Pesticidal molecules, intermediates, compositions and methods relating thereto

Abstract

To provide novel compounds effective for controlling pests.SOLUTION: The invention provides molecules of formula 1, and N-oxides, agriculturally acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, resolved stereoisomers, tautomers, and pro-insecticides thereof. [R1 to R5, R7 to R8, and R11 to R14 represent H, halogen, or the like; R6 and R9 represent H; R10 represents H, alkyl, or the like; and Q1 and Q2 represent O or S.]SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is incorporated herein by reference in its entirety as if fully set forth in U.S. Provisional Application No. 62 / 40, all filed October 12, 2016. The benefit of priority to Patent Application Nos. 7092 and 62 / 407118 is claimed. The entire contents of all applications are incorporated by reference into this application.

[0002] Field of the Disclosure The present disclosure relates to the phyla Arthropoda, Mollusca, and Nematoda. Molecules with pesticidal activity against harmful animals in the genus Matoda, and the manufacture of such molecules methods for making such compounds, intermediates used in such methods, and compounds containing such molecules pesticidal compositions and methods for using such pesticidal compositions against such pests. These pesticidal compositions are useful as, for example, acaricides, insecticides, and the like. It can be used as an acaricide, molluscicide and nematicide. [Background technology]

[0003] "Many of the most dangerous human diseases are transmitted by insect vectors" (Rivero et al.). In general, malaria, dengue fever, yellow fever, plague, filariasis, louse-borne typhus, and sleep deprivation Sleeping sickness, leishmaniasis, and other vector-borne diseases occurred between the 17th and early 20th centuries. Over the years, it has been responsible for more human disease and death than all other causes combined." (Gubler). Vector-borne diseases are responsible for approximately 17% of the world's parasitic and infectious diseases. Malaria alone causes over 800,000 deaths per year, 85% of cases occur in children under the age of five. There are approximately 50 million to 100 million cases of dengue fever each year. Additionally, there are 250,000 to 500,000 cases of dengue hemorrhagic fever each year. Vector control is an important step in the prevention and control of infectious diseases (Matthews). However, insecticide resistance, including resistance to multiple insecticides, , which occur in all insect species that are major vectors of human disease (Rivero et al.). More than 50 arthropod species have developed resistance to at least one pesticide. Furthermore, in the case of insect resistance, herbicide resistance and fungicide resistance are also being investigated (Whalon et al.). continues to far exceed resistance (Sparks et al.).

[0004] Each year, over 40% of all food production is wasted due to insects, plant pathogens and weeds. This loss is due to the application of pesticides and many other methods such as crop rotation and biological control. Despite the use of various non-chemical control methods, it is still occurring. If we can do this, we can use it to feed the more than 3 billion undernourished people in the world. Can be used for (Pimental).

[0005] Plant-parasitic nematodes are among the most widespread pests and often the most oily. Losses due to nematodes are one of the most indestructible and costly. It is estimated that the rate is between 15% (developed countries) and 15% (developing countries). In a 35-state study of various crops, losses from nematodes were found to be up to 25%. showed (Nicol et al.).

[0006] Gastropods (slugs and snails) are of greater economic importance than other arthropods or nematodes. Although it is a less important pest, in certain locations it can substantially reduce yield and affect the quality of the crop. have a significant impact on the environment and can transmit human, animal and plant diseases; Note that only a few dozen species of gastropods are serious local pests, and a few Species are important pests worldwide. Gastropods in particular are known to cause damage to arable crops, pasture crops and Affects a wide range of agricultural and horticultural crops, including fiber crops, vegetables, fruit trees, herbs, and ornamentals. Influence (Speiser).

[0007] Termites can infest all types of private and public buildings, as well as agricultural and forestry resources. In 2005, termites caused over US$50 billion in damage to the world each year. It was estimated that the damage would be widespread (Korb).

[0008] Therefore, for many reasons, including those mentioned above, it is expensive (in 2010 (estimated at approximately US$256 million per pesticide), and a significant amount of time new pesticides, which are both necessary (average of about 10 years per pesticide) and difficult to There is a continuing need for development (CropLife America).

[0009] Certain References Cited in This Disclosure

[0010] 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 Agrochemic al Research, Modern Methods in Crop Protection Research, Part I, Methods for the Design and Optimization of New Active Ingredients, Edited by Jeschke, P., Krame r, W., Schirmer, U., and Matthias W., p. 1-20, 2012。 Gubler, D., Resurgent Vector-Borne Diseases as a Global Health Problem, Emergi ng 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 o f 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 V ector-Borne Diseases: When is Insect Resistance a Problem? Public Library of Sci ence Pathogens, Vol. 6, No. 8, p. 1-9, 2010。 Sparks T.C., Nauen R., IRAC: Mode of action classification and insecticide res istance management, Pesticide Biochemistry and Physiology (2014) available onlin e 4 December 2014。 Speiser, B., Molluscicides, Encyclopedia of Pest Management, Ch. 219, p. 506-5 08, 2002。 Whalon, M., Mota-Sanchez, D., Hollingworth, R., Analysis of Global Pesticide R esistance in Arthropods, Global Pesticide Resistance in Arthropods, Ch. 1, p. 5- 33, 2008。 Summary of the Invention

[0011] Definitions Used in the Present Disclosure The examples provided in these definitions are generally not exhaustive and are not intended to limit the present disclosure. A substituent group does not conform to the rules of chemical bonding with respect to the particular molecule to which it is attached. and steric compatibility constraints. These definitions are intended to be used in the context of this disclosure. It is to be used only for the purpose for which it was intended.

[0012] The term "active ingredient" refers to a substance having an activity useful in controlling pests, and and / or substances useful in the adjunction of other substances with better activity in controlling pests. Examples of such substances include, but are not limited to, miticides, algaecides, anticides, and the like. Antifeedants, bird killers, bactericides, bird repellents, sterilizers, fungicides, herbicide antidotes, herbicides , insect attractants, insect repellents, insecticides, mammal repellents, mating disruptors, molluscicides, These include nematicides, plant activators, plant growth regulators, rodenticides, synergists and virucides. (See alanwood.net) Examples of such substances include, but are not limited to: However, the substances listed in Active Ingredient Group Alpha are not included.

[0013] The term "Alpha Active Ingredients Group" (hereinafter referred to as "AIGA") collectively refers to the following: This refers to the following substances:

[0014] (1)(3-ethoxypropyl)mercury bromide, 1,2-dibromoethane, 1,2-dichloro chloroethane, 1,2-dichloropropane, 1,3-dichloropropene, 1-MCP, 1-methylpropane 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, 2i P, 2-methoxymethylmercury 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-hydroxyquinone mercury sulfate, 8-phenylmercuryoxyquinoline, abamectin, abamectin-aminomethicone le, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acetion , acetochlor, acetophenate, acetophos, acetoprole, acibenzolar, Acifluorfen, Aclonifen, ACN, Aclep, Acrinathrin, Acrole In, acrylonitrile, acipetax, afidopiropen, afoxolaner, ara Chlor, Alanap, Alanycarb, Albendazole, Aldicarb, Aldicarb Sulfone, aldimorph, aldoxicarb, aldrin, allethrin, allicin, ali Dochlor, Allosamidin, Alloxydim, Allyl Alcohol, Alixicarb, Alora ac, alpha-cypermethrin, alpha-endosulfan, alphamethrin, Lutretamine, aluminum phosphide, aluminum phosphide minum phosphide), ametocladine, ametridione, ametryn, ametryn Phosphorus (ametryne), amivudine, amicarbazone, amicarthiazole, amidithione, Amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminopyrachlor Ralido, aminotriazole, amiprofos-methyl, amiprofos amiprophos-methyl, amisulbrom, amiton, amitra Z, amitrole, ammonium sulfamate, amber, amorphous silica gel, Amorphous silicon dioxide, ampropylphos, AMS, anabasine, ancymidol, Anilazine, Anilofos, Anisrone, Anthraquinone, Anz, Aphorate, Aramay To, alprocarb, arsenic trioxide, asomethane, aspirin, ashram, acidation , Atraton, Atrazine, Aureofungin, Avermectin B1, AVG, Avigli Syn, azaconazole, azadirachtin, azafenidin, azamethiphos, azidithion , Azimsulfuron, Azinphos ethyl, Azinphos-ethyl, Azinphos methyl, Azin Amphos-methyl, Aziprotryn, Aziprotryne, A Dithiram, azobenzene, azocyclotin, azotoate, azoxystrobin, bakume Desh, barban, barbanate, barium hexafluorosilicate, barium polysulfide, silicofluoride Barium chloride, Bartholin, basic copper carbonate, basic copper chloride, basic copper sulfate, BCPC, Bef Rubutamide, Benalaxyl, Benalaxyl-M, Benazolin, Bencarbazone, Benclo Chiaz, Bendakingbingchi, Bendiocarb, Benzoxide, Benefin, Ben Fluralin, Benfuracarb, Benfuresate, Benmihuancaoan, Benodani, Benodanil Nomil, Benoxacor, Benoxafos, Benquinox, Bensulfuron, Bensulide , bensultap, bentallon, bentazon, bentazon , benthiavalicarb, benthiazole, benthiocarb, bentranil, benzadox Benzalkonium chloride, benzamacryl, benzamisole, benzamorph, benzene Hexachloride, benzfendizone, benzimine, benzipram, benzobicyclon , Benzoepin, Benzofenap, Benzofluor, Benzohydroxamic acid, Benzome phosphate, benzophosphate, benzothiadiazole, benzovindiflupyr, benzoxyl Mate, Benzoylprop, Benzthiazuron, Benzokaotong, Benzoic acid benzyl beta-cyfluthrin, beta-cypermethrin, Bethoxadin, BHC, bialaphos, bicyclopyrone, bifenazate, bifenox , Bifenthrin, Bifjunchi, Bilanaphos, Binapacryl, Binqingxiao, Bioa Lethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bi Sazil, bismerthiazole, bismerthiazole-copper, bisphenylmercury methylenedi( x-naphthalene-y-sulfonate), Bispyribac, Bistrifluron, Bisultat P, Bitertanol, Bithionol, Bixafen, Blasticidin-S, Borax, Rudo solution, boric acid, boscalid, BPPS, brassinolide, brassinolide-ethyl, Vicomin, Brodifacoum, Brofenprox, Brofenvalerate, Broflani Lid, broflutrinate, bromacil, bromadiolone, bromclofos, bromethalin Bromethrin, Bromfenvinphos, Bromoacetamide, Bromobornyl, Bromo Butide, Bromocyclen, Bromocyclen, Bromo-D DT, bromofenoxime, bromophos, bromomethane, bromophos ophos), bromophos-ethyl, bromopropylate, bromotaloni ru, bromoxynil, brompyrazone, bromuconazole, bronopol, BRP, BT H, bucarbolate, bufencarb, buminafos, bupirimate, buprofezin, b Rugogne's solution, busulfan, busulphan, butacarb, Butachlor, butafenacil, butam, butamifos, butane-fipronil, butathio Phos, butachlor, butene-fipronil, butetryn, butidazole, buthiobate , butiuron, butiphos, butocarboxim, butonate, butopyronoxyl, butoxy Carboxim, Butralin, Butrizol, Butroxydim, Buturon, Butylamine, Butyrate, Butylchlorophos, Butylene-Fipronil, Cacodylic Acid, Cadusafos, Cacodylate Fenestrol, calciferol, calcium arsenate, calcium chlorate, calcium Cyanamide, calcium cyanide, calcium polysulfide, carbinphos, camphendichlor , camphechlor, camphor, captafol, captan, carbam, carbamorph, Carbanolate, carbaryl, carbaslam, carbaryl Rubathion, carbendazim, carbendazole, carbetamide, carbofenothion, Carbofuran, carbon disulfide, carbon tetrachloride, carbonyl sulfide, carbophenothione, carbo Phos, carbosulfan, carboxazole, carboxide, carboxin, carphen Trathrazone, Carpropamid, Cartap, Carvacrol, Carvone, CAVP, CDA A, CDEA, CDEC, Celocidin, CEPC, Cerala, Selenox, Cevadila, Cheshunt liquid, quinalphos, quinalphos-methyl, quinomethio chinomethionat, chinomethionate, chiralaxyl, chi Tosan, clobenziazone, clomethoxyfen, chloralose, chloramben, chlora Minphosphorus, chloramphenicol, chloraniformethane, chloranil, chloranox chlorantraniliprole, chlorradifop, chlorazine, chlorbeneside, chlor Rubenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, Roldecon, chlordimeform, chlorempentrin, chlorethazate, chloracefo Chlorethoxyphos, chloreturon, chlorfenac, chlorfenapyr, chlorf Chlorphenazole, chlorphenetole, chlorphenidim, chlorfenprop, chlorf Chlorphenesulfide, chlorfenvinphos, chlorfenvinphos-meth Chil, Chlorfluazuron, Chlorflurazole, Chlorflurechol, Chlorflurane , chlorflurenol, chloridazon, chlorimuron, chlorinate, chloro-IPC, Chlormephos, chlormequat, chlormethron, chlormethoxynil, chlornidine, Clornitrofen, chloroacetic acid, chlorobenzilate, chlorodinitronaphthalene, chloro Rofenisone, chloroform, chloromebform, chloromethiron, chloroneb, cloromethane Lophacinone, chlorophos, chloropicrin, chloropon, chloroparethrin, chlorop Lopirate, chlorothalonil, chlorotoluron, chloroxyphenidim, chloroxuron , chloroxynil, chlorphonium, chlorphoxim, chlorprazophos, chlorproca Rub, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox , chlorsulfuron, chlorthal, chlorthiamid, chlorthiophos, chlortoluron , chlozolinate, curtosan, cholecalciferol, choline chloride, chromafenozide , cycloheximide, simetacarb, simetacarb, cinerin I, cinerin II, cinerin Phosphorus, Cinidon-ethyl, Cinmethylin, Cinosulfuron, Cintofen, Ciobutide, Cisanilide, cismethrin, clasifos, clefoxydim, clenpirin ), clenpyrin, clethodim, climbazole, clonidine, cloprid Dinafop, cloetocarb, clofencet, clofenotan, clofentezine, Clofenvinphos, clofibric acid, clofop, clomazone, clomeprop, Lonitralid, cloprop, cloproxyzim, clopyralid, cloquintocet, Loransulam, closantel, clothianidin, clotrimazole, cloxifonac, Cloxylacon, Clozylacon, CMA, CMMP, CMP, CMU, Codlerua, Colle Calciferol, colophonate, copper-8-quinolinolate, copper acetate, copper acetoarsenite, Copper arsenate, basic copper carbonate, copper hydroxide, copper naphthenate, copper oleate, basic copper chloride, silicic acid Copper, copper sulfate, basic copper sulfate, copper zinc chromate, coumachlor, coumafen, coumaphos (coum afos), coumafuryl, coumaphos, coumatetralyl, methoxystrobin , Cumitoate, Cumoxystrobin, CPMC, CPMF, CPPC, Cledazin, Resole, cresylic acid, crimidine, crotamiton, crotoxyfos, Crotoxyphos, crufomate, cryolite, cuurua, kufraneb, kumi Leron, Cumilron, Cuprobam, Cuprous Oxide, Curcumenol, CVMP, Cyanamide , cyanatrin, cyanazine, cyanofenphos, cyanogen, cyanophos, cyanthoate , Cyantraniliprole, Cyanuric acid, Cyazofamid, Sibutrin, Cyclafuramid , cyclanilide, cyclaniliprole, cyclethrin, cycloate, cycloheximide , cycloplate, cycloprothrin, cyclopyrimorate, cyclosulfamuron, cloxydim, cyclouron, cyenopyrafen, cyflufenamid, cyflumetofen, Cyfluthrin, cyhalodiamide, cyhalofop, cyhalothrin, cyhexatin, cimiazol chloral, cymoxanil, siometrinil, cypendazole, cypermethrin, cypercort , cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprazole Lofram, Cypromide, Cyprosulfamide, Cyromazine, Cythioate, Citrex , Dimuron, Dalapon, Daminozide, Dioutong, Dazomet, DB CP, d-camphor, DCB, DCIP, DCPA (Japan), DCPA (USA), DC PTA, DCU, DDD, DDPP, DDT, DDVP, debacarb, decaphentin, Decamethrin, decarbofuran, DEET, dehydroacetic acid, diquat, de Lacroix, De Lunab, Deltamethrin, Demefion, Demefion-O, Demefion-S, Demet Demeton, Demeton-methyl, Demeton-O, Demeton-O-methyl, Demeton-S, Demeton -S-methyl, Demeton-S-methyl sulfone, Demeton-S-methyl Methylsulphon, DEP, Deparethrin, Derris, Desmedipham, Desmetryn, Desmetryne, D-Fansilk Ebinge Juzi (fanshiluquebingjuzhi), diafenthiuron, dialifol, dialifos, jia Diallate, di-allate, diamidaphos, dianat, diatomaceous earth, silica Algae rock, diazinon, dibromide, dibutyl phthalate, dibutyl succinate, dicamba, zika apton, dichlobenil, diclobenthiazox, diclofenthion, dichlofluanid , Dichloron, Dichloralurea, Dichlorbenzuron, Dichlorphenidim, Dichlorf Lurecol, dichloroflurenol, dichlormate, dichlormid, dichloromethane, di Chlorphen, dichlorprop, dichlorprop-P, dichlorvos, dichlozolin (dichlozolin), dichlozoline, diclobutrazol, diclocimetidine diclofop, diclomedine, dicloran, dichloromezothiazol, diclosulam, Cofol, dicophane, dicoumarol, dicresyl, dicrotophos, dicri dicyclanil, dicyclonon, dieldrin, dieno Chlor, Diethamcoat, Dieththyl, Diethion, Diethion ), Diethofencarb, Dietholate, Diethon, Diethyl Pyrocarbonate, Diethyltulure Mido, Difenacoum, Difenoconazole, Difenopentene, Difenoxuron, Di Fenzoquat, difethialone, diflobidazine, diflubenzuron, diflufenica diflufenicanil, diflufenzopyr, diflumetrim, dikeglac, Ziro Dimatif, Dimefluthrin, Dimefox, Dimeflon, Dimehypo, Dimepipere Dimethachlone, dimethan, dimethacarb, dimethachlone hlone), dimethachlor, dimethamethrin, dimethenamid, dimethenamid-P, dimethine Pine, dimethirimol, dimethoate, dimethomorph, dimethrine, dimethylcarbamate , dimethyl disulfide, dimethyl phthalate, dimethylvinphos, dimethyllan, dimexa No, Dimidazon, Dimoxystrobin, Dimpirate, Dimuron, Gine Xu, Jingu Junezuo, Diniconazole, Diniconazole-M, Dinitramine, Dinitr Lofenol, Dinobuton, Dinocap, Dinocap-4, Dinocap-6, Dinoctone , Dinophenate, Dinopentone, Dinoprop, Dinosam, Dinoseb, Dinosulfone, Dinotefuran, dinoterb, dinoterbone, diofenolan, dioxabenzophos, dio Xacarb, dioxathion, dioxation, difacine diphenamide, diphacinone, diphenadione, diphenamide, diph enamide), diphenyl sulfone, diphenylamine, diphenyl sulfide, diprog Dipropionate, Dipropetrine, Dipterex, Dipimethitron, Dipyrithione , diquat, disodium tetraborate, disosultap, disparlure, di Sugran, Disul, Disulfiram, Disulfoton, Ditalimphos, Dithianon, Dichik Rohos, dithioether, dithiometon, dithiopyr, diuron, dixanthogen, d- Limonene, DMDS, DMPA, DNOC, Dodemorph, Dodzin, Dodine, Dofenapi N, Doguazine, Dominicalle, Doramectin, DPC, Drazoxolone, DSMA, d -Trans-allethrin, d-trans-resmethrin, Zuflin, Dymron ), EBEP, EBP, Ebufos, Ecdysterone, Eclomezole, EDB, EDC, EDDP, edifenphos, eglinadin, emamectin, EMPC, empenthrin, Enadenine, endosulfan, endothal, endothall ), Endothion, Endrin, Enestrobulin, Enilconazole, Enoxastrol Bin, Efilsulfonate, EPN, Epocholeon, Epofenonane, Epoxyconazo Eprinomectin, Epronaz, Epsilon-Metofluthrin, Epsilon-Mon Fluorotrin, EPTC, Ervon, Ergocalciferol, Elludioxycaoa , esdeparethrin, esfenvalerate, ESP, esprocarb, etaceracil , etaconazole, etaphos, etem, ethaboxam, ethaclor, ethalfluralin , ethametsulfuron, ethaprochlor, ethephon, etidimuron, ethiofencal Bu, Ethiolate, Ethion, Ethiozine, Ethiprole, Ethirimol, Ethoate Methyl, etobenzanide, ethofumesate, ethohexadiol, etho Propylene glycol, ethoprophos, ethoxyphene, ethoxyquin, ethoxysulfuron, ethix Roseate, Ethyl Formate, Ethyl Pyrophosphate, Ethylane, Ethyl-DDD, Ethylene, Dibromide Ethylene chloride, ethylene dichloride, ethylene oxide, ethylmercury 2,3-dichloride Hydroxypropyl mercaptide, ethyl mercury acetate, ethyl mercury bromide, ethyl mercury chloride, Ethylmercuric phosphate, ethinofen, ETM, etonipromide, etobenzanide d), etofenprox, etoxazole, etridiazole, etrimfos (etrim fos), etrimphos, eugenol, EXD, famoxadone, Famfu Fenamine, Fenac, Fenamidon, Fenaminosulf, Fenaminestrobin, Fena Mifos, fenapanil, fenarimol, fenashlam, fenazaflor, fenazaquin , fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorphos, Fenclofos, fenclorim, fenetacarb, fenfluthrin, fenfuram, Fenhexamid, phenidine, fenitropan, fenitrothion, phenisone, fe Njuntong, fenobucarb, fenorobo, fenoprop, fenothiocarb, f Fenoxacrim, Fenoxanil, Fenoxaprop, Fenoxaprop-P, Fenoxacrim Noxasulfone, fenoxycarb, fenpiclonil, fenpyrithrin, fenpro Patrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroxy Mate, Fenquinotrione, Fenridazon, Fensone, Fensulfothion, Fen Nteracol, fenthiaprop, fenthion, fenthion-ethion Fentiaprop, fentin, fentrazamide, fentrif Fenil, Fenuron, Fenuron-TCA, Fenvalerate, Ferbam, Felimzo ferric phosphate, ferrous sulfate, fipronil, flamprop, flamprop-M, Flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, flonamor Rupiruxifen, Fluacrypyrim, Fluazaindolizine, Fluazifop, Flu Azifop-P, fluazinam, fluazolate, fluazuron, flubendiamide, Rubendimine, flubrocythrinate, flucarbazone, flucetosulfuron, fluclox Larin, Flucofuron, Flucycloxuron, Flucythrinate, Fludioxonil, Fluenethyl, fluenetil, fluensulfone, flufe Nacet, Flufenerim, Flufenican, Flufenoxuron, Flufenoxyst Robin, Flufenprox, Flufenpyr, Flufenzin, Flufiprole, Fluhexafon, Flumethrin, Flumetobel, Flumetralin, Flumetsulam, Flume Flumiclorac, Flumioxazin, Flumipropion, Flumorph, Fluometz Ron, Fluopicolide, Fluopyram, Fluobenside, Fluoride amide, Fluoroa Cetamide, fluoroacetic acid, fluorochloridone, fluorodifen, fluoroglycophen Fluorimide, Fluoromidine, Fluoronitrofen, Fluoroxin Sipil, Fluothiuron, Fluotrimazole, Fluoxastrobin, Flupoxam, Flupropacil, Flupropazine, Flupropanate, Flupyradifurone, Flupyrsul CFC, fluquinconazole, fluralaner, flurazole, flurecol, flureno Fluridone, Flurochloridone, Fluromidine, Fluroxypyr, Flurprimido Flusulfamide, Flutamone, Flusilazole, Flusulfamide, Flutendi fluthiacet, fluthiamide, flutianil, flutolanil, flutriafol, Fluvalinate, fluxametamide, fluxapyroxad, fluxofenim, forper , folpet, fomesafen, fonofos, foramsulfuron, forchlorfenuron , formaldehyde, formetanate, formothion, formparanate, fosamine, fo Cetyl (fosetyl), fosmetilan, fospirate, fosthiazate, fostietan, Rontalin, Fusalide, Fuberidazole, Fukaojin, Fukaomi, Fujunmanchi, Fu Rumi, Fumarine, Funaihekaoring, Fufenthiourea, Furaran, Furalaxyl, furametrin, furametpyr, furan tebufenozide, furathiocarb, furucarbanil , fluconazole, fluconazole-cis, freslin, furfural, furilazole, Flumecyclox, furophanate, furiloxifene, gamma-BHC, gamma-C Halothrin, gamma-HCH, genit, gibberellic acid, gibberellin A3, gibberellin, Griftol, Gritol, Glucochloralose, Glufosinate, Glufosinate-P, Glyodin, glyoxime, glyphosate, glyphosine, gossip lure, grand lure, Griseofulvin, guanectin, guazatine, halacrinate, haloxifene, ha Rufenprox, halofenozide, halosaphen, halosufuron, haloxydine, Haloxyfop, haloxyfop-P, haloxyfop-R, HCA, HCB, HCH, Hemel, Hempa, HEOD, Heptachlor, Heptafluthrin, Heptenophos, Heptopa Lugil, Herbimycin, Herbimycin A, Heterofos, Hexachlor, Hexachlor hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachloro Rolofen, hexaconazole, hexaflumuron, hexafluoramine, hexaflur hexalure, hexamide, hexazinone, hexylthiophos, hexythiazox, HHDN, Holosulf, Homobrassinolide, Huangkaiwo, Huangchongjing, Hu Ankaolin, Huangjunzuo, Hydramethylnon, Hydralgaphen, Slaked lime, Hydrogen Cyanamide, hydrogen cyanide, hydroprene, hydroxyisoxazole, hymexazole , Hikincarb, IAA, IBA, IBP, Icaridin, Imazalil, Imazamethabenz , Imazamox, Imazapic, Imazapyr, Imazaquin, Imazethapyr, Imazosul CFCs, imibenconazole, imidazole, imidacloprid, imidacloth, imidacloprid Noctadine, Imiprothrin, Inabenfide, Indanofan, Indaziflam, In Doxacarb, Inedin, Infusoria soil, Iodobornyl, Iodocarb, Iodofenphos, Iodo Iodomethane, iodosulfuron, iofensulfuron, ioxynil, ipazine, I PC, ipconazole, ipfencarbazone, ipfentrifluconazole, ipro Benhos, Iprodione, Iprovalicarb, Iprimidum, Ipsdienol, Ipse Nol, IPSP, IPX, Isamidophos, Isazophos, Isobenzane, Isocarbamide (isocarbamid), isocarbamide, isocarbophos, isosyl, iso Dorin, Isofenphos, Isofenphos-methyl, Isofetamide, Isorane, Isome Thiozin, Isonoruron, Isopamphos, Isoporinate, Isoprocarb, Isoproxin Isopropyl isopropazole, isoprothiolane, isoproturon, isopyrazam, isopirimo ol, isothioate, isotianil, isouron, isovalerion, isoxaben, Soxaclortol, Isoxadifen, Isoxaflutole, Isoxapyrifop, Isochlortol Soxathion, Islon, Ivermectin, Isoxaben, Izopanfos , Izopanhos, Japonirua, Japotrins, Jasmolin I, Ja Sumolin II, jasmonic acid, diazhizenxiaorin, diazhizenxiaorin Axiangjunji, Jiekaowan, Jiekaoxi, Jinggangmycin A, Iodophen Juvenile hormone I, juvenile hormone II, juvenile hormone III, kappa -Bifenthrin, kappa-tefluthrin, carbutyrate, caletazan, kasugamai Kejunrin, Kereban, Ketospiradox, Diatomaceous Earth, Kinetin, Kinoprene, Kinetin Laraxyl, kresoxim-methyl, quicaoxy, lactofen, lambda-cyhalotri Lancotrione, Latilia, Lead Arsenate, Lenacil, Lepimectin, Leptophos, Lian Benzinchu, lime sulfur mixture, lindane, lineatin, linuron, lilinphos, litol A, Lupu Lua, Lufenuron, Lufuqingchongxianan, Luxiang Kaolin, Lubjing Junchi, Lubfumi Jibuchi, Lubxian Kaolin, Lichi Dathion, M-74, M-81, MAA, magnesium phosphide, malathion, Margisone , Maleic hydrazide, Malonophen, Maltodextrin, MAMA, Mancopper, Mancozeb, mandestrobin, mandipropamide, maneb, matrine, magidox, MCC, MCP, MCPA, MCPA-thioethyl, MCPB, MCPP, mebenyl, mebenyl Carbam, mecarbinzide, mecarfone, mecoprop, mecoprop-P, medimefol mefenacet, mefenoxam, mefenpyr, mefe Ntrifluconazole, Mefluidide, Megatomoic acid, Melissyl alcohol, Mellitoxin , MEMC, Menasone, MEP, Mepanipyrim, Meperfluthrin, Mephenate, Mefox Suhoran, Mepiquat, Mepronil, Meptyldinocap, Mercaptodimetr, Merca Putophos, mercaptophos thiol, mercaptothione, mercuric chloride, mercuric oxide, Mercurous chloride, merphos, merphos oxide, mesoprazine, mesosulfuron, mesotri mesulfen, mesulfenphos, mesulfen, mesulfen Tacresol, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metaldehyde Tam, Metamifop, Metamitron, Metaphos, Metaxone, Metazachlor, Metazos Lufron, metazoxolone, metconazole, metepa, metoflurane, methabenzthia Zulon, methacrifos, methalproparin, metham, methamidophos, methasulfocarb, Methazole, metofloxam, methybenzuron, methidathion, methiobencarb, methy Ocarb, thiopyrisulfuron, methiotepa, methiozolin, methiuron, metoclotopho metolcarb, metometon, methomyl, methoprene, metoprothrin ), metoprothrin, methoquin-butyl, methothrin, methoxychlor methyl aphorate, methyl bromide, methyl o Igenol, methyl iodide, methyl isothiocyanate, methyl parathion, methyl acetonitrile Phos, methyl chloroform, methyl dithiocarbamate, methyl dymron, methylene chloride Methyl-isofenphos, methylmercaptophos, methylmercaptophos oxide, Methylmercaptophosthiol, methylmercury benzoate, methylmercury dicyandiamide , methylmercury pentachlorophenoxide, methyl neodecaneamide, methyl nitrophos, Methyltriazothion, methiozoline, metiram, metiram-zinc, metobenzuron, me Tobromuron, metofluthrin, metolachlor, metolcarb, metometuron, metomi Nostrobin, Metosulam, Methoxadiazone, Metoxuron, Metrafenone, Metri Am, metribuzin, metrifonate, metriphonate ), metsulfobax, metsulfuron, mevinphos, mexacarbate, miesch Wei, Mie Shuang, Mie Wen Zhuchi, Milbemectin, Milbemycin oxime, Milneb, Mimanan, Mipafox, MIPC, Mylex, MNAF , Mogchun, Molinate, Morosultap, Monfluorotrin, Monalid, Monis monochloroacetic acid, monocrotophos, monolinuron, monomethyproline , Monosulfiram, Monosulfuron, Monosultap, Monuron, Monuron-TC A, Morphamcort, Moroxydine, Morphothion, Morzide, Moxidectin, MP MC, MSMA, MTMC, Muscarua, Myclobutanil, Myclozolin, Myricial Cole, N-(ethylmercury)-p-toluenesulfonanilide, NAA, NAAm, Naba Naphthalophos, Naled, Naphthalene, Naphthaleneacetamide, Naphthalic anhydride, Naphthalophos, naphthoxyacetic acid, naphthylacetic acid, naphthylindan-1,3-dione, Phthyloxyacetic acid, naproanilide, napropamide, napropamide-M, naptalam, na tamimicin, NBPOS, Nebrair, Nebron, Nendrin, neonicotine, nichlorofo nicol, niclofen, niclosamide, nicobifen, nicosulfuron, nicotine, nicotine sulfate tin, nifluridide, nikkomycin, NIP, nipiraclofen, nipiralofen, Nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen , nitrofluorfen, nitrostyrene, nitrotar-isopropyl, noborumid, Nonanol, norbormide, norea, norflurazon, nornicotine, norlo Novaluron, Noviflumuron, NPA, Nuarimol, Nuranon, OCH, Octaclo Dipropyl ether, octilinone, o-dichlorobenzene, ofrace, ometoane o-phenylphenol, orbencarb, orfural, orthobencarb, or Dichlorobenzene, orthosulfamuron, oryctalua, orysastrobin, ory Zarin, Osthol, Osthole, Ostramon, Obatron, Obex, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, Oxamate, oxamyl, oxapyrazon, oxapyraz one), oxasulfuron, oxathiapiprolin, oxaziclomefone, oxine-copper , Oxine-Cu, Oxolinic acid, Oxpoconazole, Oxycarboxin, Oxide Meton-methyl, oxydeprophos, oxydisulfoton, oxyenadenine, oxyf Luolfen, oxymatrine, oxytetracycline, oxythioquinox, PA C, Paclobutrazol, Paichondine, Parethrin, PAP, Para-dichlorobenzene , Parafluron, Paraquat, Parathion, Parathion-methyl, Parinol, Parisg Lean, PCNB, PCP, PCP-Na, p-dichlorobenzene, PDJ, pebulate , Pezinex, Pefurazoate, Pelargonic acid, Penconazole, Pencycuron, Pen Dimethalin, Penfenate, Penflufen, Penfluron, Penoxalin, Penox Suslam, pentachlorophenol, pentachlorophenyl laurate, pentanochlor Penthiopyrad, Pentomethrin, Pentoxazone, Perchlordecone, Perflui Don, Permethrin, Petoxamid, PHC, Fenamacryl, Fenamacryl-ethyl , Fenaminosulf, Phenazine oxide, Fenetacarb, Fenisopham, Fenca Phenoplon, Phenmedipham, Phenmedipham-ethyl, Fenobenzuron, Fenobenzuron Thiol, fenothrin, fenproxide, phenthoate, phenylmercury urea, acetic acid Phenylmercury, phenylmercury chloride, phenylmercury derivatives of pyrocatechol, phenyl nitrate Mercury, phenylmercuric salicylate, phorate, fosacetin, phosalone, fosamethin, fosaze fosazetim, foscyclotin, phosdifen, fosetyl, phosphoramidite Phosphorane, Phosphorane-methyl, Phosglycine, Phosmet, Phosniclor, Phosphamide, Phosphamidon, Phosphine, Phosphinothricin, Phosphocarb, Phosphate, Phostin, Phosphamidon Oxime, phoxim-methyl, phthalide, phthalophos, phthalthrin, picarbutrazox , picaridin, picloram, picolinafen, picoxystrobin, pimaricin, pindo pinoxaden, piperaline, piperazine, piperonyl butoxide, piperonyl cyclohexyl Nene, piperophos, piproctanly, piproctanyl, Piprotal, pirimetaphos, pirimicarb, piriminyl, pirimiox Cyphos, Pirimiphos-ethyl, Pirimiphos-methyl, Pival, Pivaldione, Purife Polycarbonate, PMA, PMP, polybutene, polycarbamate, polychlorocamphene, poly Ethoxyquinoline, Polyoxin D, Polyoxin, Polyoxorim, Polythialan, Nitrous Potassium arsenate, potassium azide, potassium cyanate, potassium ethyl xanthate, sodium Potassium phthalate, potassium polysulfide, potassium thiocyanate, pp'-DDT, Praleto Phosphorus, Precocene I, Precocene II, Precocene III, Pretilachlor, Primid Primidophos, primisulfuron, probenazole, prochloraz, proclono ol, procyazin, procymidone, prodiamine, profenofos, profluazole , Profluralin, Profluthrin, Profoxydim, Proflit-Aminium, Pro Glynadin, Prohexadione, Prohydrojasmone, Promacyl, Promecarb, Pro Rometon, prometryn, prometryne, promrit, Pronamide, propachlor, propafos, propamidine, propamocarb , propanil, propaphos, propaquizafop, propargite, propa rusulin, propazine, propetamphos, propham, propiconazole, propizine, Propineb, propisochlor, propoxor, propoxycarbazone, propylisom, Propyrisulfuron, propyzamide, proquinazide, prosrel, prosulfarin, pro Rosulfocarb, prosulfuron, prothidathion, prothiocarb, prothioconazole Prothiofos, Protoate, Protrifenbut, Proxan, Primidophos (pr ymidophos), prinachlor, psoralen, psoralene, pi Danone, pydiflumetofen, piflubumid, pymetrozine, pyracarbollide, pyraclo Phos, pyraclonil, pyraclostrobin, pyraflufen, pyrafluprole, pyrama pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyraziflumid , pyrazolate, pyrazolinate, pyrazone, pyrazophos, pyrazosulfuron, pyrazot On, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrin , Pyribambenz-isopropyl, Pyribambenz-propyl, Pyribencarb, Piribe Nzoxime, pyributicarb, pyrichlor, pyridaben, pyridafol, pyridalyl, Pyridaphenthion, pyridaphenthion, pyridaphenthion ridate, pyridinitrile, pyrifenox, pyrifluquinazone, pyriftalid, pyri Metaphos, pyrimethanil, pirimicarb, pyrimidifen, pyriminova Pirimiphos-ethyl, Pirimiphos-methyl, Pirimisulfa Pyrimithate, Pyrinuron, Pyriophenone, Pyriprole, Pyripropanol, Pyriprole Riproxifen, pyrisoxazole, pyrithiobac, pyrrolan, pyroquilon, pyroxine Sasulfon, Piroxsulam, Piroxchlor, Piroxiflur, Kinkaosuan, King Kling, Cassia , quinacetol, quinalphos, quinalphos-methyl, quinazamide, quinclorac, quin Conazole, quinmelac, quinoclamine, quinofumelin, quinomethionate, quinonami Do, quinothione, quinoxyfen, quinthiofos, quintozene, quizalofop, quizalofop Rup-P, Quench, Quingzing, Rabenzazole, Rafoxanide, R-Zinico Nazol, Levemid, Reglon, Lenriduron, Lescale, Resmethrin, Rodetani Rhodethanil, Rhodojaponin-III, Ribavirin, Rimsulfuron, Rizazo R-metalaxyl, rodetanil, ronnel, rotenone, riania, sa Bajra, Saflufenacil, Saijunmao, Saisentong, Salicylanilide, Sali Fluofen, sanguinarine, santonin, S-bioallethrin, Schrader, Cirilo Cid, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, sesa Mex, Sesamolin, Sesone, Sethoxydim, Sevin, Shuangjiaan Kaolin, Shuangjianan Kaolin, S-Hydroprene, Siduron, Sifumijibuchi, Sigurua , silafluofen, silatrane, silica aerogel, silica gel, silthiofam (si lthiofam, silthiopham, silthiophan, Silvex, Shimaji simeconazole, simeton, simetryn, simetryne, Synthophene, S-kinoprene, hydrated lime, SMA, S-methoprene, S-metolachlor , sodium arsenite, sodium azide, sodium chlorate, sodium cyanide, fluoride Sodium chloride, sodium fluoroacetate, sodium hexafluorosilicate, naphthenic acid Sodium, Sodium o-phenylphenoxide, Sodium orthophenylphenoxide Cid, Sodium Pentachlorophenol, Sodium Pentachlorophenoxide, Polysulfur Sodium fluoride, sodium silicofluoride, sodium tetrathiocarbonate, sodium thiocyanate Um, Solan, Sofamid, Spinetoram, Spinosad, Spirodiclofen, Spirome Sifen, spirotetramat, spiroxamine, stirophos, streptomycin, streptomycin Liquinine, sulcatol, sulcofuron, sulcotrione, sulfurate, sulfe thorazone, sulfiram, sulfuramide, sulfodiazole, sulfometuron, sulfuramide Sulfosate, sulfosulfuron, sulfotep, sulfotep fotepp), sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfur fluoride sulphur, sulglicapine, sulfosate, sulprofos, sultropene, Epp, tau-fluvalinate, tablon, tazimcarb, TBTO, TBZ, TCA, TCBA, TCMTB, TCNB, TDE, tebuconazole, tebufenozide, tebufe ampirad, tebufloquine, tebupirimfos, tebutam, tebuthiuron, tecloftalam, Tecnazen, Tecoram, Tedione, Teflubenzuron, Tefluthrin, Tefurtrione , tembotrione, temefos, temephos, tepa, TEPP, te Praroxydim, Teproxydim, Teralethrin, Terbacil, Terbucarb, Terbu Chlor, terbufos, terbumeton, terbuthylazine, terbutol, terbutryn (te rbutryn), terbutryne, terachlor, terramicin, Terramycin, tetracycline, tetrachloroethane, tetrachlorbine Phos, Tetraconazole, Tetradifon, Tetradisulf, Tetrafluron, Tetrametri Tetramethylfluthrin, Tetramine, Tetranactin, Tetraniliprol, Tet Rapion, tetrasul, thallium sulfate, thallium sulphate sulfate), thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid Thiadiazine, thiadifluor, thiamethoxam, thiameturon, tiapronil, Azafluron, thiazafluron, thiazone, thiazopyridine ru, cyclophos, thithiofen, thidiazimine, thidiazuron, thiencarbazone, thif Ensulfuron, Thifluzamide, Thimerosal, Thimet, Thiobencarb, Thiocarb oxime, thiochlorfenphim, thiochlorfenphim chlorphenphime), thiocyanatodinitrobenzene, thiocyclam, thiodan, thiodia Zol-copper, thiodicarb, thiofanocarb, thiofanox, thiofluoxime Thiometon, thiophene, thiomersal, thiometon, thionazine, thiophanate, thiofa nate-ethyl, thiophanate-methyl, thiophos, thioquinox, thiosemicarba Zide, thiosultap, thiotepa, thioxamyl, thiram, thiram, thuringien thiazin, thiabendazole, tiadinil, thiaphenacyl, thiaodian, TIBA, Fatol, thiocarbazil, thiochlorim, thioxazafen, tioximide, tilpa methylpropional, TMTD, tolclofos-methyl, tolfenpyrad, tolprocarb, tolpira Late, trifluanid, tolylfluanid, tolylmercuric acetate, tomaline, topramezone , toxaphene, TPN, tralkoxydim, tralocitrin, tralomethrin, tralo Piril, transfluthrin, transpermethrin, tretam, triacontanol , triadimefon, triadimenol, triafamone, triallate, Triallate, triamiphos, triapentenol, triaten, tri Alimol, triasulfuron, triazamate, triazbutyl, triaziflam, Riazofos, triazothion, triazoxide, tribasic copper chloride, tribasic copper sulfate, tri Benuron, tribufos, tributyltin oxide, tricamba, trichlamide, trichlor Trichlopyr, trichlorfon, trichlormethaphos-3, trichlormethaphos chloronate, trichloronat, trichlorotrichloro Nitrobenzene, trichlorphon, triclopyr, tri Clopyricarb, tricresol, tricyclazole, tricyclohexyltin hydroxide, Tridemorph, Tridiphan, Trietazine, Trifenmorph, Trifenofos, Tri Floxystrobin, trifloxyflufurone, trifludimoxazine, triflumezopy Rim, Triflumizole, Triflumuron, Trifluralin, Triflusulfuron, Tri Hops, Trifopsim, Triforine, Trihydroxytriazine, Trimedrua, Trime Tacarb, trimeturon, trinexapac, triphenyltin, triplen, triplo Pindan, Triptolide, Tritac, Trithialan, Triticonazole, Tritosulf Ron, Trunk-Cole, Tsoyelin, Uniconazole, Uniconazole-P, Ulva Cid, Uredep, Valerate, Validamycin, Validamycin A, Valifenalate, Ba Ron, Vamidothion, Vanguard, Vaniliprole, Vernalate, Vinclozolin, Tamin D3, warfarin, Xiaochunliurin, Xinchunan, Siwochun-a Xylamine, Xylenol, Xylamine, Xylamine, Xylamine, Xylamine Azole, Ishidin, Zarilamide, Zeatin, Zengxiaoan, Zengxiaorin , Zeta-cypermethrin, Zinc naphthenate, Zinc phosphide, Zinc thiazole, Thiozole Zinc, zinc trichlorophenol, zinc trichlorophenoxide, zineb, ziram, zolapro Hos, Zucoumarin, Zoxamide, Tsoanthunzi, Tsocaoan, Tsoanthunzi , Zuomi Huanglong, α-chlorohydrin, α-ecdysone, α-multistria tin, α-naphthylacetic acid and β-ecdysone; (2) The following molecule (a) N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl )-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide ( Hereinafter referred to as "AI-1")

