, 2H), 3.71 (d, J = 8.4 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H), 1.42 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.94, -112.62, -116.86, -116.90, -117.75, -117.77,
-121.51, -121.53 F1383 147-153 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₃₃ H ₂₉ Cl ₅ F ₃ N ₃ O ₆ , 795.0443; found, 795.0451 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.11 (s, 1H), 10.61 (s, 1H), 7.89 (dd, J = 11.3, 2.4 Hz, 1H) , 7.80 (t, J = 8.1 Hz, 1H), 7.67 (dd, J = 2.5, 1.3 Hz, 1H), 7.64 (t, J = 1.9 Hz, 1H), 7.60 - 7.52 (m, 3H), 3.65 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H), 1, 42 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.62, -117.75, -117.77,
-121.51, -121.53 F1384 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (300 MHz, acetone- _d6 ) δ 10.36 (s, 1H), 10.22 (s, 1H), 10.02 (s, 1H), 8.09 - 7.99 (m, 3H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.61 (ddd, J = 7.0, 2.2, 0.7 Hz, 1H), 7.55 - 7.40 (m, 2H), 7.36 (t, J = 8.8 Hz, 1H), 3.62 (dt, J = 8.3, 0.8 Hz, 1H), 3.36 ( d, J = 8.3 Hz, 1H) F1385 ESIMS m/z 667 ([M+H] ⁺ ) ^1H NMR (300 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.49 (s, 1H), 8.87 (s, 1H), 8.11 - 7.97 (m, 2H), 7.81 (ddd, J = 11.3, 7.0, 2.6 Hz, 3H), 7.48 (t, J = 8.9 Hz, 2H), 7.09 (td, J = 9.3, 2.0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.44 (t , J = 7.3 Hz, 2H), 1.72 (h, J = 7.3 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H), -3.91 (s, 1H) F1386 ESIMS m/z 689 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.65 (d, J = 37.4 Hz, 1H), 8.45 - 8.19 (m, 1H) , 8.07 (dt, J = 11.6, 2.7 Hz, 1H), 7.92 - 7.72 (m, 3H), 7.47 (dd, J = 11.3, 8.8 Hz , 2H), 7.25 (dtd, J = 29.5, 9.3, 2.0 Hz, 1H), 6.54 (dt, J = 257.6, 52.7 Hz, 1H), 3, 72 (d, J = 8.2 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 3.32 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.78, -117.44, -125.25,
-126.59, -130.27 F1387 ESIMS m/z 553 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.50 (s, 1H), 7.95 (dd, J = 8.3, 2.5 Hz, 2H) , 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 (dd, J = 9.0, 2.5 Hz, 1H), 7.65 - 7.55 (m , 1H), 7.50 - 7.41 (m, 2H), 7.36 (t, J = 8.8 Hz, 1H), 6.93 (d, J = 9.0 Hz, 1H), 5 .48 (s, 2H), 3.65 - 3.58 (m, 1H), 3.35 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-118.23 F1388 ESIMS m/z 649 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.53 (s, 1H), 10.21 (s, 1H), 10.05 (s, 1H), 8.38 (d, J = 2, 5 Hz, 1H), 8.12 (dd, J = 8.9, 2.5 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.84 - 7.69 ( m, 2H), 7.61 (ddd, J = 7.0, 2.3, 0.8 Hz, 1H), 7.54 - 7.42 (m, 2H), 7.36 (t, J = 8.9 Hz, 1H), 3.62 (dt, J = 8.4, 0.9 Hz, 1H), 3.36 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-76.16, -118.22 F1389 ESIMS m/z 589 ([M+H] ^{+ 1H} NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 8.90 (s, 1H), 7.98 (d, J = 2.6 Hz, 1H), 7.87 - 7.70 (m, 3H), 7.52 - 7.40 (m, 2H), 7.06 (d, J = 8.4 Hz, 1H), 6.60 (d, J = 8.4 Hz, 1H), 4.39 (s, 2H), 3.70 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 2.24 ( s, 3H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.84, -117.64 F1390 ESIMS m/z 596 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.53 (s, 1H), 7.97 (dd, J = 6.9, 2.5 Hz, 2H) , 7.74 (ddd, J = 18.1, 8.8, 2.5 Hz, 2H), 7.62 - 7.54 (m, 1H), 7.46 - 7.37 (m, 2H) , 7.42 - 7.28 (m, 1H), 6.94 (d, J = 8.8 Hz, 1H), 5.09 (s, 2H), 3.65 - 3.57 (m, 1H ), 3.34 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-63.23, -118.03 F1391 82-86 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₄ H ₁₄ Cl ₃ F ₆ N ₃ O ₂ , 595.0056; found, 595.0065 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.15 (s, 1H), 7.93 - 7.79 (m, 3H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.64 - 7.51 (m, 2H), 7.21 - 7.08 (m, 2H), 5.11 (s, 2H), 3 .69 (d, J = 8.6 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.94, -116.89, -116.93,
-116.96, -116.99, -134.18,
-135.44 F1392 ESIMS m/z 685 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 10.04 (s, 1H), 9.24 (s, 1H), 8.02 (d, J = 2, 7 Hz, 1H), 7.87 - 7.76 (m, 3H), 7.54 (d, J = 8.5 Hz, 1H), 7.48 (dt, J = 9.8, 5.1 Hz, 2H), 7.26 (d, J = 8.5 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.33 (s, 3H), 2.22 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -76.00, -117.58 F1393 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 10.16 (s, 1H), 10.04 (s, 1H), 8.40 (d, J = 2, 5 Hz, 1H), 8.15 (dd, J = 8.7, 2.4 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.70 - 7.57 (m, 2H), 7.54 - 7.41 (m, 2H), 7.36 (t, J = 8.8 Hz , 1H), 3.66 - 3.58 (m, 1H), 3.36 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.73, -76.30, -118.20 F1394 ESIMS m/z 675 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.67 (s, 1H), 9.51 (s, 1H), 8.66 (t, J = 8, 1 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.95 - 7.75 (m, 3H), 7.48 (t, J = 9.0 Hz, 2H) , 7.29 (t, J = 10.3 Hz, 1H), 6.41 (t, J = 53.7 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3 .43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.89, -117.63, -124.54,
-127.18 F1395 111-118 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₄ F ₄ N ₃ O ₂ , 578.9698; found, 578.9700 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.26 (s, 1H), 7.88 (dd, J = 11.3, 2.4 Hz, 1H) , 7.72 (dd, J = 7.2, 1.8 Hz, 1H), 7.60 (dd, J = 2.4, 1.2 Hz, 1H), 7.52 - 7.42 (m , 2H), 7.21 - 7.07 (m, 2H), 5.13 (s, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.76, -117.23, -133.98,
-135.70 F1396 119-124 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₅ F ₃ N ₃ O ₂ , 594.9402; found, 594.9401 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.26 (s, 1H), 7.88 (dd, J = 11.3, 2.4 Hz, 1H) , 7.77 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.60 (dd, J = 2.4, 1.2 Hz, 1H), 7.44 (dd, J = 8.7, 2.1 Hz, 1H), 7.21 - 7.09 (m, 2H), 5.13 (s, 2H), 3.62 (d , J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.75, -133.98, -135.70 F1397 129-134 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₃ H ₁₂ Cl ₆ F ₃ N ₃ O ₂ , 628.9013; found, 628.9006 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.11 (s, 1H), 10.26 (s, 1H), 7.88 (dd, J = 11.3, 2.4 Hz, 1H) , 7.81 (d, J = 0.7 Hz, 2H), 7.61 (dd, J = 2.4, 1.2 Hz, 1H), 7.25 - 7.08 (m, 2H), 5.13 (s, 2H), 3.65 (d, J = 8.4 Hz, 1H), 3.56 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.73, -133.98, -135.71 F1398 112-117 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₄ H ₁₃ Cl ₃ F ₇ N ₃ O ₂ , 612.9962; found, 612.9964 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.14 (s, 1H), 10.26 (s, 1H), 8.03 - 7.75 (m, 3H), 7.65 - 7, 54 (m, 2H), 7.24 - 7.09 (m, 2H), 5.14 (s, 2H), 3.71 (d, J = 8.4 Hz, 1H), 3.52 (d , J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91, -59.94, -112.75, -116.83,
-116.87, -116.90, -116.94,
-133.98, -135.71 F1399 119-125 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₃ H ₁₃ Cl ₅ F ₃ N ₃ O ₂ , 594.9402; found, 594.9395 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.10 (s, 1H), 10.26 (s, 1H), 7.88 (dd, J = 11.3, 2.4 Hz, 1H) , 7.63 (t, J = 1.9 Hz, 1H), 7.60 (dd, J = 2.5, 1.2 Hz, 1H), 7.56 (dd, J = 2.0, 0 .7 Hz, 2H), 7.22 - 7.10 (m, 2H), 5.13 (s, 2H), 3.64 (d, J = 8.4 Hz, 1H), 3.53 (d , J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.75, -133.98, -135.70 F1400 108-113 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₅ H ₁₃ Cl ₄ F ₆ N ₃ O ₃ , 656.9615; found, 656.9617 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.74 (s, 1H), 10.62 (s, 1H), 8.08 (t, J = 8, 1 Hz, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H), 7.72 (dd, J = 7.3, 1.8 Hz, 1H), 7.65 ( dd, J = 2.4, 1.3 Hz, 1H), 7.56 (t, J = 10.3 Hz, 1H), 7.51 - 7.44 (m, 2H), 6.47 (t , J = 53.5 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (400 MHz, DMSO-d ₆ ) δ
-112.62, -117.22, -120.03,
-120.04, -120.54, -120.56,
-125.66 F1401 115-120 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₂ Cl ₄ F ₇ N ₃ O ₃ , 674.9521; found, 674.9519 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.38 (s, 1H), 11.15 (s, 1H), 10.67 (s, 1H), 7.96 (t, J = 8, 0 Hz, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H), 7.72 (dd, J = 7.1, 1.9 Hz, 1H), 7.67 ( dd, J = 2.4, 1.3 Hz, 1H), 7.62 (t, J = 10.3 Hz, 1H), 7.53 - 7.43 (m, 2H), 3.61 (d , J = 8.4 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.89, -112.64, -117.23,
-118.59, -118.60, -118.98,
-118.99 F1402 112-116 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₃ Cl ₅ F ₅ N ₃ O ₃ , 672.9320; found, 672.9314 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.74 (s, 1H), 10.62 (s, 1H), 8.08 (t, J = 8, 1 Hz, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H), 7.77 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.65 (dd, J = 2.4, 1.3 Hz, 1H), 7.56 (t, J = 10.3 Hz, 1H), 7.47 - 7, 41 (m, 1H), 6.47 (t, J = 53.5 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.48 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.61, -120.03, -120.05,
-120.54, -120.56, -125.65 F1403 100-105 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₂ Cl ₅ F ₆ N ₃ O ₃ , 690.9225; found, 690.9221 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.38 (s, 1H), 11.15 (s, 1H), 10.67 (s, 1H), 7.96 (t, J = 8, 0 Hz, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H), 7.77 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.67 (dd, J = 2.4, 1.2 Hz, 1H), 7.62 (t, J = 10.3 Hz, 1H), 7.48 - 7, 41 (m, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.49 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.88, -112.62, -118.59,
-118.61, -118.97, -118.99 F1404 112-117 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₂ Cl ₆ F ₅ N ₃ O ₃ , 706.8930; found, 706.8922 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.13 (s, 1H), 10.74 (s, 1H), 10.62 (s, 1H), 8.09 (t, J = 8, 1 Hz, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H), 7.82 (s, 2H), 7.66 (dd, J = 2.4, 1.2 Hz, 1H), 7.57 (t, J = 10.3 Hz, 1H), 6.48 (t, J = 53.5 Hz, 1H), 3.66 (d, J = 8.4 Hz, 1H), 3.57 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.59, -120.01, -120.02,
-120.54, -120.55, -125.68 F1405 126-131 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₁ Cl ₆ F ₆ N ₃ O ₃ , 724.8836; found, 724.8828 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.38 (s, 1H), 11.14 (s, 1H), 10.67 (s, 1H), 7.96 (t, J = 8, 0 Hz, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H), 7.82 (s, 2H), 7.71 - 7.57 (m, 2H), 3, 66 (d, J = 8.4 Hz, 1H), 3.57 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.89, -112.61, -118.59,
-118.61, -118.97, -118.99 F1406 98-103 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₃ Cl ₃ F ₉ N ₃ O ₃ , 690.9879; found, 690.9874 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.16 (s, 1H), 10.74 (s, 1H), 10.62 (s, 1H), 8.09 (t, J = 8, 1 Hz, 1H), 7.96 - 7.79 (m, 3H), 7.66 (dd, J = 2.4, 1.2 Hz, 1H), 7.59 (q, J = 10.2 Hz, 2H), 6.48 (t, J = 53.5 Hz, 1H), 3.72 (d, J = 8.4 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -112.60, -116.83,
-116.87, -116.90, -116.93,
-120.01, -120.02, -120.54,
-120.55, -125.68 F1407 121-126 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₂ Cl ₃ F ₁₀ N ₃ O ₃ , 708.9785; found, 708.9779 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.38 (s, 1H), 11.16 (s, 1H), 10.67 (s, 1H), 7.90 (ddt, J = 22, 0, 19.9, 6.8 Hz, 4H), 7.70 - 7.55 (m, 3H), 3.71 (d, J = 8.4 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -59.94, -73.89,
-112.62, -116.83, -116.86,
-116.90, -116.93, -118.60,
-118.61, -118.98, -118.99 F1408 119-124 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₃ Cl ₅ F ₅ N ₃ O ₃ , 672.9320; found, 672.9312 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.12 (s, 1H), 10.74 (s, 1H), 10.62 (s, 1H), 8.09 (t, J = 8, 1 Hz, 1H), 7.90 (dd, J = 11.3, 2.4 Hz, 1H), 7.65 (dt, J = 7.7, 1.6 Hz, 2H), 7.61 - 7.51 (m, 3H), 6.48 (t, J = 53.5 Hz, 1H), 3.65 (d, J = 8.4 Hz, 1H), 3.54 (d, J = 8 .5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.61, -120.00, -120.02,
-120.53, -120.55, -125.68 F1409 126-131 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₂ Cl ₅ F ₆ N ₃ O ₃ , 690.9225; found, 690.9215 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.38 (s, 1H), 11.12 (s, 1H), 10.67 (s, 1H), 7.96 (t, J = 8, 0 Hz, 1H), 7.89 (dd, J = 11.3, 2.4 Hz, 1H), 7.70 - 7.55 (m, 5H), 3.65 (d, J = 8.4 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.88, -112.63, -118.60,
-118.62, -118.98, -118.99 F1410 ESIMS m/z 686 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.79 (s, 1H), 10.50 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.82 (dd, J = 6.7, 2.1 Hz, 1H), 7.78 - 7.67 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.39 (m, 2H), 7.27 (td, J = 9.2, 1.8 Hz, 1H), 6.54 (t, J = 53.2 Hz , 1H), 3.59 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-109.32, -120.69 (d, J = 2.8 Hz), -124.26, -125.74 F1411 ESIMS m/z 700 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.79 (s, 1H), 10.50 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.88 (d, J = 2.0 Hz, 1H), 7.79 - 7.64 (m, 3H), 7.56 (d, J = 8.7 Hz, 1H) , 7.46 (dd, J = 8.6, 2.1 Hz, 1H), 7.34 - 7.20 (m, 1H), 6.54 (t, J = 53.2 Hz, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.68, -124.25, -125.76 F1412 ESIMS m/z 672 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.30 (s, 1H), 9.32 (s, 1H), 9.09 (s, 1H), 8.22 - 8.13 (m, 1H), 8.06 (d, J = 2.6 Hz, 1H), 7.83 (dp, J = 10.7, 3.8, 3.0 Hz, 3H), 7.55 - 7.43 (m, 3H), 3.71 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H), 2.18 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.84, -117.57 F1413 ESIMS m/z 575 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.26 (s, 1H), 9.66 (s, 1H), 8.36 (d, J = 2.2 Hz, 1H), 7.92 - 7.83 (m, 2H), 7.78 (dt, J = 9.3, 2.4 Hz, 2H), 7.73 - 7.64 (m, 1H), 7.50 - 7.35 (m, 3H), 7.14 - 7.07 (m, 1H), 3.66 (d, J = 8.3 Hz, 1H), 3.37 (d, J = 8.3 Hz, 1H) , 2.19 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.80, -117.56 F1414 ESIMS m/z 706 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.25 (s, 1H), 10.95 (s, 1H), 10.53 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 5.9, 2.4 Hz, 3H), 7.69 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.30 (t, J = 9.2 Hz, 1H), 7.08 - 6, 71 (m, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.15, -123.61, -124.45,
-138.93 (t, J = 6.8 Hz) F1415 ESIMS m/z 645 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.47 (s, 1H), 10.25 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.0, 2.3 Hz, 2H), 7.68 (dd, J = 12.0, 7.9 Hz, 2H), 7.56 ( d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.28 - 7.19 (m, 1H), 4.03 - 4 .01 (m, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.50 (d, J = 3.0 Hz), -124.20 (d, J = 3.4 Hz) F1416 ESIMS m/z 672 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.48 (s, 1H), 10.19 (s, 1H), 7.98 (dd, J = 1, 8, 0.8 Hz, 1H), 7.93 (d, J = 2.6 Hz, 1H), 7.75 (dt, J = 5.8, 2.9 Hz, 2H), 7.73 - 7.65 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.36 (dd , J = 3.5, 0.8 Hz, 1H), 7.30 - 7.20 (m, 1H), 6.73 (dd, J = 3.5, 1.8 Hz, 1H), 3, 61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.42 (d, J = 3.4 Hz), -124.40 (d, J = 3.4 Hz) F1417 ESIMS m/z 660 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.63 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.66 - 7.57 (m, 1H), 7, 55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.19 (t, J = 9.2 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.27 (d, J = 7.0 Hz, 2H), 1, 11 - 0.98 (m, 1H), 0.55 - 0.44 (m, 2H), 0.22 (d, J = 5.0 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.45 (d, J = 4.1 Hz), -124.41 (d, J = 3.9 Hz) F1418 ESIMS m/z 688 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.47 (s, 1H), 10.23 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 5.9, 2.4 Hz, 2H), 7.68 (t, J = 9.0 Hz, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.29 - 7.17 (m, 1H), 3.65 - 3.54 (m , 3H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.60, -120.65 (d, J = 3.2 Hz),
-124.30 (d, J = 3.2 Hz) F1419 ESIMS m/z 678 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.76 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.62 (q, J = 8.4 Hz, 1H) , 7.55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.18 (t, J = 9.2 Hz, 1H), 3.71 - 3.57 (m, 3H), 3.51 - 3.39 (m, 3H), 2.59 (t, J = 6.3 Hz, 2H), 1.11 (t , J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.32 (d, J = 3.6 Hz), -124.34 (d, J = 4.0 Hz) F1420 ESIMS m/z 692 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (br s, 1H), 9.37 (br s, 1H), 8.67 (t, J = 8.0 Hz, 1H), 8 .09 (br s, 1H), 7.82 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.67 (d, J = 2 ,1 Hz, 1H), 7.62 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.3, 1.7 Hz, 1H), 7.17 (t, J = 10.5 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H), 1.50(s,9H);
¹⁹ F NMR (376 MHz, acetone) δ
-128.55, -128.68 F1421 ESIMS m/z 728 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.37 (s, 1H), 8.68 (q, J = 7.9 Hz, 1H), 8.09 (br s, 1H), 7.83 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.70 (s, 2H), 7, 17 (t, J = 10.4 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.48 (d, J = 8.3 Hz, 1H), 2.41 ( d, J = 2.9 Hz, 3H), 1.50 (s, 9H);
^19F NMR (376 MHz, acetone- _d6 ) δ -128.52, -128.65 F1422 ESIMS m/z 709 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.12 (s, 1H), 9.37 (s, 1H), 8.67 (t, J = 8.2 Hz, 1H), 8.10 (s, 1H), 7.87 - 7.78 (m, 3H), 7.78 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.7 Hz, 1H) , 7.17 (t, J = 10.4 Hz, 1H), 3.71 (d, J = 8.2 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2 .41 (s, 3H), 1.50 (s, 9H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87 (d, J = 12.6 Hz), -117.66 (q, J = 12.8 Hz), -128.55 (d, J = 2.6 Hz), -128.68 (d, J = 2.7 Hz) F1423 ESIMS m/z 792 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.52 (s, 1H), 8.18 (tt, J = 8.8, 5.6 Hz, 1H) , 7.84 (d, J = 2.7 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.67 (d, J = 2.2 Hz, 1H), 7 .63 (d, J = 8.3 Hz, 1H), 7.45 (dd, J = 8.4, 2.2 Hz, 1H), 7.19 (td, J = 9.3, 2.0 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H), 1.45 ( s, 18H);
¹⁹ F NMR (376 MHz, acetone) δ
-125.62, -130.74 F1424 ESIMS m/z 827 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.52 (s, 1H), 8.18 (td, J = 8.9, 5.3 Hz, 1H) , 7.84 (d, J = 2.6 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.71 (d, J = 0.7 Hz, 2H), 7 .19 (td, J = 9.3, 1.9 Hz, 1H), 3.66 (d, J = 8.3 Hz, 1H), 3.47 (d, J = 8.3 Hz, 1H) , 2.41 (s, 3H), 1.45 (s, 18H);
¹⁹ F NMR (376 MHz, acetone) δ
-125.62, -125.66, -130.77,
-130.88 F1425 ESIMS m/z 810 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.52 (s, 1H), 8.18 (tt, J = 8.9, 5.7 Hz, 1H) , 7.87 - 7.80 (m, 3H), 7.77 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.19 ( td, J = 9.2, 2.0 Hz, 1H), 3.71 (d, J = 8.2 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2, 41 (s, 3H), 1.45 (s, 18H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88 (d, J = 12.4 Hz), -117.67 (q, J = 12.8 Hz), -125.62 (d, J = 1.9 Hz), -130.76 (d, J = 2.0 Hz) F1426 ESIMS m/z 594 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.07 (s, 1H), 9.16 (s, 1H), 7.80 - 7.70 (m, 3H), 7.67 (d, J = 2.1 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.4, 1.7 Hz, 1H), 6.97 ( t, J = 10.7 Hz, 1H), 4.68 (apparent d, J = 9.4 Hz, 2H), 3.63 (d, J = 8.3 Hz, 1H), 3.37 (d , J = 8.3 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-137.48, -137.49, -137.52,
-137.53, -139.86, -139.88,
-139.89, -139.98, -140.01,
-140.02 F1427 ESIMS m/z 628 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.05 (s, 1H), 9.14 (s, 1H), 7.81 - 7.71 (m, 3H), 7.70 (s, 2H), 6.96 (t, J = 10.7 Hz, 1H), 4.67 (ad, J = 9.4 Hz, 2H), 3.65 (d, J = 8.3 Hz, 1H) , 3.43 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-137.48, -137.49, -137.52,
-137.53, -139.86, -139.88,
-139.89, -139.98, -140.00,
-140.02 F1428 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.07 (s, 1H), 9.16 (s, 1H), 7.83 (d, J = 6.7 Hz, 2H), 7.80 - 7.67 (m, 3H), 7.48 (t, J = 9.9 Hz, 1H), 6.96 (t, J = 10.7 Hz, 1H), 4.67 (ad, J = 9.3 Hz, 2H), 3.71 (d, J = 8.5 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88 (d, J = 12.7 Hz), -117.65 (q, J = 12.8 Hz), -137.46 (d, J = 3.3 Hz), -139.85 (d, J = 5.2 Hz) F1429 ESIMS m/z 672 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.12 (s, 1H), 9.68 (s, 1H), 9.48 (s, 1H), 8.71 - 8.63 (m, 1H), 7.82 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.5 Hz, 1H), 7.67 (d, J = 2.1 Hz, 1H) , 7.62 (d, J = 8.4 Hz, 1H), 7.44 (dd, J = 8.4, 2.1 Hz, 1H), 7.29 (t, J = 10.3 Hz, 1H), 6.41 (t, J = 53.7 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H) , 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-124.63, -124.68, -124.70,
-124.81, -124.82, -127.22 F1430 ESIMS m/z 690 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (br s, 2H), 9.54 (s, 1H), 8.54 (td, J = 8.1, 5.0 Hz, 1H ), 7.84 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.5 Hz, 1H), 7.67 (d, J = 2.1 Hz, 1H), 7.62 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.3, 2.2 Hz, 1H), 7.33 (t, J = 10.2 Hz, 1H ), 3.62 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -76.03, -122.71, -122.72,
-122.73, -122.74, -123.49,
-123.50, -123.61, -123.62 F1431 ESIMS m/z 704 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 9.70 (s, 1H), 9.50 (s, 1H), 8.67 (tt, J = 8, 2, 4.1 Hz, 1H), 7.82 (d, J = 2.5 Hz, 1H), 7.77 (d, J = 2.5 Hz, 1H), 7.70 (d, J = 0.7 Hz, 2H), 7.29 (t, J = 10.3 Hz, 1H), 6.41 (t, J = 53.7 Hz, 1H), 3.65 (d, J = 8, 3 Hz, 1H), 3.46 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-124.54, -124.55, -124.56,
-124.57, -124.65, -124.66,
-124.68, -124.77, -124.79,
-124.79, -127.18, -127.23 F1432 ESIMS m/z 722 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (br s, 2H), 9.55 (s, 1H), 8.55 (td, J = 8.1, 5.1 Hz, 1H ), 7.84 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.71 (d, J = 0.7 Hz, 2H), 7.34 (t, J = 10.3 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.48 (dd, J = 8.3, 1.2 Hz, 1H ), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-76.03, -122.70, -122.72,
-122.72, -122.74, -123.48,
-123.50, -123.60, -123.61 F1433 ESIMS m/z 653 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.05 (s, 1H), 10.41 (s, 1H), 9.80 (s, 1H), 7.97 (ddd, J = 12, 2, 6.7, 2.5 Hz, 1H), 7.79 (d, J = 0.7 Hz, 2H), 7.73 (dt, J = 4.7, 2.1 Hz, 1H), 7.70 - 7.61 (m, 1H), 7.26 - 7.14 (m, 1H), 3.65 (d, J = 8.6 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 2.10 (s, 3H);
¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 168.35, 162.71, 161.57, 156.37, 153.87, 152.24, 150.57, 150.44, 149.75, 148 ,14, 148.00, 142.00, 135.29, 135.26, 135.19, 134.80, 132.95, 129.83, 129.50, 125.89, 125.77, 123.70 , 121.98, 121.86, 115.35, 115.18, 110.98, 110.76, 110.37, 110.16, 61.98, 39.52, 38.57, 36.43, 22 ,40;
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.27 (d, J = 3.9 Hz), -124.71 (d, J = 4.0 Hz), -135.59 (d, J = 23.8 Hz), -144.65 ( d, J = 23.8 Hz) F1434 ESIMS m/z 699 ([M+Na] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.38 (s, 1H), 9.03 (s, 1H), 7.89 (d, J = 2, 8 Hz, 2H), 7.76 (dd, J = 8.8, 2.5 Hz, 1H), 7.62 (d, J = 1.9 Hz, 1H), 7.59 - 7.51 ( m, 3H), 7.39 (t, J = 10.3 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 1.46 (s, 9H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.51, -122.95 (td, J = 10.2, 9.3, 4.0 Hz) F1435 ESIMS m/z 699 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.38 (s, 1H), 9.03 (s, 1H), 7.89 (t, J = 4, 1 Hz, 2H), 7.80 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H) , 7.47 - 7.34 (m, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.51, -122.94 (td, J = 10.1, 9.2, 4.0 Hz) F1436 ESIMS m/z 737 ([M+Na] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.38 (s, 1H), 9.04 (s, 1H), 7.94 - 7.85 (m, 2H), 7.80 (s, 2H), 7.76 (dd, J = 8.7, 2.6 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7, 39 (t, J = 10.3 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 1.46 ( s, 7H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.51, -122.95 (td, J = 10.1, 9.2, 4.0 Hz) F1437 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 10.79 (s, 1H), 10.47 (s, 1H), 8.06 - 7.89 (m, 2H), 7.80 (s, 2H), 7.79 - 7.67 (m, 2H), 7.28 (td, J = 9.3, 1.9 Hz, 1H), 6.48 (d , J = 53.1 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.44 (d, J = 2.7 Hz), -124.35 (d, J = 2.9 Hz), -125.79, -135.59 (d, J = 23.8 Hz), -144.69 (d, J = 24.0 Hz) F1438 ESIMS m/z 729 ([M+H ₂ O] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.58 (s, 1H), 11.05 (s, 1H), 10.53 (s, 1H), 7.97 (ddd, J = 12, 3, 6.9, 2.6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 3H), 7.74 (p, J = 2.0 Hz, 1H), 7.34 ( td, J = 9.2, 1.8 Hz, 1H), 3.65 (dt, J = 8.5, 0.7 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.85, -120.41 - -122.08 (m),
-124.48 (d, J = 2.3 Hz), -135.55 (d, J = 23.7 Hz), -144.65 (d, J = 23.8 Hz) F1439 ESIMS m/z 624 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.04 (s, 1H), 10.42 (s, 1H), 9.80 (s, 1H), 7.96 (ddd, J = 12, 4, 6.8, 2.6 Hz, 1H), 7.72 (dt, J = 4.7, 2.1 Hz, 1H), 7.70 - 7.60 (m, 2H), 7.56 (d, J = 1.9 Hz, 2H), 7.26 - 7.17 (m, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 2.09 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.27 (d, J = 4.1 Hz), -124.71 (d, J = 3.9 Hz), -135.62 (d, J = 23.9 Hz), -144.73 ( d, J = 23.9 Hz) F1440 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 10.81 (s, 1H), 10.49 (s, 1H), 7.96 (ddd, J = 12, 4, 6.8, 2.6 Hz, 1H), 7.80 - 7.69 (m, 2H), 7.63 (t, J = 1.9 Hz, 1H), 7.56 (dd, J = 1.9, 0.7 Hz, 2H), 7.29 (td, J = 9.2, 1.8 Hz, 1H), 6.56 (t, J = 53.2 Hz, 1H), 3 .64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.44 (d, J = 2.9 Hz), -124.34 (d, J = 2.9 Hz), -125.78, -135.60 (d, J = 23.9 Hz), -144.71 (d, J = 23.6 Hz) F1441 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.60 (s, 1H), 11.05 (s, 1H), 10.53 (s, 1H), 7.96 (ddd, J = 12, 4, 6.9, 2.6 Hz, 1H), 7.79 (td, J = 8.7, 5.7 Hz, 1H), 7.73 (dt, J = 4.5, 2.1 Hz , 1H), 7.62 (t, J = 1.9 Hz, 1H), 7.55 (d, J = 1.8 Hz, 2H), 7.34 (td, J = 9.2, 1, 8 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.84, -120.86, -124.51, -135.58 (d, J = 23.7 Hz), -144.70 (d, J = 23.8 Hz) F1442 ESIMS m/z 641 ([M+H ₂ O] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.07 (s, 1H), 10.41 (s, 1H), 9.80 (s, 1H), 7.98 (ddd, J = 12, 1, 6.8, 2.6 Hz, 1H), 7.75 (d, J = 2.1 Hz, 1H), 7.74 - 7.71 (m, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.66 (s, 1H), 7.49 - 7.38 (m, 1H), 7.28 - 7.11 (m, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.10 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.29, -124.72 (d, J = 4.1 Hz), -135.64 (d, J = 23.4 Hz), -144.71 (d, J = 23.6 Hz) F1443 ESIMS m/z 658 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.08 (s, 1H), 10.83 (s, 1H), 10.49 (s, 1H), 7.99 (ddd, J = 12, 4, 6.7, 2.5 Hz, 1H), 7.82 - 7.72 (m, 3H), 7.68 (d, J = 8.3 Hz, 1H), 7.47 - 7.38 (m, 1H), 7.29 (td, J = 9.2, 1.8 Hz, 1H), 6.56 (t, J = 53.2 Hz, 1H), 3.63 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.45, -124.34 (d, J = 2.7 Hz), -125.73, -135.61 (d, J = 23.7 Hz), -144.68 (d, J = 23 .7 Hz) F1444 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.58 (s, 1H), 11.08 (s, 1H), 10.53 (s, 1H), 7.98 (ddd, J = 12, 3, 6.9, 2.6 Hz, 1H), 7.86 - 7.72 (m, 3H), 7.69 (d, J = 8.3 Hz, 1H), 7.49 - 7.41 (m, 1H), 7.34 (td, J = 9.2, 1.8 Hz, 1H), 3.63 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.87, -119.99 - -122.29 (m),
-122.71 - -127.10 (m), -135.58 (d, J = 23.8 Hz), -144.69 (d, J = 23.8 Hz) F1445 ESIMS m/z 681 ([M+H ₂ O] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.38 (s, 1H), 9.04 (s, 1H), 7.90 (t, J = 5, 2 Hz, 2H), 7.81 - 7.67 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.50 - 7.36 (m, 3H), 3, 59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 1.46 (s, 9H);
¹⁹ F NMR (376 MHz, DMSO-d) δ
-112.54 (q, J = 7.2 Hz), -117.76, -118.19 (td, J = 9.9, 9.3, 4.0 Hz) F1446 ESIMS m/z 592 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.07 (s, 1H), 9.18 (s, 1H), 7.80 (d, J = 2.6 Hz, 1H), 7.76 (d, J = 2.5 Hz, 1H), 7.67 (d, J = 2.1 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.45 (dd , J = 8.5, 2.2 Hz, 1H), 7.42 - 7.35 (m, 1H), 6.94 - 6.84 (m, 1H), 4.75 (ad, J = 8 .6 Hz, 2H), 3.63 (d, J = 8.3 Hz, 1H), 3.37 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-137.48, -137.52, -137.55,
-137.55, -144.41, -144.44,
-144.56, -144.59 F1447 ESIMS m/z 624 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.12 (s, 1H), 9.75 (s, 1H), 9.41 (s, 1H), 8.33 (t, J = 2, 0 Hz, 1H), 8.04 - 7.90 (m, 2H), 7.78 (dt, J = 8.0, 1.2 Hz, 1H), 7.73 - 7.57 (m, 2H ), 7.54 - 7.37 (m, 2H), 7.16 (td, J = 9.3, 2.0 Hz, 1H), 6.45 (t, J = 53.5 Hz, 1H) , 3.64 (d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -122.84, -126.98, -127.11 F1448 ESIMS m/z 575 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.06 (s, 1H), 7.99 (d, J = 2.6 Hz, 1H), 7.87 - 7.73 (m, 3H), 7.47 (dd, J = 11.0, 8.7 Hz, 2H), 7.00 - 6.87 (m, 2H), 6.64 (dd, J = 7.7, 1.5 Hz, 1H), 4.51 (s, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz , 1H), 2.15 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.84, -117.58 F1449 ESIMS m/z 626 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.06 (s, 1H), 9.19 (s, 1H), 7.80 (d, J = 2.5 Hz, 1H), 7.75 (d, J = 2.6 Hz, 1H), 7.70 (s, 2H), 7.39 (tt, J = 8.5, 5.7 Hz, 1H), 6.89 (ddd, J = 10.8, 9.0, 2.1 Hz, 1H), 4.76 (s, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8 .3 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -137.44, -137.48, -137.51,
-144.39, -144.42, -144.54,
-144.57 F1450 ESIMS m/z 793 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.42 (s, 1H), 10.19 (s, 1H), 9.59 (s, 1H), 8.22 (td, J = 8, 8, 5.6 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.47 (t, J = 9.7 Hz, 2H), 7.25 (td, J = 9.2, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8 ,3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -61.89, -81.45, -117.55, -120.63, -123.35, -127.76, -128.52 F1451 ESIMS m/z 671([M+H] ⁺ ) ^1H NMR (300 MHz, _CDCl3 ) δ 9.51 (s, 1H), 8.98 (s, 1H), 8.81 (s, 1H), 7.57 (dd, J = 8.7, 2.5 Hz, 1H), 7.44 (dd, J = 6.6, 2.9 Hz, 2H), 7.28 - 7.10 (m, 3H), 7.09 - 6.96 (m , 2H), 6.89 (d, J = 2.5 Hz, 1H), 3.50 (d, J = 8.0 Hz, 1H), 3.03 (d, J = 8.2 Hz, 1H ), 1.86 (s, 3H) F1452 ESIMS m/z 703 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.63 (d, J = 35.4 Hz, 1H), 8.46 - 8.20 (m, 1H) , 8.15 - 8.00 (m, 1H), 7.89 - 7.71 (m, 3H), 7.58 - 7.41 (m, 2H), 7.27 (dtd, J = 25, 2, 9.3, 2.0 Hz, 1H), 6.50 (dt, J = 269.9, 52.7 Hz, 1H), 3.95 - 3.78 (m, 2H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 1.20 (dt, J = 19.5, 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.81, -117.47, -123.70,
-125.37, -128.84 F1453 ESIMS m/z 762 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 10.32 (s, 1H), 8.02 (dd, J = 6.2, 2.7 Hz, 1H) , 7.89 - 7.78 (m, 1H), 7.78 - 7.64 (m, 3H), 7.47 - 7.33 (m, 2H), 7.33 - 7.20 (m, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.16, -123.60, -126.41 F1454 ESIMS m/z 639 ([M+H] ⁺ ) ^1H NMR (300 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.48 (s, 1H), 9.05 (s, 1H), 8.79 (t, J = 8, 3 Hz, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.88 - 7.74 (m, 3H), 7.53 - 7.40 (m, 2H), 7, 16 (t, J = 10.4 Hz, 1H), 3.76 - 3.66 (m, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.18 (s, 3H ), -3.79 (s, 1H) F1455 ESIMS m/z 790 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.11 (s, 1H), 9.50 (s, 1H), 8.23 (t, J = 8.2 Hz, 1H), 7.83 (d, J = 2.5 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.67 (d, J = 2.1 Hz, 1H), 7.63 (d , J = 8.3 Hz, 1H), 7.44 (dd, J = 8.3, 2.3 Hz, 1H), 7.27 (t, J = 10.1 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H), 1.47 (s, 18H);
^19F NMR (376 MHz, acetone- _d6 ) δ -123.28 (d, J = 5.5 Hz), -123.63 (d, J = 5.5 Hz) F1456 ESIMS m/z 824 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.50 (s, 1H), 8.23 (t, J = 8.2 Hz, 1H), 7.84 (d, J = 2.2 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.70 (s, 2H), 7.27 (t, J = 10.1 Hz , 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.47 (d, J = 8.4 Hz, 1H), 2.41 (s, 3H), 1.47 (s , 18H);
^19F NMR (376 MHz, acetone- _d6 ) δ -123.29 (d, J = 5.5 Hz), -123.63 (d, J = 5.5 Hz) F1457 ESIMS m/z 808 ([MH] ^- ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 9.50 (s, 1H), 8.27 - 8.20 (m, 1H), 7.88 - 7, 81 (m, 3H), 7.77 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.27 (t, J = 10.1 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H), 1.47 ( s, 18H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.89 (d, J = 12.9 Hz), -117.67 (q, J = 12.8 Hz), -123.28 (d, J = 5.5 Hz), -123.39 (d, J = 5.5 Hz), -123.62 (d, J = 5.6 Hz), -123.65 (d, J = 5.6 Hz) F1458 ESIMS m/z 610 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.08 (s, 1H), 9.20 (s, 1H), 7.87 - 7.79 (m, 3H), 7.76 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.39 (tt, J = 8.5, 5.8 Hz, 1H), 6.89 ( ddd, J = 10.8, 9.0, 2.1 Hz, 1H), 4.75 (ad, J = 8.5 Hz, 2H), 3.71 (d, J = 8.3 Hz, 1H ), 3.42 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88 (d, J = 12.7 Hz), -117.65 (q, J = 12.7 Hz), -137.48 (at, J = 13.1 Hz), -144.47 (add, J = 54.6, 12.4 Hz) F1459 ESIMS m/z 564 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.88 (s, 1H), 9.97 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 6.3, 2.7 Hz, 1H), 7.88 - 7.78 (m, 1H), 7.78 - 7.73 (m, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.43 (ddd, J = 8.4, 2.1, 0.7 Hz, 1H), 7.36 (t, J = 9.4 Hz, 1H), 6.96 - 6.77 (m, 2H), 5.31 (s, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.36, -134.03 (d, J = 13.9 Hz), -138.55 (d, J = 13.9 Hz) F1460 ESIMS m/z 654 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) rotary isomers δ 10.97 (s, 1H), 10.65 (s, 0.7H), 10.56 (s, 0.3H), 8.04 - 7.90 (m, 2H), 7.87 - 7.66 (m, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7.51 - 7.43 (m, 2H) , 7.35 (dtd, J = 18.5, 9.4, 2.0 Hz, 1H), 7.04 (t, J = 52.2 Hz, 0.3H), 6.35 (t, J = 52.0 Hz, 0.7H), 3.63 - 3.55 (m, 1H), 3.49 - 3.38 (m, 2H), 3.25 (s, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -117.27 (d, J = 3.3 Hz), -122.13 (d, J = 7.4 Hz),
-123.14 (d, J = 3.2 Hz), -124.05 - -124.51 (m), -125.56 (d, J = 9.3 Hz), -126.21, -126 .48 (dd, J = 6.2, 3.2 Hz) F1461 ESIMS m/z 704 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) rotary isomers δ 10.97 (s, 1H), 10.65 (s, 0.7H), 10.56 (s, 0.3H), 8.04 - 7.90 (m, 1H), 7.87 - 7.66 (m, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7.52 - 7.43 (m, 2H) , 7.35 (dtd, J = 18.5, 9.4, 2.0 Hz, 1H), 7.04 (t, J = 52.2 Hz, 0.3H), 6.35 (t, J = 52.0 Hz, 0.7H), 3.65 - 3.53 (m, 1H), 3.50 - 3.38 (m, 2H), 3.25 (s, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -117.27 (d, J = 3.2 Hz), -122.13 (d, J = 7.5 Hz),
-123.14 (d, J = 3.3 Hz), -125.56 (d, J = 9.4 Hz), -126.21, -126.48 (dd, J = 6.7, 3, 3 Hz) F1462 ESIMS m/z 670 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) rotary isomers δ 10.94 (s, 1H), 10.65 (s, 0.7H), 10.56 (s, 0.3H), 8.02 - 7.90 (m, 1.7H), 7.87 - 7.78 (m, 0.3H), 7.74 (dt, J = 8.8, 2.9 Hz, 1H), 7.63 ( t, J = 1.9 Hz, 1H), 7.60 - 7.53 (m, 3H), 7.44 - 7.27 (m, 1H), 7.04 (t, J = 52.2 Hz , 0.3H), 6.35 (t, J = 52.0 Hz, 0.7H), 3.62 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8, 5 Hz, 1H), 3.41 (s, 1H), 3.24 (s, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -122.12 (d, J = 7.1 Hz), -123.13 (d, J = 3.4 Hz),
-124.26 (dt, J = 24.2, 6.1 Hz),
-125.56 (d, J = 9.5 Hz), -126.21, -126.49 (dd, J = 6.7, 3.2 Hz) F1463 ESIMS m/z 774 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 11.60 (s, 1H), 10.96 (s, 1H), 10.57 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.76 (td, J = 5.2, 4.6, 2.7 Hz, 3H), 7.70 (d, J = 8.4 Hz, 1H), 7.57 ( d, J = 8.8 Hz, 1H), 7.48 - 7.40 (m, 1H), 7.33 (t, J = 9.2 Hz, 1H), 3.61 (d, J = 8 .5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-80.07 (t, J = 8.2 Hz), -119.32,
-121.35, -124.67, -126.83 F1464 98-103 HRMS-ESI (m/z) [M+H] ⁺ calculated for C ₂₃ H ₁₂ Cl ₄ F ₄ N ₂ O ₂ , 563.9589; found, 563.9584 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.73 (s, 2H), 8.11 (t, J = 8.5 Hz, 1H), 7.84 (td, J = 8.9, 6.1 Hz, 1H), 7.68 (dd, J = 7.0, 2.2 Hz, 1H), 7.55 - 7.34 (m, 4H), 7.16 (td, J = 8 ,4, 4.7 Hz, 1H), 3.66 (d, J = 8.6 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-113.01, -113.03, -117.27,
-117.96, -117.97, -124.77 F1465 107-111 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₃ H ₁₃ Cl ₄ F ₃ N ₂ O ₂ , 545.9683; found, 545.9683 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.73 (s, 1H), 8.10 (t, J = 8.6 Hz, 1H), 7.78 - 7.63 (m, 3H), 7.55 - 7.38 (m, 3H), 7.23 (t, J = 8.8 Hz, 2H), 3.65 (d, J = 8.6 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.26, -117.95, -124.89 F1466 113-118 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₃ H ₁₄ Cl ₄ F ₂ N ₂ O ₂ , 527.9777; 527.9781 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 10.73 (s, 1H), 8.10 (t, J = 8.6 Hz, 1H), 7.69 (dd, J = 11.6, 7.9 Hz, 3H), 7.53 - 7.32 (m, 5H), 7.15 (t, J = 7.4 Hz, 1H), 3.66 ( d, J = 8.6 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -124.97 F1467 ESIMS m/z 762 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.28 (s, 1H), 8.02 (dd, J = 6.3, 2.7 Hz, 1H) , 7.83 (ddd, J = 8.9, 4.4, 2.8 Hz, 1H), 7.80 - 7.72 (m, 2H), 7.70 (d, J = 8.4 Hz , 1H), 7.55 (t, J = 10.2 Hz, 1H), 7.47 - 7.32 (m, 2H), 3.60 (d, J = 8.5 Hz, 1H), 3 .45 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.67 (d, J = 6.6 Hz), -119.08, -121.92 (d, J = 6.8 Hz) F1468 ESIMS m/z 688 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s,1H), 9.69 (s,1H), 9.49 (s,1H), 8.67 (q, J=7, 8 Hz, 1H), 7.86 - 7.81 (m, 3H), 7.78 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H) , 7.29 (t, J = 10.3 Hz, 1H), 6.41 (t, J = 53.7 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3 .45 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -61.88 (d, J = 12.9 Hz), -117.68 (q, J = 12.8, 12.0 Hz), -124, 65 (d, J = 43.5 Hz), -124.79 (d, J = 45.3 Hz), -127.21 (d, J = 20.0 Hz), -127.27 (d, J = 19.9 Hz) F1469 ESIMS m/z 706 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (br s, 2H), 9.55 (s, 1H), 8.55 (td, J = 8.1, 5.1 Hz, 1H ), 7.85 (d, J = 2.8 Hz, 2H), 7.83 (d, J = 2.9 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.34 (t, J = 10.2 Hz, 1H), 3.71 (d, J = 8.4 Hz, 1H), 3, 47 (dd, J = 8.3, 1.4 Hz, 1H), 2.41 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.88 (d, J = 12.5 Hz), -76.02,
-117.69 (qd, J = 12.9, 1.9 Hz),
