MICROBIOCIDAL OXADIAZOLE DERIVATIVES

Abstract

Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as fungicides.

##STR00001##

Claims

1. A compound of formula (I): ##STR00081## wherein n represents 1 or 2; A.sup.1 represents N or CR.sup.1, wherein R.sup.1 represents hydrogen, halogen, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or difluoromethoxy; A.sup.2 represents N or CR.sup.2, wherein R.sup.2 represents hydrogen, halogen, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or difluoromethoxy; A.sup.3 represents N or CR.sup.3, wherein R.sup.3 represents hydrogen or halogen; A.sup.4 represents N or CR.sup.4, wherein R.sup.4 represents hydrogen or halogen; and wherein no more than two of A.sup.1 to A.sup.4 are N; R.sup.5 represents OR.sup.6, wherein R.sup.6 represents phenyl, phenylC.sub.1-4alkyl, heteroaryl which is a 5-membered aromatic ring comprising 1, 2 or 3 heteroatoms individually selected from N, O and S, heteroaryl which is a 6-membered aromatic ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heteroarylC.sub.1-4alkyl wherein the heteroaryl moiety is 5- or 6-membered aromatic ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S and wherein when the heteroaryl moiety is pyridyl the alkyl moiety is C.sub.2-4alkyl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.1-4alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic monocyclic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, wherein for R.sup.6: phenyl, heteroaryl, C.sub.3-8cycloalkyl and heterocyclyl are optionally substituted by 1 to 4 substituents independently selected from R.sup.9, or phenyl, heteroaryl, C.sub.3-8cycloalkyl and heterocyclyl are optionally substituted by 1 or 2 substituents independently selected from R.sup.10, or phenyl, heteroaryl, C.sub.3-8cycloalkyl and heterocyclyl are optionally substituted by 1 to 3 substituents independently selected from R.sup.9 and 1 substituent selected from R.sup.10; or R.sup.5 represents NR.sup.7R.sup.8, wherein R.sup.7 represents hydrogen, C.sub.1-4alkyl, C.sub.1-4alkoxy, C.sub.1-2alkylC.sub.1-4alkoxy, C.sub.3-4alkenyl or C.sub.3-4 alkynyl; and R.sup.8 represents phenyl, phenylC.sub.1-4alkyl, heteroaryl or heteroarylC.sub.1-4alkyl wherein the heteroaryl moiety is 5- or 6-membered aromatic ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.1-4alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic monocyclic ring r comprising 1, 2 or 3 heteroatoms individually selected from N, O and S, wherein for R.sup.8: phenyl, heteroaryl, C.sub.3-8cycloalkyl, or heterocyclyl are optionally substituted by 1 to 4 substituents independently selected from R.sup.9, or phenyl, heteroaryl, C.sub.3-8cycloalkyl or heterocyclyl are optionally substituted by 1 or 2 substituents independently selected from R.sup.L0, or phenyl, heteroaryl, C.sub.3-8cycloalkyl or heterocyclyl are optionally substituted by 1 to 3 substituents independently selected from R.sup.9 and 1 substituent selected from R.sup.10; or R.sup.7 and R.sup.8 together with the nitrogen atom they share form a heteroaryl moiety which is 5-membered aromatic ring optionally comprising 1, 2 or 3 additional nitrogen atoms, or a heterocyclyl moiety which is a 5- or 6-membered non-aromatic monocyclic ring optionally comprising an additional heteroatom selected from N, O or S, wherein the heteroaryl and heterocyclyl moieties are optionally substituted by 1 to 4 substituents independently selected from R.sup.9, 1 or 2 substituents independently selected from R.sup.10, or 1 to 3 substituents independently selected from R.sup.9 and 1 substituent selected from R.sup.10; R.sup.9 is halogen, cyano, hydroxy, C.sub.1-4alkyl, C.sub.1-4alkoxy, C.sub.1-4alkoxyC.sub.1-4alkyl, haloC.sub.1-4alkyl, haloC.sub.1-4alkoxy, C.sub.1-4alkylcarbonyl, C.sub.1-4alkoxycarbonyl, C.sub.1-4alkylcarbonyloxy, NC.sub.1-4alkylamino, N,N-diC.sub.1-4alkylamino, NC.sub.1-4alkylaminocarbonyl, N,N-diC.sub.1-4alkylaminocarbonyl, NC.sub.1-4alkylaminosulfonyl, N,N-diC.sub.1-4alkylaminosulfonyl or C.sub.1-4alkylsulfanyl; R.sup.10 is phenyl optionally substituted by 1 to 3 substituents independently selected from R.sup.11, or heterocyclyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic monocyclic ring comprising 1, 2 or 3 heteroatoms individually selected from N, O and S optionally substituted by 1 to 3 substituents independently selected from R.sup.11; R.sup.11 is flouro, chloro, cyano, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy or difluoromethoxy; or a salt or an N-oxide thereof.