[0015] [ka]

[0016] (b) the following structure:

[0017] [ka]

[0018] the molecule known as lotilaner, which has the formula:

[0019] (c) The following molecules in Table A:

[0020] [Table 1-1]

[0021] [Table 1-2]

[0022] As used in this disclosure, each of the above is an active ingredient. information, including the online version of "The Pesticide Manual" (at bcpcdata.com) See the "Compendium of Pesticide Common Names" and its various editions at Alanwood.net I would like you to think about it.

[0023] Particularly preferred selected active ingredients are 1,3-dichloropropene, chlorpyrifos, Xaflumuron, methoxyfenozide, noviflumuron, spinetoram, spinosad and and sulfoxaflor (hereinafter referred to as "AIGA-2").

[0024] Additionally, other particularly preferred selected active ingredients include acequinocyl, acetamiprid, acequinocyl ... Cetoprol, avermectin, azinphos-methyl, bifenazate, bifenthrin , carbaryl, carbofuran, chlorfenapyr, chlorfluazuron, chromafenazi Do, clothianidin, cyfluthrin, cypermethrin, deltamethrin, diafenthin Ron, Emamectin Benzoate, Endosulfan, Esfenvalerate, Ethipro ru, etoxazole, fipronil, flonicamid, fluacrypyrim, gamma-cyhalo thrin, halofenozide, indoxacarb, lambda-cyhalothrin, lufenuron, Lathion, methomyl, novaluron, permethrin, pyridalyl, pyrimidifen, spiro Diclofen, tebufenozide, thiacloprid, thiamethoxam, thiodicarb, tolu Fenpyrad and zeta-cypermethrin (hereinafter referred to as "AIGA-3") .

[0025] The term "alkenyl" refers to an acyclic, unsaturated (at least Branched or unbranched substituents of the carbon-carbon double bond, e.g., vinyl, It means allyl, butenyl, pentenyl and hexenyl.

[0026] The term "alkenyloxy" refers to an alkenyl having an additional carbon-oxygen single bond, e.g. For example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy .

[0027] The term "alkoxy" refers to an alkyl having an additional carbon-oxygen single bond, e.g., methyl ethoxy, propoxy, isopropoxy, butoxy, isobutoxy and tert-butyloxy. It means t-butoxy.

[0028] The term "alkyl" refers to an acyclic, saturated, branched or unbranched alkyl group consisting of carbon and hydrogen. is an unbranched substituent, for example, methyl, ethyl, propyl, isopropyl, butyl, and It means tert-butyl.

[0029] The term "alkynyl" refers to an acyclic, unsaturated (at least branched or unbranched substituents of one or more carbon-carbon triple bonds, such as ethynyl, It means propargyl, butynyl and pentynyl.

[0030] The term "alkynyloxy" refers to an alkynyl having an additional carbon-oxygen single bond, e.g. For example, pentynyloxy, hexynyloxy, heptynyloxy and octynyloxy. means.

[0031] The term "aryl" refers to a cyclic, aromatic substituent consisting of hydrogen and carbon, e.g., Examples include phenyl, naphthyl and biphenyl.

[0032] The term "biopesticide" is generally applied in the same way as chemical pesticides. Usually these are bacteria, but Trichoderma spp. and Ampelomyces quiscalis Examples of well-known biopesticides include scale fungus, Pseudomonas quisqualis. It is a bacterial disease of the orders Lepidoptera, Coleoptera and Diptera. The Bacillus species is a type of biopesticide. For example, Metarhizium anisopliae, entomopathogenic nematodes ( For example, Steinernema feltiae, and entomopathogenic fungi Based on viruses (e.g., Cydia pomonella granulovirus) Other examples of entomopathogenic organisms include, but are not limited to, insect pathogens. For the avoidance of doubt, biocides include: The biocide is the active ingredient.

[0033] The term "cycloalkenyl" refers to a monocyclic or polycyclic alkenyl group consisting of carbon and hydrogen. , unsaturated (at least one carbon-carbon double bond) substituents, such as cyclobutenyl, Cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl means tetrahydronaphthyl, hexahydronaphthyl and octahydronaphthyl do.

[0034] The term "cycloalkenyloxy" refers to a cycloalkenyl group containing an additional carbon-oxygen single bond. Alkenyl, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy The term "bicyclo[2.2.2]octenyloxy" refers to cyclo[2.2.2]octenyloxy and bicyclo[2.2.2]octenyloxy.

[0035] The term "cycloalkyl" refers to a monocyclic or polycyclic ring system consisting of carbon and hydrogen. Saturated substituents, such as cyclopropyl, cyclobutyl, cyclopentyl, norbornyl , bicyclo[2.2.2]octyl and decahydronaphthyl.

[0036] The term "cycloalkoxy" refers to a cycloalkyl group having an additional carbon-oxygen single bond. , for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, means runyloxy and bicyclo[2.2.2]octyloxy.

[0037] The term "halo" means fluoro, chloro, bromo and iodo.

[0038] The term "haloalkoxy" further includes from one to the maximum possible number of identical or different alkyl groups. Alkoxy having a halo such as fluoromethoxy, trifluoromethoxy, 2, 2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethane It refers to trifluoroethoxy and pentafluoroethoxy.

[0039] The term "haloalkyl" further includes from one to the maximum possible number of identical or different alkyl groups. alkyl having a halo, for example, fluoromethyl, trifluoromethyl, 2,2-difluoromethyl, Fluoropropyl, chloromethyl, trichloromethyl and 1,1,2,2-tetrafluoro It means ethyl.

[0040] The term "heterocyclyl" refers to any group that is aromatic, fully saturated, or partially or completely saturated. means a cyclic substituent, which may be unsaturated, where the cyclic structure has at least one carbon atom and at least one heteroatom, said heteroatom being nitrogen, sulfur or oxygen An example is: (1) Aromatic heterocyclyl substituents include, but are not limited to, benzofuranosides, nyl, benzisothiazolyl, benzisoxazolyl, benzothienyl, benzothiazo aryl, benzoxazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, Indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl Sadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, chiral, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, tri azinyl, and triazolyl; (2) Fully saturated heterocyclyl substituents include, but are not limited to, piperazine. Razinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl and tetrahydrofuranyl tetrahydropyranyl; (3) Partially or fully unsaturated heterocyclyl substituents are limited but not 4,5-dihydro-isoxazolyl, 4,5-dihydro-oxazolyl, 4,5-Dihydro-1H-pyrazolyl, 2,3-dihydro-[1,3,4]-oxadiazol- zolyl and 1,2,3,4-tetrahydroquinolinyl; and (4) Additional examples of heterocyclyl include:

[0041] [ka]

[0042] The term "area" refers to an area in which a pest is growing, may grow, or may pass through. A territory means a habitat, breeding ground, plant, seed, soil, material or environment. crops, trees, fruits, grains, fodder species, vines, turf and / or ornamental plants areas where things grow; areas where livestock live; interior or exterior surfaces of buildings (where crops grow) storage places, etc.); construction materials used in buildings (impregnated wood, etc.); and buildings The soil surrounding the

[0043] The term "MoA substance" is used by IRAC at irac-online.org. Means an active ingredient having a mechanism of action ("MoA") as shown in the MoA Classification 7.4 edition, and A group of

[0044] (1) Acetylcholinesterase (AChE) inhibitors, which contain the following active ingredients: Phate, Alanycarb, Aldicarb, Azamethiphos, Azinphos-ethyl, Azinphos -methyl, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim Sim, cadusafos, carbaryl, carbofuran, carbosulfan, chlorethoxyphos , chlorfenvinphos, chlormephos, chlorpyrifos, chlorpyrifos-methyl, Mahos, Cyanophos, Demeton-S-methyl, Diazinon, Dichlorvos / DDVP, Dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethiphen Carb, Ethion, Ethoprophos, Famfur, Fenamiphos, Fenitrothion, F Fenobcarb, fenthion, formetanate, fosthiazate, furathiocarb, hep Tenofos, Imicyaphos, Isofenphos, Isoprocarb, Isopropyl O-(methoxamer) (Ciaminothio-phosphoryl) salicylate, isoxathion, malathion, mecarbam, Methamidophos, methidathion, methiocarb, methomyl, metolcarb, mevinphos, mo Nocrotophos, naled, omethoate, oxamyl, oxydemeton-methyl, parathiol Parathion, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphatase Midon, Phoxim, Pirimicarb, Pirimiphos-methyl, Profenofos, Propetamfo s, propoxar, prothiofos, pyraclofos, pyridaphenthion, quinalphos, s Ruhotep, tebupirimphos, temephos, terbufos, tetrachlorvinphos, thiodicar Bu, thiofanox, thiometon, triazamate, triazophos, trichlorfon, Includes trimethacarb, vamidothion, XMC and xylylcarb.

[0045] (2) GABA-gated chloride channel antagonists, which are the following active ingredients: These include dane, endosulfan, ethiprole and fipronil.

[0046] (3) Sodium channel modulators, which include the following active ingredients: acrinathrin, Allethrin, d-cis-trans-allethrin, d-trans-allethrin, Bifent Phosphorus, Bioallethrin, Bioallethrin-S-cyclopentenyl, Bioresmethrin, Chloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin thrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, beta- Cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin [ (1R)-trans isomer], deltamethrin, empenthrin [(EZ)-(1R) isomer] Sexual form], esfenvalerate, ethofenprox, fenpropathrin, fenba Rhelate, flucythrinate, flumethrin, tau-fluvalinate, Halfenpro ox, imiprothrin, kadethrin, permethrin, phenothrin [(1R)-trans isomers], prallethrin, pyrethrins (Ceratitis gracile), resmethrin, silafluof phen, tefluthrin, tetramethrin, tetramethrin [(1R) isomer], tralomet Phosphorus, and transfluthrin, and methoxychlor.

[0047] (4) Nicotinic acetylcholine receptor (nAChR) agonists, which have the following active components: Includes minutes. (4A) Acetamiprid, clothianidin, dinotefuran, imidacloprid, niten Pyram, thiacloprid, thiamethoxam, (4B) Nicotine, (4C) sulfoxaflor, (4D) flupyradifurone, (4E) Triflumezopyrim and dichloromezothiaz.

[0048] (5) Nicotinic acetylcholine receptor (nAChR) allosteric activators, which contains the following active ingredients: spinetoram and spinosad.

[0049] (6) Chloride channel activators, which contain the following active ingredients: abamectin, emame Includes cutin benzoate, lepimectin and milbemectin.

[0050] (7) Juvenile hormone mimetics, including the following active ingredients: hydroprene, kinoprene, methotrexate, These include phenoxycarb, fenoxycarb, and pyriproxyfen.

[0051] (8) Various non-specific (multi-site) inhibitors, including the following active ingredients: methyl bromide, chloramphenicol, Chloropicrin, sulfuryl fluoride, borax, boric acid, disodium octaborate, sodium borate Contains sodium, sodium metaborate, tartar emetic, dazomet, and metam.

[0052] (9) Chordotonal organ modulators, which include the following active ingredients: pymetrozine and flonizine Contains amide.

[0053] (10) Mite growth inhibitors, which include the following active ingredients: clofentezine, hexythiazoline Contains benzodiazepine, diflobidazine and etoxazole.

[0054] (11) Microbial disruptors of insect midgut membranes, which contain the following active ingredients: Bacillus thuringiensis Bacillus thuringiensis subsp. israelensis, Bacillus thuringiensis subsp. aizawai ), Bacillus thuringiensis subsp. kurstaki (Bacillus thuringiensis subsp. kurstaki), Bacillus thuringiensis subspecies tenebrionensis (Bacillus thuringie nsis subsp. tenebrionenis), Bt crop proteins (Cry1Ab, Cry1Ac, C ry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3 Ab, Cry3Bb, Cry34Ab1 / Cry35Ab1) and Bacillus sphaeroides Contains Bacillus sphaericus.

[0055] (12) Mitochondrial ATP synthase inhibitors, which include the following active ingredients: tetradifon , propargite, azocyclotin, cyhexatin, fenbutatin oxide and diaphen Contains penthiuron.

[0056] (13) Oxidative phosphorylation uncouplers that disrupt the proton gradient, which include the following active ingredients: Contains chlorfenapyr, DNOC, and sulfluramide.

[0057] (14) Nicotinic acetylcholine receptor (nAChR) channel blockers, which are The following active ingredients: Bensultap, Cartap Hydrochloride, Thiocyclam and Thiosultap Contains sodium.

[0058] (15) Chitin biosynthesis inhibitor, type 0, which contains the following active ingredients: bistrifluron, Chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, he Xaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron and Contains triflumuron.

[0059] (16) Chitin biosynthesis inhibitors, type 1, which contain the following active ingredient: buprofezin nothing.

[0060] (17) Dipteran molting disruptors, which contain the following active ingredient: cyromazine.

[0061] (18) Ecdysone receptor agonists, which include the following active ingredients: chromafenozide, Includes halofenozide, methoxyfenozide and tebufenozide.

[0062] (19) Octopamine receptor agonists, which include the following active ingredient: amitraz.

[0063] (20) Mitochondrial electron transport chain complex III inhibitors, which include the following active ingredients: Includes lamethylnon, acequinocyl, and fluacrypyrim.

[0064] (21) Mitochondrial electron transport chain complex I inhibitors, which include the following active ingredients: Kin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolf Includes phenpirad and rotenone.

[0065] (22) Voltage-dependent sodium channel blockers, which contain the following active ingredients: indoxine Includes sacarb and metaflumizone.

[0066] (23) Acetyl CoA carboxylase inhibitors, which are the following active ingredients: Spirodic These include brophene, spiromesifen and spirotetramat.

[0067] (24) Mitochondrial electron transport chain complex IV inhibitors, which contain the following active ingredients: phosphorus acid Includes aluminum, calcium phosphide, phosphine, zinc phosphide and cyanide.

[0068] (25) Mitochondrial electron transport chain complex II inhibitors, which are the following active ingredients: Includes rafen, cyflumetofen and piflubumid.

[0069] (28) Ryanodine receptor modulators, which are the following active ingredients: chlorantranil These include prole, cyantraniliprole and flubendiamide.

[0070] Groups 26 and 27 are not assigned in this version of the classification scheme. In addition, There is a group of UN drugs that contain active ingredients with unknown or unidentified mechanisms of action. This group includes the following active ingredients: Active ingredients, azadirachtin, benzoximate, bifenazate, bromopropylate, These include nomethionate, cryolite, dicofol, pyridalyl and pyrifluquinazone.

[0071] The term "pest" refers to any organism that is harmful to humans or to any matter of human concern (e.g., to crops, food, livestock, etc.). The term "organisms harmful to animals" refers to organisms that are harmful to animals, such as Arthropoda, soft-shelled animals, and soft-shelled animals. They are from the phylum Mollusca or Nematoda. Specific examples are ants, Aphids, bedbugs, beetles, silverfish, caterpillars, cockroaches, crickets, earwigs, fleas, gnats Bugs, grasshoppers, grubs, wasps, jassids, leafhoppers, lice , locusts, maggots, mealybugs, mites, moths, nematodes, mirid bugs, planthoppers, Psyllids, sawflies, scale insects, silverfish, slugs, snails, spiders, and spider bugs Moths, stink bugs, comb bugs, termites, thrips, ticks, wasps, whiteflies and It's a horsehair worm.

[0072] Additional examples are the following pests:

[0073] (1) The subphyla Chelicerata, Myriapoda, and Hexapoda.

[0074] (2) Arachnida, Symphyla, and Insecta.

[0075] (3) Anoplura. A non-exhaustive list of specific genera includes, but is not limited to: However, Haematopinus spp., Hoplopleura spp. ra spp.), Linognathus spp., Pediculus spp. ), Polyplax spp., Solenopotes spp. and and Neohaematopinis spp. A non-exhaustive list of specific species A comprehensive list includes, but is not limited to, Haematopinus asini asini), Haematopinus suis, Linognathus setosus (L Linognathus setosus, Linognathus ovillus, brown fly Human lice (Pediculus humanus capitis), head lice (Pediculus humanus humanus) and An example is Pthirus pubis.

[0076] (4) Coleoptera. A non-exhaustive list of specific genera includes, but is not limited to: However, Acanthoscelides spp., Agriotes spp. es spp.), Anthonomus spp., Apion spp., Apo Apogonia spp., Araecerus spp., Aulacophora Aulacophora spp., Bruchus spp., Cerostelina spp. erna spp.), Cerotoma spp., Ceutorhynchus sp. p.), Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala Cyclocepahla spp., Diabrotica spp., Dinoderus spp. Dinoderus spp., Gnathocerus spp., Hemicoerus spp. elus spp., Heterobostruchus spp., Hypera spp. spp.), Ips spp., Lyctus spp., Megaceris spp. gascelis spp., Meligethes spp., Mezium spp. , Niptus spp., Otiorhynchus spp., Pantomo Pantomorus spp., Phyllophaga spp., Phyllotoreta Phyllotreta spp., Ptinus spp., Rhizotr ogus spp., Rhynchites spp., Rhynchophorus spp. s spp.), Scolytus spp., Sphenophorus spp. p.), Sitophilus spp., Tenebrio spp. and Tribolium spp. A non-exhaustive list of specific species includes: Examples include, but are not limited to, Acanthoscelides obtectus tectus), Agrilus planipennis, Ahasberus ad Ahasverus advena, Alphitobius diaperinus ), Anoplophora glabripennis, Antonomus Anthonomus grandis, Anthrenus verbasci, Anthrenus falvipes, Attaenius spretus aenius spretulus, Atomaria linearis, Atoma Attagenus unicolor, Bothynoderes punctiventris unctiventris), Bean weevil (Bruchus pisorum), Calosobrux maculatus (Cal losobruchus maculatus), chestnut-eared beetle (Carpophilus hemipterus), Cassida Cassida vittata, tobacco leaf beetle (Cathartus quadricollis), Ceratopogon Cerotoma trifurcata, Ceutorhynchus assimilis us assimilis), Ceutorhynchus napi, Conoderus scalarii Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Clio Crioceris asparagi, Cryptolestes f errugineus), Cryptolestes pusillus, Cryptolestes Cryptolestes turcicus, Cylindrocoptulus adespersus (Cylindrocopturus adspersus), Deporaus marginatus , Dermestes lardarius, Dermestes m aculatus), ladybird beetle (Epilachna varivestis), Eubulileta peltata (Eu vrilletta peltata), Faustinus cubae, Hirobius pare Hylobitus pales, Hylotrupes bajulus, Alfalfa Coffee weevil (Hypera postica), coffee flea beetle (Hypothenemus hampei ), cigarette beetle (Lasioderma serricorne), Colorado potato beetle (Leptinotarsa ​​dece mlineata), Limonius canus, Liogenys fuscus fuscus), Liogenys suturalis, rice water weevil (Lisso rhoptrus oryzophilus), the narrow-legged red widow (Lophocateres pusillus), and the rictus Lyctus planicollis, Maecolaspis joli veti), Melanotus communis, Meligetes aeneus gethes aeneus), Melolontha melolontha, red-footed deer Necrobia rufipes, Oberea brevis, Oberea linea Squirrel (Oberea linearis), Taiwanese rhinoceros beetle (Oryctes rhinoceros), giant sawfly Oryzaephilus mercator, Oryzaephilus suriname nsis), Oulema melanopus, rice leaf beetle (Oulema oryza e), Phyllophaga cuyabana, Policaon stoiti ycaon stoutti), Japanese beetle (Popillia japonica), large grain bollworm (Prosteph anus truncatus), Rhyzopertha dominica, Sitna lineatus ( Sitona lineatus, Sitophilus granarius, Coccophyllum Oryzae beetle (Sitophilus oryzae), rice weevil (Sitophilus zeamais), Japanese cereal weevil Stegobium paniceum, red beetle (Tenebroides mauritanicus), red beetle Tribolium castaneum, Tribolium confusum, and Hime Trogoderma granarium, Trogoderma v ariabile), Xestobium rufovillosum and Zabul Examples include Zabrus tenebrioides.

[0077] (5) Dermaptera. A non-exhaustive list of specific species includes, but is not limited to: Although there is no known species, Forficula auricularia is one example.

[0078] (6) Blattaria. A non-exhaustive list of specific species includes but is not limited to: Although not the German cockroach (Blattella germanica), Blattella asahinai (B Lattella asahinai, Blatta orientalis, Turkestan Cockroach (Blatta lateralis), Parcoblatta pennsy lvanica), American cockroach (Periplaneta americana), American cockroach (Periplaneta australasiae), brown cockroach (Periplaneta brunnea), American cockroach (Peripla neta fuliginosa), the Ogasawara cockroach (Pycnoscelus surinamensis) and the Chaobi An example is the cockroach (Supella longipalpa).

[0079] (7) Diptera. A non-exhaustive list of specific genera includes, but is not limited to: However, Aedes spp., Agromyza spp., Anastrepha spp. Anastrepha spp., Anopheles spp., Bactrocera spp. trocera spp.), Ceratitis spp., Chrysops spp. ), Cochliomyia spp., Contarinia spp. , Culex spp., Culicoides spp., Dasineula spp. (Dasineura spp.), Delia spp., Drosophila spp. pp.), Fannia spp., Hylemya spp., Liliomi Liriomyza spp., Musca spp., Phorbia spp. ), Pollenia spp., Psychoda spp., Simulium spp. Simulium spp., Tabanus spp., and Tipula spp. A non-exhaustive list of specific species includes, but is not limited to, Agromyza Frontella (Agromyza frontella), Caribbean fruit fly (Anastrepha suspensa), Anas Anastrepha ludens, Western Indian fruit fly (Anasstrepha obliqua) ), melon fly (Bactrocera cucurbitae), oriental fruit fly (Bactrocera dorsalis), Bactrocera invadens, Bactrocera zonata ocera zonata), Mediterranean fruit fly (Ceratitis capitata), Radish gall midge (Dasi neura brassicae), Delia platura, Fannia caniculatus ularis, Fannia scalaris, Gasterophilus intes Gasterophilus intestinalis, Gracillia persea eae), Horn fly (Haematobia irritans), Hypoderma lineatum (Hypoderma li neatum), Liriomyza brassicae, tomato leafminer (L iriomyza sativa), Melophagus ovinus, Musca autumn Musca autumnalis, house fly (Musca domestica), sheep fly (Oestrus ov is), Oscinella frit, Pegomya betae, Chi Carrot fly (Piophila casei), carrot rust fly (Psila rosae), Lagoletis selasi (Rhagoletis cerasi), Rhagoletis pomonella, Rhagoletis Mendax (Rhagoletis mendax), Sitodiplosis mocellana (Sitodiplosis mocellana) sellana and stable flies (Stomoxys calcitrans).

[0080] (7) Hemiptera. A non-exhaustive list of specific genera includes, but is not limited to: However, Adelges spp., Aulacaspis spp. , Aphrophora spp., Aphis spp., Bemisia spp. (Bemisia spp.), Ceroplastes spp., Chionaspis spp. naspis spp., Chrysomphalus spp., Coccus spp. spp.), Empoasca spp., Euschistus spp. , Lepidosaphes spp., Lagynotomus spp. , Lygus spp., Macrosiphum spp., Nehotetchkis Nephotettix spp., Nezara spp., Nilaparva spp. ta spp.), Philaenus spp., Phytocoris spp. ), Piezodorus spp., Planococcus spp. , Pseudococcus spp., Rhopalosiphum spp. .), Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Tria Trialeurodes spp., Triatoma spp. and Unas Unaspis spp. A non-exhaustive list of specific species includes, but is not limited to: Although not commonly used, Acrosternum hilare, Asyltosif Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, citrus cotton whitefly (Ale urothrixus floccosus), Amrasca biguttula biguttula ), red scale insect (Aonidiella aurantii), black bean aphid (Aphis fabae ), cotton aphid (Aphis gossypii), soybean aphid (Aphis glycines), Aphi Aphis pomi, potato aphid (Aulacorthum solani), tapir Bactericera cockerelli, Bagrada hila ris), silverleaf whitefly (Bemisia argentifolii), tobacco whitefly (Bemis ia tabaci), Blissus leucopterus, Boisea triv Boisea trivittata, Brachycorynella asparagi i), Brevennia rehi, radish aphid (Brevicoryne brassicae) icae), Cacopsylla pyri, Cacopsylla py ricola), Calocoris norvegicus, Ruby wax scale Ceroplastes rubens, Cimex hemipterus, Cimex lectularius (Cimex lectularius), citrus scale (Coccus pseudomagn oliarum), Dagbertus fasciatus, Dicelops fulca Dichelops furcatus, Diuraphis noxia, Orange Lice (Diaphorina citri), plantain aphid (Dysaphis plantaginea), Zildel Dysdercus suturellus, Edessa meditab unda), Empoasca vitis, apple aphid (Eriosoma lan igerum), Erythroneura elegantula, Eurygaster mau Eurygaster maura, Euschistus conspersus, Euschistus heros, Euschistus serbus vus), Brown marmorated stink bug (Halyomorpha halys), Helopeltis antonii antonii), peach aphid (Hyalopterus pruni), Helopertis antonii (Helopeltis antonii), Helopeltis theivora, Iseria Scale insect (Icerya purchasi), Idioscopus nitidulus s), Tea green leafhopper (Jacobiasca formosana), Small brown planthopper (Laodelpha x striatellus), dogwood scale (Lecanium corni), Leptocorysa orato Leptocorisa oratorius, Spider bug (Leptocorisa varicornis), Lygus hesperus, Maconellicoccus hirsutus s hirsutus), Tulip aphid (Macrosiphum euphorbiae), Wheat beard Macrosiphum granarium, Macrosiphum r osae), Macrosteles quadrilineatus, Mahana Mahanarva frimbiolata, Taiwan spotted stink bug (Megacopta c ribraria), wheat aphid (Metopolophium dirhodum), Mictis longicornis Mictis longicornis, green peach aphid (Myzus persicae), lettuce higeona Gadget aphid (Nasonovia ribisnigri), green rice leafhopper (Nephotettix cincticeps) , Neurocolpus longirostris, Southern blue heron Nezara viridula, brown planthopper (Nilaparvata lugens), Paracoccus marmoratus Paracoccus marginatus, Paratrioza cockerel li), Parlatoria pergandii, Pa rlatoria ziziphi), corn planthopper (Peregrinus maidis), grape aphid (Phylloxera vitifoliae), Physokermes piceae, Phy Phytocoris californicus, Phytocoris relatives (Phytocoris relativus), Piezodorus guildinii, Mi Planococcus citri, Planococcus ficus ficus), Poecilocapsus lineatus, Psalus tapir Psallus vaccinicola, Pseudacysta perseae ), pineapple mealybug (Pseudococcus brevipes), quadrupedus Quadraspidiotus perniciosus, Rhopa losiphum maidis), wheat neck aphid (Rhopalosiphum padi), olive leaf aphid Saissetia oleae, Scaptocoris castanea , wheat green aphid (Schizaphis graminum), Sitobion avenae (Sitobion av enae), white-backed planthopper (Sogatella furcifera), greenhouse whitefly (Trialeurodes va porariorum), Trialeurodes abutiloneus, Yano Root scale (Unaspis yanonensis) and Zulia entrerri ana) is an example.

