FUNGICIDAL COMPOSITIONS

Abstract

A fungicidal composition comprising a mixture of components (A) and (B), wherein component (A) is a 8-fluoroquinoline-3-carboxamide of formula I and component (B) is selected from the group consisting of pydiflumetofen, benzovindiflupyr, difenoconazole, hexaconazole, azoxystrobin, fludioxonil, cyprodinil, fluazinam, isopyrazam, pyroquilon, tricyclazole, chlorothalonil, propiconazole, aminopyrifen, penconazole, prothioconazole, mancozeb, fenproprimorph, fenpropidin, sulphur and Bacillus subtilis strains, as well as to the use of the compositions in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably, fungi.

Claims

1. A fungicidal composition comprising a mixture of components (A) and (B), wherein component (A) is a compound of formula (I) ##STR00204## wherein R.sub.1 is hydrogen or methyl; R.sub.2 is hydrogen or methyl; R.sub.3 is hydrogen or methyl; R.sub.4 is —C(Cl)═CH.sub.2, isopropyl, 1-methylcyclopropyl, trifluoromethyl, —C(CH.sub.3)═CH.sub.2 or tert-butyl; or a salt, enantiomer and/or N-oxide thereof; and component (B) is a compound selected from the group consisting of pydiflumetofen, benzovindiflupyr, Difenoconazole, Hexaconazole, Azoxystrobin, Fludioxonil, Cyprodinil, Fluazinam, Isopyrazam, Pyroquilon, Tricyclazole, Chlorothalonil, Propiconazole, Aminopyrifen, Penconazole, Prothioconazole, Mancozeb, Fenpropimorph, Fenpropidin, Sulfur, and a biofungicide comprising Bacillus subtilis strains, such as Taegro® (a biofungicide comprising Bacillus subtilis var. amyloliquefaciens strain FZB24, available from Novozymes Biologicals Inc., 5400 Corporate Circle, Salem, Va. 24153, U.S.A.), Serenade® (based on strain QST713) or Subtilex® (based on strain MBI600); wherein the weight ratio of component (A) to component (B) is from 20:1 to 1:40.

2. The fungicidal composition according claim 1, wherein component (A) is a compound selected from 2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-3-(1-methylcyclopropyl)propanamide (E-99), 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2-methyl-3-(1-methylcyclopropyl)propanamide (E-100), 2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-3-(1-methylcyclopropyl)propanamide (E-89), 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-3-(1-methylcyclopropyl)propanamide (E-90), 2-benzyl-N-(8-fluoro-3-quinolyl)-3-(1-methylcyclopropyl)propanamide (E-91), 2-benzyl-N-(8-fluoro-3-quinolyl)-2-methyl-3-(1-methylcyclopropyl)propanamide (E-70), 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pent-4-enamide (E-65), 2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-2,4-dimethyl-pent-4-enamide (E-66), 2-benzyl-N-(8-fluoro-3-quinolyl)-2,4-dimethyl-pent-4-enamide (E-74), 2-benzyl-4-chloro-N-(8-fluoro-4-methyl-3-quinolyl)-2-methyl-pent-4-enamide (E-20), 2-benzyl-4-chloro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-pent-4-enamide (E-21), 2-benzyl-4-chloro-N-(8-fluoro-3-quinolyl)-2-methyl-pent-4-enamide (E-53), 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-butanamide (E-47), 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-4-methyl-3-quinolyl)-2-methyl-butanamide (E-50), 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide (E-80), 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pentanamide (E-84), 2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-2,4-dimethyl-pentanamide (E-86), 2-benzyl-N-(8-fluoro-3-quinolyl)-2,4-dimethyl-pentanamide (E-87), 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-4,4-dimethyl-pentanamide (E-96), 2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-4,4-dimethyl-pentanamide (E-97) and 2-benzyl-N-(8-fluoro-3-quinolyl)-4,4-dimethyl-pentanamide (E-98), or a salt, enantiomer or N-oxide thereof.

3. The fungicidal composition according to claim 1, wherein component (A) is 2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-2,4-dimethyl-pentanamide (E-86); or a salt, enantiomer or N-oxide thereof.

4. The fungicidal composition according to claim 1, wherein component (A) is 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-butanamide (E-47); or a salt, enantiomer or N-oxide thereof.

5. The fungicidal composition according to claim 1, wherein component (A) is 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-4-methyl-3-quinolyl)-2-methyl-butanamide (E-50); or a salt, enantiomer or N-oxide thereof.

6. The fungicidal composition according to claim 1, wherein component (A) is 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pentanamide (E-84); or a salt, enantiomer or N-oxide thereof.

7. The fungicidal composition according to claim 1 wherein component (A) is present as the (S)-enantiomer, or a salt or N-oxide thereof.

8. The fungicidal composition according to claim 1, wherein component (A) is present as the (R)-enantiomer, or a salt or N-oxide thereof.

9. The fungicidal composition according to claim 1, wherein component (B) is a compound selected from the group consisting of pydiflumetofen, benzovindiflupyr [1072957-71-1], Difenoconazole, Hexaconazole, Prothioconazole, Mancozeb, Azoxystrobin, Fludioxonil, Cyprodinil, Fluazinam, Isopyrazam, Propiconazole, Aminopyrifen, Pyroquilon, Tricyclazole, Chlorothalonil, Penconazole, Fenpropimorph, Fenpropidin, Sulfur, and a biofungicide comprising Bacillus subtilis strains, such as Taegro® (a biofungicide comprising Bacillus subtilis var. amyloliquefaciens strain FZB24, available from Novozymes Biologicals Inc., 5400 Corporate Circle, Salem, Va. 24153, U.S.A.).

10. The fungicidal composition according to claim 1, wherein component (B) is a compound selected from the group consisting of pydiflumetofen, benzovindiflupyr [1072957-71-1], Difenoconazole, Hexaconazole, Prothioconazole, Mancozeb, Azoxystrobin, Fludioxonil, Cyprodinil, Fluazinam, Isopyrazam, Propiconazole, Aminopyrifen, Pyroquilon, Tricyclazole and Chlorothalonil.

11. The fungicidal composition according to claim 1, wherein the composition comprises one or more further pesticides selected from the group consisting of: a fungicide, selected from etridiazole, fluazinam, benalaxyl, benalaxyl-M (kiralaxyl), furalaxyl, metalaxyl, metalaxyl-M (mefenoxam), dodicin, N′-(2,5-Dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine, N′-[4-(4,5-Dichloro-thiazol-2-yloxy)-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine, N′-[4-[[3-[(4-chlorophenyl)methyl]-1,2,4-thiadiazol-5-yl]oxy]-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine, ethirimol, 3′-chloro-2-methoxy-N-[(3RS)-tetrahydro-2-oxofuran-3-yl]acet-2′,6′-xylidide (clozylacon), cyprodinil, mepanipyrim, pyrimethanil, dithianon, aureofungin, blasticidin-S, biphenyl, chloroneb, dicloran, hexachlorobenzene, quintozene, tecnazene, (TCNB), tolclofos-methyl, Aminopyrifen, metrafenone, 2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide, fluopicolide (flupicolide), tioxymid, flusulfamide, benomyl, carbendazim, carbendazim chlorhydrate, chlorfenazole, fuberidazole, thiabendazole, thiophanate-methyl, benthiavalicarb, chlobenthiazone, probenazole, acibenzolar, bethoxazin, pyriofenone (IKF-309), acibenzolar-S-methyl, pyribencarb (KIF-7767), butylamine, 3-iodo-2-propinyl n-butylcarbamate (IPBC), iodocarb (isopropanyl butylcarbamate), isopropanyl butylcarbamate (iodocarb), picarbutrazox, polycarbamate, propamocarb, tolprocarb, 3-(difluoromethyl)-N-(7-fluoro-1,1,3,3-tetramethyl-indan-4-yl)-1-methyl-pyrazole-4-carboxamide diclocymet, N-[(5-chloro-2-isopropyl-phenyl)methyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-pyrazole-4-carboxamide N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-[(2-isopropylphenyl)methyl]-1-methyl-pyrazole-4-carboxamide carpropamid, chlorothalonil, flumorph, oxine-copper, cymoxanil, phenamacril, cyazofamid, flutianil, thicyofen, chlozolinate, iprodione, procymidone, vinclozolin, bupirimate, dinocton, dinopenton, dinobuton, dinocap, meptyldinocap, diphenylamine, phosdiphen, 2,6-dimethyl-[1,4]dithiino[2,3-c:5,6-c′]dipyrrole-1,3,5,7(2H,6H)-tetraone, azithiram, etem, ferbam, mancozeb, maneb, metam, metiram (polyram), metiram-zinc, nabam, propineb, thiram, vapam (metam sodium), zineb, ziram, dithioether, isoprothiolane, ethaboxam, fosetyl, phosetyl-Al (fosetyl-al), methyl bromide, methyl iodide, methyl isothiocyanate, cyclafuramid, fenfuram, validamycin, streptomycin, (2RS)-2-bromo-2-(bromomethyl)glutaronitrile (bromothalonil), dodine, doguadine, guazatine, iminoctadine, iminoctadine triacetate, 2,4-D, 2,4-DB, kasugamycin, dimethirimol, fenhexamid, hymexazole, hydroxyisoxazole imazalil, imazalil sulphate, oxpoconazole, pefurazoate, prochloraz, triflumizole, fenamidone, Bordeaux mixture, calcium polysulfide, copper acetate, copper carbonate, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper oxyquinolate, copper silicate, copper sulphate, copper tallate, cuprous oxide, sulphur, carbaryl, phthalide (fthalide), dingjunezuo (Jun Si Qi), oxathiapiprolin, fluoroimide, mandipropamid, KSF-1002, benzamorf, dimethomorph, fenpropimorph, tridemorph, dodemorph, diethofencarb, fentin acetate, fentin hydroxide, carboxin, oxycarboxin, drazoxolon, famoxadone, m-phenylphenol, p-phenylphenol, tribromophenol (TBP), 2-[2-[(7,8-difluoro-2-methyl-3-quinolyl)oxy]-6-fluoro-phenyl]propan-2-ol 2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolyl)oxy]phenyl]propan-2-ol cyflufenamid, ofurace, oxadixyl, flutolanil, mepronil, isofetamid, fenpiclonil, fludioxonil, pencycuron, edifenphos, iprobenfos, pyrazophos, phosphorus acids, tecloftalam, captafol, captan, ditalimfos, triforine, fenpropidin, piperalin, osthol, 1-methylcyclopropene, 4-CPA, chlormequat, clofencet, dichlorprop, dimethipin, endothal, ethephon, flumetralin, forchlorfenuron, gibberellic acid, gibberellins, hymexazol, maleic hydrazide, mepiquat, naphthalene acetamide, paclobutrazol, prohexadione, prohexadione-calcium, thidiazuron, tribufos (tributyl phosphorotrithioate), trinexapac, uniconazole, a-naphthalene acetic acid, polyoxin D (polyoxrim), BLAD, chitosan, fenoxanil, folpet, 3-(difluoromethyl)-N-methoxy-1-methyl-N-[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]pyrazole-4-carboxamide, bixafen, fluxapyroxad, furametpyr, isopyrazam, penflufen, penthiopyrad, sedaxane, fenpyrazamine, diclomezine, pyrifenox, boscalid, fluopyram, diflumetorim, fenarimol, 5-fluoro-2-(p-tolylmethoxy)pyrimidin-4-amine ferimzone, dimetachlone (dimethaclone), pyroquilon, proquinazid, ethoxyquin, quinoxyfen, 4,4,5-trifluoro-3,3-dimethyl-1-(3-quinolyl)isoquinoline 4,4-difluoro-3,3-dimethyl-1-(3-quinolyl)isoquinoline 5-fluoro-3,3,4,4-tetramethyl-1-(3-quinolyl)isoquinoline 9-fluoro-2,2-dimethyl-5-(3-quinolyl)-3H-1,4-benzoxazepine, tebufloquin, oxolinic acid, chinomethionate (oxythioquinox, quinoxymethionate), spiroxamine, (E)-N-methyl-2-[2-(2, 5-dimethylphenoxymethyl) phenyl]-2-methoxy-iminoacetamide, (mandestrobin), azoxystrobin, coumoxystrobin, dimoxystrobin, enestroburin, enoxastrobin fenamistrobin, flufenoxystrobin, fluoxastrobin, kresoxim-methyl, mandestrobin, metaminostrobin, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, pyrametostrobin, pyraoxystrobin, triclopyricarb, trifloxystrobin, amisulbrom, dichlofluanid, tolylfluanid, but-3-ynyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate, dazomet, isotianil, tiadinil, thifluzamide, benthiazole (TCMTB), silthiofam, zoxamide, anilazine, tricyclazole, (.+-.)-cis-1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)-cycloheptanol (huanjunzuo), 1-(5-bromo-2-pyridyl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1,2,4-triazol-1-yl)propan-2-ol 2-(1-tert-butyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ol (TCDP), azaconazole, bitertanol (biloxazol), bromuconazole, climbazole, cyproconazole, difenoconazole, dimetconazole, diniconazole, diniconazole-M, epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, Mefentrifluconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triazoxide, triticonazole, 2-[[(1R,5S)-5-[(4-fluorophenyl)methyl]-1-hydroxy-2,2-dimethyl-cyclopentyl]methyl]-4H-1,2,4-triazole-3-thione 2-[[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl]-4H-1,2,4-triazole-3-thione, ametoctradin (imidium), iprovalicarb, valifenalate, 2-benzyl-4-chlorophenol (Chlorophene), allyl alcohol, azafenidin, benzalkonium chloride, chloropicrin, cresol, daracide, dichlorophen (dichlorophene), difenzoquat, dipyrithione, N-(2-p-chlorobenzoylethyl)-hexaminium chloride, NNF-0721, octhilinone, oxasulfuron, propamidine and propionic acid; or an insecticides selected from abamectin, acephate, acetamiprid, amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, cartap, chlorantraniliprole (DPX-E2Y45), chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos, halofenozide, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, pymetrozine, pyrafluprole, pyrethrin, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen (BSN 2060), spirotetramat, sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, trichlorfon and triflumuron; or a bactericides selected from streptomycin; or an acaricide selected from amitraz, chinomethionat, chlorobenzilate, cyenopyrafen, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; or a biological agents selected from Bacillus thuringiensis, Bacillus thuringiensis delta endotoxin, baculovirus, and entomopathogenic bacteria, virus and fungi.

