MICROBIOCIDAL DERIVATIVES

Abstract

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

##STR00001##

Claims

1. A compound of formula (I): ##STR00054## wherein R.sup.1 is hydrogen, cyano, formyl, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkoxycarbonyl, C.sub.1-C.sub.6haloalkylcarbonyl, C.sub.1-C.sub.6alkoxyC.sub.1-C.sub.6alkylcarbonyl, C.sub.3-C.sub.6cycloalkylcarbonyl, C.sub.1-C.sub.6alkoxyC.sub.1-C.sub.3alkoxycarbonyl, C.sub.1-C.sub.6alkoxyoxalyl, C.sub.1-C.sub.6alkoxycarbonylC.sub.1-C.sub.4alkylC.sub.1-C.sub.6alkoxycarbonyl, C.sub.2-C.sub.6alkenyloxycarbonyl, or C.sub.2-C.sub.6alkynyloxycarbonyl; R.sup.2 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, halogen, hydroxy, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.3-C.sub.6cycloalkyloxy, C.sub.3-C.sub.6halocycloalkyloxy, C.sub.2-C.sub.6alkenyloxy, C.sub.2-C.sub.6haloalkenyloxy, C.sub.2-C.sub.6alkynyloxy, C.sub.2-C.sub.6haloalkynyloxy, C.sub.1-C.sub.6cyanoalkyloxy, C.sub.1-C.sub.6alkoxyC.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.6alkoxyC.sub.1-C.sub.2alkyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, or C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.2alkoxy; R.sup.3 is Ci-Csalkyl, Ci-Cshaloalkyl, Ci-Csalkoxy, C.sub.3-C.sub.8alkynyl, C.sub.3-Cscycloalkyl, C.sub.3-C.sub.8cycloalkylC.sub.1-C.sub.2alkyl, phenyl, phenylC.sub.1-C.sub.3alkyl, phenoxyC.sub.1-C.sub.3alkyl, heteroaryl, heteroarylCi-C.sub.2alkyl, heteroarylC.sub.1-C.sub.2alkoxyiminoC.sub.1-C.sub.2alkyl, wherein the heteroaryl is a 5- or 6-membered aromatic monocyclic ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclyl, heterocyclylC.sub.1-C.sub.2alkyl, wherein the heterocyclyl is a 4-, 5- or 6-membered non-aromatic monocyclic ring comprising 1, 2 or 3 heteroatoms individually selected from N, O, and S, and wherein the cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are each optionally substituted with 1 to 3 groups represented by R.sup.5 or 1 group represented by R.sup.6; and wherein when R.sup.3 is a substituted heterocyclyl, these cycles may contain a carbonyl (C═O) or sulfonyl (S(O).sub.2) group; or R.sup.3 is a 6- to 10-membered annulated ring system optionally comprising 1, 2, or 3 heteroatoms individually selected from N, O and S, optionally substituted with 1 or 2 groups represented by R.sup.5, and optionally bonded to the rest of the molecule through a C.sub.1-C.sub.2alkylene linker; or R.sup.3 is a 5- to 10-membered non-aromatic spirocyclic carbobi- or carbotri-cyclyl ring system optionally comprising 1, 2, 3, 4 or 5 heteroatoms individually selected from N, O and S, optionally substituted with 1 to 3 groups represented by R.sup.5, and optionally bonded to the rest of the molecule through a C.sub.1-C.sub.2alkylene linker; R.sup.4 is Ci-Csalkyl, hydroxyCi-Csalkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.3-C.sub.8cycloalkylC.sub.1-C.sub.2alkyl, phenyl, heteroaryl, wherein heteroaryl is a 5- or 6-membered aromatic monocyclic ring comprising 1, 2 or 3 heteroatoms individually selected from N, O and S, heterocyclyl, wherein the heterocyclyl is a 4-, 5- or 6-membered non-aromatic monocyclic ring or a 9- to 10-membered non-aromatic bicyclic ring comprising 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein the cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are each optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R.sup.8; R.sup.5 is halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl, or C.sub.1-C.sub.4haloalkoxy; R.sup.6 is C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.8cycloalkyl, phenyl, benzyl, phenoxy, or pyridyl, wherein each cycloalkyl, phenyl or pyridyl group is optionally substituted by 1 group represented by R.sup.7; R.sup.7 is halogen, C.sub.1-C.sub.4haloalkyl or C.sub.1-C.sub.4haloalkoxy; R.sup.8 is halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkyl; or a salt or an N-oxide thereof.