[0081] (9) Hymenoptera. A non-exhaustive list of specific genera includes: Although not a common species, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Dolichovesp Dolichovespula spp., Formica spp., Monomorium spp. (Monomorium spp.), Neodiprion spp., Paratrechina spp. ratrechina spp., Pheidole spp., Pogonomyrmex spp. myrmex spp.), Polistes spp., Solenopsis spp. .), Technomyrmex spp., Tetramorium spp. spp.), Vespula spp., Vespa spp. and Xylocopa spp. Species (Xylocopa spp.) include: Although not common, some species include the turnip sawfly (Athalia rosae), Atta texana, Caliroa cerasi, Cimbex america na), Iridomyrmex humilis, Linepithema humilis epithema humile), African honeybee (Mellifera scutellata), Monomorium miniature Monomorium minimum, Monomorium pharaonis, pine sawfly (Neodiprion sertifer), fire ants (Solenopsis invicta), red fire ants (Solenopsis geminata), Solenopsis molesta, Solenopsis licteri (Solenopsis richtery), Solenopsis xyloni, Tapinoma Tapinoma sessile and Wasmannia auropunctata punctata).

[0082] (10) Isoptera. A non-exhaustive list of specific genera includes, but is not limited to: However, Coptotermes spp., Cornitermes spp. spp.), Cryptotermes spp., Heterot ermes spp.), Kalotermes spp., Incisit ermes spp.), Macrotermes spp., Marginitermes spp. initermes spp.), Microcerotermes spp., Procorniter Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp. and Zootermo psis spp. A non-exhaustive list of specific species includes, but is not limited to: However, Coptotermes acinaciformis, Copt Coptotermes curvignathus, Coptotermes Frenchii Coptotermes frenchi), Coptotermes formosanus, Coptotermes Coptotermes gestroi, Cryptotermes brevis is), Heterotermes aureus, Heterotermes tenui Heterotermes tenuis, Incisitermes minor, Incisitermes snyderi, Microtermes obesi mes obesi), Nasutitermes corniger, Odontotermes Odontotermes formosanus, Odontotermes obesus otermes obesus), Reticulitermes banyulensis , Reticulitermes grassei, Reticulitermes fura Reticulitermes flavipes, Reticulitermes hage ni), Reticulitermes hesperus, Reticulitermes Santonensis (Reticulitermes santonensis), Japanese termite (Reticulitermes s peratus, Reticulitermes tibialis and Reticulitermes One example is Reticulitermes virginicus.

[0083] (11) Lepidoptera. A non-exhaustive list of specific genera includes, but is not limited to: Although not the same as Adoxophyes spp., Agrotis spp. pp.), Argyrotaenia spp., Cacoecia spp. ), Caloptilia spp., Chilo spp., Chrysodeichis Chrysodeixis spp., Colias spp., Crambus spp. spp.), Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimetheus spp. (Epimecis spp.), Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indal Indarbela spp., Lithocolletis spp., Roxaglochia Loxagrotis spp., Malacosoma spp., Nemapogon spp. mapogon spp., Peridroma spp., Phyllo norycter spp., Pseudaletia spp., Plutella spp. spp.), Sesamia spp., Spodoptera spp., China Examples include Synanthedon spp. and Yponomeuta spp. A non-exhaustive list of specific species includes, but is not limited to, Sirahosia Achaea janata, Adoxophyes orana, Tama Agrotis ipsilon, Alabama argillacea, Amor Amorbia cuneana, Amyelois transitera lla), Anacamptodes defectaria, Anacamptodes Anarsia lineatella, Anomis sabulifera, and Anticha Anticarsia gemmatalis, Archips argyrospira argyrospila), Archips rosana, Argyrotaen ia citrana), Autographa gamma, Bonagota cranaodes gota cranaodes), Borbo cinnara, Buccleuchus thurbergii Bucculatrix thurberiella, Capua reticulana, Peach Carposina niponensis, Chlumetia transversa sversa), Choristoneura rosaceana, rice leafroller (C naphalocrocis medinalis), Conopomorpha cramerella , Corcyra cephalonica, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia Molesta (Cydia molesta), pea moth (Cydia nigricana), codling moth (Cy dia pomonella), Darna diducta, Diaphania nitidaris aphania nitidalis, Diatraea saccharalis, Diatraea Diatraea grandiosella, Earias insula na), Earias vittella, Ecdytropha aurantianum olopha aurantianum), corn moth (Elasmopalpus lignosellus), striped moth Ephestia cautella, Ephestia elutella, Striped moth Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax thrax), Estigmene acrea, Eupoecilia ambiguella), Euxoa auxiliaris, wax moth (Galleria mellonella), Oriental fruit moth (Grapholita molesta), Oriental fruit moth Helicoverpa armigera, Helicoverpa indicata, Helicoverpa indicata Zea (Helicoverpa zea), Heliothis virescens, Haima Hellula undalis, Keiferia lycopersicella icella), eggplant moth (Leucinodes orbonalis), coffee leafminer moth (Leucoptera c offeella), Leucoptera malifoliella, Lobesia Lobesia botrana, Loxagrotis albicosta ), gypsy moth (Lymantria dispar), peach leafminer moth (Lyonetia clerkella), Mahase Mahasena corbetti, armyworm moth (Mamestra brassicae), tobacco tin Manduca sexta, Bean moth (Maruca testulalis), Metisa plana plana), American armyworm (Mythimna unipuncta), Neoleucinenodes elegantarii Neoleucinodes elegantalis, Nymphula depunctalis ), Winter moth (Operophtera brumata), European corn borer (Ostrinia nubila lis), Oxydia vesulia, Pandemis celasana rasana), Pandemis heparana, African swallowtail butterfly (Papilio demodoc) us), red bollworm moth (Pectinophora gossypiella), false stag beetle moth (Peridroma sa ucia), Perileucoptera coffeella, potato tuber moth (Ph thorimaea operculella), citrus leafminer (Phyllocnistis citrella), phyllocellarum Phyllonorycter blancardella, Cabbage white butterfly (Pieris ra pae), Plathypena scabra, Platinota idaeusariis ( Platynota idaeusalis), Indian meal moth (Plodia interpunctella), diamondback moth (Plu tella xylostella), Polychrosis viteana, Price et Prays endocarpa, Prays oleae, Pseudaletia Unipuncta (Pseudaletia unipuncta), Pseudoplesia inculdens (Pseud oplusia includens), Rachiplusia nu, One-leaf moth (Sci rpophaga incertulas), rice armyworm (Sesamia inferens), Sesamia nonagrioide Sesamia nonagrioides, Setora nitens, Sitotroga cerealella), Japanese bush moth (Sparganothis pilleriana), beet armyworm (Spod optera exigua), Spodoptera frugiperda, Spodoptera Spodoptera eridania, Thecla basilides, Tinea pellionella, Tineola bisselliella, and Tinea stag beetle richoplusia ni), Tuta absoluta, Zeu zera coffeae and Zeuzea pyrina.

[0084] (12) Mallophaga. A non-exhaustive list of specific genera includes: Although not the same as the Anaticola spp., Bovicola spp. , Chelopistes spp., Goniodes spp., Menaka Menacanthus spp. and Trichodectes spp. are examples. A non-exhaustive list of specific species includes, but is not limited to, cowrie Lice (Bovicola bovis), goat louse (Bovicola caprae), sheep louse (Bovicol a ovis), horn louse (Chelopistes meleagridis), cockroach louse (Goniodes di ssimilis), brown louse (Goniodes gigas), and bag louse (Menacanthus stra mineus), chicken louse (Menopon gallinae) and dog louse (Trichodectes c anis) are examples.

[0085] (13) Orthoptera. A non-exhaustive list of specific genera includes: Melanoplus spp. and Pterophylla spp. A non-exhaustive list of specific species includes, but is not limited to: Burr, European house cricket (Acheta domesticus), Anabulus simplex (A nabrus simplex), mole cricket (Gryllotalpa africana), Gryllotalpa australis (Gr Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratorya igratoria), Microcentrum retinerve, Desert croaker Grasshopper (Schistocerca gregaria) and Scudderia furcata Examples include:

[0086] (14) Psocoptera. A non-exhaustive list of specific species includes: Although they are not commonly found, psocids (Liposcelis decolor), stag beetles (Liposcelis elis entomophila), Lachesilla quercus and Trog ium pulsatorium).

[0087] (15) Siphonaptera. A non-exhaustive list of specific species includes, but is not limited to: Although not the same as the Japanese flea (Ceratophyllus gallinae), Ceratophyllus niger ( Ceratophyllus niger), dog flea (Ctenocephalides canis), cat flea (Ctenocephali des felis and the human flea (Pulex irritans).

[0088] (16) Thysanoptera. A non-exhaustive list of specific genera includes, but is not limited to: Although not the same as the genus Caliothrips, the genus Frankliniella kliniella spp.), Scirtothrips spp. and T hrips spp. A non-exhaustive list of specific species includes, but is not limited to: However, there are some species of Caliothrips phaseoli, Frankliniella bifida, spinosa (Frankliniella bispinosa), light brown thrips (Frankliniella fusca), Frankliniella occidentalis, Frankliniella schultz Zei (Frankliniella schultzei), Frankliniella triti (Frankliniella triti ci), Frankliniella williamsi, Heliothrips Heliothrips haemorrhoidalis, Lipihorothrips cruenta Rhipiphorothrips cruentatus, Scirtothrips citr i), tea tree thrips (Scirtothrips dorsalis), Taeniothrips rhopala Antennalis (Taeniothrips rhopalantennalis), flower thrips (Thrips hawaiiensis ), Thrips nigropilosus, Thrips orientalis (T hrips orientalis), southern melon thrips (Thrips palmi) and onion thrips ( Thrips tabaci).

[0089] (17) Thysanura. A non-exhaustive list of specific genera includes: However, Lepisma spp. and Thermobia spp. ) are mentioned.

[0090] (18) Acarina. A non-exhaustive list of specific genera includes, but is not limited to: Although there are no known species, Acarus spp., Aculops spp., and Argus spp. Argus spp., Boophilus spp., Demodex spp. spp.), Dermacentor spp., Epitrimerus spp. ), Eriophyes spp., Ixodes spp., Oligo Oligonychus spp., Panonychus spp., Rhizoglyphus spp. Rhizoglyphus spp. and Tetranychus spp. A non-exhaustive list of specific species includes, but is not limited to, Acarapaceae, is woodi), Acarus siro, Aceria mangiferae ngiferae), tomato rust mite (Aculops lycopersici), Aculus perekassii (Aculus pelekassi), Aculus schlechtendali, Amblyomma Amblyomma americanum, Brevipalpus obovatus, Southern spider mite (Brevipalpus phoenicis), Dermacentor variabilis (Dermace ntor variabilis), Dermatophagoides pteronyssinus, Eotet Eotetranychus carpini, Liponysoides sanguineus onyssoides sanguineus, Notoedres cati, Mango - Spider mites (Oligonychus coffeae), small spider mites (Oligonychus ilicis), house mites Mite (Ornithonyssus bacoti), citrus red mite (Panonychus citri), apple red mite (Pa nonychus ulmi), Phyllocoptruta oleivora, Chano Dust mite (Polyphagotarsonemus latus), brown dog tick (Rhipicephalus san guineus), Sarcoptes scabiei, Tegolophus perseaphroae phus perseaflorae, Tetranychus urticae, Chirophaga Tyrophagus longior and Varroa destructor r) are mentioned.

[0091] (19) Araneae. A non-exhaustive list of specific genera includes, but is not limited to: However, Loxosceles spp., Latrodectus spp. and and Atrax spp. A non-exhaustive list of specific genera includes: Examples include, but are not limited to, brown recluse spiders (Loxosceles reclusa), black widow spiders (Latr odectus mactans and the Sydney funnel-web spider (Atrax robustus).

[0092] (20) Symphyla. A non-exhaustive list of specific species includes, but is not limited to: Although there is no known species, Scutigerella immaculata is one example.

[0093] (21) Collembola. A non-exhaustive list of specific species includes: Although they are not common species, the yellow-spotted springtail (Bourletiella hortensis) and the white springtail (On ychiurus armatus, Onychiurus fimetarius, and An example is the yellow-spotted springtail (Sminthurus viridis).

[0094] (22) Nematoda. A non-exhaustive list of specific genera includes, but is not limited to: Although not a member of the family, Aphelenchoides spp., Belonoraimus spp. (Belonolaimus spp.), Criconemella spp., Ditylenchus spp. Ditylenchus spp., Globodera spp., Heterodera spp. spp.), Hirschmanniella spp., Hoplolimus spp. lolaimus spp., Meloidogyne spp., Pratylenchus spp. lenchus spp. and Radopholus spp. A non-exhaustive list includes, but is not limited to, Dirofilaria immiti s), potato white cyst nematode (Globodera pallida), soybean cyst nematode (Heterodera glycines), Heterodera zeae, sweet potato root Nematode (Meloidogyne incognita), Meloidogyne javanica (Meloidogyne javanica) ica), Onchocerca volvulus, Pratylenchus p enetrans), banana rootworm (Radopholus similis) and Rottlenculus . Examples include Rotylenchulus reniformis.

[0095] (23) Mollusca. A non-exhaustive list of specific species includes, but is not limited to: Although not the same species as Arion vulgaris, Cornu aspersum), field slug (Deroceras reticulatum), red slug (Limax flavu s), garden slug (Milax gagates) and apple snail (Pomacea canaliculata) lata) are examples.

[0096] A particularly preferred group of pests to be controlled are sap-feeding pests. Pests generally have sucking and / or suction mouthparts that feed on plant sap and the inner plant. Examples of sap-feeding pests of particular concern to agriculture include but are not limited to: Although not common, it is effective against aphids, leafhoppers, moths, scale insects, thrips, and psyllids. , mealybugs, stink bugs and whiteflies. Examples of orders that include sap-feeding pests include, but are not limited to, lice. Hemiptera are of concern in agriculture. Illustrative examples of the order Hemiptera include, but are not limited to, Aulacaspis species (A ulacaspis spp.), Aphrophora spp., Aphis spp. ), Bemisia spp., Coccus spp., Eusistus spp. (Euschistus spp.), Lygus spp., Macrosiphum spp. .), Nezara spp. and Rhopalosiphum spp. can be done.

[0097] Another particularly preferred group of pests to be controlled are chewing pests. Chewing pests generally feed on root , stems, leaves, buds and reproductive tissues (including but not limited to flowers, fruits and seeds) They have mouthparts that allow them to chew plant tissue, including plant matter. Chewing pests of particular concern to agriculture Examples of insects include, but are not limited to, caterpillars, beetles, grasshoppers, and locusts. Examples of orders of chewing pests of concern in agriculture include, but are not limited to: Although not all insects are categorized as insects, they are classified as Coleoptera and Lepidoptera. Examples of Coleoptera of concern include, but are not limited to, Amphibians. Anthonomus spp., Cerotoma spp., Chaetocnema spp. (Chaetocnema spp.), Colaspis spp., Cyclocephala spp. cephala spp.), Diabrotica spp., Hypera spp., Phyllophaga spp., Phyllotreta spp., Suf Examples include Sphenophorus spp. and Sitophilus spp. can be done.

[0098] The phrase "pesticidally effective amount" means a compound that has an observable effect on pests, e.g., necrosis. the effectiveness of killing, delaying, preventing, eliminating, destroying, or otherwise preventing the growth of pests in an area. The amount of pesticide required to achieve a reduction in occurrence and / or activity This effect means that if a population of pests is repelled from an area, the pests will and / or if the pest is neutralized in or around the area. This can occur if the zoo is exterminated in the vicinity. Of course, a combination of these effects can also occur. Generally, pest populations, activity, or both should preferably be reduced by more than 50 percent. , preferably by more than 90 percent, and most preferably by more than 99 percent. For agricultural purposes, the pesticidal effective dose is approximately 0.0001 grams per hectare. About 5000 grams per hectare, preferably about 0.0 grams per hectare. 0.01 grams to about 500 grams per hectare, and even more preferably The average annual average annual yield is about 0.0001 grams per hectare to about 50 grams per hectare.

[0099] Detailed Description of the Disclosure This document is based on the formula 1

[0100] [ka]

[0101] [In the formula, (A)R 1 are H, F, Cl, Br, I, CN, NO2, SF5 and (C1-C3) halides. selected from the group consisting of alkyl; (B)R 2 are H, F, Cl, Br, I, CN, NO2, SF5 and (C1-C3) halides. selected from the group consisting of alkyl; (C)R 3 are H, F, Cl, Br, I, CN, NO2, SF5 and (C1-C3) halides. selected from the group consisting of alkyl; (D)R 4 are H, F, Cl, Br, I, CN, NO2, SF5 and (C1-C3) halides. selected from the group consisting of alkyl; (E)R 5are H, F, Cl, Br, I, CN, NO2, SF5 and (C1-C3) halides. selected from the group consisting of alkyl; (F)R 6 is 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 is H; (J)Q 1 is selected from the group consisting of O and S; (K)Q 2 is selected from the group consisting of O and S; (L)R 10 is H, (C1-C3) alkyl, (C2-C3) alkenyl, (C2-C 3) Alkynyl, (C1-C3) alkyl, O(C1-C3) alkyl and (C1-C3 ) alkylOC(=O)(C1-C3) alkyl; (M)R 11 are H, F, Cl, Br, I, CN, NO2, (C1-C3) alkyl, ( selected from the group consisting of (C1-C3)haloalkyl and (C1-C3)alkoxy; (N)R 12 are H, F, Cl, Br, I, CN, NO2, (C1-C3) alkyl, ( selected from the group consisting of (C1-C3)haloalkyl and (C1-C3)alkoxy; (O)R 13 are H, F, Cl, Br, I, CN, NO2, (C1-C3) alkyl, ( selected from the group consisting of (C1-C3)haloalkyl and (C1-C3)alkoxy; (P)R 14 are H, F, Cl, Br, I, CN, NO2, (C1-C3) alkyl, ( selected from the group consisting of (C1-C3)haloalkyl and (C1-C3)alkoxy; (Q)X 3teeth, (1)N(R 15a )(R 15b )(in the formula, (a) The above R 15a is H, (C1-C3) alkyl, (C2-C3) alkenyl, (C2-C3) alkynyl, (C1-C3) haloalkyl, (C1-C3) alkylphenyl Nyl, (C1-C3) alkylO(C1-C3) alkyl, (C1-C3) alkylOC The group consisting of (=O)(C1-C3) alkyl and C(=O)(C1-C3) alkyl is selected from (b) The above R 15b is a substituted or unsubstituted phenyl, and the substituted phenyl is H, F, Cl, Br, I, CN, NO2, NH2, OH, SF5, (C1~C3)alkyl (C1-C3) haloalkyl, (C2-C3) alkenyl, (C2-C3) haloalkenyl alkoxy, (C=O)O(C1-C3) alkyl, O(C=O )(C1-C3) 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(C1-C3) 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 )(C1-C3) alkyl X 4 , N(R15c )(CH(O(C1-C3)alkyl)2), N(R 15c )((C 1-C3) alkylOC(=O)(C1-C3) alkyl), N(R 15c )((C1~ C3) alkylC(=O)N(R 15c )2), N(R 15c )C(=O)(R 15c ) , N(R 15c )C(=O)X 4 , N(R 15c )(C(=O))2X 4 , N(R 15c )(C(=O))2OX 4 , N(R 15c )(C(=O))2N(R 15c )X 4 , N( C(=O)O(C1-C6) alkyl)2, N(R 15c )C(=O)O(C1~C6) Alkyl, N(R 15c )C(=O)N(R 15c )C(=O)O(R 15c ), N(R 15C )(C(=O)O(C1-C6) alkyl), N(R 15C )(C(=O)O(C 1-C6) haloalkyl), N((C1-C3) alkylOC(=O)(C1-C6) alkyl alkyl)(C(=O)(C1-C6) alkyl), N((C1-C3) alkylO(C1 ~C6) alkyl) (C(=O)O(C1~C6) alkyl), and N(R 15c )C (=S)X 4 and having one or more substituents selected from the group consisting of: (1) The above R 15c are each independently H, (C1-C3) alkyl, (C2- C3) alkenyl, (C2-C3) alkynyl, (C1-C3) haloalkyl, (C2- C3) haloalkenyl, (C1-C3) alkylphenyl, (C1-C3) alkylO( C1-C3) alkyl, (C1-C3) alkylOC(=O)(C1-C3) alkyl, C(=O)(C1-C3)alkyl, and phenyl; So, N(R 15c )2, the N(R 15c )2 is a ring of one nitrogen atom and 3 to A heterohydrocarbyl ring containing 5 carbon ring atoms, said ring being substituted or unsubstituted. It may be exchangeable; (2) The above X 4 is (C1-C6) alkyl, (C1-C6) haloalkyl, (C1 ~C3) alkylO(C1~C3) alkyl, O(C1~C6) alkyl, (C3~C6 ) cycloalkyl, (C1-C6) alkylphenyl, phenyl, aryl, and hetero and cyclocyclyl, each of which is selected from the group consisting of F, Cl, Br, I, CN, OH , NO2, NH2, oxo, (C1-C3) alkyl, (C1-C3) haloalkyl, N H(C1-C3) alkyl, N((C1-C3) alkyl)2, O(C1-C6) alkyl O(C1-C6) haloalkyl, N(R 15c )C(=O)O(C1~C6)Alky Lu, N(R 15c )S(=O)2(R 15c ), S(=O)2(R 15c ), (C1~C 3) alkylO(C1-C3) alkyl, (C3-C6) cycloalkyl optionally substituted with one or more selected substituents, In (1)(a) and (1)(b), the alkyl, alkenyl, and a Each of alkynyl, cycloalkyl, phenyl, aryl and heterocyclyl is F , Cl, Br, I, CN, OH, NO2, NH2, NH(C1-C3) alkyl, N(( C1-C3) alkyl)2, O(C1-C6) alkyl, (C1-C3) alkylO(C 1 is selected from the group consisting of (1-C3) alkyl and (C3-C6) cycloalkyl; may be substituted with the above substituents); (2)N(R 16a )(R 16b )(in the formula, (a) The above R 16a is H, (C1-C3) alkyl, (C2-C3) alkenyl, (C2-C3) alkynyl, (C1-C3) haloalkyl, (C1-C3) alkylO( C1-C3) alkyl, (C1-C3) alkylOC(=O)(C1-C3) alkyl, and C(═O)(C1-C3)alkyl; (b) The above R 16b is a substituted or unsubstituted (C1-C8) alkyl, Substituted (C1-C8) alkyl is F, Cl, Br, I, CN, NO2, O(C1-C8) alkyl alkyl, (C3-C8) cycloalkyl, (C1-C8) alkylphenyl, (C2-C 8) Alkenyl, (C2-C8) alkynyl, S(C1-C8) alkyl, S(O)(C 1~C8) alkyl, S(O)2(C1~C8) alkyl, Ophenyl, O(C2~C8 ) alkenyl, O(C1-C8) alkyl (C3-C8) cycloalkyl, O(C1-C 8) Alkylphenyl, O(C1-C8) alkyl(C3-C8) cycloalkyl, O( C1-C8) alkyl, C(=O)O(C1-C8) alkyl, OC(=O)(C1-C 8) Alkyl, C(=O)N(R 16a )(C1-C8) alkyl, N(R 16a )C( =O)(C1-C8)alkyl, S(C1-C8)alkyl, S(O)(C1-C8)a alkyl, S(O)2(C1-C8) alkyl, S(O)2NH2, and N(R 16a ) S(O)2(C1-C8) alkyl, In (2)(a) and (2)(b), alkyl, alkenyl, alkyl Each of cycloalkyl, cycloalkyl, and phenyl is selected from F, Cl, Br, I, CN, OH, NH2, NO2, (C1-C8) alkyl, (C1-C8) alkoxy, (C1-C8) Haloalkyl, N((C1-C8) alkyl)2 and C(=O)O(C1-C8) alkyl optionally substituted with one or more substituents selected from the group consisting of alkyl; (3)N(R 17a )(N(R 17b )(R 17c ))(In the formula, (a) The above R 17a is H, (C1-C3) alkyl, (C2-C3) alkenyl, (C2-C3) alkynyl, (C1-C3) haloalkyl, (C1-C3) alkylO( C1-C3) alkyl, (C1-C3) alkylOC(=O)(C1-C3) alkyl, and C(═O)(C1-C3)alkyl; (b) The above R 17b is H, (C1-C3) alkyl, (C2-C3) alkenyl, (C2-C3) alkynyl, (C1-C3) haloalkyl, (C1-C3) alkylO( C1-C3) alkyl, (C1-C3) alkylOC(=O)(C1-C3) alkyl, and C(═O)(C1-C3)alkyl; (c) Said R 17c is H, substituted or unsubstituted phenyl, substituted or unsubstituted heptane cyclocyclyl, substituted or unsubstituted (C1-C8) alkyl, substituted or unsubstituted (C3- C8) Cycloalkyl, C(=O)X 5 and C(=S)X 5 is selected from the group consisting of (1) The above X 5 is a substituted or unsubstituted phenyl, a substituted or unsubstituted heterocyclyl substituted or unsubstituted (C1-C8) alkyl, O(C1-C8) alkyl, O(C1 ~C8) haloalkyl, O(substituted or unsubstituted) phenyl, N(R 17a )(C1~C 8) Alkyl, N(R 17a )(C1-C8)haloalkyl, N(R 17a )(C3~C 8) Cycloalkyl, N(R 17a ) (substituted and unsubstituted phenyl) and (C C6) cycloalkyl; (2) The substituted phenyl in (3)(c) above is selected from the group consisting of F, Cl, Br, I, CN, and NO. 2, selected from the group consisting of OH, (C1-C3)alkoxy and (C1-C3)alkyl and having one or more substituents, (3) The substituted heterocyclyl in (3)(c) is F, Cl, Br, I, CN , NO2, OH, (C1-C3)alkoxy and (C1-C3)alkyl and having one or more substituents selected from (4) The substituted (C1-C8) alkyl in (3)(c) is F, Cl, Br, I, CN, OH, NO2, NH2, O(C1~C8) alkyl, (C3~C8) cycloa alkyl, phenyl, (C2-C8) alkenyl, (C2-C8) alkynyl, S(C1- C8) alkyl, S(O)(C1-C8) alkyl, S(O)2(C1-C8) alkyl , Ophenyl, O(C2-C8)alkenyl, O(C1-C8)alkyl(C3-C8) Cycloalkyl, O(C1-C8) alkylphenyl, O(C1-C8) alkyl(C3 ~C8)cycloalkyl, C(=O)NH(C1~C8)alkyl, NHC(=O)(C 1~C8) alkyl, S(O)2NH2, NH(C1~C3) alkyl, N((C1~C 3) alkyl)2) one or more substituents selected from the group consisting of (5) The substituted (C3-C8) cycloalkyl is F, Cl, Br, I, CN, OH , (C1-C3)alkoxy and (C1-C3)alkyl; having one or more substituents, In (2)(a), (2)(b) and (2)(c), alkyl, alkoxy, alkynyl, cycloalkyl, haloalkyl, phenyl, and heterocyclyl Each is optionally selected from F, Cl, Br, I, CN, OH, NH2, NO2, (C1~ C8) alkyl, (C1-C8) alkoxy, (C1-C8) haloalkyl, N((C1 C(=O)O(C1-C8)alkyl)2 and C(=O)O(C1-C8)alkyl and optionally substituted with one or more substituents, such as (N(R 17b )(R 17 c )) is a heterohydrocarbyl group containing one nitrogen ring atom and 3 to 5 carbon ring atoms. a cyclic ring, which may be substituted or unsubstituted; (4)N(R 18a )(N=C(R 18b )(R 18c )) (a) The above R 18a is H, (C1-C3) alkyl, (C2-C3) alkenyl, (C2-C3)alkynyl, (C1-C3)alkylO(C1-C3)alkyl, (C1 ~C3) alkylOC(=O)(C1-C3) alkyl and C(=O)(C1-C3) is selected from the group consisting of alkyl, (b) The above R 18b is selected from the group consisting of H and (C1-C3) alkyl; (c) Said R 18c is a substituted or unsubstituted phenyl, a substituted or unsubstituted heterocyclic acrylic, substituted or unsubstituted (C1-C8) alkyl, substituted or unsubstituted (C3-C8 ) cycloalkyl; (1) The substituted phenyl in (4)(c) above is selected from the group consisting of F, Cl, Br, I, CN, and NO. 2, OH, (C1-C3) alkoxy, (C1-C3) alkyl, (C1-C3) halo one or more substituents selected from the group consisting of alkoxy and (C1-C3)haloalkyl and (2) The substituted heterocyclyl in (4)(c) is F, Cl, Br, I, CN , NO2, OH, (C1-C3) alkoxy, (C1-C3) alkyl, (C1-C3) one or more selected from the group consisting of haloalkoxy and (C1-C3)haloalkyl; has a substituent, (3) The substituted (C1-C8) alkyl is F, Cl, Br, I, CN, NO2, O (C1-C8) alkyl, (C3-C8) cycloalkyl, phenyl, (C2-C8) aryl Alkenyl, (C2-C8)alkynyl, S(C1-C8)alkyl, S(O)(C1-C 8) Alkyl, S(O)2(C1-C8) alkyl, Ophenyl, O(C2-C8) alkoxy cycloalkyl, O(C1-C8)alkyl(C3-C8)cycloalkyl, O(C1-C8)a alkylphenyl, O(C1-C8) alkyl(C3-C8) cycloalkyl, C(=O) NH(C1-C8) alkyl, NHC(=O)(C1-C8) alkyl, and S(O) 2NH2, (4) The substituted (C3-C8) cycloalkyl is F, Cl, Br, I, CN, OH , (C1-C3)alkoxy and (C1-C3)alkyl; having one or more substituents, In (4)(a), (4)(b) and (4)(c), alkyl, alkoxy, alkynyl, cycloalkyl, haloalkyl, phenyl, and heterocyclyl Each of them is F, Cl, Br, I, CN, OH, NH2, NO2, (C1-C8) alkyl (C1-C8) alkoxy, (C1-C8) haloalkyl, N((C1-C8) alkyl) one or more selected from the group consisting of C(=O)O(C1-C8)alkyl and optionally, C(R 18b )(R 18c ) is 3 to 5 a hydrocarbyl ring containing 10 carbon ring atoms, said ring being substituted or unsubstituted; Optionally, one or more of said carbon ring atoms may instead be a nitrogen atom, an oxygen atom or may be a sulfur atom] and N-oxides, agriculturally acceptable acid addition salts, and salt derivatives of the molecules of formula 1. , solvates, ester derivatives, crystalline polymorphs, isotopes, resolved stereoisomers, tautomers , discloses insecticide prodrugs.

[0102] In another embodiment, in a molecule according to formula 1, said molecule has the formula:

[0103] [ka]

[0104] It has.

[0105] In another embodiment, in the molecules according to Formula 1 and Formula 2, R1 But H, F, Cl, Br , SF5 and CF3.

[0106] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 2 But H, F, Cl, Br , SF5 and CF3.

[0107] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 3 But H, F, Cl, Br , SF5 and CF3.

[0108] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 4 But H, F, Cl, Br , SF5 and CF3.

[0109] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 5 But H, F, Cl, Br , SF5 and CF3.

[0110] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 2 , R 3 and R 4 Few At least one of them is SF5.

[0111] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 8 But it is Cl.

[0112] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 8 But it is Cl.

[0113] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 7 and R 8 But it is not the same do not have.

[0114] In another embodiment, in the molecules according to Formula 1 and Formula 2, Q 1 But it is O.

[0115] In another embodiment, in the molecules according to Formula 1 and Formula 2, Q 2 But it is O.

[0116] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 10 But it's H.

[0117] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 11 But it's H.

[0118] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 12 But H, F, Cl, C H3 and CF3.

[0119] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 13 However, F, Cl, CH3 and OCH3.

[0120] In another embodiment, in the molecules according to Formula 1 and Formula 2, R 14 But H, F and Cl is selected from the group consisting of:

[0121] In another embodiment, in the molecules according to Formula 1 and Formula 2: R 1 is selected from the group consisting of H, F, Cl, Br, SF5 and CF3; R 2 is selected from the group consisting of H, F, Cl, Br, SF5 and CF3; R 3 is selected from the group consisting of H, F, Cl, Br, SF5 and CF3; R 4is selected from the group consisting of H, F, Cl, Br, SF5 and CF3; R 5 is selected from the group consisting of H, F, Cl, Br, SF5 and CF3; R 7 is Cl; R 8 is Cl; Q 1 But O; Q 2 But O; R 10 But H; R 11 But H; R 12 is selected from the group consisting of H, F, Cl, CH3 and CF3; R 13 is selected from the group consisting of F, Cl, CH3 and OCH3; R 14 is selected from the group consisting of H, F and Cl.

[0122] In another embodiment, in the molecules according to Formula 1 and Formula 2, X 3 But N(R 15a )(R 15b )

[0123] In another embodiment, in the molecules according to Formula 1 and Formula 2, X 3 But N(R 15a )(R 15b ) and said R 15b But N(R 15c )C(=O)(R 15c ) and N(R 15c )C(=O)X 4 wherein R is selected from the group consisting of 15c However, each independently, (C1-C3) alkyl, (C2-C3) alkenyl, (C1-C3) haloalkyl and and (C1-C3) alkylO(C1-C3) alkyl, 4 (C1-C6) alkyl, (C1-C6) haloalkyl and (C1-C3) alkyl and arylO(C1-C3)alkyl, wherein the alkyl, haloalkyl and and alkenyl are each selected from F, Cl, CN, and (C3-C6)cycloalkyl. For the avoidance of doubt, it is optionally substituted by one or more substituents selected from the group consisting of: This includes, for example, being substituted with haloalkyl, which can have one or more substituents, e.g. For example, it includes the term "alkyl" with CN or (C3-C6)cycloalkyl.