12. The fungicidal composition according to claim 1, wherein the composition further comprises an agriculturally acceptable carrier and, optionally, a surfactant and/or formulation adjuvants.

13. A method of controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi, on useful plants or on propagation material thereof, which comprises applying to the useful plants, the locus thereof or propagation material thereof a fungicidal composition as defined in claim 1.

14. The method according to claim 13 wherein the composition components (A) and (B) are applied in a sequential manner.

15. A compound selected from ##STR00205## or a compound selected from: ##STR00206## ##STR00207##

Description

EXAMPLES

[0411] The Examples which follow serve to illustrate the invention. Certain compounds and compositions of the invention can be distinguished from known compounds and compositions by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.

[0412] Throughout this description, temperatures are given in degrees Celsius and “m.p.” means melting point. LC/MS means Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the methods are:

[0413] Method G:

[0414] Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, SQDII or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 1.2 min; Flow (ml/min) 0.85

[0415] Method H:

[0416] Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, SQDII or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 2.7 min; Flow (ml/min) 0.85

FORMULATION EXAMPLES

[0417]

TABLE-US-00004 Wettable powders a) b) c) active ingredient [compound of formula (I)] 25% 50% 75% sodium lignosulfonate  5%  5% — sodium lauryl sulfate  3% —  5% sodium diisobutylnaphthalenesulfonate —  6% 10% phenol polyethylene glycol ether —  2% — (7-8 mol of ethylene oxide) highly dispersed silicic acid  5% 10% 10% Kaolin 62% 27% —
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.

TABLE-US-00005 Powders for dry seed treatment a) b) c) active ingredient [compound of formula (I)] 25% 50% 75% light mineral oil  5%  5%  5% highly dispersed silicic acid  5%  5% — Kaolin 65% 40% — Talcum — — 20%
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.

TABLE-US-00006 Emulsifiable concentrate active ingredient [compound of formula (I)] 10% octylphenol polyethylene glycol ether  3% (4-5 mol of ethylene oxide) calcium dodecylbenzenesulfonate  3% castor oil polyglycol ether (35 mol of ethylene oxide)  4% Cyclohexanone 30% xylene mixture 50%
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

TABLE-US-00007 Dusts a) b) c) Active ingredient [compound of formula (I)]  5%  6%  4% talcum 95% — — Kaolin — 94% — mineral filler — — 96%
Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.

TABLE-US-00008 Extruder granules Active ingredient [compound of formula (I)] 15% sodium lignosulfonate  2% carboxymethylcellulose  1% Kaolin 82%
The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

TABLE-US-00009 Coated granules Active ingredient [compound of formula (I)] 8% polyethylene glycol (mol. wt. 200) 3% Kaolin 89% 
The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.

TABLE-US-00010 Suspension concentrate active ingredient [compound of formula (I)] 40% propylene glycol 10% nonylphenol polyethylene glycol ether (15 mol of ethylene oxide)  6% Sodium lignosulfonate 10% carboxymethylcellulose  1% silicone oil (in the form of a 75% emulsion in water)  1% Water 32%
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

TABLE-US-00011 Flowable concentrate for seed treatment active ingredient [compound of formula (I)] 40% propylene glycol  5% copolymer butanol PO/EO  2% tristyrenephenole with 10-20 moles EO  2% 1,2-benzisothiazolin-3-one (in the form of a 20%   0.5% solution in water) monoazo-pigment calcium salt  5% Silicone oil (in the form of a 75% emulsion in water)   0.2% Water   45.3%
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

Slow Release Capsule Suspension

[0418] 28 parts of a combination of the compound of formula I are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

PREPARATION EXAMPLES

Example 1: Preparation of 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide

Step 1: Preparation of ethyl 2-benzyl-4,4,4-trifluoro-2-methyl-butanoate

[0419] ##STR00040##

[0420] n-Butyl lithium (2.5 M in hexanes, 100 mL, 248.9 mmol) was added slowly to a solution of diisopropyl amine (35.2 mL, 248.9 mmol) in tetrahydrofuran (400 mL) at −70° C. The resulting solution was aged for 30 min at −70° C. and then ethyl 4,4,4-trifluorobutyrate (36 g, 207.4 mmol) was added drop wise. The reaction was stirred for 2 h at −70° C., benzyl bromide (43.2 g, 248.9 mmol) was added and the reaction mixture was gradually warmed to room temperature over ca. 2 h. Saturated NH.sub.4Cl solution was added and the mixture was extracted with methyl tertbutyl ether. The organic layer was washed with water, brine, dried over MgSO.sub.4, filtrated and concentrated in vacuo. The residual oil was passed through a short pad of silica gel, the pad was rinsed with cyclohexane:ethyl acetate (2:1) and the filtrate was concentrated in vacuo, affording ethyl 4,4,4-trifluoro-2-methyl-butanoate as light orange oil.

[0421] n-Butyl lithium (2.5 M in hexanes, 99 mL, 247.2 mmol) was added slowly to a solution of diisopropyl amine (35 mL, 247.2 mmol) in tetrahydrofuran (380 mL) at −70° C. The resulting solution was aged for 30 min at −70° C. and then the crude product obtained above (49.5 g, 190.2 mmol, diluted with tetrahydrofuran (30 mL)) was added slowly at −70° C. The resulting dark solution was stirred for 2 h at −70° C. before methyl iodide (13.1 mL, 209.3 mmol) was added. The reaction mixture was gradually warmed to 20° C. over ca. 3 h, then quenched with saturated NH.sub.4Cl solution and extracted with methyl tertbutylether. The organic layer was washed with water, brine, dried over MgSO.sub.4, filtrated and concentrated in vacuo. The residual oil was passed through a short pad of silica gel, the pad was rinsed with cyclohexane:ethyl acetate (2:1) and the filtrate was concentrated in vacuo, affording the title compound as light brown oil (ca. 80% pure).

[0422] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.05-7.33 (m, 5H), 4.13 (q, 2H), 2.98 (d, 1H), 2.81-2.72 (m, 2H), 2.11-2.32 (m, 1H), 1.28 (s, 3H), 1.21 (t, 3H).

Step 2: Preparation of 2-benzyl-4,4,4-trifluoro-2-methyl-butanoic Acid

[0423] ##STR00041##

[0424] A solution of ethyl 2-benzyl-4,4,4-trifluoro-2-methyl-butanoate (25.5 g, 93.0 mmol) in 1,4-dioxane (45 mL)/ethanol (45 mL) was treated with NaOH (7.6 g, 186 mmol) at room temperature, the resulting solution was warmed to 90° C. and aged for 1 h at 90° C. After cooling to room temperature, the reaction mixture was concentrated to about 50% of the original volume. The residue was diluted with water and washed with cyclohexane. The water layer was then acidified with HCl (conc.) under ice cooling at temp <25° C. and the mixture was extracted with DCM. The organic layer were washed with brine, dried with Na.sub.2SO.sub.4, filtrated and concentrated in vacuo to afford 2-benzyl-4,4,4-trifluoro-2-methyl-butanoic acid as dark yellow oil which solidified upon standing at room temperature.

[0425] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.07-7.37 (m, 3H), 7.07-7.19 (m, 2H), 3.02 (d, 1H), 2.86 (d, 1H), 2.70-2.83 (m, 1H), 2.17-2.35 (m, 1H), 1.31 (s, 3H).

Step 3: Preparation of 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide

[0426] ##STR00042##

[0427] Oxalyl chloride (0.15 mL, 1.66 mmol) was added to a solution of 2-benzyl-4,4,4-trifluoro-2-methyl-butanoic acid (0.4 g, 1.38 mmol) and 2 drops of dimethyl formamide in dichloromethane (4 mL) at room temperature. The resulting solution was stirred for 1 h at room temperature and then concentrated in vacuo an oily residue. This residue was taken up in dichloromethane (2 mL) and slowly added to a solution of 8-fluoro-quinolin-3-amine (0.22 g, 1.38 mmol), 4-dimethylaminopyridine (ca. 5 mg) and triethylamine (0.58 mL, 4.14 mmol) in dichloromethane (5 mL). The resulting solution was stirred at room temperature overnight, diluted with ethyl acetate and quenched with water. The organic layer was washed with aqueous NaHCO.sub.3 and brine, dried over MgSO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide as light brown foam.

[0428] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.73 (s, 1H), 8.44 (d, 1H), 7.62 (d, 1H), 7.53-7.48 (m, 1H), 7.00-7.40 (m, 6H), 3.11-3.34 (m, 2H), 2.74 (d, 1H), 2.21-2.45 (m, 1H), 1.53 (s, 3H).

Example 2: Preparation of the Single Isomers

(S)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide and (R)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide

[0429] The 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide mixture was submitted to chiral resolution by preparative HPLC chromathography using the conditions outlined hereafter.

Analytical HPLC Method

SFC: Waters Acquity UPC.SUP.2./QDa

PDA Detector Waters Acquity UPC.SUP.2

[0430] Column: Daicel SFC CHIRALPAK® OZ, 3 um, 0.3 cm×10 cm, 40° C.
Mobile phase: A: CO.sub.2 B: EtOH gradient: 20% B in 1.8 min

ABPR: 1800 psi

[0431] Flow rate: 2.0 ml/min

Detection: 250 nm

[0432] Sample concentration: 1 mg/mL in ACN/iPr 50/50

Injection: 1 uL

Preparative HPLC Method:

[0433] Autopurification System from Waters: 2767 sample Manager, 2489 UV/Visible Detector, 2545 Quaternary Gradient Module.
Column: Daicel CHIRALPAK® IB, 5 um, 1.0 cm×25 cm
Mobile phase: Hept/EtOH 90/10
Flow rate: 10 ml/min

Detection: UV 265 nm

[0434] Sample concentration: 100 mg/mL in MeOH/DCM (1/1)

Injection: 250 μl

Results (Analytical Method/Preparative Method):

[0435]

TABLE-US-00012 First eluting enantiomer Second eluting enantiomer Retention time (min) Retention time (min) ~ 0.78 / ~ 3.71 ~ 1.60 / ~ 5.99 Chemical purity (area % Chemical purity (area % at 220 nm) 99 at 220 nm) 99 Enantiomeric excess (%) > 99 Enantiomeric excess (%) > 99

[0436] The compound with the elution time of 0.78 minute is (2R)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide, corresponding to compound F-24.

[0437] The compound with the elution time of 1.60 minutes is (2S)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide, corresponding to compound F-23.

Example 3: Preparation of 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pent-4-enamide

Step 1: Preparation of 8-fluoro-3-iodo-4-methyl-quinoline

[0438] ##STR00043##

[0439] To a suspension of 2-fluoroaniline (25 g, 214 mmol) and potassium carbonate (29.8 g, 214 mmol) in acetone (430 mL) was added 1-bromo-2-butyne (26.1 g, 192 mmol) at room temperature. The resulting mixture was warmed to 70° C. and stirred for 22 h at this temperature. After cooling to room temperature, approx. 200 mL of the solvent was removed in vacuo and the water was added. The mixture was extracted with tertbutyl methyl ether, the organic layer was washed with water, brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The dark yellow residue was filtrated through a plug of silica gel and the filtrate was concentrated to a yellow liquid consisting of a mixture of N-but-2-ynyl-2-fluoro-aniline and N,N-bis(but-2-ynyl)-2-fluoro-aniline.

[0440] This oil was diluted with acetonitrile (2000 mL), NaHCO.sub.3 (34.6 g, 408 mmol) and iodine (104 g, 408 mmol) was added and the resulting dark brown solution was stirred for 3 h at room temperature. Aqueous Na.sub.2S.sub.2O.sub.3 solution was then added and the mixture was extracted multiple times with ethyl acetate. The combined organic layers were washed with water and brine; dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford 8-fluoro-3-iodo-4-methyl-quinoline as light yellow solid.

[0441] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.15 (s, 1H), 7.77-7.91 (m, 1H), 7.51 (dt, 1H), 7.36-7.47 (m, 1H), 2.87 (s, 3H).

[0442] .sup.19F NMR (377 MHz CDCl.sub.3) δ −124.00 (s, 1F).

Step 2: Preparation of 8-fluoro-4-methyl-quinolin-3-amine

[0443] ##STR00044##

[0444] A pressure resistant vessel was charged with 8-fluoro-3-iodo-4-methyl-quinoline (1 g, 3.5 mmol), Cs.sub.2CO.sub.3 (2.3 g, 7.0 mmol), pentane-2,4-dione (0.14 g, 1.4 mmol), copper(II)acetylacetonate (0.09 g, 0.35 mmol) and N,N-dimethylformamide (7 mL). The resulting mixture was purged with N.sub.2, aqueous ammonia (25%, 1 mL, 14 mmol) was then added, and the vessel was sealed and warmed to 90° C. After stirred for 24 h at 90° C., the resulting dark solution was cooled to room temperature, diluted with water and extracted several times with ethyl acetate. The combined organic layers were washed with water and brine; dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford 8-fluoro-4-methyl-quinolin-3-amine as brown solid.

[0445] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.51 (s, 1H), 7.63 (d, 1H), 7.40 (dt, 1H), 7.14 (ddd, 1H), 3.93 (br s, 2H), 2.43 (s, 3H).

Step 3: Preparation of methyl 2-methyl-3-phenyl-propanoate

[0446] ##STR00045##

[0447] A solution of methyl-3-phenylpropionate (5.0 g, 30 mmol) in tetrahydrofuran (15 mL) was added slowly to lithium diisopropylamide (prepared from n-butyl lithium [2.5 M in hexanes, 14 mL, 36 mmol] and diisopropylamine [5.2 mL, 37 mmol] in tetrahydrofuran [15 mL]) at −78° C. The reaction was aged for 2 h at −78° C., iodomethane (2.8 mL, 45 mmol) was added and the resulting solution was gradually warmed to 0° C. over 3 h. Saturated, aq. NH.sub.4Cl solution was then added and the mixture was extracted with tertbutyl methyl ether. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford methyl 2-methyl-3-phenyl-propanoate as colourless liquid.

[0448] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.98-7.29 (m, 5H), 3.56 (s, 3H), 2.96 (dd, 1H), 2.53-2.73 (m, 2H), 1.08 (d, 3H).