2. The compound according to claim 1, wherein R.sup.1 is hydrogen, cyano, C.sub.1-C.sub.3alkylcarbonyl, or C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.2alkylcarbonyl.

3. The compound according to claim 1 , wherein R.sup.1 is hydrogen, cyano or acetyl.

4. The compound according to claim 1, wherein R.sup.2 is hydrogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.3haloalkyl, halogen, hydroxy, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.3-C.sub.4cycloalkyloxy, C.sub.3-C.sub.4alkenyloxy, C.sub.3-C.sub.4alkynyloxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.2alkyl, C.sub.1-C.sub.3haloalkoxy, or C.sub.3-C.sub.5alkynyl.

5. The compound according to claim 1, wherein R.sup.3 is Ci-Csalkyl, C.sub.3-C.sub.7alkynyl, C.sub.3-C.sub.4cycloalkyl, C.sub.3-C.sub.4cycloalkylC.sub.1-C.sub.2alkyl, phenylC.sub.1-C.sub.3alkyl, phenoxyC.sub.1-C.sub.3alkyl, heteroaryl, heteroarylC.sub.1-C.sub.2alkyl, heteroarylC.sub.1-C.sub.2alkoxyiminoC.sub.1-C.sub.2alkyl, wherein the heteroaryl is a 5- or 6-membered aromatic monocyclic ring comprising 1, 2, or 3 heteroatoms individually selected from N and O, heterocyclyl, heterocyclylC.sub.1-C.sub.2alkyl, wherein the heterocyclyl is a 5- or 6-membered non-aromatic monocyclic ring comprising 1, 2 or 3 heteroatoms individually selected from N, O, and S, and wherein the cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are each optionally substituted with 1 or 2 groups represented by R.sup.5 or 1 group represented by R.sup.6; and wherein when R.sup.3 is a substituted heterocyclyl, these cycles may contain a carbonyl (C═O) or sulfonyl (S(O).sub.2) group; or R.sup.3 is a 7- to 9-membered annulated ring system optionally comprising 1, 2, or 3 heteroatoms individually selected from N and O, optionally substituted with 1 or 2 groups represented by R.sup.5, and optionally bonded to the rest of the molecule through a C.sub.1-C.sub.2alkylene linker; or R.sup.3 is a 6- to 9-membered non-aromatic spirocyclic carbobicyclyl ring system optionally comprising 1, 2, or 3 heteroatoms individually selected from N and O, optionally substituted with 1 or 2 groups represented by R.sup.5, and optionally bonded to the rest of the molecule through a C.sub.1-C.sub.2alkylene linker.

6. The compound according to claim 1, wherein R.sup.3 is t-butyl, isopentyl, 2,2-dimethylpropyl, 1-methylcyclopropyl, 2,2-dimethylcyclobutyl, or spiro[3.4]octan-3-yl.

7. The compound according to claim 1, wherein R.sup.4 is C.sub.1-C.sub.6alkyl, hydroxyC.sub.1-C.sub.4alkyl, C.sub.3-Cscycloalkyl, C.sub.3-C.sub.4cycloalkylC.sub.1-C.sub.2alkyl, phenyl, heteroaryl, wherein heteroaryl is a 5- or 6-membered aromatic monocyclic ring comprising 1 or 2 heteroatoms individually selected from N, O and S, and wherein the cycloalkyl, phenyl, and heteroaryl moieties are each optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.8.

8. The compound according to claim 1, wherein R.sup.4 is C.sub.1-C.sub.6alkyl, hydroxyC.sub.1-C.sub.4alkyl, C.sub.3-Cscycloalkyl, C.sub.3-C.sub.4cycloalkylC.sub.1-C.sub.2alkyl, phenyl, heteroaryl, wherein heteroaryl is a 5- or 6-membered aromatic monocyclic ring comprising 1 or 2 heteroatoms individually selected from N, O and S, and wherein the cycloalkyl, phenyl, and heteroaryl moieties are each optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.8.