2. A compound according to claim 1, wherein n is 1.

3. A compound according to claim 1, wherein A.sup.1 to A.sup.4 are CH; A.sup.1 is N and A.sup.2 to A.sup.4 are CH; A.sup.1 is CF and A.sup.2 to A.sup.4 are CH; or A.sup.3 is CF and A.sup.1, A.sup.2 and A.sup.4 are CH.

4. A compound according to claim 1, wherein R.sup.6 is phenyl, phenylC.sub.1-4alkyl, C.sub.3-6cycloalkyl, C.sub.3-6cycloalkylC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.1-4alkyl wherein the heterocyclyl moiety comprises 1 or 2 heteroatoms selected from N, O or S, wherein for R.sup.6: phenyl, phenylC.sub.1-4alkyl, C.sub.3-6cycloalkyl, or heterocyclyl are optionally substituted by 1 to 4 substituents independently selected from R.sup.9, or phenyl, phenylC.sub.1-4alkyl, C.sub.3-6cycloalkyl, and heterocyclyl are optionally substituted by 1 or 2 substituents independently selected from R.sup.10, or phenyl, phenylC.sub.1-4alkyl, C.sub.3-6cycloalkyl, and 5- or 6-membered heterocyclyl are optionally substituted by 1 to 3 substituents independently selected from R.sup.9 and 1 substituent selected from R.sup.10.

5. A compound according to claim 1, wherein R.sup.6 is phenyl, phenylC.sub.1-4alkyl, C.sub.3-6cycloalkyl, C.sub.3-4cycloalkylC.sub.1-4alkyl or tetrahydropyranyl, each optionally substituted by 1 to 3 substituents independently selected from R.sup.9, wherein R.sup.9 is selected from halogen, cyano, hydroxy, C.sub.1-4alkyl, C.sub.1-4alkoxy, haloC.sub.1-4alkyl and haloC.sub.1-4alkoxy.

6. A compound according to claim 5, wherein R.sup.6 is phenyl, benzyl, cyclopropyl, cyclopropylmethyl or tetrahydropyranyl, each optionally substituted by 1 to 3 substituents independently selected from R.sup.9, wherein R.sup.9 is selected from fluoro, chloro, cyano, hydroxy, methyl, ethyl, methoxy, trifluoromethyl and difluoromethoxy.

7. A compound according to claim 1, wherein R.sup.7 is hydrogen, methyl, ethyl or prop-2-ynyl.

8. A compound according to claim 1, wherein R.sup.8 is phenyl, phenylC.sub.1-4alkyl, heteroaryl or heteroarylC.sub.1-4alkyl wherein the heteroaryl moiety comprises 1 or 2 heteroatoms individually selected from N, O and S, C.sub.3-6cycloalkyl, C.sub.3-6 cycloalkylC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.l-4alkyl wherein the heterocyclyl moiety comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein for R.sup.8: phenyl, heteroaryl, C.sub.3-6cycloalkyl and heterocyclyl are optionally substituted by 1 to 4 substituents independently selected from R.sup.9, or phenyl, heteroaryl, C.sub.3-6cycloalkyl and heterocyclyl are optionally substituted by 1 or 2 substituents independently selected from R.sup.10, or phenyl, heteroaryl, C.sub.3-6cycloalkyl and heterocyclyl are optionally substituted by 1 to 3 substituents independently selected from R.sup.9 and 1 substituent selected from R.sup.10.

9. A compound according to claim 8, wherein R.sup.8 is selected from phenyl, phenylC.sub.1-4alkyl, furanyl, furanylmethyl, C.sub.3-6cycloalkyl, C.sub.3-6cycloalkylC.sub.1-2alkyl, tetrahydrofuranyl, oxetanyl or dioxolanylmethyl, each optionally substituted by 1 to 3 substituents independently selected from R.sup.9, wherein R.sup.9 is selected from halogen, cyano, hydroxy, C.sub.1-4alkyl, C.sub.1-4alkoxy, haloC.sub.1-4alkyl and haloC.sub.1-4alkoxy.

10. A compound according to claim 9, wherein R.sup.8 is selected from phenyl, benzyl, 1-phenylethyl, furanyl, furanylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, tetrahydrofuranyl, oxetanyl or dioxolanylmethyl each optionally substituted by 1 to 3 substituents independently selected from R.sup.9, wherein R.sup.9 is selected from fluoro, chloro, cyano, hydroxy, methyl, ethyl, methoxy, trifluoromethyl and difluoromethoxy.

11. A compound according to claim 1, wherein R.sup.7 and R.sup.8 together with the nitrogen atom they share form an imidazolyl, isoxazolidinyl, pyrrolidinyl or morpholinyl moiety, each optionally substituted by 1 to 3 substituents independently selected from R.sup.9, wherein R.sup.9 is selected from fluoro, chloro, cyano, hydroxy, methyl, ethyl, methoxy, trifluoromethyl and difluoromethoxy.

12. An agrochemical composition comprising a fungicidally effective amount of a compound of formula (I) according to claim 1.

13. The composition according to claim 12, further comprising at least one additional active ingredient and/or an agrochemically-acceptable diluent or carrier.

14. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I) according to claim 1, or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.