Step 4: Preparation of methyl 2-benzyl-2,4-dimethyl-pent-4-enoate

[0449] ##STR00046##

[0450] A solution of methyl 2-methyl-3-phenyl-propanoate (1.40 g, 7.86 mmol) in tetrahydrofuran (4 mL) was added slowly to lithium diisopropylamide (prepared from n-butyl lithium [2.5 M in hexanes, 3.8 mL, 9.4 mmol] and diisopropylamine [1.38 mL, 9.8 mmol] in tetrahydrofuran [4 mL]) at −78° C. The reaction was aged for 2 h at −78° C., 3-bromo-2-methylpropene (1.22 mL, 11.8 mmol) was added and the resulting solution was gradually warmed to 0° C. over 3 h. Saturated, aq. NH.sub.4Cl solution was then added and the mixture was extracted with tertbutyl methyl ether. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford methyl 2-benzyl-2,4-dimethyl-pent-4-enoate as colourless liquid.

[0451] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.98-7.43 (m, 5H), 4.87 (s, 1H), 4.72 (s, 1H), 3.68 (s, 2H), 3.14 (d, 1H), 2.69 (t, 2H), 2.18 (d, 1H), 1.71 (s, 3H), 1.12 (s, 3H).

Step 5: Preparation of 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pent-4-enamide

[0452] ##STR00047##

[0453] To a suspension of methyl 2-benzyl-2,4-dimethyl-pent-4-enoate (0.10 g, 0.5 mmol) and 8-fluoro-4-methyl-quinolin-3-amine (0.08 g, 0.5 mmol) in toluene (1 mL) was added trimethyl aluminium (2 M in toluene, 0.3 mL, 0.6 mmol) at room temperature. The resulting mixture was warmed to 90° C. and stirred for 64 h at this temperature. The reaction was then cooled to room temperature and added into aq. NaOH (1 M) solution. The mixture was extracted with ethyl acetate, the organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford 2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pent-4-enamide as yellow solid, m.p. 105-109° C.

[0454] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.83 (s, 1H), 7.73 (d, 1H), 7.53-7.48 (m, 1H), 6.99-7.45 (m, 7H), 4.99 (s, 1H), 4.89 (s, 1H), 3.35 (d, 1H), 3.02 (d, 1H), 2.66 (d, 1H), 2.29 (s, 3H), 2.22 (d, 1H), 1.86 (s, 3H), 1.42 (s, 3H)

[0455] .sup.19F NMR (377 MHz CDCl.sub.3) δ −124.67 (s, 1F)

Example 4: Preparation of 2-benzyl-2,4-dimethyl-N-(3-quinolyl)pentanamide

Step 1: Preparation of ethyl 2-benzyl-2,4-dimethyl-pentanoate

[0456] ##STR00048##

[0457] A solution of ethyl 2,4-dimethylpentanoate (1.0 g, 5.1 mmol, prepared according to Synthesis, 2005, p. 272-278) in tetrahydrofuran (5 mL) was added slowly to lithium diisopropylamide (prepared from n-butyl lithium [1.6 M in hexanes, 3.8 mL, 6.1 mmol] and diisopropylamine [0.85 mL, 6.1 mmol] in tetrahydrofuran [5 mL]) at −78° C. The reaction was aged for 2 h at −78° C., benzylbromide (0.95 g, 5.56 mmol) and, 3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.1 mL) was added and the resulting solution was gradually warmed to 20° C. over 3 h. Saturated, aq. NH.sub.4Cl solution was then added and the mixture was extracted with tertbutyl methyl ether. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford ethyl 2-benzyl-2,4-dimethyl-pentanoate as colourless liquid.

[0458] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.02-7.26 (m, 5H), 4.07 (q, 2H), 3.03 (d, 1H), 2.60 (d, 1H), 1.64-1.91 (m, 2H), 1.38 (dd, 1H), 1.22 (t, 3H), 1.09 (s, 3H), 0.91 (d, 3H), 0.83 (d, 3H).

Step 2: Preparation of 2-benzyl-2,4-dimethyl-N-(3-quinolyl)pentanamide

[0459] ##STR00049##

[0460] To a suspension of ethyl 2-benzyl-2,4-dimethyl-pentanoate (0.09 g, 0.35 mmol) and quinolin-3-amine (0.05 g, 0.35 mmol) in toluene (0.7 mL) was added trimethyl aluminium (2 M in toluene, 0.22 mL, 0.45 mmol) at room temperature. The resulting solution was warmed to 90° C. and stirred for 24 h at this temperature. The reaction was then cooled to room temperature and added into aq. NaOH (1 M) solution. The mixture was extracted with ethyl acetate, the organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford 2-benzyl-2,4-dimethyl-N-(3-quinolyl)pentanamide as yellow solid, m.p. 147-148° C.

[0461] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.66 (d, 1H), 8.43 (d, 1H), 8.03 (d, 1H), 7.81 (dd, 1H), 7.44-7.72 (m, 2H), 7.05-7.23 (m, 5H), 3.19 (d, 1H), 2.64 (d, 1H), 2.05 (dd, 1H), 1.73-1.92 (m, 1H), 1.45-1.52 (m, 1H), 1.34 (s, 3H), 1.00 (d, 3H), 0.92 (d, 3H).

Example 5: Preparation of (S)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-4-methyl-3-quinolyl)-2-methyl-butanamide

Step 1: Preparation of (S)-2-benzyl-4,4,4-trifluoro-2-methyl-butanoic Acid

[0462] ##STR00050##

[0463] To a solution of 2-benzyl-4,4,4-trifluoro-2-methyl-butanoic acid (20.35 g, 82.65 mmol) in cyclopentyl methyl ether (CPME) (275 mL) was added (S)-(−)-1-phenylethylamine (5.11 g, 41.32 mmol) at ambient temperature, resulting in the formation of a white precipitate. The slurry was gradually heated to 60° C., stirred at this temperature for ˜3 h and then the mixture was allowed to cool to ambient temperature overnight (˜18 h). The white precipitate was collected by filtration, was washed with CPME and dried in vacuo to afford the ammonium salt as off-white solid.

[0464] The salt was suspended in tertbutyl methyl ether (100 mL) and treated with aqueous HCl (2 M) and the mixture was stirred until a clear colorless emulsion was formed. The layers were separated and the organic layer was washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo to afford (S)-2-benzyl-4,4,4-trifluoro-2-methyl-butanoic acid as pale yellow oil (e.r.=95:5, retention time minor enantiomer: 2.67 min, retention time major enantiomer: 3.50 min, Daicel SFC CHIRALPAK® IG, CO.sub.2/MeOH).

[0465] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.30-7.35 (m, 3H), 7.15-7.18 (m, 2H), 3.05 (d, 1H), 2.76-2.90 (m, 2H), 2.21-2.33 (m, 1H), 1.33 (s, 3H). .sup.19F NMR (400 MHz, CDCl.sub.3) δ 60.06 (s, 3F).

Step 2: Preparation of (S)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-4-methyl-3-quinolyl)-2-methyl-butanamide

[0466] ##STR00051##

[0467] To a solution of (S)-2-benzyl-4,4,4-trifluoro-2-methyl-butanoic acid (6.70 g, 27.2 mmol) in DCM (80 mL) was added DMF (5 drops) followed by oxalyl chloride (4.23 g, 32.7 mmol) over a period of 2 h. The mixture was stirred at ambient temperature for additional 80 min until the gas evolution ceased. The solution was concentrated in vacuo to remove all volatiles and afforded crude (S)-2-benzyl-4,4,4-trifluoro-2-methyl-butanoyl chloride as yellow oil. This material was dissolved in DCM (55 mL) and used directly in the following step.

[0468] To a solution of 8-fluoro-4-methyl-quinolin-3-amine (5.27 g, 29.9 mmol) and 1-methylimidazole (6.77 g, 81.6 mmol) in DCM (90 mL) was added a solution of (S)-2-benzyl-4,4,4-trifluoro-2-methyl-butanoyl chloride in DCM (as prepared above) over a period of ˜10 min. The resulting brown solution was stirred at ambient temperature for 2 h. The reaction mixture was diluted with additional DCM and washed with water and brine. The organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo to afford a dark yellow oil. The residue was purified by medium pressure chromatography (silica gel, cyclohexane:EtOAc) to afford (S)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-4-methyl-3-quinolyl)-2-methyl-butanamide as off white solid. [α].sup.D: −128° (CHCl.sub.3, c=1.00), (e.r. 95:5 {retention time minor enantiomer: 1.71 min, retention time major enantiomer: 0.71 min, Daicel SFC CHIRALPAK® ID, CO.sub.2/iPrOH})

[0469] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.51 (s, 1H), 7.76 (d, 1H), 7.49-7.54 (m, 1H), 7.32-7.42 (m, 4H), 2.20-2.22 (dd, 2H), 7.03 (s, 1H), 3.22-3.35 (m, 2H), 2.67 (d, 1H), 2.35 (s, 3H), 2.22-2.31 (m, 1H), 1.59 (s, 3H). .sup.19F NMR (400 MHz, CDCl.sub.3) δ 60.03 (s, 3F), 124.18 (s, 1F).

Example 6: Preparation of 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-butanamide

[0470] ##STR00052##

[0471] To a solution of 2-benzyl-4,4,4-trifluoro-2-methyl-butanoic acid (0.50 g, 2.0 mmol) in DCM (6 mL) was added DMF (2 drops) followed by oxalyl chloride (0.32 g, 0.22 mmol) over a period of 30 min. The mixture was stirred at ambient temperature for additional 70 min until the gas evolution ceased. The solution was concentrated in vacuo to remove all volatiles and afforded crude 2-benzyl-4,4,4-trifluoro-2-methyl-butanoyl chloride as yellow oil. This material was dissolved in DCM (6 mL) and used directly in the following step.

[0472] To a solution of 8-fluoro-2-methyl-quinolin-3-amine (0.39 g, 2.2 mmol) and 1-methylimidazole (0.51 g, 6.1 mmol) in DCM (6 mL) was added a solution of 2-benzyl-4,4,4-trifluoro-2-methyl-butanoyl chloride (as prepared above) over a period of 5 min. The resulting brown solution was stirred at ambient temperature for 1 h. The reaction mixture was diluted with additional DCM and washed with water and brine. The organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo to afford a dark yellow oil. The residue was purified by medium pressure chromatography (silica gel, cyclohexane:EtOAc) to afford 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-butanamide as off white solid, m.p. 137-140° C.

[0473] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (d, 1H), 7.61 (d, 1H), 7.45 (td, 1H), 7.21-7.37 (m, 4H), 7.00-7.19 (m, 3H), 3.20-3.39 (m, 2H), 2.70 (d, 1H), 2.24-2.36 (m, 1H), 2.28 (s, 3H), 1.55 ppm (s, 3H). .sup.19F NMR (377 MHz, CDCl.sub.3) δ −60.03 (s, 3F), −126.77 ppm (s, 1F).

Example 7: Preparation of the Single Isomers

(S)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-butanamide and (R)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-butanamide

[0474] The 2-benzyl-4,4,4-trifluoro-N-(8-fluoro-2-methyl-3-quinolyl)-2-methyl-butanamide mixture was submitted to chiral resolution by preparative HPLC chromathography using the conditions outlined hereafter.

[0475] Analytical HPLC method:

[0476] SFC: Waters Acquity UPC.sup.2/QDa

[0477] PDA Detector Waters Acquity UPC.sup.2

[0478] Column: Daicel SFC CHIRALPAK® OZ, 3 μm, 0.3 cm×10 cm, 40° C.

[0479] Mobile phase: A: CO2 B: EtOH gradient: 20% B in 1.8 min

[0480] ABPR: 1800 psi

[0481] Flow rate: 2.0 ml/min

[0482] Detection: 244 nm

[0483] Sample concentration: 1 mg/mL in ACN/iPr 50/50

[0484] Injection: 1 μL

[0485] Preparative HPLC Method:

[0486] Autopurification System from Waters: 2767 sample Manager, 2489 UV/Visible

[0487] Detector, 2545 Quaternary Gradient Module.

[0488] Column: Daicel CHIRALPAK® IE, 5 μm, 1.0 cm×25 cm

[0489] Mobile phase: Hept/EtOH 95/05

[0490] Flow rate: 10 ml/min

[0491] Detection: UV 265 nm

[0492] Sample concentration: 50 mg/mL in DCM

[0493] Injection: 90 μl-180 μl

Results (Analytical Method/Preparative Method):

[0494]

TABLE-US-00013 First eluting enantiomer Second eluting enantiomer Retention time (min) Retention time (min) ~ 1.39 / ~ 9.16 ~ 0.70 / ~ 12.76 Quantity (mg) return Quantity (mg) return fraction solution fraction solution Chemical purity (area % Chemical purity (area % at 220 nm) 99 at 220 nm) 99 Enantiomeric excess (%) > 99 Enantiomeric excess (%) > 99

[0495] The compound with the elution time of 1.39 minute is (2S)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide, corresponding to compound F-12.

[0496] The compound with the elution time of 0.70 minutes is (2R)-2-benzyl-4,4,4-trifluoro-N-(8-fluoro-3-quinolyl)-2-methyl-butanamide, corresponding to compound F-11.

Example 8: Preparation of (R)-2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pentanamide

Step 1: Preparation of methyl 2-methyl-3-phenyl-propanoate

[0497] ##STR00053##

[0498] A solution of methyl-3-phenylpropionate (5.0 g, 30 mmol) in tetrahydrofuran (15 mL) was added slowly to lithium diisopropylamide (prepared from n-butyl lithium [2.5 M in hexanes, 14 mL, 36 mmol] and diisopropylamine [5.2 mL, 37 mmol] in tetrahydrofuran [15 mL]) at −78° C. The reaction was aged for 2 h at −78° C., iodomethane (2.8 mL, 45 mmol) was added and the resulting solution was gradually warmed to 0° C. over 3 h. Saturated, aq. NH.sub.4Cl solution was then added and the mixture was extracted with tertbutyl methyl ether. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford methyl 2-methyl-3-phenyl-propanoate as colourless liquid.

[0499] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.98-7.29 (m, 5H), 3.56 (s, 3H), 2.96 (dd, 1H), 2.53-2.73 (m, 2H), 1.08 (d, 3H).