[0124] In another embodiment, in the molecules according to Formula 1 and Formula 2, X 3 is N(R 16a )(R 16b )

[0125] In another embodiment, in the molecules according to Formula 1 and Formula 2, X3 is N(R 17a )(N (R 17b )(R 17c )) is.

[0126] In another embodiment, in the molecules according to Formula 1 and Formula 2, X 3 is N(R 18a )(N =C(R 18b )(R 18c )) is.

[0127] In another embodiment, the molecule is selected from Table 2, preferably F1007, F1079, F1108, F1147, F1185, F1234, F1241, F1246, F124 7, F1248, F1250, F1460, F1465, F1593, F1598, F1 613, F1627, F1657, F1694, F1696, F1697, F1702, F1703, F1704, F1708, F1711, F1740, F2016, F201 7, F2021, F2027, F2039, F2042, F2078 and F2081 The molecules were selected from the group consisting of:

[0128] The molecules of formula 1 may exist in different geometric or optical isomeric forms, or in different tautomeric forms. One or more asymmetric centers may be present in the form of a molecule of formula 1 in the form of a pure enantiomer. -, mixture of enantiomers, pure diastereomers or mixture of diastereomers Those skilled in the art will appreciate that one stereoisomer may be present in a compound other than the compound. It will be appreciated that individual stereoisomers may be more active than known selections. by conventional synthetic procedures using resolved starting materials, or by conventional synthetic procedures using resolved starting materials. The compounds of formula 1 can be obtained as single geometric isomers (cis or or trans, E or Z), or geometric isomers (cis or trans, E or Z) If they can exist as a mixture, double bonds may be present in the molecule. The present disclosure is directed to all such isomers, tautomers, and their equivalents in all proportions. The present disclosure encompasses all mixtures thereof. The structures disclosed in this disclosure may be presented as one or more of the following for clarity: Although it may only be drawn in a few forms, it is intended to represent all geometric forms of the molecule.

[0129] Preparation of molecules of formula 1 Preparation of cyclopropyl carboxylic acids R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 as disclosed above. Benzophenone 1-1 can be prepared by the reaction of chloroform with chloroform in a polar protic solvent such as water at a temperature of about 0°C to about 40°C. a carbene source such as fluorine or bromoform and N-benzyl-N,N-diethylethane Treated with a base such as sodium hydroxide in the presence of a phase transfer catalyst such as aminium chloride R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 is disclosed above This affords the diarylcyclopropane 1-2 (Scheme 1, Step a). Ruiha, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 is as disclosed above Stilbene 1-1 is converted to tetrahydrofuran at temperatures of approximately 80°C to approximately 120°C under microwave irradiation conditions. In polar aprotic solvents such as hydrofuran, trimethyl(trifluoromethyl)silane It is treated with a salt such as sodium iodide in the presence of a carbene source such as methyl iodide to give R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 is as disclosed above This affords cyclopropane 1-2 (Scheme 1, Step a). , preferably in a solvent mixture of water, ethyl acetate and acetonitrile, with sodium periodate. Ruthenium(III) chloride is a stoichiometric oxidant for transition metals such as ruthenium(III) chloride. Treatment of diarylcyclopropanes 1-2 with R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 cyclopropyl carboxylic acids 1-3, wherein (Scheme 1, step b).

[0130] [ka]

[0131] Preparation of stilbenes Stilbene 1-1 was prepared by several different methods, as outlined in Scheme 2. R 1 , R 2 , R 3 , R 4 , R 5 and R 6 as disclosed above. The arylcarbonyl 2-1 is reacted with N,N-dimethylformamide at a temperature of about -10°C to about 30°C. In polar aprotic solvents such as alkoxysilane, in the presence of a base such as sodium methoxide, The compound is treated with dibenzyl phosphonate 2-2 and subsequently heated to a temperature of 40°C to about 80°C. This can give stilbene 1-1 (Scheme 2, Step a). 1 , R 2 , R 3 , R 4 and R 5 The aryl halide 2-3, wherein the formula is as disclosed above, is heated at about 60° C. to about 1 At a temperature of 00°C, in a basic solvent such as triethylamine, Transition metal catalysts and bisphosphatase inhibitors such as 1,1'-bis(diphenylphosphino)ferrocene In the presence of fin ligands, R 6 and R 9 Vinylbenzene 2, -4 to give stilbene 1-1 (Scheme 2, step b).

[0132] [ka]

[0133] In yet another embodiment, stilbene 1-1 is also shown in Scheme 2.5 Wittig olefination method (Chalal, M.; Vervandier-Fasseur, D.; Meunier, P.; C attey, H.; Hierso, J.-C. Tetrahedron 2012, 68, 3899-3907) .R 1 , R 2 , R 3 , R 4 and R 5 is as disclosed above, and R 6 is H Phenylcarbonyl 2-1 can be reacted with tetrahydrofuran or the like at temperatures between about -78°C and ambient temperature. In polar aprotic solvents, in the presence of a base such as n-butyllithium, alkoxybenzene is treated with methyltriphenylphosphonium chloride 2.5-2 to give stilbene 1-1 (Scheme 2.5, step a).

[0134] [ka]

[0135] Preparation of cyclopropylamides Q 1 is O and R 1 , R 2 , R 3 , R 4 , R5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , Q 2 and X 3 is as disclosed above. Propylamide 3-3 can be prepared by the reaction of dichloromethane, tetrahydrofuran, and methylpropanol at temperatures between about 0°C and about 120°C. chlorofuran, 1,2-dichloroethane, dimethylformamide or any combination thereof In an anhydrous aprotic solvent such as triethylamine, diisopropyl ethyl amine, R 10 , R 11 , R 12 , R 13 , R 14 , Q 2 and X 3 as disclosed above. amine or amine salt 3-2, and A is an active group and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 with activated carboxylic acid 3-1, which is as disclosed above. (Scheme 3, step a).

[0136] Carboxylic acid 3-1, where A is an active group, can be converted to an acid chloride, acid bromide, or acid fluoride. Acid halides; para-nitrophenyl esters, pentafluorophenyl esters, ethoxylated Chill (hydroxyimino) cyanoacetate ester, methyl ester, ethyl ester , benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzotri Azol-1-yl ester or hydroxypyridyltriazol-1-yl ester carboxylic acid esters such as benzoates; O-acylisourea; acid anhydrides; or thioesters. Acid chlorides can be obtained by treatment with dehydrochlorinating reagents such as oxalyl chloride or thionyl chloride. The activated carboxylic acid ester 3-1 can be prepared from the corresponding carboxylic acid by the following reaction: -[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b] Pyridinium 3-oxide hexafluorophosphate (HATU), O-(benzotriazole) Azol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate phosphate (HBTU) or (1-cyano-2-ethoxy-2-oxoethylideneamine) (C)dimethylamino-morpholino-carbenium hexafluorophosphate They can be prepared in situ from carboxylic acids using uronium salts such as UR (OMU). The activated carboxylic acid ester 3-1 can also be prepared by the reaction of benzotriazol-1-yl-oxytripyro Phosphonium salts such as lysinophosphonium hexafluorophosphate (PyBop) Activated carboxylic acid ester 3-1 can be prepared in situ from a carboxylic acid using also hydroxybenzotriazole monohydrate (HoBt) or 1-hydroxy-7 -1-(3-dimethylbenzothiazolinone) in the presence of a triazole such as azabenzotriazole (HoAt) (aminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide It can be prepared in situ from a carboxylic acid using a coupling reagent such as O- Acyl isourea is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide Alternatively, it can be prepared using a dehydrated carbodiimide such as dicyclohexylcarbodiimide. The activated carboxylic acid ester 3-1 can also be synthesized by the reaction of 1-hydroxy-7-azabenzotriazole with In the presence of a triazole such as HoAt, 2-chloro-1,3-dimethylimidazoline Coupling reagents such as cinium hexafluorophosphate (CIP) can be used to The activated carboxylic acid ester 3-1 can also be prepared in situ from the carboxylic acid. In the presence of a base such as 2,4,6-tripropyl-1,3,5,2,4,6-triol, Couplings such as trioxatriphosphinane 2,4,6-trioxide (T3P®) They can be prepared in situ from carboxylic acids using a coupling reagent.

[0137] R 15b contains sulfide, and R 15a is as disclosed above The amide 3-3 can be prepared by the reaction of 2-chloro-3-methyl-2-propanol with dichloromethane (sulfoxide) at a temperature between about 0°C and about 40°C. about 1 equivalent of metachloroperoxybenzoic acid in a polar aprotic solvent such as Treatment with 2 equivalents of metachloroperoxybenzoic acid (sulfone) affords the corresponding sulfonyl Alternatively, R 15b Cyclohexyl sulfide The methylpropylamide 3-3 can be prepared by the reaction of 1 equivalent of sodium perborate in a protic solvent such as acetic acid. by treatment with 2 equivalents of sodium perborate (sulfoxide) or 2 equivalents of sodium perborate (sulfone) , can be oxidized to the corresponding sulfoxide or sulfone. Preferably, the oxidation is at about 1.5 The chloroform reaction is carried out using an equivalent amount of sodium perborate at a temperature between about 40°C and about 100°C. Chromatographically separable sulfoxides and sulfonecyclopropylamides 3-3 Alternatively, the sulfide-containing cyclopropylamide 3-3 gives a mixture of about At temperatures between 0°C and about 40°C, in a polar protic solvent such as methanol, an amine such as anamide, about 1 equivalent of a base such as potassium tert-butoxide, and by treatment with between 2 and 2 equivalents of an oxidizing agent such as N-bromosuccinimide, The sulfilimine can be oxidized to the corresponding sulfilimine at temperatures between about 0°C and about 40°C. In a mixture of solvents such as 2:1:1 ethanol:dichloromethane:water, approximately 1 equivalent of methyl Treatment with benzoic acid and approximately 2 equivalents of potassium carbonate affords the corresponding It can be further oxidized to the sulfoximine.

[0138] R 3 Cyclopropylamide 3-3, in which the aryl group is NO2, can be reacted with methyl ... ammonium chloride in a polar protic solvent such as ethanol, water, or any combination thereof. It can be reduced to the corresponding NH2 by treatment with an acid source such as ammonium and iron.

[0139] Q 2 The amine or amine salt 3-2 in which is O reacts with tetrahydrofuran at a temperature of about 40°C to about 120°C. dichloromethane, chloroform, toluene or pyridine; 1,1,1,3,3,3-hexamethyldisiloxane (disoloxa with or without additives such as phosphorus pentasulfide or 2,4-bis(4-methoxyphenyl) (phenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawson It is directly treated with a sulfur source such as a sulfur reagent, 2Amine or amine salt 3-2 having S is added. Possible.

[0140] [ka]

[0141] 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 X 3 is as disclosed above. Propylamide 4-3 can be prepared by the reaction of 4-hydroxypropyl amide 4-3 with dichloromethane, tetrahydrofuran, and tetrahydrofuran at temperatures between about 0°C and about 120°C. chlorofuran, 1,2-dichloroethane, dimethylformamide or any combination thereof In an anhydrous aprotic solvent such as triethylamine, diisopropyl ethyl amine, with a base such as methylmorpholine, 4-methylmorpholine, pyridine, or 4-dimethylaminopyridine To, X 3 as disclosed above, and A is an active is a 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 14is as disclosed above. (Scheme 4, step a).

[0142] The activated carboxylic acid 4-1 can be prepared by converting it into an acid halide such as an acid chloride, acid bromide, or acid fluoride. Para-nitrophenyl ester, pentafluorophenyl ester, ethyl (hydrogen (oximino) cyanoacetate ester, methyl ester, ethyl ester, benzyl ester ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazole-1 hydroxypyridyltriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester The acid may be a carboxylic acid ester; an O-acylisourea; an acid anhydride; or a thioester. Chlorides can be removed by treatment with dehydrochlorinating reagents such as oxalyl chloride or thionyl chloride. The activated carboxylic acid ester 4-1 can be prepared from the corresponding carboxylic acid. Methylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-Oxidohexafluorophosphate (HATU), O-(benzotriazole-1 -yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate ( HBTU) or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)di Methylamino-morpholino-carbenium hexafluorophosphate (COMU), etc. It can be prepared in situ from a carboxylic acid using the uronium salt of The acid ester 4-1 can also be prepared by the reaction of benzotriazol-1-yl-oxytripyrrolidinophosphoric acid with benzotriazol-1-yl-oxytripyrrolidinophosphoric acid. Phosphonium salts such as pentyl hexafluorophosphate (PyBop) are used to The activated carboxylic acid ester 4-1 can also be prepared in situ from the carboxylic acid. Trihydroxybenzotriazole monohydrate (HoBt) or 1-hydroxy-7-azabenzo In the presence of a triazole, such as 1-(3-dimethylaminopropyl) Coupling agents such as dicyclohexyl-3-ethylcarbodiimide or dicyclohexylcarbodiimide It can be prepared in situ from a carboxylic acid using a ring reagent. The rare is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dihydroxy It can be prepared using a dehydrated carbodiimide such as diisopropylhexylcarbodiimide. The carboxylic acid ester 4-1 can also be synthesized by the synthesis of 1-hydroxy-7-azabenzotriazole (HoAt ) in the presence of a triazole such as 2-chloro-1,3-dimethylimidazolidinium hexahydrate. In situ using coupling reagents such as trifluorophosphate (CIP), The activated carboxylic acid ester 4-1 can also be prepared from a salt such as pyridine. In the presence of the group 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphos Coupling reagents such as phenanthrin 2,4,6-trioxide (T3P®) were used. They can be prepared in situ from carboxylic acids.

[0143] [ka]

[0144] Cyclopropylamide 5-2(X 3 is N(R 15a )(R 15b ) and R 15b but N(R 15c )2(where R 15c One of the groups is (C1-C3) alkylphenyl. ), and Q is a substituted phenyl having one or more substituents including2 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 15a (as disclosed above) can be reacted with an acid such as acetic acid at about room temperature. with or without reduction such as sodium cyanoborohydride in a solvent such as methanol In the presence of an agent, aldehydes such as benzaldehyde are reacted with amine 5-1(X 3 is N(R 15a )(R 15b ) and R 15b is N(R 15c )2(where R 15 is H) and Q is a substituted phenyl having one or more substituents including 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 15a can be prepared by processing (as disclosed above) Scheme 5, step a).

[0145] Cyclopropylamide 5-4(X 3 is N(R 15a)(R 15b ) and R 15b but N(R 15c )2(where R 15c at least one of which is (C1-C3) alkyl) Q is a substituted phenyl having one or more substituents, 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 oh Yobi R 15a (as disclosed above) can be heated at a temperature between about 0°C and about 120°C. Chloromethane, tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylform In an anhydrous aprotic solvent such as triethylamine, methyl ... amine, diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridin with an alkylating agent 5-3 such as an alkyl halide in the presence of a base such as benzene or pyridine , amine 5-1(X 3 is N(R 15a )(R 15b ) and R 15b is N(R 15c ) 2 (where R 15c is H) , Q 2 is O and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R9 , Q 1 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15a as disclosed above) It can be prepared by treating the compound (Scheme 5, step b).

[0146] Cyclopropylamide 5-6(X 3 is N(R 15a )(R 15b ) and R 15b but N(R 15c )C(=O)X 4 and Q is a substituted phenyl having one or more substituents including 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 15a as disclosed above) is about At temperatures between 0°C and approximately 120°C, dichloromethane, tetrahydrofuran, 1,2-dichloromethane, anhydrous ethane, N,N-dimethylformamide, or any combination thereof In an aprotic solvent, activated carboxylic acid 5-5, where A is an active group, and triethylamine , diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridine or or pyridine to form amine 5-1(X 3 is N(R 15a )(R 15b ) and R15b is N(R 15c )2(where R 15c is H) is a substituted phenyl having 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 15a The above (Scheme 5, Step Pc).

[0147] The activated carboxylic acid 5-5 can be an acid chloride, acid bromide, acid fluoride, or chloroformate. Which acid halides; p-nitrophenyl esters, pentafluorophenyl esters, Ethyl (hydroxyimino) cyanoacetate ester, methyl ester, ethyl ester benzyl ester, N-hydroxysuccinimidyl ester, hydroxybenzoate Triazol-1-yl ester or hydroxypyridyltriazol-1-yl ester carboxylic acid esters such as esters; O-acylisourea; acid anhydrides; or thioesters The acid chloride can be reacted with a dehydrochlorinating reagent such as oxalyl chloride or thionyl chloride. The activated carboxylic acid ester 5-5 can be prepared from the corresponding carboxylic acid by the following procedure: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b ]pyridinium 3-oxide hexafluorophosphate (HATU), O-(benzothiazolinone) (triazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluoro Phosphate (HBTU) or (1-cyano-2-ethoxy-2-oxoethylidene (aminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate ( can be prepared in situ from carboxylic acids using uronium salts such as COMU The activated carboxylic acid ester 5-5 can also be prepared by the reaction of benzotriazol-1-yl-oxytriptyline. Phosphonium salts such as lolidinophosphonium hexafluorophosphate (PyBop) The activated carboxylic acid ester 5- 5 can also be prepared as hydroxybenzotriazole monohydrate (HoBt) or 1-hydroxy- In the presence of a triazole such as 7-azabenzotriazole (HoAt), 1-(3-dimethyl- (ethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide It can be prepared in situ from a carboxylic acid using a coupling reagent such as HCl. -acylisourea is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide prepared using dehydrated carbodiimides such as dicyclohexylcarbodiimide or dicyclohexylcarbodiimide. The activated carboxylic acid ester 5-5 can also be obtained by the reaction of 1-hydroxy-7-azabenzotriazo In the presence of a triazole such as 2-chloro-1,3-dimethylimidazoline (HoAt), Coupling reagents such as cysteine ​​hexafluorophosphate (CIP) can be used to The activated carboxylic acid ester 5-5 can also be prepared in situ from the carboxylic acid. In the presence of a base such as lysine, 2,4,6-tripropyl-1,3,5,2,4,6-tri Cups such as oxatriphosphinane 2,4,6-trioxide (T3P®) It can be prepared in situ from a carboxylic acid using the ring reagent. In each case, X 4 is as defined above.

[0148] [ka]

[0149] Cyclopropylamide 6-4(X 3 is N(R 15a )(R 15b ) and R 15b but N(R 15c )2(where R 15c is H) phenyl, and 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 15a is disclosed above (as shown) can be prepared by reacting a solvent such as ethyl acetate with hydrogen gas at a temperature of about 25°C to about 60°C. In the presence of any reducing agent, such as metals like palladium on carbon, or methanol and water In a solvent mixture such as 6-1 (X 3 is N(R 15a )(R 15b ) and R 15b contains one or more substituents including NO2 is a substituted phenyl having 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 as disclosed above (Scheme 6, step a).

[0150] Alternatively, cyclopropylamide 6-4(X 3 is N(R 15a )(R 15b ) and R 15b is N(R 15c )2(where R 15c is H) is a substituted phenyl having 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 15a The above (as disclosed in 1,4-dioxane and dichloromethane) at a temperature of about 25° C. 6-2(X) with anhydrous acid solution such as hydrochloric acid in ethanol. 3 is N(R 15a )(R 15b ) and , R 15b is N(R15c )C(=O)O(C1-C6) alkyl (where R 15c teeth , H), and Q is a substituted phenyl having one or more substituents including 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 15a as disclosed above) by processing , can be prepared (Scheme 6, step c).

[0151] Alternatively, cyclopropylamide 6-4(X 3 is N(R 15a )(R 15b ) and R 15b is N(R 15c )2(where R 15c is H) is a substituted phenyl having 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 15a The above (as disclosed in 1,4-dioxane and dichloromethane) at a temperature of about 25° C. 6-3(X) in anhydrous acid solution such as hydrochloric acid in ethanol 3 is N(R 15a )(R 15b ) and , R 15b has one or more substituents containing N(C(=O)O(C1-C6)alkyl)2 Q is a substituted phenyl; 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 15a As mentioned above as shown) (Scheme 6, step c ).

[0152] Cyclopropylamide 6-6(X 3 is N(R 15a )(R 15b ) and R 15b but NH(R 15c ) (where R 15c is (C1-C3) alkyl) and Q is a substituted phenyl having a substituent of 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 R1 5a as disclosed above) is reacted with 1,4-dioxane and 6-5(X) in anhydrous acid solution such as hydrochloric acid in dichloromethane 3 is N(R 15a )(R 15 b ) and R 15b is N(R 15c )(C(=O)O(C1-C6) alkyl)(where So, R 15c is a (C1-C3) alkyl) phenyl 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 15a as disclosed above) It can be prepared by treating the hydroxybenzoates with 1,2-dichlorobenzofuran (Scheme 6, step d).

[0153] [ka]

[0154] Cyclopropylamide 7-2(X 3 is N(R 15a )(R 15b ) and R 15b but One or more substituted (C2-C3) alkenyl or (C2-C3) haloalkenyl groups is a substituted phenyl having a group, 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 15a but (as disclosed above) is reacted with a non-propanediol such as 1,4-dioxane at a temperature of about 90°C. Metals such as bis(triphenylphosphine)palladium(II) dichloride in rotonic solvents In the presence of a catalyst, 7-2(R 15c is a (C2-C3) alkenyl group or a (C2-C3) halo group aryl halide 7-1 (X 3 is N(R 15a )(R 15b ) and R 15b has one or more substituents containing Br or I is a substituted phenyl, and 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 15a As disclosed above (Scheme 7, step a), which As a result, Br or I is not a (C2-C3) alkenyl group or a (C2-C3) haloalkenyl group. It is substituted by an aryl group.

[0155] [ka]

[0156] Cyclopropylamide 8-3(Q 1 is 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 1 7b and R 17c as disclosed above) is heated at a temperature between about 0°C and about 120°C Dichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide triethylamine in an anhydrous aprotic solvent such as methyl amine, ... diisopropylethylamine, 4-methylmorpholine or 4-dimethylaminopyridine bases such as amines or amine salts 8-2(R 10 , R 11 , R 12 , R 13 , R 14 , Q 2 , R 17a , R 17b and R 17c as disclosed above), then and activated carboxylic acid 8-1 (A is the active group and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8and R 9 as disclosed above) (Scheme 8, step a).

[0157] The activated carboxylic acid 8-1 can be prepared by converting it into an acid halide such as an acid chloride, acid bromide, or acid fluoride. Para-nitrophenyl ester, pentafluorophenyl ester, ethyl (hydrogen (oximino) cyanoacetate ester, methyl ester, ethyl ester, benzyl ester ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazole-1 hydroxypyridyltriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester The acid may be a carboxylic acid ester; an O-acylisourea; an acid anhydride; or a thioester. Chlorides can be removed by treatment with dehydrochlorinating reagents such as oxalyl chloride or thionyl chloride. The activated carboxylic acid ester 8-1 can be prepared from the corresponding carboxylic acid. Methylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-Oxidohexafluorophosphate (HATU), O-(benzotriazole-1 -yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate ( HBTU) or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)di Methylamino-morpholino-carbenium hexafluorophosphate (COMU), etc. It can be prepared in situ from a carboxylic acid using the uronium salt of The acid ester 8-1 can also be prepared by the reaction of benzotriazol-1-yl-oxytripyrrolidinophosphoric acid ester 8-2 with benzotriazol-1-yl-oxytripyrrolidinophosphoric acid ester 8-3 with benzotriazol-1-yl-oxytripyrrolidinophosphoric acid ester 8-4 with benzotriazol-1-yl-oxytripyrrolidinophosphoric acid ester 8-5 with benzotriazol-1 Phosphonium salts such as pentyl hexafluorophosphate (PyBop) are used to The activated carboxylic acid ester 8-1 can also be prepared in situ from the carboxylic acid. Trihydroxybenzotriazole monohydrate (HoBt) or 1-hydroxy-7-azabenzo In the presence of a triazole, such as 1-(3-dimethylaminopropyl) Coupling agents such as dicyclohexyl-3-ethylcarbodiimide or dicyclohexylcarbodiimide It can be prepared in situ from a carboxylic acid using a ring reagent. The rare is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dihydroxy It can be prepared using a dehydrated carbodiimide such as diisopropylhexylcarbodiimide. The carboxylic acid ester 8-1 was also synthesized by the synthesis of 1-hydroxy-7-azabenzotriazole (HoAt ) in the presence of a triazole such as 2-chloro-1,3-dimethylimidazolidinium hexahydrate. In situ using coupling reagents such as trifluorophosphate (CIP), The activated carboxylic acid ester 8-1 can also be prepared from a salt such as pyridine. In the presence of the group 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphos Coupling reagents such as phenanthrin 2,4,6-trioxide (T3P®) were used. They can be prepared in situ from carboxylic acids.

[0158] [ka]

[0159] Cyclopropylamide 9-3(Q 2 is O and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R8 , R 9 , Q 1 , R 10 , R 11 , R 12 , R 13 , R 14 , R 17a , R 1 7b and R 17c as disclosed above) is heated at a temperature between about 0°C and about 120°C Dichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide triethylamine in an anhydrous aprotic solvent such as methyl amine, ... diisopropylethylamine, 4-methylmorpholine or 4-dimethylaminopyridine hydrazine or hydrazine salt 9-2(R 17a , R 17b and R 17c as disclosed above), and activated carboxylic acid 9-1 (where A is an activated group). Yes, 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 as disclosed above) by processing , can be prepared (Scheme 9, step a).

[0160] The activated carboxylic acid 9-1 can be prepared by converting it into an acid halide such as an acid chloride, acid bromide, or acid fluoride. Para-nitrophenyl ester, pentafluorophenyl ester, ethyl (hydrogen (oximino) cyanoacetate ester, methyl ester, ethyl ester, benzyl ester ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazole-1 hydroxypyridyltriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester The acid may be a carboxylic acid ester; an O-acylisourea; an acid anhydride; or a thioester. Chlorides can be removed by treatment with dehydrochlorinating reagents such as oxalyl chloride or thionyl chloride. The activated carboxylic acid ester 9-1 can be prepared from the corresponding carboxylic acid. Methylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-Oxidohexafluorophosphate (HATU), O-(benzotriazole-1 -yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate ( HBTU) or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)di Methylamino-morpholino-carbenium hexafluorophosphate (COMU), etc. It can be prepared in situ from a carboxylic acid using the uronium salt of Acid ester 9-1 can also be prepared by the synthesis of benzotriazol-1-yl-oxytripyrrolidinophosphoric acid ester 9-2. Phosphonium salts such as pentyl hexafluorophosphate (PyBop) are used to The activated carboxylic acid ester 9-1 can also be prepared in situ from the carboxylic acid. Trihydroxybenzotriazole monohydrate (HoBt) or 1-hydroxy-7-azabenzo In the presence of a triazole, such as 1-(3-dimethylaminopropyl) Coupling agents such as dicyclohexyl-3-ethylcarbodiimide or dicyclohexylcarbodiimide It can be prepared in situ from a carboxylic acid using a ring reagent. The rare is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dihydroxy It can be prepared using a dehydrated carbodiimide such as diisopropylhexylcarbodiimide. The carboxylic acid ester 9-1 was also synthesized by the reaction of 1-hydroxy-7-azabenzotriazole (HoAt ) in the presence of a triazole such as 2-chloro-1,3-dimethylimidazolidinium hexahydrate. In situ using coupling reagents such as trifluorophosphate (CIP), The activated carboxylic acid ester 9-1 can also be prepared from a salt such as pyridine. In the presence of the group 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphos Coupling reagents such as phenanthrin 2,4,6-trioxide (T3P®) were used. They can be prepared in situ from carboxylic acids.

[0161] [ka]

[0162] Cyclopropylamide 10-2(Q 2 is O and R 17a and R 17b However, H,( (C1-C3) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl or ( C1-C6) 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 as disclosed above (This is a soluble form of HCl in 1,4-dioxane and dichloromethane at a temperature of about 25°C.) In an acid solution of water, 10-1 (Q 2 is O and 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 1 4 as disclosed above) (Scheme 1 0, step a).

[0163] Cyclopropylamide 10-4(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 Oh BiR 17b is as disclosed above, and X 5 substituted or unsubstituted phenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C1-C8) alkyl, O(C1 ~C8) alkyl, O(C1~C8) haloalkyl, (C3~C8) cycloalkyl and and O (substituted and unsubstituted) phenyl) at temperatures between about 0°C and about 120°C. Chloromethane, tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylform In an anhydrous aprotic solvent such as triethylamine, methyl ... amine, diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridin The cyclopropyl amide 10-2 (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 as disclosed above), and Active carboxylic acid or chloroformate 10-3 (A is the active group and X 5 is disclosed above (Scheme 10, step b).

[0164] The activated carboxylic acid 10-3 can be prepared by activating an acid halide such as an acid chloride, an acid bromide, or an acid fluoride. para-nitrophenyl ester, pentafluorophenyl ester, ethyl (hydrogen (oxyimino) cyanoacetate ester, methyl ester, ethyl ester, benzyl Ester, N-hydroxysuccinimidyl ester, hydroxybenzotriazole- hydroxypyridyltriazol-1-yl ester or hydroxypyridyltriazol-1-yl ester It may be a carboxylic acid ester; an O-acylisourea; an acid anhydride; or a thioester. Acid chlorides can be obtained by treatment with dehydrochlorinating reagents such as oxalyl chloride or thionyl chloride. The activated carboxylic acid ester 10-3 can be prepared from the corresponding carboxylic acid. (Dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridin Umium 3-oxide hexafluorophosphate (HATU), O-(benzotriazole) -1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) or (1-cyano-2-ethoxy-2-oxoethylideneaminooxy ) Dimethylamino-morpholino-carbenium hexafluorophosphate (COMU) The active carboxylic acid may be prepared in situ using uronium salts such as The benzoate ester 10-3 also reacts with benzotriazol-1-yl-oxytripyrrolidino Using phosphonium salts such as phosphonium hexafluorophosphate (PyBop) The activated carboxylic acid ester 10-3 can also be prepared in situ from the carboxylic acid. Also, hydroxybenzotriazole monohydrate (HoBt) or 1-hydroxy-7-benzotriazole In the presence of a triazole such as benzotriazole (HoAt), 1-(3-dimethylazoline) (aminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide The O-acid can be prepared in situ from a carboxylic acid using a coupling reagent such as The phenylurea is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or can be prepared using a dehydrated carbodiimide such as dicyclohexylcarbodiimide. The activated carboxylic acid ester 10-3 can also be synthesized by the synthesis of 1-hydroxy-7-azabenzotriazole. In the presence of a triazole such as (HoAt), 2-chloro-1,3-dimethylimidazolidin Coupling reagents such as tetrahydrofuran (CIP) were used to The activated carboxylic acid ester 10-3 can also be prepared from pyridinium phosphate. In the presence of a base such as 2,4,6-tripropyl-1,3,5,2,4,6-triol, Couplings such as trioxatriphosphinane 2,4,6-trioxide (T3P®) They can be prepared in situ from carboxylic acids using a coupling reagent.

[0165] Cyclopropylamide 10-6(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 Oh BiR 17b is as disclosed above, and X 5 But N(R 17a )(C1~C8) Al Kill, N(R 17a )(C1-C8)haloalkyl, N(R 17a )(C3~C8) Shik alkyl and N(R 17a ) (substituted and unsubstituted phenyl)) is at about 0°C to isopropyl alcohol in an anhydrous solvent such as tetrahydrofuran or ethanol at a temperature between about 80°C. Cyanate or isothiocyanate 10-5 (Q 4 are O or S, respectively. , X 5is as disclosed above), and cyclopropylamide 10-2 (Q 2 is O Yes, 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 as disclosed above) (Scheme 10, step c).

[0166] Cyclopropylamide 10-7(Q 2 is O and R 17b is H and R 17c but, Substituted or unsubstituted heterocyclyl, substituted or unsubstituted (C1-C8) alkyl and ( C3-C6) cycloalkyl, 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 17a As disclosed above (as shown) is a polar non-proton such as ethanol at temperatures between about 0°C and about 80°C. in an aqueous solvent, in the presence of an acid such as acetic acid, and a reducing agent such as sodium cyanoborohydride , R 17cis as disclosed above, Mid 10-2 (Q 2 is O and 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 As disclosed above (Scheme 10, step b) ).

[0167] [ka]

[0168] Cyclopropylamide 11-3(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 18a , R 18b and R 18c as disclosed above) is heated at a temperature between about 0°C and about 80°C in a polar aprotic solvent such as ethanol, with or without an acid such as acetic acid, R 18b and R 18caldehyde or ketone 11-2, wherein , hydrazide 11-1(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 As mentioned above as shown) (Scheme 11, Step a).

[0169] [ka]

[0170] In some embodiments, 1-3 is an α,β-unsaturated aldehyde 12-1 (R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 can be prepared from the compound Product 12-1 is prepared by the aldol synthesis of appropriately substituted commercially available aldehydes and acetaldehyde. Condensation (Yoshikawa, M.; Kamei, T., PCT International Application No. 2010123006, 2010 It will be understood by those skilled in the art that the compound can be synthesized via a process such as the steps of: Hydrobromic acid in a (C1-C6) alkanol solvent at ambient temperature and pressure, N-Bromosuccinimide, Hydrochloric Acid, N-Chlorosuccinimide and Pyridinium p-Tocopherol Orthoformic acid in the presence of an acid with a pH of 0-5, such as propylene sulfonate (PPTS) Treatment of 12-1 with (C1-C6) alkyl affords acetal 12-2 (R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 is as disclosed above, and R a However, (C1~C6 ) alkyl or R a and R a can combine to form a cyclic acetal ) (Scheme 12, Step a). Acetal 12-2 can be prepared from approximately ambient temperature to Sodium hydroxide or potassium hydroxide or charcoal at a temperature below the boiling point of haloform Inorganic bases such as sodium carbonate or potassium carbonate, and benzyltriethyl chloride ammonium, (-)-N-dodecyl-N-methylephedrinium bromide, tetrabromide Methylammonium, tetrapropylammonium bromide, tetrabutyl tetrafluoroborate methylammonium chloride, tetramethylammonium chloride or tetramethyl hexafluorophosphate haloforms, e.g., bromoform or methylammonium in the presence of a phase transfer catalyst can be treated with a carbene source such as chloroform to give the cyclopropyl acetal 12- 3(R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R a As disclosed above (Scheme 12, step b). Note: Step B This is an exothermic reaction and careful control of the exotherm must be exercised when carrying out this reaction. Cyclopropyl acetal 12-3 is easily oxidized in acetone, acetonitrile, methyl ... Methanol, ethanol, nitromethane, N,N-dimethylformamide, dimethyl sulfonate selected from the group consisting of tetrahydrofuran, ethyl acetate, tetrahydrofuran, and 1,4-dioxane In a polar solvent, an aqueous solution selected from the group consisting of nitric acid, hydrochloric acid, hydrobromic acid and sulfuric acid is used. In the presence of mineral acid, aldehyde 12-4(R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 as disclosed above) can be converted to (Scheme 12, Step c ). Cyclopropyl acid 1-3(R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 as disclosed above) at a temperature of about 0° C. to about ambient temperature, Acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, A polar non-protonated compound selected from the group consisting of tetrahydrofuran and 1,4-dioxane. In aqueous solvents, oxidizing agents such as sodium permanganate or potassium permanganate are used. or by oxidation of aldehyde 12-4 under Pinnick oxidation conditions (Scheme 12, step d). This reaction may be exothermic, so use standard Appropriate safety measures must be taken.