15. Use of a compound of formula (I) according to claim 1 as a fungicide.

Description

EXAMPLES

[0229] The examples which follow serve to illustrate the invention. The compounds of the invention can be distinguished from known compounds 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.

[0230] Compounds of Formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).

[0231] Throughout this description, temperatures are given in degrees Celsius ( C.) and mp means melting point.

[0232] LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the method (Methods A and B) is as follows:

The description of the LC/MS apparatus and the method A is:
SQ Detector 2 from Waters
Ionisation method: Electrospray
Polarity: positive and negative ions

Capillary (kV) 3.0, Cone (V) 30.00, Extractor (V) 2.00. Source Temperature ( C.) 150, Desolvation

Temperature ( C.) 350, Cone Gas Flow (L/Hr) 0, Desolvation Gas Flow (L/Hr) 650

[0233] Mass range: 100 to 900 Da
DAD Wavelength range (nm): 210 to 500
Method Waters ACQUITY UPLC with the following HPLC gradient conditions:
(Solvent A: Water/Methanol 20:1+0.05% formic acid and Solvent B: Acetonitrile+0.05% formic acid)

TABLE-US-00007 Flow rate Time (minutes) A (%) B (%) (ml/min) 0 100 0 0.85 1.2 0 100 0.85 1.5 0 100 0.85
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60 C.
The description of the LC/MS apparatus and the method B is:
SQ Detector 2 from Waters
Ionisation method: Electrospray
Polarity: positive ions

Capillary (kV) 3.5, Cone (V) 30.00. Extractor (V) 3.00, Source Temperature ( C.) 150, Desolvation

Temperature ( C.) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700

[0234] Mass range: 140 to 800 Da
DAD Wavelength range (nm): 210 to 400
Method Waters ACQUITY UPLC with the following HPLC gradient conditions
(Solvent A: Water/Methanol 9:1+0.1% formic acid and Solvent B: Acetonitrile+0.1% formic acid)

TABLE-US-00008 Flow rate Time (minutes) A (%) B (%) (ml/min) 0 100 0 0.75 2.5 0 100 0.75 2.8 0 100 0.75 3.0 100 0 0.75
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60 C.

[0235] Where necessary, enantiomerically pure final compounds may be obtained from racemic materials as appropriate via standard physical separation techniques, such as reverse phase chiral chromatography, or through stereoselective synthetic techniques, eg, by using chiral starting materials.

Formulation Examples

[0236]

TABLE-US-00009 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%

[0237] 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-00010 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%

[0238] 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-00011 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%

[0239] Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

TABLE-US-00012 Dusts a) b) c) Active ingredient [compound of formula (I)] 5% 6% 4% Talcum 95% Kaolin 94% mineral filler 96%

[0240] 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-00013 Extruder granules Active ingredient [compound of formula (I)] 15% sodium lignosulfonate 2% Carboxymethylcellulose 1% Kaolin 82%

[0241] 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-00014 Coated granules Active ingredient [compound of formula (I)] 8% polyethylene glycol (mol. wt. 200) 3% Kaolin 89%

[0242] 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-00015 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% [0243] 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-00016 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% solution in 0.5% water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2% Water 45.3%

[0244] 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

[0245] 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.

[0246] 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.

[0247] The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

Preparation Examples

[0248] Throughout this description, temperatures are given in degrees Celsius ( C.) and mp means melting point. LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the methods used for LC/MS analysis are given below.

LIST OF ABBREVIATIONS

[0249] AIBN=azobisisobutyronitrile [0250] BOP-Cl=phosphoric acid bis(2-oxooxazolidie) chloride [0251] DIBAL-H=diisobutylaluminium hydride [0252] DIPEA=N,N-diisopropylethylamine [0253] DMA=dimethylacetamide [0254] DMF=dimethylformamide [0255] DMSO=dimethylsulfoxide [0256] EtOAc=ethyl acetate [0257] EtOH=ethyl alcohol [0258] HCl=hydrochloric acid [0259] HOAt=1-hydroxy-7-azabenzotriazole [0260] HATU=1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid-hexafluorophosphate [0261] mp=melting point [0262] MeOH=methyl alcohol [0263] NaOH=sodium hydroxide [0264] NBS=N-bromosuccinimide [0265] RT=room temperature (25 C.) [0266] TFAA=trifluoroacetic acid anhydride [0267] THF=tetrahydrofuran [0268] DBU=2,3,4,6,7,8,9,10-octahydropyrimido[, 2-a]azepine

Example 1: Preparation of tetrahydropyran-4-yl N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]carbamate (Compound 1.2 of Table T1)

[0269] ##STR00024##

Step 1: Preparation of N-hydroxy-4-methyl-benzamidine

[0270] ##STR00025##

[0271] To a stirring suspension of 4-methylbenzonitrile (35 g, 0.29 mol) in ethanol (220 mL) and water (440 mL) was added at RT hydroxylamine hydrochloride (41.1 g, 0.58 mol), potassium carbonate (65.4 g, 0.47 mol) and 8-hydroxyquinoline (0.22 g, 1.5 mmol). The reaction mixture was heated at 80 C. for 4 hours. The mixture was cooled to RT and diluted with 2N HCl until pH 8. Ethanol was evaporated under reduced pressure then the mixture was filtered, washed with water, and dried under vacuum to afford 39.1 g of the title compound which was used without further purification. LC/MS (Method A) retention time=0.23 minutes, 151.0 (M+H).