-122.71 (d, J = 5.1 Hz), -122.74 (d, J = 5.0 Hz), -123.52 (d, J = 5.3 Hz), -123.64 ( d, J = 4.9 Hz) F1470 ESIMS m/z 592 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.08 (s, 1H), 9.17 (s, 1H), 7.83 - 7.69 (m, 3H), 7.67 (d, J = 2.1 Hz, 1H), 7.62 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.5, 2.2 Hz, 1H), 6.97 ( t, J = 10.7 Hz, 1H), 4.68 (br s, 2H), 3.62 (d, J = 8.3 Hz, 1H), 3.37 (d, J = 8.3 Hz , 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-137.43, -139.81 F1471 ESIMS m/z 732 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.93 (s, 1H), 10.50 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.80 - 7.65 (m, 6H), 7.64 - 7.51 (m, 4H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H ), 7.27 (td, J = 9.2, 1.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz , 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-100.77, -121.14 (d, J = 2.5 Hz), -124.68 F1472 ESIMS m/z 634 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.69 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.1, 2.3 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.66 - 7.57 ( m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.23 - 7.15 (m , 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.37 (q, J = 7.6 Hz, 2H ), 1.10 (t, J = 7.6 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.54 (d, J = 3.5 Hz), -124.55 (d, J = 4.1 Hz) F1473 ESIMS m/z 648 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.70 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.65 - 7.57 (m, 1H), 7, 55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.18 (dd, J = 10.1, 8.3 Hz , 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.33 (t, J = 7.2 Hz, 2H ), 1.62 (h, J = 7.4 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.55 (d, J = 4.1 Hz), -124.55 (d, J = 4.0 Hz) F1474 ESIMS m/z 662 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.70 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.66 - 7.57 (m, 1H), 7, 55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.22 - 7.14 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.35 (t, J = 7.4 Hz, 2H), 1.59 (p , J = 7.4 Hz, 2H), 1.35 (h, J = 7.3 Hz, 2H), 0.91 (t, J = 7.3 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.59 (d, J = 4.1 Hz), -124.58 (d, J = 4.0 Hz) F1475 ESIMS m/z 674 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 10.11 (s, 1H), 7.93 (d, J = 2, 7 Hz, 1H), 7.75 (dd, J = 7.3, 2.3 Hz, 2H), 7.66 (dd, J = 23.4, 7.5 Hz, 2H), 7.56 ( d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.26 - 7.17 (m, 1H), 3.61 (d , J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 3.44 - 3.35 (m, 2H), 3.28 - 3.12 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.67 (d, J = 3.4 Hz), -124.53 (d, J = 3.5 Hz) F1476 ESIMS m/z 650 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.43 (s, 1H), 9.21 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.66 - 7.57 (m, 1H), 7, 55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.19 (t, J = 9.2 Hz, 1H), 4.11 (q, J = 7.1 Hz, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 1, 22 (t, J = 7.3 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.50, -125.55 F1477 ESIMS m/z 626 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.08 (s, 1H), 9.18 (s, 1H), 7.81 - 7.75 (m, 1H), 7.77 - 7, 72 (m, 2H), 7.70 (s, 2H), 6.97 (t, J = 10.7 Hz, 1H), 4.70 (br s, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-137.44, -137.48, -139.86,
-139.99 F1478 ESIMS m/z 610 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.08 (s, 1H), 9.18 (s, 1H), 7.86 - 7.81 (m, 2H), 7.82 - 7, 69 (m, 3H), 7.49 (t, J = 9.9 Hz, 1H), 6.97 (t, J = 10.7 Hz, 1H), 4.69 (ad, J = 9.4 Hz, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.88 (d, J = 12.9 Hz), -117.66 (q, J = 12.8 Hz), -137.47,
-137.50, -139.86, -139.88,
-139.89, -139.98, -140.01,
-140.02 F1479 ESIMS m/z 732 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.51 (s, 1H), 9.24 (s, 1H), 8.09 (td, J = 8, 8, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.82 (td, J = 8.8, 2.7 Hz, 3H), 7.47 ( dt, J = 8.2, 5.0 Hz, 2H), 7.13 (td, J = 9.3, 2.0 Hz, 1H), 4.83 (q, J = 6.8 Hz, 1H ), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.86 (d, J = 6.8 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.82, -117.52, -123.04,
-128.46 F1480 ESIMS m/z 695 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.48 (s, 1H), 8.98 (s, 1H), 8.10 - 7.99 (m, 2H), 7.81 (ddt, J = 8.8, 6.2, 2.7 Hz, 3H), 7.47 (dt, J = 8.1, 5.1 Hz, 2H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 4.02 (t, J = 8.2 Hz, 1H), 3.94 - 3.65 (m, 4H), 3.42 ( d, J = 8.3 Hz, 1H), 3.35 (p, J = 7.7 Hz, 1H), 2.29 - 2.11 (m, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.58, -123.27,
-128.69 F1481 ESIMS m/z 751 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.49 (d, J = 17.9 Hz, 2H), 8.12 (td, J = 8.8, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.53 - 7.43 (m, 2H), 7.16 (td, J = 9.3, 2.0 Hz, 1H), 4.12 (dddd, J = 18.4, 16.5, 10.3, 3.7 Hz, 1H), 3, 72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 3.12 (dtdd, J = 20.1, 14.4, 8.7, 5.3 Hz, 1H), 2.89 (dddt, J = 22.3, 15.1, 11.4, 7.5 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -109.32, -109.86,
-110.80, -111.37, -116.22,
-116.77, -117.58, -123.03,
-124.29, -124.83, -128.19 F1482 ESIMS m/z 715 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.27 (s, 1H), 9.62 (d, J = 37.7 Hz, 1H), 8.35 (td, J = 8.9, 5.7 Hz, 1H), 8.14 - 8.00 (m, 1H), 7.92 - 7.70 (m, 3H), 7.58 - 7.35 (m, 2H), 7.34 - 7.17 (m, 1H), 6.53 (dt, J = 258.4, 52.6 Hz, 1H), 5.86 (dq, J = 16.9, 7.5 Hz, 1H), 5.36 - 5.05 (m, 2H), 4.42 (dd, J = 48.0, 6.6 Hz, 2H), 3.72 (d, J = 8.3 Hz, 1H), 3 .46 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.58, -123.17,
-125.48, -128.47 F1483 ESIMS m/z 667 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.46 (s, 1H), 8.80 (s, 1H), 8.08 - 7.97 (m, 2H), 7.81 (ddd, J = 11.4, 6.4, 2.3 Hz, 3H), 7.47 (dd, J = 10.0, 8.0 Hz, 2H), 7.09 (td, J = 9.2, 2.0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 2 .79 (h, J = 6.8 Hz, 1H), 1.21 (d, J = 6.8 Hz, 6H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.80, -117.52, -117.55,
-128.84 F1484 ESIMS m/z 670 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.79 (br s, 1H), 9.52 (s, 1H), 8.19 (ddd, J = 8 .9, 5.7, 3.2 Hz, 1H), 7.85 (d, J = 2.5 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.68 (d, J = 2.1 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.45 (ddd, J = 8.4, 2.2, 0.7 Hz, 1H), 7.20 (td, J = 9.3, 2.0 Hz, 1H), 6.46 (t, J = 53.5 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.41 (dd, J = 8.3, 1.2 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-123.33, -123.38, -127.08,
-127.15, -128.62, -128.74 F1485 ESIMS m/z 688 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.28 (s, 1H), 9.53 (s, 1H), 8.24 - 8.09 (m, 2H), 7.85 (d, J = 2.5 Hz, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.67 (d, J = 2.1 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.4, 2.1 Hz, 1H), 7.21 (td, J = 9.2, 1.8 Hz, 1H), 3, 62 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.4 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -75.33, -75.64, -76.01, -123.74, -123.79, -128.88, -129.00 F1486 ESIMS m/z 704 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.78 (br s, 1H), 9.52 (s, 1H), 8.19 (ddd, J = 14 ,4, 8.9, 5.5 Hz, 1H), 7.84 (d, J = 2.5 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.71 (s, 2H), 7.20 (td, J = 9.3, 2.1 Hz, 1H), 6.46 (t, J = 53.5 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.47 (dd, J = 8.3, 1.0 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-123.31, -123.36, -127.08,
-127.15, -128.62, -128.73 F1487 ESIMS m/z 722 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.33 (s, 1H), 9.53 (s, 1H), 8.22 - 8.11 (m, 2H), 7.85 (d, J = 2.5 Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.71 (s, 2H), 7.21 (td, J = 9.0, 1.4 Hz, 1H), 3.65 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 2.40 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-75.34, -75.62, -76.00, -123.76, -123.81, -128.88, -129.01 F1488 ESIMS m/z 707 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.50 (s, 1H), 9.10 (s, 1H), 8.09 - 7.99 (m, 2H), 7.80 (ttd, J = 8.6, 5.7, 2.5 Hz, 3H), 7.47 (dt, J = 8.4, 5.1 Hz, 2H), 7.11 (td, J = 9.2, 1.9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (dd, J = 10.5, 7.9 Hz, 2H), 2.55 - 2.27 (m, 4H), 2.31 - 2.17 (m, 1H), 2.21 - 2.10 (m, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.80, -117.48, -123.12,
-128.57 F1489 ESIMS m/z 683 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.47 (s, 1H), 8.88 (s, 1H), 8.10 - 7.98 (m, 2H), 7.81 (ddd, J = 11.4, 6.0, 3.7 Hz, 3H), 7.52 - 7.43 (m, 2H), 7.10 (td, J = 9, 2, 2.0 Hz, 1H), 3.75 - 3.65 (m, 3H), 3.42 (d, J = 8.3 Hz, 1H), 3.32 (s, 3H), 2, 70 (t, J = 6.1 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.58, -122.97,
-128.46 F1490 ESIMS m/z 562 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.88 (s, 1H), 9.94 (s, 1H), 8.02 - 7.93 (m, 1H), 7.82 (dd, J = 8.7, 4.0 Hz, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.43 ( dd, J = 8.5, 2.1 Hz, 1H), 7.35 (t, J = 9.4 Hz, 1H), 7.22 - 7.08 (m, 2H), 5.11 (s , 2H), 3.60 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.49, -134.28, -135.72 F1491 ESIMS m/z 640 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 10.80 (s, 1H), 10.29 (d, J = 1.6 Hz, 1H), 8.03 (dd, J = 6.3, 2.8 Hz, 1H), 7.87 - 7.79 (m, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.74 - 7.67 (m, 2H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.38 (t, J = 9.4 Hz, 1H), 7.32 - 7 .22 (m, 1H), 6.54 (t, J = 53.2 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8, 5 Hz, 1H)
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.20, -120.74, -124.37,
-125.73 (d, J = 25.0 Hz) F1492 ESIMS m/z 658 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.57 (s, 1H), 10.89 (s, 1H), 10.33 (s, 1H), 8.04 (dd, J = 6, 2, 2.8 Hz, 1H), 7.86 - 7.79 (m, 1H), 7.79 - 7.73 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H ), 7.46 - 7.27 (m, 3H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.80, -119.18, -121.17,
-124.45 F1493 ESIMS m/z 604 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 10.22 (s, 1H), 9.78 (s, 1H), 8.02 (d, J = 3, 6 Hz, 1H), 7.89 - 7.79 (m, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H) , 7.62 (d, J = 7.0 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.38 (t, J = 9.4 Hz, 1H), 7.18 (t, J = 9.2 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H) , 2.08 (s, 3H),1 ⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -119.23, -120.52, -124.74 (d, J = 4.0 Hz). F1494 ESIMS m/z 688 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.78 (br s, 1H), 9.52 (s, 1H), 8.19 (ddd, J = 14 .5, 9.0, 5.6 Hz, 1H), 7.88 - 7.80 (m, 3H), 7.77 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.21 (td, J = 9.2, 2.1 Hz, 1H), 6.46 (t, J = 53.5 Hz, 1H), 3.71 ( d, J = 8.3 Hz, 1H), 3.46 (dd, J = 8.3, 1.1 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ δ
-61.87 (d, J = 12.9 Hz), -117.68 (q, J = 12.7 Hz), -123.32,
-123.37, -127.09, -127.16,
-128.61, -128.73 F1495 ESIMS m/z 706 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.34 (s, 1H), 9.54 (s, 1H), 8.17 (ddd, J = 14.3, 9.0, 5.6 Hz, 1H), 7.89 - 7.79 (m, 3H), 7.77 (d, J = 2.1 Hz, 1H), 7.48 (t, J = 9.6 Hz, 1H), 7.22 (td, J = 9.2, 1.9 Hz, 1H), 3.70 (d, J = 8.3 Hz, 1H), 3.49 (dd, J = 8.3, 1, 5 Hz, 1H), 2.40 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.87 (d, J = 12.9 Hz), -75.67,
-117.71 (q, J = 12.8 Hz),
-123.71, -123.75, -128.81,
-128.93 F1496 ESIMS m/z 670 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.71 (br s, 1H), 9.50 (s, 1H), 8.67 (td, J = 8 ,0, 5.4 Hz, 1H), 7.83 (d, J = 2.6 Hz, 1H), 7.78 (d, J = 2.5 Hz, 1H), 7.68 (d, J = 2.1 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.45 (dd, J = 8.3, 2.2 Hz, 1H), 7.30 (t , J = 10.3 Hz, 1H), 6.42 (t, J = 53.7 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-124.61, -124.69, -124.71,
-124.82, -124.83, -127.20,
-127.26 F1497 ESIMS m/z 688 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.29 (br s, 2H), 9.56 (s, 1H), 8.55 (td, J = 8.1, 5.1 Hz, 1H ), 7.85 (d, J = 2.5 Hz, 1H), 7.78 (d, J = 1.9 Hz, 1H), 7.68 (d, J = 2.1 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.45 (dd, J = 8.4, 2.1 Hz, 1H), 7.34 (t, J = 10.2 Hz, 1H ), 3.62 (d, J = 8.3 Hz, 1H), 3.44 (dd, J = 8.3, 1.7 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-75.32, -76.01, -122.67, -122.68, -122.69, -122.70, -123.48,
-123.49, -123.60, -123.61 F1498 ESIMS m/z 704 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.72 (s, 1H), 9.51 (s, 1H), 8.71 - 8.63 (m, 1H), 7.83 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.71 (d, J = 0.7 Hz, 2H) , 7.29 (t, J = 10.3 Hz, 1H), 6.42 (t, J = 53.7 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3 .48 (dd, J = 8.3, 1.1 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-124.56, -124.65, -124.66,
-124.77, -124.78, -127.17,
-127.23 F1499 ESIMS m/z 722 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.31 (br s, 2H), 9.56 (s, 1H), 8.54 (t, J = 8.1 Hz, 1H), 7, 85 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.71 (d, J = 0.7 Hz, 2H), 7.34 ( t, J = 10.2 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.52 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -75.99, -122.63 (d, J = 5.3 Hz),
-123.45 (d, J = 4.9 Hz) F1500 ESIMS m/z 688 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.36 (s, 1H), 9.74 (s, 1H), 9.51 (s, 1H), 8.71 - 8.61 (m, 1H), 7.89 - 7.81 (m, 3H), 7.79 (d, J = 2.6 Hz, 1H), 7.48 (t, J = 9.8 Hz, 1H), 7, 29 (t, J = 10.3 Hz, 1H), 6.42 (t, J = 53.7 Hz, 1H), 3.70 (d, J = 8.3 Hz, 1H), 3.52 ( d, J = 8.3 Hz, 1H), 2.41 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.87 (d, J = 12.9 Hz), -75.45,
-117.73 (q, J = 12.7 Hz),
-124.47, -124.48, -124.65,
-124.66, -127.16, -127.22 F1501 ESIMS m/z 706 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (br s, 2H), 9.56 (s, 1H), 8.54 (t, J = 8.1 Hz, 1H), 7, 88 - 7.79 (m, 3H), 7.77 (d, J = 2.5 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.34 (t, J = 10.3 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.47 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -61.87 (d, J = 12.8 Hz), -76.00, -117.68 (q, J = 12.8 Hz), -122 .67 (d, J = 5.1 Hz), -123.49 (d, J = 4.9 Hz) F1502 ESIMS m/z 638 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.33 (s, 1H), 9.53 (s, 1H), 8.85 (s, 1H), 8.15 - 8.01 (m, 1H), 7.94 (dd, J = 11.2, 2.4 Hz, 1H), 7.71 (s, 1H), 7.51 (s, 3H), 7.12 (t, J = 9 .4 Hz, 1H), 3.68 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.15 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-113.59, -113.61, -123.20,
-123.25, -128.79, -128.89 F1503 ESIMS m/z 681 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.51 (s, 1H), 9.18 (s, 1H), 8.11 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 8.1 , 5.1 Hz, 2H), 7.15 (td, J = 9.2, 2.0 Hz, 1H), 5.17 (ddd, J = 9.1, 6.6, 1.2 Hz, 1H), 4.83 - 4.70 (m, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 3, 11 (dtd, J = 11.5, 8.8, 6.7 Hz, 1H), 2.71 (ddt, J = 11.4, 8.8, 6.9 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.56, -123.24,
-128.87 F1504 ESIMS m/z 672 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.35 (s, 1H), 9.54 (s, 1H), 8.88 (s, 1H), 8.05 (td, J = 8, 7, 5.5 Hz, 1H), 7.92 (dd, J = 11.2, 2.4 Hz, 1H), 7.70 (s, 3H), 7.12 (t, J = 9.2 Hz, 1H), 3.68 (d, J = 8.3 Hz, 1H), 3.46 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-113.51, -123.11, -128.68 F1505 ESIMS m/z 638 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.34 (s, 1H), 9.49 (s, 1H), 8.99 (s, 1H), 8.80 (t, J = 8, 1 Hz, 1H), 7.95 (dd, J = 11.2, 2.4 Hz, 1H), 7.70 (t, J = 1.9 Hz, 1H), 7.50 (s, 3H) , 7.19 (t, J = 10.4 Hz, 1H), 3.67 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H), 2 ,17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-113.54, -127.01, -127.39 F1506 ESIMS m/z 653 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.63 (s, 1H), 8.22 (td, J = 8.9, 5.7 Hz, 1H) , 8.18 - 8.00 (m, 1H), 7.87 - 7.75 (m, 3H), 7.48 (t, J = 9.7 Hz, 2H), 7.26 (td, J = 9.3, 2.1 Hz, 1H), 3.72 (d, J = 8.2 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H), 3.18 (s , 3H), 1.85 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.54, -125.34,
-130.61 F1507 ESIMS m/z 721 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.51 (s, 1H), 9.14 (s, 1H), 8.12 - 8.00 (m, 2H), 7.87 - 7.76 (m, 3H), 7.47 (dt, J = 8.2, 5.0 Hz, 2H), 7.13 (td, J = 9.2, 1, 9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.54 (dd, J = 17.4, 6.6 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 3.32 (dd, J = 8.8, 6.6 Hz, 1H), 3.16 (dd, J = 17.3, 8.8 Hz, 1H), 1, 35 (s, 3H), 1.18 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.54, -122.55,
-127.95 F1508 140-144 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₃ H ₁₃ Cl ₄ F ₄ N ₃ O ₂ , 579.9698; found, 579.9689 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.72 (s, 1H), 10.49 (s, 1H), 8.10 (t, J = 8.6 Hz, 1H), 7.68 (dd, J = 7.0, 2.1 Hz, 1H), 7.54 - 7.36 (m, 3H), 6.99 - 6.85 (m, 2H), 5.33 (s, 2H ), 3.66 (d, J = 8.5 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27, -124.86, -133.83,
-133.86, -138.78, -138.82 F1509 ESIMS m/z 642 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 10.73 (s, 1H), 10.27 (s, 1H), 8.10 - 7.98 (m, 2H), 7.84 (ddd, J = 8.9, 4.4, 2.7 Hz, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.55 (t, J = 10.3 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.38 (t , J = 9.4 Hz, 1H), 6.47 (t, J = 53.5 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.21, -119.89 (d, J = 5.2 Hz), -120.93 (d, J = 5.3 Hz), -125.61 F1510 ESIMS m/z 658 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.37 (s, 1H), 10.90 (s, 1H), 10.32 (d, J = 1.9 Hz, 1H), 8.04 (dd, J = 6.2, 2.8 Hz, 1H), 7.93 (t, J = 8.0 Hz, 1H), 7.85 (ddd, J = 9.0, 4.4, 2 .8 Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.60 (t, J = 10.2 Hz, 1H), 7.47 - 7.33 (m, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.89, -118.46 (d, J = 6.2 Hz),
-119.18, -119.37 (d, J = 6.2 Hz) F1511 ESIMS m/z 606 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.88 (s, 1H), 10.19 (s, 1H), 9.80 (s, 1H), 8.14 (t, J = 8, 3 Hz, 1H), 7.99 (dd, J = 6.2, 2.8 Hz, 1H), 7.88 - 7.80 (m, 1H), 7.76 (d, J = 2.2 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.49 - 7.33 (m, 3H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.25, -122.31 (d, J = 4.6 Hz), -123.02 (d, J = 4.3 Hz) F1512 ESIMS m/z 640 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.75 (s, 1H), 10.27 (s, 1H), 8.08 - 7.97 (m, 1H), 7.89 - 7.79 (m, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7, 63 (td, J = 8.7, 5.7 Hz, 1H), 7.46 - 7.36 (m, 2H), 7.27 (t, J = 9.1 Hz, 1H), 6.47 (t, J = 53.4 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.21, -119.65, -124.30,
-125.59 F1513 ESIMS m/z 658 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.39 (s, 1H), 10.90 (s, 1H), 10.29 (s, 1H), 8.03 (dd, J = 6, 3, 2.7 Hz, 1H), 7.85 (dd, J = 8.5, 4.0 Hz, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.69 ( d, J = 8.4 Hz, 1H), 7.52 (td, J = 8.6, 5.6 Hz, 1H), 7.46 - 7.35 (m, 2H), 7.35 - 7 .27 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.86, -117.85, -119.22,
-122.94 F1514 ESIMS m/z 606 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.20 (s, 1H), 9.82 (s, 1H), 8.08 - 7.97 (m, 1H), 7.91 - 7.80 (m, 1H), 7.80 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.48 - 7 .35 (m, 2H), 7.17 (t, J = 9.1 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.45 (d, J = 8, 5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.24, -122.74, -126.69 F1515 147-151 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₅ Cl ₆ F ₂ N ₃ O ₃ , 652.9213; found, 652.9210 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.39 (s, 1H), 9.83 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.79 (d, J = 8.8 Hz, 4H), 7.58 (d, J = 8.8 Hz, 1H), 7.25 - 7.11 (m, 1H) , 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 2.09 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.81, -126.35 F1516 152-157 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₂ Cl ₆ F ₅ N ₃ O ₃ , 706.8930; found, 706.8915 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.40 (s, 1H), 10.96 (s, 1H), 10.50 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.80 (s, 3H), 7.63 - 7.47 (m, 2H), 7.32 (t, J = 8.7 Hz, 1H), 3.65 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.88, -117.79, -122.73 F1517 156-161 HRMS-ESI (m/z) [M+H] ⁺ calculated for C ₂₅ H ₁₅ Cl ₆ F ₂ N ₃ O ₃ , 652.9213; found, 652.9204 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.40 (s, 1H), 9.80 (s, 1H), 8.13 (t, J = 8, 2 Hz, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7.78 (d, J = 17.6 Hz, 3H), 7.55 (d, J = 8.7 Hz , 1H), 7.44 (t, J = 10.4 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.4 Hz, 1H ), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.22, -122.23, -122.80,
-122.81 F1518 127-132 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₃ Cl ₆ F ₄ N ₃ O ₃ , 688.9024; found, 688.9028 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.72 (s, 1H), 10.51 (s, 1H), 8.05 (t, J = 8, 1 Hz, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7.78 (d, J = 18.2 Hz, 3H), 7.55 (dd, J = 11.4, 9.5 Hz, 2H), 6.47 (t, J = 53.5 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8, 5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.84, -119.85, -120.76,
-120.77, -125.64 F1519 128-133 HRMS-ESI (m/z) [M+] ⁺ calculated for C25H12Cl6F5N3O3, 706.8930; found, 706.8923 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.36 (s, 1H), 10.94 (s, 1H), 10.55 (s, 1H), 7.98 - 7.87 (m, 2H), 7.78 (d, J = 20.4 Hz, 3H), 7.64 - 7.52 (m, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3, 55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.86, -118.50, -119.25,
-119.27 F1520 ESIMS m/z 672 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.38 (s, 1H), 9.49 (s, 1H), 9.00 (s, 1H), 8.86 - 8.74 (m, 1H), 7.95 (dd, J = 11.2, 2.4 Hz, 1H), 7.71 (s, 3H), 7.19 (t, J = 10.4 Hz, 1H), 3, 68 (d, J = 8.3 Hz, 1H), 3.48 (d, J = 8.3 Hz, 1H), 2.18 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -113.50, -126.99, -127.36 F1521 ESIMS m/z 695 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.48 (s, 1H), 8.93 (s, 1H), 8.07 (td, J = 8, 7, 5.6 Hz, 1H), 8.02 (d, J = 2.7 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 8.0 , 5.1 Hz, 2H), 7.11 (td, J = 9.2, 2.0 Hz, 1H), 4.48 (ddd, J = 8.4, 5.3, 1.0 Hz, 1H), 4.08 (dt, J = 8.3, 6.4 Hz, 1H), 3.89 (q, J = 7.2 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.37 - 2.23 (m, 1H), 2.17 - 2.03 (m, 1H), 1.96 (p, J = 6.9 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.61, -123.32,
-128.96 F1522 ESIMS m/z 638 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.36 (s, 1H), 9.49 (s, 1H), 8.99 (s, 1H), 8.80 (t, J = 8, 3 Hz, 1H), 7.95 (dd, J = 11.3, 2.4 Hz, 1H), 7.70 (br s, 1H), 7.68 (d, J = 1.8 Hz, 1H ), 7.63 (d, J = 8.3 Hz, 1H), 7.45 (ddd, J = 8.4, 2.1, 0.7 Hz, 1H), 7.20 (t, J = 10.4 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -113.56, -127.05 (d, J = 3.2 Hz), -127.42 (d, J = 3.4 Hz) F1523 ESIMS m/z 634 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 9.37 (s, 1H), 8.98 (s, 1H), 8.81 (t, J = 8, 5 Hz, 1H), 7.81 (d, J = 2.5 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.67 (d, J = 2.1 Hz , 1H), 7.62 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.4, 2.1 Hz, 1H), 7.18 (t, J = 10, 4 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H), 2.41 (s, 3H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-127.12, -127.63 F1524 ESIMS m/z 668 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.09 (s, 1H), 9.37 (s, 1H), 8.97 (s, 1H), 8.88 - 8.76 (m, 1H), 7.80 (d, J = 2.6 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.71 (d, J = 0.7 Hz, 2H) , 7.18 (t, J = 10.4 Hz, 1H), 3.66 (d, J = 8.2 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H), 2 .41 (s, 3H), 2.17 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -127.15 (d, J = 3.1 Hz), -127.66 (d, J = 3.3 Hz) F1525 ESIMS m/z 652 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 9.35 (s, 1H), 8.96 (s, 1H), 8.86 - 8.77 (m, 1H), 7.86 - 7.80 (m, 3H), 7.78 (d, J = 2.5 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7, 18 (t, J = 10.4 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.41 ( s, 3H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88 (d, J = 12.9 Hz), -117.67 (q, J = 12.8 Hz), -127.17 (d, J = 3.3 Hz), -127.67 (d, J = 3.3 Hz) F1526 ESIMS m/z 691 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.56 (s, 1H), 10.87 (s, 1H), 10.34 (d, J = 1.7 Hz, 1H), 8.04 (dd, J = 6.2, 2.8 Hz, 1H), 7.89 - 7.72 (m, 4H), 7.45 - 7.27 (m, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.82, -119.14, -121.15,
-124.44 F1527 ESIMS m/z 674 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.87 (s, 1H), 10.79 (s, 1H), 10.29 (s, 1H), 8.03 (dd, J = 6, 3, 2.8 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.72 (q, J = 8.0, 7.5 Hz, 1H), 7.38 (t, J = 9.4 Hz, 1H), 7.33 - 7.22 (m, 1H), 6.54 (t, J = 53.2 Hz, 1H), 3.63 (d, J = 8.5 Hz , 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.17, -120.75, -124.38,
-125.73 F1528 ESIMS m/z 638 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 10.22 (s, 1H), 9.77 (s, 1H), 8.02 (dd, J = 6, 3, 2.8 Hz, 1H), 7.88 - 7.76 (m, 3H), 7.62 (d, J = 7.3 Hz, 1H), 7.37 (t, J = 9.4 Hz, 1H), 7.18 (t, J = 9.2 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.4 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.21, -120.53 (d, J = 3.5 Hz), -124.73 (d, J = 4.0 Hz) F1529 ESIMS m/z 674 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.56 (s, 1H), 10.90 (s, 1H), 10.34 (s, 1H), 8.05 (dd, J = 6, 2, 2.8 Hz, 1H), 7.92 - 7.71 (m, 4H), 7.59 (dd, J = 10.7, 8.6 Hz, 1H), 7.39 (t, J = 9.4 Hz, 1H), 7.36 - 7.28 (m, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.5 Hz , 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.7 Hz), -73.82,
-116.97 (q, J = 12.4 Hz),
-119.19, -121.17, -124.45 F1530 ESIMS m/z 656 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.80 (s, 1H), 10.30 (d, J = 1.7 Hz, 1H), 8.04 (dd, J = 6.3, 2.8 Hz, 1H), 7.90 - 7.79 (m, 3H), 7.73 (q, J = 7.9 Hz, 1H), 7.59 ( dd, J = 10.6, 8.6 Hz, 1H), 7.39 (t, J = 9.4 Hz, 1H), 7.28 (td, J = 9.2, 1.8 Hz, 1H ), 6.55 (t, J = 53.2 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.7 Hz), -116.96 (q, J = 12.4 Hz), -119.20,
-120.73 (d, J = 2.9 Hz), -124.33 (d, J = 2.8 Hz), -125.78 F1531 ESIMS m/z 622 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 10.22 (s, 1H), 9.77 (s, 1H), 8.03 (dd, J = 6, 3, 2.7 Hz, 1H), 7.92 - 7.78 (m, 3H), 7.69 - 7.55 (m, 2H), 7.38 (t, J = 9.4 Hz, 1H ), 7.18 (t, J = 9.3 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 2.08 (d, J = 2.9 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.6 Hz), -116.97 (q, J = 12.7 Hz), -119.24,
-120.54, -124.74 (d, J = 3.6 Hz) F1532 209-213 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₅ Cl ₆ F ₂ N ₃ O ₃ , 652.9213; found, 652.9207 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.43 (s, 1H), 9.77 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.61 (q, J = 8.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.18 (t, J = 9.1 Hz, 1H), 3.67 - 3.61 (m, 1H), 3.55 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.45, -120.46, -124.55,
-124.56 F1533 141-145 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₂ Cl ₆ F ₅ N ₃ O ₃ , 706.8930; found, 706.8920 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.56 (s, 1H), 10.94 (s, 1H), 10.55 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.85 - 7.69 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.33 (td, J = 9.2, 1.8 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.82, -73.84, -73.85, -121.08, -124.43 F1534 116-121 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₃ Cl ₆ F ₆ N ₃ O ₃ , 738.8992; found, 738.8984 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.14 (s, 1H), 10.93 (s, 1H), 10.54 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.86 (t, J = 8.0 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.57 (t, J = 9.8 Hz, 2H), 6.87 (tt, J = 51.5, 5.4 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-118.60, -119.00, -123.82,
-123.84, -123.86, -138.90,
-138.92, -138.94 F1535 111-116 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₄ Cl ₅ F ₆ N ₃ O ₃ , 704.9382; found, 704.9391 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.14 (s, 1H), 10.95 (s, 1H), 10.54 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.86 (t, J = 8.0 Hz, 1H), 7.76 (dt, J = 5.8, 3.0 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.57 (dd, J = 10.7, 9.5 Hz, 2H), 7.47 - 7.40 (m, 1H), 6.87 (tt, J = 51 ,5, 5.4 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-118.60, -119.00, -123.83,
-123.84, -123.86, -138.90,
-138.92, -138.94 F1536 217-221 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₆ Cl ₅ F ₂ N ₃ O ₃ , 618.9602; found, 618.9605 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 10.39 (s, 1H), 9.83 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.83 - 7.74 (m, 3H), 7.70 (d, J = 8.3 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H) , 7.44 (ddd, J = 8.3, 2.2, 0.7 Hz, 1H), 7.22 - 7.13 (m, 1H), 3.62 (d, J = 8.5 Hz , 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.09 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.82, -126.36 F1537 138-143 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₅ H ₁₃ Cl ₅ F ₅ N ₃ O ₃ , 672.9320; found, 672.9312 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.40 (s, 1H), 10.98 (s, 1H), 10.49 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.84 - 7.74 (m, 2H), 7.70 (d, J = 8.3 Hz, 1H), 7.62 - 7.48 (m, 2H), 7, 43 (dd, J = 8.7, 2.1 Hz, 1H), 7.32 (td, J = 9.2, 1.6 Hz, 1H), 3.62 (d, J = 8.5 Hz , 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.88, -117.81, -122.74 F1538 187-190 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₃ Cl ₃ F ₉ N ₃ O ₃ , 690.9879; found, 690.9881 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.40 (s, 1H), 10.99 (s, 1H), 10.50 (s, 1H), 7.95 (d, J = 2, 6 Hz, 1H), 7.91 - 7.75 (m, 3H), 7.66 - 7.48 (m, 3H), 7.37 - 7.27 (m, 1H), 3.70 (d , J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.94, -73.89, -116.89, -116.93, -116.96, -116.99,
-117.78, -122.72 F1539 131-136 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₆ Cl ₃ F ₆ N ₃ O ₃ , 637.0161; found, 637.0167 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.40 (s, 1H), 9.80 (s, 1H), 8.13 (t, J = 8, 2 Hz, 1H), 7.96 - 7.74 (m, 4H), 7.66 - 7.51 (m, 2H), 7.44 (t, J = 10.4 Hz, 1H), 3, 70 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -116.90, -116.93, -116.96, -117.00, -122.22,
-122.23, -122.80, -122.82 F1540 113-118 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₄ Cl ₃ F ₈ N ₃ O ₃ , 672.9973; found, 672.9982 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.73 (s, 1H), 10.51 (s, 1H), 8.05 (t, J = 8, 1 Hz, 1H), 7.96 - 7.73 (m, 4H), 7.65 - 7.49 (m, 3H), 6.47 (t, J = 53.5 Hz, 1H), 3, 70 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.94, -116.89, -116.92, -116.96, -116.99, -119.82,
-119.84, -120.76, -120.77,
-125.65 F1541 101-107 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₃ Cl ₃ F ₉ N ₃ O ₃ , 690.9879; found, 690.9888 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.36 (s, 1H), 10.97 (s, 1H), 10.55 (s, 1H), 7.99 - 7.72 (m, 5H), 7.64 - 7.53 (m, 3H), 3.69 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91, -59.94, -73.88, -116.89, -116.92, -116.95, -116.99,
-118.45, -119.23, -119.25 F1542 114-119 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₉ H ₂₂ Cl ₃ F ₆ N ₃ O ₄ , 695.0580; found, 695.0581 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.39 (s, 1H), 9.04 (s, 1H), 7.96 - 7.73 (m, 5H), 7.65 - 7.52 (m, 2H), 7.40 (t, J = 10.3 Hz, 1H), 3.70 (d, J = 8.4 Hz, 1H), 3, 51 (d, J = 8.5 Hz, 1H), 1.46 (s, 9H);
¹⁹ F NMR (400 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -116.90,
-116.90, -116.93, -116.96,
-117.00, -122.51, -122.95,
-122.96 F1543 ESIMS m/z 634 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 9.43 (s, 1H), 8.86 (s, 1H), 8.07 (td, J = 8, 8, 5.7 Hz, 1H), 7.81 (d, J = 2.6 Hz, 1H), 7.75 (d, J = 2.5 Hz, 1H), 7.67 (d, J = 1.8 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.44 (dd, J = 8.3, 1.7 Hz, 1H), 7.10 (t, J = 9.1 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.37 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H) , 2.15 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-123.49, -128.99 F1544 ESIMS m/z 668 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.11 (s, 1H), 9.43 (s, 1H), 8.87 (s, 1H), 8.07 (td, J = 8, 7, 5.6 Hz, 1H), 7.81 (d, J = 2.6 Hz, 1H), 7.75 (d, J = 2.5 Hz, 1H), 7.70 (d, J = 0.8 Hz, 2H), 7.10 (td, J = 9.2, 2.0 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H), 2.15 (s, 3H);
¹⁹ F NMR (376 MHz, acetone) δ
-123.47, -128.98 F1545 ESIMS m/z 652 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.11 (s, 1H), 9.42 (s, 1H), 8.85 (s, 1H), 8.08 (td, J = 8, 6, 5.7 Hz, 1H), 7.87 - 7.79 (m, 3H), 7.76 (d, J = 2.5 Hz, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.15 - 7.07 (m, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.41(s, 3H), 2.15(s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -61.88 (d, J = 12.7 Hz), -117.66 (q, J = 12.8 Hz), -123.55,
-129.04 F1546 ESIMS m/z 634 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 9.38 (s, 1H), 8.99 (s, 1H), 8.81 (t, J = 8, 3 Hz, 1H), 7.80 (d, J = 2.5 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.67 (d, J = 2.0 Hz , 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.43 (dd, J = 8.3, 1.7 Hz, 1H), 7.17 (t, J = 10, 4 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.3 Hz, 1H), 2.40 (s, 3H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -127.05 (d, J = 3.5 Hz), -127.57 (d, J = 3.4 Hz) F1547 ESIMS m/z 668 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.09 (s, 1H), 9.37 (s, 1H), 8.98 (s, 1H), 8.81 (t, J = 8, 3 Hz, 1H), 7.80 (d, J = 2.7 Hz, 1H), 7.76 (d, J = 2.2 Hz, 1H), 7.70 (d, J = 0.8 Hz , 2H), 7.17 (t, J = 10.4 Hz, 1H), 3.65 (d, J = 8.5 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H ), 2.40 (s, 3H), 2.17 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -127.10 (d, J = 3.4 Hz), -127.61 (d, J = 3.4 Hz) F1548 ESIMS m/z 652 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 9.37 (s, 1H), 8.98 (s, 1H), 8.81 (t, J = 8, 4 Hz, 1H), 7.86 - 7.80 (m, 3H), 7.77 (d, J = 2.3 Hz, 1H), 7.48 (t, J = 9.7 Hz, 1H) , 7.18 (t, J = 10.4 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2 .40 (s, 3H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87 (d, J = 13.0 Hz), -117.66 (q, J = 12.8 Hz), -127.11 (d, J = 3.3 Hz), -127.62 (d, J = 3.3 Hz) F1549 ESIMS m/z 692 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.47 (s, 1H), 7.93 (d, J = 2.6 Hz, 1H), 7.80 - 7.63 (m, 4H), 7.56 (d, J = 8.8 Hz, 1H), 7.47 - 7.40 (m, 1H), 7.28 - 7.18 (m, 1H ), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 3.13 (s, 1H), 3.10 (s, 2H ), 1.47 (s, 2H), 1.33 (s, 6H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.28, -126.11 (dd, J = 9.4, 3.4 Hz) F1550 ESIMS m/z 594 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.18 (s, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.48 - 7.40 ( m, 1H), 7.00 - 6.83 (m, 2H), 5.28 (d, J = 6.6 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.91 (dt, J = 5.5, 2.6 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-132.00 (d, J = 13.0 Hz), -136.93 (d, J = 13.1 Hz) F1551 ESIMS m/z 694 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.36 (s, 1H), 10.87 (s, 1H), 10.30 (s, 1H), 8.02 (dd, J = 6, 3, 2.8 Hz, 1H), 7.92 (t, J = 8.0 Hz, 1H), 7.87 - 7.75 (m, 3H), 7.59 (t, J = 10.3 Hz, 1H), 7.38 (t, J = 9.4 Hz, 1H), 3.63 (d, J = 8.6 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.85, -118.50, -119.16,
-119.41 F1552 ESIMS m/z 674 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.87 (s, 1H), 10.72 (s, 1H), 10.28 (s, 1H), 8.12 - 7.96 (m, 2H), 7.91 - 7.77 (m, 3H), 7.55 (t, J = 10.3 Hz, 1H), 7.38 (t, J = 9.4 Hz, 1H), 6, 47 (t, J = 53.5 Hz, 1H), 3.67 - 3.60 (m, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.17, -119.87, -120.93 (d, J = 5.4 Hz), -125.62 F1553 ESIMS m/z 640 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.86 (s, 1H), 10.20 (s, 1H), 9.80 (s, 1H), 8.14 (t, J = 8, 3 Hz, 1H), 8.00 (dd, J = 6.2, 2.7 Hz, 1H), 7.88 - 7.76 (m, 3H), 7.44 (t, J = 10.4 Hz, 1H), 7.37 (t, J = 9.4 Hz, 1H), 3.63 (dt, J = 8.6, 0.7 Hz, 1H), 3.54 (d, J = 8 .5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.22, -122.31 (d, J = 4.5 Hz), -123.02 (d, J = 4.3 Hz) F1554 ESIMS m/z 692 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.39 (s, 1H), 10.88 (s, 1H), 10.29 (s, 1H), 8.03 (dd, J = 6, 2, 2.7 Hz, 1H), 7.85 (dt, J = 9.0, 3.0 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.52 ( td, J = 8.7, 5.6 Hz, 1H), 7.40 (t, J = 9.4 Hz, 1H), 7.36 - 7.26 (m, 1H), 3.64 (dt , J = 8.5, 0.7 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.86, -117.85, -119.18,
-122.93 F1555 ESIMS m/z 674 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.88 (s, 1H), 10.75 (s, 1H), 10.27 (s, 1H), 8.03 (dd, J = 6, 3, 2.7 Hz, 1H), 7.91 - 7.82 (m, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.63 (td, J = 8.7 , 5.6 Hz, 1H), 7.40 (t, J = 9.4 Hz, 1H), 7.32 - 7.22 (m, 1H), 6.47 (t, J = 53.4 Hz , 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.17, -119.60, -124.27,
-125.61 F1556 ESIMS m/z 638 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.88 (s, 1H), 10.20 (s, 1H), 9.82 (s, 1H), 8.09 - 7.97 (m, 1H), 7.93 - 7.69 (m, 4H), 7.39 (t, J = 9.4 Hz, 1H), 7.17 (t, J = 9.1 Hz, 1H), 3, 64 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H), 2.09 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-119.20, -122.73, -126.68 F1557 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.37 (s, 1H), 10.90 (s, 1H), 10.50 - 10.22 (m, 1H), 8.04 (dd, J = 6.2, 2.8 Hz, 1H), 7.92 (t, J = 8.0 Hz, 1H), 7.89 - 7.79 (m, 3H), 7.64 - 7.54 (m, 2H), 7.39 (t, J = 9.4 Hz, 1H), 3.70 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.5 Hz , 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.94 (d, J = 12.5 Hz), -73.89,
-116.97 (q, J = 12.7 Hz), -118.46 (d, J = 6.2 Hz), -119.20, -119.39 (d, J = 6.1 Hz) F1558 ESIMS m/z 658 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.90 (s, 1H), 10.73 (s, 1H), 10.41 - 10.20 (m, 1H), 8.14 - 7, 96 (m, 2H), 7.85 (dtd, J = 11.0, 6.4, 2.3 Hz, 3H), 7.57 (dt, J = 14.9, 10.5 Hz, 2H) , 7.39 (t, J = 9.4 Hz, 1H), 6.48 (t, J = 53.4 Hz, 1H), 3.70 (d, J = 8.4 Hz, 1H), 3 .50 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.94 (d, J = 12.3 Hz), -116.97 (q, J = 12.4 Hz), -119.21,
-119.86 (d, J = 5.3 Hz), -120.95 (d, J = 5.3 Hz), -125.65 F1559 ESIMS m/z 622 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 10.24 - 10.15 (m, 1H), 9.80 (s, 1H), 8.15 (t, J = 8.2 Hz, 1H), 8.01 (dd, J = 6.2, 2.8 Hz, 1H), 7.93 - 7.77 (m, 3H), 7.59 (dd, J = 10.7, 8.6 Hz, 1H), 7.44 (t, J = 10.4 Hz, 1H), 7.37 (t, J = 9.4 Hz, 1H), 3.70 (d , J = 8.4 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.93 (d, J = 12.7 Hz), -116.97 (q, J = 12.4 Hz), -119.26,
-122.33 (d, J = 4.2 Hz), -123.03 (d, J = 4.3 Hz) F1560 ESIMS m/z 674 ([M+H] ^- ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.39 (s, 1H), 10.91 (s, 1H), 10.52 - 10.03 (m, 1H), 8.04 (dd, J = 6.3, 2.7 Hz, 1H), 7.84 (dt, J = 10.2, 6.7 Hz, 3H), 7.59 (dd, J = 10.4, 8.9 Hz , 1H), 7.52 (td, J = 8.7, 5.6 Hz, 1H), 7.40 (t, J = 9.4 Hz, 1H), 7.31 (dd, J = 9, 9, 8.2 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H), 3.49 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.8 Hz), -73.87,