Step 2: Preparation of methyl 2-benzyl-2,4-dimethyl-pent-4-enoate

[0500] ##STR00054##

[0501] A solution of methyl 2-methyl-3-phenyl-propanoate (1.40 g, 7.86 mmol) in tetrahydrofuran (4 mL) was added slowly to lithium diisopropylamide (prepared from n-butyl lithium [2.5 M in hexanes, 3.8 mL, 9.4 mmol] and diisopropylamine [1.38 mL, 9.8 mmol] in tetrahydrofuran [4 mL]) at −78° C. The reaction was aged for 2 h at −78° C., 3-bromo-2-methylpropene (1.22 mL, 11.8 mmol) was added and the resulting solution was gradually warmed to 0° C. over 3 h. Saturated, aq. NH.sub.4Cl solution was then added and the mixture was extracted with tertbutyl methyl ether. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford methyl 2-benzyl-2,4-dimethyl-pent-4-enoate as colourless liquid.

[0502] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.98-7.43 (m, 5H), 4.87 (s, 1H), 4.72 (s, 1H), 3.68 (s, 2H), 3.14 (d, 1H), 2.69 (t, 2H), 2.18 (d, 1H), 1.71 (s, 3H), 1.12 (s, 3H).

Step 3: Preparation of 2-benzyl-2,4-dimethyl-pent-4-enoic Acid

[0503] ##STR00055##

[0504] A solution of methyl 2-benzyl-2,4-dimethyl-pent-4-enoate (1.68 g, 6.51 mmol) in 1,4-dioxane (13 mL)/ethanol (13 mL) was treated with solid NaOH (1.3 g, 32.5 mmol), the resulting mixture was warmed to 90° C. and aged at this temperature for 2 h. All volatiles were then removed in vacuo and the residue was taken up in a mixture of water and dichloromethane. The layers were separated, the aqueous layer was acidified with HCl (4 M) to pH 2 and extracted with dichloromethane. This organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo to afford 2-benzyl-2,4-dimethyl-pent-4-enoic acid as a low melting, white solid.

[0505] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.12-7.39 (m, 5H), 4.90 (s, 1H), 4.77 (s, 1H), 3.15 (d, 1H), 2.71 (d, 2H), 2.21 (d, 1H), 1.77 (s, 3H), 1.11 ppm (s, 3H).

Step 4: Preparation of (R)-2-benzyl-2,4-dimethyl-pent-4-enoic Acid

[0506] ##STR00056##

[0507] To a solution of 2-benzyl-2,4-dimethyl-pent-4-enoic acid (1 g, 4.1 mmol) in ethanol (10 mL) was added (S)-(−)-1-(2-naphthyl)ethylamine (99% ee, 0.36 g, 2.1 mmol) in ethanol (20 mL) at RT. The resulting suspension was warmed to 60° C. and stirred at this temperature for 3 h. After cooling to RT, the precipitate was collected by suction filtration, rinsed with several portions of ethanol and dried in vacuo to afford the ammonium salt as white solid.

[0508] The salt obtained above was taken up in aqueous NaOH (2 N) and the solution washed with tertbutyl methyl ether. The aqueous layer was acidified with aqueous HCl (4 M) to pH 2 and extracted several times with tertbutyl methyl ether. The organic layer was dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo to afford (R)-2-benzyl-2,4-dimethyl-pent-4-enoic acid (e.r.=93:7 {retention time minor enantiomer: 2.91 min, retention time major enantiomer: 3.51 min. Daicel SFC CHIRALPAK® IG, CO.sub.2/MeOH}) as white solid.

Step 5: Preparation of (2R)-2-benzyl-2,4-dimethyl-pentanoic Acid

[0509] ##STR00057##

[0510] A solution of (R)-2-benzyl-2,4-dimethyl-pent-4-enoic acid (3.45 g, 15.8 mmol) in EtOH (70 mL) was treated with Pd/C (10%-Pd, 1.0 g) and stirred was stirred for 2 h under an atmosphere of H.sub.2 at ambient temperature. The reaction mixture was then filtrated through celite, the filter cake was rinsed with EtOAc and the filtrate was concentrated in vacuo to afford the title compound as colourless gum.

[0511] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.07-7.37 (m, 5H), 3.09 (d, 1H), 2.67 (d, 1H), 1.71-1.94 (m, 2H), 1.38-1.55 (m, 1H), 1.13 (s, 3H), 0.95 ppm (dd, 6H).

Step 6: Preparation of ((2R)-2-benzyl-N-(8-fluoro-4-methyl-3-quinolyl)-2,4-dimethyl-pentanamide

[0512] ##STR00058##

[0513] To a solution of (2R)-2-benzyl-2,4-dimethyl-pentanoic acid (0.50 g, 2.27 mmol) in dichloromethane (7 mL) and N,N-dimethyl formamide (2 drops) was slowly added oxalyl chloride (0.35 g, 2.73 mmol) at ambient temperature. The resulting colourless solution was stirred until gas evolution ceased (ca. 45 min). All volatiles were then removed in vacuo at 50° C. to afford crude (R)-2-benzyl-2,4-dimethyl-pentanoyl chloride as pale oil which was used as such.

[0514] The oil obtained above was taken up in dichloromethane (3 mL) and slowly added to a solution of 8-fluoro-4-methyl-quinolin-3-amine (0.44 g, 2.5 mmol) and N-methyl imidazole (0.56 g, 6.8 mmol) in dichloromethane (4 mL) at ambient temperature. The resulting solution was stirred for 2 h at ambient temperature. Additional dichloromethane was then added and the solution was washed with water, brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The brown residue was purified by medium pressure chromatography (silica gel, cyclohexane/ethyl acetate) to afford the title compound as yellow solid, m.p. 134-136° C.

[0515] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.75 (s, 1H), 7.68 (d, 1H), 7.46 (td, 1H), 7.06-7.40 (m, 7H), 3.22 (d, 1H), 2.61 (d, 1H), 2.24 (s, 3H), 2.13 (dd, 1H), 1.79-1.96 (m, 1H), 1.49 (dd, 1H), 1.41 (s, 3H), 1.02 ppm (dd, 6H).

[0516] [α].sup.D: −103° (CHCl.sub.3, c=1.00), (e.r. 93:7 {retention time minor enantiomer: 4.28 min, retention time major enantiomer: 3.10 min Daicel SFC CHIRALPAK® IF, CO.sub.2/EtOH})

Example 9: Preparation of (R)-2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-2,4-dimethyl-pentanamide

[0517] ##STR00059##

[0518] To a solution of (2R)-2-benzyl-2,4-dimethyl-pentanoic acid (4.55 g, 20.7 mmol) in dichloromethane (100 mL) and N,N-dimethyl formamide (3 drops) was slowly added oxalyl chloride (3.15 g, 24.8 mmol) at ambient temperature. The resulting colourless solution was stirred until gas evolution ceased (ca. 60 min). All volatiles were then removed in vacuo at 50° C. to afford crude (R)-2-benzyl-2,4-dimethyl-pentanoyl chloride as pale oil which was used as such.

[0519] The oil obtained above was taken up in dichloromethane (40 mL) and slowly added to a solution of 8-fluoro-2-methyl-quinolin-3-amine (4.0 g, 22.7 mmol) and N-methyl imidazole (5.14 g, 61.9 mmol) in dichloromethane (100 mL) at ambient temperature. The resulting solution was stirred for 6 h at ambient temperature. Additional dichloromethane was then added and the solution was washed with water, brine, dried over Na.sub.2SO.sub.4, filtrated and concentrated in vacuo. The brown residue was purified by medium pressure chromatography (silica gel, cyclohexane/ethyl acetate) to afford the title compound as white solid (e.r.=89:11 {retention time minor enantiomer: 3.29 min, retention time major enantiomer: 1.74 min, Daicel SFC CHIRALPAK® ID, CO.sub.2/iPrOH}).

[0520] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.93 (d, 1H), 7.60 (d, 1H), 7.43 (td, 1H), 7.29-7.35 (m, 1H), 7.18-7.25 (m, 3H), 7.03-7.17 (m, 3H), 3.19 (d, 1H), 2.64 (d, 1H), 2.29 (s, 3H), 2.14 (dd, 1H), 1.79-1.93 (m, 1H), 1.52 (dd, 1H), 1.39 (s, 3H), 1.04 (d, 3H), 0.96 ppm (d, 3H).

[0521] .sup.19F NMR (377 MHz, CDCl.sub.3) δ −127.06 ppm (s, 1F).