[0171] [ka]

[0172] In some embodiments, cyclopropyl acid 1-3 (R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 as disclosed above) are Kovalenko VN, Kulinkovich OG Tetrahedron: Asymmetry 2011, 22, 26, It is known by those skilled in the art that the compound can be resolved into its (R,R) and (S,S) enantiomers. It will be understood (Scheme 13, step a).

[0173] [ka]

[0174] In another embodiment, cyclopropyl acid R1-3 (R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 as disclosed above) can be prepared by the method in Scheme R1 can be resolved into its (R,R) and (S,S) enantiomers via

[0175] [ka]

[0176] In the formula, XR is selected from the group consisting of C1-C4 alkyl or benzyl.

[0177] In Scheme R1, the (±)-trans-racemate (i.e., trans) of Formula R1-1 is 2,2-dichloro-3-(substituted phenyl)cyclopropanecarboxylic acid (R,R) and a mixture of (S,S) enantiomers) can be prepared by reacting a compound of formula R2-1 or formula R2 in a suitable solvent. - in combination with a resolving agent, which is one of the two enantiomeric amines, and the resulting mixture Selective crystallization or precipitation of formula R3-1A or formula R3-1B

[0178] [ka]

[0179] Or, formula R3-2A or formula R3-2B

[0180] [ka]

[0181] Then, the compound of formula R3-1A or formula R3-1B is reacted with the compound of formula R3-1A to give a diastereomeric amine salt of formula R3-1B, or the diastereomeric amine salt of formula R3-2A or formula R3-2B is obtained from the mixture by and treated with an acid to give (1R,3R) compounds of formula R1-2A or R1-2B, respectively. or (1S,3S)-2,2-dihalo-3-(substituted phenyl)cyclopropanecarboxylic acid Give acid. [Example]

[0182] These examples are for illustrative purposes only and should not be construed as limiting the scope of the present disclosure. It should not be construed as being limited to only the illustrated embodiments.

[0183] Starting materials, reagents, and solvents obtained from commercial sources were used without further purification. Anhydrous solvents were purchased from Aldrich as Sure / Seal™ and used as is. Melting points were measured using a Thomas Hoover Unimelt capillary melting point apparatus. or the OptiMelt automatic from Stanford Research Systems Melting point measurements were taken with a melting point system and are uncorrected. Examples using "room temperature" are from about 20°C to about 2 The experiments were carried out in a temperature- and humidity-controlled laboratory at temperatures ranging from 4°C to 4°C. According to the naming program in Draw, ChemDraw or ACD Name Pro The program assigns the molecule its publicly known name. If not, such molecules are named using conventional naming conventions. the law of nature, 1 H NMR spectral data are in ppm (δ) and are 300 MHz, 400 MHz z, recording at 500MHz or 600MHz; 13 C NMR spectral data are pm(δ) and recorded at 75 MHz, 100 MHz or 150 MHz; 19 FN MR spectral data are in ppm (δ) and were recorded at 376 MHz.

[0184] [Example 1] trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2-methyl-4-(2,2,2-triphenylphosphine) Preparation of (fluoroacetamido)phenyl)benzamide (F1061)

[0185] [ka] trans-N-(4-amino-2-methylphenyl)-2-methyl ... 2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclo[2.2.1]phenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclo[2.2.1]phenyl) Propane-1-carboxamido)benzamide (DP1) (0.100 g, 0.179 m A solution of 1000mg of tetrahydrofuran (0.037 mL, 0.269 mmol) and triethylamine (0.037 mL, 0.269 mmol) was added to Trifluoroacetic anhydride (0.030 mL, 0.215 mmol) was added to the reaction mixture. The mixture was stirred at room temperature for 18 hours. The reaction mixture was then directly loaded onto a Celite® cartridge. The flash column was loaded using 0-40% ethyl acetate / hexane as the eluent. Purification by chromatography gave the title compound as a white solid (0.080 g, 68%) was obtained as.

[0186] The following compounds were prepared in a manner similar to the procedure outlined in Example 1. trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl) Cyclopropane-1-carboxamide)-N-(4-(2,2-difluoroacetamide) )-2-Methylphenyl)benzamide (F1062)

[0187] [ka] Isolated as a white solid (0.109 g, 95%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-Trifluoroacetamido)phenyl)benzamide (F1064)

[0188] [ka] Isolated as a pale yellow solid (0.103 g, 89%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- (mido)-2,4-difluorophenyl)benzamide (F1065)

[0189] [ka] 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)

[0190] [ka] Isolated as an off-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-trimethylsilyl) Fluoroacetamido)phenyl)benzamide (F1121)

[0191] [ka] Isolated as a pale yellow solid (0.111 g, 85%). trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl) Cyclopropane-1-carboxamide)-N-(4-(2,2-difluoroacetamide) )-3,5-difluorophenyl)benzamide (F1122)

[0192] [ka] Isolated as an off-white solid (0.066 g, 58%). trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl) Cyclopropane-1-carboxamide)-N-(2-(2,2-difluoroacetamide) )-4-Fluorophenyl)benzamide (F1123)

[0193] [ka] Isolated as an off-white solid (0.0885 g, 74%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) cyclopropane-1-carboxamido)-N-(2,6-difluoro-4-(2,2 ,2-Trifluoroacetamido)phenyl)benzamide (F1261)

[0194] [ka] Isolated as a pale yellow foam (0.065 g, 69%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenoxy) cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1330 )

[0195] [ka] Isolated as a white powder (0.068 g, 98%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- (mido)-2,4-difluorophenyl)-3-fluorobenzamide (F1333)

[0196] [ka] Isolated as an off-white powder (0.069 g, 100%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichloro) phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-( 2,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1 334)

[0197] [ka] Isolated as an off-white powder (0.062 g, 100%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichloro) (phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro ... Cetamido)-2,4-difluorophenyl)-3-fluorobenzamide (F1335 )

[0198] [ka] Isolated as a pale yellow powder (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)

[0199] [ka] Isolated as an off-white solid (0.046 g, 37%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (3-(2,2-difluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluorophenyl)cyclopropane-1-carboxamido) Acetamido)-2,4-difluorophenyl)-3-fluorobenzamide (F125 6)

[0200] [ka] Isolated as a light tan foam (0.184 g, 56%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- (mido)-2,4-difluorophenyl)-3-fluorobenzamide (F1287)

[0201] [ka] Isolated as a white solid (0.064 g, 90%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F1288 )

[0202] [ka] Isolated as a white solid (0.068 g, 93%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)-cyclopropane-1-carboxamido)-N-(3-( 2,2-Difluoroacetamido)-2,4-difluorophenyl)-3-fluorobenzyl Zuamide (F1289)

[0203] [ka] Isolated as a white solid (0.065g, 91%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(2,2,2-trifluoroacetamido)phenyl)-3-fluoro Benzamide (F1290)

[0204] [ka] Isolated as a white solid (0.068 g, 93%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (2,4-difluoro-3-phenyl)cyclopropane-1-carboxamido (2,2,2-trifluoroacetamido)phenyl)-3-fluorobenzamide (F 1291)

[0205] [ka] Isolated as a white solid (0.062 g, 95%).

[0206] [Example 2] N-(3-acetamido-2,4-difluorophenyl)-2-chloro-5-((1R, 3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylate Preparation of ruboxamidobenzamide (F1083)

[0207] [ka] N-(3-amino-)- 2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro -3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido To a solution of DP2 (0.06 g, 0.104 mmol), acetic anhydride (9.77 μl, The reaction mixture was stirred at room temperature for 18 hours and then diluted with water (3 mL). The mixture was quenched and extracted with ethyl acetate (10 mL). The organic layer was washed with hydrochloric acid (1N) and brine. The organic layer was concentrated under reduced pressure to give a residue. by column chromatography using 0-30% ethyl acetate / hexane as the synergist. Purification gave the title compound as a white solid (0.043 g, 67%).

[0208] The following compounds were prepared in a similar manner to the procedure outlined in Example 2. 2-chloro-N-(3-(2-chloro-2,2-difluoroacetamido)-2,4-di fluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl) (phenyl)cyclopropane-1-carboxamido)benzamide (F1248)

[0209] [ka] Isolated as a white solid (0.089 g, 74%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,3,3,3-Pentafluoropropanamido)phenyl)benzamide (F1251)

[0210] [ka] Isolated as a white solid (0.072 g, 57%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-dichloroacetamido) (2,4-difluorophenyl)benzamide (F1252)

[0211] [ka] 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-carboxylate Ruboxamido)benzamide (F1262)

[0212] [ka] Isolated as a white solid (0.022 g, 26%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(4-(2,2-dichloroacetamido) (2,6-difluorophenyl)benzamide (F1272)

[0213] [ka] Isolated as a white solid (0.028 g, 29%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (3-(2,2-difluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluorophenyl)cyclopropane-1-carboxamido) Acetamido)-2,6-difluorophenyl)benzamide (F1234)

[0214] [ka] Isolated as a white foamy solid (0.083 g, 66%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichloro) (phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro ... Cetoamido)-2,6-difluorophenyl)benzamide (F1238)

[0215] [ka] Isolated as an off-white foamy solid (0.090 g, 72%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- (mido)-2,6-difluorophenyl)benzamide (F1240)

[0216] [ka] Isolated as a white foamy solid (0.100 g, 84%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- (mido)-2,6-difluorophenyl)benzamide (F1241)

[0217] [ka] Isolated as a white foamy solid (0.086 g, 68%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(5-(2,2-difluoroacetamido)- (mido)-2,4-difluorophenyl)benzamide (F1242)

[0218] [ka] Isolated as a glassy solid (0.074 g, 59%). 2-chloro-N-(5-(2-chloro-2,2-difluoroacetamido)-2,4-di fluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl) (phenyl)cyclopropane-1-carboxamido)benzamide (F1243)

[0219] [ka] Isolated as a white foamy solid (0.065 g, 49%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(5-(2,2-dichloroacetamido) (2,4-difluorophenyl)benzamide (F1244)

[0220] [ka] Isolated as an off-white foamy solid (0.035 g, 28%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) cyclopropane-1-carboxamido)-N-(2,4-difluoro-5-(2,2 ,2-Trifluoroacetamido)phenyl)benzamide (F1245)

[0221] [ka] Isolated as a white foamy 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-carboxylate Ruboxamido)benzamide (F1246)

[0222] [ka] Isolated as an off-white foamy solid (0.080 g, 71%). trans-N-(4-acetamido-3,5-difluorophenyl)-2-chloro-5 -(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carbo Oxamido)benzamide (F1124)

[0223] [ka] Isolated as an off-white solid (0.042 g, 39%). trans-N-(2-acetamido-4-fluorophenyl)-2-chloro-5-(2 ,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamine C)benzamide (F1125)

[0224] [ka] Isolated as an off-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-trimethylsilyl) Chloroacetamido)phenyl)benzamide (F1126)

[0225] [ka] Isolated as a pale yellow solid (0.078 g, 59%).

[0226] [Example 3] 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(2,2,2-trifluoroacetamido)phenyl)benzamide ( Preparation of F1169

[0227] [ka] Trifluoroacetic anhydride (0.035 g, 0.251 mmol) was dissolved in anhydrous dichloromethane. N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2-chloro ... ((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl) )phenyl)cyclopropane-1-carboxamido)benzamide (DP9) (0.10 0g, 168mmol) and triethylamine (0.051g, 0.503mmol) The solution was stirred at 23°C for 12 hours and concentrated. Purification by flash chromatography gave the title compound as a white foam (0.084 g, 69%).

[0228] The following compounds were prepared in a similar manner to the procedure outlined in Example 3. 2-chloro-N-(3-(2-chloro-2,2-difluoroacetamido)-2,4-di fluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(Trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzal Mid (F1170)

[0229] [ka] Isolated as a white solid (0.089 g, 71%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2 ,2-Dichloroacetamido)-2,4-difluorophenyl)benzamide (F117 4)

[0230] [ka] Isolated as a white foam (0.058 g, 46%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2 ,2-Difluoroacetamido)-2,4-difluorophenyl)benzamide (F11 75)

[0231] [ka] 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)

[0232] [ka] Isolated as a white foam (0.015 g, 12%). N-(3-(2-bromo-2,2-difluoroacetamido)-2,4-difluorophenyl)- (1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(Trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzal Mido (F1276)

[0233] [ka] Isolated as a white solid (0.078 g, 59%). trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluoro) (3-(2,2-difluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluorophenyl)cyclopropane-1-carboxamido) (2,4-difluorophenyl)benzamide (F1331)

[0234] [ka] Isolated as a white foam (0.037 g, 62%). trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluoro) (2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3 -(2,2,2-trifluoroacetamido)phenyl)benzamide (F1332)

[0235] [ka] Isolated as a white solid (0.031 g, 51%).

[0236] [Example 4] tert-Butyl (4-((3-(2-chloro-5-((1R,3R)-2,2-dichloro) 3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzal (F)-2,6-difluorophenyl)amino)-4-oxobutyl)carbamate Preparation of 1199)

[0237] [ka] N-(3-amino-2,4-difluorophenyl)-2,4-difluorophenyl ether in ethyl acetate (2 mL) stirred at room temperature (1R,3R)-2,2-dichloro-3-(3,4-dichloro- (phenyl)cyclopropane-1-carboxamido)benzamide (DP2) (0.10 0g, 0.173mmol) was added to a solution of 4-((tert-butoxycarbonyl)amino ) butanoic acid (0.035 g, 0.173 mmol) and pyridine (0.028 mL, 0 2,4,6-tripropyl-1,3,5,2,4,6- Trioxatriphosphinane 2,4,6-trioxide (T3P®); 165m g, 0.259 mmol) was added as a 50% solution in ethyl acetate. The reaction mixture was heated to 50°C. The mixture was heated for 18 hours, then cooled to room temperature and concentrated under a stream of nitrogen. Purification by column chromatography using ethyl acetate / hexane gave the title compound was obtained as a white solid (0.111 g, 84%).

[0238] The following compounds were prepared in a similar manner to the procedure outlined 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)

[0239] [ka] Isolated as a white solid (0.097 g, 72%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-difluoropropane) Amido)-2,4-difluorophenyl)benzamide (F1249)

[0240] [ka] 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-carboxylate Ruboxamido)benzamide (F1253)

[0241] [ka] Isolated as a light brown solid (0.076 g, 64%).

[0242] [Example 5] trans-N-(3-acetamido-2-chloro-4-fluorophenyl)-2-chloro 5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1- Preparation of carboxamido)benzamide (F1160)

[0243] [ka] 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2 4,6-trioxide (T3P®, 50% solution in ethyl acetate; 0.281 g , 0.441 mmol) in anhydrous ethyl acetate (3 mL) -(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo N-(3-amino-)benzoic acid (C12) (0.100 g, 220 mmol), 2-chloro-6-fluorophenyl)acetamide (C194) (0.048g, 0.2 dropwise to a stirred solution of 1000 mg of pyridine (0.053 g, 0.661 mmol) and 1000 mg of pyridine (0.053 g, 0.661 mmol). The solution was stirred at 23°C for 12 hours and concentrated. Purification by chromatography gave the title compound as a white foam (0.105 g, 71%). Ta.

[0244] The following compounds were prepared in a similar manner to the procedure outlined in Example 5. N-(3-acetamido-2-chloro-4-fluorophenyl)-2-chloro-5-(( 1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)fluoromethyl) (phenyl)cyclopropane-1-carboxamido)benzamide (F1161)

[0245] [ka] Isolated as a white foam (0.052 g, 71%).

[0246] [Example 6] 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(4-fluorobenzamido)phenyl)benzamide (F1204) Preparation of

[0247] [ka] 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2 4,6-trioxide (T3P®, 50% solution in ethyl acetate; 0.213 g , 0.335 mmol) in anhydrous ethyl acetate (3 mL) Difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-( 4-Fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamide (D)benzamide (DP9) (0.100 g, 0.168 mmol), 4-fluorobenzoate Benzoic acid (0.028 g, 0.201 mmol) and pyridine (0.040 g, 0.50 The solution was stirred at 50°C for 12 hours and concentrated. Purification by silica gel flash chromatography gave the title compound as a white foam (0 Obtained as 0.029g, 23%).

[0248] The following compounds were prepared in a similar manner to the procedure outlined in Example 6. 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(4-methoxybenzamido)phenyl)benzamide (F1205)

[0249] [ka] 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)benzoate (2,6-difluorophenyl)nicotinamide (F1206)

[0250] [ka] 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)

[0251] [ka] 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)benzoate (2,6-difluorophenyl)-6-fluoronicotinamide (F1258 )

[0252] [ka] Isolated as a white solid (0.019 g, 15%). 2-chloro-N-(3-(1-cyanocyclopropane-1-carboxamide)-2,4- 5-((1R,3R)-2,2-dichloro-3-(4-fluorophenyl)- -3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benz Amide (F1263)

[0253] [ka] Isolated as a white foam (0.078 g, 64%). 2-chloro-N-(3-(cyclopropanecarboxamido)-2,4-difluorophenyl) (1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)-5-( ... (O-methyl)phenyl)cyclopropane-1-carboxamido)benzamide (F126) 4)

[0254] [ka] Isolated as a white foam (0.100 g, 85%). 2-chloro-N-(3-(2,2-dichloro-1-methylcyclopropane-1-carboxylate) 5-((1R,3R)-2,2-dichloro-)-2,4-difluorophenyl)-5-((1R,3R)-2,2-dichloro- 3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamide Voxamido)benzamide (F1273)

[0255] [ka] Isolated as a white solid (0.078 g, 30%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-pivalamidophenyl)benzamide (F1274)

[0256] [ka] Isolated as a white solid (0.014 g, 12%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3-(2 ,2-Difluorocyclopropane-1-carboxamido)-2,4-difluorophenyl ) Benzamide (F1275)

[0257] [ka] Isolated as a white solid (0.135 g, 73%). 2-chloro-N-(3-(cyclohex-3-ene-1-carboxamide)-2,4-di fluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(4-fluoro- 3-(Trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzal Mido (F1297)

[0258] [ka] Isolated as a white solid (0.119 g, 96%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(2-oxo-2-phenylacetamido)phenyl)benzamide ( F1298)

[0259] [ka] Isolated as a clear, colorless oil (0.087 g, 68%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(2-(methylsulfonyl)acetamido)phenyl)benzamide ( F1299)

[0260] [ka] Isolated as a white foam (0.111 g, 88%). N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro) (3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzoate (2,6-difluorophenyl)furan-2-carboxamide (F1300)

[0261] [ka] Isolated as a white solid (0.085 g, 70%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(2,2,3,3-tetrafluoropropanamido)phenyl)benz Amide (F1301)

[0262] [ka] Isolated as a white foam (0.103 g, 81%). N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro) (3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzoate 2,6-difluorophenyl-5-methylthiophene-2-carboxamide Do (F1302)

[0263] [ka] Isolated as a white solid (0.035 g, 28%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(3-oxocyclobutane-1-carboxamido)phenyl)benzal Mido (F1303)

[0264] [ka] Isolated as a white solid (0.093 g, 76%).

[0265] [Example 7] trans-N-(4-acetamido-2-methylphenyl)-2-chloro-5-(2, 2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamide ) Preparation of benzamide (F1059)

[0266] [ka] trans-N-(4-amino-2-methylphenyl)-2-methyl ... 2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclo[2.2.1]phenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclo[2.2.1]phenyl) Propane-1-carboxamido)benzamide (DP1) (0.100 g, 0.179 m mol) and triethylamine (0.037 mL, 0.269 mmol), Acetyl chloride (0.015 g, 0.197 mmol) was added. 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; 2x) and brine. Celite® was added to the organic layer and the mixture was concentrated under reduced pressure. Flash column chromatography using 0-40% ethyl acetate / hexane as synergist. Purification by HPLC gave the title compound as an off-white solid (0.079 g, 73%). Got it.

[0267] The following compounds were prepared in a similar manner to the procedure outlined in Example 7. trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2-methyl-4-(2,2,2-trimethylcyclopropane) (Iroacetamido)phenyl)benzamide (F1060)

[0268] [ka] Isolated as a white solid (0.060 g, 47%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(2,2 ,2-Trichloroacetamido)phenyl)benzamide (F1063)

[0269] [ka] Isolated as a white solid (0.039 g, 34%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (2,4-difluoro-3-(2-methyl-2-methylpropane-1-carboxamido)-N-(2,4-difluoro-3-( ... (Trimethoxyacetamido)phenyl)benzamide (F1254)

[0270] [ka] Isolated as a white solid (0.072 g, 64%).

[0271] [Example 8] 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(N-(methylsulfonyl)methylsulfonamido)phenyl)benz Preparation of amide (F1277)

[0272] [ka] Methanesulfonyl chloride (0.029 g, 0.251 mmol) was dissolved in anhydrous dichloromethane. N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2-chloro ... -((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl) (phenyl)cyclopropane-1-carboxamido)benzamide (DP9) (0.1 00g, 168mmol) and triethylamine (0.051g, 0.503mmol The solution was stirred at 23°C for 12 hours and concentrated. Purification by rush chromatography gave the title compound as a white foam (0.044 g , 33%).

[0273] [Example 9] 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-(phenylsulfonamido)phenyl)benzamide (F1295) preparation

[0274] [ka] Benzenesulfonyl chloride (0.044 g, 0.251 mmol) was dissolved in acetonitrile N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2-chloro ... ((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl) )phenyl)cyclopropane-1-carboxamido)benzamide (DP9) (0.10 The solution was stirred at 70°C for 36 hours and concentrated. Purification by silica gel flash chromatography gave the title compound as a pink solid. (0.112 g, 86%)

[0275] [Example 10] trans-2-chloro-N-(4-((4-chlorobenzyl)amino)-2-methyl (phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane Preparation of 1-carboxamido)benzamide (F1010)

[0276] [ka] 4-Chlorobenzaldehyde (0.0252 g, 0.179 mmol) was dissolved in methanol. (20 mL), water (15 mL) and acetic acid (3 mL) in trans-N-(4-aminomethylpropional) -2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro) (phenyl)cyclopropane-1-carboxamido)benzamide (DP4) (0.10 0g, 0.179mmol) and sodium acetate (29.4mg, 0.359mmol The resulting heterogeneous mixture was stirred at 25°C for 3 hours. Sodium borohydride (0.0158 g, 0.251 mmol) was added in one portion. The resulting colorless solution was stirred at ambient temperature for an additional 4 hours. The reaction mixture was quenched with water (50 mL). The organic extract was washed with water and saturated sodium hydroxide. The mixture was washed successively with aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then rotary evaporated. The mixture was concentrated under vacuum on an evaporator and purified by silica gel flash chromatography. Preparation gave the title compound as a yellow foam (0.087 g, 68%).

[0277] The following compounds were prepared in a similar manner to the procedure outlined 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)

[0278] [ka] Isolated as a yellow foam (0.095 g, 74%). trans-2-chloro-N-(4-((4-cyanobenzyl)amino)-2-methyl (phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane -1-carboxamido)benzamide (F1040)

[0279] [ka] Isolated as a yellow solid (0.097g, 76%). trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2-methyl-4-((4-methylbenzyl) (phenyl)amino)phenyl)benzamide (F1041)

[0280] [ka] Isolated as a yellow solid (0.081 g, 65%). trans-2-chloro-5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)-2,2-dichloro-3-(trifluoromethyl)phenyl) (fluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoromethyl)phenyl Fluoro-3-((4-methoxybenzyl)amino)phenyl)benzamide (F1096 )

[0281] [ka] Isolated as a white foam (0.059 g, 47%). trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2-methyl-4-((4-(trifluoromethyl) (trimethoxy)benzyl)amino)phenyl)benzamide (F1117)

[0282] [ka] 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-nitrobenzene (phenyl)amino)phenyl)benzamide (F1166)

[0283] [ka] 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) (trimethyl)benzyl)amino)phenyl)benzamide (F1165)

[0284] [ka] 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-carboxamide Samido)benzamide (F1176)

[0285] [ka] 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)

[0286] [ka] 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-phenylpropane) Phenyl)amino)phenyl)benzamide (F1178)

[0287] [ka] Isolated as a pale yellow foam (0.055 g, 58%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluoro-3-((4-nitrobenzyl)amino)phenyl)benzamide (F129) 6)

[0288] [ka] Isolated as a yellow oil (0.008 g, 4%).

[0289] [Example 11] trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(4-fluoro-3-vinylphenyl)benzyl Preparation of benzonamide (F1311)

[0290] [ka] trans-N-(3-bromo)- -4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)- (chlorophenyl)cyclopropane-1-carboxamido)benzamide (F1304) (0 A solution of 0.4 g, 0.64 mmol) of tributylvinyltin (0.26 mL, 0.89 mmol) and bis(triphenylphosphine)palladium(II) dichloride (0. 044g, 0.064mmol) was added and the reaction mixture was irradiated in a microwave at 90 °C for 1 hour. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate (2 x 10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. by column chromatography using 15-20% ethyl acetate / petroleum ether Purification gave the title compound as an off-white solid (0.11 g, 40%).

[0291] The following compounds were prepared in a similar manner to the procedure outlined in Example 11. trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(4-fluoro-2-vinylphenyl)benzyl Menzamide (F1312)

[0292] [ka] Isolated as an off-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)benzyl Menzamide (F1313)

[0293] [ka] Isolated as an off-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)

[0294] [ka] Isolated as an off-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)

[0295] [ka] Isolated as an off-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)

[0296] [ka] Isolated as an off-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)

[0297] [ka] Isolated as an off-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)

[0298] [ka] Isolated as an off-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)

[0299] [ka] Isolated as an off-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)

[0300] [ka] Isolated as an off-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-fluoro) (Vinyl)phenyl)benzamide (F1321)

[0301] [ka] Isolated as an off-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-fluoro) (Vinyl)phenyl)benzamide (F1322)

[0302] [ka] Isolated as an off-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-fluoro) (Vinyl)phenyl)benzamide (F1323)

[0303] [ka] Isolated as an off-white solid (0.11 g, 58%).

[0304] [Example 12] trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(4-((2-hydroxyethyl)amino) Preparation of )-2-methylphenyl)benzamide (F1130)

[0305] [ka] 4 M hydrogen chloride in 1,4-dioxane (0.370 mL, 1.479 mmol) was added to the dioxane trans-2-((tert-butoxycarbonyl)(4- (2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropyl) Pan-1-carboxamido)benzamido)-3-methylphenyl)amino)ethyl acetate The resulting solution was added dropwise to a stirred solution of (F1129) (0.110 g, 0.148 mmol). The resulting suspension of solid was stirred at 23°C for 12 hours, then saturated aqueous sodium bicarbonate (5 ml) was added. The aqueous mixture was extracted with ethyl acetate (3 x 5 mL) and the organic extracts were Wash with aqueous sodium chloride (5 mL) and concentrate under vacuum on a rotary evaporator. Purification by silica gel flash chromatography gave the title compound as a pale yellow solid. as a foam (0.050 g, 53%).

[0306] The following compounds were prepared in a similar manner to the procedure outlined in Example 12. 2-((4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro) (3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzyl (3-methylphenyl)amino)ethyl acetate (F1144)

[0307] [ka] Isolated as a clear, colorless oil (0.043 g, 31%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(4-fluoro-3-(trichloroethane) (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-(( 2-Hydroxyethyl)amino)-2-methylphenyl)benzamide (F1145)

[0308] [ka] Isolated as a pale yellow foam (0.040 g, 31%). trans-N-(4-((3-amino-3-oxopropyl)amino)-2-methyl (phenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Chlopropane-1-carboxamido)benzamide (F1158)

[0309] [ka] Isolated as a grey 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)

[0310] [ka] Isolated as a pale yellow foam (0.062 g, 86%).

[0311] [Example 13] N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R) -2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1- Preparation of carboxamido-3-fluorobenzamide (F1255)

[0312] [ka] tert-Butyl-N-tert-butoxycarbonyl-N in dioxane (1 mL) -[3-[[2-chloro-5-[[(1R,3R)-2,2-dichloro-3-(3-chloro) (4-fluorophenyl)cyclopropane-carbonyl]amino]-3-fluorobenzyl [Diazolidinyl]amino]-2,6-difluorophenyl]carbamate (F1239) (0.1 A solution of 66 g (0.21 mmol) of hydrogen chloride in dioxane (0.53 mL, 2.12 mmol) was added and the colorless solution was stirred at room temperature for 16 hours. The solution was concentrated, and the residue was dissolved in 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 x 2.5 mL). The combined organic extracts were washed with brine (3 mL), dried over sodium sulfate, and filtered. The residue was dissolved in a minimum amount of ethyl acetate and filtered through Celite The eluent was a gradient of 0-40% ethyl acetate in hexane. The title compound was purified by automated flash chromatography to give a white solid (0. Obtained as 111g, 88%).

[0313] The following compounds were prepared in a similar manner to the procedure outlined 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):

[0314] [ka] 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 Propane-1-carboxamido)benzamide (F1201)

[0315] [ka] Isolated as a white foam (0.077g, 81%). trans-N-(4-(4-aminobutanamido)-2-methylphenyl)-2-chloro 5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1- Carboxamido)benzamide (F1202)

[0316] [ka] 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-carboxamide Samido)benzamide (F1227)

[0317] [ka] Isolated as a brown foamy 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-carbonyl Ruboxamido)benzamide (F1228)

[0318] [ka] Isolated as an off-white foam (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)

[0319] [ka] Isolated as a white foamy 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-carboxamide Samid)benzamide (F1250)

[0320] [ka] Isolated as a white foamy 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-carboxamide samido)-N-methylbenzamide (F1056)

[0321] [ka] 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-carboxamide Mido)benzamide (F1080)

[0322] [ka] Isolated as an off-white powder (0.94 g, 94%). N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R) -2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide samido)-3-fluorobenzamide (F1324)

[0323] [ka] Isolated as a pale 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-carbonyl Ruboxamido-3-fluorobenzamide (F1325)

[0324] [ka] Isolated as an off-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-carboxamide samido-3-fluorobenzamide (F1336)

[0325] [ka] Isolated as a tan powder (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)

[0326] [ka] Isolated as a light tan solid (0.034g, 76%). trans-N-(3-amino-2,4-difluorophenyl)-3-(2,2-dichloro chloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamide -2,6-Difluorobenzamide (F1111)

[0327] [ka] Isolated as a tan solid (0.044g, 80%). trans-N-(4-amino-3,5-difluorophenyl)-2-chloro-5-(2 ,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamine Do)benzamide (DP3)

[0328] [ka] Isolated as a light brown foam (1.59 g, 93%). trans-N-(3-amino-2,4-difluorophenyl)-5-(2,2-dichloro chloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamide -2-Fluoro-3-methylbenzamide (F1151)

[0329] [ka] 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-chlor Voxamido)-3-fluorobenzamide (F1156)

[0330] [ka] 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-chlor Voxamido)-3-methylbenzamide (F1222)

[0331] [ka] Isolated as a tan solid (0.054g, 46%). trans-N-(3-amino-2,4-difluorophenyl)-3-chloro-5-(2 ,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-chlor Voxamido)-2-methylbenzamide (F1223)

[0332] [ka] Isolated as a tan 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-chlor Voxamido-3-(trifluoromethyl)benzamide (F1225)

[0333] [ka] 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-carboxamide )-3-Fluoro-2-methoxybenzamide (F1226)

[0334] [ka] 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-carboxamide samido-3-fluorobenzamide (F1284)

[0335] [ka] 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)cyclohexyl Isopropane-1-carboxamido-3-fluorobenzamide (F1285)

[0336] [ka] Isolated as a white solid (0.208 g, 93%). trans-N-(3-amino-2,4-difluorophenyl)-5-(2,2-dichloro chloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamide -3-Fluoro-2-methylbenzamide (F1286)

[0337] [ka] Isolated as a white solid (0.062 g, 89%). trans-N-(4-amino-2-methylphenyl)-2-chloro-5-(2,2-diaminophenyl)- Chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoate Zuamide (DP4)

[0338] [ka] 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-carboxamide samido)benzamide (DP2)

[0339] [ka] 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-carboxamide samido)benzamide (DP5)

[0340] [ka] Isolated as a white solid (0.107g, 96%).

[0341] [Example 14] trans-N-(2-amino-4-fluorophenyl)-2-chloro-5-(2,2- Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamide Preparation of benzoxamide (DP6)

[0342] [ka] trans-2- in a 4:1 mixture of methanol (14 mL) and water (4.7 mL) Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane- 1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide (DP 13) (0.880 g, 1.49 mmol) was added to a slurry of iron powder (0.415 g, 7.4 4 mmol) and ammonium chloride (0.239 g, 4.46 mmol) were added and mixed. The mixture was warmed to 55°C and stirred for 21 hours. The filtrate was concentrated under reduced pressure and the residue was extracted with ethyl acetate. The mixture was partitioned between methanol (100 mL) and water (60 mL). The phases were separated and the organic phase was diluted with magnesium sulfate. The residue was washed with a minimum of ethyl acetate and concentrated to a dark residue. The eluent was hexane (0-40%). Purification by automated flash chromatography using a gradient of 2% ethyl acetate gave the title compound. The compound was obtained as a yellow foam (0.66 g, 75%).

[0343] The following compounds were prepared in a similar manner to the procedure outlined in Example 14. N-(2-amino-3-fluorophenyl)-2-chloro-5-((1R,3R)-2, 2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carbohydrate Oxamido)benzamide (F1133)

[0344] [ka] Isolated as a light brown powder (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)

[0345] [ka] 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)

[0346] [ka] Isolated as a pale blue solid (0.050 g, 59%).

[0347] [Example 15] trans-N-(4-amino-2,3-dimethylphenyl)-2-chloro-5-(2, 2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide ) Preparation of benzamide (F1229)

[0348] [ka] Iron powder (325 mesh; 0.065 g, 1.163 mmol) was dissolved in ethanol (10 ml To a stirred solution of 10 mL of HCl (0.01 mL, 0.116 mmol) was added concentrated HCl (0.01 mL, 0.116 mmol). The solution was heated at 65°C for 1 hour and then cooled to 55°C. Ammonium chloride in water (3 mL) A solution of 1,2-dichloro-5-(2-chloro-2-methyl-2-propanol) was added to the solution of 1,2-dichloro-5-(2-methyl-2-propanol) (0.045 g, 0.838 mmol) followed by trans-2-chloro-5-(2-methyl-2-propanol). -(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo oxamido)-N-(2,3-dimethyl-4-nitrophenyl)benzamide (F1180 ) (0.140 g, 0.233 mmol) was added. The reaction mixture was heated to 60° C. for 2 hours. The mixture was cooled and filtered through a pad of Celite®. The filtrate was diluted with ethyl acetate ( The combined organic extracts were washed with water and brine, and extracted with anhydrous sulfuric acid. It was dried over magnesium, filtered and concentrated under reduced pressure on a rotary evaporator. The product was purified by silica gel flash chromatography to give the title compound as a tan color. as a solid (0.032 g, 23%).

[0349] The following compounds were prepared in a similar manner to the procedure outlined in Example 15. trans-N-(4-amino-2,5-dimethylphenyl)-2-chloro-5-(2, 2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide ) Benzamide (F1257)

[0350] [ka] Isolated as a golden foam (0.047g, 36%).