9. The compound according to claim 1, wherein R.sup.5 is chloro, fluoro, methyl, difluoromethyl or trifluoromethyl.

10. The compound according to claim 1, wherein R.sup.6 is cyclopropyl, phenyl, phenoxy, or pyridyl, wherein each cyclopropyl, phenyl or pyridyl group is optionally substituted by 1 group represented by R.sup.7.

11. The compound according to claim 1, wherein R.sup.7 is chloro, fluoro, trifluoromethyl or trifluoromethoxy.

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, 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.

16. The compound according to claim 2, wherein R.sup.1 is hydrogen, cyano or acetyl.

17. 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 a composition according to claim 12, is applied to the plants, to parts thereof or the locus thereof.

Description

EXAMPLES

[0233] 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.

[0234] 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)

LIST OF ABBREVIATIONS

[0235] .sup.◦C = degrees Celsius, CDCl.sub.3 = chloroform-d, d = doublet, DIPEA = N,N-diisopropylethylamine, DMF = dimethylformamide, HAUT = 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate, m = multiplet, MHz = mega hertz, N = normal, s = singlet

[0236] Example 1: This example illustrates the preparation of 6-(3,5-difluoroanilino)-N-(2,2-dimethylpropyl)-3-methoxy-pyraxine-2-carboxamide (Compound P-39, Table 3)

##STR00037##

A) Preparation of Methyl 6-bromo-3-methoxy-pyrazine-2-carboxylate

[0237] ##STR00038##

[0238] Methyl 3-amino-6-bromo-pyrazine-2-carboxylate (1.0 g, 4.31 mmol) was dissolved in concentrated sulfuric acid (5.86 mL) and the mixture was stirred at 0° C. Next sodium nitrite (2.0 equlv.) was added, the reaction was stirred for 30 min at 0° C. The mixture was slowly poured into methanol (53 mL) at room temperature and the resulting mixture was stirred for 5 additional hours. Next the methanol was distilled off and the residue poured into ice cold water (100 mL). The aqueous phase was extracted three times with dichloromethane and the combined organic phases washed with saturated sodium bicarbonate aqueous solution, brine and then dried over sodium sulphate. The volatiles were removed in vacuo and the crude purified by chromatography on silica gel (eluent: mixtures cyclohexane ethyl acetate). The desired methyl 6-bromo-3-methoxy-pyrazine-2-carboxylate was obtained. .sup.1H-NMR (400 MHz, (CD.sub.3).sub.2SO): δ = 3.87 (s, 3 H), 3.98 (s, 3 H), 8.19 (s, 1 H).

B) Preparation of Methyl 6-(3.5-difluoroanilino)-3-methoxy-pyrazine-2-carboxylate

[0239] ##STR00039##

[0240] Under an argon atmosphere, BrettPhos-G3-palladacycle ([(2-Di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropy-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate methanesulfonate, 0.1 equiv.) and cesium carbonate (2.5 equiv.) were added to a degassed, stirred mixture of methyl 6-bromo-3-methoxy-pyrazine-2-carboxylate (2.0 g, 8.1 mmol, 1 equiv.) and 3,5-difluoro aniline (1.1 equiv.) in THF (32.5 mL). The reaction was heated to 80° C. and stirred for 1 hour, then the mixture was cooled to room temperature. The volatiles were removed using a rotatory evaporator and the residue was dissolved in ethyl acetate. The organic phase was washed twice with water, dried over anhydrous sodium sulphate and concentrated in vacuo. Purification by column chromatography on silica gel (eluent: mixtures cyclohexane ethyl acetate) afforded the desired methyl 6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxytate. .sup.1H-NMR (400 MHz. (CD.sub.3)2SO): δ = 3.85 (s, 3 H), 3.92 (s. 3 H), 6.60-6.70 (m, 1 H), 7.40-7.50 (m, 2 H), 8.16 (s. 1H).

C) Preparation of 6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxylic Acid

[0241] ##STR00040##

[0242] Lithium hydroxide monohydrate (4 equiv.) was added to a solution of methyl 6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxylate (2.10 g, 3.16 mmol) in a mixture of tetrahydrofuran (72 mL) and water (36 mL). The reaction mixture was stirred 1 hour at room temperature, then the solvents were removed in vacuo. The residue was diluted with ethyl acetate and water, then 2 N hydrochloric acid was slowly added until a pH of 2 - 3 was reached. The phases were separated and the aqueous layer was extracted three times with ethyl acetate. Then the combined organic phases were dried over sodium sulphate and all the volatiles evaporated using a rotatory evaporator. The obtained 6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxylic acid was directly used in the next step without further purification.