Step 2: Preparation of 3-(p-tolyl)-5 (trifluoromethyl)-1,2,4-oxadiazole

[0272] ##STR00026##

[0273] To a stirring solution of N-hydroxy-4-methyl-benzamidine (38.7 g, 0.25 mol) in 2-methyltetrahydrofuran (750 mL) was added TFAA at 0 C. The reaction mixture was stirred at 15 C. for two hours then diluted with water. The organic layer was separated, washed successively with an aqueous sodium bicarbonate solution, aqueous ammonium chloride solution, and water. The organic phase was then dried over sodium sulfate, filtered and evaporated to dryness. The crude was subject to flash chromatography over silica gel (750 g prepacked column; eluent heptane/EtOAc 99:1 to 90:10) to afford 54.1 g of the title compound as clear oil, which solidified after storage.

[0274] LC/MS (Method A) retention time=1.15 minutes, mass not detected. .sup.1H NMR (400 MHz. CDCl.sub.3) ppm: 8.00 (d, 2H), 7.32 (d, 2H), 2.45 (s, 3H).

[0275] .sup.19F NMR (400 MHz, CDCl.sub.3) ppm: 65.41 (s).

Step 3a: Preparation of 3-[4-(bromomethyl)phenyl]-5-(trifluoromethyl)1,2,4-oxadiazole

[0276] ##STR00027##

[0277] A stirring mixture of 3-(p-tolyl)-5-(trifluoromethyl)-1,2,4-oxadiazole (56.0 g, 0.24 mol) and NBS (45.4 g, 0.25 mol) in tetrachloromethane (480 mL) under argon was heated to 70 C. AIBN (4.03 g, 24 mmol) was added and the reaction mixture was stirred at 65 C. for 18 hours. The mixture was cooled to 25 C. and diluted with dichloromethane and water. The organic layer was washed with sodium bicarbonate solution, dried over sodium sulfate, filtered and evaporated to dryness. The crude was subject to flash chromatography over silica gel (750 g pre packed column; eluent cyclohehane/EtOAc 100:0 to 95:5) to afford 44.7 g of the title compound as a white solid mp: 58-63 C.

[0278] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.11 (d, 2H), 7.55 (d, 2H), 4.53 (s, 2H).

[0279] .sup.19F NMR (400 MHz, CDCl.sub.3) ppm: 65.32 (s).

[0280] 3-[4-(dibromomethyl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole (see below) was isolated as by-product as white solid (mp 61-66 C.).

##STR00028##

[0281] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.15 (d, 2H), 7.73 (d, 2H), 6.68 (s.1H).

[0282] .sup.19F NMR (400 MHz, CDCl.sub.3) ppm: 65.34 (s).

Step 3b: Preparation of 3-[4-(bromomethyl)phenyl]-5-(trifluoromethyl-1,2,4-oxadiazole

[0283] ##STR00029##

[0284] To a stirring 1:9 ratio mixture of 3-[4-(bromomethyl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole and 3-[4-(dibromomethyl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole (10.2 g) in acetonitrile (95 mL), water (1.9 mL) and DIPEA (6.20 ml, 35.7 mmol) was added diethylphosphite (4.7 ml, 35.7 mmol) at 5 C. The mixture was stirred at 5-10 C. for two hours, water and 1M HCl were added, and acetonitrile was evaporated under reduced pressure. The white slurry was extracted with dichloromethane and the combined organic layers were dried over sodium sulfate, and filtered. The solvent was removed under reduced pressure and the resultant crude was subject to flash chromatography over silica gel (40 g prepacked column; eluent cyclohexane/EtOAc 99:1 to 9:1) to afford 7.10 g of 3-[4-(bromomethyl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole.

[0285] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.11 (d, 2H), 7.55 (d, 2H), 4.53 (s, 2H).

[0286] .sup.19F NMR (400 MHz, CDCl.sub.3) ppm: 65.32 (s).