[0351] [Example 16] trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-hydroxybenzoate) Preparation of (phenyl)benzamide (F1203)

[0352] [ka] trans-3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Phenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl Dissolve phenyl acetate (F1193) (0.067 g, 0.108 mmol) in methanol ( 2.2 mL) and add saturated sodium bicarbonate solution (0.5 mL) at room temperature while stirring. After 1 hour, the reaction mixture was purified by thin layer chromatography (2:1 hexane-ethyl acetate). Analysis of the reaction mixture indicated that the reaction was complete. The reaction mixture was diluted with ethyl acetate and 1N sodium hydroxide. Partitioned between aqueous acid, separated the layers, and dried the organic layer over sodium sulfate. Chromatography (20 × 20 × 0.2 cm plates, 3:1 hexane-ethyl acetate) ) to give the title compound as a tan foam (0.06 g, 96%).

[0353] [Example 17] tert-Butyl-N-tert-butoxycarbonyl-N-[3-[2-chloro-[5 -[[(1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane [propanecarbonyl]amino]-3-fluorobenzoyl]amino]-2,6-difluoro Preparation of [phenyl]carbamate (F1292)

[0354] [ka] (1R,3R)-2,2-dichloro-3-(3 ,5-dichlorophenyl)cyclopropane-1-carboxylic acid (C91) (0.131 g, 0.436 mmol) was added to oxalyl chloride (0.382 mL, 4.3 6 mmol) and 1 drop of N,N-dimethylformamide. After gas evolution ceased, the solution was concentrated to give a clear oil. tert-Butoxycarbonyl-N-(3-(5-amino-2-chloro-3-fluorobenzyl) Benzamido)-2,6-difluorophenyl)carbamate (C108) (0.225g , 0.436 mmol) and sodium bicarbonate (0.110 g, 1.31 mmol) The solid was added to the flask, followed by ethyl acetate (4 mL), and the cloudy mixture was cooled to room temperature. The mixture was stirred at room temperature for 18 hours. An aliquot was analyzed by liquid chromatography / mass spectroscopy. The reaction mixture was diluted with ethyl acetate and sodium bicarbonate. The layers were separated and the organic layer was partitioned between an aqueous mixture of sodium sulfate and sodium chloride. This was dried over hexane, filtered and concentrated to give an oil. The compound was obtained as an off-white solid (0.347 g, 100%).

[0355] The following compounds were prepared in a similar manner to the procedure outlined in Example 17. tert-Butyl-N-tert-butoxycarbonyl-N-(3-(2-chloro-5- ((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclo Propane-1-carboxamido)-3-fluorobenzamido)-2,6-difluoro Phenyl)carbamate (F1294)

[0356] [ka] Isolated as an off-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-fluorobenzyl Benzamido)-2,6-difluorophenyl)carbamate (F1326)

[0357] [ka] Isolated as a yellow glass (0.257g, 100%). tert-Butyl (3-(2-chloro-5-((1R,3R)-2,2-dichloro-3- (3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-3-fluoro Orobenzamido-2,4-difluorophenyl)carbamate (F1327)

[0358] [ka] Isolated as a yellow glass (0.240 g, 99%). tert-Butyl (3-(2-chloro-5-((1R,3R)-2,2-dichloro-3- (3,4-Dichlorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzyl Benzamido)-2,4-difluorophenyl)carbamate (F1328)

[0359] [ka] Isolated as a yellow glass (0.245 g, 100%). tert-Butyl (3-(2-chloro-5-((1R,3R)-2,2-dichloro-3- (4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamide samido)-3-fluorobenzamido)-2,4-difluorophenyl)carbamate ( F1329)

[0360] [ka] Isolated as a pale yellow glass (0.242 g, 100%).

[0361] [Example 18] trans-5-(3-(3-bromo-4,5-dichlorophenyl)-2,2-dichloro Cyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzyl Preparation of benzonamide (F1005)

[0362] [ka] Dichloromethane (2 mL) was added to 5-amino-2-chloro-N-(4-fluorophenyl) ) Benzamide (C98) (0.105g, 0.396mmol), 4-dimethylamino Pyridine (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) 20 ml of propyl carbodiimide hydrochloride (0.114 g, 0.594 mmol) The reaction mixture was stirred at room temperature for 72 hours, concentrated, and dissolved. Silica gel flash column analysis using 0-100% ethyl acetate / hexane as the synergist. Purification by chromatography gave the title compound as a yellow foam (0.118 g, 45%). was obtained as.

[0363] The following compounds were prepared in a similar manner to the procedure outlined in Example 18. trans-2-chloro-5-(2,2-dichloro-3-(2-chloro-5-(trifluoromethyl)phenyl)-2,2-dichloro-3-(trifluoromethyl)phenyl) (2,4-difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoromethyl)phenyl)cyclopropane-1-carboxamido (O-phenyl)benzamide (F1004)

[0364] [ka] Isolated as a white foam (0.056 g, 61%). trans-5-(3-(3-bromo-4,5-dichlorophenyl)-2,2-dichloro Cyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzyl Menzamide (F1005)

[0365] [ka] Isolated as a yellow foam (0.1182 g, 45%). trans-5-(3-(4-bromo-3,5-dichlorophenyl)-2,2-dichloro Cyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl) Benzamide (F1006)

[0366] [ka] Isolated as a yellow foam (0.0959 g, 77%). trans-5-(3-(3-bromo-4,5-dichlorophenyl)-2,2-dichloro Cyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl) Benzamide (F1007)

[0367] [ka] Isolated as a yellow foam (0.0878 g, 70%). trans-2-chloro-5-(2,2-dichloro-3-(perfluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide (F1009)

[0368] [ka] Isolated as a white foam (0.068 g, 71%). trans-5-(3-(3-bromo-4,5-difluorophenyl)-2,2-dichloro 2-chloro-N-(2,4-difluorophenyl)cyclopropane-1-carboxamido Nyl)benzamide (F1011)

[0369] [ka] Isolated as a white foam (0.060 g, 43%). cis-5-(3-(3-bromo-4,5-difluorophenyl)-2,2-dichlorophenyl)- Chlopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl) ) Benzamide (F1012)

[0370] [ka] Isolated as a white foam (0.031 g, 22%). trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluoro) (2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)cyclopropane-1-carboxamido Nyl)benzamide (F1024)

[0371] [ka] Isolated as a white foam (0.071 g, 49%). cis-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluoro) (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl ) Benzamide (F1025)

[0372] [ka] Isolated as a white solid (0.023 g, 16%). trans-5-(3-(3-bromo-5-(pentafluoro-λ 6 -sulfanyl)f (phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N- (2,4-Difluorophenyl)benzamide (F1031)

[0373] [ka] Isolated as a white foam (0.066g, 52%). cis-5-(3-(3-bromo-5-(pentafluoro-λ 6 -sulfanyl)pheny 2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2 ,4-Difluorophenyl)benzamide (F1032)

[0374] [ka] Isolated as a clear, colorless oil (0.031 g, 24%). cis-2-chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluoro) (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl ) Benzamide (F1033)

[0375] [ka] Isolated as a white foam (0.043 g, 29%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluoromethyl)-2,4-difluoromethyl) (2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)cyclopropane-1-carboxamido Nyl)benzamide (F1034)

[0376] [ka] Isolated as a white foam (0.033 g, 22%). trans-2-cyano-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-N-methyl Chilbenzamide (F1039)

[0377] [ka] Isolated as a white foam (0.043 g, 38%). trans-N-allyl-2-chloro-N-(2-cyano-4-fluorophenyl)-5 -(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo Oxamido)benzamide (F1055)

[0378] [ka] Isolated as an orange foam (0.144 g, 47%). trans-2-chloro-5-(3-(3,5-dichlorophenyl)-2,2-difluoro Isocyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide (F1057)

[0379] [ka] Isolated as an off-white solid (0.128 g, 84%). trans-2-chloro-5-(3-(3,5-dichlorophenyl)-2,2-difluoro Isocyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benz Amide (F1058)

[0380] [ka] Isolated as a white powder (0.127 g, 80%). trans-tert-butyl(3-(2-chloro-5-(3-(3,5-dichlorophenyl) Nyl)-2,2-difluorocyclopropane-1-carboxamido)benzamide)-2 ,6-difluorophenyl)carbamate (F1070)

[0381] [ka] Isolated as a white powder (0.150 g, 83%). trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-(methylamino) (N-phenyl)-N-methylbenzamide (F1071)

[0382] [ka] 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-carboxamide)- N-(prop-2-yn-1-yl)benzamide (F1072)

[0383] [ka] 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-carboxamide Benzamido)methyl acetate (F1084)

[0384] [ka] Isolated as a yellow film (0.026 g, 22%). trans-2-chloro-5-(2,2-dichloro-3-(4-iodophenyl)cyclo[2.0.1.2.2.1.3.2.1.2.2.1 ... propane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide ( F1087)

[0385] [ka] Isolated as an off-white powder (0.14 g, 72%). trans-2-chloro-5-(2,2-dichloro-3-(3-iodophenyl)cyclo[2.0.1.2.2.1.3.2.1.2.2.1 ... propane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide ( F1088)

[0386] [ka] Isolated as a brown semi-solid (0.14 g, 68%). trans-2-chloro-5-(2,2-dichloro-3-(4-(pentafluoro-λ 6 -sulfanyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-di Fluorophenyl)benzamide (F1089)

[0387] [ka] 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-di Fluorophenyl)benzamide (F1090)

[0388] [ka] Isolated as a brown semi-solid (0.15 g, 73%). trans-2-chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2- Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide)- N-Ethylbenzamide (F1091)

[0389] [ka] 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-chlor Voxamido)benzamide (F1099)

[0390] [ka] 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-carboxamide Menzamide (F1140)

[0391] [ka] Isolated as an off-white powder (0.087 g, 42%). trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2 ,2-Dichloro-3-(3-iodophenyl)cyclopropane-1-carboxamide Menzamide (F1141)

[0392] [ka] Isolated as a grey foam (0.081 g, 40%). trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2 ,2-dichloro-3-(4-(pentafluoro-λ 6 -sulfanyl)phenyl)cyclo Propane-1-carboxamido)benzamide (F1142)

[0393] [ka] Isolated as a white powder (0.073 g, 36%). trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2 ,2-dichloro-3-(3-(pentafluoro-λ 6 -sulfanyl)phenyl)cyclo Propane-1-carboxamido)benzamide (F1143)

[0394] [ka] Isolated as an off-white foam (0.074 g, 36%). trans-2-chloro-5-(2,2-dichloro-3-(3-iodophenyl)cyclo[2.0.1.2.2.1.3.2.1.2.2.1 ... propane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)-2 ,4-Difluorophenyl)benzamide (F1281)

[0395] [ka] Isolated as a tan powder (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 (F129 3)

[0396] [ka] 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)cyclopro [Pancarbonyl]amino]benzoyl]-methyl-amino]-2,6-difluoro- Nyl]carbamate (CF1)

[0397] [ka] 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 (d d, 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 -1 19.20, -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-methylbenzal (mido)-2,6-difluorophenyl)(methyl)carbamate (CF2)

[0398] [ka] Isolated as a white foam (0.081 g, 40.6%): 1 H NMR (500 MHz, methanol d4) 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), 3.2 2 (q, J = 3.3 Hz, 1H), 3.18 (s, 0H), 3.14 (d, J = 8.1 Hz, 1H), 3.09 (s, 1H), 2.9 3 (s, 2H), 1.53 - 1.45 (m, 2H), 1.39 - 1.27 (m, 6H), 1.26 - 1.15 (m, 3H); 19 FNM R (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)cyclohexyl Isopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carboxamide Bamate (DP7)

[0399] [ka] 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)

[0400] [ka] 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)

[0401] [ka] Isolated as a pale orange foam (0.266 g, 66%).

[0402] [Example 19] trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2 ,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane Preparation of propane-1-carboxamido)-N-methylbenzamide (F1112)

[0403] [ka]

[0404] Step 1: tert-Butyl N-tert-butoxycarbonyl-N-[3-[(2 -chloro-5-nitro-benzoyl)-methyl-amino]-2,6-difluoro-phenyl [C144] carbamate (0.138g, 0.225mmol), ammonium chloride (0.0409 g, 0.764 mmol) and iron powder (0.0711 g, 1.273 mmol) mol) in methanol (2.4 mL) and water (0.8 mL) to give a black suspension. The reaction mixture was heated to 60° C. for 5 hours. The reaction mixture was filtered, and the filtrate was extracted with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate and evaporated to The crude material was obtained as an orange oil which was used without purification.

[0405] Step 2: Dissolve the crude aniline in dichloromethane (2422 μL) to give an orange solution. 4.0 M hydrogen chloride in 1,4-dioxane (606 μL, 2.422 mmol) was added. The reaction mixture was stirred at room temperature overnight. The volatiles were removed. The residue was diluted with dichloromethane. trans-2,2-dichloro-3-(4-fluoro-3-(trimethylsilyl)methyl)-2,2-dichloro-3-(trimethylsilyl)methyl) Fluoromethyl)phenyl)cyclopropane-1-carboxylic acid (C76) (0.077g , 0.242 mmol) and N,N-dimethylpyridin-4-amine (0.0592 g N-(3-dimethylaminopropyl)propanol was added to give a yellow suspension. (propyl)-N'-ethylcarbodiimide hydrochloride (69.6 mg, 0.363 mmol) Upon addition, everything went into solution and the reaction mixture darkened to a deep blue color. The mixture was stirred at room temperature for 3 hours. The volatiles were removed. 0-100% ethyl acetate / hexane was used as the eluent. The title compound was purified by flash column chromatography using a PEG-4000 HPLC to give a pale yellow This was obtained as a colored foam (0.061 g, 39%).

[0406] The following compounds were prepared in a similar manner to the procedure outlined in Example 19. trans-N-allyl-N-(3-amino-2,4-difluorophenyl)-2-chloro 5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)- (I)cyclopropane-1-carboxamido)benzamide (F1113)

[0407] [ka] 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 propane-1-carboxamido)-N-(prop-2-yn-1-yl)benzamide (F 1114)

[0408] [ka] Isolated as a yellow foam (0.054 g, 35%).

[0409] [Example 20] trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)cyclopropane-1-carboxamido Preparation of (Nyl)benzamide (F1105):

[0410] [ka] trans-2,2-dichloro-3-(3-chloro-4-furan) in ethyl acetate (4 mL) (fluorophenyl)cyclopropane-1-carboxylic acid (C40) (0.040g, 0.14 mmol), 3-amino-2,6-dichloro-N-(2,4-difluorophenyl)benzene amide (C129) (0.045 g, 0.14 mmol) and pyridine (0.034 g, 0.43 mmol) in ethyl acetate. 50% solution of 5,2,4,6-trioxatriphosphinane 2,4,6-trioxide ( The resulting colorless solution was heated at 50°C for 16 hours. The reaction mixture was stirred and cooled to room temperature, and then adsorbed onto Celite® (approximately 1.5 g). and automated flash chromatography using a gradient of 0-55% ethyl acetate in hexane as the eluent. Purification by chromatography gave the title compound as a white solid (0.083 g, 100%) was obtained as.

[0411] The following compounds were prepared in a similar manner to the procedure outlined in Example 20. tert-Butyl-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3 -(4-Fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carbo Oxamido)benzamido)-2,6-difluorophenyl)carbamate (F1053)

[0412] [ka] 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-carboxamide)-N-( 2,4-Difluorophenyl)benzamide (F1066)

[0413] [ka] Isolated as a white foam (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)

[0414] [ka] Isolated as a white foam (0.050 g, 26%). trans-tert-butyl-(3-(5-(3-(3-bromo-5-(trifluoro Methyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro (chlorobenzamido)-2,6-difluorophenyl)carbamate (F1073)

[0415] [ka] 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-carbo Oxamido)benzamido)-2,6-difluorophenyl)carbamate (F1074)

[0416] [ka] 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-carboxamine (d)benzamido)-2,6-difluorophenyl)carbamate (F1077)

[0417] [ka] 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-carboxamide (mido)benzamido)-2,6-difluorophenyl)carbamate (F1078)

[0418] [ka] Isolated as a white solid (0.984g, 85%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,4-difluorophenyl)-2,6-dipropane-1-carboxamido Fluorobenzamide (F1086)

[0419] [ka] 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-carboxamide (Mido)benzamido)-2,6-difluorophenyl)carbamate (F1092)

[0420] [ka] Isolated as a white solid (0.199 g, 86%). trans-5-(3-(3-bromo-2,5-difluorophenyl)-2,2-dichloro 2-chloro-N-(2,4-difluorophenyl)cyclopropane-1-carboxamido Nyl)benzamide (F1093)

[0421] [ka] Isolated as a white foam (0.033 g, 30%). cis-5-(3-(3-bromo-2,5-difluorophenyl)-2,2-dichlorophenyl) Chlopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl) ) Benzamide (F1094)

[0422] [ka] Isolated as a clear, colorless oil (0.042 g, 38%). trans-tert-butyl-(3-(5-(3-(3-bromo-2,5-difluoro) Phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobene (2,6-difluorophenyl)carbamate (F1095)

[0423] [ka] Isolated as a white solid (0.058 g, 26%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(4-fluorophenyl)-2,6-difluoropropane-1-carboxamido ) Benzamide (F1100)

[0424] [ka] 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-difluoro Fluorobenzamide (F1101)

[0425] [ka] Isolated as a white solid (0.030 g, 90%). trans-N-(4-acetamidophenyl)-2,6-dichloro-3-(2,2-di Chloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamine C)benzamide (F1102)

[0426] [ka] Isolated as a white solid (0.032 g, 71%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl) Benzamide (F1103)

[0427] [ka] Isolated as a white solid (0.068 g, 88%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (F)(fluorophenyl)cyclopropane-1-carboxamido)-N-phenylbenzamide 1104)

[0428] [ka] 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-carboxamide)- N-Methylbenzamide (F1106)

[0429] [ka] Isolated as a tan solid (0.038g, 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-difluoro- Phenyl]carbamate (F1107)

[0430] [ka] Isolated as a white solid (0.086 g, 80%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-2,6-difluoro-N-phenylbenzamide ( F1108)

[0431] [ka] 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)cyclopropanecarbonate [Carbonyl]amino]-2,6-difluorobenzoyl]amino]-2,6-difluoro Phenyl]carbamate (F1109)

[0432] [ka] Isolated as a tan solid (0.101 g, 73%). trans-tert-butyl-(3-(5-(3-(4-bromo-3-(trifluoro Methyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro (2,6-difluorophenyl)chlorobenzamidocarbamate (F1115)

[0433] [ka] Isolated as a white foam (0.179 g, 85%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)-2,2-dichloro-3-(trifluoromethyl)phenyl) (2,4-difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoromethyl)phenyl)cyclopropane-1-carboxamido (O-phenyl)benzamide (F1118)

[0434] [ka] Isolated as a white foam (0.078 g, 83%). trans-tert-butyl-(3-(2-chloro-5-(2,2-dichloro-3-( 3-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamine (d)benzamido)-2,6-difluorophenyl)carbamate (F1119)

[0435] [ka] Isolated as a white solid (0.197g, 88%). trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-( (trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4- Difluorophenyl)benzamide (F1147)

[0436] [ka] Isolated as a pale yellow foam (0.094 g, 52%). cis-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-(trifluoromethyl)methyl) (fluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoromethyl)phenyl (Fluorophenyl)benzamide (F1148)

[0437] [ka] 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-carboxamide)-N-( 2,4-Difluorophenyl)benzamide (F1163)

[0438] [ka] 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)

[0439] [ka] Isolated as a white foam (0.040 g, 22%). trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluoro) (2,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)cyclopropane-1-carboxamido Nyl)benzamide (F1172)

[0440] [ka] Isolated as a white foam (0.076 g, 39%). cis-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluoro) (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl ) Benzamide (F1173)

[0441] [ka] Isolated as a white foam (0.032 g, 17%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(pentafluoropropane) Luoro-λ 6 -sulfanyl)phenyl)cyclopropane-1-carboxamido)-N- (2,4-Difluorophenyl)benzamide (F1232)

[0442] [ka] Isolated as a white foam (0.088 g, 50%). cis-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-(pentafluoro) Rho-λ 6-sulfanyl)phenyl)cyclopropane-1-carboxamido)-I-(2 ,4-Difluorophenyl)benzamide (F1233)

[0443] [ka] 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)cyclopropane [propanecarbonyl]amino]-3-fluorobenzoyl]amino]-2,6-difluoro Phenyl]carbamate (F1282)

[0444] [ka] 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) methyl)phenyl]cyclopropanecarbonyl]amino]-3-fluoro-benzoyl]a [amino]-2,6-difluorophenyl]carbamate (F1283)

[0445] [ka] Isolated as a white solid (0.298 g, 83%). trans-2-chloro-5-(2,2-dichloro-3-(2-chloro-5-(trifluoromethyl)phenyl)-2,2-dichloro-3-(trifluoromethyl)phenyl) (2,2,2-trimethylphenyl)-cyclopropane-1-carboxamido Trifluoroethyl)benzamide (F2001)

[0446] [ka] Isolated as a white foam (0.047 g, 52%). trans-2-chloro-5-(2,2-dichloro-3-(perfluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzaldehyde Mido (F2002)

[0447] [ka] Isolated as a white solid (0.069 g, 76%). trans-5-(3-(3-bromo-4,5-difluorophenyl)-2,2-dichloro Isocyclopropane-1-carboxamido)-2-chloro-N-(2,2,2-trifluoromethyl) (triethyl)benzamide (F2003)

[0448] [ka] Isolated as a white foam (0.067g, 51%). cis-5-(3-(3-bromo-4,5-difluorophenyl)-2,2-dichlorophenyl)- Chloropropane-1-carboxamido)-2-chloro-N-(2,2,2-trifluoroethane Benzamide (F2004)

[0449] [ka] Isolated as a white foam (0.029 g, 22%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (2,2,3,3,3-phenyl)cyclopropane-1-carboxamido)-N-(2,2,3,3,3-phenyl)cyclopropane-1-carboxamido (pentafluoropropyl)benzamide (F2005)

[0450] [ka] Isolated as a white solid (0.068 g, 93%). trans-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluoro) (2,2,2-trifluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluorophenyl)cyclopropane-1-carboxamido (triethyl)benzamide (F2006)

[0451] [ka] Isolated as a clear, colorless oil (0.077 g, 56%). cis-2-chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-fluoro) (phenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethylene Benzamide (F2007)

[0452] [ka] Isolated as a clear, colorless oil (0.022 g, 16%). trans-5-(3-(3-bromo-5-(pentafluoro-λ 6 -sulfanyl)f (phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N- (2,2,2-trifluoroethyl)benzamide (F2008)

[0453] [ka] Isolated as a white foam (0.065 g, 54%). cis-5-(3-(3-bromo-5-(pentafluoro-λ 6 -sulfanyl)pheny 2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2 ,2,2-trifluoroethyl)benzamide (F2009)

[0454] [ka] Isolated as a clear, colorless oil (0.028 g, 23%). cis-2-chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluoro) (phenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethylene Chill)benzamide (F2010)

[0455] [ka] Isolated as a white foam (0.039 g, 28%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-2,4-difluoromethyl)-2,4-difluoromethyl) (2,2,2-trifluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluorophenyl)cyclopropane-1-carboxamido (triethyl)benzamide (F2011)

[0456] [ka] 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-carboxamide)-N-( 2,2,2-trifluoroethyl)benzamide (F2012)

[0457] [ka] 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)

[0458] [ka] Isolated as a white foam (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)

[0459] [ka] Isolated as a white foam (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)

[0460] [ka] Isolated as a golden oil (0.045 g, 25%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 1,2-Difluoro-2,6-difluorobenzamide (F 2016)

[0461] [ka] Isolated as a white solid (0.068 g, 91%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,2,2-trifluoropropane-1-carboxamido)-2,6-difluoro- (Oroethyl)benzamide (F2017)

[0462] [ka] Isolated as a white solid (0.081 g, 96%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2,6-difluoro-N-(2,2,3,3,3-propane-1-carboxamido)- Pentafluoropropyl)benzamide (F2018)

[0463] [ka] Isolated as a white solid (0.068 g, 94%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (O-phenyl)cyclopropane-1-carboxamido)-N-ethylbenzamide (F2 019)

[0464] [ka] Isolated as a white solid (0.077g, 88%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (2,2,2-trifluorophenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluorophenyl)cyclopropane-1-carboxamido (triethyl)benzamide (F2020)

[0465] [ka] Isolated as a white solid (0.052 g, 66%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-2,6-difluoro-N-propylbenzamide ( F2021)

[0466] [ka] Isolated as a white foam (0.084 g, 91%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (F)(fluorophenyl)cyclopropane-1-carboxamido)-N-propylbenzamide 2022)

[0467] [ka] Isolated as a white solid (0.077g, 90%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2,6-difluoro-N-(3,3,3-trifluoropropane-1-carboxamido)- (Oropropyl)benzamide (F2023)

[0468] [ka] Isolated as a white solid 0.067g, 82%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (3,3,3-trifluorophenyl)cyclopropane-1-carboxamido)-N-(3,3,3-trifluorophenyl)cyclopropane-1-carboxamido (propyl)benzamide (F2024)

[0469] [ka] Isolated as a white solid (0.071 g, 92%). trans-2,6-dichloro-3-(2,2-dichloro-3-(3-chloro-4-fluoro) (2-fluorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoroethyl)benzyl Menzamide (F2025)

[0470] [ka] 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 Menzamide (F2026)

[0471] [ka] Isolated as a white solid (0.070 g, 88%). trans-3-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-2,6-difluoro-N-(2-fluoroethyl) Benzamide (F2027)

[0472] [ka] Isolated as a white solid (0.088 g, 96%). trans-N-(3-chloropropyl)-3-(2,2-dichloro-3-(3-chloropropyl)- -4-fluorophenyl)cyclopropane-1-carboxamido)-2,6-difluoro Benzamide (F2028)

[0473] [ka] Isolated as a white solid (0.083 g, 98%).

[0474] [Example 21] trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2 ,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane Preparation of propane-1-carboxamido)benzamide (DP8)

[0475] [ka]

[0476] Step 1: trans-tert-butyl-N-tert-butoxycarbonyl-N -[3-(5-(3-(4-fluoro-3-trifluoromethyl)phenyl)-2,2-di Chlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-di Preparation of trans-2-fluorophenyl]carbamate. Anhydrous ethyl acetate (3 mL) was added to ,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane propane-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. The solution was added to a 10 mL glass tube containing 100 mL of HCl (0.079 g, 0.158 mmol) at room temperature. The resulting solution was added with pyridine (0.0374 g, 0.473 mmol) and 2,4, 6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6- trioxide (T3P®, 50% solution in ethyl acetate; 0.201 g, 0.31 The solution was stirred at 24°C for 12 hours, concentrated to dryness, and 0.5 mmol was added as the eluent. Silica gel flash column chromatography using ~50% ethyl acetate / hexane and purified by trans-tert-butyl-N-tert-butoxycarbonyl -N-[3-(5-(4-fluoro-3-(trifluoromethyl)phenyl)-2,2- Dichlorocyclopropane-1-carboxamide)-2-chlorobenzamide)-2,6- difluorophenyl]carbamate as a white solid (0.114 g, 86%).

[0477] Step 2: trans-N-(3-amino-2,4-difluorophenyl)-2-chloride 5-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)methyl)-4-fluoro- ... Preparation of (cyclopropane-1-carboxamido)benzamide. Anhydrous hydrogen chloride solution ( 4.0 M in dioxane; 0.326 mL, 1.305 mmol) t-Butyl-N-tert-butoxycarbonyl-N-[3-(5-(3-(4-fluoro (3-trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carbo oxamido)-2-chlorobenzamido)-2,6-difluorophenyl]carbamate ( The suspension was stirred at 24°C for 12 hours. The dichloromethane was then removed under a stream of nitrogen and the sample was dissolved in ethyl acetate (20 mL). and saturated aqueous sodium bicarbonate solution (5 mL) and saturated aqueous sodium chloride solution (5 mL). The ethyl acetate solution was dried over anhydrous magnesium sulfate, filtered, and The residue was concentrated under vacuum on a condenser evaporator. Purification by silica gel flash chromatography using ethanol / hexane gave the title compound. The product was obtained as a white foam (0.043 g, 53%).

[0478] The following compounds were prepared in a similar manner to the procedure outlined in Example 21. trans-N-(3-amino-2,4-difluorophenyl)-5-(3-bromophenyl)- Mo-5-(pentafluoro-λ 6 -sulfanyl)phenyl)-2,2-dichlorocyclo Propane-1-carboxamido)-2-chlorobenzamide (F1042)

[0479] [ka] Isolated as a white foam (0.079 g, 74%). cis-N-(3-amino-2,4-difluorophenyl)-5-(3-(3-bromo- 5-(pentafluoro-λ 6 -sulfanyl)phenyl)-2,2-dichlorocyclopro Pan-1-carboxamido-2-chlorobenzamide (F1043)

[0480] [ka] Isolated as a clear, colorless oil (0.028 g, 56%). trans-N-(3-amino-2,4-difluorophenyl)-5-(3-bromophenyl)- (4,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamide (mido)-2-chlorobenzamide (F1044)

[0481] [ka] 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-carboxamide )-2-chlorobenzamide (F1045)

[0482] [ka] 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)

[0483] [ka] Isolated as a white foam (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-carboxylate Ruboxamido)benzamide (F1047)

[0484] [ka] 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)

[0485] [ka] Isolated as a white foam (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)

[0486] [ka] 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-carboxamide)-N-( 2,4-Difluorophenyl)benzamide (F1050)

[0487] [ka] Isolated as a white foam (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)

[0488] [ka] Isolated as a white foam (0.063 g, 46%). N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R) -2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclohexyl Dipropane-1-carboxamido)benzamide (DP9)

[0489] [ka] 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 (I)cyclopropane-1-carboxamido)benzamide (F1068)

[0490] [ka] Isolated as a white foam (0.042 g, 44%). cis-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-((ci s)-2,2-Dichloro-3-(4-fluoro-3-methyl-5-(trifluoromethyl) )phenyl)cyclopropane-1-carboxamido)benzamide (F1069)

[0491] [ka] Isolated as a white foam (0.032 g, 51%). trans-N-(3-amino-2,4-difluorophenyl)-5-(3-bromophenyl)- (5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxylate Ruboxamido-2-chlorobenzamide (F1075)

[0492] [ka] 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 Pan-1-carboxamido)benzamide (F1079)

[0493] [ka] Isolated as a white foam (0.068 g, 68%). cis-(3-amino-2,4-difluorophenyl)-5-(3-(3-bromo-2, 5-Difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamide)- 2-Chlorobenzamide (F1097)

[0494] [ka] Isolated as a clear, colorless oil (0.019 g, 58%). trans-N-(3-amino-2,4-difluorophenyl)-5-(3-bromophenyl)- (2,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamide (mido)-2-chlorobenzamide (F1098)

[0495] [ka] Isolated as a clear, colorless oil (0.014 g, 32%). trans-N-(3-amino-2,4-difluorophenyl)-5-(3-(4-bromophenyl)- (3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxylate Ruboxamido-2-chlorobenzamide (F1116)

[0496] [ka] Isolated as a white foam (0.140 g, 86%). trans-N-(3-amino-2,4-difluorophenyl)-2-chloro-5-(2 ,2-Dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropane Pan-1-carboxamido)benzamide (F1127)

[0497] [ka] 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)cyclohexyl Isopropane-1-carboxamido)benzamide (F1149)

[0498] [ka] Isolated as a white foam (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 Propane-1-carboxamido)benzamide (F1150)

[0499] [ka] 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 (I)cyclopropane-1-carboxamido)benzamide (F1167)

[0500] [ka] Isolated as a white foam (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)

[0501] [ka] 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)

[0502] [ka] Isolated as a white foam (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-carboxylate Ruboxamido)benzamide (F1182)

[0503] [ka] Isolated as a white foam (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)phen Nyl)cyclopropane-1-carboxamido)benzamide (F1259)

[0504] [ka] 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)

[0505] [ka] Isolated as a clear, colorless oil (0.032 g, 67%).

[0506] [Example 22] trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-methoxyphenyl) Preparation of (Nyl)benzamide (F1171)

[0507] [ka] trans-2-chloro-5-(2,2-dicylic acid) as a slurry in toluene (2 mL) 3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoin Acid (C12) (0.1 g, 0.22 mmol) was added to oxalyl chloride ( 0.0.097 mL 1.1 mmol) and 1 drop of N,N-dimethylformamide. After the mixture became homogeneous and gas evolution ceased, the solution was concentrated to give a clear oil. It was then cooled in an ice bath under nitrogen. 35 g, 0.22 mmol) as a solution in pyridine (2 mL) was added with stirring to the reaction mixture. The reaction mixture was allowed to warm to room temperature and stirred overnight. An aliquot was removed and diluted with dimethyl sulfoxide. and examined by liquid chromatography / mass spectroscopy, these were the desired products The reaction mixture was diluted with ethyl acetate and aqueous hydrochloric acid (1N The layers were separated and the organic phase was dried over sodium sulfate. Purification by column chromatography (3:1 hexane-ethyl acetate) gave the title compound The product was obtained as a greenish solid (0.075 g, 57%).

[0508] The following compounds were prepared in a similar manner to the procedure outlined in Example 22. trans-3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenoxy)methyl) Nyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl Nyl acetate (F1193)

[0509] [ka] Isolated as a pale yellow foam (0.105 g, 52%). trans-methyl 3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichloro) (phenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluoro Isobenzoate (F1265)

[0510] [ka] Isolated as a white foam (0.060 g, 44%).

[0511] [Example 23] trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamido)-N-(4-hydroxy-2-methylphenyl) Preparation of benzamide (F1224)

[0512] [ka] trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl) ) Cyclopropane-1-carboxamido) benzoic acid (C12) (0.221g, 0.48 7mmol), 4-amino-3-methylphenol (0.072g, 0.59mmol) and 4-dimethylaminopyridine (0.071 g, 0.59 mmol) were weighed into a round-bottom N,N-dimethylformamide (2 mL) was added via syringe to the flask. ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride at room temperature while stirring. Salt (0.19 g, 0.97 mmol) was added. After 64 hours, an aliquot was removed and Dilution with dimethyl sulfoxide and analysis by liquid chromatography / mass spectroscopy After 120 hours, the reaction mixture was washed with ethyl acetate and brine. The layers were separated and the organic phase was dried over sodium sulfate. The product was purified by HPLC and eluted in the order of trans-2-chloro-5-(2,2-dichloro-3 -(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-chlorophenyl) (hydroxy-2-methylphenyl)benzamide was obtained as an off-white solid (0.022 g , 8%) and trans-4-amino-3-methylphenyl 2-chloro-5- (2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide The benzoate was isolated as an off-white solid (0.064 g, 24%). Ta. 1 H NMR (400 MHz, acetone-d6) 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), 4.4 7 (ad, J = 10.7 Hz, 2H), 3.67 (d, J = 8.3 Hz, 1H), 3.46 (d, J = 8.4 Hz, 1H), 2.1 7 (s, 3H); 13 C NMR (101 MHz, acetone-d6) 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;ESIMSm / z559([M+H ] + ).