D) Preparation of 6-(3,5-difluoroanilino)-N-(2,2-dimethylpropyl)-3-methoxy-pyrazine-2-carboxamide (Compound P-39, Table 3)

[0243] ##STR00041##

[0244] 2,2-dimethylpropan-1-amine (1.1 equiv.), 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 1.1. equiv.) and N,N-diisopropylethylamine (2.6 equiv.) were added in sequence to a DMF solution (2.5 mL) of 6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxylic acid (70 mg., 0.25 mmol, 1 equiv.). The resulting solution was stirred at room temperature for 2 hours until consumption of starting material (LCMS control). Then a saturated NaHCO.sub.3 solution was added to the mixture and the solution extracted three times with ethyl acetate, the organic phases combined, dried over sodium sulphate and all the volatiles removed by rotatory evaporator. Purification by column chromatography on silica gel (eluent: mixtures of cyclohexane/ethyl acetate) gave the desired product 6-(3,5-difluoroanilino)-N-(2,2-dimethylpropyl)-3-methoxy-pyrazine-2-carboxamide. .sup.1H-NMR (400 MHz, CDCl.sub.3): d = 1.02 (s, 9 H), 3.30 (d. 2 H), 4.02 (s. 3 H), 6.35-6.45 (m, 1 H), 7.00 - 7.10 (m, 2 H), 7.75 - 7.85 (m, 2 H), 8.16 (s, 1 H).

[0245] Throughout this description, temperatures are given in degrees Celsius (°C) and “m.p.” means melting point LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the method is: (Method A: ACQUITY UPLC from Waters, Waters UPLC HSS T3, 1.8 .Math.m particle size, 30 x 2.1 mm column, 0.85 mL/min., 60° C., H.sub.2O/MeOH 95:5 + 0.05% HCOOH (90%) / CH.sub.3CN + 0.05% HCOOH (10%) - 1.2 min. - CH.sub.3CN +0.05% HCOOH (100%) - 0.30 min., ACQUITY SQD Mass Spectrometer from Waters, ionization method: electrospray (ESI), Polarity: positive ions, Capillary (kV) 3.00, 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). Method B: ACQUITY UPLC from Waters, Waters UPLC HSS T3. 1.8 .Math.m particle size, 30 x 2.1 mm column, 0.85 mL/min., 60° C., H.sub.2O/MeOH 95:5 + 0.05% HCOOH (90%) / CH.sub.3CN + 0.05% HCOOH (10%) - 2.7 min. - CH.sub.3CN + 0.05% HCOOH (100%) - 0.30 min., ACQUITY SQD Mass Spectrometer from Waters, ionization method: electrospray (ESI), Polarity: positive ions. Capillary (kV) 3.00, 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). Method C: ACQUITY Mass Spectrometer from Waters Corporations (SQD or SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150° C., Desolvation Temperature: 400° C., Cone Gas Flow: 60 L/hr, Desolvation Gas Flow: 700 L/hr, Mass range: 140 to 800 Da) and an ACQUITY UPLC from Waters Corporations with solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 .Math.m, 30 x 2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A = Water/Methanol 9:1 + 0.1%, formic acid, B= Acetonitrile + 0.1% formic acid, gradient: 0-100% B in 2.5 min; Flow (ml/min) 0.75.).