TABLE-US-00014 TABLE E Physical data of compounds of formula X inc. compounds of formula I RT [M + H] MP Entry IUPAC name STRUCTURE (min) (measured) Method ° C. E-1 2-benzyl-2-fluoro-N- 8-fluoro-3-quinolyl)- 4-methyl-pentanamide [00060] 1.12 370 G E-2 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 2-methyl-pent-4- ynamide [00061] 1.07 361 G E-3 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 2-methyl-pent-4- ynamide [00062] 1.08 397 G 61-65 E-4 2-benzyl-4-chloro- N-(8-fluoro-2-methyl- 3-quinolyl)pent-4- enamide [00063] 1.08 383 G 96-99 E-5 2-benzyl-4-chloro-N- (8-fluoro-4-methyl- 3-quinolyl)pent-4- enamide [00064] 1.04 383 G 53-58 E-6 2-benzyl-4-chloro-N- (8-fluoro-3-quinolyl)- pent-4-enamide [00065] 1.08 369 G 166-168 E-7 2-[(3-fluorophenyl)- methyl]-N-(8-fluoro- 3-quinolyl)-2,4- dimethyl-pentanamide [00066] 1.17 384 G E-8 4,4,4-trifluoro-N-(8- fluoro-2-methyl-3- quinolyl)-2-[(3- fluorophenyl)methyl]- 2-methyl-butanamide [00067] 1.08 423 G E-9 2-benzyl-N-(8-chloro- 3-quinolyl)-2,4- dimethyl-pentanamide [00068] 1.21 381 G 163-165 E-10 N-(8-fluoro-2-methyl- 3-quinolyl)-2-[(3- fluorophenyl)methyl]- 2,4-dimethyl-pentan- amide [00069] 1.18 398 G 93-95 E-11 2-[(3-fluorophenyl)- methyl]-N-(8-fluoro- 3-quinolyl)-2,4- dimethyl-pent-4- enamide [00070] 1.14 381 G 125-127 E-12 N-(8-fluoro-2-methyl- 3-quinolyl)-2-[(3- fluorophenyl)methyl]- 2,4-dimethyl-pent-4- enamide [00071] 1.15 396 G 124-126 E-13 2-benzyl-N-(8-chloro- 2-methyl-3-quinolyl)- 2,4-dimethyl-pentan- amide [00072] 1.26 396 G 99-100 E-14 2-benzyl-N-(8-chloro- 4-methyl-3-quinolyl)- 2,4-dimethyl-pentan- amide [00073] 1.18 395 G 124-126 E-15 2-benzyl-N-(8-chloro- 4-methyl-3-quinolyl)- 4,4,4-trifluoro-2- methyl-butanamide [00074] 1.10 421 G 73-75 E-16 4,4,4-trifluoro-N-(8- fluoro-2-methyl-3- quinolyl)-2-[(4- fluorophenyl)methyl]- 2-methyl-butanamide [00075] 1.09 424 G E-17 2-benzyl-N-(8-chloro- 2-methyl-3-quinolyl)- 4,4,4-trifluoro-2- methyl-butanamide [00076] 1.15 421 G 47-50 E-18 4,4,4-trifluoro-2-[(4- fluorophenyl)methyl]- N-(8-fluoro-3- quinolyl)-2-methyl- butanamide [00077] 1.08 409 G E-19 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 4-methyl-pentanamide [00078] 1.07 365 G E-20 2-benzyl-4-chloro-N- (8-fluoro-4-methyl-3- quinolyl)-2-methyl- pent-4-enamide [00079] 1.08 397 G 124-126 E-21 2-benzyl-4-chloro-N- (8-fluoro-2-methyl-3- quinolyl)-2-methyl- pent-4-enamide [00080] 1.12 397 G 121-123 E-22 4,4,4-trifluoro-2-[(3- fluorophenyl)methyl]- N-(8-fluoro-3- quinolyl)-2-methyl- butanamide [00081] 1.08 410 G E-23 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- 4-(trifluoromethyl)- pent-4-enamide [00082] 1.13 418 G E-24 2-benzyl-N-(8-fluoro- 3-quinolyl)-3- (trifluoromethyl)but- 3-enamide [00083] 1.75 389 H E-25 2-benzyl-3-(1-fluoro- cyclopropyl)-N-(8- fluoro-3-quinolyl)-2- methyl-propanamide [00084] 1.07 381 G 162-164 E-26 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- pent-4-ynamide [00085] 1.02 347 G 189-191 E-27 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- hexanamide [00086] 1.20 365 G 135-137 E-28 (Z)-2-benzyl-N-(8- fluoro-3-quinolyl)-2- methyl-hex-4-enamide [00087] 1.12 363 G 128-130 E-29 2-benzyl-N-(8-fluoro- 3-quinolyl)hex-4- ynamide [00088] 1.04 347 G 218-220 E-30 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- hex-4-ynamide [00089] 1.07 361 G 136-138 E-31 N-(8-fluoro-3- quinolyl)-2-methyl- 3-phenyl-propan- amide [00090] 0.97 309 G 188-190 E-32 (E)-2-benzyl-N-(8- fluoro-3-quinolyl)- 2,4-dimethyl-hex-4- enamide [00091] 1.16 377 G E-33 2-benzyl-4,4,4- trifluoro-N-(8-fluoro- 3-quinolyl)-N- (methoxymethyl)-2- methyl-butanamide [00092] 1.11 435 G 108-110 E-34 2-benzyl-5,5-difluoro- N-(8-fluoro-3- quinolyl)-2-methyl- pentanamide [00093] 1.05 387 G E-35 2-benzyl-N-(8-fluoro- 3-quinolyl)-4-methyl- pentanamide [00094] 1.10 365 G 89-91 E-36 2-benzyl-N-(8-fluoro- 3-quinolyl)-2,4- dimethyl-hexanamide [00095] 0.90 377 G E-37 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 2-methoxy-4-methyl- pentanamide [00096] 1.21 395 G 92-94 E-38 2-benzyl-N-(8-fluoro-3- quinolyl)-2-methoxy-4- methyl-pentanamide [00097] 1.15 381 G 133-135 E-39 N-(8-fluoro-2-methyl- 3-quinolyl)-2-iso- propoxy-2-methyl-3- phenyl-propanamide [00098] 1.18 381 G E-40 N-(8-fluoro-3-quinol- yl)-2-isopropoxy-2- methyl-3-phenyl- propanamide [00099] 1.13 367 G E-41 N-(8-fluoro-2-methyl- 3-quinolyl)-2- methoxy-2-methyl-3- phenyl-propanamide [00100] 1.05 353 G E-42 2-benzyl-4,4,4- trifluoro-N-(8-fluoro- 3-quinolyl)-N,2- dimethyl-butanamide [00101] 110 405 G 137-139 E-43 N-(8-fluoro-3- quinolyl)-2-methoxy- 2-methyl-3-phenyl- propanamide [00102] 1.00 339 G 107-109 E-44 2-benzyl-4,4,4- trifluoro-N-(8-fluoro- 2-methyl-3-quinolyl)- butanamide [00103] 1.04 391 G E-45 2-benzyl-4,4,4- trifluoro-N-(8-fluoro- 4-methyl-3-quinolyl)- butanamide [00104] 1.00 391 G 165-167 E-46 2-benzyl-2-ethyl-N-(8- fluoro-3-quinolyl)-4- methyl-pent-4-enamide [00105] 1.17 377 G E-47 2-benzyl-4,4,4- trifluoro-N-(8-fluoro- 2-methyl-3-quinolyl)- 2-methyl-butanamide [00106] 1.07 405 G 130-132 E-48 2-benzyl-N-(8- fluoro-3-quinolyl)- 2,4-dimethyl-pent- 3-enamide [00107] 1.14 363 G 167-169 E-49 2-benzyl-4,4,4- trifluoro-N-(5-fluoro- 3-quinolyl)-2-methyl- butanamide [00108] 1.10 392 G 140-142 E-50 2-benzyl-4,4,4- trifluoro-N-(8-fluoro- 4-methyl-3-quinolyl)- 2-methyl-butanamide [00109] 1.05 406 G 106-109 E-51 2-benzyl-N-(8-chloro- 3-quinolyl)-4,4,4- trifluoro-2-methyl- butanamide [00110] 1.13 408 G 104-106 E-52 2-benzyl-4,4,4- trifluoro-N-(7-fluoro- 3-quinolyl)-2-methyl- butanamide [00111] 1.09 392 G 180-182 E-53 2-benzyl-4-chloro-N- (8-fluoro-3-quinolyl)- 2-methyl-pent-4- enamide [00112] 1.09 383 G 148-150 E-54 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- 4-methylene-hexan- amide [00113] 1.17 377 G 118-120 E-55 2-benzyl-4,4-difluoro- N-(8-fluoro-3-quinol- yl)-2-methyl-butan- amide [00114] 1.03 373 G E-56 2-benzyl-4-chloro- 4,4-difluoro-N-(8- fluoro-3-quinolyl)-2- methyl-butanamide [00115] 1.10 408 G E-57 2-benzyl-4,4-difluoro- N-(8-fluoro-3-quinol- yl)-2-methyl-but-3- enamide [00116] 1.08 371 G E-58 2-benzyl-4-chloro-4,4- difluoro-N-(8-fluoro- 3-quinolyl)butanamide [00117] 1.06 395 G 65-70 E-59 2-benzyl-4,4,4-tri- fluoro-2-methyl-N-(8- methyl-3-quinolyl)- butanamide [00118] 1.14 387 G 123-125 E-60 2-benzyl-N-(7,8- difluoro-3-quinolyl)- 4,4,4-trifluoro-2- methyl-butanamide [00119] 1.12 409 G 183-186 E-61 2-benzyl-N-(8- fluoro-3-quinolyl)-N- methoxy-2,4-dimethyl- pentanamide [00120] 1.25 396 G E-62 2-benzyl-N-(6- methoxy-3-quinolyl)- 2,4-dimethyl-pent-4- enamide [00121] 1.08 376 G E-63 2-benzyl-N-(8- bromo-3-quinolyl)- 2,4-dimethyl-pent- 4-enamide [00122] 1.20 425 G 165-169 E-64 2-benzyl-2,4-dimethyl- N-(3-quinolyl)pent-4- enamide [00123] 1.09 346 G E-65 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 2,4-dimethyl-pent-4- enamide [00124] 1.11 378 G 105-109 E-66 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 2,4-dimethyl-pent-4- enamide [00125] 1.16 378 G E-67 N-(8-fluoro-3-quinol- yl)-N-isobutoxy-2,2- dimethyl-3-phenyl- propanamide [00126] 1.28 395 G E-68 2-benzyl-4,4-difluoro- N-(8-fluoro-3-quinol- yl)-2-methyl-pentan- amide [00127] 1.06 387 G 156-158 E-69 N-(8-fluoro-3-quinol- yl)-2,2-dimethyl-3- phenyl-propanamide [00128] 1.04 323 G E-70 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- 3-(1-methylcyclo- propyl)propanamide [00129] 1.17 377 G 149-151 E-71 2-benzyl-4-fluoro-N- (8-fluoro-3-quinolyl)- 2-methyl-pent-4- enamide [00130] 1.06 367 G 132-134 E-72 2-benzyl-3-(2,2- difluorocyclopropyl)- N-(8-fluoro-3-quinol- yl)-2-methyl-propan- amide [00131] 1.10 399 G E-73 2-benzyl-3-(2,2- difluorocyclopropyl)- N-(8-fluoro-3-quinol- yl)-2-methyl-propan- amide [00132] 1.09 400 G E-74 2-benzyl-N-(8- fluoro-3-quinolyl)- 2,4-dimethyl-pent- 4-enamide [00133] 1.13 363 G 147-149 E-75 2-benzyl-3-(2,2- dichlorocyclopropyl)- N-(8-fluoro-3-quinol- yl)-2-methyl-propan- amide [00134] 1.17 431 G E-76 2-benzyl-3-cyclo- propyl-N-(8-fluoro-3- quinolyl)-2-methyl- propanamide [00135] 1.12 363 G 157-159 E-77 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- pentanamide [00136] 1.06 387 G 156-158 E-78 2-benzyl-N-(8-fluoro- 3-quinolyl)-2-methyl- pent-4-enamide [00137] 1.08 349 G 146-149 E-79 2-benzyl-4,4,4-tri- fluoro-N-(3-quinol- yl)butanamide [00138] 1.00 359 G E-80 2-benzyl-4,4,4- trifluoro-N-(8-fluoro- 3-quinolyl)-2-methyl- butanamide [00139] 1.08 391 G E-81 2-benzyl-4,4,4-tri- fluoro-2-methyl-N-(3- quinolyl)butanamide [00140] 1.03 373 G E-82 2-benzyl-4,4,4-tri- fluoro-N-(8-fluoro-3- quinolyl)butanamide [00141] 1.03 377 G 161-164 E-83 2-benzyl-2-cyano-N- (8-fluoro-3-quinolyl)- 4-methyl-pentanamide [00142] 1.14 376 G E-84 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 2,4-dimethyl-pentan- amide [00143] 0.88 379 G 73-79 E-85 2-benzyl-2,4-dimethyl- N-(3-quinolyl)-pentan- amide [00144] 0.88 347 G 147-148 E-86 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 2,4-dimethyl-pentan- amide [00145] 0.95 379 G E-87 2-benzyl-N-(8-fluoro- 3-quinolyl)-2,4-di- methyl-pentanamide [00146] 1.15 365 G 140-142 E-88 2-benzyl-N-(8-fluoro- 3-quinolyl)-3,3-di- methyl-butanamide [00147] 0.98 351 G 212-215 E-89 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 3-(1-methylcyclo- propyl)propanamide [00148] 1.12 377 G 162-163 E-90 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 3-(1-methylcyclo- propyl)propanamide [00149] 1.07 377 G 144-146 E-91 2-benzyl-N-(8-fluoro- 3-quinolyl)-3-(1- methylcyclopropyl)- propanamide [00150] 1.12 363 G 135-136 E-92 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 4-methyl-pent-4- enamide [00151] 1.08 363 G 97-99 E-93 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 4-methyl-pent-4- enamide [00152] 1.05 363 G 116-118 E-94 2-benzyl-N-(8-fluoro- 3-quinolyl)-4-methyl- pent-4-enamide [00153] 1.08 349 G 170-172 E-95 [00154] 0.94 347 G E-96 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 4,4-dimethyl-pentan- amide [00155] 1.15 379 G 135-136 E-97 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 4,4-dimethyl-pentan- amide [00156] 1.15 379 G E-98 2-benzyl-N-(8-fluoro- 3-quinolyl)-4,4-di- methyl-pentanamide [00157] 1.15 365 G E-99 2-benzyl-N-(8-fluoro- 2-methyl-3-quinolyl)- 2-methyl-3-(1-methyl- cyclopropyl)propan- amide [00158] 1.19 391 151-152 E-100 2-benzyl-N-(8-fluoro- 4-methyl-3-quinolyl)- 2-methyl-3-(1-methyl- cyclopropyl)propan- amide [00159] 1.13 391 163-164