[0513] [Example 24] trans-tert-butyl-(4-(2-chloro-5-(2,2-dichloro-3-( 3,5-Dichlorophenyl)cyclopropane-1-carboxamido)benzamide)-3 Preparation of (-methylphenyl)carbamate (DP10)

[0514] [ka] tert-Butyl(4-amino-3-methylphenyl) in dichloromethane (2 mL) A solution of carbamate (C184) (0.052 g, 0.233 mmol) was added to 3-((( Ethylimino)methylene)amino)-N,N-dimethylpropan-1-amine hydrochloride(0 0.045g, 0.233mmol), N,N-dimethylpyridin-4-amine (0.02 1g, 0.171mmol) and trans-2-chloro-5-(2,2-dichloro- 3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C 12) (0.075 g, 0.155 mmol) was added. The reaction was stirred at room temperature for 14 hours. The reaction mixture was loaded directly onto a Celite-packed column and eluted with 0–30% acetic acid ethanol. Purification by flash column chromatography using a gradient of ethyl acetate / hexanes The title compound was obtained as a white solid (0.056 g, 55%). 1 H 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 ;ES IMS656([MH] - ).

[0515] [Example 25] 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- Preparation of difluorophenyl]carbamate (F1239)

[0516] [ka] 2-Chloro-5-((1R,3R)-2,2-dichloro) -3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamide)- To a solution of 3-fluorobenzoic acid (C1) (0.360 g, 0.79 mmol), tert -butyl N-(3-amino-2,6-difluoro-phenyl)-N-tert-butoxy Carbonyl carbamate (C182) (0.327 g, 0.95 mmol) and pyridinium 2,4-Dimethyl-2,5-diol (0.188 g, 0.191 mL, 2.37 mmol) in ethyl acetate. 4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4, A 50% solution of 6-trioxide (0.94 mL, 1.58 mmol) was added, and the resulting The golden solution was warmed to 45° C. and stirred for 68 h. The reaction mixture was concentrated to a viscous, amber color. The residue was dissolved in a minimum amount of methylene chloride (approximately 3 mL) and absorbed onto Celite®. The adsorbed material was separated using a gradient of 0-25% ethyl acetate in hexane as the eluent. Purification by automated flash chromatography gave the title compound (0.166 g, 8 7%) as a white solid.

[0517] The following compounds were prepared in a similar manner to the procedure outlined in Example 25. 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (3-fluoro-2-nitrophenyl)cyclopropane-1-carboxamido Phenyl)benzamide (F1081)

[0518] [ka] Isolated as a yellow solid (0.056 g, 43%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (2-fluorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-methyl (5-nitrophenyl)benzamide (F1082)

[0519] [ka] Isolated as an off-white foam (0.109 g, 81%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (4,5-difluoro-2-phenyl)cyclopropane-1-carboxamido Nitrophenyl)benzamide (F1085)

[0520] [ka] Isolated as a yellow film (0.039 g, 28%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenoxy) (cyclopropane-1-carboxamido)-N-(3-(2,2-difluoroacetamido)- (mido)-2,4-difluorophenyl)benzamide (F1268)

[0521] [ka] Isolated as a white powder (0.049 g, 34%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichloro) (phenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluoro ... Cetoamido)-2,4-difluorophenyl)benzamide (F1269)

[0522] [ka] Isolated as a white solid (0.078 g, 55%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (3-(2,2-difluorophenyl)cyclopropane-1-carboxamido)-N-(3-(2,2-difluorophenyl)cyclopropane-1-carboxamido) Acetamido)-2,4-difluorophenyl)benzamide (F1270)

[0523] [ka] Isolated as a white foam (0.084 g, 58%). 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenoxy) (3-(2,2-difluoro-N-methyl)cyclopropane-1-carboxamido)-N-( ... (2,4-difluorophenyl)benzamide (F1271)

[0524] [ka] Isolated as a white foam (0.090 g, 61%). trans-N-(3-bromo-4-fluorophenyl)-2-chloro-5-(2,2- Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide Menzamide (F1304)

[0525] [ka] Isolated as an off-white solid (0.18 g, 33%). trans-N-(2-bromo-4-fluorophenyl)-2-chloro-5-(2,2- Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide Menzamide (F1305)

[0526] [ka] Isolated as an off-white solid (0.18 g, 37%). trans-N-(4-bromo-2-fluorophenyl)-2-chloro-5-(2,2- Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide Menzamide (F1306)

[0527] [ka] Isolated as an off-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-carboxamine C)benzamide (F1307)

[0528] [ka] Isolated as an off-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-carboxamine C)benzamide (F1308)

[0529] [ka] Isolated as an off-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-carboxamine C)benzamide (F1309)

[0530] [ka] Isolated as an off-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-carboxamine D)benzamide (DP11)

[0531] [ka] Isolated as an off-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)

[0532] [ka] Isolated as a white foam (0.012 g, 8%). trans-tert-butyl-(3-(2-chloro-5-(2,2-dichloro-3-( 3,5-Dichlorophenyl)cyclopropane-1-carboxamido)benzamide)-2 ,4-difluorophenyl)carbamate (F1023)

[0533] [ka] Isolated as a white foam (0.088 g, 56%). trans-N-(3-acetamido-2,4-dimethylphenyl)-2-chloro-5- (2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide Samido)benzamide (F1128)

[0534] [ka] 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)

[0535] [ka] 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)

[0536] [ka] Isolated as a white solid (0.041 g, 12%). trans-N-(4-bromo-2-methylphenyl)-2-chloro-5-(2,2-di Chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoate Zuamide (F1054)

[0537] [ka] Isolated as a white powder (0.46 g, 84%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(4-fluorophenyl)cyclopropane-1-carboxamido Phenylbenzamide (F1152)

[0538] [ka] Isolated as a pale yellow solid (0.065 g, 88%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl) -3-Fluorobenzamide (F1153)

[0539] [ka] 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-carboxamide)- 3-Fluorobenzamide (F1154)

[0540] [ka] Isolated as a white solid (0.077g, 97%). trans-tert-butyl-N-tert-butoxycarbonyl-N-[3-[[2 -chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl [3-fluoropropanecarbonyl]amino]-3-fluorobenzoyl]amino]-2,6-difluoro [Orophenyl]carbamate (F1155)

[0541] [ka] Isolated as a pale yellow solid (0.0185 g, 85%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-methyl-N-phenylbenzamido Do(F1183)

[0542] [ka] Isolated as a white solid (0.072 g, 89%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-3- Methylbenzamide (F1184)

[0543] [ka] Isolated as a tan solid (0.071 g, 86%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl) -3-Methylbenzamide (F1185)

[0544] [ka] 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-carboxamide)- 3-Methylbenzamide (F1186)

[0545] [ka] Isolated as a pale pink solid (0.067g, 74%). trans-tert-butyl-N-tert-butoxycarbonyl-N-[3-[[2 -chloro-5-[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl [3-methylbenzoyl]amino]-2,6-difluoro [phenyl]carbamate (F1187)

[0546] [ka] Isolated as a light tan solid (0.109 g, 88%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-methyl-N-phenylbenzamido Do(F1188)

[0547] [ka] Isolated as a white solid (0.073 g, 93%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2- Methylbenzamide (F1189)

[0548] [ka] Isolated as a light tan solid (0.072 g, 89%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl) -2-Methylbenzamide (F1190)

[0549] [ka] Isolated as a light tan solid (0.073 g, 90%). trans-N-(4-acetamidophenyl)-3-chloro-5-(2,2-dichloro)- -3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamide)- 2-Methylbenzamide (F1191)

[0550] [ka] 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)cyclohexyl [2-methylbenzoyl]amino]-2,6-difluoro [phenyl]carbamate (F1192)

[0551] [ka] Isolated as a white solid (0.131 g, 99%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-fluoro-N-phenylbenzal Mid (F1194)

[0552] [ka] Isolated as an off-white solid (0.043 g, 44%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)cyclopropane-1-carboxamido Phenyl)benzamide (F1195)

[0553] [ka] Isolated as an off-white solid (0.072 g, 71%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl) -2-Fluorobenzamide (F1196)

[0554] [ka] Isolated as an off-white solid (0.064 g, 61%). trans-N-(4-acetamidophenyl)-3-chloro-5-(2,2-dichloro)- -3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamide)- 2-Fluorobenzamide (F1197)

[0555] [ka] 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)cyclohexyl [2-fluoropropanecarbonyl]amino]-2-fluorobenzoyl]amino]-2,6-difluoro [Orophenyl]carbamate (F1198)

[0556] [ka] Isolated as an off-white solid (0.099 g, 65%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-2,3-difluoro-N-phenylbenzamide ( F1207)

[0557] [ka] Isolated as an off-white solid (0.066 g, 67%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(4-fluorophenyl)-2,3-difluoropropane-1-carboxamido ) Benzamide (F1208)

[0558] [ka] Isolated as a white solid (0.079 g, 77%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,4-difluorophenyl)-2,3-dihydropropane-1-carboxamido Fluorobenzamide (F1209)

[0559] [ka] 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-difluoro Fluorobenzamide (F1210)

[0560] [ka] 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)cyclopropanecarbonate [Carbonyl]amino]-2,3-difluorobenzoyl]amino]-2,6-difluoro Phenyl]carbamate (F1211)

[0561] [ka] Isolated as a pale yellow solid (0.130 g, 89%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-phenyl-3-(trifluoromethyl) Benzamide (F1212)

[0562] [ka] Isolated as a tan solid (0.060 g, 76%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-3-fluoro-2-methoxy-N-phenylbenz Amide (F1213)

[0563] [ka] Isolated as a tan solid (0.067g, 86%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-3- (Trifluoromethyl)benzamide (F1214)

[0564] [ka] Isolated as a tan solid (0.066g, 83%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl) -3-(trifluoromethyl)benzamide (F1215)

[0565] [ka] Isolated as a tan foam (0.072 g, 88%). trans-N-(4-acetamidophenyl)-2-chloro-5-(2,2-dichloro)- -3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamide)- 3-(Trifluoromethyl)benzamide (F1216)

[0566] [ka] 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-fluoro-phenyl)silyl Chloropropanecarbonyl]amino]-3-(trifluoromethyl)-benzoyl]amino ]-2,6-difluorophenyl]carbamate (F1217)

[0567] [ka] Isolated as a pale yellow solid (0.098 g, 86%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(4-fluorophenyl)-3-fluoropropane-1-carboxamido -Methoxybenzamide (F1218)

[0568] [ka] Isolated as a tan foam (0.072 g, 89%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,4-difluorophenyl)-3-fluoropropane-1-carboxamido 2-Methoxybenzamide (F1219)

[0569] [ka] 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)

[0570] [ka] Isolated as a pale yellow solid (0.075 g, 87%). trans-tert-butyl-N-tert-butoxycarbonyl-N-[3-[[5 -[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonate [Carbonyl]amino]-3-fluoro-2-methoxybenzoyl]amino]-2,6-difluoro [Fluorophenyl]carbamate (F1221)

[0571] [ka] Isolated as a pale yellow solid (0.109 g, 94%). trans-tert-butyl-N-tert-butoxycarbonyl-N-[4-[[2 -chloro-5-[[2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane Benzyl]amino]benzoyl]amino]-2,6-difluoro-phenyl]carba Mate (F1266)

[0572] [ka] 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)cyclohexyl Isopropane-1-carboxamido)benzamido)-2,4-difluorophenyl)carboxamide Bamate (DP12)

[0573] [ka] 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)benzyl Nzumid (DP13)

[0574] [ka] Isolated as a yellow solid (0.8 g, 42%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(4-fluorophenyl)-3-fluoropropane-1-carboxamido -Methylbenzamide (F1278)

[0575] [ka] Isolated as a light tan solid (0.058 g, 85%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,4-difluorophenyl)-3-fluoropropane-1-carboxamido 2-methylbenzamide (F1279):

[0576] [ka] Isolated as a light tan solid (0.059 g, 84%). trans-tert-butyl-N-tert-butoxycarbonyl-N-[3-[[5 -[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonate [Carbonyl]amino]-3-fluoro-2-methylbenzoyl]amino]-2,6-difluoro [Orophenyl]carbamate (F1280)

[0577] [ka] Isolated as a white solid (0.099 g, 100%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-N-ethyl-2-fluoro-3-methylbenzamido Do (F2029)

[0578] [ka] Isolated as a white solid (0.068 g, 83%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2-fluoro-3-methyl-N-(2,2,2-trimethylpropane-1-carboxamido) Trifluoroethyl)benzamide (F2030)

[0579] [ka] Isolated as a white solid (0.077g, 84%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2-fluoro-3-methyl-N-(2,2,3,3-propane-1-carboxamido) ,3-pentafluoropropyl)benzamide (F2031)

[0580] [ka] Isolated as a white solid (0.083 g, 82%). trans-N-(3-chloropropyl)-5-(2,2-dichloro-3-(3-chloropropyl)- -4-fluorophenyl)-cyclopropane-1-carboxamido)-2-fluoro-3 -Methylbenzamide (F2032)

[0581] [ka] Isolated as a white solid (0.069 g, 78%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-ethyl-3-fluorobenzamido Do (F2033)

[0582] [ka] Isolated as a white solid (0.046 g, 71%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(2,2,2-triphenyl)cyclopropane-1-carboxamido Trifluoroethyl)benzamide (F2034)

[0583] [ka] Isolated as a white solid (0.061 g, 85%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- phenyl)cyclopropane-1-carboxamido)-3-fluoro-N-(2,2,3,3 ,3-pentafluoropropyl)benzamide (F2035)

[0584] [ka] 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-fluoro Fluorobenzamide (F2036)

[0585] [ka] Isolated as a white solid (0.063 g, 87%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-ethyl-3-methylbenzamide (F2037)

[0586] [ka] Isolated as a white solid (0.055 g, 77%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-methyl-N-(2,2,2-triphenyl)cyclopropane-1-carboxamido Fluoroethyl)benzamide (F2038)

[0587] [ka] Isolated as a tan solid (0.052 g, 66%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- phenyl)cyclopropane-1-carboxamido)-3-methyl-N-(2,2,3,3, 3-Pentafluoropropyl)benzamide (F2039)

[0588] [ka] 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-methyl Chilbenzamide (F2040)

[0589] [ka] Isolated as a white solid (0.054 g, 69%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-ethyl-2-methylbenzamide (F2041)

[0590] [ka] Isolated as a white solid (0.031 g, 44%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-methyl-N-(2,2,2-triphenyl)cyclopropane-1-carboxamido Fluoroethyl)benzamide (F2042)

[0591] [ka] Isolated as a white solid (0.066g, 83%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- phenyl)cyclopropane-1-carboxamido)-2-methyl-N-(2,2,3,3, 3-Pentafluoropropyl)benzamide (F2043)

[0592] [ka] 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-methyl Chilbenzamide (F2044)

[0593] [ka] Isolated as a tan solid (0.050 g, 64%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(2,2,2-triphenyl)cyclopropane-1-carboxamido Trifluoroethyl)benzamide (F2045)

[0594] [ka] Isolated as a white solid (0.047g, 47%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- phenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(2,2,3,3 ,3-pentafluoropropyl)benzamide (F2046)

[0595] [ka] Isolated as an off-white solid (0.074 g, 68%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-ethyl-2-fluorobenzamido Do(F2047)

[0596] [ka] Isolated as an off-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-fluoro Fluorobenzamide (F2048)

[0597] [ka] Isolated as an off-white solid (0.062 g, 63%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,2,2-trifluoropropane-1-carboxamido)-2,3-difluoro- (Oroethyl)benzamide (F2049)

[0598] [ka] Isolated as a white solid (0.079 g, 79%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,2,3,3,3-chloropropane-1-carboxamido)-2,3-difluoro- Pentafluoropropyl)benzamide (F2050)

[0599] [ka] Isolated as a white solid (0.092 g, 84%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 1-propane-1-carboxamido)-N-ethyl-2,3-difluorobenzamide (F 2051)

[0600] [ka] Isolated as a white solid (0.073 g, 82%). trans-N-(3-chloropropyl)-5-(2,2-dichloro-3-(3-chloropropyl)- -4-fluorophenyl)cyclopropane-1-carboxamido)-2,3-difluoro Benzamide (F2052)

[0601] [ka] Isolated as a white solid (0.075 g, 76%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-ethyl-3-(trifluoromethyl Benzamide (F2053)

[0602] [ka] Isolated as a pale yellow solid (0.045 g, 64%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,2,2-trifluoroethyl (trifluoromethyl)benzamide (F2054)

[0603] [ka] Isolated as a white foam (0.062 g, 80%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-(trifluoromethyl)-N-( 3,3,3-trifluoropropyl)benzamide (F2055)

[0604] [ka] Isolated as a white solid (0.063 g, 79%). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,2,3,3,3-pentaphenyl) (fluoropropyl)-3-(trifluoromethyl)benzamide (F2056)

[0605] [ka] Isolated as a white foam (0.053 g, 62%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-N-ethyl-3-fluoro-2-methoxybenzaldehyde Mid (F2057)

[0606] [ka] Isolated as a white foam (0.054 g, 76%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2,2,2-propane-1-carboxamido)-3-fluoro-2-methoxy-N-(2,2,2- Trifluoroethyl)benzamide (F2058)

[0607] [ka] Isolated as a white foam (0.069 g, 86%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 3-fluoro-2-methoxy-N-(3,3,3-propane-1-carboxamido) Trifluoropropyl)benzamide (F2059)

[0608] [ka] Isolated as a white foam (0.070 g, 86%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2-Methoxy-N-(2,2,3,3-propane-1-carboxamido)-3-fluoro-2-methoxy-N-(2,2,3, 3,3-Pentafluoropropyl)benzamide (F2060)

[0609] [ka] Isolated as a white foam (0.069 g, 81%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-methoxy-N-(2,2,2-trimethylphenyl)cyclopropane-1-carboxamido Trifluoroethyl)benzamide (F2061)

[0610] [ka] Isolated as a white solid (0.060 g, 77%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- phenyl)cyclopropane-1-carboxamido)-2-methoxy-N-(2,2,3,3 ,3-pentafluoropropyl)benzamide (F2062)

[0611] [ka] Isolated as a white solid (0.075 g, 88%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2,2,2-trimethyl-N-(2,2,2-propane-1-carboxamido)-3-fluoro-2-methyl-N-(2,2,2-trimethyl-N-propane-1-carboxamido) Trifluoroethyl)benzamide (F2063)

[0612] [ka] Isolated as a white solid (0.063 g, 96%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) 2-methyl-N-(2,2,3,3-propane-1-carboxamido)-3-fluoro-2-methyl-N-(2,2,3,3 ,3-pentafluoropropyl)benzamide (F2064)

[0613] [ka] Isolated as a white solid (0.059 g, 81%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(4-fluorophenyl)-2-fluoropropane-1-carboxamido -Methylbenzamide (F1136)

[0614] [ka] Isolated as a tan solid (0.078g, 81%). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) N-(2,4-difluorophenyl)-2-fluoropropane-1-carboxamido 3-methylbenzamide (F1137)

[0615] [ka] Isolated as a tan foam (0.082 g, 87%). trans-tert-butyl-N-tert-butoxycarbonyl-N-[3-[[5 -[[2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarbonate carboxyl]amino]-2-fluoro-3-methylbenzoyl]amino]-2,6-difluoro [Orophenyl]carbamate (F1138)

[0616] [ka] 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)

[0617] [ka] Isolated as a white solid (0.088 g, 85%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2- Methoxybenzamide (F1235)

[0618] [ka] Isolated as a white solid (0.048 g, 60%). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl) -2-Methoxybenzamide (F1236)

[0619] [ka] 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)cyclohexyl [2-Methoxybenzoyl]amino]-2,6-difluoropropanecarbonyl]amino] [Orophenyl]carbamate (F1237)

[0620] [ka] Isolated as an off-white solid (0.059 g, 52%).

[0621] [Example 26] trans-2-((tert-butoxycarbonyl)(4-(2-chloro-5-(2, 2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide Preparation of )benzamido)-3-methylphenyl)amino)ethyl acetate (F1129) Made

[0622] [ka]

[0623] Step 1: 2-((tert-butoxycarbonyl)(3-methyl-4-nitrophenyl)-2-methyl-2-phenylpropanol) Preparation of (N,N-(methylamino)ethyl acetate. Anhydrous N,N-dimethylformamide (5 mL) tert-Butyl (3-methyl-4-nitrophenyl) carbamate (C22 3) (1.0 g, 3.96 mmol) in anhydrous N,N-dimethylformamide (50 mL A stirred suspension of sodium hydride (60% oil dispersion, 0.206 g, 5.15 mmol) in HCl (200 ml) was The suspension was added dropwise at a rate that maintained the temperature below 30° C. Once the addition was complete, the resulting The orange solution was stirred at room temperature for 30 minutes, followed by addition of 2-bromoethyl acetate (0.662 g, 3. The resulting solution was stirred at room temperature for 12 hours and then carefully diluted with water. (100 mL) and extracted with ethyl acetate (3 x 50 mL). and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, Concentrated under vacuum on a rotary evaporator. Silica gel flash chromatography Purification by column chromatography gave the title compound as a yellow oil (0.658 g, 47%). 1 H NMR (400 MHz, CDCl3) 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 (10 1 MHz, CDCl3) 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, 2 0.70; ESIMS m / z 339 ([M+H]+).

[0624] Step 2: 2-((4-amino-3-methylphenyl)(tert-butoxycarbonyl) Preparation of palladium hydroxide (10% w / w; 0.135 g, 0.096 mmol) was dissolved in ethyl acetate (50 mL) (3-methyl-4-nitrophenyl)amino)ethyl acetate (0 To a stirred solution of 1.650 g (1.92 mmol) of HCl was added the following: The flask was evacuated and a balloon The reaction mixture was filled with hydrogen via an adapter and the resulting black suspension was stirred at room temperature for 13 hours. The mixture was filtered through a pad of Celite® and evaporated on a rotary evaporator. and concentrated in vacuo to give the title compound as a brown solid (0.527 g, 85%). 1 H NMR (400 MHz, CDCl3) 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] + ).

[0625] Step 3: trans-2-((tert-butoxycarbonyl)(4-(2-chloro) 5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1- Carboxamido)benzamido)-3-methylphenyl)amino)ethyl acetate (F Preparation of 1129) 2,4,6-tripropyl-1,3,5,2,4,6-trioxat Triphosphinane 2,4,6-trioxide (T3P®, 50% solution in ethyl acetate) solution (0.281 g, 0.441 mmol) in anhydrous ethyl acetate (3 mL) -2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane) Pan-1-carboxamido)benzoic acid (C12) (0.100 g, 220 mmol), 2 -((4-amino-3-methylphenyl)(tert-butoxycarbonyl)amino)e ethyl acetate (0.068 g, 0.220 mmol) and pyridine (0.053 g, The solution was stirred at 23°C for 12 hours and concentrated. Purification by silica gel flash chromatography gave the title compound as a white foam. This was obtained as a solid (0.149 g, 86%).

[0626] The following compounds were prepared in a similar manner to the procedure outlined in Example 26. trans-tert-butyl-(4-(2-chloro-5-(2,2-dichloro-3-( 3,5-Dichlorophenyl)cyclopropane-1-carboxamido)benzamide)-3 -methylphenyl)(2-cyanoethyl)carbamate (F1157)

[0627] [ka] 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)benzamide)-3 -methylphenyl)(2-methoxyethyl)carbamate (F1159)

[0628] [ka] Isolated as a clear, colorless oil (0.121 g, 73%).

[0629] [Example 27] N-(4-amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R) -2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide Preparation of thamidobenzamide (F1027)

[0630] [ka] 2-chloro-5-((1R,3R)-2,2-dichloro-3-( ...(1R,3R)-2,2-dichloro-3-((1R,3R)-2,2-dichloro-3-((1R,3R)-2,2-dichloro- -(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C1 3) (0.100 g, 0.220 mmol) and tert-butyl-N-((tert -butoxy)carbonyl)-N-(4-amino-3,5-difluorophenyl)carbamate A solution of methyl acrylate (C181) (0.076 g, 0.220 mmol) was added to pyridine (0.03 6 mL, 0.441 mmol), and 2,4,6-trimethylsilyl as a 50% solution in ethyl acetate Tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-triol oxido (T3P®) (0.210 g, 0.331 mmol) was added. The mixture was warmed to 45°C for 48 hours. The reaction mixture was cooled to room temperature and concentrated under a stream of nitrogen. The fraction was subjected to flash column chromatography using 0-30% ethyl acetate / hexane as the eluent. The product fractions were combined and concentrated under reduced pressure. The material was dissolved in dichloromethane (2 mL) and diluted with a 4 M solution of hydrogen chloride in dioxane (0.54 mL). 5 mL, 2.18 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The phases were separated and the organic layer was washed with saturated aqueous sodium bicarbonate and brine, then The mixture was then passed through a phase separator to dry, and the solvent was concentrated. The title compound was purified by flash column chromatography using ethanol / hexane. The product was obtained as a white solid (0.025 g, 19%).

[0631] The following compounds were prepared in a similar manner to the procedure outlined in Example 27. N-(4-amino-2,6-difluorophenyl)-2-chloro-5-((1R,3R) -2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamide Samido)benzamide (F1028)

[0632] [ka] 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-carbonyl Ruboxamido)benzamide (F1029)

[0633] [ka] 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)

[0634] [ka] 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 Pan-1-carboxamido)benzamide (F1036)

[0635] [ka] 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 Benzamide (1-carboxamido) (F1037)

[0636] [ka] 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 Benzamide (1-carboxamido) (F1038)

[0637] [ka] Isolated as a pale 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-carboxamine C)benzamide (F1026)

[0638] [ka] Isolated as a white foam (0.037 g, 76%). trans-N-(4-amino-2-methylphenyl)-2-chloro-5-(2,2-diaminophenyl)- Chloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzoate Zuamide (DP1)

[0639] [ka] Isolated as a white foam (0.838 g, 99%).

[0640] [Example 28] trans-2,2-dichloro-N-(4-chloro-3-(2-pyridin-2-yl) Hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane Preparation of propane-1-carboxamide (F2502)

[0641] [ka] trans-2-chloro-5-(2,2-dichloro-) in ethyl acetate (2 mL) at room temperature 3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C 12) (0.080 g, 0.176 mmol) and 2-(1-methylhydrazinyl)piperidin A solution of lysine (0.033 g, 0.265 mmol) was added to diisopropylethylamine ( 0.123 mL, 0.706 mmol), and 2,4 as a 50% solution in ethyl acetate ,6-Tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6 -trioxide (T3P®; 0.225 g, 0.353 mmol) was added sequentially. The reaction mixture was stirred at room temperature for 18 hours and then concentrated under a stream of nitrogen. Purify by column chromatography using 0-100% ethyl acetate / hexane. , affording the title compound as a yellow solid (0.019 g, 20%).

[0642] The following compounds were prepared in a similar manner to the procedure outlined 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)

[0643] [ka] Isolated as a pale yellow foam (0.058 g, 44%). trans-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-pyridine) -2-yl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl Cyclopropane-1-carboxamide (F2503)

[0644] [ka] Isolated as a yellow solid (0.046 g, 47%). trans-2,2-dichloro-N-(4-chloro-3-(2-(5-chloropyridine- 2-yl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl ) Cyclopropane-1-carboxamide (F2504)

[0645] [ka] Isolated as an off-white solid (0.045 g, 44%). trans-2,2-dichloro-N-(4-chloro-3-(2-(3-chloropyridine- 2-yl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl ) Cyclopropane-1-carboxamide (F2505)

[0646] [ka] Isolated as an off-white solid (0.036 g, 35%). trans-2,2-dichloro-N-(4-chloro-3-(2-(6-chloropyridazine -3-yl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl Cyclopropane-1-carboxamide (F2506)

[0647] [ka] Isolated as a pale yellow solid (0.070 g, 69%). trans-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-(4-( (trifluoromethyl)pyridin-2-yl)hydrazine-1-carbonyl)phenyl)-3 -(3,5-Dichlorophenyl)cyclopropane-1-carboxamide (F2507)

[0648] [ka] Isolated as a white solid (0.096 g, 86%). trans-2,2-dichloro-N-(4-chloro-3-(2-pyrimidin-2-yl) )hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Propane-1-carboxamide (F2508)

[0649] [ka] Isolated as a white solid (0.027 g, 28%). trans-2,2-dichloro-N-(4-chloro-3-(2-pyrimidin-4-yl) )hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Propane-1-carboxamide (F2509)

[0650] [ka] Isolated as a white solid (0.016 g, 17%). (1R,3R)-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-phenyl) (3,5-dichlorophenyl)cyclo(1-carbonyl)phenylhydrazine Propane-1-carboxamide (F2510)

[0651] [ka] Isolated as a white solid (0.045 g, 37%). (1R,3R)-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-phenyl) (1-carbonyl)phenyl)-3-(3,4,5-trichlorophenyl)hydrazine Cyclopropane-1-carboxamide (F2511)

[0652] [ka] Isolated as a white solid (0.048 g, 40%). (1R,3R)-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-phenyl) (3-chloro-4-fluorophenyl)-3-((1-chloro-1-carbonyl)phenyl)-hydrazine ) Cyclopropane-1-carboxamide (F2512)

[0653] [ka] Isolated as a white solid (0.041 g, 33%). (1R,3R)-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-phenyl) (3,4-dichlorophenyl)cyclo(1-carbonyl)phenylhydrazine Propane-1-carboxamide (F2513)

[0654] [ka] 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)cyclo Propane-1-carboxamide (F2553)

[0655] [ka] 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 Propane-1-carboxamide (F2554)

[0656] [ka] Isolated as a thin foam (0.070 g, 63%). trans-2,2-dichloro-N-(4-chloro-3-(2-(4-nitrophenyl) Hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane Propane-1-carboxamide (F2555)

[0657] [ka] 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- Ruboxamide (F2556)

[0658] [ka] Isolated as an off-white foam (0.0911 g, 82%). trans-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-phenyl)methyl) 3-(3,5-dichlorophenyl)cyclopropane-1-carbonylphenyl)cyclopropane Pan-1-carboxamide (F2557)

[0659] [ka] Isolated as an off-white foam (0.094 g, 85%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,5-difluoromethyl) (phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamide (F2558)

[0660] [ka] Isolated as an off-white foam (0.0796 g, 72%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,4-difluoromethyl) (phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamide (F2559)

[0661] [ka] Isolated as an off-white foam (0.089 g, 80%). trans-2,2-dichloro-N-(4-chloro-3-(2-(3,4-dichlorophenoxy) (1-carbonyl)hydrazine-1-phenyl)-3-(3,5-dichlorophenyl) Chlopropane-1-carboxamide (F2560)

[0662] [ka] Isolated as a light brown foam (0.072 g, 60%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,5-dichlorophenoxy)methyl) (1-carbonyl)hydrazine-1-phenyl)-3-(3,5-dichlorophenyl) Chlopropane-1-carboxamide (F2561)

[0663] [ka] Isolated as a light brown foam (0.095 g, 79%). trans-2,2-dichloro-N-(4-chloro-3-(2-(4-fluoro-2-methyl) (1-carbonyl)phenyl)hydrazine-3-(3,5-dichlorophenyl) Nyl)cyclopropane-1-carboxamide (F2562)

[0664] [ka] 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)cyclo Propane-1-carboxamide (F2563)

[0665] [ka] Isolated as a light brown foam (0.039 g, 35%). trans-2,2-dichloro-N-(4-chloro-3-(2-(4-trifluoromethyl) (3,5-dichloro)phenyl)hydrazine-1-carbonyl)phenyl Phenyl)cyclopropane-1-carboxamide (F2564)

[0666] [ka] Isolated as a light brown foam (0.082 g, 63%). trans-2,2-dichloro-N-(4-chloro-3-(2-(4-perfluoroethane) (3,5-dichloro)phenyl)hydrazine-1-carbonyl)phenyl Phenyl)cyclopropane-1-carboxamide (F2565)

[0667] [ka] 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) (phenyl)cyclopropane-1-carboxamide (F2571)

[0668] [ka] Isolated as an off-white foam (0.048 g, 38%). trans-2,2-dichloro-N-(4-chloro-3-(2-(3-trifluoromethyl) (phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) (phenyl)cyclopropane-1-carboxamide (F2572)

[0669] [ka] 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) (phenyl)cyclopropane-1-carboxamide (F2573)

[0670] [ka] Isolated as a light brown foam (0.107 g, 86%). trans-2,2-dichloro-N-(4-chloro-3-(2-methyl-2-(m-trichloro) (phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclohexyl Isopropane-1-carboxamide (F2574)

[0671] [ka] Isolated as an off-white foam (0.103 g, 88%). trans-2,2-dichloro-N-(4-chloro-3-(2-(p-tolyl)hydrazine) (3,5-dichlorophenyl)cyclopropane- 1-Carboxamide (F2575)

[0672] [ka] 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 Propane-1-carboxamide (F2576)

[0673] [ka] Isolated as a pale yellow foam (0.058 g, 50%).

[0674] [Example 29] trans-N-(3-(2-acetylhydrazine-1-carbonyl)-4-chlorophenoxy)- (3,5-dichlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylate Preparation of ruboxamide (F2514)

[0675] [ka] trans-2,2-dichloro-N-(4-chloro)- -3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Propane-1-carboxamide hydrochloride (F2567) (0.25 g, 0.498 mmol ), triethylamine (0.15 g, 1.49 mmol) and acetic anhydride (0. 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 water (2× The organic layer was washed with water (10 mL) and brine (5 mL). The organic layer was dried over anhydrous sodium sulfate. The column was eluted with 40-60% ethyl acetate / petroleum ether. The title compound was purified by column chromatography to give the title compound as a white solid (0.08 g, 32%) was obtained as.