-116.97 (q, J = 12.7 Hz),
-117.82, -119.22, -122.92 F1561 ESIMS m/z 656 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.75 (s, 1H), 10.27 (s, 1H), 8.04 (dd, J = 6, 4, 2.8 Hz, 1H), 7.93 - 7.77 (m, 3H), 7.69 - 7.52 (m, 2H), 7.40 (t, J = 9.3 Hz, 1H ), 7.27 (td, J = 9.2, 1.7 Hz, 1H), 6.47 (t, J = 53.4 Hz, 1H), 3.69 (d, J = 8.5 Hz , 1H), 3.50 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (dd, J = 12.6, 3.5 Hz),
-116.97 (q, J = 12.6 Hz),
-119.22, -119.62, -124.28,
-125.61 F1562 ESIMS m/z 622 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.90 (s, 1H), 10.20 (s, 1H), 9.82 (s, 1H), 8.08 - 8.00 (m, 1H), 7.94 - 7.71 (m, 4H), 7.66 - 7.54 (m, 1H), 7.39 (t, J = 9.4 Hz, 1H), 7.17 (t , J = 9.2 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.49 (d, J = 8.4 Hz, 1H), 2.09 (s, 3H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.9 Hz), -116.98 (d, J = 12.5 Hz), -119.26,
-122.75, -126.69 F1563 131-136 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₃₄ H ₃₀ Cl ₃ F ₆ N ₃ O ₆ , 795.1104; found, 795,1094 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.50 (s, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.90 - 7.71 (m, 4H), 7.63 - 7.50 (m, 3H), 3.69 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -116.89, -116.92, -116.96, -116.99, -117.58,
-117.60, -121.80, -121.81 F1564 106-110 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₇ H ₁₄ Cl ₃ F ₁₀ N ₃ O ₃ , 722.9941; found, 722.9931 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.97 (s, 1H), 10.54 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.90 - 7.80 (m, 3H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.58 (ddd, J = 10.3 , 8.7, 4.9 Hz, 3H), 6.87 (tt, J = 51.5, 5.4 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3 .51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.94, -116.89, -116.92, -116.95, -116.99, -118.59,
-118.98, -118.99, -123.84,
-123.86, -123.88, -138.91,
-138.92, -138.94 F1565 116-121 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₄ Cl ₅ F ₆ N ₃ O ₃ , 704.9382; found, 704.9371 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.96 (s, 1H), 10.54 (s, 1H), 7.99 - 7.81 (m, 2H), 7.76 (dt, J = 5.2, 2.7 Hz, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.58 (dd, J = 11.7 , 9.4 Hz, 2H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 6.87 (tt, J = 51.6, 5.4 Hz, 1H), 3 .61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-118.59, -118.97, -118.99,
-123.84, -123.86, -123.87,
-138.90, -138.92, -138.94 F1566 96-100 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₄ H ₁₄ Cl ₃ F ₆ N ₃ O ₂ , 595.0056 found, 595.0076 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.14 (s, 1H), 7.92 - 7.79 (m, 3H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.64 - 7.50 (m, 2H), 7.20 - 7.07 (m, 2H), 5.11 (s, 2H), 3 .69 (dd, J = 8.5, 0.9 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.90, -59.93, -116.90, -116.93, -116.96, -117.00, -134.18,
-135.44 F1567 129-134 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₃ Cl ₆ F ₆ N ₃ O ₃ , 738.8992; found, 738.8988 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.25 (s, 1H), 10.94 (s, 1H), 10.53 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.83 - 7.71 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.38 - 7.25 (m, 1H), 6, 89 (tt, J = 51.4, 5.2 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.14, -123.59, -123.61,
-123.63, -124.45, -138.90,
-138.92, -138.94 F1568 125-130 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₃ Cl ₆ F ₆ N ₃ O ₃ , 738.8992; found, 738.8986 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.14 (s, 1H), 10.94 (s, 1H), 10.54 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.87 (t, J = 8.0 Hz, 1H), 7.83 - 7.73 (m, 3H), 7.63 - 7.52 (m, 2H), 6, 87 (tt, J = 51.5, 5.3 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H)
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-118.59, -118.97, -118.99,
-123.83, -123.85, -123.87,
-138.90, -138.92, -138.93 F1569 107-112 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₇ H ₁₄ Cl ₃ F ₁₀ N ₃ O ₃ , 722.9941; found, 722.9939 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.15 (s, 1H), 10.97 (s, 1H), 10.55 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.90 - 7.80 (m, 3H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.66 - 7.51 (m, 3H ), 6.87 (tt, J = 51.5, 5.4 Hz, 1H), 3.70 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz , 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91, -59.94, -116.88, -116.91, -116.95, -116.98, -118.59,
-118.98, -118.99, -123.84,
-123.86, -123.88, -138.90,
-138.92, -138.94 F1570 ESIMS m/z 638.2 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.06 (s, 1H), 10.41 (s, 1H), 9.78 (s, 1H), 7.95 (dd, J = 11, 1, 6.1 Hz, 1H), 7.91 - 7.79 (m, 2H), 7.71 (s, 1H), 7.68 - 7.52 (m, 2H), 7.19 (t , J = 9.2 Hz, 1H), 3.70 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.8 Hz), -116.93 (t, J = 12.6 Hz), -119.98 -
-121.00 (m), -124.71, -135.63 (d, J = 23.9 Hz), -144.76 (d, J = 23.9 Hz) F1571 ESIMS m/z 674.0 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.02 - 7.85 (m, 2H), 7.73 (dd, J = 5.1, 2.4 Hz, 1H), 7.66 ( dt, J = 4.3, 2.4 Hz, 2H), 7.37 (t, J = 9.8 Hz, 1H), 7.14 (td, J = 9.2, 2.0 Hz, 1H ), 6.29 (t, J = 53.5 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, methanol- _d4 ) δ -62.85 (d, J = 12.9 Hz),
-117.72 (q, J = 12.8 Hz), -122.26 (d, J = 2.3 Hz), -127.86 (d, J = 14.3 Hz), -137.20 ( d, J = 21.8 Hz), -146.13 (d, J = 21.9 Hz) F1572 ESIMS m/z 692.0 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.96 (dtd, J = 15.0, 8.7, 7.9, 4.2 Hz, 2H), 7.74 (dt, J = 4 ,8, 2.3 Hz, 1H), 7.72 - 7.64 (m, 2H), 7.38 (t, J = 9.9 Hz, 1H), 7.18 (td, J = 9, 2, 2.0 Hz, 1H), 3.65 (d, J = 8.2 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H), 1 ⁹ F NMR (376 MHz, methanol-d ₄ ) δ -62.90 (d, J = 12.9 Hz), -76.74, -117.82 (q, J = 12.9 Hz),
-122.58, -128.01, -137.32 (d, J = 21.8 Hz), -146.26 (d, J = 21.8 Hz) F1573 ESIMS 674.1 m/z ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.05 - 7.89 (m, 1H), 7.75 (q, J = 3.7 Hz, 2H), 7.68 (dd, J = 6.4, 2.6 Hz, 2H), 7.38 (t, J = 9.7 Hz, 1H), 7.15 (td, J = 9.1, 2.1 Hz, 1H), 6, 25 (t, J = 53.7 Hz, 1H), 3.65 (d, J = 8.2 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, methanol- _d4 ) δ -62.89 (d, J = 12.9 Hz),
-117.82 (d, J = 12.7 Hz), -121.23 (d, J = 3.3 Hz), -127.21, -127.95, -137.17 (d, J = 21 .6 Hz), -146.03 (d, J = 21.8 Hz) F1574 ESIMS m/z 692.0 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.98 (ddd, J = 12.2, 7.0, 2.7 Hz, 1H), 7.75 (dd, J = 5.1, 2 .6 Hz, 1H), 7.72 - 7.65 (m, 2H), 7.65 - 7.54 (m, 1H), 7.38 (t, J = 9.8 Hz, 1H), 7 .18 (td, J = 9.1, 1.9 Hz, 1H), 3.65 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H) ;
¹⁹ F NMR (376 MHz, methanol- _d4 ) δ -62.88 (d, J = 12.8 Hz), -76.89, -117.80 (t, J = 12.8 Hz), -119 .72 (d, J = 3.6 Hz), -125.57 (d, J = 3.9 Hz), -137.10 (d, J = 21.7 Hz), -145.96 (d, J = 21.5 Hz) F1575 ESIMS m/z 621.9 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.96 (ddd, J = 12.0, 6.9, 2.5 Hz, 1H), 7.82 (td, J = 8.8, 5 .5 Hz, 1H), 7.77 - 7.69 (m, 1H), 7.59 - 7.46 (m, 2H), 7.29 (dd, J = 8.5, 2.1 Hz, 1H), 7.13 - 7.00 (m, 1H), 3.56 (d, J = 8.3 Hz, 1H), 3.20 (d, J = 8.3 Hz, 1H), 2, 17 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -123.48, -129.19, -137.09 (d, J = 21.7 Hz), -145.96 (d, J = 21.7 Hz) F1576 ESIMS m/z 638.0 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.98 (ddt, J = 9.6, 7.0, 2.6 Hz, 1H), 7.82 (td, J = 8.8, 5 .5 Hz, 1H), 7.74 (s, 1H), 7.71 - 7.64 (m, 2H), 7.38 (t, J = 9.8 Hz, 1H), 7.07 (dt , J = 9.2, 4.9 Hz, 1H), 3.65 (d, J = 8.1 Hz, 1H), 3.24 (dd, J = 8.2, 1.0 Hz, 1H) , 2.17 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -62.89 (d, J = 12.8 Hz),
-117.81 (d, J = 12.8 Hz),
-123.56, -129.23, -137.17 (d, J = 21.5 Hz), -146.04 (d, J = 21.6 Hz) F1577 ESIMS m/z 658.0 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.97 (ddd, J = 12.1, 6.8, 2.6 Hz, 1H), 7.74 (q, J = 5.2 Hz, 2H), 7.59 - 7.49 (m, 2H), 7.29 (dd, J = 8.3, 2.2 Hz, 1H), 7.14 (td, J = 9.2, 2, 0 Hz, 1H), 6.25 (t, J = 53.7 Hz, 1H), 3.56 (d, J = 8.3 Hz, 1H), 3.20 (d, J = 8.2 Hz , 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -121.10 (d, J = 3.2 Hz),
-127.15 (d, J = 3.3 Hz), -127.88, -137.03 (d, J = 21.8 Hz), -145.89 (d, J = 21.5 Hz) F1578 ESIMS m/z 675.9 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.04 - 7.93 (m, 1H), 7.74 (d, J = 4.7 Hz, 1H), 7.59 (dt, J = 8.7, 4.2 Hz, 1H), 7.56 - 7.51 (m, 2H), 7.30 (dd, J = 8.6, 2.2 Hz, 1H), 7.18 (td , J = 9.1, 2.0 Hz, 1H), 3.57 (d, J = 8.3 Hz, 1H), 3.20 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, methanol- _d4 ) δ -76.88, -119.72 (d, J = 4.1 Hz), -125.58 (d, J = 4.1 Hz), -137 .11 (d, J = 21.7 Hz), -145.94 F1579 ESIMS m/z 709.0 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.24 (t, J = 7.9 Hz, 1H), 7.95 (ddd, J = 12.1, 7.0, 2.7 Hz, 1H), 7.72 (dt, J = 4.1, 1.7 Hz, 1H), 7.52 (d, J = 0.8 Hz, 2H), 7.27 (t, J = 10.1 Hz, 1H), 3.56 (dt, J = 8.3, 0.8 Hz, 1H), 3.23 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, methanol- _d4 ) δ -76.84, -122.03 (d, J = 5.7 Hz), -122.44 (d, J = 6.0 Hz), -137 .17 (d, J = 21.8 Hz), -146.01 (d, J = 21.8 Hz) F1580 ESIMS m/z 691.2 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.38 (t, J = 8.0 Hz, 1H), 7.95 (ddd, J = 12.2, 6.9, 2.7 Hz, 1H), 7.71 (dt, J = 4.9, 2.3 Hz, 1H), 7.52 (d, J = 0.8 Hz, 2H), 7.24 (t, J = 10.2 Hz, 1H), 6.25 (t, J = 53.7 Hz, 1H), 3.56 (dt, J = 8.2, 0.8 Hz, 1H), 3.23 (d, J = 8 ,3 Hz, 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -123.52 (dd, J = 84.5, 5.1 Hz), -127.86, -137.16 (d, J = 21.8 Hz ), -146.03 (d, J = 21.9 Hz) F1581 ESIMS m/z 655.5 ([MH] ^- ) ^1H NMR (400 MHz, CDCl ₃ ) δ 10.83 (t, J = 8.1 Hz, 1H), 10.38 (dq, J = 10.0, 3.4, 2.7 Hz, 1H) , 10.16 - 10.08 (m, 1H), 9.95 (s, 2H), 9.59 (t, J = 10.2 Hz, 1H), 5.99 (d, J = 8.2 Hz, 1H), 5.66 (d, J = 8.0 Hz, 1H), 4.60 (s, 3H);
¹⁹ F NMR (376 MHz, methanol-d ₄ ) δ -125.20 (d, J = 4.6 Hz),
-125.35 (d, J = 4.5 Hz), -137.21 (d, J = 22.0 Hz), -146.13 (d, J = 21.7 Hz) F1582 ESIMS m/z 676.1 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.22 (t, J = 7.9 Hz, 1H), 7.97 (ddd, J = 12.1, 7.0, 2.7 Hz, 1H), 7.81 - 7.67 (m, 1H), 7.59 - 7.45 (m, 2H), 7.35 - 7.16 (m, 2H), 3.62 - 3.50 ( m, 1H), 3.20 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -76.88, -122.02 (d, J = 5.6 Hz), -122.38 (d, J = 5.8 Hz), -137 .30 (d, J = 21.8 Hz), -146.20 (d, J = 21.9 Hz) F1583 ESIMS m/z 658 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.37 (t, J = 8.0 Hz, 1H), 7.97 (ddd, J = 12.1, 7.0, 2.7 Hz, 1H), 7.72 (dd, J = 4.8, 2.3 Hz, 1H), 7.57 - 7.50 (m, 2H), 7.33 - 7.21 (m, 2H), 6 .25 (t, J = 53.7 Hz, 1H), 3.61 - 3.50 (m, 1H), 3.19 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -123.48 (dd, J = 85.8, 5.1 Hz), -127.89, -137.24 (d, J = 21.7 Hz ), -146.16 (d, J = 21.9 Hz) F1584 ESIMS m/z 691.6 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.24 (t, J = 7.9 Hz, 1H), 7.97 (ddd, J = 12.1, 7.0, 2.7 Hz, 1H), 7.73 (dt, J = 4.8, 2.1 Hz, 1H), 7.71 - 7.61 (m, 2H), 7.46 - 7.32 (m, 1H), 7 .27 (t, J = 10.1 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, methanol- _d4 ) δ -62.86 (d, J = 12.9 Hz), -76.86, -117.75 (d, J = 12.9 Hz), -122 .03 (d, J = 6.0 Hz), -122.42 (d, J = 5.7 Hz), -137.24 (d, J = 21.8 Hz), -146.13 (d, J = 21.8 Hz) F1585 ESIMS m/z 623.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.40 (t, J = 8.2 Hz, 1H), 7.96 (ddd, J = 12.2, 7.0, 2.7 Hz, 1H), 7.70 (dt, J = 4.8, 2.1 Hz, 1H), 7.51 (d, J = 2.4 Hz, 2H), 7.28 (ddd, J = 8.3 , 2.2, 0.7 Hz, 1H), 7.16 (t, J = 10.3 Hz, 1H), 3.55 (d, J = 8.3 Hz, 1H), 3.19 (d , J = 8.3 Hz, 1H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, methanol-d ₄ ) δ -125.18 (d, J = 4.3 Hz),
-125.33 (d, J = 4.5 Hz), -137.23 (d, J = 21.8 Hz), -146.19 (d, J = 21.8 Hz) F1586 ESIMS m/z 673.9 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.37 (t, J = 8.0 Hz, 1H), 7.97 (ddd, J = 12.2, 7.0, 2.7 Hz, 1H), 7.72 (p, J = 2.0 Hz, 1H), 7.70 - 7.61 (m, 2H), 7.37 (t, J = 9.8 Hz, 1H), 7. 24 (t, J = 10.2 Hz, 1H), 6.25 (t, J = 53.7 Hz, 1H), 3.63 (d, J = 8.3 Hz, 1H), 3.24 ( d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -62.86 (d, J = 12.9 Hz),
-117.76 (d, J = 12.7 Hz), -123.38 (d, J = 5.3 Hz), -123.61 (d, J = 5.2 Hz), -127.90, -137.24 (d, J = 21.8 Hz), -146.16 (d, J = 21.8 Hz) F1587 ESIMS m/z 638.1 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.40 (t, J = 8.1 Hz, 1H), 7.96 (ddd, J = 12.1, 6.9, 2.7 Hz, 1H), 7.75 - 7.69 (m, 1H), 7.67 (dd, J = 6.3, 2.8 Hz, 2H), 7.37 (t, J = 9.8 Hz, 1H ), 7.16 (t, J = 10.3 Hz, 1H), 3.63 (d, J = 8.2 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H), 2.17(s, 3H);
¹⁹ F NMR (376 MHz, methanol-d ₄ ) δ -62.85 (d, J = 12.8 Hz),
-117.78 (t, J = 12.9 Hz), -125.18 (d, J = 4.6 Hz), -125.33 (d, J = 4.4 Hz), -137.27, -146.20 (d, J = 21.9 Hz) F1588 ESIMS m/z 709.9 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.09 - 7.91 (m, 1H), 7.74 (s, 1H), 7.66 - 7.50 (m, 3H), 7, 18 (td, J = 9.1, 2.0 Hz, 1H), 3.59 (dt, J = 8.4, 0.8 Hz, 1H), 3.24 (d, J = 8.3 Hz , 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -76.88, -119.72 (d, J = 4.0 Hz), -125.58 (d, J = 4.0 Hz), -137 .09 (d, J = 21.6 Hz), -145.92 (d, J = 21.6 Hz) F1589 ESIMS m/z 691.8 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.96 (ddd, J = 12.2, 6.7, 2.5 Hz, 1H), 7.82 - 7.68 (m, 2H), 7.61 - 7.49 (m, 2H), 7.14 (td, J = 9.1, 2.0 Hz, 1H), 6.25 (t, J = 53.7 Hz, 1H), 3 .57 (d, J = 8.2 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, methanol-d ₄ ) δ -121.05 (d, J = 3.1 Hz),
-126.83 - -127.29 (m), -127.85, -136.97 (d, J = 21.8 Hz), -145.78 (d, J = 21.7 Hz) F1590 ESIMS m/z 655.2 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.96 (ddd, J = 12.3, 6.9, 2.6 Hz, 1H), 7.82 (td, J = 8.7, 5 .5 Hz, 1H), 7.77 - 7.68 (m, 1H), 7.53 (d, J = 0.8 Hz, 2H), 7.07 (td, J = 9.1, 1, 9 Hz, 1H), 3.58 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -123.49, -129.20, -137.08 (d, J = 21.7 Hz), -145.91 (d, J = 21.7 Hz) F1591 ESIMS m/z 590 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.27 (s, 1H), 8.01 (d, J = 2.7 Hz, 1H), 7.80 (dd, J = 8.7, 2.7 Hz, 1H), 7.62 - 7.54 (m, 2H), 7.46 (d, J = 8.7 Hz, 1H), 7.42 - 7.31 (m, 3H), 6.89 (ddd, J = 10.8, 9.1, 2.1 Hz, 1H), 4.77 (s, 2H), 3.58 (d, J = 8.3 Hz, 1H), 3.30 (d, J = 8.4 Hz, 1H). ¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -137.05, -144.01. F1592 ESIMS m/z 529 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.27 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.7 Hz, 1H), 7.50 - 7.43 (m, 1H), 7.48 - 7.38 (m, 2H), 7.37 (td, J = 8.6, 5.5 Hz, 1H), 7.23 - 7.12 (m, 2H), 6.89 (ddd, J = 10.8, 9.0, 2.1 Hz, 1H), 4.77 (s, 2H), 3.62 - 3.55 (m, 1H), 3.28 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -115.61, -137.08, -144.05 F1593 ESIMS m/z 546 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.29 (s, 1H), 8.02 (d, J = 2.7 Hz, 1H), 7.79 (dd, J = 8.8, 2.6 Hz, 1H), 7.48 - 7.31 (m, 6H), 6.88 (ddd, J = 11.0, 9.1, 1.9 Hz , 1H), 4.76 (s, 2H), 3.59 (d, J = 8.3 Hz, 1H), 3.29 (d, J = 8.4 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -136.87, -143.86 F1594 ESIMS m/z 590 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.27 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.7 Hz, 1H), 7.61 (t, J = 1.9 Hz, 1H), 7.55 (dt, J = 7.9, 1.6 Hz, 1H), 7.50 - 7.32 (m, 4H), 6.89 (ddd, J = 11.0, 9.1, 2.0 Hz, 1H), 4.77 (s, 2H), 3 .62 (d, J = 8.3 Hz, 1H), 3.35 (d, J = 8.4 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -137.09, -144.08 F1595 ESIMS m/z 546 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.30 (s, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.79 (dd, J = 8.7, 2.7 Hz, 1H), 7.49 - 7.31 (m, 6H), 6.88 (ddd, J = 10.9, 9.0, 2.1 Hz , 1H), 3.67 - 3.59 (m, 1H), 3.35 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -136.89, -143.92 F1596 ESIMS m/z 529 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.31 (s, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.49 - 7.30 (m, 3H), 7.27 - 7.19 (m, 1H), 7.19 (dt, J = 9.9, 2.1 Hz, 1H), 7.17 - 7.07 (m, 1H), 6.88 (ddd, J = 10.8, 9.1, 2.0 Hz, 1H), 4.75 (s, 2H), 3.63 (d, J = 8.3 Hz, 1H), 3.32 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -114.14, -136.67, -143.71 F1597 ESIMS m/z 668 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.76 (s, 1H), 9.55 (s, 1H), 8.17 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.8, 2.7 Hz, 1H), 7.66 - 7.53 (m, 2H), 7.48 (d, J = 8.8 Hz, 1H), 7.43 - 7.33 (m, 2H), 7.20 (td, J = 9.3, 2.0 Hz, 1H), 6.45 (t, J = 53.5 Hz, 1H), 3.58 (d, J = 8.4 Hz, 1H), 3.30 (d, J = 8, 4 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -123.07, -127.06, -128.41 F1598 ESIMS m/z 607 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.78 (s, 1H), 9.57 (s, 1H), 8.17 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.7 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.51 - 7.37 (m, 3H), 7.28 - 7.09 (m, 3H), 6.46 (t, J = 53.5 Hz, 1H), 3.59 (d, J = 8.0 Hz , 1H), 3.29 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -115.65, -123.06, -127.05,
-128.40 F1599 ESIMS m/z 624 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.77 (s, 1H), 9.57 (s, 1H), 8.16 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.44 ( s, 5H), 7.20 (td, J = 9.2, 2.0 Hz, 1H), 6.46 (t, J = 53.5 Hz, 1H), 3.60 (d, J = 8 .4 Hz, 1H), 3.30 (d, J = 8.4 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -122.99, -127.03, -128.36 F1600 ESIMS m/z 668 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.77 (s, 1H), 9.56 (s, 1H), 8.17 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 - 7.32 (m, 5H), 7.20 (td, J = 9.3, 2.1 Hz, 1H), 6.46 (t, J = 53.5 Hz, 1H), 3.62 (d , J = 8.4 Hz, 1H), 3.37 (d, J = 8.4 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -123.10, -127.07, -128.45 F1601 ESIMS m/z 624 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.76 (s, 1H), 9.56 (s, 1H), 8.17 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.7 Hz, 1H), 7.81 (dd, J = 8.7, 2.7 Hz, 1H), 7.56 - 7.35 (m, 5H), 7.20 (td, J = 9.3, 2.0 Hz, 1H), 6.46 (t, J = 53.5 Hz, 1H), 3.63 (d , J = 8.3 Hz, 1H), 3.36 (d, J = 8.4 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -123.07, -127.05, -128.42 F1602 ESIMS m/z 607 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.77 (s, 1H), 9.57 (s, 1H), 8.16 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.7 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.53 - 7.37 (m, 2H), 7.33 - 7.08 (m, 4H), 6.46 (t, J = 53.5 Hz, 1H), 3.63 (d, J = 8.4 Hz , 1H), 3.34 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -114.36, -122.94, -127.01,
-128.33 F1603 ESIMS m/z 711 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.45 (s, 1H), 8.84 (s, 1H), 8.14 - 7.99 (m, 2H), 7.87 - 7.78 (m, 3H), 7.48 (dt, J = 9.7, 5.2 Hz, 2H), 7.12 (td, J = 9.2, 2, 0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.58 (q, J = 7.0 Hz, 2H), 3.49 - 3.39 (m, 1H) , 1.45 (s, 6H), 1.24 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87, -117.59, -123.42,
-129.11 F1604 ESIMS m/z 678 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.65 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.67 - 7.61 (m, 1H), 7, 56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.20 (td, J = 9.1, 1.7 Hz , 1H), 4.01 (q, J = 6.7 Hz, 1H), 3.66 - 3.42 (m, 4H), 1.34 (d, J = 6.7 Hz, 3H), 1 .20 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.91 (d, J = 3.4 Hz), -124.71 (d, J = 4.0 Hz) F1605 ESIMS m/z 692 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.45 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.65 (td, J = 9.0, 6.1 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.19 (td, J = 9 ,1, 1.8 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.53 - 3.40 (m, 3H), 1.38 (s, 6H), 1 .22 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.03 (d, J = 3.9 Hz), -124.93 (d, J = 3.7 Hz) F1606 ESIMS m/z 650 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.42 (s, 1H), 9.63 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.61 (dt, J = 8.7, 4.4 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.23 - 7.14 (m , 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.67 (p, J = 6.9 Hz, 1H ), 1.13 (d, J = 6.8 Hz, 6H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.86 (d, J = 3.9 Hz), -124.73 (d, J = 4.1 Hz) F1607 ESIMS m/z 756 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.69 (s, 1H), 10.53 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 - 7.71 (m, 3H), 7.69 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H) , 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.29 (td, J = 9.1, 1.8 Hz, 1H), 5.12 (p, J = 7 .9 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.66, -121.32 (d, J = 2.6 Hz),
-124.62 (d, J = 2.6 Hz) F1608 ESIMS m/z 682 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.47 (s, 1H), 10.30 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.65 (dt, J = 8.6, 4.4 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.27 - 7.18 (m , 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.89 (dt, J = 13.7, 9, 5 Hz, 1H), 2.09 - 1.92 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.63 (d, J = 3.3 Hz), -124.11 - -125.17 (m), -139.72 (d, J = 149.1 Hz) F1609 ESIMS m/z 671 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.47 (s, 1H), 10.06 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.72 - 7.63 (m, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7, 43 (dd, J = 8.5, 2.1 Hz, 1H), 7.22 (td, J = 9.1, 1.7 Hz, 1H), 3.61 (d, J = 8.4 Hz , 1H), 3.47 (d, J = 8.5 Hz, 1H), 1.77 (q, J = 4.5, 3.9 Hz, 2H), 1.65 (q, J = 5, 3, 4.6 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.93 (d, J = 3.2 Hz), -124.55 (d, J = 3.2 Hz) F1610 ESIMS m/z 678 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.88 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 - 7.73 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.62 (td, J = 8.6, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.20 (td, J = 9 ,2, 1.8 Hz, 1H), 3.96 (t, J = 8.2 Hz, 1H), 3.83 - 3.66 (m, 3H), 3.61 (d, J = 8, 5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 3.25 (p, J = 7.4 Hz, 1H), 2.19 - 2.00 (m, 2H) ;
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.76 (d, J = 3.5 Hz), -124.57 (d, J = 4.0 Hz) F1611 ESIMS m/z 678 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.61 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.68 - 7.60 (m, 1H), 7, 55 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.26 - 7.13 (m, 1H), 4.46 (dd, J = 8.3, 5.1 Hz, 1H), 4.07 - 3.95 (m, 1H), 3.84 (dt, J = 8.0, 6.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.23 (dq, J = 11.9, 7.7 Hz, 1H ), 2.02 - 1.77 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.93 (d, J = 3.6 Hz), -124.76 (d, J = 4.0 Hz) F1612 ESIMS m/z 709 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.48 (s, 1H), 8.80 (s, 1H), 8.07 (td, J = 8, 7, 5.6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.82 (dq, J = 11.3, 2.7 Hz, 3H), 7.48 ( dt, J = 8.1, 5.1 Hz, 2H), 7.11 (td, J = 9.2, 2.0 Hz, 1H), 4.46 (ddd, J = 8.8, 4, 8, 0.9 Hz, 1H), 4.18 (dp, J = 8.6, 6.0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 ( d, J = 8.3 Hz, 1H), 2.42 - 2.21 (m, 1H), 2.15 - 2.06 (m, 1H), 2.26 - 2.00 (m, 1H) , 1.52 (ddt, J = 12.1, 9.5, 8.3 Hz, 1H), 1.35 (d, J = 6.1 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.55, -123.28,
-128.97 F1613 ESIMS m/z 657 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.31 (s, 1H), 8.85 (s, 1H), 8.05 (d, J = 2, 6 Hz, 1H), 7.88 - 7.79 (m, 3H), 7.54 - 7.44 (m, 2H), 7.20 - 7.10 (m, 1H), 3.72 (d , J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.60, -117.63,
-118.16, -121.74 F1614 ESIMS m/z 690 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.96 (s, 1H), 10.66 (s, 0.8H), 10.60 (s, 0.2H), 8.00 - 7.89 (m, 2H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.56 (d, J = 8.8 Hz , 1H), 7.48 - 7.35 (m, 2H), 3.60 (d, J = 8.5 Hz, 1H), 3.49 (d, J = 1.8 Hz, 0.6H) , 3.46 (d, J = 8.5 Hz, 1H), 3.34 (s, 2.4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -69.34, -70.10 (t, J = 3.5 Hz), -122.72 (d, J = 7.6 Hz), -123.11 (dt, J = 11.0, 3.7 Hz),
-125.91 (dd, J = 28.4, 3.9 Hz),
-126.01 (d, J = 11.7 Hz) F1615 ESIMS m/z 738 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.96 (s, 1H), 10.66 (s, 0.85H), 10.60 (s, 0.15H), 7.98 - 7.88 (m, 2H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.8 Hz , 1H), 7.43 (dd, J = 8.6, 2.2 Hz, 1.7H), 7.39 (dd, J = 5.4, 1.7 Hz, 0.3H), 3, 60 (d, J = 8.4 Hz, 1H), 3.54 (t, J = 2.6 Hz, 0.45H), 3.46 (d, J = 8.5 Hz, 1H), 3, 34 (s, 2.55H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -81.63 (d, J = 15.8 Hz), -115.97, -116.41 (dd, J = 22.4, 4, 8 Hz), -122.97 (d, J = 9.3 Hz), -123.07 - -123.60 (m),
-126.01 (d, J = 26.6 Hz), -126.26 (d, J = 11.8 Hz) F1616 ESIMS m/z 692 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) rotary isomers δ 10.96 (s, 1H), 10.59 (d, J = 5.0 Hz, 0.8H), 10.48 (s, 0. 2H), 7.98 - 7.90 (m, 1H), 7.88 - 7.77 (m, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.60 - 7.52 (m, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.40 - 7.31 (m , 0.8H), 7.25 (t, J = 9.4 Hz, 0.2H), 4.60 - 4.50 (m, 0.2H), 3.89 - 3.76 (m, 0 ,8H), 3.60 (d, J = 8.5 Hz, 1H), 3.55 - 3.48 (m, 0.4H), 3.47 (d, J = 8.5 Hz, 1H) , 3.37 (s, 0.6H), 3.25 - 3.05 (m, 4H), 1.34 (dd, J = 6.6, 1.4 Hz, 0.6H) 1.21 - 1.05 (m, 3H), 1.01 - 0.91 (m, 2.4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -122.18, -123.55,
-125.08 (d, J = 6.5 Hz), -126.24 (d, J = 16.5 Hz) F1617 ESIMS m/z 659 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.96 (s, 1H), 10.62 (s, 0.6H), 10.51 (s, 0.4H), 7.99 - 7.88 (m, 1.4H), 7.79 - 7.67 (m, 3.6H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.37 (t, J = 9.2 Hz, 0.6H), 7.27 (t, J = 9.2 Hz, 0.4H), 4, 44 (s, 0.8H), 3.86 - 3.68 (m, 1.2H), 3.60 (dd, J = 8.5, 3.3 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 3.29 (s, 1.2H), 3.17 (s, 1.8H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -121.63 (d, J = 5.7 Hz), -122.66 (d, J = 13.3 Hz),
-125.06 (d, J = 8.5 Hz), -125.89 (d, J = 19.3 Hz) F1618 ESIMS m/z 700 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.79 (s, 1H), 10.51 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 - 7.66 (m, 4H), 7.63 - 7.53 (m, 2H), 7.34 - 7.21 (m, 1H), 6.54 (t , J = 53.2 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.67, -124.25, -125.77 F1619 ESIMS m/z 858 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.51 (s, 1H), 7.92 (dd, J = 4.6, 2.3 Hz, 2H) , 7.82 (d, J = 2.0 Hz, 1H), 7.79 - 7.69 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.27 ( t, J = 9.2 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-123.51 (d, J = 2.0 Hz), -126.49 F1620 ESIMS m/z 852 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.51 (s, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.83 - 7.70 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.27 (td, J = 9.3, 1.7 Hz, 1H), 7.17 ( dd, J = 9.8, 8.5 Hz, 1H), 3.44 (s, 2H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.05, -123.51 (d, J = 2.1 Hz), -126.48 (d, J = 2.1 Hz) F1621 ESIMS m/z 812 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.51 (s, 1H), 7.94 (t, J = 1.8 Hz, 2H), 7.83 - 7.69 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.27 (td, J = 9.2, 1.8 Hz, 1H), 3.72 ( d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.16, -123.51 (d, J = 2.1 Hz),
-126.51 (d, J = 2.2 Hz) F1622 ESIMS m/z 656 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.18 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.84 - 7.70 (m, 3H), 7.54 (d, J = 8.8 Hz, 1H), 7.17 (dd, J = 9.8, 8.4 Hz, 1H), 6.96 - 6.85 (m, 1H), 6.79 (td, J = 8.4, 5.6 Hz, 1H), 5.31 (s, 2H), 3.44 (s, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.04, -133.96 (d, J = 14.0 Hz), -138.04 (d, J = 14.0 Hz) F1623 ESIMS m/z 736 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.79 (s, 1H), 10.51 (s, 1H), 7.92 (dd, J = 7, 7, 2.3 Hz, 2H), 7.82 (d, J = 2.0 Hz, 1H), 7.73 (ddd, J = 14.8, 8.6, 4.0 Hz, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.27 (dd, J = 9.9, 8.1 Hz, 1H), 6.54 (t, J = 53.2 Hz, 1H ), 3.63 (d, J = 8.5 Hz, 1H), 3.54 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.68, -124.25, -125.76 F1624 ESIMS m/z 734 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.79 (s, 1H), 10.51 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.85 - 7.67 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.33 - 7.24 (m, 1H), 7, 17 (dd, J = 9.8, 8.4 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3.44 (s, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.03, -120.64 (d, J = 2.7 Hz), -124.21 (d, J = 2.8 Hz), -125.81 F1625 ESIMS m/z 709 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.52 (s, 1H), 9.25 (s, 1H), 8.20 - 8.08 (m, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.82 (ddd, J = 10.3, 6.0, 2.3 Hz, 3H), 7.47 (dt, J = 8.3, 5.1 Hz, 2H), 7.15 (td, J = 9.2, 1.9 Hz, 1H), 5.19 (ddd, J = 7.9, 6.3, 1 .1 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.82 - 2.54 (m, 3H ), 2.40 (dddd, J = 10.2, 8.9, 7.9, 4.9 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.54, -123.11,
-128.67 F1626 ESIMS m/z 723 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.48 (s, 1H), 8.75 (s, 1H), 8.14 - 7.99 (m, 2H), 7.82 (dq, J = 11.2, 2.8 Hz, 3H), 7.53 - 7.43 (m, 2H), 7.11 (td, J = 9.2, 2, 0 Hz, 1H), 4.48 (dd, J = 8.7, 4.8 Hz, 1H), 3.96 (dq, J = 8.8, 6.2 Hz, 1H), 3.71 ( d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.41 - 2.24 (m, 1H), 2.23 - 2.00 (m , 2H), 1.78 (dp, J = 14.5, 7.4 Hz, 1H), 1.71 - 1.45 (m, 2H), 0.98 (t, J = 7.5 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.55, -123.26,
-128.95 F1627 ESIMS m/z 624 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.34 (s, 1H), 8.89 (s, 1H), 8.05 (d, J = 2, 6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 - 7.58 (m, 1H), 7.53 - 7.42 (m, 2H ), 7.36 (t, J = 8.8 Hz, 1H), 7.20 - 7.09 (m, 1H), 3.66 - 3.58 (m, 1H), 3.36 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -117.47, -118.02, -118.22,
-121.67 F1628 ESIMS m/z 640 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.34 (s, 1H), 8.89 (s, 1H), 8.05 (d, J = 2, 5 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.49 (d, J = 3.1 Hz, 4H), 7.19 - 7.09 ( m, 1H), 3.66 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -117.45, -118.00, -121.67 F1629 ESIMS m/z 640 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.35 (s, 1H), 8.90 (s, 1H), 8.05 (d, J = 2, 5 Hz, 1H), 7.82 (dd, J = 8.7, 2.6 Hz, 1H), 7.69 - 7.57 (m, 2H), 7.49 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.19 - 7.09 (m, 1H), 3.63 (d, J = 8.3 Hz , 1H), 3.39 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -117.44, -117.97, -121.64 F1630 ESIMS m/z 666 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) rotary isomers δ 10.96 (s, 1H), 10.57 (s, 0.7H), 10.48 (s, 0.3H), 7.98 - 7.91 (m, 1H), 7.86 - 7.77 (m, 0.9H), 7.78 - 7.72 (m, 2.1H), 7.69 (d, J = 8.4 Hz, 1H), 7.56 (dd, J = 8.7, 3.6 Hz, 1H), 7.43 (dd, J = 8.8, 2.1 Hz, 1H), 7.34 (td , J = 9.3, 1.8 Hz, 0.7H), 7.29 - 7.21 (m, 0.3H), 4.38 (s, 0.6H), 3.80 (s, 1 ,4H), 3.61 (dd, J = 8.4, 2.3 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 3.36 (s, 0.9H) , 3.26 (s, 0.9H), 3.18 (s, 2.1H), 3.15 (s, 2.1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -121.72 (dd, J = 7.0, 2.6 Hz), -123.13, -125.47 (dd, J = 5, 8, 2.9 Hz), -126.31 (d, J = 8.9 Hz) F1631 ESIMS m/z 614 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.12 (s, 1H), 10.18 (s, 1H), 7.96 - 7.90 (m, 2H), 7.84 - 7, 73 (m, 3H), 7.54 (d, J = 8.8 Hz, 1H), 6.91 (ddd, J = 10.6, 8.9, 1.8 Hz, 1H), 6.81 (td, J = 8.5, 5.6 Hz, 1H), 4.68 (s, 2H), 3.72 (d, J = 8.5 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.15, -133.88 (d, J = 13.8 Hz), -137.94 (d, J = 13.7 Hz) F1632 ESIMS m/z 621.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.01 (d, J = 2.6 Hz, 1H), 7.68 (dd, J = 8.8, 2.7 Hz, 2H), 7 .47 (d, J = 8.8 Hz, 1H), 7.43 (t, J = 1.9 Hz, 1H), 7.34 (dd, J = 1.9, 0.7 Hz, 2H) , 6.93 (ddd, J = 9.9, 8.5, 2.8 Hz, 1H), 3.57 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8 .3 Hz, 1H), 2.17 (s, 3H);
¹⁹ F NMR (376 MHz, methanol-d ₄ ) δ -112.21 (d, J = 6.8 Hz),
-117.47 (d, J = 6.5 Hz) F1633 ESIMS m/z 621.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.08 (d, J = 2.6 Hz, 1H), 7.69 (dd, J = 8.7, 2.6 Hz, 1H), 7 .50 (d, J = 8.8 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.35 (dd, J = 1.9, 0.7 Hz, 2H), 6, 95 (ddd, J = 9.9, 8.5, 2.9 Hz, 1H), 3.58 (d, J = 8.3 Hz, 1H), 3.25 (d, J = 8.3 Hz , 1H), 2.18 (s, 3H);
¹⁹ F NMR (376 MHz, methanol-d ₄ ) δ -112.12 (d, J = 7.0 Hz),
-116.01 (d, J = 6.9 Hz) F1634 ESIMS m/z 621.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.06 (d, J = 2.6 Hz, 1H), 7.76 - 7.59 (m, 2H), 7.54 - 7.41 ( m, 3H), 7.34 (dd, J = 1.9, 0.7 Hz, 2H), 3.57 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8 .3 Hz, 1H), 2.15 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -137.33 - -143.53 (m) F1635 ESIMS m/z 603.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.17 (dd, J = 6.9, 2.7 Hz, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7 .73 (dd, J = 8.8, 2.6 Hz, 1H), 7.52 - 7.40 (m, 3H), 7.34 (dd, J = 1.9, 0.7 Hz, 2H ), 7.13 (dd, J = 10.3, 9.0 Hz, 1H), 3.57 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8.3 Hz , 1H), 2.12 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -131.21 F1636 ESIMS m/z 604.0 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.06 (d, J = 2.6 Hz, 1H), 7.69 (dd, J = 8.8, 2.6 Hz, 1H), 7 .48 (d, J = 8.8 Hz, 1H), 7.46 - 7.38 (m, 2H), 7.38 - 7.30 (m, 3H), 7.10 (ddd, J = 9 .7, 8.2, 1.4 Hz, 1H), 3.57 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -119.88 F1637 ESIMS m/z 603.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.07 (d, J = 2.6 Hz, 1H), 7.69 - 7.57 (m, 2H), 7.48 (d, J = 8.7 Hz, 1H), 7.47 - 7.36 (m, 2H), 7.35 (dd, J = 1.9, 0.8 Hz, 2H), 3.58 (d, J = 8 .3 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -116.39 F1638 ESIMS m/z 604.0 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.23 (dd, J = 7.0, 2.7 Hz, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7 .70 (dd, J = 8.8, 2.6 Hz, 1H), 7.54 (ddd, J = 8.9, 4.4, 2.7 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.42 (t, J = 1.9 Hz, 1H), 7.33 (dd, J = 1.9, 0.7 Hz, 2H), 7.14 (dd , J = 10.4, 8.9 Hz, 1H), 3.56 (d, J = 8.3 Hz, 1H), 3.23 (d, J = 8.3 Hz, 1H), 2.17 (s, 3H);
^19F NMR (376 MHz, methanol- _d4 ) δ -131.81 F1639 ESIMS m/z 657.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 7.93 (d, J = 2.6 Hz, 1H), 7.87 (dt, J = 2.4, 1.2 Hz, 1H), 7 .70 (dd, J = 8.8, 2.6 Hz, 1H), 7.50 - 7.40 (m, 3H), 7.37 - 7.29 (m, 3H), 3.57 (d , J = 8.3 Hz, 1H), 3.23 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -77.04, -112.31 F1640 ESIMS m/z 656.1 ([MH] ^- ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.35 (dd, J = 6.8, 2.7 Hz, 1H), 7.96 (d, J = 2.6 Hz, 1H), 7 .73 (dd, J = 8.8, 2.6 Hz, 1H), 7.57 (ddd, J = 9.0, 4.2, 2.7 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H), 7.42 (t, J = 1.9 Hz, 1H), 7.37 - 7.30 (m, 2H), 7.23 (dd, J = 10.2, 8.9 Hz, 1H), 3.57 (d, J = 8.3 Hz, 1H), 3.24 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -76.98, -128.84 F1641 ESIMS m/z 657.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, methanol- _d4 ) δ 8.04 (dd, J = 6.8, 2.7 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7 .70 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (ddd, J = 9.0, 4.3, 2.7 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.42 (t, J = 1.9 Hz, 1H), 7.33 (dd, J = 1.9, 0.7 Hz, 2H), 7.23 (dd , J = 10.0, 9.0 Hz, 1H), 3.56 (d, J = 8.3 Hz, 1H), 3.23 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, methanol- _d4 ) δ -76.84, -128.30 F1642 ESIMS m/z 681 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.45 (s, 1H), 8.82 (s, 1H), 8.10 - 7.98 (m, 2H), 7.87 - 7.76 (m, 3H), 7.52 - 7.43 (m, 2H), 7.09 (td, J = 9.2, 2.0 Hz, 1H), 3 .71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.63 - 2.51 (m, 1H), 1.81 - 1, 64 (m, 1H), 1.58 - 1.43 (m, 1H), 1.19 (d, J = 6.8 Hz, 3H), 0.97 (t, J = 7.4 Hz, 3H );
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.58, -123.17,
-128.70 F1643 ESIMS m/z 693 ([M+H] ⁺ ) ¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.57, -123.28,
-128.81 F1644 ESIMS m/z 715 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.49 (s, 1H), 9.08 (s, 1H), 8.12 - 8.00 (m, 2H), 7.86 - 7.76 (m, 3H), 7.47 (dt, J = 9.9, 5.1 Hz, 2H), 7.12 (td, J = 9.2, 1, 9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 3.37 - 3.27 (m, 1H) , 2.97 - 2.77 (m, 4H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -82.47, -82.98, -83.77,
-84.28, -95.95, -96.46, -97.19,
-97.70, -117.56, -123.25,
-128.66 F1645 ESIMS m/z 712 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 9.66 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.81 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.5 Hz, 1H), 7.65 (td, J = 8.8, 5.8 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.26 - 7.14 (m, 1H), 4.01 (q, J = 6 .6 Hz, 1H), 3.67 - 3.44 (m, 4H), 1.34 (d, J = 6.7 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.91 (d, J = 2.6 Hz), -124.72 (d, J = 3.8 Hz) F1646 ESIMS m/z 684 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.44 (s, 1H), 9.71 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 (td, J = 8.7, 5.6 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.20 (td, J = 9.2, 1.8 Hz, 1H), 4, 07 (s, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 3.40 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.58 (d, J = 3.5 Hz), -124.46 (d, J = 3.7 Hz) F1647 ESIMS m/z 710 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.44 (s, 1H), 9.61 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 - 7.60 ( m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.19 (td, J = 9.3, 1.7 Hz, 1H), 4.46 (dd, J = 8 ,3, 5.1 Hz, 1H), 4.01 (dt, J = 7.9, 6.5 Hz, 1H), 3.84 (dt, J = 8.0, 6.7 Hz, 1H) , 3.64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 2.23 (dq, J = 11.8, 7.6 Hz, 1H), 2.02 - 1.82 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.94 (d, J = 3.6 Hz), -124.76 (d, J = 3.6 Hz) F1648 ESIMS m/z 706 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.48 (s, 1H), 10.19 (s, 1H), 7.98 (dd, J = 1, 7, 0.8 Hz, 1H), 7.93 (d, J = 2.6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.70 (td, J = 8.6, 5.7 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7, 36 (dd, J = 3.5, 0.8 Hz, 1H), 7.25 (td, J = 9.3, 1.7 Hz, 1H), 6.73 (dd, J = 3.5, 1.8 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.41 (d, J = 3.4 Hz), -124.40 (d, J = 3.4 Hz) F1649 ESIMS m/z 708 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.45 (s, 1H), 10.10 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (q, J = 8.1 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.21 (t, J = 9.2 Hz, 1H), 3.63 (d, J = 8, 5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 3.49 - 3.33 (m, 3H), 3.29 - 3.16 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.68 (d, J = 3.8 Hz), -124.53 (d, J = 3.7 Hz) F1650 ESIMS m/z 679 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.48 (s, 1H), 10.26 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.6 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 - 7.62 ( m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.23 (dd, J = 10.1, 8.3 Hz, 1H), 4.02 (s, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.50 (d, J = 3.1 Hz), -124.19 (d, J = 3.3 Hz) F1651 ESIMS m/z 722 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.48 (s, 1H), 10.24 (s, 1H), 7.92 (d, J = 2, 5 Hz, 1H), 7.81 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.5 Hz, 1H), 7.67 (td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.29 - 7.18 (m, 1H), 3.69 - 3.52 (m , 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.60, -120.65 (d, J = 3.1 Hz),