Step 4: Preparation of [4-[5-(trifluoromethyl-1,2,4-oxadiazol-3-yl]phenyl]methanamine hydrochloride

[0287] ##STR00030##

[0288] A dry flask equipped with a mechanical stirrer under argon was charged with sodium hydride (2 equiv., 3.13 mmol, 60 mass % NaH) and tetrahydrofuran (25 mL). To this stirring white suspension was added tert-butyl N-tert-butoxycarbonylcarbamate (1.1 equiv, 1.72 mmol) and for 5 min gas evolution was observed, 3-[4-(bromomethyl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole (0.50 g, 1.56 mmol) was then introduced and the contents were stirred for 12 hours. Upon reaction completion, the solution was poured into water and extracted with ethyl acetate (230 mL). The organic layers were combined and dried over sodium sulfate, filtered, and concentrated at reduced pressure to produce a pale yellow oil which partially crystalize upon sitting. The yellow material was dissolved in dioxane (5 mL) and 4M hydrogen chloride in dioxane (15 equiv., 24.7 mmol) was introduced dropwise. After stirring overnight at 25 C. the reaction solution was diluted with ether which produced a white precipitate (70% yield) whose analytics matched the reported values and which was used without further purification. mp: >200 C., LC/MS (Method A) retention time=0.61 minutes. 244 (M-Cl). [0289] .sup.1H NMR (400 MHz, DMSO) ppm: 8.56 (S,.sub.br, 2H), 8.13 (d, 2H), 7.75 (d, 2H), 4.15 (s, 2H). [0290] .sup.19F NMR (400 MHz, DMSO) ppm: 64.69 (s).

Step 5: Preparation of tetrahydropyran-4-yl N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]carbamate (Compound 1.2 of Table T1i)

[0291] To a stirring solution of carbonyl carbonyldiimidazole (0.15 g, 0.93) in THF (4 mL) under an atmosphere of nitrogen was added 2-tetrahydropyran-4-ol (0.09 g, 0.93 mmol) at 5 C. The resulting mix was stirred at room temperature for one hour and then added to a stirring mix of [4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanamine hydrochloride (0.26 g, 0.93 mmol) and DBU in tetrahydrofuran (2 mL). The reaction mixture was allowed to react for 18 hours at room temperature then poured onto water and extracted with ethyl acetate. The combined organic layers were, dried over sodium sulfate, and filtered. The solvent was removed under reduced pressure and the resultant crude residue was purified by reverse phase high pressure liquid chromatography to afford 0.13 g of the titled compound as a yellow oil. LC/MS (Method A) retention time=1.01 minutes, minutes, 372 (M+H).

[0292] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.11 (d, 2H), 7.45 (d, 2H), 5.10 (s.sub.br, 2H), 4.89 (m, 2H), 4.47 (d, 2H), 3.92 (m, 2H), 3.34 (m, 2H), 1.97 (m, 2H), 1.69 (m, 2H).

[0293] .sup.19F NMR (400 MHz, CDCl.sub.3) ppm: 65.34 (s).

Example 2: Preparation of 1-(cyclopropylmethyl)-3-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea (Compound 2.1 of Table T2)

[0294] ##STR00031##

[0295] To a stirring suspension of [4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanamine hydrochloride (0.14 g, 0.50 mmol) (refer step 4 of Example 1) in dichloromethane (2.0 mL) and DMF (0.8 mL) under an atmosphere of nitrogen was added carbonyldiimidazole (0.166 g, 1.0 mmol) at room temperature. After two hours, the suspension turns into a clear solution 1-cyclopropylmethanamine (0.217 mL, 5 mmol) was added. The reaction mixture was allowed to react for 4 hours at room temperature then poured onto water. The organic layer were washed with water, dried over sodium sulfate, and filtered. The solvent was removed under reduced pressure and the resultant crude residue (453 mg containing solvents) was absorbed on Isolute and subjected to combi flash over 12 g pre-packed silica gel column (cyclohexane: EtOAc eluent gradient 99:1 to 7:3) to afford 1-(cyclopropylmethyl)-3-[[4-[5-(trifluoromethyl)-1,24-oxadiazol-3-yl]phenyl]methyl]urea (0.11 g) as a white solid.

[0296] LC/MS (Method A) retention time=0.96 minutes, 341 (M+H).

[0297] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.01 (d, 2H), 7.41 (d, 2H), 5.05 (m, 1H), 4.77 (m, 1H), 4.43 (d, 2H), 3.06 (q, 2H), 0.93 (m, 1H), 0.48 (m, 2H), 0.17 (m, 2H).

Example 3: Preparation of 1-cyclopropyl-3-[2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]urea (Compound 2.32 of Table T2)

[0298] ##STR00032##

Step 1: Preparation of tert-butyl N-[2-(4-cyanophenyl)ethyl]carbamate

[0299] ##STR00033##

[0300] To a solution of 2-(4-cyanophenyl)ethylammonium chloride (3.0 g, 16 mmol) in THF (70 mL) was added triethylamine (6.9 mL, 49 mmol) and DMAP (200 mg, 1.6 mmol). The resulting beige solution was cooled using an ice bath and tert-butoxycarbonyl tert-butyl carbonate (5.4 g, 25 mmol) was introduced dropwise as a THF solution (12 mL). The ice bath was removed and stirring continued overnight. Ice and water were added and extraction was carried out with Et.sub.2O (240 mL). The combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure to afford a light yellow solid. The resulting crude residue was absorbed on isolute and purified via combiflash column chromatography using a cyclohexane/ethylacetate eluent gradient to afford 1.56 g of tert-butyl N-[2-(4-cyanophenyl)ethyl]carbamate as a white solid. mp, 70-74 C.