[0676] The following compounds were prepared in a similar manner to the procedure outlined in Example 29. trans-2,2-dichloro-N-(4-chloro-3-(2-(2,2,2-trifluoromethyl)phenyl) ... (perfluoroacetyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) Nyl)cyclopropane-1-carboxamide (F2515)

[0677] [ka] Isolated as a white solid (0.06 g, 21%). trans-2,2-dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoromethyl)phenyl) ... (1-Carbonyl)phenyl)-3-(3,5-dichloro)-1-chloropropanoylhydrazine Phenyl)cyclopropane-1-carboxamide (F2516)

[0678] [ka] Isolated as a white solid (0.06 g, 26%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,2-difluoromethyl) Chloropropane-1-carbonyl)hydrazine-1-carbonyl)phenyl)-3-(3, 5-Dichlorophenyl)cyclopropane-1-carboxamide (F2517)

[0679] [ka] Isolated as a white solid (0.07g, 31%). trans-2,2-dichloro-N-(4-chloro-3-(2-(1-cyanocyclopropyl) Pan-1-carbonyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dic (chlorophenyl)cyclopropane-1-carboxamide (F2518)

[0680] [ka] Isolated as a white solid (0.07g, 31%). trans-N-(3-(2-benzoylhydrazine-1-carbonyl)-4-chlorohydrazine) (phenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1- Carboxamide (F2519)

[0681] [ka] 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)cyclopro Pan-1-carboxamide (F2522)

[0682] [ka] Isolated as an off-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)

[0683] [ka] Isolated as an off-white solid (0.085 g, 38%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2-cyclopropyl) Cetyl)-2-methylhydrazine-1-carbonyl)phenyl)-3-(3,5-dichloro (phenyl)cyclopropane-1-carboxamide (F2524)

[0684] [ka] Isolated as an off-white solid (0.04 g, 18%). trans-2,2-dichloro-N-(4-chloro-3-(2-(1-cyanocyclopropyl) Pan-1-carbonyl)-2-methylhydrazine-1-carbonyl)phenyl)-3-( 3,5-Dichlorophenyl)cyclopropane-1-carboxamide (F2525)

[0685] [ka] Isolated as an off-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)

[0686] [ka] Isolated as an off-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 Propane-1-carboxamide (F2527)

[0687] [ka] Isolated as an off-white solid (0.12 g, 48%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2-cyclopropyl) Cetylhydrazine-1-carbonylphenyl)-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamide (F2528)

[0688] [ka] 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)cyclo Propane-1-carboxamide (F2529)

[0689] [ka] Isolated as an off-white solid (0.09 g, 42%). trans-2,2-dichloro-N-(4-chloro-3-(2-dimethylglycyl)methyl)- 3-(3,5-dichlorophenyl)cyclopropane-1-carbonylphenyl)cyclopropane Pan-1-carboxamide (F2530)

[0690] [ka] Isolated as an off-white foam (0.06 g, 25%). trans-2,2-dichloro-N-(4-chloro-3-(2-picolinoylhydrazine) -1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1 -Carboxamide (F2531)

[0691] [ka] Isolated as an off-white solid (0.055 g, 26%). trans-2,2-dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoromethyl)phenyl) ... (2-(trifluoromethyl)propanoyl)hydrazine-1-carbonyl)phenyl (3,5-dichlorophenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F25 32)

[0692] [ka] Isolated as an off-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)

[0693] [ka] Isolated as an off-white solid (0.085 g, 38%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,2-difluoromethyl) Chloropropane-1-carbonyl)-2-methylhydrazine-1-carbonyl)phenyl) -3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F2534 )

[0694] [ka] Isolated as an off-white solid (0.065 g, 29%).

[0695] [Example 30] trans-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenoxy)methyl) N-(2,2,2-triphenyl)cyclopropane-1-carboxamido)benzoyl Preparation of (fluoroethyl)hydrazine-1-carboxamide (F2535)

[0696] [ka] trans-2,2-dichloro-N-(4-chloro) -3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Propane-1-carboxamide hydrochloride (F2567) (0.175 g, 0.347 mmol) l) with triethylamine (0.105 g, 1.04 mmol) and 1,1,1 -Trifluoro-2-isocyanatoethane (0.052 g, 0.417 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The material was dissolved in ethyl acetate (20 mL) and washed with water (2 x 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 60% ethyl acetate / petroleum ether The title compound was obtained as an off-white solid (0.10 g, 48%).

[0697] The following compounds were prepared in a similar manner to the procedure outlined in Example 30. trans-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenoxy)methyl) N-(Nyl)cyclopropane-1-carboxamido)benzoyl)-N-isopropylhydrazine Benzene-1-carboxamide (F2536)

[0698] [ka] Isolated as an off-white solid (0.13 g, 61%). trans-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenoxy)methyl) N-phenyl)cyclopropane-1-carboxamido)benzoyl)-N-phenylhydrazine- 1-Carboxamide (F2537)

[0699] [ka] Isolated as an off-white solid (0.06 g, 26%). trans-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenoxy)methyl) N-(cyclopropylmethyl)benzoylcyclopropane-1-carboxamido (I)hydrazine-1-carboxamide (F2538)

[0700] [ka] Isolated as an off-white solid (0.11 g, 50%).

[0701] [Example 31] trans-2,2-dichloro-N-(4-chloro-3-(2-((2,2,2-trichloro- (Fluoroethyl)carbamothioyl)hydrazine-1-carbonyl)phenyl)-3-(3 Preparation of (5-dichlorophenyl)cyclopropane-1-carboxamide (F2539)

[0702] [ka] trans-2,2-dichloro-N-(4-chloro) -3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Propane-1-carboxamide hydrochloride (F2567) (0.190 g, 0.377 mmol) l) with triethylamine (0.114 g, 1.13 mmol) and 1,1,1 -trifluoro-2-isothiocyanatoethane (0.064 g, 0.452 mmol) The mixture was added at 0° C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (20 mL) and diluted with water (2 x 10 mL) and brine (5 mL The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Purification was performed by column chromatography eluting with 0-60% ethyl acetate / petroleum ether. This gave the title compound as an off-white solid (0.08 g, 35%).

[0703] The following compounds were prepared in a similar manner to the procedure outlined in Example 31. trans-2,2-dichloro-N-(4-chloro-3-(2-isopropylcarbamoyl) Thioyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl ) Cyclopropane-1-carboxamide (F2540)

[0704] [ka] Isolated as an off-white solid (0.06 g, 27%). trans-2,2-dichloro-N-(4-chloro-3-(2-phenylcarbamothio) (yl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)silane Chlopropane-1-carboxamide (F2541)

[0705] [ka] Isolated as an off-white solid (0.07 g, 26%).

[0706] [Example 32] trans-ethyl 2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichloro) (phenyl)cyclopropane-1-carboxamido)benzoyl)hydrazine-1-carboxamide Preparation of carboxylate (F2542)

[0707] [ka] trans-2,2-dichloro-N-(4-chloro) -3-(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Propane-1-carboxamide hydrochloride (F2567) (0.175 g, 0.347 mmol) l) was treated with triethylamine (0.114 g, 1.13 mmol) and chloroformic acid Ethyl acetate (0.049 g, 0.452 mmol) was added at 0° C. The reaction mixture was stirred at room temperature for 1 The mixture was stirred for 6 hours, concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (20 mL). The organic layer was extracted with anhydrous sodium sulfate and washed with water (2×10 mL) and brine (5 mL). The mixture was dried over silica gel, filtered, and concentrated under reduced pressure. The title compound was purified by column chromatography eluting with HCl to give an off-white solid ( Obtained as 0.04g, 19%).

[0708] The following compounds were prepared in a similar manner to the procedure outlined in Example 32. trans-trifluoromethyl 2-(2-chloro-5-(2,2-dichloro-3-(3 ,5-Dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)hydrazine Benzene-1-carboxylate (F2543)

[0709] [ka] Isolated as an off-white solid (0.05 g, 21%).

[0710] [Example 33] trans-2,2-dichloro-N-(4-chloro-3-(2-(4-fluorobenzyl )hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Preparation of propane-1-carboxamide (F2570)

[0711] [ka] In a 50 mL flask, add trans-2,2-dichloro-N-(4-chloro-3-(hydroxybenzoyl) (3,5-dichlorophenyl)cyclopropane- 1-Carboxamide (F2567) (0.10 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 diluted with 0 Purification by column chromatography using ∼100% ethyl acetate / hexanes The imine product was obtained as a colorless foam. The foam was dissolved in methanol (3 mL) and the solution sodium borohydride (0.081 g, 1.283 mmol) and acetic acid (0.02 4 mL, 0.428 mmol) were added sequentially. The reaction mixture was stirred at room temperature overnight. Aqueous sodium bicarbonate (5 mL) was carefully added to the reaction mixture and the mixture was diluted with ethyl acetate ( The organic layer was dried over sodium sulfate, filtered, and concentrated to give the title compound. The mixture was obtained as a colorless foam (0.065 g, 48%).

[0712] The following compounds were prepared in a similar manner to the procedure outlined in Example 33. trans-2,2-dichloro-N-(4-chloro-3-(2-(4,4-difluoromethyl) (cyclohexyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) Nyl)cyclopropane-1-carboxamide (F2569)

[0713] [ka] Isolated as an off-white foam (0.030 g, 22%).

[0714] [Example 34] trans-2,2-dichloro-N-(4-chloro-3-(2-(2,4-difluorobenzyl) (phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) Preparation of cyclopropane-1-carboxamide (F2547)

[0715] [ka] trans-2,2-dichloro-N-(4-chloro-3-( 2-(2,4-difluorobenzylidene)hydrazine-1-carbonyl)phenyl)-3 -(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F3004) ( To a solution of 0.20 g (0.34 mmol) of acetic acid (0.1 mL) and cyanoborohydride Sodium chloride (0.107 g, 1.7 mmol) was added at 0°C, and the reaction mixture was stirred at room temperature for 1 The reaction mixture was stirred for 6 hours, poured into water (10 mL) and diluted with ethyl acetate (2 x 10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Column chromatography using 20-40% ethyl acetate / petroleum ether as the solvent Further purification gave the title compound as an off-white solid (0.155 g, 77%).

[0716] The following compounds were prepared in a similar manner to the procedure outlined in Example 34. trans-2,2-dichloro-N-(4-chloro-3-(2-(1-phenylethyl) Hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane Propane-1-carboxamide (F2548)

[0717] [ka] Isolated as an off-white solid (0.175 g, 70%). trans-2,2-dichloro-N-(4-chloro-3-(2-cyclopropylmethyl )hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclo Propane-1-carboxamide (F2549)

[0718] [ka] Isolated as an off-white solid (0.085 g, 40%). trans-2,2-dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoromethyl)phenyl) ... (1-Carbonyl)phenyl)-3-(3,5-dichlorophenyl)-1-(2-chloropropyl)hydrazine Nyl)cyclopropane-1-carboxamide (F2550)

[0719] [ka] Isolated as an off-white solid (0.080 g, 35%). trans-2,2-dichloro-N-(4-chloro-3-(2-(1-methoxypropane -2-yl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl (I)cyclopropane-1-carboxamide (F2551)

[0720] [ka] Isolated as an off-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)

[0721] [ka] Isolated as an off-white solid (0.10 g, 55%). trans-N-(3-(2-benzylhydrazine-1-carbonyl)-4-chlorophenoxy)- (3,5-dichlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylate Ruboxamide (F2545)

[0722] [ka] Isolated as an off-white solid (0.100 g, 28%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,5-difluorobenzyl) (phenyl)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamide (F2546)

[0723] [ka] Isolated as an off-white solid (0.04 g, 32%).

[0724] [Example 35] trans-N-(3-(2-benzylidenehydrazine-1-carbonyl)-4-chloro (phenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1 -Preparation of carboxamide (F3001)

[0725] [ka] trans-2,2-dichloro-N-(4-chloro-3 -(hydrazinecarbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopro Pan-1-carboxamide hydrochloride (F2567) (0.300 g, 0.60 mmol) Sodium acetate trihydrate (0.099 g, 1.2 mmol) was added to the solution at room temperature and mixed. The mixture was stirred for 15 minutes. Benzaldehyde (0.19 g, 1.8 mmol) was added, followed by acetic acid. Acid (0.1 mL) was added and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water (1 The organic layer was poured into anhydrous sodium sulfate (2×10 mL) and extracted with ethyl acetate (2×10 mL). The mixture was dried over silica gel, filtered, and concentrated under reduced pressure. Purification by column chromatography using oil ether gave the title compound as a light brown solid. Obtained as a solid (0.110 g, 35%).

[0726] The following compounds were prepared in a similar manner to the procedure outlined in Example 35. trans-2,2-dichloro-N-(4-chloro-3-(2-pyridin-2-ylmethyl)methyl) (ethylene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl) Cyclopropane-1-carboxamide (F3002)

[0727] [ka] Isolated as an off-white solid (0.125 g, 33%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,5-difluorobenzyl) (phenylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl (I)cyclopropane-1-carboxamide (F3003)

[0728] [ka] Isolated as an off-white solid (0.13 g, 34%). trans-2,2-dichloro-N-(4-chloro-3-(2-(2,4-difluorobenzyl) (phenylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl Cyclopropane-1-carboxamide (F3004)

[0729] [ka] Isolated as an off-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)cyclohexyl Isopropane-1-carboxamide (F3005)

[0730] [ka] Isolated as an off-white solid (0.100 g, 38%). trans-2,2-dichloro-N-(4-chloro-3-(2-thiazol-2-yl) Methylene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl ) Cyclopropane-1-carboxamide (F3006)

[0731] [ka] Isolated as a pale yellow solid (0.080 g, 30%). trans-2,2-dichloro-N-(4-chloro-3-(2-cyclopropylmethyl) )hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclohexyl Isopropane-1-carboxamide (F3007)

[0732] [ka] Isolated as a pale yellow solid (0.100 g, 30%). trans-2,2-dichloro-N-(4-chloro-3-(2-(3,3,3-trifluoromethyl)phenyl) ... (1-chloropropylidene)hydrazine-1-carbonyl)phenyl)-3-(3,5-dichloro Phenyl)cyclopropane-1-carboxamide (F3008)

[0733] [ka] Isolated as an off-white solid (0.300 g, 40%). trans-2,2-dichloro-N-(4-chloro-3-(2-propane-2-ylidene) )hydrazine-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclohexyl Isopropane-1-carboxamide (F3010)

[0734] [ka] Isolated as an off-white foam (0.05 g, 41%).

[0735] [Example 36] trans-2,2-dichloro-N-(4-chloro-3-(1-methyl-2-(3,3, 3-trifluoropropylidene)hydrazine-1-carbonyl)phenyl)-3-(3, Preparation of 5-dichlorophenyl)cyclopropane-1-carboxamide (F3009)

[0736] [ka] trans-2-chloro-5-(2,2-dichloro-) in dichloromethane (10 mL) 3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid (C A solution of 12) (0.50 g, 1.10 mmol) was added to N,N-dimethylformamide (3 0.14 mL, 1.66 mmol) and oxalyl chloride (0.14 mL, 1.66 mmol) were added successively at 0°C, and the reaction The reaction mixture was stirred at room temperature for 3 hours. Then, the reaction mixture was concentrated under reduced pressure (bath temperature was reduced to 3 The acid chloride was dissolved in dichloromethane (6 mL) and 1-Methyl-2-(3,3,3-trifluoropropylidene)hydrazine in water (10 mL) A mixture of 1000 mg of dimethylformamide (C220) (0.600 g (crude)) and triethylamine (0.46 mL, 3 The reaction mixture was stirred at room temperature for 10 hours. The mixture was diluted with dichloromethane (20 mL) and washed with water. The organic layer was extracted with anhydrous sodium sulfate. The mixture was dried over ice, filtered, and concentrated under reduced pressure using 20-40% ethyl acetate / petroleum as the eluent. Purification by column chromatography using ether gave the title compound as a pink solid. (0.320 g, 50%)

[0737] [Example 37] trans-2,2-dichloro-N-(4-chloro-3-(hydrazinecarbonyl)phenyl) (3,5-dichlorophenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide hydrochloride Preparation of (F2567)

[0738] [ka] trans-tert-butyl 2-(2-chloro-5-methyl-2-methylpropional) in dichloromethane (10 mL) -(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo Oxamido)benzoyl)hydrazine-1-carboxylate (F2566) (1.00g To a solution of 1.77 mmol) was added 5 mL of 4 M HCl in 1,4-dioxane at 0°C. The reaction mixture was stirred at 20° C. for 16 hours. The reaction mixture was concentrated under reduced pressure. The material was triturated with diethyl ether and the resulting solid was filtered and dried under vacuum. The material was isolated as an off-white solid (0.600 g, 68%).

[0739] The following compounds were prepared in a similar manner to the procedure outlined in Example 37. trans-2,2-dichloro-N-(4-chloro-3-(2-methylhydrazine-1- (carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carbohydrate Voxamide hydrochloride (F2521)

[0740] [ka] Isolated as a white solid (2.6 g, 78%).

[0741] [Example 38] trans-tert-butyl 2-(2-chloro-5-(2,2-dichloro-3-(3, 5-Dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)hydrazine Preparation of α-1-carboxylate (F2566)

[0742] [ka] trans-2-chloro-5-(2,2-dichloro)methane (200 mL) -3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoic acid ( C12) (7.60 g, 16.9 mmol) was added to a solution of tert-butylhydrazine chloride. carboxylate (2.20 g, 16.9 mmol) and 3-(((ethylimino)methyl N,N-dimethylpropan-1-amine hydrochloride (EDC; 3.20 g, 1 6.9 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was then heated under reduced pressure. The mixture was concentrated under reduced pressure, and the residue was dissolved in water and extracted with ethyl acetate (2 x 200 mL). Wash with saturated aqueous sodium bicarbonate (50 mL), dry over anhydrous sodium sulfate, and filter. The extract was filtered and concentrated under reduced pressure. Column chromatography was performed eluting with 10% ethyl acetate in petroleum ether. Purification by chromatography gave the title compound as an off-white solid (1.20 g, 22%). I got it.

[0743] The following compounds were prepared in a similar manner to the procedure outlined in Example 38. trans-tert-butyl 2-(2-chloro-5-(2,2-dichloro-3-(3, 5-Dichlorophenyl)cyclopropane-1-carboxamido)benzoyl)-1-methyl Hydrazine-1-carboxylate (F2520)

[0744] [ka] Isolated as an off-white solid (2.6 g, 78%).

[0745] [Example 39] 2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluoro) (C1) (3-fluorophenyl)cyclopropane-1-carboxamido)-3-fluorobenzoic acid preparation

[0746] [ka]

[0747] Step 1: (1R,3R)-2,2-dichloroethane (10 mL) C12-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid 93) (0.445 g, 1.57 mmol) in a suspension of 2 drops of N,N-dimethylform. The amide was added, followed by the dropwise addition of oxalyl dichloride (1.992 g, 15.7 mmol). The resulting pale yellow mixture was stirred at room temperature for 16 hours. The salil was evaporated under reduced pressure and the resulting golden oil was dissolved in 1,2-dichloroethane (10 mL ) and concentrated (repeated 2x) to give the intermediate acid chloride as a golden oil, which This was used without purification.

[0748] Step 2: 5-amino-2-chloro-3- in 1,2-dichloroethane (15 mL) Fluorobenzoic acid (C196) (0.357 g, 1.88 mmol) and triethylamine A mixture of freshly prepared acid chloride, (1R ,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane A solution of benzophenone-1-carbonyl chloride (0.474 g, 1.57 mmol) was added dropwise at 0°C. The resulting green solution was stirred under nitrogen while warming to room temperature over 1 hour, then The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated to give a dark oil, which was then extracted with ethyl acetate ( The mixture was partitioned between 1N aqueous hydrogen chloride (100 mL) and 1N aqueous hydrogen chloride (25 mL). The layer was extracted with additional ethyl acetate (25 mL). The combined organic extracts were washed with brine (50 mL). L), dried over sodium sulfate, filtered, and concentrated to give an amber oil. The precipitate was dissolved in a minimum amount of ethyl acetate and adsorbed onto Celite®. The material was purified using a reversed-phase automated flask with a gradient of 10-100% acetonitrile in water as the eluent. The title compound was purified by flash chromatography to give a pale tan solid (0.398 g , 55%). mp 205-208℃; 1 H 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 FN MR (376 MHz, DMSO-d6) δ -111.57, -117.24;HRMS-ESI(m / z) C 17 H9 Cl4F2NO3 [M + ] + Calculated value: 452.9305; Measured value: 452.9303.

[0749] The following compounds were prepared in a similar manner to the procedure outlined in Example 39. trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-fluorobenzoic acid (C2)

[0750] [ka] Isolated as a light tan solid (0.740 g, 50%): mp 186 - 189°C; 1 H 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-d6) δ -111.54, -117.23; ESIMS m / z 454 ([M- H] - ). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-2-fluoro-3-methylbenzoic acid (C3)

[0751] [ka] Isolated as a tan solid (1.229 g, 87%): mp 228 - 235°C; 1 H NMR (400 M Hz, 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-d6) δ -117.31, -120.17; ESIMS m / z 434 ([M−H] - ). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-methylbenzoic acid (C4)

[0752] [ka] Isolated as a light tan solid (0.875 g, 69%): mp 218 - 222°C; 1 H 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 H z, 1H), 2.38 (s, 3H); 19 F NMR (376 MHz, DMSO-d6) δ -117.29; ESIMS m / z 450 ([MH ] - ). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-methylbenzoic acid (C5)

[0753] [ka] Isolated as a tan solid (0.780 g, 63%): mp 219 - 225°C; 1 H NMR (400 M Hz, 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- d6) δ -117.29; ESIMS m / z 450 ([MH] - ). trans-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-3-(trifluoromethyl)benzoic acid (C6)

[0754] [ka] Isolated as an off-white solid (0.800 g, 47%): mp 216 - 219°C; 1 H NMR (400 MHz, DMSO-d6) δ 14.00 (s, 1H), 11.23 (s, 1H), 8.33 - 8.23 ​​(m, 2H), 7.72 (d d, 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-d6) δ -61.39, -117.21; ESIMS m / z 503 ( [M-2H] - ). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido)-3-fluoro-2-methoxybenzoic acid (C7)

[0755] [ka] Isolated as a tan solid (0.760 g, 50%): mp 183 - 186°C; 1 H NMR (400 M Hz, DMSO-d6) 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-d6) δ -117.29, -128.27; ESIMS m / z 45 0 ([MH] - ). trans-3-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)- (phenyl)cyclopropane-1-carboxamido)-2-fluorobenzoic acid (C8)

[0756] [ka] Isolated as a tan solid (0.82 g, 48%): mp 217 - 224°C; 1 H 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-d6) δ -117.25, -119.42; ESIMS m / z 453 ([MH] - ). trans-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclohexyl) Isopropane-1-carboxamido-2,3-difluorobenzoic acid (C9) ...

Claims

1. The formula: 【Chemistry 1】 [In the formula, 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 is O; Q 2 is O; R 10 is H; R 11 is 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 ; R 14 is selected from the group consisting of H, F and Cl; X3 is (1) N(R 15a )(R 15b ) (wherein, (a) said R 15a is H, (C 1 -C 3 ) alkyl, (C 2 -C 3 ) alkenyl; (C 2 -C 3 ) alkynyl, (C 1 -C 3 ) haloalkyl, (C 1 -C 3 ) alkylphenyl nyl, (C 1 -C 3 ) alkylO(C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkylOC The group consisting of (=O)(C 1 -C 3 )alkyl, and C(=O)(C 1 -C 3 )alkyl is selected from (b) R 15b is a substituted or unsubstituted phenyl, and the substituted phenyl is 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, aryl, (C 1 -C 3 )alkoxy, (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(R15c)C(=S)N(R15c)X4, N(R15c)(C1-C3)alkyl X 4 , N(R 15c )(CH(O(C 1 -C 3 )alkyl) 2 ), N(R 15c )((C 1 -C 3 ) alkylOC(═O)(C 1 -C 3 ) alkyl), N(R 15c ) ((C 1 - C3) alkylC(=O)N(R15c)2), N(R15c)C(=O)(R15c) , 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(C1-C6) alkyl) 2, N(R15c)C(=O)O(C1-C6) 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-C6) haloalkyl), N((C1-C3) alkylOC(=O)(C1-C6) a alkyl)(C(=O)(C 1 -C 6 ) alkyl), N((C 1 -C 3 ) alkylO(C 1 -C 6 ) alkyl) (C(═O)O(C 1 -C 6 ) alkyl), and N(R 15c )C (=S)X 4 ; (1) Each R 15c is independently H, (C 1 -C 3 ) alkyl, (C 2 - (C3) alkenyl, (C2-C3) alkynyl, (C1-C3) haloalkyl, (C2- C 3 ) haloalkenyl, (C 1 -C 3 ) alkylphenyl, (C 1 -C 3 ) alkylO( C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkylOC(═O)(C 1 -C 3 ) alkyl, C(═O)(C 1 -C 3 )alkyl, and phenyl; With respect to N(R 15c ) 2 , said N(R 15c ) 2 is a ring having one nitrogen atom and 3 to 4 carbon atoms. A heterohydrocarbyl ring containing 5 carbon ring atoms, said ring being saturated or unsaturated. It may be sum; (2) X 4 is (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C -C3) alkylO(C1-C3) alkyl, O(C1-C6) alkyl, (C3-C6 ) cycloalkyl, (C 1 -C 6 ) alkylphenyl, phenyl, aryl, and heptane; and cyclocyclyl, each of which is selected from the group consisting of F, Cl, Br, I, CN, OH , NO 2 , NH 2 , oxo, (C 1 -C 3 ) alkyl, (C 1 -C 3 ) haloalkyl, N H(C 1 -C 3 )alkyl, N((C 1 -C 3 )alkyl) 2 , O(C 1 -C 6 )alkyl haloalkyl, 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 to C 3) alkylO(C 1 -C 3 ) alkyl, (C 3 -C 6 ) cycloalkyl may be substituted with one or more selected substituents, In the above (1)(a) and (1)(b), the alkyl, alkenyl, a Each of alkynyl, cycloalkyl, phenyl, aryl and heterocyclyl is 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 ) alkylO(C 1 -C 3 ) alkyl and (C 3 -C 6 ) cycloalkyl; may be substituted with the above substituents; (2) N(R 16a )(R 16b ) (wherein, (a) said R 16a is H, (C 1 -C 3 ) alkyl, (C 2 -C 3 ) alkenyl; (C 2 -C 3 ) alkynyl, (C 1 -C 3 ) haloalkyl, (C 1 -C 3 ) alkylO( C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkylOC(═O)(C 1 -C 3 ) alkyl, and C(═O)(C 1 -C 3 )alkyl; (b) said R 16b is a substituted or unsubstituted (C 1 -C 8 ) alkyl; The substituted (C 1 -C 8 ) alkyl is F, Cl, Br, I, CN, NO 2 , O(C 1 -C 8 ) alkyl. alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkylphenyl, (C 2 -C 8) alkenyl, (C2-C8) alkynyl, S(C1-C8) alkyl, S(O)(C 1 -C 8 ) alkyl, S(O) 2 (C 1 -C 8 ) alkyl, Ophenyl, 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 )a 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; In the above, in (2)(a) and (2)(b), alkyl, alkenyl, alkyl Each of nyl, cycloalkyl and phenyl is F, Cl, Br, I, CN, OH, NH2, NO2, (C1-C8) alkyl, (C1-C8) alkoxy, (C1-C8) Haloalkyl, N((C 1 -C 8 )alkyl) 2 and C(═O)O(C 1 -C 8 )alkyl (optionally substituted with one or more substituents selected from the group consisting of alkyl); (3) N(R 17a )(N(R 17b )(R 17c )) (in the formula, (a) said R 17a is H, (C 1 -C 3 ) alkyl, (C 2 -C 3 ) alkenyl; (C 2 -C 3 ) alkynyl, (C 1 -C 3 ) haloalkyl, (C 1 -C 3 ) alkylO( C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkylOC(═O)(C 1 -C 3 ) alkyl, and C(═O)(C 1 -C 3 )alkyl; (b) said R 17b is H, (C 1 -C 3 ) alkyl, (C 2 -C 3 ) alkenyl; (C 2 -C 3 ) alkynyl, (C 1 -C 3 ) haloalkyl, (C 1 -C 3 ) alkylO( C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkylOC(═O)(C 1 -C 3 ) alkyl, and C(═O)(C 1 -C 3 )alkyl; (c) R 17c is H, a substituted or unsubstituted phenyl, a substituted or unsubstituted heptane, cyclocyclyl, substituted or unsubstituted (C 1 -C 8 ) alkyl, substituted or unsubstituted (C 3 - C8) cycloalkyl, C(=O)X5 and C(=S)X5; (1) X 5 is a substituted or unsubstituted phenyl, a substituted or unsubstituted heterocyclyl aryl, substituted or unsubstituted (C 1 -C 8 )alkyl, O(C 1 -C 8 )alkyl, O(C -C 8 ) haloalkyl, O (substituted or 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) The substituted phenyl in (3)(c) is F, Cl, Br, I, CN, NO 2, OH, (C 1 -C 3 )alkoxy and (C 1 -C 3 )alkyl; and having one or more substituents, (3) The substituted heterocyclyl in (3)(c) is F, Cl, Br, I, CN , NO 2 , OH, (C 1 -C 3 )alkoxy and (C 1 -C 3 )alkyl. having one or more substituents selected from (4) The substituted (C 1 -C 8 ) alkyl in (3)(c) is F, Cl, Br, I, CN, OH, NO2, NH2, O(C1-C8) alkyl, (C3-C8) cycloalkyl alkyl, 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 , Ophenyl, O(C2-C8)alkenyl, O(C1-C8)alkyl(C3-C8) 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-C8) alkyl, S(O)2NH2, NH(C1-C3) alkyl, N((C1-C 3) alkyl) 2) having one or more substituents selected from the group consisting of: (5) The substituted (C 3 -C 8 )cycloalkyl is F, Cl, Br, I, CN, OH , (C 1 -C 3 )alkoxy and (C 1 -C 3 )alkyl; has one or more substituents, In the above, in (2)(a), (2)(b) and (2)(c), alkyl, arylene aryl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl Each is optionally selected from F, Cl, Br, I, CN, OH, NH 2 , NO 2 , (C 1 - C 8 ) alkyl, (C 1 -C 8 ) alkoxy, (C 1 -C 8 ) haloalkyl, N((C 1 C(═O)O(C 1 -C 8 )alkyl) 2 and C(═O)O(C 1 -C 8 )alkyl; and optionally substituted with one or more substituents such as (N(R 17b )(R 17 c)) is a heterohydrocarbyl group containing one nitrogen ring atom and 3 to 5 carbon ring atoms; a cyclic ring, which may be saturated or unsaturated; (4) N(R 18a ) (N=C(R 18b )(R 18c )) (a) said R 18a is H, (C 1 -C 3 ) alkyl, (C 2 -C 3 ) alkenyl; (C2-C3)alkynyl, (C1-C3)alkylO(C1-C3)alkyl, (C1 -C3) alkylOC(=O)(C1-C3) alkyl and C(=O)(C1-C3) is selected from the group consisting of alkyl, (b) said R 18b is selected from the group consisting of H and (C 1 -C 3 ) alkyl; (c) R 18c is a substituted or unsubstituted phenyl, a substituted or unsubstituted heterocyclic aryl, substituted or unsubstituted (C 1 -C 8 ) alkyl, substituted or unsubstituted (C 3 -C 8 ) cycloalkyl; (1) The substituted phenyl in (4)(c) is F, Cl, Br, I, CN, NO 2, OH, (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloa one or more substituents selected from the group consisting of alkoxy and (C 1 -C 3 )haloalkyl; having (2) The substituted heterocyclyl in (4)(c) is F, Cl, Br, I, CN , NO2, OH, (C1-C3)alkoxy, (C1-C3)alkyl, (C1-C3) one or more selected from the group consisting of haloalkoxy and (C 1 -C 3 )haloalkyl; has a substituent, (3) The substituted (C 1 -C 8 ) alkyl is F, Cl, Br, I, CN, NO 2 , O (C 1 -C 8 ) alkyl, (C 3 -C 8 ) cycloalkyl, phenyl, (C 2 -C 8 ) a alkenyl, (C2-C8)alkynyl, S(C1-C8)alkyl, S(O)(C1-C 8) alkyl, S(O) 2 (C 1 -C 8 ) alkyl, Ophenyl, O(C 2 -C 8 ) aryl aryl, O(C 1 -C 8 )alkyl(C 3 -C 8 )cycloalkyl, O(C 1 -C 8 )a 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) 2NH2; (4) The substituted (C 3 -C 8 )cycloalkyl is F, Cl, Br, I, CN, OH , (C 1 -C 3 )alkoxy and (C 1 -C 3 )alkyl; has one or more substituents, In the above, in (4)(a), (4)(b) and (4)(c), alkyl, a alkenyl, alkynyl, cycloalkyl, haloalkyl, phenyl and heterocyclyl are F, Cl, Br, I, CN, OH, NH2, NO2, (C1-C8) alkane, alkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )haloalkyl, N((C 1 -C 8 )a one or more alkyl groups selected from the group consisting of C(═O)O(C 1 -C 8 )alkyl; and optionally C(R 18b )(R 18c ) is selected from the group consisting of 3 to A hydrocarbyl ring containing 5 carbon ring atoms, said ring being saturated or unsaturated. Optionally, one or more of said carbon ring atoms may be replaced by a nitrogen atom, an oxygen atom or or a sulfur atom] Among the molecules having the formula shown in Table 2 below: 【Table 2-1】 【Table 2-2】 【Table 2-3】 【Table 2-4】 【Table 2-5】 【Table 2-6】 【Table 2-7】 【Table 2-8】 【Table 2-9】 【Table 2-10】 【Table 2-11】 【Table 2-12】 【Table 2-13】 【Table 2-14】 【Table 2-15】 【Table 2-16】 【Table 2-17】 【Table 2-18】 【Table 2-19】 【Table 2-20】 and resolved stereoisomers thereof, and (b) an active ingredient selected from the group consisting of abamectin, acephate, acrinathrin, afidopiropen, chloranraniprol, chlorfenapyr, cyantraniliprole, cycloprothrin, cyfluthrin, cypermethrin, dinotefuran, fluxamethamide, imidacloprid, methoxyfenozide, oxamyl, prallethrin, pyriproxyfen, resmethrin, spiromesifen, spirotetramethrin, tetramethrin, thiamethoxam, transfluthrin, and triflumezopyrim; A composition comprising: The weight ratio of said molecule to said active ingredient is （１）１００：１～１：１００ （２）５０：１～１：５０ （３）２０：１～１：２０ （４）１０：１～１：１０ （５）５：１～１：５ （６）３：１～１：３ (7) 2:1 to 1:2, and （８）１：１、 The composition is selected from:

2. The composition described in claim 1, wherein the active ingredient is abamectin.

3. The composition described in claim 1, wherein the active ingredient is acephate.

4. The composition described in claim 1, wherein the active ingredient is acrinathrin.

5. The composition described in claim 1, wherein the active ingredient is afidopiropen.

6. The composition described in claim 1, wherein the active ingredient is chloranraniprole.

7. The composition of claim 1, wherein the active ingredient is chlorfenapyr.

8. The composition described in claim 1, wherein the active ingredient is cyantraniliprole.

9. The composition of claim 1, wherein the active ingredient is cloprothrin.

10. The composition of claim 1, wherein the active ingredient is cyfluthrin.

11. The composition described in claim 1, wherein the active ingredient is cypermethrin.

12. The composition described in claim 1, wherein the active ingredient is dinotefuran.

13. The composition of claim 1, wherein the active ingredient is fluxamethamide.

14. The composition of claim 1, wherein the active ingredient is imidacloprid.

15. The composition of claim 1, wherein the active ingredient is methoxyfenozide.

16. The composition of claim 1, wherein the active ingredient is oxamyl.

17. The composition of claim 1, wherein the active ingredient is prallethrin.

18. The composition described in claim 1, wherein the active ingredient is pyriproxyfen.

19. The composition of claim 1, wherein the active ingredient is resmethrin.

20. The composition of claim 1, wherein the active ingredient is spiromesifen.

21. The composition of claim 1, wherein the active ingredient is spirotetramethrin.

22. The composition of claim 1, wherein the active ingredient is tetramethrin.

23. The composition of claim 1, wherein the active ingredient is thiamethoxam.

24. The composition of claim 1, wherein the active ingredient is transfluthrin.

25. The composition of claim 1, wherein the active ingredient is triflumezopyrim.

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