-124.30 (d, J = 2.9 Hz) F1652 ESIMS m/z 808 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 11.61 (s, 1H), 10.95 (s, 1H), 10.57 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.83 - 7.71 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.33 (t, J = 9.2 Hz, 1H) , 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-80.06 (t, J = 8.3 Hz), -119.31,
-121.35, -124.67, -126.81 F1653 ESIMS m/z 694 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.44 (s, 1H), 9.63 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 (s, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.62 (td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.19 (td, J = 9.2, 1.7 Hz, 1H), 3.64 (d, J = 8 .5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 2.27 (d, J = 7.0 Hz, 2H), 1.12 - 0.97 (m, 1H ), 0.59 - 0.42 (m, 2H), 0.30 - 0.15 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.45 (d, J = 3.6 Hz), -124.41 (d, J = 4.0 Hz) F1654 ESIMS m/z 668 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.42 (s, 1H), 9.69 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.6 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 - 7.51 ( m, 2H), 7.18 (td, J = 9.3, 1.6 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8 .5 Hz, 1H), 2.37 (q, J = 7.6 Hz, 2H), 1.10 (t, J = 7.6 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.54, -124.55 F1655 ESIMS m/z 682 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.44 (s, 1H), 9.71 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.81 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.67 - 7.58 ( m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.18 (t, J = 9.0 Hz, 1H), 3.70 - 3.60 (m, 1H), 3.55 (d, J = 8.5 Hz, 1H), 2.33 (t, J = 7.2 Hz, 2H), 1.62 (h, J = 7.3 Hz, 2H), 0, 93 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.55 (d, J = 3.6 Hz), -124.55 (d, J = 4.1 Hz) F1656 ESIMS m/z 708 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.56 (s, 1H), 10.97 (s, 1H), 10.55 (s, 1H), 7.97 - 7.91 (m, 2H), 7.84 - 7.71 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.37 - 7.28 (m, 1H), 3.72 (d , J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.15, -73.82, -121.09, -124.43 F1657 ESIMS m/z 690 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.79 (s, 1H), 10.51 (s, 1H), 7.94 (d, J = 2, 4 Hz, 2H), 7.84 - 7.68 (m, 4H), 7.57 (d, J = 8.7 Hz, 1H), 7.28 (td, J = 9.2, 1.8 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3.72 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.15, -120.67 (d, J = 2.7 Hz),
-124.22 (d, J = 2.8 Hz), -125.81 F1658 ESIMS m/z 656 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.43 (s, 1H), 9.77 (s, 1H), 7.95 - 7.90 (m, 2H), 7.83 - 7.72 (m, 3H), 7.65 - 7.58 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.18 (t , J = 9.1 Hz, 1H), 3.72 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.14, -120.46 (d, J = 3.6 Hz),
-124.56 (d, J = 3.8 Hz) F1659 ESIMS m/z 684 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.43 (s, 1H), 9.70 (s, 1H), 7.93 (dd, J = 5, 5, 2.3 Hz, 2H), 7.83 - 7.71 (m, 3H), 7.62 (td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.18 (td, J = 9.2, 1.7 Hz, 1H), 3.72 (d, J = 8.5 Hz, 1H), 3.53 (d , J = 8.5 Hz, 1H), 2.33 (t, J = 7.2 Hz, 2H), 1.62 (h, J = 7.3 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.15, -120.55 (d, J = 3.9 Hz),
-124.55 (d, J = 4.1 Hz) F1660 ESIMS m/z 714 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.65 (s, 1H), 7.97 - 7.89 (m, 2H), 7.84 - 7.71 (m, 3H), 7.65 (td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H ), 7.20 (td, J = 9.2, 1.7 Hz, 1H), 4.01 (q, J = 6.7 Hz, 1H), 3.72 (d, J = 8.5 Hz , 1H), 3.63 - 3.44 (m, 3H), 1.34 (d, J = 6.7 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.15, -120.92 (d, J = 3.1 Hz),
-124.72 (d, J = 3.9 Hz) F1661 ESIMS m/z 712 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.43 (s, 1H), 9.61 (s, 1H), 7.97 - 7.89 (m, 2H), 7.83 - 7.72 (m, 3H), 7.69 - 7.60 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.24 - 7 .15 (m, 1H), 4.46 (dd, J = 8.3, 5.1 Hz, 1H), 4.06 - 3.95 (m, 1H), 3.84 (dt, J = 8 ,0, 6.7 Hz, 1H), 3.72 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H), 2.23 (dq, J = 11.9, 7.7 Hz, 1H), 1.93 (ddd, J = 28.7, 13.5, 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.14, -120.94 (d, J = 3.5 Hz),
-124.76 (d, J = 3.9 Hz) F1662 ESIMS m/z 714 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.45 (s, 1H), 9.55 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.7, 2.4 Hz, 2H), 7.72 - 7.60 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.22 (t, J = 9.1 Hz, 1H), 3.61 (d, J = 8 .4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 1.54 - 1.45 (m, 2H), 1.46 - 1.36 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-65.81, -121.08, -124.62 F1663 ESIMS m/z 677 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.42 (s, 1H), 9.69 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.3, 2.4 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.67 - 7.58 ( m, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.17 (dd, J = 10 ,0, 8.3 Hz, 1H), 3.76 (dd, J = 8.9, 5.2 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 2.97 - 2.83 (m, 2H), 2.12 - 1.97 (m, 1H), 1.79 (dq, J = 12.4 , 6.5 Hz, 1H), 1.71 - 1.60 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.02 (d, J = 4.0 Hz), -124.91 (d, J = 3.9 Hz) F1664 ESIMS m/z 677 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.42 (s, 1H), 9.69 (s, 1H), 7.91 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.2, 2.4 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.66 - 7.58 ( m, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.22 - 7.13 (m , 1H), 3.75 (dd, J = 8.8, 5.2 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8, 5 Hz, 1H), 2.90 (q, J = 6.5 Hz, 2H), 2.13 - 2.00 (m, 1H), 1.79 (dq, J = 12.2, 6.5 Hz, 1H), 1.73 - 1.59 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.02 (d, J = 3.9 Hz), -124.92 (d, J = 4.0 Hz) F1665 ESIMS m/z 779 ([M+H] ⁺ ) ^1H NMR (400 MHz, _CDCl3 ) δ 9.39 (s, 1H), 8.46 (d, J = 2.4 Hz, 1H), 8.29 (td, J = 8.8, 5, 5 Hz, 1H), 7.94 (d, J = 2.7 Hz, 1H), 7.73 (dd, J = 8.8, 2.6 Hz, 1H), 7.62 - 7.55 ( m, 1H), 7.53 - 7.43 (m, 3H), 7.35 (d, J = 8.8 Hz, 1H), 6.95 (td, J = 9.1, 1.8 Hz , 1H), 3.61 (d, J = 8.2 Hz, 1H), 3.00 (d, J = 8.2 Hz, 1H), 1.44 (s, 18H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-62.58, -122.95, -132.63 F1666 ESIMS m/z 579 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.33 (s, 1H), 8.30 (d, J = 2.1 Hz, 1H), 7.96 (dd, J = 8.8, 2, 7 Hz, 1H), 7.66 (d, J = 2.7 Hz, 1H), 7.59 (d, J = 7.7 Hz, 1H), 7.52 - 7.41 (m, 3H) , 7.37 (dd, J = 18.7, 8.3 Hz, 2H), 6.82 - 6.72 (m, 1H), 3.74 (s, 2H), 3.60 (d, J = 8.2 Hz, 1H), 2.96 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-62.63, -134.53, -145.15 F1667 ESIMS m/z 688 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.50 (s, 1H), 9.22 (s, 1H), 8.10 (td, J = 8, 7, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.86 - 7.77 (m, 3H), 7.48 (dt, J = 10.1 , 5.1 Hz, 2H), 7.14 (td, J = 9.2, 2.0 Hz, 1H), 4.80 (q, J = 6.8 Hz, 1H), 3.71 (d , J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.74 (d, J = 6.8 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.80, -117.55, -123.17,
-128.61 F1668 ESIMS m/z 702 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.48 (s, 1H), 9.04 (s, 1H), 8.12 - 7.98 (m, 2H), 7.82 (dq, J = 8.8, 2.6 Hz, 3H), 7.47 (dt, J = 8.1, 5.0 Hz, 2H), 7.11 (td, J = 9.2, 1.9 Hz, 1H), 4.56 (dt, J = 7.7, 6.3 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3 .42 (d, J = 8.3 Hz, 1H), 2.95 (q, J = 14.9 Hz, 2H), 1.64 - 1.52 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.81, -117.57, -122.89,
-128.32 F1669 ESIMS m/z 702 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.50 (s, 1H), 9.22 (s, 1H), 8.11 (tt, J = 8, 7, 4.8 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.91 - 7.77 (m, 3H), 7.48 (dt, J = 9.7 , 5.1 Hz, 2H), 7.15 (td, J = 9.2, 2.0 Hz, 1H), 4.61 (t, J = 6.7 Hz, 1H), 3.71 (d , J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.24 - 1.92 (m, 2H), 1.13 - 0.99 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.52, -123.09,
-128.55 F1670 ESIMS m/z 811 ([M+H] ⁺ ) ^1H NMR (400 MHz, _CDCl3 ) δ 9.28 (s, 1H), 8.64 (d, J = 3.0 Hz, 1H), 8.30 (t, J = 8.1 Hz, 1H ), 8.18 (dd, J = 8.8, 2.7 Hz, 1H), 7.92 (d, J = 2.7 Hz, 1H), 7.52 (dq, J = 8.4, 4.7, 3.4 Hz, 2H), 7.44 (d, J = 8.8 Hz, 1H), 7.20 (t, J = 9.2 Hz, 1H), 3.58 (d, J = 8.2 Hz, 1H), 3.14 (d, J = 8.2 Hz, 1H), 2.21 (t, J = 1.8 Hz, 3H), 1.44 (s, 18H) ;
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-61.39, -115.13, -126.42,
-129.59 F1671 ESIMS m/z 674 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.87 (s, 1H), 10.52 (s, 1H), 8.87 (d, J = 2, 0 Hz, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.80 - 7.66 (m, 4H), 7.56 (d, J = 8.8 Hz, 1H) , 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.35 - 7.25 (m, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.33, -124.13 F1672 ESIMS m/z 691 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.77 (s, 1H), 10.52 (s, 1H), 8.77 (d, J = 1, 8 Hz, 1H), 8.13 (d, J = 1.9 Hz, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.80 - 7.65 (m, 4H) , 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.8, 2.1 Hz, 1H), 7.36 - 7.25 (m, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.25, -124.01 F1673 ESIMS m/z 696 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 10.02 (s, 1H), 7.90 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.67 - 7.59 (m, 1H), 7, 55 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.39 - 7.30 (m, 4H), 7.26 (h, J = 4.2 Hz, 1H), 7.23 - 7.14 (m, 1H), 3.71 (s, 2H), 3.61 (d, J = 8.5 Hz, 1H) , 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.54 (d, J = 3.5 Hz), -124.42 (d, J = 3.5 Hz) F1674 ESIMS m/z 611 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.17 (s, 1H), 7.99 (d, J = 2.6 Hz, 1H), 7.87 - 7.76 (m, 3H), 7.57 (t, J = 8.8 Hz, 1H), 7.48 (t, J = 9.5 Hz, 2H), 4.60 (s, 2H) , 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.24 - 2.13 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87, -117.61, -142.04,
-144.40 F1675 ESIMS m/z 657 ([M+H] ⁺ ) ^1H NMR (400 MHz, _CDCl3 ) δ 9.41 (s, 1H), 8.73 (s, 1H), 8.58 (s, 1H), 7.91 (td, J = 8.8, 5.5 Hz, 1H), 7.75 - 7.35 (m, 6H), 7.19 (d, J = 8.7 Hz, 1H), 6.94 - 6.73 (m, 1H), 6.10 (t, J = 53.8 Hz, 1H), 3.56 (d, J = 8.1 Hz, 1H), 2.98 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-62.66, -120.71, -125.80,
-127.81 F1676 ESIMS m/z 677 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.48 (s, 1H), 8.93 (s, 1H), 8.13 - 7.99 (m, 2H), 7.85 - 7.62 (m, 5H), 7.47 (d, J = 8.8 Hz, 1H), 7.11 (td, J = 9.2, 2.0 Hz, 1H ), 4.48 (ddd, J = 8.4, 5.3, 1.2 Hz, 1H), 4.08 (dt, J = 8.3, 6.4 Hz, 1H), 3.89 ( q, J = 7.2 Hz, 1H), 3.73 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.4 Hz, 1H), 2.30 (dq, J = 12.3, 7.8 Hz, 1H), 2.17 - 2.04 (m, 1H), 1.96 (p, J = 6.9 Hz, 2H);
^19F NMR (376 MHz, acetone- _d6 ) δ -63.04, -123.30, -128.94 F1677 ESIMS m/z 707 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.58 (s, 1H), 8.21 (td, J = 8.8, 5.6 Hz, 1H) , 8.06 (d, J = 2.6 Hz, 1H), 7.88 - 7.60 (m, 6H), 7.49 (d, J = 8.7 Hz, 1H), 7.24 ( td, J = 9.3, 2.0 Hz, 1H), 6.66 (tt, J = 52.1, 5.4 Hz, 1H), 3.74 (d, J = 8.3 Hz, 1H ), 3.47 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.07, -123.29, -125.64,
-128.54, -140.27 F1678 ESIMS m/z 621 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.49 (s, 1H), 8.91 (s, 1H), 8.11 - 7.99 (m, 2H), 7.85 - 7.63 (m, 5H), 7.48 (d, J = 8.7 Hz, 1H), 7.10 (td, J = 9.3, 2.0 Hz, 1H ), 3.73 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -63.05, -123.25, -128.77 F1679 ESIMS m/z 635 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.47 (s, 1H), 8.81 (s, 1H), 8.10 - 7.99 (m, 2H), 7.85 - 7.62 (m, 5H), 7.47 (d, J = 8.8 Hz, 1H), 7.10 (td, J = 9.3, 2.0 Hz, 1H ), 3.73 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.48 (q, J = 7.5 Hz, 2H), 1.18 (t, J = 7.6 Hz, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -63.05, -123.25, -128.79 F1680 ESIMS m/z 689 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.64 (s, 1H), 9.48 (s, 1H), 8.50 (t, J = 8, 1 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.92 - 7.75 (m, 3H), 7.48 (dt, J = 9.7, 5.5 Hz, 2H), 6.41 (t, J = 53.7 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.25 (d, J = 2.1 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.57, -127.10,
-128.94, -129.07 F1681 ESIMS m/z 797 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.24 (s, 1H), 8.45 (d, J = 2.4 Hz, 1H), 8.31 (td, J = 8.8, 5, 5 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.41 - 7.26 ( m, 3H), 7.19 (dt, J = 8.9, 1.9 Hz, 1H), 6.97 (td, J = 9.0, 1.8 Hz, 1H), 3.60 (d , J = 8.1 Hz, 1H), 2.97 (d, J = 8.2 Hz, 1H), 1.45 (s, 18H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-62.76, -109.97, -122.94,
-132.74 F1682 ESIMS m/z 679 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.48 (s, 1H), 8.79 (s, 1H), 8.09 - 7.98 (m, 2H), 7.81 (ddd, J = 11.2, 6.2, 3.0 Hz, 3H), 7.52 - 7.43 (m, 2H), 7.09 (td, J = 9, 2, 2.0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.38 (d, J = 7.0 Hz, 2H), 1.24 - 1.07 (m, 1H), 0.61 - 0.48 (m, 2H), 0.26 (dt, J = 6.1, 4.5 Hz , 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.52, -117.59,
-128.48 F1683 ESIMS m/z 707 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.52 (s, 1H), 9.30 (s, 1H), 8.10 (td, J = 8, 7, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 9.1, 6.1 Hz, 3H), 7.47 ( dt, J = 8.4, 5.1 Hz, 2H), 7.14 (td, J = 9.3, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H ), 3.60 (q, J = 10.7 Hz, 2H), 3.43 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.82, -63.57, -117.56, -123.12, -128.37 F1684 ESIMS m/z 654 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.06 (s, 1H), 8.10 (d, J = 2.6 Hz, 1H), 7.91 - 7.78 (m, 3H), 7.53 - 7.43 (m, 2H), 7.23 (d, J = 8.5 Hz, 1H), 6.68 (d, J = 8.6 Hz, 1H), 4.76 (s, 2H), 3.76 - 3.69 (m, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.24 (s, 3H );
^19F NMR (376 MHz, acetone- _d6 ) δ -61.86, -117.66 F1685 ESIMS m/z 724 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.59 (s, 1H), 10.50 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.73 - 7.65 ( m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.26 (dd, J = 10.1, 8.3 Hz, 1H), 6.77 (s, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-118.72 - -122.23 (m), -124.44 F1686 ESIMS m/z 727 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.94 (s, 1H), 10.54 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.79 - 7.71 (m, 2H), 7.57 (d, J = 8.8 Hz, 1H) , 7.32 (t, J = 9.2 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.04, -121.25, -124.54 F1687 ESIMS m/z 597 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.25 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.7, 2.6 Hz, 1H), 7.73 - 7.67 (m, 1H), 7.61 (dt, J = 9.5, 1.9 Hz, 1H), 7.55 (dt, J = 8.7, 1.9 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.38 (td, J = 8.6, 5, 5 Hz, 1H), 6.89 (ddd, J = 10.9, 9.1, 2.0 Hz, 1H), 4.77 (s, 2H), 3.77 (d, J = 8.3 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.19, -111.80, -137.23,
-144.25 F1688 ESIMS m/z 684 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.53 (s, 1H), 8.07 (d, J = 2.7 Hz, 1H), 7.89 (d, J = 8.7 Hz, 1H), 7.81 (ddd, J = 11.5, 6.5, 1.8 Hz, 3H), 7.71 (d, J = 8.7 Hz, 1H), 7.47 (dd, J = 10.8, 8.2 Hz, 2H), 3.76 - 3.69 (m, 1H), 3.43 (d, J = 8.3 Hz, 1H ), 2.35 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.80, -117.39 F1689 ESIMS m/z 683 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.49 (s, 1H), 8.92 (s, 1H), 8.13 - 7.99 (m, 2H), 7.87 - 7.77 (m, 3H), 7.52 - 7.43 (m, 2H), 7.12 (td, J = 9.2, 1.9 Hz, 1H), 3 .95 (q, J = 6.7 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.50 - 3.40 (m, 4H), 1.42 (d, J = 6.7 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.55, -123.23,
-128.85 F1690 ESIMS m/z 654 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.18 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.87 - 7.73 (m, 3H), 7.47 (t, J = 9.3 Hz, 2H), 7.29 (d, J = 8.6 Hz, 1H), 6.88 (d, J = 8.6 Hz, 1H), 4.81 (s, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2 .24(s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.83, -117.53 F1691 ESIMS m/z 695 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.49 (s, 1H), 8.95 (s, 1H), 8.12 - 7.98 (m, 2H), 7.87 - 7.76 (m, 3H), 7.52 - 7.43 (m, 2H), 7.11 (td, J = 9.2, 2.0 Hz, 1H), 4 .48 (dd, J = 8.4, 5.3 Hz, 1H), 4.08 (dt, J = 8.2, 6.4 Hz, 1H), 3.89 (dt, J = 8.2 , 6.9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.30 (dq, J = 12 .5, 7.8 Hz, 1H), 2.17 - 2.05 (m, 1H), 1.96 (p, J = 6.9 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.80, -117.53, -123.22,
-128.86 F1692 ESIMS m/z 695 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.50 (s, 1H), 8.95 (s, 1H), 8.12 - 7.98 (m, 2H), 7.87 - 7.76 (m, 3H), 7.52 - 7.42 (m, 2H), 7.11 (td, J = 9.2, 1.9 Hz, 1H), 4 .48 (dd, J = 8.4, 5.3 Hz, 1H), 4.08 (dt, J = 8.2, 6.4 Hz, 1H), 3.89 (dt, J = 8.2 , 6.9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.30 (dq, J = 12 .5, 7.9 Hz, 1H), 2.17 - 2.05 (m, 1H), 1.95 (p, J = 6.9 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.53, -123.20,
-128.84 F1693 110-113 ESIMS m/z 547 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.36 (s, 1H), 7.90 (d, J = 2.4 Hz, 1H), 7.80 - 7.69 (m, 2H), 7.58 - 7.44 (m, 3H), 7.41 - 7.31 (m, 1H), 7.13 (br t, J = 7.8 Hz, 1H), 3.60 (d, J = 8.3 Hz, 1H), 3.47 (d, J = 8.3 Hz, 1H) F1694 ESIMS m/z 606 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.43 (s, 1H), 9.77 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.65 - 7.57 (m, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.24 - 7.13 (m, 1H) , 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -120.45 (d, J = 3.5 Hz), -124.55 (d, J = 3.8 Hz) F1695 ESIMS m/z 658 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.56 (s, 1H), 10.96 (s, 1H), 10.55 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.76 (ddd, J = 8.7, 5.5, 2.8 Hz, 2H), 7.71 (dd, J = 7.1, 2.0 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.51 - 7.42 (m, 2H), 7.33 (td, J = 9.2, 1.8 Hz, 1H), 3 .59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.83, -117.28, -121.06 (d, J = 2.0 Hz), -124.40 (d, J = 2.2 Hz) F1696 ESIMS m/z 708 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.61 (s, 1H), 10.95 (s, 1H), 10.56 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.82 - 7.73 (m, 2H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.51 - 7.42 (m, 2H), 7.38 - 7.29 (m, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-82.44, -117.28, -121.40,
-121.69, -124.66 F1697 ESIMS m/z 674 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.96 (s, 1H), 10.54 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.80 - 7.68 (m, 3H), 7.57 (d, J = 8.8 Hz, 1H), 7.51 - 7.41 (m, 2H), 7, 32 (t, J = 9.2 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.03, -117.28, -121.26,
-124.53 F1698 ESIMS m/z 662 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.44 (s, 1H), 9.65 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.68 - 7.60 (m, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.20 (t, J = 9.1 Hz , 1H), 4.01 (q, J = 6.7 Hz, 1H), 3.64 - 3.56 (m, 2H), 3.56 - 3.45 (m, 1H), 3.44 ( d, J = 8.5 Hz, 1H), 1.34 (d, J = 6.7 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -120.92 (d, J = 3.1 Hz), -124.72 (d, J = 3.6 Hz) F1699 ESIMS m/z 660 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.44 (s, 1H), 9.61 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.64 ( td, J = 8.6, 5.7 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.25 - 7 .12 (m, 1H), 4.46 (dd, J = 8.3, 5.1 Hz, 1H), 4.08 - 3.95 (m, 1H), 3.84 (dt, J = 8 ,0, 6.7 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 2.23 (dq, J = 11.8, 7.7 Hz, 1H), 2.03 - 1.81 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -120.93 (d, J = 3.7 Hz), -124.76 (d, J = 3.5 Hz) F1700 ESIMS m/z 629 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.47 (s, 1H), 10.26 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 2.0 Hz, 1H), 7.68 - 7.62 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.27 - 7.19 (m, 1H) , 4.02 (s, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -120.50 (d, J = 3.0 Hz), -124.19 (d, J = 3.1 Hz) F1701 ESIMS m/z 672 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.47 (s, 1H), 10.23 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 2.0 Hz, 1H), 7.69 - 7.62 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.23 (td, J = 9.3, 1.7 Hz, 1H), 3.66 - 3.53 (m, 3H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.60, -117.29, -120.65 (d, J = 3.1 Hz), -124.30 (d, J = 3.3 Hz) F1702 ESIMS m/z 644 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.43 (s, 1H), 9.63 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.65 - 7.58 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.51 - 7.41 (m, 2H), 7.19 (dd, J = 9.9, 8.2 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 2.27 (d, J = 7, 0 Hz, 2H), 1.14 - 0.96 (m, 1H), 0.57 - 0.43 (m, 2H), 0.22 (dt, J = 4.9, 2.3 Hz, 2H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29, -120.45 (d, J = 3.4 Hz), -124.41 (d, J = 3.8 Hz) F1703 ESIMS m/z 690 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.25 (s, 1H), 10.95 (s, 1H), 10.53 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.73 (ddd, J = 17.4, 7.9, 2.2 Hz, 3H), 7.56 (d, J = 8.8 Hz, 1H), 7.51 - 7.42 (m, 2H), 7.36 - 7.25 (m, 1H), 6.89 (tt, J = 51.7, 5.2 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -121.14, -123.63 (t, J = 6.8 Hz), -124.44, -138.94 (t, J = 6.8 Hz) F1704 ESIMS m/z 619 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.69 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.65 - 7.53 (m, 2H), 7.51 - 7.41 (m, 2H), 7.22 - 7.14 (m, 1H), 3.59 (d, J = 8.4 Hz, 1H) , 3.44 (d, J = 8.5 Hz, 1H), 2.37 (q, J = 7.6 Hz, 2H), 1.10 (t, J = 7.6 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -120.54 (d, J = 4.1 Hz), -124.55 (d, J = 3.9 Hz) F1705 ESIMS m/z 632 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.70 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.61 ( td, J = 8.6, 5.7 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.23 - 7 .14 (m, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 2.33 (t, J = 7, 2 Hz, 2H), 1.62 (h, J = 7.3 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -120.55 (d, J = 4.0 Hz), -124.55 (d, J = 3.8 Hz) F1706 ESIMS m/z 695 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.47 (s, 1H), 8.92 (s, 1H), 8.08 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 ( s, 1H), 7.58 (ddt, J = 23.5, 8.7, 2.0 Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H), 7.11 (td , J = 9.2, 2.0 Hz, 1H), 4.48 (ddd, J = 8.4, 5.3, 1.0 Hz, 1H), 4.08 (dt, J = 8.3 , 6.4 Hz, 1H), 3.89 (q, J = 7.2 Hz, 1H), 3.77 (d, J = 8.3 Hz, 1H), 3.50 (d, J = 8 .4 Hz, 1H), 2.30 (dq, J = 12.4, 7.8 Hz, 1H), 2.17 - 2.01 (m, 2H), 1.96 (p, J = 6, 9 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.18, -111.78, -123.35,
-129.00 F1707 ESIMS m/z 725 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (d, J = 9.5 Hz, 2H), 9.59 (s, 1H), 8.21 (td, J = 8.8, 5.6 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.72 - 7, 40 (m, 4H), 7.24 (td, J = 9.2, 2.0 Hz, 1H), 6.60 (tdt, J = 52.2, 43.6, 5.2 Hz, 1H) , 3.78 (d, J = 8.3 Hz, 1H), 3.51 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.20, -111.80, -123.27,
-125.64, -128.52, -139.60 F1708 ESIMS m/z 639 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.49 (s, 1H), 8.92 (s, 1H), 8.11 - 7.98 (m, 2H), 7.80 (dd, J = 8.7, 2.6 Hz, 1H), 7.69 (s, 1H), 7.58 (ddt, J = 23.1, 8.6, 2, 0 Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H), 7.10 (td, J = 9.3, 2.0 Hz, 1H), 3.77 (d, J = 8.3 Hz, 1H), 3.50 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.17, -111.77, -123.24,
-128.75 F1709 ESIMS m/z 653 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.47 (s, 1H), 8.82 (s, 1H), 8.10 - 7.98 (m, 2H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 (s, 1H), 7.58 (ddt, J = 23.0, 8.7, 2, 1 Hz, 2H), 7.47 (d, J = 8.8 Hz, 1H), 7.09 (td, J = 9.3, 1.9 Hz, 1H), 3.77 (d, J = 8.3 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H), 2.48 (q, J = 7.6 Hz, 2H), 1.18 (t, J = 7, 6 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.18, -111.76, -123.26,
-128.78 F1710 ESIMS m/z 707 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.51 (s, 1H), 9.31 (s, 1H), 8.11 (td, J = 8, 8, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 ( s, 1H), 7.58 (ddt, J = 24.0, 8.6, 2.1 Hz, 2H), 7.48 (d, J = 8.8 Hz, 1H), 7.15 (td , J = 9.2, 1.9 Hz, 1H), 3.77 (d, J = 8.3 Hz, 1H), 3.66 - 3.44 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.19, -63.58, -111.77, -123.19, -128.43 F1711 ESIMS m/z 675 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.78 (s, 1H), 9.57 (s, 1H), 8.17 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.7 Hz, 1H), 7.81 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 - 7.41 (m, 3H), 7.20 (td, J = 9.2, 2.0 Hz, 1H), 6.46 (t, J = 53.5 Hz, 1H), 3.77 (d , J = 8.3 Hz, 1H), 3.50 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.18, -111.76, -123.06,
-127.05, -128.40 F1712 ESIMS m/z 683 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.50 (s, 1H), 8.93 (s, 1H), 8.08 (td, J = 8, 7, 5.6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.82 (dq, J = 11.5, 2.7 Hz, 3H), 7.48 ( dt, J = 8.2, 5.1 Hz, 2H), 7.12 (td, J = 9.3, 1.9 Hz, 1H), 3.95 (q, J = 6.7 Hz, 1H ), 3.71 (d, J = 8.3 Hz, 1H), 3.50 - 3.39 (m, 4H), 1.42 (d, J = 6.7 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.55, -123.22,
-128.83 F1713 ESIMS m/z 608 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.28 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.84 - 7.70 (m, 2H), 7.53 - 7.42 (m, 2H), 7.42 - 7.28 (m, 2H), 6.89 (ddd, J = 10.9, 9, 0, 2.0 Hz, 1H), 4.78 (s, 2H), 3.66 - 3.59 (m, 1H), 3.35 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -110.04, -137.06, -144.06 F1714 ESIMS m/z 706 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.46 (s, 1H), 8.91 (s, 1H), 8.08 (td, J = 8, 7, 5.5 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.85 - 7.71 (m, 2H), 7.55 - 7.44 (m, 2H ), 7.34 (t, J = 8.6 Hz, 1H), 7.12 (td, J = 9.2, 2.0 Hz, 1H), 4.48 (dd, J = 8.3, 5.3 Hz, 1H), 4.08 (dt, J = 8.2, 6.4 Hz, 1H), 3.90 (q, J = 7.1 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.35 (d, J = 8.3 Hz, 1H), 2.30 (dq, J = 12.5, 7.8 Hz, 1H), 2.17 - 2.05 (m, 1H), 1.96 (p, J = 6.9 Hz, 2H);
^19F NMR (376 MHz, acetone- _d6 ) δ -110.16, -123.38, -129.03 F1715 ESIMS m/z 736 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (d, J = 17.9 Hz, 2H), 9.57 (s, 1H), 8.21 (td, J = 8.8, 5.6 Hz, 1H), 8.02 (dd, J = 15.9, 2.6 Hz, 1H), 7.86 - 7.69 (m, 2H), 7.61 - 7.43 (m , 2H), 7.34 (t, J = 8.6 Hz, 1H), 7.24 (td, J = 9.3, 2.0 Hz, 1H), 6.96 - 6.50 (m, 1H), 3.78 - 3.58 (m, 1H), 3.36 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -110.16, -123.33, -125.66,
-128.57, -140.28 F1716 ESIMS m/z 650 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.48 (s, 1H), 8.90 (s, 1H), 8.11 - 7.98 (m, 2H), 7.84 - 7.71 (m, 2H), 7.55 - 7.44 (m, 2H), 7.34 (t, J = 8.6 Hz, 1H), 7.10 (td , J = 9.3, 2.0 Hz, 1H), 3.66 - 3.58 (m, 1H), 3.35 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -110.14, -123.27, -128.77 F1717 ESIMS m/z 664 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.47 (s, 1H), 8.82 (s, 1H), 8.11 - 7.98 (m, 2H), 7.84 - 7.71 (m, 2H), 7.54 - 7.43 (m, 2H), 7.33 (t, J = 8.6 Hz, 1H), 7.10 (td , J = 9.3, 2.0 Hz, 1H), 3.66 - 3.58 (m, 1H), 3.34 (d, J = 8.3 Hz, 1H), 2.48 (q, J = 7.6 Hz, 2H), 1.18 (t, J = 7.6 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -110.10, -123.20, -128.73 F1718 ESIMS m/z 718 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.49 (s, 1H), 9.26 (s, 1H), 8.12 (td, J = 8, 8, 5.6 Hz, 1H), 8.03 (d, J = 2.5 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.75 ( dd, J = 6.6, 2.3 Hz, 1H), 7.56 - 7.45 (m, 2H), 7.34 (t, J = 8.6 Hz, 1H), 7.16 (td , J = 9.3, 2.0 Hz, 1H), 3.66 - 3.53 (m, 3H), 3.36 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.60, -110.17, -123.32,
-128.53 F1719 ESIMS m/z 724 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.97 (s, 1H), 10.54 (s, 1H), 7.94 (t, J = 2, 6 Hz, 2H), 7.84 - 7.70 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.32 (t, J = 9.2 Hz, 1H) , 3.72 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.15, -63.04, -121.25, -124.53 F1720 ESIMS m/z 683 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.48 (s, 1H), 8.91 (s, 1H), 8.08 (td, J = 8, 7, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.82 (ddd, J = 8.9, 5.5, 1.7 Hz, 3H), 7.48 (dt, J = 8.2, 5.1 Hz, 2H), 7.13 (td, J = 9.2, 2.0 Hz, 1H), 3.95 (q, J = 6, 7 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.50 - 3.40 (m, 4H), 1.41 (d, J = 6.7 Hz, 3H) ;
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.58, -123.30,
-128.90 F1721 ESIMS m/z 711 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.46 (s, 1H), 9.00 (s, 1H), 8.11 - 7.98 (m, 2H), 7.82 (td, J = 8.7, 8.3, 2.6 Hz, 3H), 7.47 (dt, J = 8.3, 5.1 Hz, 2H), 7.10 (td, J = 9.2, 1.9 Hz, 1H), 4.15 (dd, J = 6.8, 4.6 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 3.01 (dt, J = 11.3, 5.5 Hz, 1H), 2.91 (dt, J = 9.4 , 6.1 Hz, 1H), 2.41 - 2.28 (m, 1H), 2.27 - 2.05 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.53, -123.10,
-128.62 F1722 ESIMS m/z 709 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.47 (s, 1H), 8.91 (s, 1H), 8.10 - 7.98 (m, 2H), 7.81 (ddd, J = 11.4, 6.0, 2.6 Hz, 3H), 7.52 - 7.42 (m, 2H), 7.09 (td, J = 9, 2, 1.9 Hz, 1H), 4.03 (ddd, J = 11.3, 4.2, 1.7 Hz, 1H), 3.81 (dd, J = 9.8, 5.5 Hz , 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.55 (dd, J = 11.3, 9.7 Hz, 1H), 3.46 - 3.33 (m, 2H), 2.79 (tt, J = 10.2, 4.0 Hz, 1H), 2.09 (dd, J = 6.0, 3.6 Hz, 1H), 1.84 (dtd, J = 13.0, 11.2, 4.3 Hz, 1H), 1.76 - 1.52 (m, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.56, -123.09,
-128.57 F1723 137-140 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₄ H ₁₄ Cl ₃ F ₅ N ₂ O ₂ , 562.0041; found, 562.0056 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.76 (s, 1H), 10.56 (s, 1H), 8.26 (d, J = 8.1 Hz, 1H), 7.87 - 7.78 (m, 2H), 7.76 - 7.66 (m, 3H), 7.59 (t, J = 9.6 Hz, 1H), 7.36 (t, J = 7.7 Hz, 2H), 7.12 (t, J = 7.4 Hz, 1H), 3.75 (d, J = 8.5 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.94 (d, J = 12.6 Hz), -116.92 (q, J = 12.7 Hz), -120.37 F1724 ESIMS m/z 669 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.51 (s, 1H), 8.90 (s, 1H), 8.09 (td, J = 8, 7, 5.6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.81 (dt, J = 11.4, 4.5 Hz, 3H), 7.53 - 7.43 (m, 2H), 7.12 (td, J = 9.2, 1.9 Hz, 1H), 4.09 (s, 2H), 3.71 (d, J = 8.3 Hz , 1H), 3.49 (s, 3H), 3.46 - 3.35 (m, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.54, -123.05,
-128.66 F1725 140-143 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₄ H ₁₃ Cl ₃ F ₆ N ₂ O ₂ , 579.9947; found, 579.9950 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.76 (s, 1H), 10.63 (s, 1H), 8.27 (d, J = 8.1 Hz, 1H), 7.82 (ddd, J = 10.8, 5.8, 2.4 Hz, 2H), 7.77 - 7.68 (m, 3H), 7.60 (dd, J = 10.7, 8.5 Hz , 1H), 7.26 - 7.17 (m, 2H), 3.75 (d, J = 8.6 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.95 (d, J = 12.4 Hz), -116.91 (q, J = 12.6 Hz), -118.38,
-120.25 F1726 ESIMS m/z 674 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.52 (s, 1H), 9.24 (s, 1H), 8.11 (td, J = 8, 8, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.87 - 7.76 (m, 3H), 7.48 (dt, J = 9.8 , 5.1 Hz, 2H), 7.15 (td, J = 9.3, 2.0 Hz, 1H), 4.38 (s, 2H), 3.72 (d, J = 8.3 Hz , 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.54, -123.09,
-128.52 F1727 82-87 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₄ H ₁₂ Cl ₃ F ₇ N ₂ O ₂ , 597.9853; found, 597.9855 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.76 (s, 1H), 10.41 (s, 1H), 8.31 (d, J = 8.1 Hz, 1H), 7.90 - 7.69 (m, 4H), 7.60 (dd, J = 10.7, 8.5 Hz, 1H), 7.37 (ddd, J = 10.7, 9.1, 2.9 Hz , 1H), 7.20 - 7.08 (m, 1H), 3.75 (d, J = 8.6 Hz, 1H), 3.70 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.95 (d, J = 12.5 Hz), -113.24 (d, J = 6.0 Hz), -116.92 (q, J = 12.4 Hz), -117.28 ( d, J = 6.1 Hz), -120.19 F1728 ESIMS m/z 722 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.51 (d, J = 5.1 Hz, 2H), 8.13 (td, J = 8.7, 5.5 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.49 (dd, J = 8.7, 3 .2 Hz, 2H), 7.17 (td, J = 9.3, 2.0 Hz, 1H), 4.95 (dd, J = 7.5, 5.3 Hz, 1H), 4.14 (dd, J = 11.2, 7.5 Hz, 1H), 4.04 (dd, J = 11.2, 5.3 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.61, -122.91,
-128.20 F1729 107-111 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₃ Cl ₃ F ₉ N ₃ O ₃ , 690.9879; found, 690.9882 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.79 (s, 1H), 10.77 (s, 1H), 10.52 (s, 1H), 8.33 (d, J = 8, 1 Hz, 1H), 7.83 (ddd, J = 10.7, 5.9, 2.3 Hz, 2H), 7.79 - 7.71 (m, 2H), 7.60 (dd, J = 10.7, 8.5 Hz, 1H), 7.28 (td, J = 9.3, 1.8 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3 .76 (d, J = 8.5 Hz, 1H), 3.70 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.94 (d, J = 12.4 Hz), -116.92 (q, J = 12.7 Hz), -120.07,
-120.71 (d, J = 2.6 Hz), -124.33 (d, J = 2.8 Hz), -125.80 F1730 123-127 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₃₄ H ₂₉ Cl ₃ F ₇ N ₃ O ₆ , 813.1010; found, 813.0988 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.77 (s, 1H), 10.52 (s, 1H), 8.32 (d, J = 8.1 Hz, 1H), 7.86 - 7.72 (m, 4H), 7.60 (dd, J = 10.7, 8.5 Hz, 1H), 7.27 (td, J = 9.2, 1.8 Hz, 1H), 3.75 (d, J = 8.5 Hz, 1H), 3.70 (d, J = 8.5 Hz, 1H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.94 (d, J = 12.4 Hz), -116.91 (q, J = 12.7 Hz), -120.01,
-123.52 (d, J = 2.0 Hz), -126.58 F1731 ESIMS m/z 698 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.65 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 - 7.58 (m, 2H ), 7.56 (d, J = 8.6 Hz, 1H), 7.20 (td, J = 9.1, 1.7 Hz, 1H), 4.01 (q, J = 6.7 Hz , 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.64 - 3.53 (m, 1H), 3.53 - 3.46 (m, 2H), 1.34 ( d, J = 6.7 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.5 Hz), -116.94 (q, J = 12.7 Hz), -120.92 (d, J = 3.8 Hz), -124.72 ( d, J = 3.6 Hz) F1732 ESIMS m/z 696 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.65 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.90 - 7.79 (m, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 (dt, J = 8.7 , 4.4 Hz, 1H), 7.62 - 7.58 (m, 1H), 7.56 (d, J = 8.6 Hz, 1H), 7.20 (td, J = 9.2, 1.8 Hz, 1H), 4.01 (q, J = 6.6 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.63 - 3.54 (m, 1H), 3.54 - 3.45 (m, 2H), 1.34 (d, J = 6.7 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.7 Hz), -116.94 (q, J = 12.5 Hz), -120.92 (d, J = 3.6 Hz), -124.72 ( d, J = 3.7 Hz) F1733 ESIMS m/z 680 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.65 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.78 - 7.73 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.65 (td, J = 8.8, 5.8 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.20 (td, J = 9 ,2, 1.7 Hz, 1H), 4.01 (q, J = 6.7 Hz, 1H), 3.64 - 3.44 (m, 4H), 1.34 (d, J = 6, 7 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H)';
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.91 (d, J = 3.9 Hz), -124.72 (d, J = 3.7 Hz) F1734 ESIMS m/z 680 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.44 (s, 1H), 9.65 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.64 (dt, J = 8.7, 4.3 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.20 (td, J = 9 ,1, 1.7 Hz, 1H), 4.01 (q, J = 6.7 Hz, 1H), 3.67 - 3.40 (m, 4H), 1.34 (d, J = 6, 7 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.92 (d, J = 3.8 Hz), -124.72 (d, J = 3.9 Hz) F1735 ESIMS m/z 671 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.49 (s, 1H), 9.05 (s, 1H), 8.12 - 7.99 (m, 2H), 7.81 (ddd, J = 11.5, 5.6, 2.2 Hz, 3H), 7.47 (dt, J = 8.2, 5.1 Hz, 2H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 4.85 (t, J = 5.7 Hz, 1H), 4.74 (t, J = 5.7 Hz, 1H), 3 .71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.94 (t, J = 5.7 Hz, 1H), 2.88 (t, J = 5.7 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ 17.90, -61.84, -117.60, -122.98, -128.41 F1736 ESIMS m/z 715 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.61 (s, 1H), 8.49 - 8.39 (m, 1H), 8.36 (s, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.82 (dh, J = 7.7, 2.2 Hz, 3H), 7.52 - 7.42 (m, 2H ), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.50 (s, 9H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.79, -61.83, -117.49, -152.01, -162.27 F1737 ESIMS m/z 679 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.47 (s, 1H), 8.89 (s, 1H), 8.13 - 8.00 (m, 2H), 7.85 - 7.62 (m, 6H), 7.48 (d, J = 8.8 Hz, 1H), 7.12 (td, J = 9.2, 1.9 Hz, 1H ), 4.04 (q, J = 6.7 Hz, 1H), 3.77 - 3.58 (m, 3H), 3.45 (d, J = 8.3 Hz, 1H), 1.42 (d, J = 6.8 Hz, 3H), 1.25 (t, J = 7.0 Hz, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -63.05, -123.26, -128.91 F1738 ESIMS m/z 689 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.51 (s, 1H), 9.29 (s, 1H), 8.11 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.7, 2.6 Hz, 1H), 7.78 ( s, 1H), 7.80 - 7.69 (m, 2H), 7.74 - 7.62 (m, 2H), 7.48 (d, J = 8.8 Hz, 1H), 7.15 (td, J = 9.2, 2.0 Hz, 1H), 3.73 (d, J = 8.3 Hz, 1H), 3.60 (q, J = 10.7 Hz, 2H), 3 .45 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -63.06, -63.58, -123.18, -128.44 F1739 ESIMS m/z 711 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.47 (s, 1H), 8.83 (s, 1H), 8.08 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.82 (ddd, J = 11.4, 6.8, 2.6 Hz, 3H), 7.47 (dt, J = 8.3, 5.1 Hz, 2H), 7.12 (td, J = 9.2, 1.9 Hz, 1H), 4.03 (q, J = 6, 8 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.58 (ddt, J = 30.2, 9.2, 6.6 Hz, 2H), 3.43 ( d, J = 8.3 Hz, 1H), 1.66 (h, J = 7.2 Hz, 2H), 1.43 (d, J = 6.7 Hz, 3H), 1.00 - 0, 83 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.82, -117.55, -123.26,
-128.90 F1740 ESIMS m/z 615 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.38 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.82 (ddd, J = 13.7, 7.9, 2.7 Hz, 3H), 7.49 (dd, J = 9.4, 6.4 Hz, 3H), 5.00 (d, J = 8 .6 Hz, 2H), 3.78 - 3.69 (m, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.65, -163.17,