[0301] LC/MS (Method A) retention time=0.94 min; mass not detected

[0302] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 7.60 (d, 2H), 7.30 (d, 2H), 4.55 (brs, 1H), 3.37 (m, 2H), 2.85 (m, 2H), 1.40 (s, 9H).

Step 2: Preparation of tert-butyl N-[2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]carbamate

[0303] ##STR00034##

[0304] To a solution of tert-butyl N-[2-(4-cyanophenyl)ethyl]carbamate (912 mg, 3.7 mmol) in ethanol (18.5 mL) was added triethylamine (1.04 mL, 7.4 mmol) followed by the portion-wise introduction hydroxylamine hydrochloride (520 mg, 7.4 mmol). The reaction mixture was then heated to 80 C. for 3.5 hours. After the reaction mixture cooled to 25 C., the ethanol was removed under reduced pressure, and the resulting crude tert-butyl N-[2-[4-[N-hydroxycarbamimidoyl]phenyl]ethyl]carbamate residue was suspended in THF (37 mL). Pyridine (1.2 mL, 14.8 mL) was introduced and the reaction contents were cooled using an ice bath. Trifluoroacetic anhydride (1.57 mL, 11.1 mmol) was then added dropwise. The ice bath was removed and stirring was continued overnight. The reaction contents were concentrated under reduced pressure and diethyl acetate and water were introduced. The layers were separated and the organic fraction was washed sequentially with an aqueous 1M NaOH solution, water, and brine then dried over sodium sulfate, filtered, and concentrated to give a yellow crude solid that was absorbed on isolute and purified via combiflash column chromatography using a cyclohexane/ethyl acetate eluent gradient to afford 826 mg of tert-butyl N-[2-[4-[5-(trifluoromethyl) -1,2,4-oxadiazol-3-yl]phenyl]ethyl]carbamate as a white solid. mp: 81-83 C.

[0305] LC/MS (Method A) retention time=1.17 min; mass not detected.

[0306] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.05 (d, 2H), 7.85 (d, 2H), 4.55 (brs, 1H), 3.48 (m, 2H), 2.88 (m 2H), 1.42 (s, 9H).

Step 3: Preparation of 2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethylammonium Chloride

[0307] ##STR00035##

[0308] To a solution of tert-butyl N-[2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]carbamate (500 mg, 1.4 mmol) in ethyl acetate (10 mL) cooled with an ice bath was introduced dropwise a 4M HCl 1,4-dioxane solution (2.8 mL, 11.2 mmol). The ice bath was removed and stirring was continued overnight. A fine white suspension slowly formed and was collected via filtration, washed twice with ethyl acetate, and dried in a vacuum oven to afford 378 mg of 2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethylammonium chloride as a white solid. mp>225 C.

[0309] LC/MS (Method A) retention time=0.67 min; 258 [M-Cl]+.

[0310] .sup.1H NMR (400 MHz, DMSO) ppm: 8.05 (d, 2H), 7.52 (d, 2H), 3.10 (m, 2H), 3.00 (m 2H).

Step 3: Preparation of 1-cyclopropyl-3-[2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]urea

[0311] To a stirring suspension of 2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethylammonium chloride (0.14 g, 0.50 mmol) in dichloromethane (0.5 mL) and DMF (0.15 mL) under an atmosphere of nitrogen was added carbonyldiimidazole (0.05 g, 0.3 mmol) at room temperature. After two hours, the suspension turns into a clear solution cyclopropanamine (0.04 g, 0.75 mmol) was added. The reaction mixture was allowed to react for 2 hours at room temperature then poured onto water. The organic layer were washed with water, dried over sodium sulfate, and filtered. The solvent was removed under reduced pressure and the resultant crude residue was absorbed on Isolute and subjected to combiflash column chromatography (cyclohexane: EtOAc eluent gradient 9:1 to 1:9) to afford 1-cyclopropyl-3-[2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]urea (35 mg) as a white solid. mp: 147-159 C.

[0312] LC/MS (Method A) retention time=0.96 minutes, 341 (M+H).

[0313] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.07 (d, 2H), 7.37 (d, 2H), 5.02 (brs, 1H), 4.75 (brs, 1H), 3.57 (m, 2H), 2.91 (m, 2H), 2.32 (m, 1H), 0.63 (m, 2H), 0.57 (m, 2H).

[0314] The following procedure was used in a combinatorial fashion with appropriate building blocks (compounds (II) and (III)) to provide compounds of Formula (I). The compounds prepared via this combinatorial protocol were analyzed using LC/MS Method B.

##STR00036##

[0315] By way of exemplification, acid derivatives of formula (III) (0.034 mmol in 375 l DMA) were transferred to a 96 slot deep well plate (DWP96) containing the [4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]aryl]methanamine derivative of formula (II) (0.03 mmol) and DIPEA (0.09 mmol) in 250 l DMA, followed by the addition of BOP-Cl (0.06 mmol) dissolved in DMA (250 l). The DWP was sealed and stirred for 18 hours at 50 C. The solvent was removed under a stream of nitrogen. The resultant crude residues were solubilized in a mixture of MeOH (250 l) and DMA (500 l) and directly submitted for preparative LC/MS purification which provided the compounds of formula (I) in 10-85% yields.