TABLE-US-00011 Melting point and LC/MS data (R.sub.t = Retention time) for selected compounds of Table 1 and Table 2. No. Compound Name Structure Mp (°C) LC/MS P-1 6-(cyclopentylamino)-N-(2,2-dimethylcyclobutyl)-3-methoxy-pyrazine-2-carboxamide 85 - 87 R.sub.t= 1.11 min (A); MS: m/z = 319 (M+1) P-2 6-(cyclobutylamino )-N-(2,2-dimethylcyclobutyl)-3 methoxy-pyrazine-2-carboxamide [00042] 70-72 R.sub.t=1.06 min (A); MS: m/z = 305 (M+1) P-3 6-(cyclopropylamino)-N-(2,2-dimethylcyclobutyl)-3-methoxy-pyrazine-2-carboxamide R.sub.t= 1.00 min (A); MS: m/z 291 (M+1) P-4 6-anilino-N-(2,2-dimethylcyclobutyl)-3-methoxy-pyrazine-2-carboxamide 67 - 69 R.sub.t= 1.06 min (A); MS: m/z = 327 (M+1) P-5 N-(2,2-dimethylcyclobutyl)-6-(3-fluoroanilino)-3-methoxy-pyrazine-2-carboxamide 69 - 71 R.sub.t= 1.08 min i (A); MS: m/z = 345 (M+1) P-6 6-(3,5-difluoroanilino)-3-methoxy-N-[2-oxo-1-[3-(trifluoromethoxy) phenyl]pyrrolidin-3-yl]pyrazine-2-carboxamide [00043] 187 - 190 R.sub.t= 1.11 min (A); MS: m/z = 524 (M+1) P-7 6-(3,5-difluoroanilino)-pyridyl)cyclopropyl]py razine-2-carboxamide R.sub.t= 0.91 min-(A); MS: m/z = 398 (M+1) P-8 N-(2,2-dimethylcyclobutyl)-6-[(2-hydroxy-2-methyl-propyl)amino]-3-methoxy-pyrazine-2-carboxamide 66 - 67 R.sub.t= 0.89 min (A); MS: m/x = 323 (M+1) P-9 6-(cyclopropylmethylam ino)-N-(2,2-dimethyylcyclobutyl)-3-methoxy-pyrazine-2-carboxamide R.sub.1=1.03 min (A), MS: m/z = 305 (M+1) P-10 6-(isothiazol-4-ylamino)-3-methoxy-N-[2-[4-(trifluoromethoxy)phe nyl]ethyl]pyrazine-2-carboxamide R.sub.1= 1.71 min: (C): MS: m/z = 440 (M+1) P-11 6-(isothiazol-4-ylamino)-3-methoxy-N- [[1-(trifluoromethyl)cyclop ropyl]methyl]pyrazine-2-carboxamide [00044] R.sub.1= 1.45 min: (C); MS: m/z = 374 (M+1) P-12 N-[(2,2-difluoro-1,3-benzodioxol-4-yl)methyl)-6-(isothiazol-4-ylamino)-3-methoxy-pyrazine-2-carboxamide R.sub.1= 1.61 min (C) : MS: m/z = 422 (M+1) P-13 6-(isothiazol-4-ylamino)-3-methoxy-N-[(4-phenoxyphenyl)methy l]pyrazine-2-carboxamide R.sub.1= 1.74 min (C) ; MS: m/z = 434 (M+1) P-14 6-(isothiazol-4-ylamino)-3-methoxy-N-[6-(trifluoromethyl)indan-1-yl]pyrazine-2-carboxamide R.sub.1= 1.73 min (C) ; MS: m/z = i 436 (M+1) P-15 6-(isothiazol-4-ylamino)-3-methoxy-N-[5-(trifluoromethyl)indan-1-yl]pyrazine-2-carboxamide [00045] R.sub.1= 1.77 min: (C); MS: m/z = 436 (M+1) P-16 6-(3,5-difiuoroanilino)-N-(7,7-dimethyl-2-oxabicyclo[3.2.0]hept an-6-yl)-3-methoxy-pyrazine-2-carboxamide R.sub.1= 1.69 min (C) : MS: m/z = 405 (M+1) P-17 N-[2-(3,5-dichloro-2-pyridyl)-2-ethoxyimino-ethyl]-6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxamide R.sub.1= 2.02 min (C) ; MS: m/z = 511 (M+1) P-18 6-(3,5-difluoroanilino)-3-methoxy-N-[2-[4-(trifluoromethoxy)phe nyl]ethyl]pyrazine-2-carboxamide R.sub.1= 2.01 min (C) ; MS: m/z = 469 (M+1) P-19 6-(3,5-difluoroanilino)-3-methoxy-N-[[1-[5-(trifluoromethyl)-2-pyridyl]cyclopropyl]me thyl]pyrazine-2-carboxamide [00046] R.sub.1= 1.97 min (C) ; MS: m/z = 480 (M+1) P-20 6-(3,5-difluoroanilino)-3-methoxy-N-(4-oxaspiro[2.4]heptan-6-yl)pyrazine-2-carboxamide R.sub.1= 1.58 min (C) ; MS: m/z = 377 (M+1) P-21 6-(3,5-difluoroanilino)-3-methoxy-N-[(3-methyltetrahydrofuran -3-yl)methyl]pyrazine-2-carboxamide R.sub.1=1.51 min (C) ; MS: m/z = 379 (M+1) P-22 6-(3,5-difluoroanilino)-3-methoxy-N-[(8-methyl-5-oxaspiro[3.5]nonan-8-yl)methyl]pyrazine-2-carboxamide R.sub.1= 1.84 min (C) ; MS: m/z = : 433 (M+1) P-23 N-[(3,5-dichloro-4-pyridyl)methyl]-6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxamide [00047] R.sub.1= 1.72 min (C) ; MS: m/z = 440 (M+1) P-24 N-(5-cyclopropyltetrahydrof