TABLE-US-00015 TABLE F Physical data of compounds of formula (I) as individual enantiomers RT MP Entry IUPAC name STRUCTURE [α] D.sub.20 (min) [M + H] Method ° C. F-1                           F-2 (2S)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-2,4- dimethyl-pent- 4-enamide                 (2R)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-2,4- dimethyl-pent- 4-enamide [00160]   [00161]  3.55                            2.44 378                           378 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO2 B: iPr isocratic: 15% B in 15 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 5 ml/min MeOH Detection: UV 254 nm Sample concentration: 54 mg/mL in MeOH Injection: 200-400 μl F-3                           F-4 (2S)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-2,4- dimethyl- pentanamide                 (2R)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-2,4- dimethyl- pentanamide [00162]   [00163]  4.23                            3.13 Column: Daicel CHIRALPAK ® IF, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO2 B: EtOH isocratic: 30% B in 30 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 3 ml/min MeOH Detection: UV 235 nm Sample concentration: 47 mg/mL in MeOH Injection: 200-400 μl F-5                           F-6 (2S)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-2,4- dimethyl-pent- 4-enamide                 (2R)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-2,4- dimethyl-pent- 4-enamide [00164]   [00165] 10.99                            7.67 377                           377 Column: Daicel CHIRALPAK ® ID, 5 μm, 1.0 cm x 25 cm Mobile phase: Heptane/EtOAc 70/30 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 15 mg/mL in EE, filtered Injection: 300 μl F-7                           F-8 (2S)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-2,4- dimethyl- pentanamide                 (2R)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-2,4- dimethyl- pentanamide [00166]   [00167]  7.02                            3.99 379                           379 Column: Daicel CHIRALPAK ® ID, 5 μm, 1.0 cm x 25 cm Mobile phase: Hept/iPr 80/20 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 93 mg/mL in DCM Injection: 50-80 μl F-9                         F- 10 (2R)-2-benzyl- N-(8-fluoro-3- quinolyl)-2- methyl-3-(1- methylcyclo- propyl) propanamide             (2S)-2-benzyl- N-(8-fluoro-3- quinolyl)-2- methyl-3-(1- methylcyclo- propyl) propanamide [00168]   [00169]  2.68                          4.72 377                         377 Column:. Daicel CHIRALPAK ® IA, 5 μm, 1.0 cm x 25 cm Mobile phase: TBME/EtOH 98/02 Flow rate: 10 ml/min Detection: UV 220 nm Sample concentration: 42 mg/mL in DCM Injection: 120-240 μl 62- 64                       58- 60 F- 11                       F- 12 (2R)-2-benzyl- 4,4,4-trifluoro- N-(8-fluoro-2- methyl-3- quinolyl)-2- methyl- butanamide             (2S)-2-benzyl- 4,4,4-trifluoro- N-(8-fluoro-2- methyl-3- quinolyl)-2- methyl- butanamide [00170]   [00171] 12.76                          9.16 405                         405 Column: Daicel CHIRALPAK ® IE, 5 μm, 1.0 cm x 25 cm Mobile phase: Hept/EtOH 95/05 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 142 mg/mL in DCM Injection: 35 μl-110 μl 137- 139                       135- 136 F- 13                       F- 14 (2R)-2-benzyl- 4,4,4-trifluoro- N-(8-fluoro-4- methyl-3- quinolyl)-2- methyl- butanamide             (2S)-2-benzyl- 4,4,4-trifluoro- N-(8-fluoro-4- methyl-3- quinolyl)-2- methyl- butanamide [00172]   [00173] 14.12                          5.67 405                         405 Column: Daicel CHIRALPAK ® IF, 5 μm, 1.0 cm x 25 cm Mobile phase: Hept/EtOH 90/10 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 250 mg/mL in DCM Injection: 100 μl 71- 73                       74- 76 F- 15                       F- 16 (2S)-2-benzyl- N-(7,8-difluoro- 3-quinolyl)- 4,4,4-trifluoro- 2-methyl- butanamide               (2R)-2-benzyl- N-(7,8-difluoro- 3-quinolyl)- 4,4,4-trifluoro- 2-methyl- butanamide [00174]   [00175] −236                         +241  4.40                          2.74 409                         409 Column: Daicel CHIRALPAK ® IA, 5 μm, 1.0 cm x 25 cm Mobile phase: TBME/EtOH 95/05 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 37 mg/mL in EE Injection: 130 μl F- 17                       F- 18 (2S)-2-benzyl- 4,4,4-trifluoro- 2-methyl-N-(8- methyl-3- quinolyl) butanamide               (2R)-2-benzyl- 4,4,4-trifluoro- 2-methyl-N-(8- methyl-3- quinolyl) butanamide [00176]   [00177] −245                         +267  9.81                          6.52 387                         387 Column: Daicel CHIRALPAK ® IB, 5 μm, 1.0 cm x 25 cm Mobile phase: Hept/iPr 95/05 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 30 mg/mL in EE, filtered!! Injection: 160-200 μl F- 19                     F- 20 (2R)-2-benzyl- N-(8-fluoro-3- quinolyl)-2,4- dimethyl- pentanamide               (2S)-2-benzyl- N-(8-fluoro-3- quinolyl)-2,4- dimethyl- pentanamide [00178]   [00179] 12.13                        4.45 365                       365 Column: Daicel CHIRALPAK ® IB, 5 μm, 1.0 cm x 25 cm Mobile phase: Hept/iPr 90/10 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 20 mg/mL in ACN filtered Injection: 500 μl F- 21                       F- 22 (2S)-2-benzyl- N-(8-fluoro-3- quinolyl)-2,4- dimethyl-pent- 4-enamide                 (2R)-2-benzyl- N-(8-fluoro-3- quinolyl)-2,4- dimethyl-pent- 4-enamide [00180]   [00181]  5.01                          3.18 363                         363 Column: Daicel CHIRALPAK ® IB, 5 μm, 1.0 cm x 25 cm Mobile phase: Hept/EtOH 90/10 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 10 mg/mL in MeOH/DCM (1/1) Injection: 250 μl 132- 135                       133- 135 F- 23                       F- 24 (2S)-2-benzyl- 4,4,4-trifluoro- N-(8-fluoro-3- quinolyl)-2- methyl- butanamide               (2R)-2-benzyl- 4,4,4-trifluoro- N-(8-fluoro-3- quinolyl)-2- methyl- butanamide [00182]   [00183]  5.99                          3.71 391                         391 Column: Daicel CHIRALPAK ® IB, 5 μm, 1.0 cm x 25 cm Mobile phase: Hept/EtOH 90/10 Flow rate: 10 ml/min Detection: UV 265 nm Sample concentration: 10 mg/mL in MeOH/DCM (1/1) Injection: 250 μl F- 25                             F- 26 (2R)-2-benzyl- 4-chloro-N-(8- fluoro-2- methyl-3- quinolyl)pent- 4-enamide                     (2S)-2-benzyl- 4-chloro-N-(8- fluoro-2- methyl-3- quinolyl)pent- 4-enamide [00184]   [00185]  3.10                                4.32 383                               383 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO2 B: iPr isocratic: 15% B in 20 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 4 ml/min EtOAc Detection: UV 235 nm Sample concentration: 19 mg/mL in MeOH Injection: 200-500 μl F- 27                             F- 28 (2R)-2-benzyl- 4-chloro-N-(8- fluoro-4- methyl-3- quinolyl)pent- 4-enamide                     (2S)-2-benzyl- 4-chloro-N-(8- fluoro-4- methyl-3- quinolyl)pent- 4-enamide [00186]   [00187]  1.16                                2.90 383                               383 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO2 B: iPr isocratic: 35% B in 13 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 1 ml/min EtOAc Detection: UV 235 nm Sample concentration: 17 mg/mL in MeOH/EtOAc Injection: 200-600 μl F- 29                             F- 30 (2S)-N-(8- fluoro- 2-methyl-3- quinolyl)-2- [(3- fluorophenyl) methyl]-2,4- dimethyl- pentanamide               (2R)-N-(8- fluoro- 2-methyl-3- quinolyl)-2- [(3- fluorophenyl) methyl]-2,4- dimethyl- pentanamide [00188]   [00189] 10.8                                6.0 397                               397 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: iPr isocratic: 20% B in 15 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 3 ml/min EtOAc Detection: UV 254 nm Sample concentration: 53 mg/mL in MeOH/EtOAc (1/1) Injection: 200-600 μl F- 31                             F- 32 (2S)-4,4,4- trifluoro-N-(8- fluoro-2- methyl-3- quinolyl)-2- [(3- fluorophenyl) methyl]-2- methyl- butanamide             (2R)-4,4,4- trifluoro-N-(8- fluoro-2- methyl-3- quinolyl)-2- [(3- fluorophenyl) methyl]-2- methyl- butanamide [00190]   [00191] 5.7                                8.80 423                               423 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® IG, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: iPr isocratic: 15% B in 15 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 3 ml/min EtOAc Detection: UV 254 nm Sample concentration: 60 mg/mL in MeOH/EtOAc (1/1) Injection: 200-300 μl F- 33                             F- 34 (2S)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-4,4- dimethyl- pentanamide                     (2R)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-4,4- dimethyl- pentanamide [00192]   [00193] 8.0                                4.05 379                               379 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: iPr isocratic: 25% B in 15 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 3 ml/min EtOAc Detection: UV 250 nm Sample concentration: 50 mg/mL in MeOH/EtOAc (1/1) Injection: 450-700 μl F- 35                             F- 36 (2S)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-4,4- dimethyl- pentanamide                     (2R)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-4,4- dimethyl- pentanamide [00194]   [00195]  8.05                                2.80 379                               379 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: iPr isocratic: 40% B in 15 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 2 ml/min EtOAc Detection: UV 250 nm Sample concentration: 50 mg/mL in MeOH/EtOAc (1/2) Injection: 450-600 μl F- 37                             F- 38 (2S)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-3-(1- methylcyclo- propyl) propanamide                   (2R)-2-benzyl- N-(8-fluoro-2- methyl-3- quinolyl)-3-(1- methylcyclo- propyl) propanamide [00196]   [00197]  7.40                               3.0 377                               377 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: iPr isocratic: 35% B in 15 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 2 ml/min EtOAc Detection: UV 220 nm Sample concentration: 50 mg/mL in MeOH/EtOAc (1/2) Injection: 450-600 μl F- 39                             F- 40 (2S)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-3-(1- methylcyclo- propyl) propanamide                   (2R)-2-benzyl- N-(8-fluoro-4- methyl-3- quinolyl)-3-(1- methylcyclo- propyl) propanamide [00198]   [00199] 13.4                                 5.80 377                               377 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: EtOH isocratic: 25% B in 15 min Backpressure: 150 bar Flow rate: 40 ml/min GLS pump: 3 ml/min MeOH Detection: UV 220 nm Sample concentration: 50 mg/mL in MeOH/EtOAc (1/2) Injection: 450-600 μl F- 41                             F- 42 (2S)-2-benzyl- 4-chloro-N-(8- fluoro-4- methyl-3- quinolyl)-2- methyl-pent-4- enamide                   (2R)-2-benzyl- 4-chloro-N-(8- fluoro-4- methyl-3- quinolyl)-2- methyl-pent-4- enamide [00200]   [00201] 6.3                                9.05 397                               397 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: EtOH isocratic: 25% B in 10 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 1 ml/min MeOH Detection: UV 220 nm Sample concentration: 24 mg/mL in MeOH Injection: 400-500 μl F- 43                             F- 44 (2R)-2-benzyl- 4-chloro-N-(8- fluoro-2- methyl-3- quinolyl)-2- methyl-pent-4- enamide                   (2S)-2-benzyl- 4-chloro-N-(8- fluoro-2- methyl-3- quinolyl)-2- methyl-pent-4- enamide [00202]   [00203] 4.8                               3.7 397                               397 Sepiatec Prep SFC 100 Column: Daicel CHIRALPAK ® ID, 5 μm, 2.0 cm x 25 cm Mobile phase: A: CO.sub.2 B: EtOH isocratic: 15% B in 10 min Backpressure: 150 bar Flow rate: 60 ml/min GLS pump: 2 ml/min MeOH Detection: UV 220 nm Sample concentration: 24 mg/mL in MeOH Injection: 400-500 μl

BIOLOGICAL EXAMPLES

[0522] Botryotinia fuckeliana (Botrytis cinerea)/Liquid Culture (Gray Mould)

[0523] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 3-4 days after application.

[0524] The following compounds of Tables E and F gave at least 80% control of Botryotinia fuckeliana at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-22, E-23, E-24, E-25, E-26, E-27, E-28, E-29, E-30, E-31, E-32, E-33, E-34, E-35, E-36, E-37, E-38, E-39, E-40, E-41, E-42, E-43, E-44, E-45, E-46, E-47, E-48, E-49, E-50, E-51, E-52, E-53, E-54, E-55, E-56, E-57, E-58, E-59, E-60, E-61, E-63, E-64, E-65, E-66, E-68, E-69, E-70, E-71, E-72, E-73, E-74, E-75, E-76, E-77, E-78, E-79, E-80, E-81, E-82, E-83, E-84, E-85, E-86, E-87, E-88, E-89, E-90, E-91, E-92, E-93, E-94, E-95, E-96, E-97, E-98, E-99, E-100, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-9, F-10, F-11, F-12, F-13, F-14, F-15, F-16, F-17, F-18, F-19, F-20, F-21, F-22, F-23, F-24, F-25, F-26, F-27, F-28, F-29, F-30, F-31, F-32, F-33, F-34, F-35, F-36, F-37, F-38, F-39, F-40, F-41, F-42, F-43, F-44
Fusarium culmorum/Liquid Culture (Head Blight)

[0525] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 3-4 days after application.

[0526] The following compounds of Tables E and F gave at least 80% control of Fusarium culmorum at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-22, E-23, E-24, E-25, E-26, E-27, E-28, E-30, E-31, E-32, E-33, E-34, E-35, E-36, E-37, E-38, E-39, E-40, E-41, E-42, E-43, E-44, E-45, E-46, E-47, E-48, E-49, E-50, E-51, E-52, E-53, E-54, E-55, E-56, E-57, E-58, E-59, E-60, E-61, E-63, E-64, E-65, E-66, E-68, E-69, E-70, E-71, E-72, E-73, E-74, E-75, E-76, E-77, E-78, E-79, E-80, E-81, E-82, E-83, E-84, E-85, E-86, E-87, E-88, E-89, E-90, E-91, E-92, E-93, E-94, E-95, E-96, E-97, E-98, E-99, E-100, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-9, F-10, F-11, F-12, F-13, F-14, F-15, F-16, F-17, F-18, F-19, F-20, F-21, F-22, F-23, F-24, F-25, F-26, F-27, F-28, F-29, F-30, F-31, F-32, F-33, F-34, F-35, F-36, F-37, F-38, F-39, F-40, F-41, F-42, F-43, F-44
Fusarium culmorum/Wheat/Spikelet Preventative (Head Blight)

[0527] Wheat spikelets cv. Monsun are placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The spikelets are inoculated with a spore suspension of the fungus 1 day after application. The inoculated spikelets are incubated at 20° C. and 60% rh under a light regime of 72 h semi darkness followed by 12 h light/12 h darkness in a climate chamber and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check spikelets (6-8 days after application).

[0528] The following compounds of Tables E and F gave at least 80% control of Fusarium culmorum at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-2, E-5, E-8, E-10, E-19, E-20, E-21, E-25, E-28, E-32, E-35, E-37, E-38, E-39, E-40, E-41, E-43, E-44, E-45, E-47, E-48, E-50, E-51, E-53, E-55, E-56, E-57, E-58, E-59, E-60, E-63, E-64, E-66, E-68, E-69, E-71, E-74, E-77, E-78, E-80, E-81, E-82, E-83, E-84, E-86, E-87, E-88, E-89, E-90, E-91, E-92, E-96, E-97, E-99, E-100, F-1, F-2, F-4, F-6, F-7, F-8, F-9, F-11, F-12, F-13, F-14, F-19, F-20, F-21, F-23, F-24, F-25, F-26, F-30, F-31, F-32, F-34, F-35, F-36, F-37, F-38, F-40, F-41, F-42, F-43, F-44
Glomerella lagenarium (Colletotrichum lagenarium)/Liquid Culture (Anthracnose)

[0529] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is measured photometrically 3-4 days after application.

[0530] The following compounds of Tables E and F gave at least 80% control of Glomerella lagenarium at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-22, E-23, E-24, E-25, E-26, E-28, E-31, E-32, E-33, E-34, E-35, E-36, E-37, E-38, E-39, E-40, E-41, E-42, E-43, E-44, E-45, E-46, E-47, E-48, E-50, E-51, E-52, E-53, E-54, E-55, E-56, E-57, E-58, E-59, E-60, E-61, E-64, E-65, E-66, E-68, E-69, E-70, E-71, E-72, E-73, E-74, E-75, E-76, E-77, E-78, E-79, E-80, E-81, E-82, E-83, E-84, E-85, E-86, E-87, E-89, E-90, E-91, E-92, E-93, E-94, E-95, E-96, E-97, E-98, E-99, E-100, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-9, F-10, F-11, F-12, F-13, F-14, F-15, F-16, F-17, F-18, F-19, F-20, F-21, F-22, F-23, F-24, F-25, F-26, F-27, F-28, F-29, F-30, F-31, F-32, F-33, F-34, F-35, F-36, F-37, F-38, F-39, F-40, F-41, F-42, F-43, F-44
Gaeumannomyces graminis/Liquid Culture (Take-all of Cereals)

[0531] Mycelial fragments of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 4-5 days after application.

[0532] The following compounds of Tables E and F gave at least 80% control of Gaeumannomyces graminis at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-65, E-66, E-68, E-69, E-70, E-71, E-72, E-73, E-74, E-75, E-76, E-77, E-82, E-83, E-85, E-87, F-20

[0533] Monographella nivalis (Microdochium nivale)/Liquid Culture (Foot Rot Cereals)

[0534] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 4-5 days after application.

[0535] The following compounds of Tables E and F gave at least 80% control of Monographella nivalis at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-3, E-5, E-6, E-7, E-9, E-10, E-11, E-12, E-13, E-15, E-17, E-18, E-20, E-22, E-23, E-24, E-26, E-27, E-28, E-30, E-32, E-36, E-37, E-39, E-40, E-41, E-43, E-46, E-50, E-51, E-52, E-53, E-55, E-56, E-57, E-58, E-59, E-60, E-61, E-62, E-64, E-65, E-66, E-68, E-69, E-71, E-72, E-74, E-76, E-77, E-78, E-80, E-82, E-83, E-84, E-86, E-87, E-89, E-90, E-91, E-93, E-94, E-95, E-96, E-97, F-3, F-5, F-6, F-7, F-8, F-9, F-10, F-12, F-13, F-14, F-15, F-16, F-17, F-18, F-20, F-21, F-22, F-23, F-24, F-27, F-28, F-29, F-30, F-34, F-35, F-36, F-38, F-40, F-41, F-42, F-44
Mycosphaerella arachidis (Cercospora arachidicola)/Liquid Culture (Early Leaf Spot)

[0536] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 4-5 days after application.

[0537] The following compounds of Tables E and F gave at least 80% control of Mycosphaerella arachidis at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

Magnaporthe grisea (Pyricularia oryzae)/Liquid Culture (Rice Blast)

[0538] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 3-4 days after application.