TABLE-US-00017 TABLE T1 Melting point (mp) data and/or retention times (t.sub.R) for the compounds of Formula (I) Retention Mass Table time t.sub.R charge mp Entry Compound name Structure (minutes) (M + H).sup.+ Method ( C.) 1.1 tetrahydropyran-4-yl N- [[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl)phenyl]methyl) carbamate [00037] 105- 108 1.2 tetrahydropyran-4-yl N- [(4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl)methyl] carbamate [00038] 104- 106 1.3 cyclopropylmethyl N- [[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl] carbamate [00039] 108.2- 109.8 1.4 benzyl N-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl] carbamate [00040] 1.79 378 B 1.5 phenyl N-[[5-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl)-2- pyridyl]methyl] carbamate [00041] 1.52 365 B 1.6 benzyl N-[[5-[5- (trifluoromethyl)-l,2,4- oxadiazol-3-yl]-2- pyridyl]methyl] carbamate [00042] 1.59 379 B 1.7 cyclopropylmethyl N- [[3-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl] carbamate [00043] 1.08 360.3 A

TABLE-US-00018 TABLE T2 Melting point (mp) data and/or retention times (t.sub.R) for the compounds of Formula (I) Retention Mass Table time t.sub.R charge mp Entry Compound name Structure (minutes) (M + H).sup.+ Method ( C.) 2.1 1-(cyclopropylmethyl)-3- [[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00044] 158.8- 165 2.2 1-(cyclopropylmethyl)-3- [[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00045] 157- 160 2.3 1-cyclopropyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00046] 176- 180.1 2.4 1-cyclopropyl-3-[[2-fluoro- 4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00047] 150.1- 152.4 2.5 1-phenyl-3-[[5-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00048] 1.39 364 B 2.6 1-cyclohexyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00049] 1.63 369 B 2.7 1-phenyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00050] 1.59 363 B 2.8 1-benzyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00051] 1.55 377 B 2.9 1-cyclobutyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00052] 1.46 341 B 2.10 1-cyclopentyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00053] 1.54 355 B 2.11 1-(2-furylmethyl)-3-[[4-[5- (trifluoromethyl)-l,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00054] 1.44 367 B 2.12 1-benzyl-3-[[5-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00055] 1.36 378 B 2.13 1-(4-fluorophenyl)-3-[[5- [5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00056] 1.42 382 B 2.14 1-cyclopentyl-3-[[5-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00057] 1.34 356 B 2.15 1-(4-chlorophenyl)-3-[[5- [5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00058] 1.55 398 B 2.16 1-(2-furylmethyl)-3-[5-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00059] 1.24 368 B 2.17 1-(3-fluorophenyl)-3-[[5- [5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00060] 1.46 382 B 2.18 1-(2-fluorophenyl)-3-[[5- [5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00061] 1.43 382 B 2.19 1-(2-chlorophenyl)-3-[[5- [5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]-2- pyridyl]methyl]urea [00062] 1.53 398 B 2.20 1-cyclopropyl-3-[[3-fluoro- 4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00063] 169- 173 2.21 1-(2-chlorophenyl)-3-[[3- fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00064] 173- 178 2.22 1-cyclopropyl-1-methyl-3- [[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00065] 1.52 341 B 2.23 1-(oxetan-3-yl)-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00066] 1.22 343 B 2.24 1-(1-cyanocyclopropyl)-3- [[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00067] 1.32 352 B 2.25 1-(1-methylcyclopropyl)-3- [[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00068] 1.45 341 B 2.26 1-cyclobutyl-1-methyl-3- [[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00069] 1.61 355 B 2.27 1-cyclopropyl-1-ethyl-3- [[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]methyl]urea [00070] 1.67 355 B 2.28 1-[1- (methoxymethyl) cyclopropyl]-1- methyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00071] 1.69 385 B 2.29 1-(cyclopropylmethyl)-l- ethyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00072] 1.74 369 B 2.30 1-cyclopropyl-1-prop-2- ynyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00073] 1.64 365 B 2.31 1-(cyclopropylmethyl)-1- methyl-3-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl]urea [00074] 1.67 355 B 2.32 1-cyclopropyl-3-[2-[4- [5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]phenyl]ethyl]urea [00075] 0.96 341 A

TABLE-US-00019 TABLE T3 Melting point (mp) data and/or retention times (t.sub.R) for the compounds of Formula (I) Retention Mass Table time t.sub.R charge mp Entry Compound name Structure (minutes) (M + H).sup.+ Method ( C.) 3.1 N-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl] imidazole-1- carboxamide [00076] 97- 102 3.2 N-[[4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]methyl] morpholine-4- carboxamide [00077] 112- 115 3.3 N-[[3-fluoro-4-[5- (trifluoromethyl)-l,2,4- oxadiazol-3- yl]phenyl]methyl] morpholine-4- carboxamide [00078] 82- 94 3.4 N-[[4-[5- (trifluoromethyl)-l,2,4- oxadiazol-3- yl]phenyl]methyl] pyrrolidine-1- carboxamide [00079] 1.44 341.15 B 3.5 N-[[4-[5- (trifluoromethyl)-l,2,4- oxadiazol-3- yl]phenyl]methyl] isoxazolidine-2- carboxamide [00080] 1.43 343.15 B