-163.22, -164.01 F1741 ESIMS m/z 758 ([M+H] ^- ) ^1H NMR (500 MHz, DMSO- _d6 ) δ 11.60 (s, 1H), 10.96 (s, 1H), 10.56 (s, 1H), 7.94 (d, J = 2, 5 Hz, 1H), 7.82 - 7.74 (m, 2H), 7.72 (dd, J = 7.1, 2.0 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.52 - 7.43 (m, 2H), 7.34 (t, J = 9.3 Hz, 1H), 3.60 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ
-80.05, -117.28, -119.31,
-121.35, -124.66, -126.81 F1742 ESIMS m/z 722 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.48 (s, 1H), 10.16 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.90 - 7.79 (m, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.67 (td, J = 8.7 , 5.6 Hz, 1H), 7.63 - 7.53 (m, 2H), 7.24 (td, J = 9.2, 1.8 Hz, 1H), 4.87 (s, 2H) , 3.69 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.23, -59.92 (d, J = 12.5 Hz),
-116.94 (d, J = 12.4 Hz),
-120.58, -124.27 F1743 ESIMS m/z 657 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.62 (s, 1H), 9.18 (s, 1H), 8.56 (d, J = 7, 8 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.52 - 7.43 (m, 2H), 3, 72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.19 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ 61.87, -117.60, -150.64,
-150.70, -162.30 F1744 ESIMS m/z 693 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.90 (s, 1H), 9.73 (s, 1H), 8.42 (dt, J = 7, 8, 3.8 Hz, 1H), 8.05 (d, J = 2.7 Hz, 1H), 7.83 (ddd, J = 9.0, 4.8, 2.3 Hz, 3H), 7.48 (dd, J = 10.8, 9.1 Hz, 2H), 6.43 (t, J = 53.6 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H ), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.61, -127.27,
-147.96, -148.26, -161.19 F1745 ESIMS m/z 723 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.48 (s, 1H), 8.87 (s, 1H), 8.08 (td, J = 8, 7, 5.6 Hz, 1H), 8.02 (d, J = 2.7 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 8.2 , 5.1 Hz, 2H), 7.12 (td, J = 9.2, 2.0 Hz, 1H), 4.09 (q, J = 6.7 Hz, 1H), 3.72 (d , J = 8.3 Hz, 1H), 3.50 (dd, J = 10.3, 6.8 Hz, 1H), 3.44 (dd, J = 10.6, 7.5 Hz, 2H) , 1.43 (d, J = 6.7 Hz, 3H), 1.22 - 1.07 (m, 1H), 0.59 - 0.44 (m, 2H), 0.27 (ttd, J = 8.0, 5.5, 3.4 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.56, -123.24,
-128.89 F1746 ESIMS m/z 725 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.48 (s, 1H), 8.77 (s, 1H), 8.08 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.7 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 9.6 , 5.1 Hz, 2H), 7.12 (td, J = 9.2, 2.0 Hz, 1H), 4.03 (q, J = 6.7 Hz, 1H), 3.71 (d , J = 8.3 Hz, 1H), 3.50 - 3.39 (m, 2H), 3.35 (dd, J = 9.0, 6.8 Hz, 1H), 1.94 (dp, J = 13.3, 6.7 Hz, 1H), 1.44 (d, J = 6.7 Hz, 3H), 0.96 (dd, J = 6.7, 1.6 Hz, 6H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.56, -123.26,
-128.91 F1747 ESIMS m/z 751 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.49 (s, 1H), 9.00 (s, 1H), 8.10 (td, J = 8, 7, 5.6 Hz, 1H), 8.03 (d, J = 2.7 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 10.0 , 5.1 Hz, 2H), 7.14 (td, J = 9.3, 2.0 Hz, 1H), 4.44 - 4.13 (m, 3H), 3.71 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 1.53 (d, J = 6.7 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -61.86, -75.08, -117.57, -123.22, -128.81 F1748 ESIMS m/z 681 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.49 (s, 1H), 8.73 (s, 1H), 8.10 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.7 Hz, 1H), 7.82 (ddd, J = 8.9, 7.2, 4.1 Hz, 3H), 7.48 (dt, J = 9.8, 5.3 Hz, 2H), 7.13 (td, J = 9.2, 2.0 Hz, 1H), 3.72 (d, J = 8, 3 Hz, 1H), 3.47 - 3.36 (m, 2H), 3.30 (qd, J = 5.1, 2.0 Hz, 1H), 1.42 (d, J = 5.1 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.63, -123.33,
-128.87 F1749 105-108 ESIMS m/z 549 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.36 (s, 1H), 7.90 (d, J = 2.4 Hz, 1H), 7.80 - 7.68 (m, 2H), 7.59 - 7.44 (m, 3H), 7.40 - 7.32 (m, 1H), 7.13 (br t, J = 8.6 Hz, 1H), 3.60 (d, J = 8.3 Hz, 1H), 3.47 (d, J = 8.3 Hz, 1H) F1750 105-108 ESIMS m/z 531 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.39 (s, 1H), 10.36 (s, 1H), 7.90 (d, J = 2, 4 Hz, 1H), 7.76 - 7.70 (m, 2H), 7.59 - 7.52 (m, 2H), 7.51 - 7.45 (m, 1H), 7.39 - 7 .32 (m, 1H), 7.28 (br d, J = 8.3 Hz, 1H), 7.13 (br t, J = 8.6 Hz, 1H), 3.57 (d, J = 8.8 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H) F1751 107-109 ESIMS m/z 531 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.36 (s, 1H), 7.90 (d, J = 2.4 Hz, 1H), 7.78 - 7.70 (m, 2H), 7.60 - 7.51 (m, 2H), 7.51 - 7.45 (m, 1H), 7.40 - 7.32 (m, 1H), 7 .28 (br d, J = 8.3 Hz, 1H), 7.13 (br t, J = 8.6 Hz, 1H), 3.57 (d, J = 8.8 Hz, 1H), 3 .41 (d, J = 8.3 Hz, 1H) F1752 ESIMS m/z 678 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (d, J = 4.4 Hz, 1H), 9.60 (d, J = 53.3 Hz, 1H), 8.45 - 8 .15 (m, 1H), 8.07 (dt, J = 20.1, 2.7 Hz, 1H), 7.89 - 7.68 (m, 3H), 7.48 (dd, J = 11 ,0, 9.1 Hz, 2H), 7.40 - 7.17 (m, 1H), 3.77 - 3.61 (m, 3H), 3.53 - 3.39 (m, 1H), 3.27(s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.55, -124.86,
-130.11 F1753 128-134 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₇ H ₁₆ Cl ₃ F ₆ N ₃ O ₅ , 681.0060; found, 681.0057 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.85 (s, 1H), 10.51 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.90 - 7.82 (m, 2H), 7.78 - 7.70 (m, 2H), 7.63 - 7.55 (m, 2H), 7.27 (td , J = 9.2, 1.8 Hz, 1H), 3.89 (s, 3H), 3.70 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8, 5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.5 Hz), -116.94 (q, J = 12.4 Hz), -120.34 (d, J = 2.7 Hz), -124.09 F1754 115-120 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₇ H ₁₆ Cl ₃ F ₆ N ₃ O ₄ , 665.0111; found, 665.0102 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.48 (s, 1H), 10.44 (s, 1H), 7.94 (d, J = 2, 6 Hz, 1H), 7.85 (dd, J = 19.0, 5.9 Hz, 2H), 7.78 - 7.67 (m, 2H), 7.63 - 7.54 (m, 2H ), 7.25 (td, J = 9.4, 8.9, 1.7 Hz, 1H), 3.70 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 2.45 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.3 Hz), -116.94 (q, J = 12.6 Hz), -120.05,
-123.75 F1755 ESIMS m/z 678 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.52 (s, 1H), 9.35 (s, 1H), 8.12 (td, J = 8, 7, 5.5 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.53 - 7.43 (m, 2H ), 7.16 (td, J = 9.3, 2.0 Hz, 1H), 4.11 (q, J = 7.2 Hz, 1H), 3.72 (d, J = 8.3 Hz , 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.65 (d, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.60, -123.38,
-128.65 F1756 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.51 (s, 1H), 9.33 (s, 1H), 8.12 (td, J = 8, 7, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.48 (dd, J = 9.3 , 7.5 Hz, 2H), 7.17 (td, J = 9.3, 2.1 Hz, 1H), 4.01 (t, J = 6.9 Hz, 1H), 3.72 (d , J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.11 (dt, J = 14.4, 7.1 Hz, 2H), 1.16 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.84, -117.63, -123.39,
-128.63. F1757 ESIMS m/z 711 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.46 (s, 1H), 8.87 (s, 1H), 8.09 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.48 (dt, J = 9.7 , 5.4 Hz, 2H), 7.13 (td, J = 9.2, 2.0 Hz, 1H), 3.88 (dd, J = 6.5, 4.9 Hz, 1H), 3 .73 (ddd, J = 13.9, 6.9, 1.7 Hz, 2H), 3.62 (dq, J = 9.4, 7.0 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 1.94 - 1.70 (m, 2H), 1.26 (t, J = 7.0 Hz, 3H), 1.00 (t, J = 7.4 Hz , 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.61, -123.23,
-128.86 F1758 ESIMS m/z 708 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.55 (s, 1H), 8.23 (td, J = 8.9, 5.8 Hz, 1H) , 8.04 (d, J = 2.6 Hz, 1H), 7.88 - 7.78 (m, 3H), 7.48 (t, J = 9.1 Hz, 2H), 7.16 ( ddd, J = 9.3, 7.4, 1.9 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H );
^19F NMR (376 MHz, acetone- _d6 ) δ -61.88, -98.97, -103.17, -117.63 F1759 ESIMS m/z 725 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.47 (s, 1H), 8.89 (s, 1H), 8.07 (td, J = 8, 7, 5.6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.81 (td, J = 8.9, 2.5 Hz, 3H), 7.47 ( dt, J = 8.3, 5.1 Hz, 2H), 7.11 (td, J = 9.2, 2.0 Hz, 1H), 3.92 (dd, J = 6.8, 5, 1 Hz, 1H), 3.81 - 3.68 (m, 2H), 3.60 (dq, J = 9.4, 7.0 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.10 - 2.00 (m, 1H), 1.82 - 1.69 (m, 1H), 1.50 (hept, J = 6.7, 5.9 Hz, 2H) , 1.26 (t, J = 7.0 Hz, 3H), 0.94 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.81, -117.53, -123.11,
-128.75 F1760 ESIMS m/z 734 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.46 (s, 1H), 10.02 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.91 - 7.80 (m, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.70 - 7.58 (m, 2H ), 7.56 (d, J = 8.6 Hz, 1H), 7.22 (t, J = 9.1 Hz, 1H), 3.70 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 2.97 - 2.80 (m, 1H), 2.72 (dd, J = 14.9, 5.1 Hz, 1H), 1 .15 (d, J = 6.9 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.7 Hz), -72.18,
-116.94 (q, J = 12.4 Hz), -120.62 (d, J = 3.4 Hz), -124.51 (d, J = 3.5 Hz) F1761 ESIMS m/z 725 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.49 (d, J = 18.7 Hz, 1H), 8.13 (td, J = 9.0, 5.8 Hz, 1H), 8.04 (t, J = 4.0 Hz, 1H), 7.82 (ddd, J = 14.6, 7.9, 2.7 Hz, 3H), 7, 48 (t, J = 9.1 Hz, 2H), 7.16 (td, J = 9.2, 2.1 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.61 (q, J = 7.1 Hz, 2H), 3.43 (d, J = 8.3 Hz, 1H), 1.43 (d, J = 66.7 Hz, 9H), 1, 24 - 1.06 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.89, -117.63, -124.27,
-129.88 F1762 ESIMS m/z 625 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.16 (s, 1H), 9.25 (s, 1H), 8.01 (d, J = 2.5 Hz, 1H), 7.90 - 7.77 (m, 3H), 7.46 (ddd, J = 12.7, 8.9, 6.3 Hz, 3H), 6.91 (ddd, J = 11.4, 9.0, 2.0 Hz, 1H), 4.46 (s, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.47 - 3.33 (m, 3H), 1.20 ( t, J = 7.1 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.63, -133.96,
-141.65 F1763 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.59 (d, J = 49.2 Hz, 1H), 8.42 - 8.16 (m, 1H) , 8.14 - 8.01 (m, 1H), 7.95 - 7.73 (m, 3H), 7.48 (dd, J = 11.6, 8.9 Hz, 2H), 7.41 - 7.16 (m, 1H), 3.90 - 3.67 (m, 3H), 3.62 (s, 2H), 3.44 (d, J = 8.3 Hz, 1H), 1, 17 (dt, J = 37.9, 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87, -117.58, -123.90,
-129.01 F1764 ESIMS m/z 706 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.82 - 9.49 (m, 1H), 8.35 (dtd, J = 39.7, 8.9 , 5.7 Hz, 1H), 8.08 (dt, J = 16.1, 2.7 Hz, 1H), 7.90 - 7.68 (m, 3H), 7.57 - 7.41 ( m, 2H), 7.33 (tdd, J = 9.5, 4.7, 1.9 Hz, 1H), 3.75 (dt, J = 14.1, 5.8 Hz, 4H), 3 .44 (d, J = 8.3 Hz, 1H), 1.66 - 1.33 (m, 3H), 1.33 - 1.00 (m, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87, -117.60, -124.55,
-129.07 F1765 ESIMS m/z 644 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.07 (s, 1H), 10.74 (s, 1H), 8.28 (td, J = 8.8, 5.3 Hz, 1H) , 7.99 (ddd, J = 12.3, 7.0, 2.6 Hz, 1H), 7.81 (s, 2H), 7.78 - 7.72 (m, 1H), 7.54 (t, J = 9.3 Hz, 1H), 3.65 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-105.40, -120.18, -135.18 (d, J = 23.6 Hz), -144.61 (d, J = 23.4 Hz) F1766 ESIMS m/z 704 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.47 (s, 1H), 10.16 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.75 (dd, J = 8.2, 2.4 Hz, 2H), 7.68 (t, J = 8.6 Hz, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.3, 2.0 Hz, 1H), 7.23 (t, J = 9.2 Hz, 1H), 4.87 (s, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.22, -120.57, -124.27 F1767 ESIMS m/z 718 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.47 (s, 1H), 10.19 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 6.7, 2.3 Hz, 2H), 7.68 (t, J = 8.2 Hz, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.23 (t, J = 9.1 Hz, 1H), 5.07 (q, J = 6.6 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 1.56 (d, J = 6.7 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-57.77, -121.15, -124.74 F1768 ESIMS m/z 688 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.47 (s, 1H), 10.16 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.71 (dddd, J = 22.5, 14.3, 8.7, 4.1 Hz, 3H), 7.56 (d, J = 8.7 Hz, 1H), 7.46 (dd, J = 8.0, 4.0 Hz, 2H), 7.24 (t, J = 9.2 Hz, 1H), 4.87 (s, 2H), 3.59 (d , J = 8.4 Hz, 1H), 3.44 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.22, -117.28, -120.57,
-124.27 F1769 ESIMS m/z 702 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.47 (s, 1H), 10.19 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.7, 2.6 Hz, 1H), 7.73 - 7.62 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.51 - 7.41 (m, 2H), 7.23 (t, J = 9.2 Hz, 1H), 5.07 (q, J = 6.7 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.6 Hz, 1H), 1.57 (d, J = 6.7 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-57.77, -117.28, -119.84 -
-122.30 (m), -124.74 F1770 ESIMS m/z 616 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.04 (s, 1H), 10.19 (s, 1H), 7.96 (s, 1H), 7.81 (s, 2H), 7 .68 (s, 1H), 6.89 (t, J = 9.2 Hz, 1H), 6.72 (q, J = 9.1 Hz, 1H), 5.12 (s, 2H), 3 .65 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H)'
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-135.39, -135.44, -138.45,
-144.97 (d, J = 23.8 Hz) F1771 ESIMS m/z 737 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.50 (s, 1H), 9.31 (s, 1H), 8.12 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 8.7, 6.0 Hz, 3H), 7.49 ( dd, J = 8.8, 3.3 Hz, 2H), 7.16 (td, J = 9.2, 2.0 Hz, 1H), 5.09 (q, J = 6.8 Hz, 1H ), 3.71 (d, J = 8.2 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 1.67 (d, J = 6.8 Hz, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -59.77, -61.87, -117.61, -123.42, -128.88 F1772 ESIMS m/z 723 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.52 (s, 1H), 9.30 (s, 1H), 8.13 (td, J = 8, 8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.70 ( s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.52 (dd, J = 24.2, 8.7 Hz, 2H), 7.17 (td, J = 9 ,2, 2.0 Hz, 1H), 4.87 (s, 2H), 3.77 (d, J = 8.3 Hz, 1H), 3.51 (d, J = 8.3 Hz, 1H );
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.66, -63.21, -111.84, -123.22, -128.63 F1773 ESIMS m/z 737 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.50 (s, 1H), 9.30 (s, 1H), 8.21 (s, 1H), 8 .12 (td, J = 8.8, 5.6 Hz, 1H), 8.06 - 8.01 (m, 1H), 7.82 (dd, J = 8.7, 2.6 Hz, 1H ), 7.70 (s, 1H), 7.61 (d, J = 9.5 Hz, 1H), 7.52 (dd, J = 24.6, 8.7 Hz, 2H), 7.16 (t, J = 9.3 Hz, 1H), 5.08 (q, J = 6.7 Hz, 1H), 3.77 (d, J = 8.3 Hz, 1H), 3.51 (d , J = 8.3 Hz, 1H), 1.67 (d, J = 6.8 Hz, 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -59.78, -63.20, -111.80, -123.46, -128.92 F1774 ESIMS m/z 705 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.53 (s, 1H), 9.31 (s, 1H), 8.21 - 8.02 (m, 2H), 7.86 - 7.69 (m, 4H), 7.67 (t, J = 7.7 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H), 7, 16 (td, J = 9.3, 2.0 Hz, 1H), 4.87 (s, 2H), 3.73 (d, J = 8.3 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.64, -63.07, -123.13, -128.55 F1775 ESIMS m/z 719 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.50 (s, 1H), 9.30 (s, 1H), 8.19 - 8.01 (m, 2H), 7.82 (dd, J = 8.7, 2.6 Hz, 1H), 7.81 - 7.69 (m, 3H), 7.67 (t, J = 7.7 Hz, 1H ), 7.48 (d, J = 8.8 Hz, 1H), 7.16 (td, J = 9.2, 2.0 Hz, 1H), 5.08 (q, J = 6.8 Hz , 1H), 3.73 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.4 Hz, 1H), 1.67 (d, J = 6.8 Hz, 3H );
^19F NMR (376 MHz, acetone- _d6 ) δ -59.77, -63.07, -123.42, -128.89 F1776 ESIMS m/z 808 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.03 (s, 1H), 8.42 (d, J = 2.5 Hz, 1H), 8.32 (td, J = 8.8, 5, 4 Hz, 1H), 7.90 (d, J = 2.7 Hz, 1H), 7.78 (dd, J = 8.7, 2.6 Hz, 1H), 7.48 - 7.34 ( m, 2H), 7.20 (ddd, J = 8.6, 4.7, 2.3 Hz, 1H), 7.11 (t, J = 8.3 Hz, 1H), 6.98 (td , J = 9.1, 1.8 Hz, 1H), 3.52 (d, J = 8.1 Hz, 1H), 2.85 (d, J = 8.1 Hz, 1H), 1.46 (s, 18H);
⁹ F NMR (376 MHz, CDCl ₃ ) δ
-107.69, -122.88, -132.77 F1777 ESIMS m/z 740 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.06 (s, 1H), 10.46 (s, 1H), 10.18 (s, 1H), 8.06 - 7.92 (m, 1H), 7.77 (d, J = 33.5 Hz, 4H), 7.33 - 7.19 (m, 1H), 4.84 (s, 2H), 3.65 (d, J = 8 .4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.13, -121.37, -125.82,
-135.29 (d, J = 23.8 Hz), -144.85 (d, J = 23.7 Hz) F1778 ESIMS m/z 712 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.06 (s, 1H), 10.43 (s, 1H), 9.56 (s, 1H), 7.97 (t, J = 10, 1 Hz, 1H), 7.81 (s, 2H), 7.72 (s, 1H), 7.62 (q, J = 7.7 Hz, 1H), 7.22 (t, J = 9, 2 Hz, 1H), 4.45 (dd, J = 8.3, 5.3 Hz, 1H), 4.00 (dt, J = 14.0, 6.9 Hz, 1H), 3.84 ( q, J = 7.1 Hz, 1H), 3.65 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 2.27 - 2, 15 (m, 1H), 2.04 - 1.92 (m, 1H), 1.88 (p, J = 6.9 Hz, 2H)
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-121.33, -125.62, -135.31 (d, J = 23.7 Hz), -144.89 (d, J = 23.4 Hz) F1779 ESIMS m/z 810 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.48 (s, 1H), 11.05 (s, 1H), 10.51 (s, 1H), 8.03 - 7.94 (m, 1H), 7.81 (s, 2H), 7.73 (s, 1H), 7.53 - 7.43 (m, 1H), 7.33 (t, J = 9.1 Hz, 1H), 3.65 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-80.06 (t, J = 8.4 Hz), -117.37,
-119.39, -122.65, -126.74,
-135.27 (d, J = 23.7 Hz), -144.82 (d, J = 23.5 Hz) F1780 ESIMS m/z 734 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.52 (s, 1H), 9.30 (s, 1H), 8.13 (td, J = 8, 8, 5.6 Hz, 1H), 8.03 (d, J = 2.5 Hz, 1H), 7.78 (ddd, J = 21.3, 7.6, 2.4 Hz, 2H), 7.55 - 7.44 (m, 2H), 7.33 (t, J = 8.6 Hz, 1H), 7.16 (td, J = 9.3, 2.0 Hz, 1H), 4 .87 (s, 2H), 3.62 (d, J = 8.3 Hz, 1H), 3.36 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.63, -110.14, -123.16,
-128.58 F1781 ESIMS m/z 748 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.51 (s, 1H), 9.31 (s, 1H), 8.12 (td, J = 8, 8, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.78 (ddd, J = 23.3, 7.7, 2.4 Hz, 2H), 7.54 - 7.43 (m, 2H), 7.33 (t, J = 8.6 Hz, 1H), 7.16 (td, J = 9.2, 2.0 Hz, 1H), 5 .09 (q, J = 6.8 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.35 (d, J = 8.2 Hz, 1H), 1.67 (d, J = 6.8 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -59.75, -110.11, -123.39,
-128.86 F1782 ESIMS m/z 821 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.38 (s, 1H), 10.20 (s, 1H), 9.59 (s, 1H), 8.22 (td, J = 8, 8, 5.6 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (t, J = 9.6 Hz, 2H), 7.26 (td, J = 9.2, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8 ,3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -82.44, -82.82, -83.92,
-84.27, -117.61, -118.95,
-123.31, -125.70, -127.38,
-128.06, -128.43, -131.03,
-131.71, -134.85, -135.52 F1783 ESIMS m/z 871 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.44 (s, 1H), 10.21 (s, 1H), 9.59 (s, 1H), 8.22 (td, J = 8, 9, 5.6 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.83 (ddd, J = 11.4, 7.7, 2.6 Hz, 3H), 7.48 (t, J = 9.7 Hz, 2H), 7.26 (td, J = 9.3, 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H ), 3.44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.90, -78.47, -78.89, -92.05,
-92.47, -117.65, -123.02,
-123.37, -123.77, -124.73,
-125.42, -127.13, -127.85,
-128.45, -133.53, -134.29,
-138.70, -139.42, -141.07,
-141.84 F1784 ESIMS m/z 810 ([M+H] ^- ) F1785 ESIMS m/z 612 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.97 (s, 0.2H), 10.77 (s, 0.8H), 7.92 - 7.78 (m, 2.2H ), 7.75 - 7.63 (m, 1H), 7.64 - 7.53 (m, 1.2H), 7.45 (d, J = 8.8 Hz, 0.8H), 7, 32 (d, J = 8.8 Hz, 0.8H), 6.99 (t, J = 9.7 Hz, 0.2H), 6.75 (t, J = 9.8 Hz, 0.8H ), 6.63 (q, J = 8.1 Hz, 0.2H), 6.51 - 6.37 (m, 0.8H), 5.41 (s, 0.4H), 5.30 ( s, 1.6H), 3.69 (d, J = 8.9 Hz, 0.2H), 3.65 (d, J = 8.5 Hz, 0.8H), 3.49 (d, J = 8.4 Hz, 0.2H), 3.45 (d, J = 8.5 Hz, 0.8H), 3.29 (s, 2.4H), 3.07 (s, 0.6H) ;
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -59.92 (d, J = 12.6 Hz), -116.44 - -117.69 (m),
-130.06, -131.36 (d, J = 16.0 Hz), -136.80, -137.96 F1786 ESIMS m/z 846 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.51 (s, 1H), 8.21 (s, 2H), 8.13 (s, 1H), 7 .94 (d, J = 2.6 Hz, 1H), 7.76 (dt, J = 10.5, 5.3 Hz, 2H), 7.57 (d, J = 8.7 Hz, 1H) , 7.33 - 7.23 (m, 1H), 3.85 (d, J = 8.5 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H), 1.40 ( s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.17, -123.50, -126.49 F1787 ESIMS m/z 856 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.51 (s, 1H), 8.04 (s, 1H), 7.99 (s, 1H), 7 .93 (d, J = 2.6 Hz, 1H), 7.87 (s, 1H), 7.79 - 7.69 (m, 2H), 7.57 (d, J = 8.7 Hz, 1H), 7.27 (t, J = 9.2 Hz, 1H), 3.73 (d, J = 8.4 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H) , 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.12, -123.51, -126.50 F1788 ESIMS m/z 796 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.51 (s, 1H), 7.93 (d, J = 2.6 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.76 (dt, J = 9.9, 5.0 Hz, 2H), 7.63 - 7.53 (m, 2H), 7.27 (t, J = 9.2 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 1.40 (s, 18H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 13.0 Hz), -116.94 (q, J = 13.2 Hz), -123.51,
-126.50 F1789 ESIMS m/z 751 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.59 (d, J = 46.9 Hz, 1H), 8.31 (td, J = 8.9, 5.6 Hz, 1H), 8.17 - 8.02 (m, 1H), 7.81 (ddd, J = 21.0, 7.9, 2.6 Hz, 3H), 7.49 (dd , J = 11.3, 9.0 Hz, 2H), 7.31 (td, J = 9.2, 2.0 Hz, 1H), 4.52 (s, 2H), 3.91 - 3, 60 (m, 3H), 3.44 (d, J = 8.3 Hz, 1H), 1.17 (dt, J = 27.3, 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -61.31, -61.86, -117.57, -124.18, -129.19 F1790 ESIMS m/z 705 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.51 (s, 1H), 9.15 (s, 1H), 8.11 (td, J = 8, 8, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.91 - 7.74 (m, 3H), 7.48 (dt, J = 10.0 , 5.2 Hz, 2H), 7.15 (td, J = 9.2, 1.9 Hz, 1H), 6.72 (t, J = 74.4 Hz, 1H), 4.64 (s , 2H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.83, -86.05, -117.59, -123.04, -128.55 F1791 ESIMS m/z 648 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.18 (s, 1H), 8.22 (s, 2H), 8.13 (s, 1H), 7 .91 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H) , 6.91 (ddd, J = 10.6, 8.9, 1.8 Hz, 1H), 6.81 (td, J = 8.4, 5.6 Hz, 1H), 5.31 (s , 2H), 3.86 (d, J = 8.5 Hz, 1H), 3.70 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.19, -133.97 (d, J = 13.8 Hz), -138.09 (d, J = 14.0 Hz) F1792 ESIMS m/z 690 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 11.61 (s, 0.35H), 11.45 (s, 0.65H), 10.97 (s, 0.35H), 10, 75 (s, 0.65H), 7.90 (d, J = 2.5 Hz, 0.35H), 7.76 (d, J = 2.1 Hz, 0.35H), 7.75 - 7 .66 (m, 3H), 7.61 (d, J = 8.8 Hz, 0.35H), 7.54 - 7.37 (m, 2.65H), 7.30 (d, J = 8 .8 Hz, 0.65H), 7.20 (t, J = 9.2 Hz, 0.65H), 3.61 (d, J = 8.5 Hz, 0.35H), 3.57 (d , J = 8.4 Hz, 0.65H), 3.45 (d, J = 8.5 Hz, 0.35H), 3.38 (d, J = 7.0 Hz, 0.65H), 3 .35 (s, 2H), 3.14 (s, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -73.80 (d, J = 25.1 Hz), -116.65, -117.78, -121.98,
-122.52 F1793 ESIMS m/z 720 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) rotary isomers δ 10.97 (s, 0.3H), 10.75 (s, 0.7H), 10.10 (s, 1H), 7.90 ( d, J = 2.5 Hz, 0.3H), 7.76 (d, J = 2.1 Hz, 0.3H), 7.74 - 7.66 (m, 2.7H), 7.64 - 7.54 (m, 1H), 7.52 - 7.27 (m, 3H), 7.09 (t, J = 9.2 Hz, 0.7H), 4.88 (s, 0.6H ), 4.78 (s, 1.4H), 3.61 (d, J = 8.6 Hz, 0.3H), 3.58 (d, J = 8.5 Hz, 0.7H), 3 .45 (d, J = 8.5 Hz, 0.3H), 3.38 (d, J = 8.6 Hz, 0.7H), 3.31 (s, 2H), 3.12 (s, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -59.23, -59.30,
-116.14, -117.20 (d, J = 4.5 Hz), -122.12, -122.56 F1794 ESIMS m/z 694 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.99 (s, 0.3H), 10.75 (s, 0.7H), 9.70 (s, 0.3H), 9, 49 (s, 0.7H), 7.89 (d, J = 2.3 Hz, 0.3H), 7.76 (s, 0.3H), 7.70 (d, J = 8.8 Hz , 2H), 7.60 (d, J = 8.8 Hz, 0.3H), 7.57 - 7.49 (m, 0.3H), 7.48 - 7.37 (m, 1.4H ), 7.36 - 7.23 (m, 1.7H), 7.05 (t, J = 9.0 Hz, 0.7H), 4.02 (d, J = 6.6 Hz, 0. 3H), 3.92 (s, 0.7H), 3.60 (t, J = 7.8 Hz, 1H), 3.56 - 3.48 (m, 1H), 3.46 (d, J = 8.4 Hz, 1H), 3.38 (d, J = 8.7 Hz, 1H), 3.31 (s, 2H), 3.11 (s, 1H), 1.39 - 1.08 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -116.40, -117.53,
-122.40, -123.28 F1795 ESIMS m/z 708 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 11.62 (s, 0.3H), 11.45 (s, 0.7H), 10.98 (s, 0.3H), 10, 76 (s, 0.7H), 7.91 (d, J = 2.4 Hz, 0.3H), 7.90 - 7.85 (m, 0.3H), 7.85 - 7.76 ( m, 1.7H), 7.76 - 7.67 (m, 1.3H), 7.65 - 7.54 (m, 1.3H), 7.53 - 7.39 (m, 1.7H ), 7.31 (d, J = 8.7 Hz, 0.7H), 7.20 (t, J = 9.2 Hz, 0.7H), 3.69 (d, J = 8.6 Hz , 0.3H), 3.65 (d, J = 8.6 Hz, 0.7H), 3.50 (d, J = 8.1 Hz, 0.3H), 3.41 (d, J = 8.7 Hz, 0.7H), 3.34 (s, 2H), 3.14 (s, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -59.96 (dd, J = 33.6, 12.5 Hz), -73.84, -116.64,
-116.79 - -117.10 (m), -117.78 (d, J = 3.9 Hz), -121.92, -122.51 F1796 ESIMS m/z 738 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.98 (s, 0.3H), 10.76 (s, 0.7H), 10.19 (s, 0.3H), 10, 07 (s, 0.7H), 7.90 (d, J = 2.4 Hz, 0.3H), 7.87 (d, J = 6.9 Hz, 0.3H), 7.85 - 7 .77 (m, 1.7H), 7.75 - 7.67 (m, 1H), 7.64 - 7.55 (m, 1.7H), 7.53 - 7.43 (m, 0. 6H), 7.39 - 7.27 (m, 1.7H), 7.09 (t, J = 9.1 Hz, 0.7H), 4.88 (s, 0.6H), 4.77 (s, 1.4H), 3.72 - 3.63 (m, 1H), 3.49 (d, J = 8.5 Hz, 0.3H), 3.42 (d, J = 8.5 Hz, 0.7H), 3.32 (s, 2H), 3.13 (s, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -59.24, -59.35, -59.92 (d, J = 12.5 Hz), -60.00 (d, J = 12 ,4 Hz), -116.16, -116.93 (q, J = 13.0 Hz), -117.21, -122.07,
-122.56 F1797 ESIMS m/z 712 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.99 (s, 0.3H), 10.75 (s, 0.7H), 9.70 (s, 0.3H), 9, 48 (s, 0.7H), 7.93 - 7.77 (m, 2.3H), 7.76 - 7.64 (m, 1H), 7.64 - 7.50 (m, 1.7H ), 7.49 - 7.41 (m, 0.6H), 7.36 - 7.24 (m, 1.7H), 7.05 (t, J = 9.1 Hz, 0.7H), 4.02 (q, J = 6.6 Hz, 0.3H), 3.92 (s, 0.7H), 3.68 (t, J = 7.0 Hz, 1H), 3.63 - 3 .52 (m, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 3.31 (s, 2H), 3 .12 (s, 1H), 1.35 (d, J = 6.7 Hz, 1H), 1.31 - 1.05 (m, 5H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -59.89 - -59.94 (m),
-59.94 - -60.00 (m), -116.93 (q, J = 12.2 Hz), -116.17, -117.52 (d, J = 5.2 Hz), -122 .38, -123.29 F1798 ESIMS m/z 710 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.99 (s, 0.3H), 10.75 (s, 0.7H), 9.67 (s, 0.3H), 9, 46 (s, 0.7H), 7.93 - 7.77 (m, 3H), 7.76 - 7.63 (m, 1H), 7.63 - 7.56 (m, 1.3H), 7.56 - 7.42 (m, 0.6H), 7.35 - 7.24 (m, 1.4H), 7.05 (t, J = 9.1 Hz, 0.7H), 4, 46 (dd, J = 8.3, 5.1 Hz, 0.3H), 4.42 - 4.31 (m, 0.7H), 4.01 (q, J = 7.3 Hz, 0. 3H), 3.93 (s, 0.7H), 3.85 (q, J = 7.2 Hz, 0.3H), 3.80 - 3.72 (m, 0.7H), 3.72 - 3.64 (m, 1H), 3.50 (d, J = 8.5 Hz, 0.3H), 3.43 (d, J = 8.6 Hz, 0.7H), 3.31 ( s, 2H), 3.11 (s, 1H), 2.29 - 2.04 (m, 1H), 2.02 - 1.72 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.88 - -59.99 (m), -116.31,
-116.92 (qd, J = 12.5, 5.0 Hz),
-117.57 (d, J = 5.4 Hz), -122.36, -123.20 F1799 ESIMS m/z 654 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) rotary isomers δ 10.98 (s, 0.3H), 10.74 (s, 0.7H), 9.83 (s, 0.3H), 9, 69 (s, 0.7H), 7.92 - 7.78 (m, 2.3H), 7.74 - 7.63 (m, 1H), 7.63 - 7.55 (m, 1.7H ), 7.54 - 7.46 (m, 0.6H), 7.34 - 7.23 (m, 1.7H), 7.06 (d, J = 9.5 Hz, 0.7H), 3.73 - 3.60 (m, 1H), 3.50 (d, J = 8.5 Hz, 0.3H), 3.44 (d, J = 8.5 Hz, 0.7H), 3 .32 (s, 2H), 3.11 (s, 1H), 2.09 (s, 1H), 1.99 (s, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) rotary isomers δ -59.89 - -59.96 (m),
-116.26, -116.86 - -117.03 (m), -117.10 (d, J = 5.5 Hz), -122.24, -122.97 F1800 ESIMS m/z 720 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 10.44 (s, 1H), 9.97 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.90 - 7.79 (m, 2H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 - 7.51 (m, 3H ), 7.20 (t, J = 9.2 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 2.73 - 2.53 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.4 Hz), -65.16,
-116.95 (q, J = 12.4 Hz), -120.48 (d, J = 3.3 Hz), -124.38 (d, J = 3.5 Hz) F1801 ESIMS m/z 742 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.56 (s, 1H), 10.96 (s, 1H), 10.56 (s, 1H), 8.21 (s, 2H), 8 .13 (s, 1H), 7.96 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.7, 2.8 Hz, 2H), 7.57 (d, J = 8.8 Hz, 1H), 7.33 (t, J = 9.2 Hz, 1H), 3.85 (d, J = 8.5 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.18, -73.83, -121.07, -124.41 F1802 ESIMS m/z 724 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.79 (s, 1H), 10.52 (s, 1H), 8.21 (s, 2H), 8 .13 (s, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7.81 - 7.68 (m, 2H), 7.57 (d, J = 8.8 Hz, 1H), 7.28 (t, J = 9.2 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 3.86 (d, J = 8.5 Hz, 1H) , 3.69 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.17, -120.66 (d, J = 2.7 Hz),
-124.22, -125.81 F1803 ESIMS m/z 688 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.78 (s, 1H), 8.21 (s, 2H), 8 .13 (s, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.66 - 7, 53 (m, 2H), 7.19 (t, J = 9.2 Hz, 1H), 3.86 (d, J = 8.5 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H), 2.08 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.18, -120.45 (d, J = 3.6 Hz),
-124.56 (d, J = 3.5 Hz) F1804 ESIMS m/z 772 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.49 (s, 1H), 10.17 (s, 1H), 8.22 (s, 2H), 8 .13 (s, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 (td, J = 8.7, 5.7 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.29 - 7.19 (m, 1H), 4.87 (s, 2H ), 3.86 (d, J = 8.5 Hz, 1H), 3.70 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.24, -61.19, -120.57, -124.26 F1805 ESIMS m/z 744 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.44 (s, 1H), 9.61 (s, 1H), 8.21 (s, 2H), 8 .13 (s, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 (td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.25 - 7.14 (m, 1H), 4.46 (dd, J = 8.3, 5.1 Hz, 1H), 4.01 (q, J = 6.8 Hz, 1H), 3.92 - 3.78 (m, 2H), 3.70 (d, J = 8.5 Hz, 1H), 2.23 (dq, J = 11.8, 7.7 Hz, 1H), 2.03 - 1.79 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.18, -120.93 (d, J = 3.8 Hz),
-124.76 (d, J = 3.8 Hz) F1806 ESIMS m/z 716 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.44 (s, 1H), 9.70 (s, 1H), 8.21 (s, 2H), 8 .13 (s, 1H), 7.93 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.62 (q, J = 8.5 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.19 (t, J = 9.1 Hz, 1H), 3.86 (d, J = 8.5 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H), 2.33 (t, J = 7.2 Hz, 2H), 1.62 (h, J = 7, 3 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.18, -120.55 (d, J = 3.6 Hz),
-124.56 (d, J = 4.0 Hz) F1807 ESIMS m/z 635 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 9.33 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 8.9, 6.2 Hz, 3H), 7.61 (td, J = 8.6, 5.4 Hz, 1H), 7.48 (dt, J = 9.7, 5 .5 Hz, 2H), 6.97 (ddd, J = 11.4, 9.1, 2.1 Hz, 1H), 5.01 (s, 1H), 4.15 - 4.08 (m, 2H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.64 (t, J = 2.4 Hz, 1H) ;
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.64, -132.75,
-140.50 F1808 ESIMS m/z 773 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.52 (s, 1H), 9.22 (s, 1H), 8.12 (td, J = 8, 7, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 9.6 , 5.3 Hz, 2H), 7.16 (td, J = 9.2, 2.0 Hz, 1H), 4.96 (s, 2H), 3.72 (d, J = 8.3 Hz , 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -61.85, -86.48, -91.19, -117.61, -123.14, -128.50 F1809 ESIMS m/z 709 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.46 (s, 1H), 8.97 (s, 1H), 8.13 - 7.99 (m, 2H), 7.90 - 7.77 (m, 3H), 7.48 (dt, J = 9.9, 5.2 Hz, 2H), 7.11 (td, J = 9.2, 2, 0 Hz, 1H), 4.06 (td, J = 7.7, 5.5 Hz, 1H), 3.98 (q, J = 7.3 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 2.37 (ddd, J = 12.4, 7.3, 5.1 Hz, 1H), 2, 08 - 1.89 (m, 2H), 1.85 (dt, J = 12.2, 8.0 Hz, 1H), 1.47 (s, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.60, -123.52,
-129.20 F1810 ESIMS m/z 702 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.29 (s, 1H), 9.71 (s, 1H), 8.37 (q, J = 8.0 Hz, 1H), 8.13 - 8.02 (m, 1H), 7.86 - 7.74 (m, 3H), 7.47 (t, J = 9.9 Hz, 2H), 7.36 - 7.26 (m, 1H ), 4.68 - 4.50 (m, 2H), 3.72 (d, J = 7.1 Hz, 3H), 3.46 (d, J = 8.3 Hz, 1H), 2.76 (t, J = 2.6 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.80, -117.47, -122.89,
-128.24 F1811 ESIMS m/z 761 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.68 (s, 1H), 8.36 (td, J = 8.8, 5.4 Hz, 1H) , 8.08 (t, J = 2.1 Hz, 1H), 7.88 - 7.75 (m, 3H), 7.54 - 7.44 (m, 2H), 7.32 (td, J = 9.2, 2.0 Hz, 1H), 4.68 - 4.49 (m, 4H), 3.72 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H), 2.76 (t, J = 2.6 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.33, -61.86, -117.63, -123.34, -128.58 F1812 ESIMS m/z 674.9722 ([M+NH ₄ ] ⁺ ) ^1H NMR (500 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.95 (s, 1H), 10.75 (s, 1H), 7.97 (dd, J = 7, 0, 2.5 Hz, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.8, 2.5 Hz, 2H), 7.69 ( d, J = 8.4 Hz, 1H), 7.58 (t, J = 6.7 Hz, 2H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7, 36 (t, J = 9.7 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ
-73.83, -125.38 F1813 ESIMS m/z 675 ([M+NH ₄ ] ⁺ ) ^1H NMR (500 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.93 (s, 1H), 10.76 (s, 1H), 7.98 (dd, J = 6, 9, 2.7 Hz, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.67 - 7.52 (m, 5H), 7.37 (dd, J = 10.0, 9.0 Hz, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.52 (d , J = 8.5 Hz, 1H);
¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ
-73.84, -125.37, -125.38 F1814 ESIMS m/z 640.1 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.95 (s, 1H), 10.75 (s, 1H), 7.97 (dd, J = 7, 0, 2.6 Hz, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 ( dd, J = 7.1, 2.0 Hz, 1H), 7.58 (t, J = 7.5 Hz, 2H), 7.53 - 7.42 (m, 2H), 7.36 (t , J = 9.5 Hz, 1H), 3.58 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-73.83, -73.84, -117.28, -125.39 F1815 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₆ H ₁₄ Cl ₃ F ₈ N ₃ O ₃ , 672.9973 found, 672.9973 ^1H NMR (500 MHz, DMSO- _d6 ) δ 11.35 (s, 1H), 10.97 (s, 1H), 10.76 (s, 1H), 7.98 (dd, J = 6, 9, 2.7 Hz, 1H), 7.91 (d, J = 2.6 Hz, 1H), 7.87 (dd, J = 6.9, 2.3 Hz, 1H), 7.83 ( ddd, J = 7.5, 4.5, 2.2 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 - 7.54 (m, 3H), 7.47 - 7.27 (m, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (471 MHz, DMSO-d ₆ ) δ
-59.91, -59.94, -73.86, -116.92, -116.93, -116.94, -125.40,
-125.40 F1816 ESIMS m/z 691 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 10.71 (s, 1H), 10.51 (s, 1H), 9.21 (d, J = 1, 8 Hz, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.79 - 7.69 (m, 2H), 7, 63 - 7.52 (m, 2H), 7.28 (t, J = 9.1 Hz, 1H), 7.06 (d, J = 1.7 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.6 Hz), -116.95 (q, J = 12.6 Hz), -120.42,
-124.22 F1817 ESIMS m/z 707 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.77 (s, 1H), 10.52 (s, 1H), 8.77 (d, J = 1, 8 Hz, 1H), 8.13 (s, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7.91 - 7.80 (m, 2H), 7.79 - 7, 68 (m, 2H), 7.66 - 7.52 (m, 2H), 7.30 (t, J = 9.2 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H ), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.6 Hz), -116.94 (q, J = 12.2 Hz), -120.27,
-124.02 F1818 ESIMS m/z 691 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.87 (s, 1H), 10.52 (s, 1H), 8.87 (d, J = 1, 9 Hz, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.79 - 7.69 (m, 2H), 7, 63 - 7.54 (m, 2H), 7.34 - 7.26 (m, 2H), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8, 5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.4 Hz), -116.94 (q, J = 12.6 Hz), -120.34,
-124.13 F1819 ESIMS m/z 772 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.47 (s, 1H), 10.03 (s, 1H), 8.04 (d, J = 2, 4 Hz, 1H), 7.93 (d, J = 2.6 Hz, 1H), 7.91 - 7.79 (m, 2H), 7.76 (dd, J = 8.8, 2.5 Hz, 1H), 7.70 (q, J = 8.4 Hz, 1H), 7.64 - 7.52 (m, 2H), 7.23 (t, J = 9.1 Hz, 1H), 6.91 (d, J = 2.5 Hz, 1H), 5.29 (q, J = 9.0 Hz, 2H), 3.69 (d, J = 8.4 Hz, 1H), 3, 51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.3 Hz), -69.99,
-116.96 (q, J = 12.4 Hz),
-120.46, -124.42 F1820 ESIMS m/z 708 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.09 (s, 1H), 10.97 (s, 1H), 10.53 (s, 1H), 9.55 (s, 1H), 7 .95 (d, J = 2.5 Hz, 1H), 7.91 - 7.79 (m, 2H), 7.79 - 7.67 (m, 2H), 7.64 - 7.53 (m , 2H), 7.31 (t, J = 9.2 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.5 Hz), -116.94 (q, J = 12.4 Hz), -120.08,
-123.75 F1821 ESIMS m/z 763 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.40 (s, 1H), 8.77 - 8.72 (m, 1H), 8.10 (q, J = 8.0 Hz, 1H), 7 .74 (s, 1H), 7.70 - 7.59 (m, 2H), 7.46 (t, J = 6.9 Hz, 2H), 7.32 - 7.17 (m, 2H), 6.93 (t, J = 9.1 Hz, 1H), 4.24 (s, 2H), 3.54 (d, J = 8.1 Hz, 1H), 2.82 (d, J = 8 .2 Hz, 1H), 1.61 - 1.49 (m, 2H), 1.12 - 1.00 (m, 2H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-60.60, -61.42, -114.89, -123.25, -129.36 F1822 ESIMS m/z 729 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.53 (d, J = 11.2 Hz, 2H), 8.14 (td, J = 8.8, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.94 - 7.73 (m, 3H), 7.57 - 7.39 (m, 2H), 7.17 (td, J = 9.3, 2.0 Hz, 1H), 5.74 (d, J = 47.9 Hz, 1H), 4.32 (qq, J = 6.8, 3, 7 Hz, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 1.29 (t, J = 7.1 Hz , 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.57, -123.01,
-128.46, -194.32 F1823 ESIMS m/z 710 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.66 (s, 1H), 8.34 (td, J = 8.7, 4.3 Hz, 1H) , 8.12 - 8.01 (m, 1H), 7.81 (ddd, J = 24.6, 8.0, 2.7 Hz, 3H), 7.49 (dd, J = 11.1, 9.0 Hz, 2H), 7.35 - 7.16 (m, 1H), 4.75 - 4.63 (m, 1H), 4.55 (t, J = 4.8 Hz, 1H), 4.13 - 4.06 (m, 1H), 4.09 - 3.99 (m, 1H), 3.76 - 3.68 (m, 2H), 3.61 (s, 1H), 3, 44 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.61, -123.85,
-129.03 F1824 ESIMS m/z 759
([MH]-) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.16 (s, 1H), 10.96 (s, 1H), 10.53 (s, 1H), 7.95 (d, J = 2, 5 Hz, 2H), 7.90 - 7.79 (m, 2H), 7.79 - 7.70 (m, 2H), 7.64 - 7.52 (m, 2H), 7.31 (t , J = 9.2 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.4 Hz), -62.09,
-116.94 (q, J = 12.5 Hz),
-120.17, -123.87 F1825 ESIMS m/z 842 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.60 (s, 1H), 10.96 (s, 1H), 10.56 (s, 1H), 8.21 (s, 2H), 8 .13 (s, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7.84 - 7.70 (m, 2H), 7.57 (d, J = 8.8 Hz, 1H), 7.33 (t, J = 9.1 Hz, 1H), 3.86 (d, J = 8.5 Hz, 1H), 3.69 (d, J = 8.5 Hz, 1H) ;
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.19, -80.07 (t, J = 8.2 Hz),
-119.32, -121.36, -124.68,
-126.82 F1826 ESIMS m/z 643 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.33 (s, 1H), 8.33 (d, J = 2.5 Hz, 1H), 7.96 (dd, J = 8.8, 2, 6 Hz, 1H), 7.72 (d, J = 2.6 Hz, 1H), 7.59 (td, J = 8.6, 5.2 Hz, 1H), 7.47 (dd, J = 6.5, 2.2 Hz, 1H), 7.42 - 7.33 (m, 2H), 7.17 (t, J = 9.2 Hz, 1H), 6.80 (ddd, J = 11 ,1, 9.0, 2.0 Hz, 1H), 4.60 (t, J = 4.7 Hz, 1H), 4.49 (t, J = 4.7 Hz, 1H), 3.99 (s, 1H), 3.64 (t, J = 4.8 Hz, 1H), 3.61 - 3.51 (m, 2H), 2.90 (d, J = 8.2 Hz, 1H) ;
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-61.44, -114.78, -130.91,