[0539] The following compounds of Tables E and F gave at least 80% control of Magnaporthe grisea at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-22, E-23, E-24, E-25, E-26, E-27, E-28, E-29, E-30, E-31, E-32, E-33, E-34, E-35, E-36, E-37, E-38, E-39, E-40, E-41, E-42, E-43, E-44, E-45, E-46, E-47, E-48, E-49, E-50, E-51, E-52, E-53, E-54, E-55, E-56, E-57, E-58, E-59, E-60, E-61, E-63, E-64, E-65, E-66, E-68, E-70, E-71, E-72, E-73, E-74, E-75, E-76, E-77, E-78, E-79, E-80, E-81, E-82, E-83, E-84, E-85, E-86, E-87, E-88, E-89, E-90, E-91, E-92, E-93, E-94, E-95, E-96, E-97, E-98, E-99, E-100, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-9, F-10, F-11, F-12, F-13, F-14, F-15, F-16, F-17, F-18, F-19, F-20, F-21, F-22, F-23, F-24, F-25, F-26, F-27, F-28, F-29, F-30, F-31, F-32, F-33, F-34, F-35, F-36, F-37, F-38, F-39, F-40, F-41, F-42, F-43, F-44
Magnaporthe grisea (Pyricularia oryzae)/Rice/Leaf Disc Preventative (Rice Blast)

[0540] Rice leaf segments cv. Ballila are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segments are inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments are incubated at 22° C. and 80% rh under a light regime of 24 h darkness followed by 12 h light/12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5-7 days after application).

[0541] The following compounds gave at least 80% control of Magnaporthe grisea at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-2, E-6, E-8, E-13, E-17, E-18, E-19, E-20, E-21, E-26, E-27, E-29, E-30, E-44, E-45, E-46, E-50, E-76, E-80, E-89, E-90, E-91, E-93, E-96, E-97, E-98, E-99, E-100, F-1, F-2, F-4, F-6, F-9, F-11, F-12, F-21, F-25, F-26, F-29, F-30, F-31, F-32, F-34, F-35, F-36, F-41, F-42, F-43, F-44
Pyrenophora teres/Barley/Leaf Disc Preventative (Net Blotch)

[0542] Barley leaf segments cv. Hasso are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segmens are inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments are incubated at 20° C. and 65% rh under a light regime of 12 h light/12 h darkness in a climate cabinet and the activity of a compound is assessed as disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5-7 days after application).

[0543] The following compounds of Tables E and F gave at least 80% control of Pyrenophora teres at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

F-3, F-20

[0544] Mycosphaerella graminicola (Septoria tritici)/Liquid Culture (Septoria Blotch)

[0545] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 4-5 days after application.

[0546] The following compounds of Tables E and F gave at least 80% control of Mycosphaerella graminicola at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

E-1, E-4, E-19, E-64, E-80, E-92, E-93, F-7, F-8, F-13, F-25, F-27, F-40

[0547] Sclerotinia sclerotiorum/Liquid Culture (Cottony Rot)

[0548] Mycelia fragments of a newly grown liquid culture of the fungus are directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format) the nutrient broth containing the fungal material is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 3-4 days after application.

[0549] The following compounds of Tables E and F gave at least 80% control of Sclerotinia sclerotiorum at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

[0550] E-5, E-8, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-22, E-25, E-45, E-47, E-50, E-51, E-53, E-56, E-74, E-80, E-81, E-84, E-86, E-87, E-89, E-90, E-91, E-93, E-96, E-100, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-9, F-10, F-11, F-12, F-13, F-14, F-15, F-20, F-21, F-23, F-26, F-28, F-29, F-30, F-31, F-32, F-34, F-36, F-38, F-40, F-41, F-42, F-44

Further biolgical test examples with mixture compositions comprising (2R)-2-benzyl-N-(8-fluoro-2-methyl-3-quinolyl)-2,4-dimethyl-pentanamide (F-8)

Example B1: Pyricularia orzyae (Rice Blast)

[0551] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format) the nutrient broth containing the fungal spores was added. The test plates were incubated at 24 C and the inhibition of growth was determined photometrically after 72 hrs.

[0552] The following mixture compositions (B:A) at the reported concentration (in ppm) gave at least 80% disease control in this test:

TABLE-US-00016 Conc. (ppm) Ratio Composition (B + A) (B:A) (B:A) Pydiflumetofen + F8 0.8 + 0.2  4:1 Pydiflumetofen + F8 0.16 + 0.04  4:1 Pydiflumetofen + F8 0.032 + 0.008  4:1 Pydiflumetofen + F8 0.2 + 0.2  1:1 Pydiflumetofen + F8 0.04 + 0.04  1:1 Pydiflumetofen + F8 0.008 + 0.008  1:1 Pydiflumetofen + F8 0.2 + 0.8  1:4 Pydiflumetofen + F8 0.04 + 0.16  1:4 Pydiflumetofen + F8 0.008 + 0.032  1:4 Benzovindiflupyr + F8 0.8 + 0.2  4:1 Benzovindiflupyr + F8 0.16 + 0.04  4:1 Benzovindiflupyr + F8 0.032 + 0.008  4:1 Benzovindiflupyr + F8 0.2 + 0.2  1:1 Benzovindiflupyr + F8 0.04 + 0.04  1:1 Benzovindiflupyr + F8 0.008 + 0.008  1:1 Benzovindiflupyr + F8 0.2 + 0.8  1:4 Benzovindiflupyr + F8 0.04 + 0.16  1:4 Benzovindiflupyr + F8 0.008 + 0.032  1:4 Difenoconazole + F8   8 + 0.2 40:1 Difenoconazole + F8  1.6 + 0.04 40:1 Difenoconazole + F8  0.32 + 0.008 40:1 Difenoconazole + F8   2 + 0.2 10:1 Difenoconazole + F8  0.4 + 0.04 10:1 Difenoconazole + F8  0.08 + 0.008 10:1 Difenoconazole + F8   2 + 0.8  5:2 Difenoconazole + F8  0.4 + 0.16  5:2 Difenoconazole + F8  0.08 + 0.032  5:2 Hexaconazole + F8   8 + 0.2 40:1 Hexaconazole + F8  1.6 + 0.04 40:1 Hexaconazole + F8  0.32 + 0.008 40:1 Hexaconazole + F8   2 + 0.2 10:1 Hexaconazole + F8  0.4 + 0.04 10:1 Hexaconazole + F8  0.08 + 0.008 10:1 Hexaconazole + F8   2 + 0.8  5:2 Hexaconazole + F8  0.4 + 0.16  5:2 Hexaconazole + F8  0.08 + 0.032  5:2 Azoxystrobin + F8 0.8 + 0.2  4:1 Azoxystrobin + F8 0.16 + 0.04  4:1 Azoxystrobin + F8 0.032 + 0.008  4:1 Azoxystrobin + F8 0.2 + 0.2  1:1 Azoxystrobin + F8 0.04 + 0.04  1:1 Azoxystrobin + F8 0.008 + 0.008  1:1 Azoxystrobin + F8 0.2 + 0.8  1:4 Azoxystrobin + F8 0.04 + 0.16  1:4 Azoxystrobin + F8 0.008 + 0.032  1:4 Fludioxonil + F8   8 + 0.2 40:1 Fludioxonil + F8  1.6 + 0.04 40:1 Fludioxonil + F8  0.32 + 0.008 40:1 Fludioxonil + F8   2 + 0.2 10:1 Fludioxonil + F8  0.4 + 0.04 10:1 Fludioxonil + F8  0.08 + 0.008 10:1 Fludioxonil + F8   2 + 0.8  5:2 Fludioxonil + F8  0.4 + 0.16  5:2 Fludioxonil + F8  0.08 + 0.032  5:2 Cyprodinil + F8   8 + 0.2 40:1 Cyprodinil + F8  1.6 + 0.04 40:1 Cyprodinil + F8  0.32 + 0.008 40:1 Cyprodinil + F8   2 + 0.2 10:1 Cyprodinil + F8  0.4 + 0.04 10:1 Cyprodinil + F8  0.08 + 0.008 10:1 Cyprodinil + F8   2 + 0.8  5:2 Cyprodinil + F8  0.4 + 0.16  5:2 Cyprodinil + F8  0.08 + 0.032  5:2 Fluazinam + F8   8 + 0.2 40:1 Fluazinam + F8  1.6 + 0.04 40:1 Fluazinam + F8  0.32 + 0.008 40:1 Fluazinam + F8   2 + 0.2 10:1 Fluazinam + F8  0.4 + 0.04 10:1 Fluazinam + F8  0.08 + 0.008 10:1 Fluazinam + F8   2 + 0.8  5:2 Fluazinam + F8  0.4 + 0.16  5:2 Fluazinam + F8  0.08 + 0.032  5:2 lsopyrazam + F8   8 + 0.2 40:1 lsopyrazam + F8  1.6 + 0.04 40:1 lsopyrazam + F8  0.32 + 0.008 40:1 lsopyrazam + F8   2 + 0.2 10:1 lsopyrazam + F8  0.4 + 0.04 10:1 lsopyrazam + F8  0.08 + 0.008 10:1 lsopyrazam + F8   2 + 0.8  5:2 lsopyrazam + F8  0.4 + 0.16  5:2 lsopyrazam + F8  0.08 + 0.032  5:2 Propiconazole + F8   8 + 0.2 40:1 Propiconazole + F8  1.6 + 0.04 40:1 Propiconazole + F8  0.32 + 0.008 40:1 Propiconazole + F8   2 + 0.2 10:1 Propiconazole + F8  0.4 + 0.04 10:1 Propiconazole + F8  0.08 + 0.008 10:1 Propiconazole + F8   2 + 0.8  5:2 Propiconazole + F8  0.4 + 0.16  5:2 Propiconazole + F8  0.08 + 0.032  5:2 Aminopyrifen + F8   8 + 0.2 40:1 Aminopyrifen + F8  1.6 + 0.04 40:1 Aminopyrifen + F8  0.32 + 0.008 40:1 Aminopyrifen + F8   2 + 0.2 10:1 Aminopyrifen + F8  0.4 + 0.04 10:1 Aminopyrifen + F8  0.08 + 0.008 10:1 Aminopyrifen + F8   2 + 0.8  5:2 Aminopyrifen + F8  0.4 + 0.16  5:2 Aminopyrifen + F8  0.08 + 0.032  5:2 Pyroquilon + F8  30 + 0.2 150:1  Pyroquilon + F8    6 + 0.04 150:1  Pyroquilon + F8   1.2 + 0.008 150:1  Pyroquilon + F8   8 + 0.2 40:1 Pyroquilon + F8  1.6 + 0.04 40:1 Pyroquilon + F8  0.32 + 0.008 40:1 Pyroquilon + F8   2 + 0.2 10:1 Pyroquilon + F8  0.4 + 0.04 10:1 Pyroquilon + F8  0.08 + 0.008 10:1 Tricyclazole + F8  30 + 0.2 150:1  Tricyclazole + F8    6 + 0.04 150:1  Tricyclazole + F8  1.2 + 0.008 150:1  Tricyclazole + F8   8 + 0.2 40:1 Tricyclazole + F8  1.6 + 0.04 40:1 Tricyclazole + F8  0.32 + 0.008 40:1 Tricyclazole + F8   2 + 0.2 10:1 Tricyclazole + F8  0.4 + 0.04 10:1 Tricyclazole + F8  0.08 + 0.008 10:1 Chlorothalonil + F8  30 + 0.2 150:1  Chlorothalonil + F8    6 + 0.04 150:1  Chlorothalonil + F8  1.2 + 0.008 150:1  Chlorothalonil + F8   8 + 0.2 40:1 Chlorothalonil + F8  1.6 + 0.04 40:1 Chlorothalonil + F8  0.32 + 0.008 40:1 Chlorothalonil + F8   2 + 0.2 10:1 Chlorothalonil + F8  0.4 + 0.04 10:1 Chlorothalonil + F8  0.08 + 0.008 10:1

Example 1B2: Botrytis cinerea (Gray Mould)

[0553] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format) the nutrient broth containing the fungal spores was added. The test plates were incubated at 24 C and the inhibition of growth was determined photometrically after 72 hrs.

[0554] The following mixture compositions (B:A) at the reported concentration (in ppm) gave at least 80% disease control in this test:

TABLE-US-00017 Conc. (ppm) Ratio Composition (B + A) (B:A) (B:A) Pydiflumetofen + F8 0.8 + 0.2  4:1 Pydiflumetofen + F8 0.2 + 0.2  1:1 Pydiflumetofen + F8 0.2 + 0.8  1:4 Pydiflumetofen + F8 0.04 + 0.16  1:4 Benzovindiflupyr + F8 0.8 + 0.2  4:1 Benzovindiflupyr + F8 0.2 + 0.2  1:1 Benzovindiflupyr + F8 0.2 + 0.8  1:4 Benzovindiflupyr + F8 0.04 + 0.16  1:4 Difenoconazole + F8   8 + 0.2 40:1 Difenoconazole + F8   2 + 0.2 10:1 Difenoconazole + F8   2 + 0.8  5:2 Difenoconazole + F8  0.4 + 0.16  5:2 Hexaconazole + F8   8 + 0.2 40:1 Hexaconazole + F8   2 + 0.2 10:1 Hexaconazole + F8   2 + 0.8  5:2 Hexaconazole + F8  0.4 + 0.16  5:2 Azoxystrobin + F8 0.8 + 0.2  4:1 Azoxystrobin + F8 0.2 + 0.2  1:1 Azoxystrobin + F8 0.2 + 0.8  1:4 Azoxystrobin + F8 0.04 + 0.16  1:4 Fludioxonil + F8   8 + 0.2 40:1 Fludioxonil + F8  1.6 + 0.04 40:1 Fludioxonil + F8  0.32 + 0.008 40:1 Fludioxonil + F8   2 + 0.2 10:1 Fludioxonil + F8  0.4 + 0.04 10:1 Fludioxonil + F8   2 + 0.8  5:2 Fludioxonil + F8  0.4 + 0.16  5:2 Cyprodinil + F8   8 + 0.2 40:1 Cyprodinil + F8  1.6 + 0.04 40:1 Cyprodinil + F8  0.32 + 0.008 40:1 Cyprodinil + F8   2 + 0.2 10:1 Cyprodinil + F8  0.4 + 0.04 10:1 Cyprodinil + F8   2 + 0.8  5:2 Cyprodinil + F8  0.4 + 0.16  5:2 Fluazinam + F8   8 + 0.2 40:1 Fluazinam + F8  1.6 + 0.04 40:1 Fluazinam + F8  0.32 + 0.008 40:1 Fluazinam + F8   2 + 0.2 10:1 Fluazinam + F8  0.4 + 0.04 10:1 Fluazinam + F8   2 + 0.8  5:2 Fluazinam + F8  0.4 + 0.16  5:2 lsopyrazam + F8   8 + 0.2 40:1 lsopyrazam + F8   2 + 0.2 10:1 lsopyrazam + F8   2 + 0.8  5:2 lsopyrazam + F8  0.4 + 0.16  5:2 Propiconazole + F8   8 + 0.2 40:1 Propiconazole + F8   2 + 0.2 10:1 Propiconazole + F8   2 + 0.8  5:2 Propiconazole + F8  0.4 + 0.16  5:2 Aminopyrifen + F8   8 + 0.2 40:1 Aminopyrifen + F8  1.6 + 0.04 40:1 Aminopyrifen + F8   2 + 0.2 10:1 Aminopyrifen + F8  0.4 + 0.04 10:1 Aminopyrifen + F8   2 + 0.8  5:2 Aminopyrifen + F8  0.4 + 0.16  5:2 Pyroquilon + F8  30 + 0.2 150:1  Pyroquilon + F8   8 + 0.2 40:1 Pyroquilon + F8   2 + 0.2 10:1 Tricyclazole + F8  30 + 0.2 150:1  Tricyclazole + F8   8 + 0.2 40:1 Tricyclazole + F8   2 + 0.2 10:1 Chlorothalonil + F8  30 + 0.2 150:1  Chlorothalonil + F8    6 + 0.04 150:1  Chlorothalonil + F8   8 + 0.2 40:1 Chlorothalonil + F8   2 + 0.2 10:1