Biological Examples

[0316] General examples of leaf disk tests in well plates:
Leaf disks or leaf segments of various plant species are cut from plants grown in a greenhouse. The cut leaf disks or segments are placed in multiwell plates (24-well format) onto water agar. The leaf disks are sprayed with a test solution before (preventative) or after (curative) inoculation. Compounds to be tested are prepared as DMSO solutions (max. 10 mg/ml) which are diluted to the appropriate concentration with 0.025% Tween20 just before spraying. The inoculated leaf disks or segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the respective test system. A single evaluation of disease level is carried out 3 to 14 days after inoculation, depending on the pathosystem. Percent disease control relative to the untreated check leaf disks or segments is then calculated.
General examples of liquid culture tests in well plates:
Mycelia fragments or conidia suspensions of a fungus prepared either freshly from liquid cultures of the fungus or from cryogenic storage, are directly mixed into nutrient broth. DMSO solutions of the test compound (max. 10 mg/ml) are diluted with 0.025% Tween20 by a factor of 50 and 10 l of this solution is pipetted into a microtiter plate (96-well format). The nutrient broth containing the fungal spores/mycelia fragments is then added to give an end concentration of the tested compound. The test plates are incubated in the dark at 24 C. and 96% relative humidity. The inhibition of fungal growth is determined photometrically after 2 to 7 days, depending on the pathosystem, and percent antifungal activity relative to the untreated check is calculated.

Example 1: Fungicidal Activity Against Puccinia recondita f, Sp. Tritici/Wheat/Leaf Disc Preventative (Brown Rust)

[0317] Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19 C. and 75% relative humidity (rh) under a light regime of 12 hours light/12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 to 9 days after application).

[0318] The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0319] Compounds (from Table T1) 1.1, 1.2, 1.3, 1.4, and 1.6.

[0320] Compounds (from Table T2) 2.1, 2.3, 2.4, 2.5, 2.7, 2.8, 2.9, 2.10, 2.12, 2.13, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.26, 2.27, 2.28, 2.29, 2.30 and 2.31.

[0321] Compounds (from Table T3) 3.1, 3.2, 3.3, 3.4 and 3.5.

Example 2: Fungicidal Activity Against Puccinia Recondite f. Sp. Tritici Wheat/Leaf Disc Curative (Brown Rust)

[0322] Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are then inoculated with a spore suspension of the fungus. Plates were stored in darkness at 19 C. and 75% relative humidity. The formulated test compound diluted in water was applied 1 day after inoculation. The leaf segments were incubated at 19 C. and 75% relative humidity under a light regime of 12 hours light/12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (6 to 8 days after application).

[0323] The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0324] Compounds (from Table T1) 1.1, 1.2, 1.3, and 1.6.

[0325] Compounds (from Table T2) 2.3, 2.4, 2.17, 2.20, 2.22, 2.24, 2.26, 2.27, 2.28, 2.30 and 2.31.

[0326] Compounds (from Table T3) 3.1, 3.2, 3.3, 3.4 and 3.5.

Example 3: Fungicidal Activity Against Phakopsora pachyrhizi/Soybean/Leaf Disc Preventative (Asian Soybean Rust)

[0327] Soybean leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. One day after application leaf discs are inoculated by spraying a spore suspension on the lower leaf surface. After an incubation period in a climate cabinet of 24-36 hours in darkness at 20 C. and 75% rh leaf disc are kept at 20 C. with 12 h light/day and 75% rh. 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 disks (12 to 14 days after application).

[0328] The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0329] Compounds (from Table T1) 1.1, 1.2, and 1.3.

[0330] Compounds (from Table T2) 2.1, 2.2, 2.3, 2.4, 2.6, 2.7, 2.17, 2.19, 2.20, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30 and 2.31.

[0331] Compounds (from Table T3) 3.1, 3.2, 3.4 and 3.5.

Example 4: Fungicidal Activity Against Glomerella Lagenarium (Colletotrichum Lagenarium) Liquid Culture/Cucumber/Preventative (Anthracnose)

[0332] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDBpotato 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 to 4 days after application.

[0333] The following compounds at 20 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control under the same conditions, which show extensive disease development.

[0334] Compounds (from Table T1) 1.1, 1.2, 1.3, 1.4, 1.5, and 1.6.

[0335] Compounds (from Table T2) 22.1, 2.2, 2.3, 2.4, 2.5, 2.7, 2.8, 2.9, 2.10, 2.11, 2.12, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.22, 2.26, 2.27. 2.28, 2.29, 2.30, and 2.31.

[0336] Compounds (from Table T3) 3.1, 3.2, 3.3, 3.4, and 3.5.