uran-3-yl)-6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2- carboxamide R.sub.1=1.62 min (C) ; MS: m/z = 391 (M+1) P-25 6-(3,5-difluoroanilino)-3-methoxy-N-[[1-(trifluoromethyl)cyclop ropyl]methyl]pyrazine-2-carboxamide R.sub.1= 1.79 min: (C); MS: m/z = 403 (M+1) P-26 6-(3,5-difluoroanilino)-N-(2,3-dihydrabenzofuran-3-ylmethyl)-3-methoxy-pyrazine-2-carboxamide R.sub.1= 1.75 min (C) ; MS: m/z = 413 (M+1) P-27 6-(3,5-difluoroanilino)-3-methoxy-N-(pyrazolo[1,5-a]pyridin-7-ylmethyl)pyrazine-2-ccarboxamide R.sub.t=1.69 min (C) : MS: m/z = 441 (M+1) P-28 6-(3,5-difluoroanilino)-3-methoxy-N-(2-oxabicyclo[3.2.0]hept an-7-yl)pyrazine-2-carboxamide [00048] R.sub.t= 1.59 min (C) : MS: m/z = 377 (M+1) P-29 6-(3,5-difluoroanilino)-N-[(2,2-difluoro-1.3-benzodioxol-4-yl)methyl]-3-methoxy-pyrazine-2-carboxamide R.sub.t= 1.91 min (C); MS: m/z = 451 (M+1) P-30 6-(3,5-difluoroanilino)-3-methoxy-N-[(4-phenoxyphenyl)methy l]pyrazine-2-carboxamide R.sub.t= 2.01 min (C) ; MS: m/z = 463 (M+1) P-31 6-(3,5-difluoroanilino)-3-methoxy-N-[6-(trifluoramethyl)indan-1-yl]pyrazine-2-carboxamide R.sub.t= 2.01 min (C) ; MS: m/z = 465 (M+1) P-32 6-(3,5-difluoroanilino)-3-methoxy-N-[5-(trifluoromethyl)indan-1-yl]pyrazine-2-carboxamide [00049] R.sub.t= 2.05 min (C) ; MS: m/z = 465 (M+1) P-33 N-(2-(3,5-dichloro-2-pyridyl)-2-ethoxyimino-ethyl]-6-[(2,6-difluoro-4-pyridyl)amino]-3-methoxy-pyrazine-2-carboxamide R.sub.t= 1.84 min (C) ; MS: m/z = 512 (M+1) P-34 6-[(2,6-difluoro-4-pyridyl)amino]-3-methoxy-N-[(8-methyl-5-oxaspiro[3,5]nonan-8-yl)methyl]pyrazine-2-carboxamide R.sub.t= 1.63 min (C) : MS: m/z = 434 (M+1) P-35 6-[(2,6-difluoro-4-pyridyl)amino]-3-methoxy-N-[[1-(trifluoromethyl)cyclop ropyl]methyl]pyrazine-2-carboxamide R.sub.t= 1.60 min (C) ; MS: m/z = 404 (M+1) P-36 6-[(2,6-difluoro-4-pyridyl)amino]-3-methoxy-N-[(4-phenoxyphenyl)methy l]pyrazine-2-carboxamide [00050] R.sub.t= 1.86 min (C) ; MS: m/z = 464 (M+1) P-37 6-(3,5-difluoroanilino)-3-methoxy-N-(1-methylcyclopropyl)pyr azine-2-carboxamide 187 - 188 R.sub.t= 0.99 min (A); MS: m/z = 335 (M+1) P-38 N-tert-butyl-6-(3,5-difluoroanilino)-3-methoxy-pyrazine-2-carboxamide 167 - 168 P-39 6-(3,5-difluoroanilino)-N-(2,2-dimethylpropyl)-3-methoxy-pyrazine-2-carboxamide 149 - 151 P-40 6-(3,5-difluoroanilino)-N-(1,5-dimethylhexyl)-3-methoxy-pyrazine-2-carboxamide 89 - 92 P-41 6-[(2,6-difluoro-4-pyridyl)amino]-N-(2,2-dimethylcyclobutyl)-3-methoxy-pyrazine-2-carboxamide [00051] 217 - 219 P-42 N-(2,2-dimethylcyclobutyl)-6-(isothiazol-4-ylamino)-3-methoxy-pyrazine-2-carboxamide 69 - 71 P-43 6-(3,5-difluoroanilino)-N-(2,2-dimethylcyclobutyl)-3-methoxy-pyrazine-2-carboxamide 149 - 151 P-44 6-(3,5-difluoroanilino)-N-isopentyl-3-methoxy-pyrazine-2-carboxamide 192 -193 P-45 6-[(2,6-difluoro-4-pyridyl)amino]-N-isopentyl-3-methoxy-pyrazine-2-carboxamide 190 - 192 P-46 6-[(2,6-difluoro-4-pyridyl)amino]-N-(2,2-dimethylcyclobutyl)pyr azine-2-carboxamide [00052] 166 - 168 R.sub.t= 0.99 min (A); MS: m/z = 334 (M+1) P-47 6-(3,5-difluoroanilino)-N-(2,2-dimethylcyclobutyl)-3-methyl-pyrazine-2-carboxamide R.sub.t= 1.12 min (A); MS: m/z = 347(M+1) P-48 6-(3,5-difluoroanilino)-N-(1-methylcyclopentyl)pyr azine-2-carboxamide 178 - 181 R.sub.t= 1.12 min : (A); MS: m/z = 333 (M+1) P-49 6-[(2,6-difluoro-4-pyridyl)amino]-N-(1-methylcyclopentyl)pyr azine-2-carboxamide R.sub.t= 1.03 min (A); MS: m/z = 334 (M+1) P-50 6-[(2,6-difluoro-4-pyridyl)amino]-N-(2,2-dimethylcyclobutyl)-3-methyl-pyrazine-2-carboxamide [00053] 98 - 99 R.sub.t= 1.02 min (A); MS: m/z = 348 (M+1)