-142.38 F1827 ESIMS m/z 725 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.59 (s, 1H), 8.36 (d, J = 2.5 Hz, 1H), 7.94 (dd, J = 8.8, 2, 6 Hz, 1H), 7.73 (d, J = 2.6 Hz, 1H), 7.60 - 7.45 (m, 2H), 7.42 - 7.31 (m, 2H), 7, 16 (t, J = 9.2 Hz, 1H), 6.77 (ddd, J = 11.0, 9.0, 1.9 Hz, 1H), 4.02 (q, J = 6.9 Hz , 1H), 3.63 (ddd, J = 8.6, 7.2, 1.5 Hz, 1H), 3.61 - 3.51 (m, 2H), 3.35 (q, J = 7 .4 Hz, 2H), 2.97 (d, J = 8.2 Hz, 1H), 1.45 (d, J = 6.9 Hz, 3H), 1.29 - 1.15 (m, 6H ) F1828 ESIMS m/z 719 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.26 (s, 1H), 9.50 (d, J = 10.8 Hz, 1H), 9.14 (s, 1H), 8.25 (s, 1H), 8.14 - 8.00 (m, 1H), 7.83 (dd, J = 7.9, 5.7 Hz, 3H), 7.48 (dt, J = 10.0 , 5.2 Hz, 2H), 7.14 (td, J = 9.3, 2.0 Hz, 1H), 5.48 (d, J = 6.8 Hz, 1H), 3.71 (d , J = 8.3 Hz, 1H), 3.46 (d, J = 8.3 Hz, 1H), 1.64 - 1.50 (m, 3H) F1829 ESIMS m/z 821 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.49 (s, 1H), 9.09 (s, 1H), 8.15 - 8.00 (m, 2H), 7.91 - 7.76 (m, 3H), 7.48 (dt, J = 9.8, 5.3 Hz, 2H), 7.18 - 7.08 (m, 1H), 3 .72 (d, J = 8.2 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.88 (t, J = 7.8 Hz, 2H), 2.69 (dt, J = 20.7, 7.8 Hz, 2H) F1830 ESIMS m/z 735 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.49 (s, 1H), 8.96 (s, 1H), 8.12 - 8.00 (m, 2H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 9.8, 5.2 Hz, 2H), 7.11 (td, J = 9.3, 1, 9 Hz, 1H), 3.71 (d, J = 8.2 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.63 (t, J = 7.3 Hz , 2H), 2.43 - 2.25 (m, 2H), 1.96 (p, J = 7.4 Hz, 2H) F1831 ESIMS m/z 800 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.50 (d, J = 8.7 Hz, 2H), 8.12 (td, J = 8.7, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 7.4, 5.6 Hz, 3H), 7.53 - 7, 43 (m, 2H), 7.16 (td, J = 9.3, 2.0 Hz, 1H), 4.97 (t, J = 6.9 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.48 - 3.30 (m, 2H), 3.02 (dqd, J = 16.0, 10.2, 6.0 Hz, 1H) F1832 ESIMS m/z 721 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.49 (s, 1H), 9.28 (s, 1H), 8.11 (td, J = 8, 7, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 7.8, 5.5 Hz, 3H), 7.48 ( dt, J = 9.6, 5.4 Hz, 2H), 7.15 (td, J = 9.2, 1.9 Hz, 1H), 3.70 (dd, J = 16.2, 8, 4 Hz, 2H), 3.44 (d, J = 8.3 Hz, 1H), 1.47 (d, J = 7.0 Hz, 3H) F1833 (thin film) 3264, 1670, 1507, 1314 ESIMS m/z 788 ([M+H] ^- ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.48 (s, 1H), 10.22 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.91 - 7.79 (m, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 - 7.61 (m, 1H ), 7.57 (dd, J = 8.9, 4.5 Hz, 2H), 7.23 (t, J = 9.2 Hz, 1H), 4.47 - 4.26 (m, 1H) , 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 3.02 (d, J = 6.3 Hz, 2H) F1834 ESIMS m/z 809 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.60 (m, 2H), 8.29 - 8.10 (m, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.90 - 7.78 (m, 3H), 7.48 (t, J = 9.0 Hz, 2H), 7.26 (td, J = 9.3 , 2.0 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -56.01, -61.87, -88.51, -117.66, -123.12, -123.66, -128.85 F1835 ESIMS m/z 735 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.47 (s, 1H), 9.09 (s, 1H), 8.15 - 8.00 (m, 2H), 7.87 - 7.78 (m, 3H), 7.48 (dt, J = 10.0, 5.2 Hz, 2H), 7.12 (td, J = 9.3, 2, 0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 3.12 - 3.02 (m, 1H) , 2.90 - 2.70 (m, 1H), 2.33 (dqd, J = 15.7, 11.2, 4.6 Hz, 1H), 1.37 (d, J = 7.0 Hz , 3H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.87, -65.46, -117.62, -123.48, -128.93 F1836 ESIMS m/z 747 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.49 (s, 1H), 9.06 (s, 1H), 8.13 - 8.00 (m, 2H), 7.82 (dq, J = 9.2, 2.6 Hz, 3H), 7.47 (dt, J = 8.1, 5.1 Hz, 2H), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.85 (s , 2H), 1.12 - 0.98 (m, 4H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -71.70, -117.56, -123.10, -128.52 F1837 ESIMS m/z 763 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.49 (s, 1H), 9.29 (s, 1H), 8.15 - 8.00 (m, 2H), 7.87 - 7.78 (m, 3H), 7.53 - 7.43 (m, 2H), 7.15 (td, J = 9.2, 1.9 Hz, 1H), 4 .67 (qd, J = 7.3, 5.8 Hz, 1H), 4.11 (td, J = 7.8, 4.8 Hz, 1H), 4.00 (td, J = 8.2 , 6.3 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.59 (td, J = 8.0, 5.9 Hz, 1H), 3.45 (d , J = 8.3 Hz, 1H), 2.54 (q, J = 7.0 Hz, 1H), 2.35 - 2.21 (m, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.88, -78.06, -117.60, -123.49, -128.83 F1838 ESIMS m/z 639 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.26 (s, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.53 - 7.39 (m, 3H), 6.90 (ddd, J = 11.4, 9.0, 2.0 Hz, 1H), 4.53 (s, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 3.37 - 3.26 (m, 2H) , 1.60 (h, J = 7.3 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.60, -133.95,
-141.63 F1839 ESIMS m/z 775 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 2H), 9.58 (s, 1H), 8.21 (td, J = 8.8, 5.6 Hz, 1H) , 8.05 (d, J = 2.6 Hz, 1H), 7.83 (ddd, J = 11.4, 6.4, 1.8 Hz, 3H), 7.48 (t, J = 9 ,0 Hz, 2H), 7.24 (td, J = 9.3, 2.0 Hz, 1H), 6.26 - 5.95 (m, 1H), 3.82 - 3.62 (m, 1H), 3.45 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.89, -74.91, -116.68, -117.57, -117.64, -121.04, -121.77,
-123.34, -128.61, -128.73 F1840 ESIMS m/z 735 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.24 (s, 1H), 9.80 (s, 1H), 9.54 (d, J = 17.1 Hz, 1H), 8.13 (dq, J = 8.5, 5.6 Hz, 1H), 8.04 (t, J = 2.8 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.53 - 7.43 (m, 2H), 7.17 (td, J = 9.0, 2.1 Hz, 1H), 6.80 (s, 1H), 6.04 (s, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.86, -75.49, -86.87, -117.62, -122.84, -128.16 F1841 ESIMS m/z 706 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.66 (s, 1H), 8.32 (td, J = 8.7, 5.5 Hz, 1H) , 8.13 - 8.02 (m, 1H), 7.87 - 7.73 (m, 3H), 7.48 (dd, J = 11.1, 9.0 Hz, 2H), 7.30 (td, J = 9.3, 2.0 Hz, 1H), 3.76 - 3.60 (m, 5H), 3.45 (d, J = 8.3 Hz, 1H), 1.55 ( h, J = 7.5 Hz, 2H), 0.92 (dt, J = 14.8, 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.81, -117.55, -123.64,
-128.78 F1842 ESIMS m/z 739 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.25 (s, 1H), 9.63 (d, J = 4.9 Hz, 1H), 8.23 (dtd, J = 12.1, 8.7, 5.7 Hz, 1H), 8.08 (dd, J = 7.4, 2.6 Hz, 1H), 7.88 - 7.76 (m, 3H), 7.54 - 7 .44 (m, 2H), 7.28 (td, J = 9.2, 1.9 Hz, 1H), 3.88 (q, J = 6.5 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.62 (td, J = 8.5, 8.0, 2.3 Hz, 2H), 3.46 (dd, J = 8.3, 2.0 Hz , 1H), 3.34 - 3.10 (m, 2H), 1.54 (h, J = 7.5 Hz, 2H), 1.17 (dd, J = 6.4, 1.6 Hz, 3H), 1.00 (qd, J = 7.0, 2.1 Hz, 3H), 0.90 (td, J = 7.3, 5.9 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.87, -117.57, -122.40,
-124.16, -127.42, -128.93 F1843 ESIMS m/z 716 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.88 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.87 (dd, J = 6.9, 2.2 Hz, 1H), 7.85 - 7.80 (m, 1H), 7.75 (dd, J = 8.8 , 2.6 Hz, 1H), 7.67 - 7.58 (m, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7.24 - 7.15 (m, 1H) , 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 2.56 (t, J = 7.7 Hz, 2H), 2 .23 (tt, J = 16.2, 7.7 Hz, 2H), 1.64 (t, J = 19.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.7 Hz), -89.33,
-116.96 (t, J = 12.5 Hz), -120.50 (d, J = 3.6 Hz), -124.48 (d, J = 3.7 Hz) F1844 ESIMS m/z 770 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.45 (s, 1H), 10.00 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.87 (d, J = 6.9 Hz, 1H), 7.85 - 7.80 (m, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 - 7.58 (m, 2H), 7.58 - 7.53 (m, 1H), 7.25 - 7.16 (m, 1H), 3.69 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 2.72 (t, J = 7.3 Hz, 2H), 2.66 - 2.52 ( m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.93 (d, J = 12.4 Hz), -84.65,
-116.94 (q, J = 12.5 Hz),
-117.20, -120.51 (d, J = 3.4 Hz), -124.40 (d, J = 3.5 Hz) F1845 ESIMS m/z 680 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.43 (s, 1H), 9.70 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.89 - 7.85 (m, 1H), 7.85 - 7.80 (m, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H ), 7.67 - 7.57 (m, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7.24 - 7.13 (m, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 2.23 (d, J = 7.2 Hz, 2H), 2.07 (dt, J = 13.6, 6.9 Hz, 1H), 0.96 (d, J = 6.6 Hz, 6H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.91 (d, J = 12.6 Hz), -116.94 (q, J = 12.5 Hz), -120.55 (d, J = 3.5 Hz), -124.54 ( d, J = 3.9 Hz) F1846 ESIMS m/z 736 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.46 (s, 1H), 9.84 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.87 (dd, J = 7.0 Hz, 1H), 7.85 - 7.79 (m, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.70 - 7.58 (m, 2H), 7.58 - 7.53 (m, 1H), 7.22 (t, J = 9.1 Hz, 1H), 4.38 (s, 2H), 4.25 (q, J = 9.3 Hz, 2H), 3.69 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz , 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.3 Hz), -72.91,
-116.94 (q, J = 12.5 Hz), -120.42 (d, J = 3.4 Hz), -124.26 (d, J = 3.5 Hz) F1847 ESIMS m/z 702 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 9.97 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 7.9, 2.2 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.63 (td, J = 8.6, 5.6 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7, 26 - 7.14 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.72 - 2.52 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-65.15, -120.48 (d, J = 3.4 Hz),
-124.38 (d, J = 3.9 Hz) F1848 ESIMS m/z 686 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 9.98 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.68 - 7.59 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.53 - 7.41 (m, 2H), 7.26 - 7.15 (m, 1H) , 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 2.72 - 2.54 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-65.15, -117.28, -120.48 (d, J = 3.6 Hz), -124.37 (d, J = 3.8 Hz) F1849 ESIMS m/z 747 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.63 (s, 1H), 9.51 (s, 1H), 8.14 (d, J = 6, 6 Hz, 1H), 8.05 (d, J = 2.5 Hz, 1H), 7.84 (q, J = 8.7, 8.0 Hz, 3H), 7.49 (t, J = 9.4 Hz, 2H), 7.18 (t, J = 9.2 Hz, 1H), 3.71 (dd, J = 8.3, 4.1 Hz, 2H), 3.62 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.52 (s, 2H), 1.29 (s, 2H);
^19F NMR (376 MHz, acetone- _d6 ) δ -61.90, -75.44, -117.64, -122.75, -128.03 F1850 128-134 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₃₀ H ₂₀ Cl ₃ F ₆ N ₃ O ₄ , 705.0424 found, 705.0416 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 10.17 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 - 7.52 (m, 3H ), 7.21 (td, J = 9.2, 1.7 Hz, 1H), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz , 1H), 2.26 (s, 3H), 1.53 - 1.46 (m, 2H), 1.46 - 1.40 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.8 Hz), -116.94 (q, J = 12.7 Hz), -120.74 (d, J = 3.4 Hz), -124.66 ( d, J = 3.5 Hz) F1851 ESIMS m/z 732 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.47 (s, 1H), 9.03 (s, 1H), 8.09 (td, J = 8, 8, 5.6 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.87 - 7.78 (m, 3H), 7.48 (dt, J = 9.7 , 5.4 Hz, 2H), 7.13 (td, J = 9.2, 2.0 Hz, 1H), 3.79 - 3.68 (m, 3H), 3.43 (d, J = 8.3 Hz, 1H), 3.12 (t, J = 6.5 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.88, -117.64, -122.98,
-128.32 F1853 ESIMS m/z 746 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.46 (s, 1H), 9.02 (s, 1H), 8.13 - 7.99 (m, 2H), 7.86 - 7.77 (m, 3H), 7.52 - 7.43 (m, 2H), 7.12 (td, J = 9.3, 1.9 Hz, 1H), 4 .62 (dp, J = 7.8, 6.6 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H) , 3.09 (h, J = 8.9, 8.4 Hz, 2H), 1.80 (d, J = 6.7 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.83, -117.59, -122.89,
-128.28 F1854 ESIMS m/z 693 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.11 (s, 1H), 9.38 (s, 1H), 8.77 (s, 1H), 8.03 - 7.89 (m, 2H), 7.78 - 7.68 (m, 3H), 7.39 (dd, J = 9.5, 6.9 Hz, 2H), 7.01 (td, J = 9.2, 2, 0 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.33 (d, J = 8.3 Hz, 1H), 2.46 (t, J = 7.4 Hz , 2H), 1.51 (q, J = 7.3 Hz, 2H), 0.71 (tt, J = 7.6, 4.9 Hz, 1H), 0.38 - 0.27 (m, 2H), -0.01 (dd, J = 4.9, 1.5 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.61, -123.15,
-128.65 F1855 ESIMS m/z 678 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.20 (s, 1H), 9.48 (s, 1H), 9.08 (s, 1H), 8.15 - 8.04 (m, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.83 (ddd, J = 8.4, 5.8, 2.5 Hz, 3H), 7.54 - 7.44 (m, 2H), 7.14 (dd, J = 10.3, 8.3 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.93 (t, J = 7.1 Hz, 2H), 2.80 (d, J = 6.9 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.89, -117.63, -123.27,
-128.48 F1856 ESIMS m/z 723 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.48 (s, 1H), 8.84 (s, 1H), 8.11 - 7.98 (m, 2H), 7.82 (ddd, J = 11.4, 7.1, 2.6 Hz, 3H), 7.48 (dd, J = 9.5, 6.8 Hz, 2H), 7.10 (td, J = 9.2, 1.9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2 .44 (t, J = 7.3 Hz, 2H), 1.69 (dtd, J = 15.1, 7.4, 4.3 Hz, 2H), 1.34 - 1.25 (m, 2H ), 0.90 (s, 9H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.85, -117.57, -123.16,
-128.68 F1857 ESIMS m/z 692 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 9.49 (s, 1H), 9.01 (s, 1H), 8.12 - 8.00 (m, 2H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 9.9, 5.1 Hz, 2H), 7.12 (td, J = 9.3, 1, 9 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.67 (t, J = 7.2 Hz , 2H), 2.59 (t, J = 7.2 Hz, 2H), 2.09 - 1.97 (m, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -61.86, -117.58, -123.18,
-128.68 F1858 ESIMS m/z 837 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.49 (s, 1H), 9.10 (s, 1H), 8.15 - 8.00 (m, 2H), 7.87 - 7.77 (m, 3H), 7.48 (dt, J = 9.8, 5.3 Hz, 2H), 7.13 (td, J = 9.2, 1, 9 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H), 2.89 (dd, J = 8.6, 5.8 Hz, 2H), 2.75 (dt, J = 15.7, 7.5 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ -53.91, -61.86, -83.72, -117.59, -123.23, -128.61, -130.79 F1860 ESIMS m/z 698 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.88 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.66 - 7.58 (m, 1H), 7, 56 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.19 (t, J = 9.1 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.56 (t, J = 7.7 Hz, 2H), 2, 22 (tt, J = 16.1, 7.7 Hz, 2H), 1.64 (t, J = 19.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-89.32, -120.49 (d, J = 4.0 Hz),
-124.48 (d, J = 3.6 Hz) F1861 ESIMS m/z 752 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 10.45 (s, 1H), 10.00 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.63 (td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.20 (td, J = 8 .9, 8.4, 1.5 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.72 (t, J = 7.3 Hz, 2H), 2.65 - 2.52 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-84.63, -117.20, -120.50 (d, J = 3.5 Hz), -124.40 (d, J = 3.6 Hz) F1862 ESIMS m/z 716 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 9.96 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.67 - 7.59 (m, 1H), 7, 55 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 7.24 - 7.15 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 3.01 - 2.85 (m, 1H), 2.79 - 2.56 ( m, 1H), 2.46 - 2.29 (m, 1H), 1.25 (d, J = 7.1 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.57, -121.06, -124.87 F1863 ESIMS m/z 718 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 9.83 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.64 (dd, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.22 (td, J = 9 ,2, 1.7 Hz, 1H), 4.38 (s, 2H), 4.25 (q, J = 9.3 Hz, 2H), 3.61 (d, J = 8.4 Hz, 1H ), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-72.91, -120.42 (d, J = 3.4 Hz),
-124.26 (d, J = 3.1 Hz) F1864 ESIMS m/z 682 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.88 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.62 ( td, J = 8.6, 5.7 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.51 - 7.42 (m, 2H), 7.23 - 7 .14 (m, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 2.56 (t, J = 7, 7 Hz, 2H), 2.22 (tt, J = 16.1, 7.8 Hz, 2H), 1.64 (t, J = 19.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-89.31, -117.28, -120.50 (d, J = 3.5 Hz), -124.48 (d, J = 3.7 Hz) F1865 ESIMS m/z 736 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.45 (s, 1H), 10.00 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.67 - 7.59 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.51 - 7.42 (m, 2H), 7.24 - 7.15 (m, 1H) , 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 2.72 (t, J = 7.3 Hz, 2H), 2 .66 - 2.52 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-84.63, -117.24 (d, J = 37.2 Hz), -120.50 (d, J = 3.4 Hz), -124.40 (d, J = 3.9 Hz) F1866 ESIMS m/z 700 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.44 (s, 1H), 9.96 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.63 ( td, J = 8.7, 5.6 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.51 - 7.40 (m, 2H), 7.24 - 7 .15 (m, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.4 Hz, 1H), 2.93 (td, J = 8, 3, 6.9, 4.1 Hz, 1H), 2.79 - 2.59 (m, 1H), 2.46 - 2.29 (m, 1H), 1.25 (d, J = 7, 1 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.57, -117.29, -121.06,
-124.87 F1867 ESIMS m/z 702 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.46 (s, 1H), 9.84 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.3, 1.9 Hz, 1H), 7.65 ( td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.26 - 7 .17 (m, 1H), 4.38 (s, 2H), 4.25 (q, J = 9.3 Hz, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3 .44 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-72.91, -117.28, -120.42,
-124.26 F1868 ESIMS m/z 665 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.47 (s, 1H), 8.87 (s, 1H), 8.07 (td, J = 8, 7, 5.6 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.53 - 7.43 (m, 2H ), 7.11 (td, J = 9.3, 2.0 Hz, 1H), 6.94 (dq, J = 15.4, 6.9 Hz, 1H), 6.25 (dq, J = 15.2, 1.7 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H), 1.89 (dd, J = 6.9, 1.7 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.87, -117.60, -123.07,
-128.56 F1869 ESIMS m/z 719 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.53 (d, J = 9.9 Hz, 2H), 8.12 (td, J = 8.8, 5.6 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.86 - 7.76 (m, 3H), 7.47 (dt, J = 9.7, 5 ,2 Hz, 2H), 7.21 - 7.06 (m, 2H), 6.96 (dq, J = 15.5, 6.7 Hz, 1H), 3.71 (d, J = 8, 3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.83, -65.68, -117.55, -122.71, -128.05 F1870 ESIMS m/z 669 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 9.50 (d, J = 30.0 Hz, 2H), 8.14 (td, J = 8.7, 5.6 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.90 - 7.77 (m, 3H), 7.48 (dd, J = 8.7, 3 .6 Hz, 2H), 7.17 (td, J = 9.3, 2.0 Hz, 1H), 5.75 (dd, J = 47.0, 3.5 Hz, 1H), 5.37 (dd, J = 15.2, 3.5 Hz, 1H), 3.71 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.84, -117.52, -119.65,
-122.85, -128.42 F1871 ESIMS m/z 650 ([M+H]-) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.49 (s, 1H), 10.37 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.79 - 7.65 (m, 4H), 7.56 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.7, 2.1 Hz, 1H), 7.25 (t, J = 9.1 Hz, 1H), 5.74 (dd, J = 47.7, 3.8 Hz, 1H), 5.50 (dd, J = 15 ,6, 3.8 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ )) δ
-117.09, -120.57, -124.35 F1872 ESIMS m/z 684 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.49 (s, 1H), 10.37 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.80 (d, J = 0.7 Hz, 2H), 7.78 - 7.66 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H) , 7.26 (td, J = 9.4, 1.6 Hz, 1H), 5.75 (dd, J = 47.6, 3.8 Hz, 1H), 5.51 (dd, J = 15 ,6, 3.8 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.11, -120.56 (d, J = 3.1 Hz), -124.33 F1873 ESIMS m/z 648 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.43 (s, 1H), 9.81 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 7.9, 2.3 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.66 - 7.58 ( m, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.46 - 7.40 (m, 1H), 7.24 - 7.14 (m, 1H), 5.96 (ddt, J = 17.0, 10.1, 6.8 Hz, 1H), 5.22 (dd, J = 17.2, 1.9 Hz, 1H), 5.16 (dq, J = 10 ,2, 1.6 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H), 3.17 (dd, J = 6.0, 2.5 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-120.51 (d, J = 3.6 Hz), -124.43 (d, J = 3.9 Hz) F1874 ESIMS m/z 664 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.43 (s, 1H), 9.81 (s, 1H), 7.93 (d, J = 2, 5 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 - 7.52 (m, 3H ), 7.19 (t, J = 9.1 Hz, 1H), 5.95 (ddd, J = 16.9, 10.4, 5.7 Hz, 1H), 5.22 (d, J = 17.3 Hz, 1H), 5.18 - 5.11 (m, 1H), 3.70 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 3.18 (d, J = 6.8 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.5 Hz), -116.94 (q, J = 12.6 Hz), -120.52 (d, J = 4.1 Hz), -124.43 ( d, J = 4.0 Hz) F1875 ESIMS m/z 682 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.06 (s, 1H), 10.42 (s, 1H), 9.86 (s, 1H), 7.98 (t, J = 9, 5 Hz, 1H), 7.87 - 7.66 (m, 4H), 7.20 (t, J = 9.2 Hz, 1H), 5.95 (ddd, J = 17.1, 10.1 , 5.3 Hz, 1H), 5.25 - 5.11 (m, 2H), 3.65 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 8.5 Hz , 1H), 3.19 (d, J = 6.9 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-122.50, -126.32, -135.30 (d, J = 23.8 Hz), -144.89 (d, J = 23.8 Hz) F1876 ESIMS m/z 630 ([M+H] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.44 (s, 1H), 9.81 (s, 1H), 7.92 (d, J = 2, 6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.62 ( td, J = 8.7, 5.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.53 - 7.42 (m, 2H), 7.24 - 7 .14 (m, 1H), 5.96 (ddt, J = 17.0, 10.1, 6.8 Hz, 1H), 5.22 (dd, J = 17.3, 1.9 Hz, 1H ), 5.16 (dq, J = 10.1, 1.6 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.44 (d, J = 8.5 Hz , 1H), 3.18 (d, J = 6.8 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -120.51 (d, J = 3.8 Hz), -124.43 (d, J = 3.8 Hz) F1877 132-137 HRMS-ESI (m/z) [M+] ⁺ calculated for C ₂₇ H ₁₆ Cl ₃ F ₆ N ₃ O ₃ , 649.0161; found, 649.0169 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.46 (s, 1H), 10.02 (s, 1H), 7.93 (d, J = 2, 6 Hz, 1H), 7.91 - 7.79 (m, 2H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.66 (dd, J = 8.7 , 5.7 Hz, 1H), 7.62 - 7.53 (m, 2H), 7.22 (td, J = 9.2, 1.8 Hz, 1H), 6.48 (dd, J = 17.1, 10.2 Hz, 1H), 6.28 (dd, J = 17.1, 1.9 Hz, 1H), 5.83 (dd, J = 10.2, 1.9 Hz, 1H ), 3.69 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.92 (d, J = 12.5 Hz), -116.94 (q, J = 12.5 Hz), -120.17,
-124.27 F1878 ESIMS m/z 647 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.21 (s, 1H), 9.48 (s, 1H), 8.88 (s, 1H), 8.11 - 7.99 (m, 2H), 7.85 - 7.62 (m, 6H), 7.47 (d, J = 8.8 Hz, 1H), 7.10 (td, J = 9.3, 2.0 Hz, 1H ), 6.05 (ddt, J = 17.1, 10.2, 6.8 Hz, 1H), 5.29 - 5.19 (m, 1H), 5.15 (dq, J = 10.2 , 1.6 Hz, 1H), 3.73 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.4 Hz, 1H), 3.27 (d, J = 6 ,9 Hz, 2H);
^19F NMR (376 MHz, acetone- _d6 ) δ -63.04, -123.14, -128.63 F1879 ESIMS m/z 665 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.48 (s, 1H), 8.89 (s, 1H), 8.11 - 7.98 (m, 2H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.69 (s, 1H), 7.64 - 7.51 (m, 2H), 7.47 (d , J = 8.7 Hz, 1H), 7.10 (td, J = 9.3, 2.0 Hz, 1H), 6.05 (ddt, J = 17.0, 10.1, 6.8 Hz, 1H), 5.29 - 5.19 (m, 1H), 5.15 (dq, J = 10.1, 1.6 Hz, 1H), 3.77 (d, J = 8.3 Hz , 1H), 3.49 (d, J = 8.3 Hz, 1H), 3.27 (d, J = 6.8 Hz, 2H);
¹⁹ F NMR (376 MHz, acetone-d ₆ ) δ -63.17, -111.74, -123.12,
-128.61 F1880 ESIMS m/z 676 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.22 (s, 1H), 9.49 (s, 1H), 8.90 (s, 1H), 8.10 - 7.98 (m, 2H), 7.84 - 7.70 (m, 2H), 7.53 - 7.43 (m, 2H), 7.33 (t, J = 8.6 Hz, 1H), 7.10 (td , J = 9.3, 2.0 Hz, 1H), 6.05 (ddt, J = 17.1, 10.2, 6.9 Hz, 1H), 5.29 - 5.19 (m, 1H ), 5.15 (dq, J = 10.2, 1.6 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.35 (d, J = 8.3 Hz , 1H), 3.27 (d, J = 6.8 Hz, 2H);
^19F NMR (376 MHz, acetone- _d6 ) δ -110.08, -123.05, -128.54 F1881 ESIMS m/z 735 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.55 (d, J = 19.2 Hz, 1H), 8.18 (td, J = 8.8, 5.7 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.88 - 7.75 (m, 3H), 7.47 (t, J = 9.2 Hz, 2H), 7.16 (tt, J = 8.7, 4.3 Hz, 1H), 4.42 (dd, J = 18.3, 2.5 Hz, 2H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d, J = 8.3 Hz, 1H), 2.81 - 2.61 (m, 1H), 1.46 (d, J = 64.9 Hz , 9H); ^19F NMR (376 MHz, acetone- _d6 ) δ -61.82,
-117.46, -123.33, -129.13 F1882 ESIMS m/z 743 ([M+H] ⁺ ) ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.64 - 9.38 (m, 1H), 8.92 - 8.39 (m, 1H), 8.33 - 8.08 (m, 1H), 8.04 - 7.78 (m, 1H), 7.78 - 7.41 (m, 3H), 7.37 - 7.13 (m, 2H), 7.04 - 6.59 (m, 1H ), 4.55 (ddq, J = 46.6, 12.0, 6.6, 6.1 Hz, 2H), 3.99 - 3.80 (m, 2H), 3.55 (dd, J = 8.6, 3.7 Hz, 1H), 2.90 (t, J = 8.3 Hz, 1H), 1.62 - 1.27 (m, 9H) F1883 ESIMS m/z 739 ([M+H] ⁺ ) ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.65 - 8.63 (m, 2H), 8.35 - 7.59 (m, 2H), 7.54 - 7.30 (m, 3H), 7.23 - 6.85 (m, 1H), 6.78 - 6.51 (m, 2H), 3.69 - 3.38 (m, 3H), 3.02 - 2.75 (m, 1H ), 1.66 - 1.30 (m, 11H), 1.05 - 0.79 (m, 3H) F2001 ESIMS m/z 569 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.17 (s, 1H), 8.24 (t, J = 6.4 Hz, 1H), 7.92 (d, J = 2.6 Hz , 1H), 7.82 (s, 1H), 7.87 - 7.74 (m, 3H), 7.46 (d, J = 8.7 Hz, 1H), 4.21 (qd, J = 9.4, 6.5 Hz, 2H), 3.67 (d, J = 8.3 Hz, 1H), 3.52 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.93, -72.59 F2002 ESIMS m/z 556 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.28 (s, 1H), 8.24 (t, J = 6.6 Hz, 1H), 7.92 (d, J = 2.6 Hz , 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 4.29 - 4.14 (m, 2H), 3.51 (d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.63, -142.49, -155.92, -164.18 F2003 ESIMS m/z 581 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.15 (s, 1H), 8.22 (t, J = 6.4 Hz, 1H), 7.91 (dd, J = 2.7, 1.0 Hz, 1H), 7.77 (ddd, J = 8.8, 2.7, 0.9 Hz, 1H), 7.62 (dt, J = 4.5, 2.0 Hz, 1H ), 7.53 (ddd, J = 11.0, 6.8, 2.1 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 4.20 (qd, J = 9.5, 6.5 Hz, 2H), 3.65 (dd, J = 8.3, 1.1 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.61, -133.28, -135.78 F2004 ESIMS m/z 581 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.07 (s, 1H), 8.20 (t, J = 6.6 Hz, 1H), 7.78 (d, J = 2.6 Hz , 1H), 7.68 (dd, J = 8.7, 2.7 Hz, 1H), 7.56 (dq, J = 5.1, 1.7 Hz, 1H), 7.51 - 7, 36 (m, 2H), 4.18 (dtd, J = 9.5, 8.1, 5.3 Hz, 2H), 3.55 (d, J = 11.2 Hz, 1H), 3.25 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.58, -134.39, -136.95 F2005 112-116 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₁ Cl ₅ F ₆ N ₂ O ₂ , 599.9167; found, 599.9165 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.40 (s, 1H), 9.47 (t, J = 6.3 Hz, 1H), 7.87 (d, J = 8.8 Hz , 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.53 - 7.39 (m, 2H), 4.17 (td, J = 15.9, 6.2 Hz, 2H), 3.72 (d, J = 8.5 Hz, 1H), 3.59 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.41, -117.27, -119.88 F2006 ESIMS m/z 553 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.18 (s, 1H), 8.25 (t, J = 6.4 Hz, 1H), 7.91 (d, J = 2.6 Hz , 1H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.58 (d, J = 2.0 Hz, 1H), 7.53 - 7.41 (m, 2H), 4.21 (qd, J = 9.5, 6.5 Hz, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.42 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.60, -112.53 F2007 ESIMS m/z 553 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.08 (s, 1H), 8.19 (t, J = 6.6 Hz, 1H), 7.77 (d, J = 2.6 Hz , 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 1H), 7.53 (q, J = 1.5 Hz, 1H), 7.49 - 7.37 (m, 2H), 4.18 (qdd, J = 9.5, 6.4, 1.4 Hz, 2H), 3.57 (d, J = 11.2 Hz, 1H), 3.28 (d, J = 11.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.60, -112.53 F2008 ESIMS m/z 671 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H), 8.06 (dt, J = 13.8, 1.9 Hz, 2H), 7.99 (s, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7.83 - 7.73 (m, 1H), 7.45 ( d, J = 8.8 Hz, 1H), 4.20 (qd, J = 9.5, 6.5 Hz, 2H), 3.80 (d, J = 8.3 Hz, 1H), 3, 52 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.60 F2009 ESIMS m/z 671 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.10 (s, 1H), 8.18 (t, J = 6.6 Hz, 1H), 8.07 - 7.89 (m, 3H) , 7.77 - 7.63 (m, 2H), 7.41 (d, J = 8.7 Hz, 1H), 4.26 - 4.09 (m, 2H), 3.69 (dd, J = 11.2, 1.1 Hz, 1H), 3.33 (d, J = 11.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.62 F2010 ESIMS m/z 537 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.13 (s, 1H), 8.31 - 8.17 (m, 1H), 7.78 (d, J = 2.5 Hz, 1H) , 7.66 (dd, J = 8.8, 2.6 Hz, 1H), 7.60 - 7.49 (m, 1H), 7.42 (dd, J = 22.1, 8.8 Hz , 1H), 7.21 (dtd, J = 17.6, 8.7, 1.9 Hz, 1H), 4.18 (qd, J = 9.6, 6.0 Hz, 2H), 3, 44 (dd, J = 11.1, 1.8 Hz, 1H), 3.28 (d, J = 11.0 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.55, -112.61, -115.81 F2011 ESIMS m/z 537 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.23 (s, 1H), 8.24 (t, J = 6.4 Hz, 1H), 7.92 (d, J = 2.6 Hz , 1H), 7.78 (dd, J = 8.7, 2.6 Hz, 1H), 7.50 - 7.37 (m, 2H), 7.25 (td, J = 8.7, 1 .9 Hz, 1H), 4.20 (ttd, J = 9.5, 6.4, 3.2 Hz, 2H), 3.63 - 3.55 (m, 1H), 3.36 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-72.60, -114.47, -115.17 F2012 ESIMS m/z 587 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 8.24 (t, J = 6.5 Hz, 1H), 7.98 (dd, J = 6.4, 2.2 Hz, 1H), 7.92 (d, J = 2.5 Hz, 1H), 7.85 - 7.74 (m, 2H), 7.46 (d, J = 8.7 Hz, 1H), 4.20 (qd, J = 9.5, 6.5 Hz, 2H), 3.70 (d, J = 8.1 Hz, 1H), 3.53 (d, J = 8.2 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.65, -72.61, -111.91 F2013 ESIMS m/z 587 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.15 (s, 1H), 8.19 (t, J = 6.5 Hz, 1H), 7.93 - 7.85 (m, 2H) , 7.75 (d, J = 2.6 Hz, 1H), 7.67 (dd, J = 8.8, 2.7 Hz, 1H), 7.41 (d, J = 8.7 Hz, 1H), 4.17 (qdd, J = 9.5, 6.5, 1.6 Hz, 2H), 3.57 (dd, J = 10.9, 1.2 Hz, 1H), 3.36 (d, J = 11.0 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-62.68, -72.60, -109.42 F2014 ESIMS m/z 566 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.14 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H), 7.92 (d, J = 2.6 Hz , 1H), 7.74 (ddd, J = 26.9, 7.8, 2.4 Hz, 2H), 7.61 (dd, J = 6.4, 2.2 Hz, 1H), 7, 45 (d, J = 8.7 Hz, 1H), 4.20 (qd, J = 9.5, 6.5 Hz, 2H), 3.65 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H), 2.38 (d, J = 2.2 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -72.62, -121.65 F2015 ESIMS m/z 566 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.04 (s, 1H), 8.18 (t, J = 6.5 Hz, 1H), 7.75 (d, J = 2.7 Hz , 1H), 7.68 (dd, J = 8.7, 2.6 Hz, 1H), 7.61 (ddd, J = 13.4, 6.7, 2.2 Hz, 2H), 7, 41 (d, J = 8.7 Hz, 1H), 4.17 (qdd, J = 9.4, 6.4, 2.3 Hz, 2H), 3.59 - 3.50 (m, 1H) , 3.25 (d, J = 11.4 Hz, 1H), 2.33 (d, J = 2.2 Hz, 3H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.85, -72.63, -122.75 F2016 184-187 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₄ Cl ₃ F ₃ N ₂ O ₂ , 464.0073; found, 464.0078 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.54 (s, 1H), 8.77 (t, J = 5.5 Hz, 1H), 7.93 (td, J = 8.9, 5.9 Hz, 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.54 - 7.39 (m, 2H), 7.17 (td, J = 8 .9, 1.6 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.57 (d, J = 8.6 Hz, 1H), 3.28 (qd, J = 7.3, 5.6 Hz, 2H), 1.11 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.30, -118.65, -118.65,
-124.00, -124.01 F2017 163-165 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₁ Cl ₃ F ₆ N ₂ O ₂ , 517.9790; found, 517.9795 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.59 (s, 1H), 9.51 (t, J = 6.3 Hz, 1H), 8.01 (td, J = 8.9, 5.9 Hz, 1H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.57 - 7.34 (m, 2H), 7.22 (td, J = 8 .9, 1.6 Hz, 1H), 4.15 (qd, J = 9.7, 6.3 Hz, 2H), 3.61 (d, J = 8.6 Hz, 1H), 3.57 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.70, -117.29, -118.59,
-118.59, -123.69, -123.70 F2018 202-205 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₁ Cl ₃ F ₈ N ₂ O ₂ , 567.9758; found, 567.9759 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.60 (s, 1H), 9.53 (t, J = 6.3 Hz, 1H), 8.01 (td, J = 8.9, 5.8 Hz, 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.55 - 7.37 (m, 2H), 7.22 (td, J = 9 ,1, 1.5 Hz, 1H), 4.20 (td, J = 15.4, 6.3 Hz, 2H), 3.61 (d, J = 8.6 Hz, 1H), 3.57 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.38, -117.30, -118.50,
-120.09, -123.69 F2019 187-190 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₄ Cl ₅ FN ₂ O ₂ , 495.9482; found, 495.9485 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.35 (s, 1H), 8.69 (t, J = 5.6 Hz, 1H), 7.83 (d, J = 8.8 Hz , 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.50 (dd, J = 16.1, 8.9 Hz, 2H), 7.43 (ddd, J = 8.6, 4.7, 2.1 Hz, 1H), 3.72 (d, J = 8.5 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H), 3.27 (p, J = 7.2 Hz, 2H), 1.13 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27 F2020 174-177 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₁ Cl ₅ F ₄ N ₂ O ₂ , 549.9199; found, 549.9199 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.40 (s, 1H), 9.46 (t, J = 6.3 Hz, 1H), 7.87 (d, J = 8.8 Hz , 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 - 7.45 (m, 1H), 7.45 - 7.41 (m, 1H), 4.20 - 4.07 (m, 2H), 3.72 (d, J = 8.6 Hz, 1H), 3.59 (d , J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.04, -117.27 F2021 83-87 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₆ Cl ₃ F ₃ N ₂ O ₂ , 478.0229; found, 478.0234 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.54 (s, 1H), 8.75 (t, J = 5.7 Hz, 1H), 7.94 (td, J = 8.9, 5.9 Hz, 1H), 7.67 (dd, J = 7.1, 2.2 Hz, 1H), 7.56 - 7.37 (m, 2H), 7.17 (td, J = 8 .9, 1.6 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.57 (d, J = 8.6 Hz, 1H), 3.22 (q, J = 6.5 Hz, 2H), 1.51 (h, J = 7.2 Hz, 2H), 0.91 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.30, -118.67, -118.68,
-124.05, -124.06 F2022 104-108 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₆ Cl ₅ FN ₂ O ₂ , 509.9638; found, 509.9644 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.35 (s, 1H), 8.69 (t, J = 5.7 Hz, 1H), 7.83 (d, J = 8.8 Hz , 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.57 - 7.37 (m, 3H), 3.72 (d, J = 8.6 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H), 3.21 (q, J = 6.5 Hz, 2H), 1.54 (h, J = 7.3 Hz, 2H) , 0.93 (t, J = 7.4 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28 F2023 78-83 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₃ Cl ₃ F ₆ N ₂ O ₂ , 531.9947; found, 531.9948 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.56 (s, 1H), 9.04 (t, J = 5.7 Hz, 1H), 7.96 (td, J = 8.9, 5.9 Hz, 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.55 - 7.40 (m, 2H), 7.19 (td, J = 8 .9, 1.6 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.57 (d, J = 8.6 Hz, 1H), 3.51 (q, J = 6.3 Hz, 2H), 2.62 - 2.53 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.82, -117.30, -118.51, -123.88 F2024 99-102 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₃ Cl ₅ F ₄ N ₂ O ₂ , 563.9356; found, 563.9358 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.38 (s, 1H), 9.01 (t, J = 5.7 Hz, 1H), 7.85 (d, J = 8.8 Hz , 1H), 7.67 (dd, J = 7.2, 2.1 Hz, 1H), 7.57 - 7.39 (m, 3H), 3.72 (d, J = 8.5 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H), 3.49 (q, J = 6.5 Hz, 2H), 2.56 (ddd, J = 11.4, 6.9 , 4.5 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.92, -117.27 F2025 174-177 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₃ Cl ₅ F ₂ N ₂ O ₂ , 513.9388; found, 513.9390 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.36 (s, 1H), 9.01 (t, J = 5.6 Hz, 1H), 7.84 (d, J = 8.8 Hz , 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.58 - 7.33 (m, 3H), 4.54 (dt, J = 47.5, 5 .0 Hz, 2H), 3.72 (d, J = 8.5 Hz, 1H), 3.63 - 3.48 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ 15.95, -117.28 F2026 140-144 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₅ Cl ₆ FN ₂ O ₂ , 543.9249; found, 543.9251 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.37 (s, 1H), 8.81 (t, J = 5.7 Hz, 1H), 7.84 (d, J = 8.8 Hz , 1H), 7.67 (dd, J = 7.1, 2.1 Hz, 1H), 7.61 - 7.31 (m, 3H), 3.78 - 3.69 (m, 3H), 3.58 (d, J = 8.5 Hz, 1H), 3.38 (q, J = 6.3 Hz, 2H), 1.99 (p, J = 6.6 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.27 F2027 174-177 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₃ Cl ₃ F ₄ N ₂ O ₂ , 481.9979; found, 481.9984 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.56 (s, 1H), 9.06 (t, J = 5.6 Hz, 1H), 7.95 (td, J = 8.9, 5.9 Hz, 1H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.55 - 7.37 (m, 2H), 7.19 (td, J = 8 ,9, 1.6 Hz, 1H), 4.53 (dt, J = 47.5, 4.9 Hz, 2H), 3.67 - 3.51 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ 15.22, -117.30, -118.47, -118.48, -123.73, -123.74 F2028 78-83 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₅ Cl ₄ F ₃ N ₂ O ₂ , 511.9840; found, 511.9844 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.56 (s, 1H), 8.87 (t, J = 5.6 Hz, 1H), 7.96 (td, J = 8.9, 5.9 Hz, 1H), 7.68 (dd, J = 7.1, 2.1 Hz, 1H), 7.55 - 7.37 (m, 2H), 7.19 (td, J = 8 .9, 1.5 Hz, 1H), 3.71 (t, J = 6.5 Hz, 2H), 3.61 (d, J = 8.6 Hz, 1H), 3.57 (d, J = 8.6 Hz, 1H), 3.39 (q, J = 6.4 Hz, 2H), 1.96 (p, J = 6.6 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.30, -118.69, -118.70,