Example 13: Glomerella Lagenarium (Syn. Colletotrichum lagenarium), Anthracnose of Cucurbits

[0555] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format) the nutrient broth containing the fungal spores was added. The test plates were incubated at 24 C and the inhibition of growth was determined photometrically after 72 hrs at 620 nm

[0556] The following mixture compositions (B:A) at the reported concentration (in ppm) gave at least 80% disease control in this test:

TABLE-US-00018 Conc. (ppm) Ratio Composition (B + A) (B:A) (B:A) Pydiflumetofen + F8 0.2 + 0.8   1:4 Benzovindiflupyr + F8 0.8 + 0.2   4:1 Benzovindiflupyr + F8 0.2 + 0.8   1:4 Difenoconazole + F8 2 + 0.8 5:2 Hexaconazole + F8 2 + 0.8 5:2 Azoxystrobin + F8 0.8 + 0.2   4:1 Azoxystrobin + F8 0.2 + 0.8   1:4 Fludioxonil + F8 8 + 0.2 40:1  Fludioxonil + F8 2 + 0.2 10:1  Fludioxonil + F8 2 + 0.8 5:2 Cyprodinil + F8 2 + 0.8 5:2 Fluazinam + F8 8 + 0.2 40:1  Fluazinam + F8 1.6 + 0.04  40:1  Fluazinam + F8 2 + 0.2 10:1  Fluazinam + F8 2 + 0.8 5:2 Fluazinam + F8 0.4 + 0.16  5:2 lsopyrazam + F8 2 + 0.8 5:2 Propiconazole + F8 2 + 0.8 5:2 Aminopyrifen + F8 8 + 0.2 40:1  Aminopyrifen + F8 2 + 0.2 10:1  Aminopyrifen + F8 2 + 0.8 5:2 Chlorothalonil + F8 30 + 0.2  150:1  Chlorothalonil + F8   6 + 0.04 150:1  Chlorothalonil + F8  8 + 0.2 40:1 

Example 1B4: Septoria tritici (Leaf Blotch)

[0557] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). A DMSO solution of the test compounds was placed into a microtiter plate (96-well format) and the nutrient broth containing the fungal spores was added to it. The test plates were incubated at 24 C and the inhibition of growth was determined photometrically after 72 hrs.

[0558] The following mixture compositions (B:A) at the reported concentration (in ppm) gave at least 80% disease control in this test:

TABLE-US-00019 Conc. (ppm) Ratio Composition (B + A) (B:A) (B:A) Pydiflumetofen + F8 0.8 + 0.2 4:1 Pydiflumetofen + F8 0.16 + 0.04 4:1 Pydiflumetofen + F8 0.032 + 0.008 4:1 Pydiflumetofen + F8 0.2 + 0.2 1:1 Pydiflumetofen + F8 0.04 + 0.04 1:1 Pydiflumetofen + F8 0.2 + 0.8 1:4 Pydiflumetofen + F8 0.04 + 0.16 1:4 Difenoconazole + F8   8 + 0.2 40:1  Difenoconazole + F8  1.6 + 0.04 40:1  Difenoconazole + F8  0.32 + 0.008 40:1  Difenoconazole + F8   2 + 0.2 10:1  Difenoconazole + F8  0.4 + 0.04 10:1  Difenoconazole + F8   2 + 0.8 5:2 Difenoconazole + F8  0.4 + 0.16 5:2 Hexaconazole + F8   8 + 0.2 40:1  Hexaconazole + F8  1.6 + 0.04 40:1  Hexaconazole + F8   2 + 0.2 10:1  Hexaconazole + F8   2 + 0.8 5:2 Azoxystrobin + F8 0.8 + 0.2 4:1 Azoxystrobin + F8 0.16 + 0.04 4:1 Azoxystrobin + F8 0.2 + 0.2 1:1 Azoxystrobin + F8 0.2 + 0.8 1:4 Fludioxonil + F8   8 + 0.2 40:1  Fludioxonil + F8   2 + 0.2 10:1  Fludioxonil + F8   2 + 0.8 5:2 Fluazinam + F8   8 + 0.2 40:1  Fluazinam + F8  1.6 + 0.04 40:1  Fluazinam + F8  0.32 + 0.008 40:1  Fluazinam + F8   2 + 0.2 10:1  Fluazinam + F8  0.4 + 0.04 10:1  Fluazinam + F8   2 + 0.8 5:2 Fluazinam + F8  0.4 + 0.16 5:2 lsopyrazam + F8   8 + 0.2 40:1  lsopyrazam + F8  1.6 + 0.04 40:1  lsopyrazam + F8   2 + 0.2 10:1  lsopyrazam + F8   2 + 0.8 5:2 Propiconazole + F8   8 + 0.2 40:1  Propiconazole + F8   2 + 0.2 10:1  Propiconazole + F8   2 + 0.8 5:2 Aminopyrifen + F8   8 + 0.2 40:1  Aminopyrifen + F8  1.6 + 0.04 40:1  Aminopyrifen + F8   2 + 0.2 10:1  Aminopyrifen + F8   2 + 0.8 5:2 Chlorothalonil + F8  30 + 0.2 150:1  Chlorothalonil + F8   6 + 0.04 150:1  Chlorothalonil + F8   8 + 0.2 40:1  Chlorothalonil + F8   2 + 0.2 10:1 

Example B5: Fusarium culmorum (Root Rot)

[0559] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). A DMSO solution of the test compounds was placed into a microtiter plate (96-well format) and the nutrient broth containing the fungal spores was added to it. The test plates were incubated at 24 C and the inhibition of growth was determined photometrically after 48 hrs.

[0560] The following mixture compositions (B:A) at the reported concentration (in ppm) gave at least 80% disease control in this test:

TABLE-US-00020 Conc. (ppm) Ratio Composition (B + A) (B:A) (B:A) Pydiflumetofen + F8 0.8 + 0.2   4:1 Pydiflumetofen + F8 0.2 + 0.2   1:1 Pydiflumetofen + F8 0.2 + 0.8   1:4 Pydiflumetofen + F8 0.04 + 0.16   1:4 Benzovindiflupyr + F8 0.8 + 0.2   4:1 Benzovindiflupyr + F8 0.2 + 0.2   1:1 Benzovindiflupyr + F8 0.2 + 0.8   1:4 Benzovindiflupyr + F8 0.04 + 0.16   1:4 Difenoconazole + F8 8 + 0.2 40:1  Difenoconazole + F8 2 + 0.2 10:1  Difenoconazole + F8 2 + 0.8 5:2 Difenoconazole + F8 0.4 + 0.16  5:2 Hexaconazole + F8 2 + 0.2 10:1  Hexaconazole + F8 2 + 0.8 5:2 Hexaconazole + F8 0.4 + 0.16  5:2 Azoxystrobin + F8 0.8 + 0.2   4:1 Azoxystrobin + F8 0.2 + 0.2   1:1 Azoxystrobin + F8 0.2 + 0.8   1:4 Azoxystrobin + F8 0.04 + 0.16   1:4 Fludioxonil + F8 8 + 0.2 40:1  Fludioxonil + F8 1.6 + 0.04  40:1  Fludioxonil + F8 2 + 0.2 10:1  Fludioxonil + F8 0.4 + 0.04  10:1  Fludioxonil + F8 2 + 0.8 5:2 Fludioxonil + F8 0.4 + 0.16  5:2 Cyprodinil + F8 8 + 0.2 40:1  Cyprodinil + F8 2 + 0.2 10:1  Cyprodinil + F8 2 + 0.8 5:2 Cyprodinil + F8 0.4 + 0.16  5:2 Fluazinam + F8 8 + 0.2 40:1  Fluazinam + F8 2 + 0.2 10:1  Fluazinam + F8 2 + 0.8 5:2 Fluazinam + F8 0.4 + 0.16  5:2 lsopyrazam + F8 8 + 0.2 40:1  lsopyrazam + F8 2 + 0.2 10:1  lsopyrazam + F8 2 + 0.8 5:2 lsopyrazam + F8 0.4 + 0.16  5:2 Propiconazole + F8 8 + 0.2 40:1  Propiconazole + F8 2 + 0.2 10:1  Propiconazole + F8 2 + 0.8 5:2 Propiconazole + F8 0.4 + 0.16  5:2 Aminopyrifen + F8 8 + 0.2 40:1  Aminopyrifen + F8 1.6 + 0.04  40:1  Aminopyrifen + F8 2 + 0.2 10:1  Aminopyrifen + F8 0.4 + 0.04  10:1  Aminopyrifen + F8 2 + 0.8 5:2 Aminopyrifen + F8 0.4 + 0.16  5:2 Pyroquilon + F8 30 + 0.2  150:1  Pyroquilon + F8 8 + 0.2 40:1  Pyroquilon + F8 2 + 0.2 10:1  Tricyclazole + F8 30 + 0.2  150:1  Tricyclazole + F8 8 + 0.2 40:1  Tricyclazole + F8 2 + 0.2 10:1  Chlorothalonil + F8 30 + 0.2  150:1  Chlorothalonil + F8 8 + 0.2 40:1  Chlorothalonil + F8 2 + 0.2 10:1 

Example 1B6: Venturia inequalis (Apple Scab)

[0561] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). A DMSO solution of the test compounds was placed into a microtiter plate (96-well format) and the nutrient broth containing the fungal spores was added to it. The test plates were incubated at 24 C and the inhibition of growth was determined photometrically after 7 days at 620 nm.

[0562] The following mixture compositions (B:A) at the reported concentration (in ppm) gave at least 80% disease control in this test:

TABLE-US-00021 Conc. (ppm) Ratio Composition (B + A) (B:A) (B:A) Pydiflumetofen + F8 0.8 + 0.2  4:1 Pydiflumetofen + F8 0.16 + 0.04  4:1 Pydiflumetofen + F8 0.032 + 0.008  4:1 Pydiflumetofen + F8 0.2 + 0.2  1:1 Pydiflumetofen + F8 0.04 + 0.04  1:1 Pydiflumetofen + F8 0.2 + 0.8  1:4 Pydiflumetofen + F8 0.04 + 0.16  1:4 Benzovindiflupyr + F8 0.8 + 0.2  4:1 Benzovindiflupyr + F8 0.16 + 0.04  4:1 Benzovindiflupyr + F8 0.2 + 0.2  1:1 Benzovindiflupyr + F8 0.2 + 0.8  1:4 Difenoconazole + F8   8 + 0.2 40:1 Difenoconazole + F8  1.6 + 0.04 40:1 Difenoconazole + F8  0.32 + 0.008 40:1 Difenoconazole + F8   2 + 0.2 10:1 Difenoconazole + F8  0.4 + 0.04 10:1 Difenoconazole + F8   2 + 0.8  5:2 Difenoconazole + F8  0.4 + 0.16  5:2 Hexaconazole + F8   8 + 0.2 40:1 Hexaconazole + F8  1.6 + 0.04 40:1 Hexaconazole + F8  0.32 + 0.008 40:1 Hexaconazole + F8   2 + 0.2 10:1 Hexaconazole + F8  0.4 + 0.04 10:1 Hexaconazole + F8   2 + 0.8  5:2 Hexaconazole + F8  0.4 + 0.16  5:2 Azoxystrobin + F8 0.8 + 0.2  4:1 Azoxystrobin + F8 0.16 + 0.04  4:1 Azoxystrobin + F8 0.2 + 0.2  1:1 Azoxystrobin + F8 0.2 + 0.8  1:4 Fludioxonil + F8   8 + 0.2 40:1 Fludioxonil + F8   2 + 0.8  5:2 Cyprodinil + F8   8 + 0.2 40:1 Cyprodinil + F8  1.6 + 0.04 40:1 Cyprodinil + F8   2 + 0.2 10:1 Cyprodinil + F8  0.4 + 0.04 10:1 Cyprodinil + F8   2 + 0.8  5:2 Cyprodinil + F8  0.4 + 0.16  5:2 Fluazinam + F8   8 + 0.2 40:1 Fluazinam + F8  1.6 + 0.04 40:1 Fluazinam + F8   2 + 0.2 10:1 Fluazinam + F8   2 + 0.8  5:2 lsopyrazam + F8   8 + 0.2 40:1 lsopyrazam + F8  1.6 + 0.04 40:1 lsopyrazam + F8   2 + 0.2 10:1 lsopyrazam + F8   2 + 0.8  5:2 Propiconazole + F8   8 + 0.2 40:1 Propiconazole + F8  1.6 + 0.04 40:1 Propiconazole + F8   2 + 0.2 10:1 Propiconazole + F8   2 + 0.8  5:2 Tricyclazole + F8  30 + 0.2 150:1  Chlorothalonil + F8  30 + 0.2 150:1  Chlorothalonil + F8   6 + 0.04 150:1  Chlorothalonil + F8  1.2 + 0.008 150:1  Chlorothalonil + F8   8 + 0.2 40:1 Chlorothalonil + F8  1.6 + 0.04 40:1 Chlorothalonil + F8   2 + 0.2 10:1 Chlorothalonil + F8  0.4 + 0.04 10:1