BIOLOGICAL EXAMPLES

Example B1: Alternaria Solani / Tomato / Leaf Disc (Early Blight)

[0246] Tomato leaf disks cv. Baby are placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf disks are incubated at 23° C. / 21° C. (day/night) and 80% rh under a light regime of 12/12 h (light/dark) 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 on untreated check disk leaf disks (5 - 7 days after application). The following compounds gave at least 80% control of Alternaria solani at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-4, P-5, P-9, P-13, P-16, P-20, P-22, P-25, P-28, P-30, P-37, P-38, P-39, P-41, P-43, and P-44.

Example B2: Glomerella Lagenarium (Colletotrichum Lagenarium) / Liquid Culture (Anthracnose)

[0247] 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. The following compounds gave at least 80% control of Glomerella lagenarium at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-1, P-2. P-3, P-4, P-5, P-6, P-8, P-9, P-10, P-11, P-12, P-13, P-14, P-15, P-16, P-17, P-18, P-19, P-20, P-21, P-22, P-23, P-24, P-25, P-26, P-27. P-28, P-29, P-30, P-31, P-32, P-33, P-34, P-35, P-36, P-37, P-38, P-39, P-40, P-41, P-43, P-44, P-45, P-46, P-47, P-48, P-49, and P-50,

Example B3:Blumeria Graminis F. Sp. Tritici (Erysiphe Graminis F. Sp. Trifici) / Wheat / Leaf Disc Preventative (Powdery Mildew On Wheat)