-124.05, -124.05 F2029 213-215 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₇ Cl ₃ F ₂ N ₂ O ₂ , 460.0324; found, 460.0319 ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.71 (s, 1H), 8.30 (s, 1H), 7.73 - 7.62 (m, 3H), 7.52 - 7, 41 (m, 2H), 3.55 (d, J = 8.5 Hz, 1H), 3.39 (d, J = 8.5 Hz, 1H), 3.27 (qd, J = 7.2 , 5.6 Hz, 2H), 2.27 (d, J = 2.1 Hz, 3H), 1.11 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.32, -124.28 F2030 206-209 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₄ Cl ₃ F ₅ N ₂ O ₂ , 514.0041; found, 514.0043 ^1H NMR (400 MHz, DMSO- _d6 ) δ d 10.76 (s, 1H), 9.00 (t, J = 6.4 Hz, 1H), 7.70 (dd, J = 6.5 , 4.0 Hz, 3H), 7.52 - 7.39 (m, 2H), 4.16 - 4.01 (m, 2H), 3.56 (d, J = 8.5 Hz, 1H) , 3.40 (d, J = 8.5 Hz, 1H), 2.28 (d, J = 2.1 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.54, -117.31, -123.99 F2031 195-197 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₄ Cl ₃ F ₇ N ₂ O ₂ , 564.0009; found, 564.0011 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.76 (s, 1H), 9.00 (t, J = 6.3 Hz, 1H), 7.70 (dt, J = 6.2, 2.9 Hz, 3H), 7.53 - 7.41 (m, 2H), 4.13 (td, J = 15.4, 6.3 Hz, 2H), 3.56 (d, J = 8 .4 Hz, 1H), 3.40 (d, J = 8.5 Hz, 1H), 2.28 (d, J = 2.1 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.42, -117.32, -120.13, -124.07 F2032 201-203 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₈ Cl ₄ F ₂ N ₂ O ₂ , 508.0090; found, 509.0094 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.72 (s, 1H), 8.49 - 8.36 (m, 1H), 7.68 (ddt, J = 11.5, 5.8 , 2.4 Hz, 3H), 7.56 - 7.41 (m, 2H), 3.70 (t, J = 6.5 Hz, 2H), 3.56 (d, J = 8.5 Hz , 1H), 3.42 - 3.34 (m, 3H), 2.27 (d, J = 2.2 Hz, 3H), 1.97 (p, J = 6.6 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.32, -124.30 F2033 186-189 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₄ Cl ₄ F ₂ N ₂ O ₂ , 479.99777 found, 479.9784 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.06 (s, 1H), 8.58 (t, J = 5.6 Hz, 1H), 7.80 (dd, J = 11.3, 2.4 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.54 - 7.42 (m, 3H), 3.59 (d, J = 8 .4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 3.30 - 3.20 (m, 2H), 1.12 (t, J = 7.2 Hz, 3H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.85, -117.24 F2034 175-178 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₁₉ H ₁₁ Cl ₄ F ₅ N ₂ O ₂ , 533.9495; found, 533.9497 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.11 (s, 1H), 9.33 (t, J = 6.3 Hz, 1H), 7.86 (dd, J = 11.3, 2.4 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.59 - 7.40 (m, 3H), 4.23 - 3.93 (m , 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.46, -112.52, -117.23 F2035 186-190 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₁ Cl ₄ F ₇ N ₂ O ₂ , 583.9463; found, 583.9465 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.12 (s, 1H), 9.35 (t, J = 6.3 Hz, 1H), 7.87 (dd, J = 11.3, 2.4 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.58 - 7.37 (m, 3H), 4.16 (td, J = 15 ,5, 6.3 Hz, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.37, -112.48, -117.24, -120.04 F2036 190-194 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₅ Cl ₅ F ₂ N ₂ O2, 527.9544; found, 527.9544 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.07 (s, 1H), 8.68 (t, J = 5.6 Hz, 1H), 7.82 (dd, J = 11.3, 2.4 Hz, 1H), 7.71 (dd, J = 7.2, 1.9 Hz, 1H), 7.53 - 7.40 (m, 3H), 3.72 (t, J = 6 .5 Hz, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.43 (d, J = 8.5 Hz, 1H), 3.40 - 3.33 (m, 2H ), 1.97 (p, J = 6.7 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.76, -117.23 F2037 118-124 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₇ Cl ₄ FN ₂ O ₂ , 476.0028; found, 476.0032 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.78 (s, 1H), 8.42 (t, J = 5.6 Hz, 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.64 (d, J = 2.5 Hz, 1H), 7.55 (d, J = 2.5 Hz, 1H), 7.51 - 7.41 (m, 2H), 3.56 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 3.29 - 3.20 (m, 2H), 2, 35 (s, 3H), 1.11 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29 F2038 194-201 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₄ Cl ₄ F ₄ N ₂ O ₂ , 529.9746; found, 529.9743 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 9.18 (t, J = 6.3 Hz, 1H), 7.73 - 7.66 (m, 2H) , 7.58 (d, J = 2.5 Hz, 1H), 7.53 - 7.39 (m, 2H), 4.14 - 4.00 (m, 2H), 3.56 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 2.37 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.43, -117.29 F2039 194-196 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₄ Cl ₄ F ₆ N ₂ O ₂ , 579.9714; found, 579.9716 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 9.19 (t, J = 6.3 Hz, 1H), 7.75 - 7.66 (m, 2H) , 7.58 (d, J = 2.5 Hz, 1H), 7.52 - 7.39 (m, 2H), 4.12 (td, J = 15.5, 6.3 Hz, 2H), 3.57 (d, J = 8.5 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H), 2.37 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.39, -117.29, -120.04 F2040 208-211 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₈ Cl ₅ FN ₂ O ₂ , 523.9795; found, 523.9794 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.79 (s, 1H), 8.53 (t, J = 5.7 Hz, 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.65 (d, J = 2.5 Hz, 1H), 7.56 (d, J = 2.5 Hz, 1H), 7.51 - 7.40 (m, 2H), 3.71 (t, J = 6.6 Hz, 2H), 3.56 (d, J = 8.5 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H) , 3.38 - 3.33 (m, 2H), 2.36 (s, 3H), 2.03 - 1.90 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29 F2041 110-116 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₇ Cl ₄ FN ₂ O ₂ , 476.0028; found, 476.0027 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.85 (s, 1H), 8.43 (t, J = 5.6 Hz, 1H), 7.88 (d, J = 2.2 Hz , 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.55 - 7.39 (m, 3H), 3.57 (d, J = 8.5 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 3.25 (p, J = 6.8 Hz, 2H), 2.27 (s, 3H), 1.11 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.29 F2042 102-108 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₄ Cl ₄ F ₄ N ₂ O ₂ , 529.9746; found, 529.9744 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 9.18 (t, J = 6.3 Hz, 1H), 7.94 (d, J = 2.2 Hz , 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.59 - 7.37 (m, 3H), 4.09 (dtd, J = 16.1, 9 ,4, 2.4 Hz, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 2.27 (s, 3H );
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.52, -117.28 F2043 177-181 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₄ Cl ₄ F ₆ N ₂ O ₂ , 579.9714; found, 579.9717 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 9.18 (t, J = 6.3 Hz, 1H), 7.95 (d, J = 2.2 Hz , 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.55 - 7.39 (m, 3H), 4.14 (td, J = 15.7, 6 .3 Hz, 2H), 3.58 (d, J = 8.5 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 2.27 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.40, -117.28, -120.07 F2044 103-110 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₈ Cl ₅ FN ₂ O ₂ , 523.9795; found, 523.9793 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.85 (s, 1H), 8.52 (t, J = 5.6 Hz, 1H), 7.90 (d, J = 2.2 Hz , 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.52 - 7.42 (m, 3H), 3.71 (t, J = 6.5 Hz, 2H), 3.57 (d, J = 8.4 Hz, 1H), 3.44 - 3.34 (m, 3H), 2.27 (s, 3H), 1.97 (p, J = 6 ,6 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28 F2045 211-214 ESIMS m/z 537 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.00 (s, 1H), 9.24 (t, J = 6.3 Hz, 1H), 8.07 (dd, J = 6.3, 2.7 Hz, 1H), 7.73 (ddd, J = 14.4, 6.2, 2.3 Hz, 2H), 7.46 (dd, J = 7.9, 4.9 Hz, 2H ), 4.18 - 4.05 (m, 2H), 3.59 (d, J = 8.5 Hz, 1H), 3.49 - 3.39 (m, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.54, -117.25, -122.97 F2046 195-198 ESIMS m/z 585 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.01 (s, 1H), 9.25 (t, J = 6.4 Hz, 1H), 8.08 (dd, J = 6.4, 2.6 Hz, 1H), 7.78 - 7.67 (m, 2H), 7.53 - 7.39 (m, 2H), 4.16 (td, J = 15.4, 6.2 Hz , 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.40, -117.25, -120.09, -123.04 F2047 221-223 ESIMS m/z 480 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 8.58 - 8.47 (m, 1H), 8.02 (dd, J = 6.4, 2.7 Hz, 1H), 7.71 (td, J = 6.7, 6.1, 2.2 Hz, 2H), 7.53 - 7.40 (m, 2H), 3.58 (d, J = 8.5 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H), 3.27 (td, J = 7.3, 5.7 Hz, 2H), 1.12 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.25, -123.20 F2048 196-198 ESIMS m/z 531 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.97 (s, 1H), 8.62 (t, J = 5.6 Hz, 1H), 8.03 (dd, J = 6.3, 2.7 Hz, 1H), 7.71 (td, J = 6.9, 6.3, 2.3 Hz, 2H), 7.46 (dd, J = 7.9, 5.1 Hz, 2H ), 3.70 (t, J = 6.5 Hz, 2H), 3.58 (d, J = 8.5 Hz, 1H), 3.45 - 3.35 (m, 3H), 1.97 (p, J = 6.7 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.25, -123.12 F2049 197-199 ESIMS m/z 518 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 9.22 (t, J = 6.3 Hz, 1H), 7.93 (ddd, J = 12.4, 6.9, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.61 (dt, J = 4.5, 2.1 Hz, 1H ), 7.54 - 7.39 (m, 2H), 4.20 - 4.03 (m, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.53, -117.26, -135.61 (d, J = 23.4 Hz), -145.44 (d, J = 23.6 Hz) F2050 57-76 ESIMS m/z 568 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 9.23 (t, J = 6.4 Hz, 1H), 7.94 (ddd, J = 12.5, 6.9, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 1.9 Hz, 1H), 7.60 (p, J = 2.0 Hz, 1H), 7, 53 - 7.41 (m, 2H), 4.17 (td, J = 15.4, 6.2 Hz, 2H), 3.59 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.4 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.41, -117.26, -120.09, -135.59 (d, J = 23.6 Hz), -145.52 (d, J = 23.6 Hz) F2051 190-194 ESIMS m/z 464 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 8.50 (t, J = 5.7 Hz, 1H), 7.88 (ddd, J = 12.4, 6.9, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 2.0 Hz, 1H), 7.63 - 7.55 (m, 1H), 7.54 - 7 .40 (m, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H), 3.28 (tt, J = 7, 2, 3.7 Hz, 2H), 1.12 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.26, -136.04 (d, J = 23.8 Hz), -145.72 (d, J = 23.9 Hz) F2052 57-86 ESIMS m/z 510 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.99 (s, 1H), 8.60 (t, J = 5.6 Hz, 1H), 7.89 (ddd, J = 12.5, 6.9, 2.6 Hz, 1H), 7.71 (dd, J = 7.1, 2.0 Hz, 1H), 7.58 (dt, J = 4.7, 2.0 Hz, 1H ), 7.52 - 7.40 (m, 2H), 3.70 (t, J = 6.5 Hz, 2H), 3.58 (d, J = 8.5 Hz, 1H), 3.44 - 3.35 (m, 3H), 1.98 (p, J = 6.6 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.26, -135.97 (d, J = 23.8 Hz), -145.63 (d, J = 23.9 Hz) F2053 198-201 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₄ Cl ₄ F ₄ N ₂ O ₂ , 529.9746; found, 529.9751 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.17 (s, 1H), 8.66 (t, J = 5.6 Hz, 1H), 8.20 (d, J = 2.5 Hz , 1H), 7.93 (d, J = 2.5 Hz, 1H), 7.72 (dd, J = 7.1, 1.9 Hz, 1H), 7.52 - 7.42 (m, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H), 3.31 - 3.21 (m, 2H), 1, 13 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.42, -117.21 F2054 99-104 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₁ Cl ₄ F ₇ N ₂ O ₂ , 583.9463; found, 583.9465 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.22 (s, 1H), 9.41 (t, J = 6.3 Hz, 1H), 8.26 (d, J = 2.5 Hz , 1H), 7.97 (d, J = 2.5 Hz, 1H), 7.76 - 7.67 (m, 1H), 7.55 - 7.40 (m, 2H), 4.21 - 4.05 (m, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.48, -70.45, -117.20 F2055 211-214 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₃ Cl ₄ F ₇ N ₂ O ₂ , 597.9619; found, 597.9617 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.19 (s, 1H), 8.92 (t, J = 5.7 Hz, 1H), 8.23 (d, J = 2.5 Hz , 1H), 7.95 (d, J = 2.5 Hz, 1H), 7.72 (dd, J = 7.1, 1.9 Hz, 1H), 7.55 - 7.37 (m, 2H), 3.60 (d, J = 8.4 Hz, 1H), 3.50 (q, J = 6.5 Hz, 2H), 3.44 (d, J = 8.5 Hz, 1H) , 2.64 - 2.51 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.46, -61.47, -63.74, -63.75,
-117.21 F2056 224-226 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₁ Cl ₄ F ₉ N ₂ O ₂ , 633.9431; found, 633.9426 ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.22 (s, 1H), 9.43 (t, J = 6.3 Hz, 1H), 8.27 (d, J = 2.5 Hz , 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.77 - 7.66 (m, 1H), 7.53 - 7.40 (m, 2H), 4.18 ( td, J = 15.8, 6.4 Hz, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.48, -83.37, -117.21, -120.02 F2057 183-187 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₇ Cl ₃ F ₂ N ₂ O ₃ , 476.0273; found, 476.0279 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 8.32 (t, J = 5.6 Hz, 1H), 7.78 (dd, J = 13.3, 2.6 Hz, 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.56 (dd, J = 2.7, 1.4 Hz, 1H), 7, 52 - 7.40 (m, 2H), 3.85 (d, J = 1.2 Hz, 3H), 3.57 (d, J = 8.5 Hz, 1H), 3.40 (d, J = 8.5 Hz, 1H), 3.28 (td, J = 7.2, 5.7 Hz, 2H), 1.12 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.30, -128.43 F2058 183-186 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₄ Cl ₃ F ₅ N ₂ O ₃ , 529.9990; found, 529.9994 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 8.95 (t, J = 6.4 Hz, 1H), 7.83 (dd, J = 13.3, 2.6 Hz, 1H), 7.70 (dd, J = 7.1, 2.0 Hz, 1H), 7.57 (dd, J = 2.7, 1.4 Hz, 1H), 7, 51 - 7.39 (m, 2H), 4.12 (qd, J = 9.6, 6.4 Hz, 2H), 3.85 (s, 3H), 3.58 (d, J = 8, 5 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.52, -117.29, -128.04 F2059 182-186 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₆ Cl ₃ F ₅ N ₂ O ₃ , 544.0147; found, 541.0152 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 8.54 (t, J = 5.8 Hz, 1H), 7.82 (dd, J = 13.3, 2.6 Hz, 1H), 7.70 (dd, J = 7.2, 2.0 Hz, 1H), 7.62 (dd, J = 2.7, 1.4 Hz, 1H), 7, 54 - 7.40 (m, 2H), 3.86 (d, J = 1.3 Hz, 3H), 3.63 - 3.48 (m, 3H), 3.40 (d, J = 8, 5 Hz, 1H), 2.65 - 2.51 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-63.80, -117.30, -128.17 F2060 171-174 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₁ H ₁₄ Cl ₃ F ₇ N ₂ O ₃ , 579.9958; found, 579.9965 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 8.94 (t, J = 6.4 Hz, 1H), 7.84 (dd, J = 13.3, 2.6 Hz, 1H), 7.70 (dd, J = 7.2, 2.0 Hz, 1H), 7.57 (dd, J = 2.7, 1.4 Hz, 1H), 7, 53 - 7.40 (m, 2H), 4.17 (td, J = 15.4, 6.2 Hz, 2H), 3.85 (d, J = 1.3 Hz, 3H), 3.58 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.49, -117.30, -120.25, -127.95 F2061 216-218 ESIMS m/z 546 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 9.06 (t, J = 6.4 Hz, 1H), 8.01 (d, J = 2.5 Hz , 1H), 7.75 - 7.64 (m, 2H), 7.53 - 7.39 (m, 2H), 4.18 - 4.03 (m, 2H), 3.77 (s, 3H ), 3.58 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.47, -117.28 F2062 76-108 ESIMS m/z 599 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 9.05 (t, J = 6.4 Hz, 1H), 8.02 (d, J = 2.5 Hz , 1H), 7.76 - 7.63 (m, 2H), 7.55 - 7.40 (m, 2H), 4.16 (td, J = 15.6, 6.4 Hz, 2H), 3.77 (s, 3H), 3.58 (d, J = 8.5 Hz, 1H), 3.41 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.50, -117.28, -120.24 F2063 99-111 HRMS-ESI (m/z)[M+] ⁺
calculated for C ₂₀ H ₁₄ Cl ₃ F ₅ N ₂ O ₂ , 514.0041; found, 514.0038 1NMR (400 MHz, DMSO-d ₆ ) δ 10.93 (s, 1H), 9.14 (t, J = 6.3 Hz, 1H), 7.74 - 7.64 (m, 2H), 7 .52 - 7.36 (m, 3H), 4.17 - 3.98 (m, 2H), 3.58 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 8 .4 Hz, 1H), 2.17 (d, J = 2.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.54, -114.09, -117.29 F2064 133-137 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₁ H ₁₄ Cl ₃ F ₇ N ₂ O ₂ , 564.0009; found, 564.0008 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 9.15 (t, J = 6.3 Hz, 1H), 7.74 - 7.64 (m, 2H) , 7.52 - 7.41 (m, 2H), 7.41 - 7.38 (m, 1H), 4.23 - 4.03 (m, 2H), 3.62 - 3.54 (m, 1H), 3.42 (d, J = 8.5 Hz, 1H), 2.17 (d, J = 2.0 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.40, -114.07, -117.29, -120.07 F2066 ESIMS m/z 592 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.85 (s, 1H), 9.44 (s, 1H), 8.59 (t, J = 5.4 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7 .55 (dd, J = 1.9, 0.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H) , 3.50 (d, J = 8.5 Hz, 1H), 3.38 (dt, J = 9.8, 5.5 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-74.40 F2067 ESIMS m/z 550 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.85 (s, 1H), 8.46 (t, J = 5.7 Hz, 1H), 7.84 (d, J = 5.8 Hz , 1H), 7.74 (d, J = 2.6 Hz, 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.55 (dd, J = 2.0, 0.7 Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.23 (q, J = 6.6 Hz, 2H), 3.10 (q, J = 6, 6 Hz, 2H) F2068 ESIMS m/z 566 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 8.46 (t, J = 5.7 Hz, 1H), 7.83 (s, 1H), 7.73 (d, J = 2.5 Hz, 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 2H), 7.63 (t, J = 1.9 Hz, 1H), 7 .55 (dd, J = 2.0, 0.7 Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H) , 3.50 (d, J = 8.6 Hz, 1H), 3.21 (t, J = 6.3 Hz, 2H), 3.04 (q, J = 6.2 Hz, 2H) F2069 ESIMS m/z 578 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 8.45 (t, J = 5.6 Hz, 1H), 7.79 (s, 1H), 7.72 (d, J = 2.6 Hz, 1H), 7.67 (dd, J = 8.7, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7 .55 (dd, J = 2.0, 0.7 Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H) , 3.50 (d, J = 8.5 Hz, 1H), 3.21 (q, J = 6.6 Hz, 2H), 3.02 (q, J = 6.6 Hz, 2H), 1 .56 - 1.25 (m, 4H) F2070 ESIMS m/z 538 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 8.49 (t, J = 5.6 Hz, 1H), 7.84 (d, J = 4.9 Hz , 1H), 7.74 (d, J = 2.6 Hz, 1H), 7.69 - 7.59 (m, 2H), 7.55 (dd, J = 1.9, 0.7 Hz, 2H), 7.46 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.49 (d, J = 8.6 Hz, 1H) , 3.41 (q, J = 6.9 Hz, 2H), 2.58 (d, J = 4.6 Hz, 3H), 2.35 (t, J = 7.3 Hz, 2H) F2071 102-106 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₁₉ H ₁₄ Cl ₄ F ₂ N ₂ O ₂ , 479.9777; found, 479.9783 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.64 (s, 1H), 8.74 (t, J = 5.6 Hz, 1H), 8.02 (t, J = 8.6 Hz , 1H), 7.67 (dd, J = 7.0, 2.2 Hz, 1H), 7.52 - 7.40 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 3.64 (d, J = 8.6 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H), 3.32 - 3.21 (m, 2H), 1, 12 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -125.27 F2072 173-176 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₁₉ H ₁₁ Cl ₄ F ₅ N ₂ O ₂ , 533.9495; found, 533.9494 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.70 (s, 1H), 9.50 (t, J = 6.3 Hz, 1H), 8.09 (t, J = 8.6 Hz , 1H), 7.67 (dd, J = 7.0, 2.2 Hz, 1H), 7.55 - 7.36 (m, 3H), 4.15 (qd, J = 9.6, 6 .4 Hz, 2H), 3.64 (d, J = 8.6 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-70.48, -117.28, -124.97 F2073 220-224 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₀ H ₁₁ Cl ₄ F ₇ N ₂ O ₂ , 583.9463; found, 583.9465 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.70 (s, 1H), 9.51 (t, J = 6.3 Hz, 1H), 8.10 (t, J = 8.6 Hz , 1H), 7.67 (dd, J = 7.1, 2.2 Hz, 1H), 7.55 - 7.37 (m, 3H), 4.20 (td, J = 15.5, 6 .3 Hz, 2H), 3.65 (d, J = 8.6 Hz, 1H), 3.58 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-83.38, -83.38, -117.28, -120.06, -124.88 F2074 178-180 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₀ H ₁₅ Cl ₅ F ₂ N ₂ O ₂ , 527.9544; found, 527.9550 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.66 (s, 1H), 8.85 (t, J = 5.7 Hz, 1H), 8.04 (t, J = 8.6 Hz , 1H), 7.67 (dd, J = 7.0, 2.2 Hz, 1H), 7.48 (t, J = 8.9 Hz, 1H), 7.45 - 7.40 (m, 1H), 7.37 (d, J = 8.9 Hz, 1H), 3.72 (t, J = 6.6 Hz, 2H), 3.64 (d, J = 8.6 Hz, 1H) , 3.58 (d, J = 8.5 Hz, 1H), 3.40 (q, J = 6.3 Hz, 2H), 1.97 (p, J = 6.6 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -125.29 F2075 189-191 ESIMS m/z 529.08 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.59 (s, 1H), 7.87 (dd, J = 2.4, 8.4 Hz, 1H), 7.64 (d, J = 2, 4 Hz, 1H), 7.43 - 7.31 (m, 2H), 7.19 (d, J = 1.2 Hz, 2H), 6.68 - 6.64 (m, 1H), 3, 92 - 3.84 (m, 2H), 3.54 (d, J = 7.8 Hz, 1H), 2.86 (d, J = 7.8 Hz, 1H), 1.71 (t, J = 17.6 Hz, 3H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-96.33 F2076 81-83 ESIMS m/z 587.12 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.53 (s, 1H), 7.91 (dd, J = 2.4, 8.8 Hz, 1H), 7.58 (d, J = 2, 4 Hz, 1H), 7.40 - 7.30 (m, 2H), 7.19 (d, J = 1.2 Hz, 2H), 6.83 (t, J = 6.4 Hz, 1H) , 4.37 (q, J = 6.8 Hz, 2H), 4.16 - 4.14 (m, 2H), 3.53 (d, J = 8.4 Hz, 1H), 2.87 ( d, J = 8.4 Hz, 1H), 1.37 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-110.63 F2077 169-171 ESIMS m/z 591.05 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.72 (s, 1H), 7.89 (dd, J = 2.4, 8.8 Hz, 1H), 7.58 - 7.41 (m, 6H), 7.39 - 7.30 (m, 2H), 7.22 - 7.14 (m, 2H), 6.69 (t, J = 6.0 Hz, 1H), 4.24 - 4 .06 (m, 2H), 3.53 (d, J = 7.8 Hz, 1H), 2.86 (d, J = 7.8 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-101.61 F2078 206-208 ESIMS m/z 590.07 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.80 (s, 1H), 8.69 (t, J = 5.6 Hz, 1H), 8.59 (t, J = 6.4 Hz , 1H), 7.80 (d, J = 2.4 Hz, 1H), 7.73 (dd, J = 2.4, 8.8 Hz, 1H), 7.62 - 7.61 (m, 1H), 7.54 (d, J = 2.4 Hz, 2H), 7.47 (d, J = 8.8 Hz, 1H), 4.00 - 3.92 (m, 4H), 3, 61 (d, J = 8.8 Hz, 1H), 3.49 (d, J = 8.8 Hz, 1H) F2079 231-233 ESIMS m/z 604.09 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.80 (s, 1H), 8.58 (t, J = 6.0 Hz, 1H), 8.48 (t, J = 5.6 Hz , 1H), 7.74 (d, J = 3.2 Hz, 1H), 7.65 (dd, J = 2.4, 8.8 Hz, 1H), 7.63 - 7.61 (m, 1H), 7.54 (d, J = 1.6 Hz, 2H), 7.46 (d, J = 8.4 Hz, 1H), 3.92 - 3.87 (m, 2H), 3, 60 (d, J = 8.4 Hz, 1H), 3.48 (d, J = 7.6 Hz, 1H), 3.46 - 3.41 (m, 2H), 2.49 - 2.46 (m, 2H) F2080 195-197 ESIMS m/z 618.07 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.80 (s, 1H), 8.49 - 8.44 (m, 2H), 7.73 - 7.61 (m, 3H), 7, 54 (d, J = 1.6 Hz, 2H), 7.46 (d, J = 8.8 Hz, 1H), 3.91 - 3.87 (m, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.48 (d, J = 8.4 Hz, 1H), 3.24 - 3.19 (m, 2H), 2.25 (t, J = 7.6 Hz , 2H), 1.77 - 1.73 (m, 2H) F2081 193-195 ESIMS m/z 604.09 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.80 (s, 1H), 8.62 (t, J = 6.0 Hz, 1H), 8.11 (t, J = 5.6 Hz , 1H), 7.80 (d, J = 2.4 Hz, 1H), 7.73 (dd, J = 3.2, 8.8 Hz, 1H), 7.62 - 7.61 (m, 1H), 7.54 - 7.53 (m, 2H), 7.47 (d, J = 8.8 Hz, 1H), 3.84 (d, J = 5.6 Hz, 2H), 3, 61 (d, J = 8.8 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H), 3.37 - 3.29 (m, 2H), 2.51 - 2.39 (m, 2H) F2082 190-192 ESIMS m/z 590.07 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 9.45 - 9.41 (m, 1H), 8.62 - 8.58 (m, 1H), 7, 77 - 7.73 (m, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.64 - 7.62 (m, 1H), 7.54 - 7.46 (m, 3H), 3.60 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H), 3.42 - 3.31 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-74.44 F2083 89-94 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₀ H ₁₄ Cl ₃ F ₅ N ₂ O ₂ , 514.0041; found, 514.0050 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.68 (s, 1H), 8.48 (t, J = 5.5 Hz, 1H), 8.12 (d, J = 8.2 Hz , 1H), 7.88 - 7.76 (m, 2H), 7.68 - 7.54 (m, 2H), 3.73 (d, J = 8.5 Hz, 1H), 3.68 ( d, J = 8.5 Hz, 1H), 3.24 (qd, J = 7.2, 5.5 Hz, 2H), 1.10 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.94 (d, J = 12.4 Hz), -116.93 (q, J = 12.6 Hz), -121.34 F2084 166-169 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₀ H ₁₁ Cl ₃ F ₈ N ₂ O ₂ , 567.9758; found, 567.9763 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.73 (s, 1H), 9.23 (t, J = 6.3 Hz, 1H), 8.19 (d, J = 8.2 Hz , 1H), 7.86 - 7.77 (m, 2H), 7.69 (d, J = 10.7 Hz, 1H), 7.59 (dd, J = 10.7, 8.5 Hz, 1H), 4.08 (qd, J = 9.7, 7.0 Hz, 2H), 3.74 (d, J = 8.6 Hz, 1H), 3.69 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.95 (d, J = 12.4 Hz), -70.43,
-116.93 (q, J = 12.5 Hz), -120.36 F2085 192-195 HRMS-ESI (m/z) [M+] ⁺
calculated for C ₂₁ H ₁₁ Cl ₃ F ₁₀ N ₂ O ₂ , 617.9726; found, 617.9733 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.73 (s, 1H), 9.23 (t, J = 6.3 Hz, 1H), 8.20 (d, J = 8.1 Hz , 1H), 7.87 - 7.78 (m, 2H), 7.69 (d, J = 10.7 Hz, 1H), 7.59 (dd, J = 10.7, 8.5 Hz, 1H), 4.12 (td, J = 15.5, 6.3 Hz, 2H), 3.74 (d, J = 8.6 Hz, 1H), 3.70 (d, J = 8.6 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.95 (d, J = 12.5 Hz), -83.40,
-116.94 (q, J = 12.5 Hz),
-120.00, -120.32 F2086 113-115 ESIMS m/z 543.06 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.83 (s, 1H), 8.88 (t, J = 6.4 Hz, 1H), 7.73 - 7.69 (m, 2H) , 7.63 - 7.61 (m, 1H), 7.54 (d, J = 1.2 Hz, 2H), 7.48 (d, J = 9.2 Hz, 1H), 3.78 - 3.68 (m, 2H), 3.61 (d, J = 8.8 Hz, 1H), 3.49 (d, J = 8.8 Hz, 1H), 2.03 - 1.85 (m , 2H), 1.00 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-103.99 F2087 176-178 ESIMS m/z 545.01 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.10 (s, 1H), 9.05 (t, J = 6.4 Hz, 1H), 7.84 (dd, J = 2.8, 11.6 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.49 (s, 1H), 3.76 - 3.67 (m, 2H), 3.63 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H), 1.67 (t, J = 18 ,8 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-94.03, -112.76 F2088 184-186 ESIMS m/z 558.98 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.10 (s, 1H), 9.02 (t, J = 5.6 Hz, 1H), 7.85 (dd, J = 1.6, 11.2 Hz, 1H), 7.63 - 7.61 (m, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.48 (s, 1H), 3.77 - 3.64 (m, 2H), 3.63 (d J = 8.4 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H), 2.00 - 1.89 (m, 2H), 1.00 (t, J = 7.2 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-103.35, -112.76 F2089 89-91 ESIMS m/z 603.10 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.12 (s, 1H), 9.18 (t, J = 6.4 Hz, 1H), 7.86 (dd, J = 2.4, 11.2 Hz, 1H), 7.63 - 7.61 (m, 1H), 7.55 (d, J = 2.0 Hz, 2H), 7.48 (s, 1H), 4.30 ( q, J = 6.8 Hz, 2H), 4.02 - 3.93 (m, 2H), 3.63 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8 ,0 Hz, 1H), 1.28 (t, J = 7.6 Hz, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-109.65, -112.62 F2090 97-100 ESIMS m/z 525.21 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.09 (s, 1H), 8.87 (t, J = 5.6 Hz, 1H), 7.86 (dd, J = 2.0, 11.2 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.56 - 7.55 (m, 3H), 4.11 (d, J = 6.0 Hz, 2H), 3.63 (d J = 8.8 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H), 2.15 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-112.70 F2091 180-182 ESIMS m/z 608.99 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.08 (s, 1H), 9.10 (t, J = 6.0 Hz, 1H), 7.79 (dd, J = 2.4, 11.6 Hz, 1H), 7.63 - 7.47 (m, 9H), 4.07 - 3.98 (m, 2H), 3.64 (d J = 8.8 Hz, 1H), 3 .51 (d, J = 8.8 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-98.61, -112.90 F2092 224-226 ESIMS m/z 618.10 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.80 (s, 1H), 8.49 (t, J = 5.2 Hz, 1H), 8.15 (t, J = 5.6 Hz , 1H), 7.76 (d, J = 2.4 Hz, 1H), 7.64 (d, J = 2.4 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H ), 7.54 (d, J = 1.2 Hz, 2H), 7.46 (d, J = 8.4 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.49 (d, J = 8.8 Hz, 1H), 3.44 - 3.39 (m, 2H), 3.31 - 3.26 (m, 2H), 2.50 - 2.35 ( m, 4H);
¹⁹ F NMR (400 MHz, DMSO-d ₆ ) δ
-63.98 F2093 177-179 ESIMS m/z 632.25 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.82 (s, 1H), 8.45 (t, J = 6.0 Hz, 1H), 8.01 (t, J = 5.2 Hz , 1H), 7.73 (d, J = 2.8 Hz, 1H), 7.67 (dd, J = 2.4, 8.8 Hz, 1H), 7.62 - 7.61 (m, 1H), 7.54 (d, J = 1.6 Hz, 2H), 7.47 (d, J = 8.8 Hz, 1H), 3.61 (d, J = 8.8 Hz, 1H) , 3.49 (d, J = 8.8 Hz, 1H), 3.29 - 3.25 (m, 2H), 3.24 - 3.18 (m, 2H), 2.50 - 2.36 (m, 2H), 2.16 (t, J = 7.2 Hz, 2H), 1.76 - 1.69 (m, 2H);
¹⁹ F NMR (400 MHz, DMSO-d ₆ ) δ
-63.91 F2094 182-184 ESIMS m/z 604.05 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.80 (s, 1H), 9.43 - 9.38 (m, 1H), 8.48 (t, J = 5.6 Hz, 1H) , 7.75 (d, J = 2.8 Hz, 1H), 7.67 (dd, J = 2.4, 8.8 Hz, 1H), 7.62 - 7.61 (m, 1H), 7.54 (d, J = 1.6 Hz, 2H), 7.47 (d, J = 8.8 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3, 50 (d, J = 8.8 Hz, 1H), 3.29 - 3.23 (m, 4H), 1.74 (t, J = 7.2 Hz, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-74.39 F2095 95-97 ESIMS m/z 618.29 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.82 (s, 1H), 9.43 - 9.47 (m, 1H), 8.48 (t, J = 5.6 Hz, 1H) , 7.73 (d, J = 2.4 Hz, 1H), 7.66 (dd, J = 2.4, 8.8 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.54 (d, J = 2.0 Hz, 2H), 7.47 (d, J = 8.8 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3, 49 (d, J = 8.8 Hz, 1H), 3.32 - 3.19 (m, 4H), 1.58 - 1.48 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-74.36 F2096 196-198 ESIMS m/z 640.18 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.82 (s, 1H), 9.54 - 9.51 (m, 1H), 8.58 - 8.54 (m, 1H), 7, 76 (d, J = 2.8 Hz, 1H), 7.66 (dd, J = 3.2, 8.8 Hz, 1H), 7.62 - 7.61 (m, 1H), 7.54 (d, J = 1.6 Hz, 2H), 7.48 (d, J = 8.8 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.49 (d , J = 8.8 Hz, 1H), 3.43 - 3.35 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-82.28, -121.82 F2097 109-112 ESIMS m/z 654.23 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.82 (s, 1H), 9.53 (t, J = 4.8 Hz, 1H), 8.50 (t, J = 6.0 Hz , 1H), 7.75 (d, J = 2.4 Hz, 1H), 7.67 (dd, J = 2.4, 8.8 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.54 (d, J = 1.2 Hz, 2H), 7.48 (d, J = 8.8 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H) , 3.49 (d, J = 8.8 Hz, 1H), 3.31 - 3.22 (m, 4H), 1.78 - 1.70 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-82.36, -121.86 F2098 209-211 ESIMS m/z 668.32 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 9.54 - 9.51 (m, 1H), 8.50 (t, J = 6.0 Hz, 1H) , 7.73 (d, J = 2.4 Hz, 1H), 7.66 (dd, J = 2.4, 8.4 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.54 (d, J = 1.6 Hz, 2H), 7.47 (d, J = 8.0 Hz, 1H), 3.61 (d, J = 8.0 Hz, 1H), 3, 49 (d, J = 8.4 Hz, 1H), 3.25 - 3.22 (m, 4H), 1.56 - 1.49 (m, 4H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-82.37, -121.83 F2099 101-104 ESIMS m/z 501 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 9.18 (br t, J = 6.1 Hz, 1H), 7.78 - 7.71 (m, 2H ), 7.59 - 7.44 (m, 3H), 7.29 (br s, 1H), 4.13 - 4.03 (m, 2H), 3.57 (d, J = 8.3 Hz , 1H), 3.39 (d, J = 8.3 Hz, 1H) F2100 105-108 ESIMS m/z 501 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.90 (s, 1H), 9.18 (t, J = 6.4 Hz, 1H), 7.78 - 7.71 (m, 2H) , 7.59 - 7.44 (m, 3H), 7.29 (br s, 1H), 4.13 - 4.03 (m, 2H), 3.57 (d, J = 8.3 Hz, 1H), 3.39 (d, J = 8.3 Hz, 1H) F2501 ESIMS m/z 647 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.50 (d, J = 2.3 Hz, 1H), 8.68 (d, J = 2.2 Hz , 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (q, J = 2, 3 Hz, 1H), 7.57 - 7.55 (m, 3H), 7.52 (d, J = 8.7 Hz, 1H), 7.26 (d, J = 2.7 Hz, 1H) , 7.07 (dd, J = 8.8, 2.7 Hz, 1H), 3.63 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.44. F2502 (thin film) 3257, 2970, 1666, 1589, 1544 ESIMS m/z 545 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.30 (d, J = 2.0 Hz, 1H), 8.62 - 8.53 (m, 1H) , 8.10 (dt, J = 4.8, 1.6 Hz, 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8, 2 .6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.59 - 7.50 (m, 4H), 6.76 - 6.68 (m, 2H), 3 .64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.6 Hz, 1H) F2503 (thin film) 3064, 2969, 1660, 1590 ESIMS m/z 559 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.74 (s, 1H), 8.20 - 8.15 (m, 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 - 7.54 (m, 5H), 6.86 (d, J = 8.5 Hz, 1H), 6.79 - 6.72 (m, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz , 1H) F2504 (thin film) 3185, 3048, 1662, 1588 ESIMS m/z 579 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.38 (s, 1H), 8.89 (s, 1H), 8.11 (d, J = 2, 5 Hz, 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.68 (dd, J = 8.9, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.58 - 7.52 (m, 3H), 6.73 (d, J = 8 .9 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F2505 (thin film) 3185, 3072, 2986, 1699, 1668 ESIMS m/z 579 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.25 (d, J = 1.8 Hz, 1H), 8.70 (d, J = 1.9 Hz , 1H), 8.09 (dd, J = 4.8, 1.5 Hz, 1H), 7.95 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8, 8, 2.6 Hz, 1H), 7.73 (dd, J = 7.7, 1.5 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.56 ( d, J = 1.9 Hz, 2H), 7.52 (d, J = 8.7 Hz, 1H), 6.80 (dd, J = 7.7, 4.8 Hz, 1H), 3, 64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H) F2506 (thin film) 3235, 3008, 1670, 1586, 1567 ESIMS m/z 580 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.59 (s, 1H), 9.44 (s, 1H), 7.90 (d, J = 2, 6 Hz, 1H), 7.81 (dd, J = 8.7, 2.6 Hz, 1H), 7.67 - 7.60 (m, 2H), 7.58 - 7.51 (m, 3H ), 7.09 (d, J = 9.3 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F2507 ESIMS m/z 627 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.04 (s, 1H), 10.95 (s, 1H), 8.53 (dd, J = 2.4, 1.2 Hz, 1H) , 7.95 (dd, J = 9.1, 2.5 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2 .6 Hz, 1H), 7.64 (t, J = 1.9 Hz, 1H), 7.59 (d, J = 8.7 Hz, 1H), 7.56 (d, J = 1.9 Hz, 2H), 6.97 (d, J = 9.0 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H), 3.40 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.45 F2508 (thin film) 3220, 3056, 1679, 1584, 1568 ESIMS m/z 546 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.27 (s, 1H), 9.20 (s, 1H), 8.41 (d, J = 4, 8 Hz, 2H), 7.88 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.56 (d, J = 1.9 Hz, 2H), 7.52 (d, J = 8.8 Hz, 1H), 6.81 (t, J = 4, 8 Hz, 1H), 3.63 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.6 Hz, 1H) F2509 (thin film) 3074, 1645, 1588, 1568, 1543 ESIMS m/z 546 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 14.12 (s, 1H), 11.46 (d, J = 10.7 Hz, 1H), 10.97 (s, 1H), 8.38 (s, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 8.8, 2.6 Hz, 1H), 7.65 - 7.50 ( m, 4H), 7.38 (t, J = 9.5 Hz, 1H), 5.91 (d, J = 9.0 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H) F2510 (thin film) 3646, 3265, 3066, 1662, 1588, 1472 ESIMS m/z 556 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.56 (s, 1H), 7.84 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (q, J = 2.9, 2.4 Hz, 1H), 7.58 - 7.51 (m, 3H), 7.33 - 7.18 (m, 2H), 6.95 - 6.87 (m, 2H), 6.80 (t, J = 7.3 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 3.20 (s, 3H) F2511 (thin film) 3265, 3064, 1665, 1547, 1473 ESIMS m/z 594 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.56 (s, 1H), 7.84 (d, J = 2.6 Hz, 1H), 7.83 - 7.76 (m, 3H), 7.55 (d, J = 8.7 Hz, 1H), 7.31 - 7.20 (m, 2H), 6.94 - 6.87 (m, 2H ), 6.80 (t, J = 7.3 Hz, 1H), 3.65 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz, 1H), 3.20 (s, 3H) F2512 ESIMS m/z 540 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.56 (s, 1H), 7.84 (d, J = 2.5 Hz, 1H), 7.80 (dd, J = 8.7, 2.6 Hz, 1H), 7.74 - 7.66 (m, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.51 - 7.38 (m, 2H), 7.31 - 7.19 (m, 2H), 6.94 - 6.88 (m, 2H), 6.80 (t, J = 7.3 Hz, 1H) , 3.60 (d, J = 8.5 Hz, 1H), 3.44 (d, J = 8.5 Hz, 1H), 3.20 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.28, -117.32 F2513 (thin film) 3264, 3029, 1662, 1588, 1473 ESIMS m/z 558 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.56 (s, 1H), 7.84 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.78 - 7.66 (m, 2H), 7.55 (d, J = 8.7 Hz, 1H), 7.50 - 7.38 (m, 1H), 7.30 - 7.19 (m, 2H), 6.94 - 6.88 (m, 2H), 6.80 (t, J = 7.3 Hz, 1H) , 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 3.20 (s, 3H) F2514 237-239 ESIMS m/z 508.1 ([M+H] ⁺ ) white solid; MP 237 - 239°C; ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.24 (s, 1H), 9.99 (d, J = 1.2 Hz, 1H), 7.84 - 7.76 (m, 2H), 7.66 - 7.62 (m, 1H), 7.55 (d, J = 3.0 Hz, 2H), 7.52 - 7.48 (m, 1H ), 3.61 (d, J = 8.8 Hz, 1H), 3.49 (d, J = 8.4 Hz, 1H), 1.91 (s, 3H) F2515 196-198 ESIMS m/z 562 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.77 (s, 1H), 10.94 (s, 1H), 10.82 (s, 1H), 7.88 (d, J = 2, 4 Hz, 1H), 7.79 (dd, J = 8.8, 3.2Hz, 1H), 7.64 - 7.62 (m, 1H), 7.58 - 7.54 (m, 3H) , 3.62 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H) F2516 249-251 ESIMS m/z 576.08 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.53 (s, 1H), 10.49 (s, 1H), 7.88 - 7.76 (m, 2H), 7.63 - 7.49 (m, 4H), 3.72 - 3.39 (m, 4H) F2517 248-250 ESIMS m/z 570.14 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.51 (s, 1H), 10.46 (s, 1H), 7.85 (s, 1H), 7 .76 (d, J = 8.4 Hz, 1H), 7.63 - 7.61 (m, 1H), 7.57 - 7.50 (m, 3H), 3.61 (d, J = 8 .7 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H), 2.74 - 2.62 (m, 1H), 2.08 - 1.88 (m, 2H) F2518 144-146 ESIMS m/z 556.8 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.43 (s, 1H), 10.38 (s, 1H), 7.85 (d, J = 2, 8 Hz, 1H), 7.76 (dd, J = 8.8, 2.4 Hz, 1H), 7.63 - 7.61 (m, 1H), 7.56 - 7.50 (m, 3H ), 3.61 (d, J = 8.0 Hz, 1H), 3.49 (d, J = 8.4 Hz, 1H), 1.72 - 1.69 (m, 2H), 1.62 - 1.58 (m, 2H) F2519 290-292 ESIMS m/z 570.2 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 11.28 (s, 1H), 10.63 (s, 1H), 10.44 (s, 1H), 7.97 - 7.92 (m, 3H), 7.82 (d, J = 9.0 Hz, 1H), 7.63 - 7.52 (m, 7H), 3.68 (d, J = 8.7 Hz, 1H), 3, 62 (d, J = 8.7 Hz, 1H) F2520 139-141 ESIMS m/z 524.1 ([M-(C4H9)+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.88 (s, 1H), 10.63 (s, 1H), 7.86 - 7.51 (m, 6H), 3.61 (d, J = 9.0 Hz, 1H), 3.49 (d, J = 8.7 Hz, 1H), 3.04 (s, 3H), 1.43 (s, 9H) F2521 225-227 ESIMS m/z 477.7 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.30 (brs, 1H), 11.04 (s, 1H), 7.92 (d, J = 2.4 Hz, 1H), 7.72 (dd, J = 5.6, 3.2 Hz, 1H), 7.64 - 7.60 (m, 1H), 7.57 - 7.54 (m, 3H), 3.61 (d, J = 8.4 Hz, 1H), 3.55 (d, J = 9.6 Hz, 1H), 2.77 (s, 3H) F2522 151-153 ESIMS m/z 521.7 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.03 (s, 1H), 10.23 (s, 1H), 7.85 (d, J = 1.8 Hz, 1H), 7.77 (dd, J = 6.0, 2.8 Hz, 1H), 7.63 - 7.55 (m, 4H), 3.63 (d, J = 8.4 Hz, 1H), 3.50 ( d, J = 8.8 Hz, 1H), 3.07 (s, 3H), 2.02 (s, 3H) F2523 146-148 ESIMS m/z 575.7 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.50 (s, 1H), 10.96 (s, 1H), 7.88 - 7.76 (m, 2H), 7.63 - 7, 54 (m, 4H), 3.65 (d, J = 8.4 Hz, 1H), 3.50 (dd, J = 8.8, 3.2 Hz, 1H), 3.24 (s, 3H ) F2524 138-140 ESIMS m/z 561.7 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.96 (s, 1H), 10.91 (s, 1H), 7.81 - 7.78 (m, 2H), 7.63 - 7, 55 (m, 4H), 3.62 (d, J = 8.8 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H), 3.08 (s, 3H), 2, 25 (s, 2H), 1.04 - 0.98 (m, 1H), 0.48 - 0.42 (m, 2H), 0.11 - 0.07 (m, 2H) F2525 188-190 ESIMS m/z 572.8 ([M+H] ⁺ ) ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 11.38 (s, 1H), 10.98 (s, 1H), 7.88 - 7.82 (m, 2H), 7.63 - 7, 61 (m, 1H), 7.57 - 7.54 (m, 3H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H ), 3.12 (s, 3H), 1.58 - 1.48 (m, 4H) F2526 173-175 ESIMS m/z 564.9 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 8.16 (s, 1H), 7.86 (d, J = 2.7 Hz, 1H), 7.76 (dd, J = 5.7, 2.7 Hz, 1H), 7.64 - 7.60 (d, J = 1.5 Hz, 1H), 7.58 - 7.54 (m, 3H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H), 3.18 (s, 2H), 3.07 (s, 3H), 2.25 (s, 6H) F2527 259-261 ESIMS m/z 583.7 ([M+H] ⁺ ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.11 (s, 1H), 10.81 (s, 1H), 7.63 - 7.58 (m, 2H), 7.56 - 7, 40 (m, 9H), 3.61 (d, J = 8.8 Hz, 1H), 3.47 (d, J = 8.8 Hz, 1H), 3.22 (s, 3H) F2528 219-221 ESIMS m/z 547.8 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.27 (s, 1H), 9.94 (s, 1H), 7.83 (d, J = 2, 1 Hz, 1H), 7.77 (dd, J = 8.4, 2.4 Hz, 1H), 7.63 - 7.62 (m, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.50 (d, J = 8.7 Hz, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H), 2.10 (d, J = 6.6 Hz, 2H), 1.03 - 0.98 (m, 1H), 0.49 - 0.44 (m, 2H), 0.22 - 0 .16 (m, 2H) F2529 130-132 ESIMS m/z 537.8 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.29 (s, 1H), 10.04 (s, 1H), 7.85 - 7.77 (m, 2H), 7.63 - 7.62 (m, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.51 (d, J = 8.7 Hz, 1H), 3, 96 (s, 2H), 3.62 (d, J = 8.4 Hz, 1H), 3.49 (d, J = 8.7 Hz, 1H), 3.36 (s, 3H) F2530 139-141 ESIMS m/z 550.8 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 10.38 (s, 1H), 9.98 (s, 1H), 7.85 - 7.76 (m, 2H), 7.63 - 7.61 (m, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.51 (d, J = 8.7 Hz, 1H), 3, 61 (d, J = 8.7 Hz, 1H), 3.51 (d, J = 8.7 Hz, 1H), 3.02 (s, 2H), 2.28 (s, 6H) F2531 154-156 ESIMS m/z 570.7 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.96 (s, 1H), 10.73 (s, 1H), 10.51 (s, 1H), 8.71 (d, J = 4, 5 Hz, 1H), 8.07 - 8.02 (m, 2H), 7.91 (d, J = 2.1 Hz, 1H), 7.82 - 7.78 (m, 1H), 7, 69 - 7.52 (m, 5H), 3.63 (d, J = 9.0 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) F2532 172-174 ESIMS m/z 643.7 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 11.02 (s, 1H), 10.98 (s, 1H), 10.91 (s, 1H), 7.89 (d, J = 2, 7 Hz, 1H), 7.77 (dd, J = 6.7, 2.4 Hz, 1H), 7.64 - 7.61 (m, 1H), 7.59 - 7.52 (m, 3H ), 4.92 - 4.77 (m, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 9.0 Hz, 1H) F2533 136-138 ESIMS m/z 588.0 ([MH] ^- ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.84 (s, 1H), 10.64 (s, 1H), 7.81 - 7.76 (m, 2H), 7.54 - 7, 50 (m, 2H), 7.47 (d, J = 2.0 Hz, 2H), 3.62 - 3.40 (m, 4H), 3.14 (s, 3H) F2534 148-150 ESIMS m/z 583.8 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) @ 90°C δ 10.92 (s, 1H), 10.63 (s, 1H), 7.82 - 7.75 (m, 2H), 7, 62 - 7.42 (m, 4H), 3.58 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.7 Hz, 1H), 3.16 (s, 3H ), 2.98 - 2.89 (m, 1H), 1.99 - 1.85 (m, 2H) F2535 247-249 ESIMS m/z 590.7 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.13 (s, 1H), 8.47 (s, 1H), 7.83 (d, J = 2, 7 Hz, 1H), 7.77 (dd, J = 6.0, 2.4 Hz, 1H), 7.63 - 7.49 (m, 4H), 6.93 - 6.87 (m, 1H ), 3.92 - 3.84 (m, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.7 Hz, 1H) F2536 245-247 ESIMS m/z 550.7 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 10.98 (s, 1H), 10.28 (s, 1H), 7.94 (s, 1H), 7.81 (d, J = 2, 7 Hz, 1H), 7.77 (d, J = 2.4 Hz, 1H), 7.74 (d, J = 2.7 Hz, 1H), 7.64 - 7.61 (m, 1H) , 7.55 (d, J = 1.8 Hz, 2H), 7.51 (d, J = 8.4 Hz, 1H), 5.99 (d, J = 7.8 Hz, 1H), 3 .82 - 3.68 (m, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.4 Hz, 1H), 1.08 (d, J = 6.6 Hz, 6H) F2537 250-252 ESIMS m/z 584.7 ([M+H] ⁺ ) ^1H NMR (300 MHz, DMSO- _d6 ) δ 11.98 (s, 1H), 10.25 (s, 1H), 8.78 (s, 1H), 8.34 (s, 1H), 7 .86 (d, J = 2.7 Hz, 1H), 7.79 (dd, J = 6.3, 2.4 Hz, 1H), 7.64 - 7.61 (m, 1H), 7. 56 - 7.50 (m, 3H), 7.46 (d, J = 7.5 Hz, 2H), 7.32 - 7.24 (m, 2H), 7.02 - 6.92 (m, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.4 Hz, 1H) F2538 232-234 ESIMS m/z 562.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.89 (s, 1H), 10.03 (d, J = 2.0 Hz, 1H), 8.04 (d, J = 1.6 Hz , 1H), 7.81 (d, J = 2.4 Hz, 1H), 7.76 (dd, J = 8.4, 2.4 Hz, 1H), 7.63 - 7.61 (m, 1H), 7.55 - 7.47 (m, 3H), 6.28 - 6.19 (m, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.50 (d , J = 8.8 Hz, 1H), 2.96 (t, J = 6.4 Hz, 2H), 0.98 - 0.88 (m, 1H), 0.43 - 0.38 (m, 2H), 0.19 - 0.15 (m, 2H) F2539 156-158 ESIMS m/z 606.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.47 (s, 1H), 10.15 (brs, 1H), 8.20 (brs, 1H), 7 .92 - 7.82 (m, 2H), 7.63 - 7.60 (m, 1H), 7.59 - 7.50 (m, 3H), 4.54 - 4.45 (m, 2H) , 3.62 (d, J = 8.8 Hz, 1H), 3.52 (d, J = 8.4 Hz, 1H) F2540 214-216 ESIMS m/z 566.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.31 (s, 1H), 9.43 (s, 1H), 7.86 - 7.79 (m, 2H), 7.64 - 7.59 (m, 1H), 7.55 - 7.51 (m, 3H), 7.25 (brs, 1H), 4.37 (brs, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.8 Hz, 1H), 1.15 (d, J = 6.4 Hz, 6H) F2541 198-200 ESIMS m/z 598.8 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.51 (s, 1H), 9.86 (brs, 2H), 7.92 (d, J = 2, 4 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.62 (s, 1H), 7.51 - 7.51 (m, 5H), 7.37 - 7, 36 (m, 2H), 7.18 - 7.15 (m, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H ) F2542 187-189 ESIMS m/z 537.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.19 (s, 1H), 9.31 (s, 1H), 7.82 - 7.75 (m, 2H), 7.64 - 7.59 (m, 1H), 7.55 - 7.49 (m, 3H), 4.09 (q, J = 6.8 Hz, 2H), 3.61 (d , J = 8.8 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H), 1.26 - 1.19 (m, 3H) F2543 224-226 ESIMS m/z 589.8 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.40 (s, 1H), 9.92 (s, 1H), 7.84 - 7.75 (m, 2H), 7.64 - 7.60 (d, J = 2.0 Hz, 1H), 7.55 - 7.51 (m, 3H), 4.82 - 4.72 (m, 2H), 3 .61 (d, J = 8.4 Hz, 1H), 3.49 (d, J = 8.4 Hz, 1H) F2544 (thin film) 3276, 3063, 1635, 1588, 1471, 749 ESIMS m/z 572 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.76 (d, J = 5.3 Hz, 1H), 7.81 - 7.71 (m, 2H), 7.68 (dd, J = 8.3, 1.3 Hz, 1H), 7.52 (dd, J = 8.9, 2.3 Hz, 1H), 7.46 - 7.37 (m, 2H), 7.25 (ddd , J = 8.6, 7.3, 3.9 Hz, 2H), 6.91 - 6.82 (m, 1H), 6.82 - 6.75 (m, 2H), 3.56 (dd , J = 8.7, 1.9 Hz, 1H), 3.40 (dd, J = 8.5, 2.9 Hz, 1H), 3.07 (d, J = 1.2 Hz, 3H) , 3.03 (d, J = 1.7 Hz, 3H) F2545 160-162 ESIMS m/z 555.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.86 (s, 1H), 9.89 (d, J = 5.6 Hz, 1H), 7.71 (d, J = 2.8 Hz , 1H), 7.66 (dd, J = 2.4, 8.4 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.54 (d, J = 2, 0 Hz, 2H), 7.45 (d, J = 8.8 Hz, 1H), 7.39 (d, J = 8.8 Hz, 2H), 7.34 (t, J = 8.0 Hz , 2H), 7.26 (d, J = 7.2 Hz, 1H), 5.54 - 5.50 (m, 1H), 3.99 (d, J = 4.8 Hz, 2H), 3 .61 (d, J = 8.0 Hz, 1H), 3.50 (d, J = 8.0 Hz, 1H) F2546 101-103 ESIMS m/z 591.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.36 (brs, 1H), 7.80 (dd, J = 2.8, 8.8 Hz, 1H), 7.73 (brs, 1H), 7 .65 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.26 - 7.15 (m, 3H), 7.06 - 6, 80 (m, 2H), 5.19 (brs, 1H), 4.17 (s, 2H), 3.54 (d, J = 8.4 Hz, 1H), 2.85 (d, J = 8 ,0 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-118.77, -124.15 F2547 102-104 ESIMS m/z 591.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.10 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.73 (s, 1H), 7.67 (s , 1H), 7.44 - 7.34 (m, 3H), 7.20 (s, 2H), 6.90 - 6.80 (m, 2H), 5.15 (brs, 1H), 4, 16 (s, 2H), 3.55 (d, J = 8.0 Hz, 1H), 2.82 (d, J = 8.0 Hz, 1H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-110.33, -113.76 F2548 106-108 ESIMS m/z 569.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 10.51 (s, 1H), 9.55 (s, 1H), 7.68 - 7.62 (m, 2H), 7 .52 (s, 1H), 7.46 (s, 2H), 7.40 - 7.36 (m, 3H), 7.33 - 7.28 (m, 2H), 7.26 - 7.20 (m, 1H), 5.31 - 5.28 (m, 1H), 4.21 - 4.18 (m, 1H), 3.61 (d, J = 8.8 Hz, 1H), 3, 48 (d, J = 8.0 Hz, 1H), 1.31 (d, J = 6.4 Hz, 3H) F2549 140-142 ESIMS m/z 519.9 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.57 (s, 1H), 7.86 - 7.82 (m, 2H), 7.67 (d, J = 2.4 Hz, 1H), 7 .37 (d, J = 8.8 Hz, 1H), 7.35 (s, 1H), 7.20 (s, 2H), 4.91 (brs, 1H), 3.54 (d, J = 8.4 Hz, 1H), 2.87 (d, J = 8.4 Hz, 1H), 2.84 (d, J = 5.6 Hz, 2H), 1.02 - 0.96 (m, 1H), 0.54 - 0.50 (m, 2H), 0.26 - 0.22 (m, 2H) F2550 126-128 ESIMS m/z 561.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 8.17 (brs, 1H), 7.82 - 7.72 (m, 3H), 7.40 (d, J = 8.8 Hz, 1H), 7 .36 (brs, 1H), 7.19 (s, 2H), 4.94 - 4.90 (m, 1H), 3.55 (d, J = 8.0 Hz, 1H), 3.30 - 3.22 (m, 2H), 2.82 (d, J = 8.0 Hz, 1H), 2.46 - 2.34 (m, 2H);
¹⁹ F NMR (376 MHz, CDCl ₃ ) δ
-64.92 F2551 89-91 ESIMS m/z 537.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.82 (s, 1H), 9.98 (s, 1H), 7.76 - 7.68 (m, 2H), 7.62 (s, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.48 (d, J = 8.8 Hz, 1H), 5.18 (brs, 1H), 3.62 (d, J = 8.8 Hz, 1H), 3.49 (d, J = 8.4 Hz, 1H), 3.32 - 3.22 (m, 5H), 3.20 - 3.14 (m, 1H ), 1.01 (d, J = 6.4 Hz, 3H) F2552 112-114 ESIMS m/z 575.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 10.62 (s, 2H), 7.64 (brs, 1H), 7.58 - 7.36 (m, 5H), 4 .99 (brs, 1H), 3.56 (d, J = 8.4 Hz, 1H), 3.40 (d, J = 8.4 Hz, 1H), 3.14 - 3.02 (m, 3H), 3.01 - 2.96 (m, 2H), 2.11 - 2.07 (m, 2H) F2553 (thin film) 3249, 3059, 1668, 1588, 1505 ESIMS m/z 562 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.29 (d, J = 2.0 Hz, 1H), 8.04 (d, J = 1.8 Hz , 1H), 7.84 (d, J = 2.6 Hz, 1H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.59 - 7.51 (m, 3H), 7.09 - 6.99 (m, 2H), 6.88 - 6.80 (m, 2H), 3.64 (d , J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F2554 152-162 ESIMS m/z 566 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.49 (d, J = 1.7 Hz, 1H), 8.95 (d, J = 1.7 Hz , 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.79 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (q, J = 1, 9 Hz, 2H), 7.61 (d, J = 1.9 Hz, 1H), 7.59 - 7.54 (m, 3H), 6.91 - 6.84 (m, 2H), 3, 63 (t, J = 9.3 Hz, 1H), 3.51 (dd, J = 15.0, 8.5 Hz, 1H) F2555 150-164 ESIMS m/z 586 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.65 (s, 1H), 9.37 (s, 1H), 8.17 - 8.08 (m, 2H), 7.91 (d, J = 2.6 Hz, 1H), 7.79 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.65 - 7.48 (m, 3H), 6.93 - 6.78 (m, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H) F2556 124-146 ESIMS m/z 541 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.26 (d, J = 2.7 Hz, 1H), 8.05 (d, J = 2.8 Hz , 1H), 7.85 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.56 (d, J = 1.9 Hz, 2H), 7.54 (d, J = 8.8 Hz, 1H), 7.23 - 7.09 (m, 2H) , 6.88 - 6.80 (m, 2H), 6.74 (t, J = 7.3 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 ( d, J = 8.5 Hz, 1H) F2557 128-146 ESIMS m/z 555.9 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.56 (s, 1H), 7.84 (d, J = 2.5 Hz, 1H), 7.80 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (q, J = 3.1, 2.5 Hz, 1H), 7.56 (d, J = 1.8 Hz, 2H), 7.54 (d, J = 3.7 Hz, 1H), 7.24 (dt, J = 9.2, 7.3 Hz, 2H), 6.94 - 6.87 (m, 2H ), 6.80 (t, J = 7.3 Hz, 1H), 3.68 - 3.55 (m, 1H), 3.52 (d, J = 8.5 Hz, 1H), 3.20 (s, 3H) F2558 ESIMS m/z 577 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.41 (d, J = 1.8 Hz, 1H), 8.35 (d, J = 1.8 Hz , 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.58 - 7.54 (m, 3H), 7.16 (ddd, J = 11.3, 8.8, 5.0 Hz, 1H), 6.67 (ddd, J = 10.2, 6.9, 3.1 Hz, 1H), 6.54 (tt, J = 8.5, 3.2 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-117.85 (d, J = 15.9 Hz), -138.07 (d, J = 15.8 Hz) F2559 ESIMS m/z 577 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.35 (d, J = 2.4 Hz, 1H), 7.94 (s, 1H), 7.87 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7 .57 - 7.51 (m, 3H), 7.24 - 7.13 (m, 1H), 6.96 (ddd, J = 9.1, 7.3, 2.5 Hz, 2H), 3 .63 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-123.63, -128.22 F2560 129-140 ESIMS m/z 613 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.42 (d, J = 2.3 Hz, 1H), 8.52 (d, J = 2.3 Hz , 1H), 7.86 (d, J = 2.5 Hz, 1H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.60 - 7.50 (m, 3H), 7.42 (d, J = 8.7 Hz, 1H), 6.99 (d, J = 2.6 Hz, 1H) , 6.80 (dd, J = 8.8, 2.6 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F2561 122-132 ESIMS m/z 611 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.48 (d, J = 1.6 Hz, 1H), 8.16 (s, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (q, J = 2.2 Hz, 1H), 7 .58 (s, 1H), 7.57 (d, J = 2.1 Hz, 2H), 7.36 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 2, 4 Hz, 1H), 6.82 (dd, J = 8.4, 2.4 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.56 - 3.44 ( m, 1H) F2562 ESIMS m/z 573 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.29 (d, J = 2.4 Hz, 1H), 7.90 (d, J = 2.6 Hz , 1H), 7.75 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (s, 1H), 7.58 - 7.55 (m, 2H), 7.53 ( s, 1H), 7.36 (d, J = 2.3 Hz, 1H), 6.92 (ddd, J = 17.8, 9.2, 2.9 Hz, 2H), 6.83 (dd , J = 8.8, 5.2 Hz, 1H), 3.64 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 2.21 (s, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-126.42 F2563 119-130 ESIMS m/z 571 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.23 (d, J = 3.4 Hz, 1H), 7.83 (d, J = 2.6 Hz , 1H), 7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.73 (d, J = 3.4 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.56 (d, J = 1.9 Hz, 2H), 7.53 (d, J = 8.7 Hz, 1H), 6.81 (s, 4H), 3.68 (s, 3H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) F2564 ESIMS m/z 625 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.36 (d, J = 2.6 Hz, 1H), 8.34 (d, J = 2.6 Hz , 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.77 (dt, J = 8.8, 2.9 Hz, 1H), 7.63 (q, J = 2, 3 Hz, 1H), 7.56 (dd, J = 4.6, 1.7 Hz, 3H), 7.20 (d, J = 8.5 Hz, 2H), 6.93 - 6.84 ( m, 2H), 3.64 (d, J = 8.6 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-57.24 F2565 ESIMS m/z 675 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.36 (d, J = 2.5 Hz, 1H), 8.35 (d, J = 2.5 Hz , 1H), 7.86 (d, J = 2.5 Hz, 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.59 - 7.50 (m, 3H), 7.18 (d, J = 8.8 Hz, 2H), 6.96 - 6.85 (m, 2H), 3, 64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-85.20, -86.88 F2566 112-128 ESIMS m/z 565 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.95 (s, 1H), 10.09 (s, 1H), 9.06 (s, 1H), 7.86 - 7.81 (m, 1H), 7.79 (d, J = 9.2 Hz, 1H), 7.62 (d, J = 1.9 Hz, 1H), 7.55 (d, J = 2.0 Hz, 2H) , 7.50 (d, J = 8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.6 Hz, 1H), 1 .44 (d, J = 3.1 Hz, 9H) F2567 87-112 ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.85 (s, 1H), 9.61 (s, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 1H), 7.62 (t, J = 1.9 Hz, 1H), 7.55 (d, J = 1.9 Hz, 2H), 7 .48 (d, J = 8.8 Hz, 1H), 4.53 (s, 2H), 3.62 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8, 6 Hz, 1H);
¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 165.36, 162.50, 137.48, 137.25, 136.06, 134.05, 130.04, 127.86, 127.66, 124 .45, 121.13, 119.48, 62.14, 38.40, 36.81 F2569 ESIMS m/z 583 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.87 (s, 1H), 9.83 (d, J = 5.9 Hz, 1H), 7.80 - 7.68 (m, 2H) , 7.63 (t, J = 1.9 Hz, 1H), 7.49 (d, J = 8.5 Hz, 1H), 5.20 (dd, J = 6.0, 3.5 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.09 (s, 1H), 2.18 - 2, 00 (m, 1H), 1.88 - 1.73 (m, 6H), 1.71 - 1.51 (m, 3H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-94.82 F2570 ESIMS m/z 575 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.84 (s, 1H), 9.86 (d, J = 6.1 Hz, 1H), 7.71 (d, J = 2.6 Hz , 1H), 7.67 - 7.61 (m, 2H), 7.55 (d, J = 1.9 Hz, 2H), 7.49 - 7.36 (m, 3H), 7.20 - 7.10 (m, 2H), 5.58 (q, J = 5.4 Hz, 1H), 3.97 (d, J = 5.0 Hz, 2H), 3.62 (d, J = 8 .5 Hz, 1H), 3.49 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-116.09 F2571 ESIMS m/z 609 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.44 (d, J = 2.0 Hz, 1H), 8.71 (d, J = 2.1 Hz , 1H), 7.88 (d, J = 2.5 Hz, 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.58 - 7.54 (m, 3H), 7.53 (d, J = 8.5 Hz, 2H), 6.94 (d, J = 8.5 Hz, 2H) , 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-59.32 F2572 ESIMS m/z 609 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.43 (d, J = 2.4 Hz, 1H), 8.54 (d, J = 2.4 Hz , 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1, 9 Hz, 1H), 7.58 - 7.53 (m, 3H), 7.42 (t, J = 7.9 Hz, 1H), 7.13 (d, J = 2.0 Hz, 1H) , 7.07 (t, J = 9.1 Hz, 2H), 3.64 (d, J = 8.4 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-61.38 F2573 ESIMS m/z 611 (M+) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.46 (d, J = 1.9 Hz, 1H), 7.97 (d, J = 2.6 Hz , 1H), 7.86 - 7.80 (m, 1H), 7.73 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.57 (d, J = 2.1 Hz, 3H), 7.51 (t, J = 8.8 Hz, 2H), 7.14 (d, J = 8.3 Hz, 1H) , 6.91 (t, J = 7.6 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-60.65 F2574 124-140 ESIMS m/z 569 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.92 (s, 1H), 10.52 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (q, J = 2.2 Hz, 1H), 7.56 (d, J = 1.7 Hz, 3H), 7 .12 (t, J = 7.8 Hz, 1H), 6.74 (t, J = 1.9 Hz, 1H), 6.70 (dd, J = 8.2, 2.5 Hz, 1H) , 6.62 (d, J = 7.4 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H), 3 .19 (s, 3H), 2.28 (s, 3H) F2575 105-124 ESIMS m/z 557 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.91 (s, 1H), 10.22 (d, J = 2.9 Hz, 1H), 7.86 (dd, J = 14.7, 2.8 Hz, 2H), 7.77 (dd, J = 8.7, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.59 - 7, 50 (m, 3H), 7.00 (d, J = 8.1 Hz, 2H), 6.82 - 6.72 (m, 2H), 3.64 (d, J = 8.5 Hz, 1H ), 3.55 - 3.49 (m, 1H), 2.20 (s, 3H) F2576 152-172 ESIMS m/z 568 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 12.81 (s, 1H), 10.93 (s, 2H), 7.98 (d, J = 2.5 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.76 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7 .61 - 7.52 (m, 3H), 7.50 (d, J = 8.4 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 3.64 (d, J = 8.5 Hz, 1H), 3.53 (d, J = 8.5 Hz, 1H) F3001 164-166 ESIMS m/z 553.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 11.96 (s, 1H), 8.44 - 8.08 (m, 2H), 7.88 - 7.62 (m, 4H), 7.58 - 7.24 (m, 7H), 3.57 (d, J = 8.8 Hz, 1H), 3.42 (d, J = 8.0 Hz, 1H) F3002 179-181 ESIMS m/z 554.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 11.98 (s, 1H), 10.62 (s, 1H), 8.57 (s, 1H), 8.44 - 7 .88 (m, 2H), 7.86 - 7.62 (m, 3H), 7.58 - 7.24 (m, 5H), 3.58 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.8 Hz, 1H) F3003 160-162 ESIMS m/z 589.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 11.98 (s, 1H), 10.62 (s, 1H), 8.68 - 8.12 (m, 2H), 7 .81 (brs, 1H), 7.70 (brs, 1H), 7.58 - 7.44 (m, 4H), 7.38 - 7.24 (m, 2H), 3.57 (d, J = 8.8 Hz, 1H), 3.42 (d, J = 8.8 Hz, 1H) F3004 148-150 ESIMS m/z 589.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 11.98 (s, 1H), 10.60 (s, 1H), 8.62 - 7.92 (m, 2H), 7 .80 (brs, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.58 - 7.42 (m, 4H), 7.32 - 7.02 (m, 2H), 3.57 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.8 Hz, 1H) F3005 197-199 ESIMS m/z 567.8 ([M+H])+ ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 10.82 (s, 1H), 10.59 (s, 1H), 7.84 - 7.52 (m, 5H), 7 .48 - 7.42 (m, 3H), 7.42 - 7.24 (m, 3H), 3.58 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 8 .4 Hz, 1H), 2.30 (s, 3H) F3006 168-170 ESIMS m/z 558.8 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 12.00 (s, 1H), 10.62 (s, 1H), 8.62 - 8.38 (m, 1H), 7 .89 (brs, 1H), 7.80 (brs, 1H), 7.72 (d, J = 8.8 Hz, 2H), 7.58 - 7.40 (m, 4H), 3.58 ( d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.4 Hz, 1H) F3007 156-158 ESIMS m/z 515.9 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 , @ 90°C) δ 11.18 (s, 1H), 10.78 (s, 1H), 7.80 - 7.62 (m, 2H), 7 .52 (t, J = 1.5 Hz, 1H), 7.48 - 7.38 (m, 3H), 7.34 - 7.12 (m, 1H), 3.57 (d, J = 8 .4 Hz, 1H), 3.42 (d, J = 8.8 Hz, 1H), 1.28 -1.20 (m, 1H), 0.98 - 0.52 (m, 4H) F3008 145-147 ESIMS m/z 559.7 ([M+H] ⁺ ) ^1H NMR (400 MHz, CDCl ₃ ) δ 9.84 (s, 1H), 9.00 (s, 1H), 7.90 (dd, J = 2.4, 8.8 Hz, 1H), 7 .59 (d, J = 5.6 Hz, 1H), 7.56 (d, J = 2.4 Hz, 1H), 7.37 (s, 1H), 7.35 (d, J = 1, 6 Hz, 1H), 7.19 (d, J = 1.6 Hz, 2H), 3.53 (d, J = 8.0 Hz, 1H), 2.98 (d, J = 8.0 Hz , 1H), 3.28 - 3.14 (m, 2H) F3009 99-101 ESIMS m/z 573.8 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.80 (s, 1H), 7.70 (d, J = 2.4 Hz, 1H), 7.64 - 7.60 (m, 1H) , 7.59 (d, J = 2.8 Hz, 1H), 7.54 (d, J = 1.6 Hz, 2H), 7.44 (d, J = 8.8 Hz, 1H), 7 .23 (t, J = 5.2 Hz, 1H), 3.59 (d, J = 8.4 Hz, 1H), 3.48 (d, J = 8.4 Hz, 1H), 3.36 (s, 3H), 3.24 - 3.14 (m, 2H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-62.95 F3010 ESIMS m/z 505 ([MH] ^- ) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ rotary isomers 10.86 (s, 0.7H), 10.80 (s, 0.3H), 10.76 (s, 0.3H), 10, 65 (s, 0.7H), 7.77 (d, J = 2.5 Hz, 0.7H), 7.73 (dd, J = 8.7, 2.6 Hz, 0.7H), 7 .67 (d, J = 2.5 Hz, 0.3H), 7.62 (d, J = 1.9 Hz, 1H), 7.60 (d, J = 2.5 Hz, 0.3H) , 7.55 (d, J = 1.8 Hz, 2H), 7.50 (d, J = 8.7 Hz, 0.7H), 7.44 (d, J = 8.7 Hz, 0. 3H), 3.67 - 3.56 (m, 1H), 3.55 - 3.45 (m, 1H), 1.99 (s, 2H), 1.90 (s, 2H), 1.89 (s, 1H), 1.74 (s, 1H).
¹³ C NMR (151 MHz, DMSO-d ₆ ) δ 163.05, 162.54, 159.82, 138.04, 137.77, 136.70, 134.53, 130.56, 128.39, 128 ,17, 124.97, 120.03, 38.89, 37.24, 25.53, 18.56, 17.81

Table 6: Analytical data for molecules in Table 3

DP2 ESIMS m/z 580 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 10.18 (s, 1H), 7.89 (d, J = 2.6 Hz, 1H), 7.75 ( dd, J = 9.7, 2.3 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.7 Hz, 1H), 7, 43 (dd, J = 8.4, 2.1 Hz, 1H), 6.91 (ddd, J = 10.6, 8.8, 1.8 Hz, 1H), 6.80 (td, J = 8.4, 5.5 Hz, 1H), 5.31 (s, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H) ^19F NMR (376 MHz, DMSO-d6) δ -133.96 (d, J = 14.0 Hz), -138.07 (d, J = 13.9 Hz) DP3 65-85 ESIMS m/z 577 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 10.48 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.79 - 7.65 (m, 3H), 7.55 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.7, 2.2 Hz, 1H), 7.31 ( dd, J = 8.6, 2.0 Hz, 2H), 5.05 (s, 2H), 3.60 (d, J = 8.5 Hz, 1H), 3.46 (d, J = 8 .5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-130.39 DP4 (thin film) 3203, 3014, 1648, 1588 ESIMS m/z 558 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO-d6) δ 10.88 (s, 1H), 9.62 (s, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.73 ( dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.56 (dd, J = 1.9, 0.6 Hz, 2H ), 7.52 (d, J = 8.7 Hz, 1H), 6.93 (d, J = 8.3 Hz, 1H), 6.45 (d, J = 2.5 Hz, 1H), 6.40 (dd, J = 8.3, 2.5 Hz, 1H), 4.99 (s, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d , J = 8.5 Hz, 1H), 2.13 (s, 3H) DP5 ESIMS m/z 580 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 10.15 (s, 1H), 7.87 (d, J = 2.6 Hz, 1H), 7.74 ( dd, J = 7.9, 2.3 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.7 Hz, 1H), 7, 43 (dd, J = 8.4, 2.1 Hz, 1H), 7.19 - 7.08 (m, 2H), 5.11 (s, 2H), 3.60 (d, J = 8, 5 Hz, 1H), 3.46 (d, J = 8.5 Hz, 1H) ¹⁹ F NMR (376 MHz, DMSO-d6) δ -134.10, -135.36 DP6 118-137 ESIMS m/z 561 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 9.75 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.81 - 7.61 (m, 3H), 7.55 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.5, 2.2 Hz, 1H), 7.25 ( dd, J = 8.8, 6.3 Hz, 1H), 6.56 (dd, J = 11.2, 2.9 Hz, 1H), 6.39 (td, J = 8.5, 2, 9 Hz, 1H), 5.21 (s, 2H), 3.61 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H);
¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ
-116.28 DP7 ESIMS m/z 779 ([MH] ^- ) ^1H NMR (300 MHz, DMSO-d6) δ 10.98 (s, 1H), 10.52 (s, 1H), 7.93 (d, J = 2.5 Hz, 1H), 7.81 - 7.67 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.4, 2.1 Hz, 1H), 7.28 (t , J = 9.2 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 1.58 - 1.23 (m, 18H) ¹⁹ F NMR (376 MHz, DMSO-d6) δ -123.51 (d, J = 2.0 Hz), -126.49 (d, J = 2.1 Hz) DP8 ESIMS m/z 597 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.27 (s, 1H), 8.01 (d, J = 2.7 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.48 (t, J = 8.3 Hz, 2H), 7.37 (td, J = 8.6, 5.6 Hz, 1H), 6.89 ( ddd, J = 10.9, 9.1, 2.0 Hz, 1H), 4.77 (d, J = 8.5 Hz, 2H), 3.72 (d, J = 8.3 Hz, 1H ), 3.43 (d, J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.83, -61.86, -117.58, -137.24,
-144.22, -144.37 DP9 161-163 ESIMS m/z 597 ([M+H] ⁺ ) ^1H NMR (400 MHz, acetone- _d6 ) δ 10.19 (s, 1H), 9.28 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.82 (dq, J = 9.1, 2.7 Hz, 3H), 7.52 - 7.43 (m, 2H), 7.37 (td, J = 8.6, 5.5 Hz, 1H), 6.94 - 6.84 (m, 1H), 4.77 (d, J = 8.5 Hz, 2H), 3.72 (d, J = 8.3 Hz, 1H), 3.43 (d , J = 8.3 Hz, 1H);
¹⁹ F NMR (376 MHz, acetone- _d6 ) δ
-61.82, -117.59, -137.17, -144.17 DP10 (thin film) 3277, 2980, 1684, 1655, 1539 ESIMS m/z 656 ([MH] ^- ) ^1H NMR (300 MHz, DMSO-d6) δ 10.91 (s, 1H), 9.90 (s, 1H), 9.32 (s, 1H), 7.90 (d, J = 2.6 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.60 - 7.51 (m , 3H), 7.38 (s, 1H), 7.25 (q, J = 8.9 Hz, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.52 (d , J = 8.5 Hz, 1H), 2.23 (s, 3H), 1.48 (s, 9H) DP11 141-143 ESIMS m/z 641 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.93 (s, 1H), 10.90 (s, 1H), 7.91 (d, J = 2.4 Hz, 1H), 7.88 - 7.84 (m, 1H), 7.82 - 7.72 (m, 2H), 7.63 - 7.62 (m, 1H), 7.58 (d, J = 8.8 Hz, 1H ), 7.55 (d, J = 1.6 Hz, 2H), 3.61 (d, J = 8.8 Hz, 1H), 3.51 (d, J = 8.4 Hz, 1H) DP12 ESIMS m/z 778 ([MH] ^- ) ^1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 10.50 (s, 1H), 7.91 (d, J = 2.6 Hz, 1H), 7.75 ( td, J = 6.1, 5.2, 3.8 Hz, 3H), 7.69 (d, J = 8.4 Hz, 1H), 7.54 (dd, J = 11.0, 9, 4 Hz, 2H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 1.41 (s, 18H) ¹⁹ F NMR (376 MHz, DMSO-d6) δ -117.58 (d, J = 6.4 Hz), -121.81 (d, J = 6.6 Hz) DP13 ESIMS m/z 591 ([M+H] ⁺ ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 11.00 (d, J = 12.4 Hz, 2H), 7.98 (dd, J = 8.5, 2.9 Hz, 1H), 7 .91 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 8.8, 2.6 Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H) , 7.73 - 7.54 (m, 4H), 7.43 (dd, J = 8.6, 2.1 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H) DP14 ESIMS m/z 656 ([MH] ^- ) ^1H NMR (400 MHz, DMSO- _d6 ) δ 10.94 (s, 1H), 9.90 (s, 1H), 9.31 (s, 1H), 7.90 (d, J = 2, 6 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H) , 7.43 (dd, J = 8.5, 2.1 Hz, 1H), 7.38 (d, J = 2.3 Hz, 1H), 7.28 (dd, J = 8.6, 2 .4 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.47 (d, J = 8.5 Hz, 1H), 2.23 (s, 3H), 1.48 (s, 9H)

Indicator table for BAW and CL Destruction, % (or mortality) Index 50-100 A More than 0 – less than 50 B Not researched C No activity detected in this biological study D

Table of indicators for GPA and YFM Destruction, % (or mortality) Index 80-100 A More than 0 – less than 80 B Not researched C No activity detected in this biological study D

Table ABC: Biological Results

No. View BAW C.L. GPA YFM F1004 A A C A F1005 A A C A F1006 A A C A F1007 A A A A F1009 A A C A F1010 A A C A F1011 A A C A F1012 A A C A F1022 A A C C F1023 A A C A F1024 A A C A F1025 A A C A F1026 A A C A F1027 A A C C F1028 A A C C F1029 A A C C F1030 A A C C F1031 A A C A F1032 A A C A F1033 A A C A F1034 A A C A F1035 A A D A F1036 A A C D F1037 A A C A F1038 A A C A F1039 A A C A F1040 A A C A F1041 A A C D F1042 A A C A F1043 A A C A F1044 A A C A F1045 A A C A F1046 A A C A F1047 A A C A F1048 A A C A F1049 A A C A F1050 A A C A F1051 A A C A F1053 A A C A F1054 A A C A F1055 A A C D F1056 A A C D F1057 A A C A F1058 A A C A F1059 A A C A F1060 A A C C F1061 A A C A F1062 A A C A F1063 A A C C F1064 A A C A F1065 A A C A F1066 A A C A F1067 A A C A F1068 A A C D F1069 A A C D F1070 A A C A F1071 A A C A F1072 A A B A F1073 A A C C F1074 A A C A F1075 A A C A F1077 A A C A F1078 A A D A F1079 A A A A F1080 A A C C F1081 A A C C F1082 A A C C F1083 A A C C F1084 A A C A F1085 C C C C F1086 A A C C F1087 A A C A F1088 A A C A F1089 A A B A F1090 A A C A F1091 A A B A F1092 A A C C F1093 A A C D F1094 A A C A F1095 A A C C F1096 A A C A F1097 A A C C F1098 A A C C F1099 A A B A F1100 A A C A F1101 A A C C F1102 A A C C F1103 A A B A F1104 A A C A F1105 A A B A F1106 A B C C F1107 D B C C F1108 A A A A F1109 A A C C F1110 A A C C F1111 A A C C F1112 A A C A F1113 A A C A F1114 A A C A F1115 A A C C F1116 A A C A F1117 A A C A F1118 A A C A F1119 A A C A F1120 A A C C F1121 A A C C F1122 A A C C F1123 A A C C F1124 A A C C F1125 A A C C F1126 A A C C F1127 A A C A F1128 A A C C F1129 D A C D F1130 A A C A F1133 A A C C F1134 A A C C F1135 A A C C F1136 A A C A F1137 A A C A F1138 B D C C F1139 A A C A F1140 A A C A F1141 A A C A F1142 A A C A F1143 A A C A F1144 A A C C F1145 A A C C F1146 A A C C F1147 A A A A F1148 A A C C F1149 A A C A F1150 A A C A F1151 A A C C F1152 A A C A F1153 A A C A F1154 A A C A F1155 A D C D F1156 A A C C F1157 D D C D F1158 A A C C F1159 A A C D F1160 A A C A F1161 A A C A F1162 A A C A F1163 A A C A F1164 A A C A F1165 A A C D F1166 A A C A F1167 A A C A F1168 A A C C F1169 A A C A F1170 A A C A F1171 A A C C F1172 A A C A F1173 A A C A F1174 A A C A F1175 A A C A F1176 A A C A F1177 A A C C F1178 A A C D F1179 A A C C F1180 A A B A F1181 A A C A F1182 A A C A F1183 A A C A F1184 A A C A F1185 A A A A F1186 A A C A F1187 C C D D F1188 A A C A F1189 A A C A F1190 A A A D F1191 A A C A F1192 C C C D F1193 D A C C F1194 A A C C F1195 A A C C F1196 A A C C F1197 A A C C F1198 D B C C F1199 C C C C F1200 C C C C F1201 A A C A F1202 A A C C F1203 B A C C F1204 A A C C F1205 A A C C F1206 A A C D F1207 A A C C F1208 A A C C F1209 A A C C F1210 A A C C F1211 A A C C F1212 A A C A F1213 D A C D F1214 A A C A F1215 A A C A F1216 A A C A F1217 C C C D F1218 A A C A F1219 A A C A F1220 A A C A F1221 C C C D F1222 A A C C F1223 A A C C F1224 A A C C F1225 A A C C F1226 A A C C F1227 A A B A F1228 A A B A F1229 A A C A F1230 D D C D F1231 A A C C F1232 A A C A F1233 A A C A F1234 A A A A F1235 A A C C F1236 A A C C F1237 B D C C F1238 A A B A F1239 C C C C F1240 A A B A F1241 A A A A F1242 A A B A F1243 A A B A F1244 A A B C F1245 A A B A F1246 A A A A F1247 A A A A F1248 A A A A F1249 A A C A F1250 A A A A F1251 A A B A F1252 A A C A F1253 A A C A F1254 A A C A F1255 A A A C F1256 A A A C F1257 A A C D F1258 A A C C F1259 A A C A F1260 A A C C F1261 A A A C F1262 A A A C F1263 A A C A F1264 A A C A F1265 A A C C F1266 C C C C F1268 A A C C F1269 A A C C F1270 A A C A F1271 A A C A F1272 A A C C F1273 A A C A F1274 A A C C F1275 A A C A F1276 A A C A F1277 A A C A F1278 A A C A F1279 A A C B F1280 C C C C F1281 A A C A F1282 C C C C F1283 C C C C F1284 A A C C F1285 A A C C F1286 A A C C F1287 A A C C F1288 A A C C F1289 A A C C F1290 A A C C F1291 A A C C F1292 C C C C F1293 A A C D F1294 C C C C F1295 A A C A F1296 A A C C F1297 A A C A F1298 A A C A F1299 A A C A F1300 A A C A F1301 A A C A F1302 A A C C F1303 A A C A F1304 A A C A F1305 A A C A F1306 A A C C F1307 A A C C F1308 A A C C F1309 A A C A F1311 A A C A F1312 A A C A F1313 A A C A F1314 A A C A F1315 A A C A F1316 A A C A F1317 A A C A F1318 A A C A F1319 A A C A F1320 A A C A F1321 A A C A F1322 A A C C F1323 A A C A F1324 A A C C F1325 A A C C F1326 C C C C F1327 C C C C F1328 C C C C F1329 C C C C F1330 A A C C F1331 A A C C F1332 A A C C F1333 A A C C F1334 A A C C F1335 A A C C F1336 A A C C F1337 A A C C F1338 A A C C F1339 A A C C F1340 A A C C F1341 A A C C F1342 A A C C F1343 A A C C F1344 A A C C F1345 A A C C F1346 A A C C F1347 A A C C F1348 A A C C F1349 C C C C F1350 A A C C F1351 A A C A F1352 A A C A F1353 A A C A F1354 A A C A F1355 A A C A F1356 A A C C F1357 A A C A F1358 A A C A F1359 A A C A F1360 D A C C F1361 A A C C F1362 A A C A F1363 A A C A F1364 A A B A F1365 A A C A F1366 A A C D F1367 A A C D F1368 A A C A F1369 A A C A F1370 A A C A F1371 A A B A F1372 A A C A F1373 C C C C F1374 A A C C F1375 A A C C F1376 C C C C F1377 A A C C F1378 B A C C F1379 C C C C F1380 C C C C F1381 C C C C F1382 C C C C F1383 C C C C F1384 A A C A F1385 A A C A F1386 A A B A F1387 A A C A F1388 A A C C F1389 A A C A F1390 A A C A F1391 A A C A F1392 A A C A F1393 A A C A F1394 A A C A F1395 A A C C F1396 A A C C F1397 A A C C F1398 A A C C F1399 A A C C F1400 A A C C F1401 A A C C F1402 A A C C F1403 A A C C F1404 A A C C F1405 A A C C F1406 A A C C F1407 A A C C F1408 A A C C F1409 A A C C F1410 A A C A F1411 A A C C F1412 A A C C F1413 D D C D F1414 A A C A F1415 A A C A F1416 A A C A F1417 A A C A F1418 A A C A F1419 A A C A F1420 C C C C F1421 C C C C F1422 C C C C F1423 C C C C F1424 C C C C F1425 C C C C F1426 A A C C F1427 A A C C F1428 A A C C F1429 A A C C F1430 A A C C F1431 A A C C F1432 A A C C F1433 A A C C F1434 C C C C F1435 C C C C F1436 C C C C F1437 A A C A F1438 A A C A F1439 A A C A F1440 A A C A F1441 A A C A F1442 A A C A F1443 A A C A F1444 A A C A F1445 C C C C F1446 A A C C F1447 A A C A F1448 A A C A F1449 A A C C F1450 A A C A F1451 A A C A F1452 A A C A F1453 C C C C F1454 A A C A F1455 C C C C F1456 C C C C F1457 C C C C F1458 A A C C F1459 A A C C F1460 A A A A F1461 A A C A F1462 A A C C F1463 A A C C F1464 A A C C F1465 A A A A F1466 A A C A F1467 C C C C F1468 A A C C F1469 A A C C F1470 A A C C F1471 A A C C F1472 A A C C F1473 A A B A F1474 A A B A F1475 A A B A F1476 A A C C F1477 A A C C F1478 A A C C F1479 A A B A F1480 A A C A F1481 A A C A F1482 A A C A F1483 A A B A F1484 A A C C F1485 A A C C F1486 A A C C F1487 A A C C F1488 A A C A F1489 A A B A F1490 A A C C F1491 A A C C F1492 A A B A F1493 A A C C F1494 A A C C F1495 A A C C F1496 A A C C F1497 A A C C F1498 A A C C F1499 A A C C F1500 A A C C F1501 A A C C F1502 A A C C F1503 A A C C F1504 A A C C F1505 A A B C F1506 A A C A F1507 A A C A F1508 A A C C F1509 A A C C F1510 A A C A F1511 A A C A F1512 A A C C F1513 A A C C F1514 A A C C F1515 A A C C F1516 A A C C F1517 A A C C F1518 A A C C F1519 A A C C F1520 A A C C F1521 A A C A F1522 A A C C F1523 A A C C F1524 A A C C F1525 A A C C F1526 A A C A F1527 A A C C F1528 A A C B F1529 A A B A F1530 A A B D F1531 A A B D F1532 A A C C F1533 A A C C F1534 A A C C F1535 A A C C F1536 A A C C F1537 A A C C F1538 A A C C F1539 A A C C F1540 A A C C F1541 A A C C F1542 C C C C F1543 A A C C F1544 A A C C F1545 A A C C F1546 A A C C F1547 A A C C F1548 A A C C F1549 C C C C F1550 A A C C F1551 A A C A F1552 A A C A F1553 A A C A F1554 A A C A F1555 A A C A F1556 A A C A F1557 A A C A F1558 A A C A F1559 A A C A F1560 A A C A F1561 A A C A F1562 A A C A F1563 C C C C F1564 A A C C F1565 A A C C F1566 A A C C F1567 A A C C F1568 A A C C F1569 A A C C F1570 A A C C F1571 A A C C F1572 A A C C F1573 A A C C F1574 A A C C F1575 A A C C F1576 A A C C F1577 A A C C F1578 A A C C F1579 A A C C F1580 A A C C F1581 A A C C F1582 A A C C F1583 A A C C F1584 A A C C F1585 A A C C F1586 A A C C F1587 A A C C F1588 A A C C F1589 A A C C F1590 A A C C F1591 A A C A F1592 A A C A F1593 A A A A F1594 A A C A F1595 A A C A F1596 A A C A F1597 A A C A F1598 A A A A F1599 A A C A F1600 A A C A F1601 A A C A F1602 A A C A F1603 A A C A F1604 A A C A F1605 A A C A F1606 A A C A F1607 A A C A F1608 A A C A F1609 A A C C F1610 A A C A F1611 A A C C F1612 A A B A F1613 A A A A F1614 A A C A F1615 A A B A F1616 A A C C F1617 A A B A F1618 A A C A F1619 C C C C F1620 C C C C F1621 C C C C F1622 A A C C F1623 A A C C F1624 A A C C F1625 A A B A F1626 A A C A F1627 A A A A F1628 A A C A F1629 A A C B F1630 A A C A F1631 A A C C F1632 A A C C F1633 A A C C F1634 A A C B F1635 A A B A F1636 A A B A F1637 A A C B F1638 A A C C F1639 A A C C F1640 A A C C F1641 A A C C F1642 A A B A F1643 A A B B F1644 A A B B F1645 A A C A F1646 A A C A F1647 A A C C F1648 A A C C F1649 A A C C F1650 A A C C F1651 A A C A F1652 A A C C F1653 A A C A F1654 A A C A F1655 A A B B F1656 A A B A F1657 A A A A F1658 A A B C F1659 A A C C F1660 A A C A F1661 A A C A F1662 A A C C F1663 A A C C F1664 A A C C F1665 A A C D F1666 A A A B F1667 A A B B F1668 A A C A F1669 A A C A F1670 B D C C F1671 A A C B F1672 A A C C F1673 A A B B F1674 A A C D F1675 A A C A F1676 A A C D F1677 A A C D F1678 A A A B F1679 A A C A F1680 A A C B F1681 A A C D F1682 A A C A F1683 A A C D F1684 A A C B F1685 A A C A F1686 A A C A F1687 A A C A F1688 A A C A F1689 A A C B F1690 A A C A F1691 A A C B F1692 A A C B F1693 A A C C F1694 A A A A F1695 A A A B F1696 A A A A F1697 A A A A F1698 A A B D F1699 A A B B F1700 A A B D F1701 A A A B F1702 A A A A F1703 A A A A F1704 A A A A F1705 A A A B F1706 A A C A F1707 A A C A F1708 A A A A F1709 A A C A F1710 A A B A F1711 A A A A F1712 A A C A F1713 A A C C F1714 A A C C F1715 A A C C F1716 A A C C F1717 A A C C F1718 A A C C F1719 A A C A F1720 A A C A F1721 A A C D F1722 A A C D F1723 A A C A F1724 A A A D F1725 A A C A F1726 A A C D F1727 A A C A F1728 A A C B F1729 A A C A F1730 D D C C F1731 A A C C F1732 A A C C F1733 A A C C F1734 A A C C F1735 A A C A F1736 A A B A F1737 A A B A F1738 A A C A F1739 A A B A F1740 A A A A F1741 A A C C F1742 A A B A F1743 A A C A F1744 A A C A F1745 A A C A F1746 A A C A F1747 A A C A F1748 A A C C F1749 A A C C F1750 A A C C F1751 A A C C F1752 A A C A F1753 A A C C F1754 A A C C F1755 A A C B F1756 A A C C F1757 A A C C F1758 A A C A F1759 A A C A F1760 A A C A F1761 A A C A F1762 A A C C F1763 A A C A F1764 A A C A F1765 A A C C F1766 A A C A F1767 A A C A F1768 A A C A F1769 A A C A F1770 A A C C F1771 A A C A F1772 A A C C F1773 A A C C F1774 A A C A F1775 A A C A F1776 A A C A F1777 A A C C F1778 A A C C F1779 A A C C F1780 A A C A F1781 A A C A F1782 A A C A F1783 A A C C F1784 C C C C F1785 C C C C F1786 C C C C F1787 C C C C F1788 C C C C F1789 A A C A F1790 A A C A F1791 A A C A F1792 A A C A F1793 A A C A F1794 A A C B F1795 A A C A F1796 A A C A F1797 A A C A F1798 A A C B F1799 A A C A F1800 A A C A F1801 A A C A F1802 A A C A F1803 A A C A F1804 A A C A F1805 A A C A F1806 A A C A F1807 A A C C F1808 A A C B F1809 A A C A F1810 A A C A F1811 A A C C F1812 A A C B F1813 A A C A F1814 A A C A F1815 A A C A F1816 A A C C F1817 A A C C F1818 A A C A F1819 A A C A F1820 A A C C F1821 A A C C F1822 A A C A F1823 A A C A F1824 A A C C F1825 A A C A F1826 A A C A F1827 A A C A F1828 A A C C F1829 A A C A F1830 A A C A F1831 A A C A F1832 A A C C F1833 A A C D F1834 A A C C F1835 A A C C F1836 A A C A F1837 A A C C F1838 A A C C F1839 A A C C F1840 A A C C F1841 A A C A F1842 A A C A F1843 A A C A F1844 A A C A F1845 A A C C F1846 A A C C F1847 A A C A F1848 A A C A F1849 A A C C F1850 A A C C F1851 A A C C F1853 A A C A F1854 A A C A F1855 A A C C F1856 A A C B F1857 A A C A F1858 A A C A F1860 A A C C F1861 A A C C F1862 A A C C F1863 A A C C F1864 A A C C F1865 A A C C F1866 A A C A F1867 A A C C F1868 A A C A F1869 A A C A F1870 A A C A F1871 A A C C F1872 A A C C F1873 A A C C F1874 A A C A F1875 A A C C F1876 A A C A F1877 A A C C F1878 A A C A F1879 A A C A F1880 A A C C F1881 C C C C F1882 C C C C F1883 C C C C F2001 A A C A F2002 A A C A F2003 A A C A F2004 A A C A F2005 A A C A F2006 A A C A F2007 A A C A F2008 A A C A F2009 A A C A F2010 A A C A F2011 A A B A F2012 A A C A F2013 A A C A F2014 A A C A F2015 A A C A F2016 A A A A F2017 A A A A F2018 A A C A F2019 A A D A F2020 A A B A F2021 A A A A F2022 A A C A F2023 A A C A F2024 A A C A F2025 A A B A F2026 A A B A F2027 A A A A F2028 A A C A F2029 A A C A F2030 A A C A F2031 A A C A F2032 A A C A F2033 A A C C F2034 A A C D F2035 A A C A F2036 A A C A F2037 A A C A F2038 A A C A F2039 A A A A F2040 A A B A F2041 A A C C F2042 A A A A F2043 A A C A F2044 A A C A F2045 A A C C F2046 A A C C F2047 A A C C F2048 A A C C F2049 A A C C F2050 A A C C F2051 A A C C F2052 A A C C F2053 A A C C F2054 A A C A F2055 A A C A F2056 A A C A F2057 D A C A F2058 A A C A F2059 A A C A F2060 A A C A F2061 A A C C F2062 A A C C F2063 A A C A F2064 A A C A F2066 A A C A F2067 A A C A F2068 A A C A F2069 A A C A F2070 A A C A F2071 A A C C F2072 A A C C F2073 A A C C F2074 A A C C F2075 A A A B F2076 D A C D F2077 A A C B F2078 A A A A F2079 A A D A F2080 A A B B F2081 A A A A F2082 A A A B F2083 D A C B F2084 A A C D F2085 A A C A F2086 A A C A F2087 A A C A F2088 A A C B F2089 A A C A F2090 A A C A F2091 A A C A F2092 A A C B F2093 A A C B F2094 A A C B F2095 A A C A F2096 A A C B F2097 A A C A F2098 A A C B F2099 A A C C F2100 A A C C F2501 A A C C F2502 A A C A F2503 A A C C F2504 A A C A F2505 A A C A F2506 A A C A F2507 A A C A F2508 A A C A F2509 A A C A F2510 A A C A F2511 A A C A F2512 A A C A F2513 A A C A F2514 A A C A F2515 A A C A F2516 A A C C F2517 A A C C F2518 A A C A F2519 A A C A F2520 A A C A F2521 A A C A F2522 A A C A F2523 A A C C F2524 A A C A F2525 A A C A F2526 A A C C F2527 A A C C F2528 A A C C F2529 A A C C F2530 A A C A F2531 A A C A F2532 A A C C F2533 A A C C F2534 A A C C F2535 A A C C F2536 A A C C F2537 A A A C F2538 A A C A F2539 A A C C F2540 A A C C F2541 A A C A F2542 A A C B F2543 A A C A F2544 A A C A F2545 A A C A F2546 A A C C F2547 A A C A F2548 A A C C F2549 A A C A F2550 B A C B F2551 A A C A F2552 A A C A F2553 A A C A F2554 A A C A F2555 A A C A F2556 A A C C F2557 A A C A F2558 A A C A F2559 A A C B F2560 A A C D F2561 A A C B F2562 A A C A F2563 A A C B F2564 A A C A F2565 A A C D F2566 A A C C F2567 A A C A F2569 A A C C F2570 A A C C F2571 C C C A F2572 A A C A F2573 A A C C F2574 A A C C F2575 A A C C F2576 A A C A F3001 A A C A F3002 A A C A F3003 A A C A F3004 A A C A F3005 A A C A F3006 A A C C F3007 A A C C F3008 A A C A F3009 A A C A F3010 A A C A

Table ABC-DP: Biological Results

DP1 A A C A DP2 A A C A DP3 A A C C DP4 A A C A DP5 A A C A DP6 A A C C DP7 A B C D DP8 A A A A DP9 A A C A DP10 A A C A DP11 A A C A DP12 A A C D DP13 C C C C DP14 C C C C

Claims (6)

1. A molecule having the following formula: ; and agriculturally acceptable acid addition salts or separated stereoisomers of the molecule. 2. The molecule according to claim 1, wherein said molecule has the following formula: 3. A method of pest control, including applying a pesticide-effective amount of a molecule according to any one of claims to the area. 12.