[0248] Wheat leaf segments cv. Kanzler are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated by shaking powdery mildew infected plants above the test plates 1 day after application. The inoculated leaf disks are incubated at 20° C. and 60% rh under a light regime of 24 h 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 leaf segments (6 - 8 days after application). The following compounds gave at least 80% control of Blumeria graminis f. sp. tritici at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-4, P-5, P-8, P-9, P-16, P-20, P-21, P-22, P-24, P-25, P-28, P-30, P-35, P-37, P-38, P-39, P-40, P-41, P-43, P-44, P-45, and P-50,

Example B4: Phaeosphaeria Nodorum (Septoria Nodorum / Wheat / Leaf Disc Preventative (Glume Blotch)

[0249] Wheat leaf segments cv. Kanzler are placed on agar in a multiwell plate (24-weli format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 2 days after application. The inoculated test leaf disks are incubated at 20° C. and 75% 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 percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application). The following compounds gave at least 80% control of Phaeosphaeria nodorum at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-29, P-38, P-39, P-43, and P-44.

Example B5: Monographella Nivalis (Microdochium Nivale) / Liquid Culture (Foot Rot Cereals)

[0250] 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. The following compounds gave at least 80% control of Monographella nivalis at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-1, P-2, P-3, P-4, P-5, P-6, P-7, P-8. P-9, P-10, P-11, P-12, P-13, P-14, P-15, P-16, P-17, P-18, P-19, P-20, P-21, P-22, P-24, P-25, P-29, P-30, P-32, P-37, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45, P-46, P-47, P-48, P-49, and P-50.

Example B6: Mycosphaerella Arachidis (Cercospora Arachidicola) / Liquid Culture (Early Leaf Spot)

[0251] 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. The following compounds gave at least 80% control of Mycosphaerella arachidis at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-1, P-4, P-5, P-9, P-13, P-16, P-20, P-22, P-24, P-25, P-29, P-30, P-38, P-39, P-40, P-43, P-44, and P-48,

Example B7: Phakopsora Pachyrhizi / Soybean / Preventative (Soybean Rust)

[0252] 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 - 14 days after application). The following compounds gave at least 80% control of Phakopsora pachyrhizi at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-4, P-37, P-38, P-41, P-43, and P-44,

Example B8: Puccinia Recondita F. Sp. Tritici / Wheat / Leaf Disc Preventative (Brown Rust)

[0253] Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments are incubated at 19° C. and 75% 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 percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 - 9 days after application). The following compounds gave at least 80% control of Puccinia recondita f. sp. tritici at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-4, P-5, P-9, P-20, P-22, P-25, P-29, P-34, P-37, P-38, P-39, P-40, P-41, P-43, P-44, and P-45.

Example B9: Magnaporthe Grisea (Pyricularia Oryzae) / Rice / Leaf Disc Preventative (Rice Blast)

[0254] 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). 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: P-5, P-6, P-13, P-14, P-16, P-19, P-20, P-21, P-22, P-23, P-25, P-26, P-28, P-29, P-30, P-34, P-35, P-36, P-37, P-38, P-39, P-40, P-41, P-42, P-43. P-44, P-45, P-47, P-49, and P-50.

Example B10: Pyrenophora Teres / Barley / Leaf Disc Preventative (Net Blotch)

[0255] 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 segments 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). The following compounds 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: P-5, P-25, P-37, P-38, P-39, P-41, P-43, P-44, and P-45.

Example B11: Sclerotinia Sclerotiorum / Liquid Culture (Cottony Rot)

[0256] Mycelia fragments of a newly grown liquid culture of the fungus 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 material is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 3-4 days after application. The following compounds 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: P-5, P-13, P-20, P-22, P-38, and P-42,

Example B12: Mycosphaerella Graminicola (Septoria Tritici) / Liquid Culture (Septoria Blotch)

[0257] 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. The following compounds gave at least 80% control of Mycosphaerella graminicola at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-1, P-2, P-4, P-5, P-9, P-11, P-12, P-13, P-14, P-15, P-16, P-20, P-21, P-22, P-24, P-25, P-29, P-30, P-31, P-32, P-37, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45, P-46, P-48, and P-49.

Example B13: Botryotinia Fuckeliana (Botrytis Cinerea) / Liquid Culture (Gray Mould)

[0258] 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. The following compound gave at least 80% control of Botryotinia fuckeliana at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: P-25.