MICROBIOCIDAL COMPOUNDS

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) ##STR00176## wherein X is CH or N; R.sup.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3alkyl and cyclopropyl; R.sup.2 is selected from the group consisting of hydrogen, halogen, methyl and methoxy; R.sup.3 is selected from the group consisting of hydrogen, halogen, methyl and methoxy; R.sup.4 is selected from the group consisting of hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.3alkynyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.3haloalkynyl, cyanoC.sub.1-C.sub.6alkyl-, cycloproylC.sub.1-C.sub.6alkyl-, methoxyC.sub.3-C.sub.6alkenyl-, cyclopropylC.sub.2-C.sub.6alkenyl-, methoxyC.sub.3-C.sub.4alkynyl-, cyclopropylC.sub.2-C.sub.3alkynyl-, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, cyclopropylC.sub.1-C.sub.6alkoxy-, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkoxy-, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.6haloalkylsulfanyl, methoxyC.sub.1-C.sub.6alkylsulfanyl-, cyclopropylC.sub.1-C.sub.6alkylsulfanyl-, C.sub.1-C.sub.3alkylsulfanylC.sub.1-C.sub.2alkyl-, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, methoxyC.sub.3-C.sub.6cycloalkyl-, cyclopropylC.sub.3-C.sub.6cycloalkyl-, C.sub.1-C.sub.2alkylC.sub.3-C.sub.6cycloalkyl-, —C(R.sup.6)═NOR.sup.6 and —CH.sub.2C(R.sup.6)═NOR.sup.6; R.sup.5 is selected from the group consisting of hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.3alkynyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.3haloalkynyl, cycloproylC.sub.1-C.sub.6alkyl-, methoxyC.sub.3-C.sub.6alkenyl-, cyclopropylC.sub.2-C.sub.6alkenyl-, methoxyC.sub.3-C.sub.4alkynyl-, cyclopropylC.sub.2-C.sub.3alkynyl-, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, cyclopropylC.sub.1-C.sub.6alkoxy-, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkoxy-, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.6haloalkylsulfanyl, methoxyC.sub.1-C.sub.6alkylsulfanyl-, cyclopropylC.sub.1-C.sub.6alkylsulfanyl-, C.sub.1-C.sub.3alkylsulfanylC.sub.1-C.sub.2alkyl-, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, methoxyC.sub.3-C.sub.6cycloalkyl-, cyclopropylC.sub.3-C.sub.6cycloalkyl-, C.sub.1-C.sub.2alkylC.sub.3-C.sub.6cycloalkyl-, —C(R.sup.6)═NOR.sup.6 and —CH.sub.2C(R.sup.6)═NOR.sup.6; and wherein R.sup.4 and R.sup.5 are not both hydrogen; each R.sup.6 is independently hydrogen or C.sub.1-C.sub.3alkyl; or an agronomically acceptable salt thereof; or an N-oxide thereof.

2. The compound according to claim 1, wherein R.sup.1 is selected from the group consisting of chloro, bromo, methyl, ethyl and cyclopropyl.

3. The compound according to claim 1, wherein R.sup.1 is methyl.

4. The compound according to claim 1, wherein R.sup.2 is hydrogen.

5. The compound according to claim 1, wherein R.sup.3 is hydrogen.

6. The compound according to claim 1, wherein R.sup.4 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.3-C.sub.6cycloalkyl and C.sub.3-C.sub.6halocycloalkyl.

7. The compound according to claim 1, wherein R.sup.4 is selected from the group consisting of chloro, bromo, iodo, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, trifluoromethyl, trifluoroethyl, iso-propyloxy, n-propyloxy, cyclopropyl and cyclobutyl.

8. The compound according to claim 1, wherein R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.3-C.sub.6cycloalkyl and C.sub.3-C.sub.6halocycloalkyl.

9. The compound according to claim 1, wherein R.sup.5 is selected from the group consisting of hydrogen, halogen, methyl and trifluoromethyl.

10. The compound according to claim 9, wherein R.sup.5 is hydrogen.

11. The compound according to claim 1, wherein X is CH.

12. An agrochemical composition comprising a fungicidally effective amount of a compound of formula (I) according to claim 1 and an agrochemically-acceptable diluent or carrier.

13. The composition according to claim 12, further comprising at least one additional active ingredient.

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 thereof, 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

[0271] 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 60 ppm, 20 ppm or 2 ppm.

[0272] 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).

[0273] 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 is as follows:

Method G:

[0274] Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 3.00 kV, Cone range: 30 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 50 I/h, Desolvation Gas Flow: 650 I/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment, diode-array detector and ELSD 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

Method H:

[0275] Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 3.00 kV, Cone range: 30V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 50 I/h, Desolvation Gas Flow: 650 I/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment, diode-array detector and ELSD 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

Method I:

[0276] 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 (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, Mass range: 140 to 800 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. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 μm; Temperature: 60° C., DAD Wavelength range (nm): 210 to 400. Solvent Gradient A: Water/Methanol 9:1,0.1% formic acid and Solvent B: Acetonitrile, 0.1% formic acid

TABLE-US-00001 Time Flow rate (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

Method J:

[0277] Spectra were recorded on a Mass Spectrometer 6410 Triple Quadruple Mass Spectrometer from Agilent Technologies equipped with an electrospray source (Positive and Negative Polarity Switch, Capillary (kV) 4.00, Scan Type MS2 Scan, Fragmentor (V) 100.00, Gas Temperature (° C.) 350, Gas Flow (L/min) 11, Nebulizer Gas (psi) 45, Mass range: 110 to 1000 Da) and an Agilent 1200 Series HPLC: DAD Wavelength range: 210 to 400 nm, Column: KINETEX EVO C18, Column length: 50 mm, Internal diameter of column: 4.6 mm, Particle Size: 2.6 μm, Column oven temperature: 40° C.

Gradient Conditions:

[0278] Solvent A: Water with 0.1% formic acid:Acetonitrile: 95:5 v/v

[0279] Solvent B: Acetonitrile with 0.1% formic acid

TABLE-US-00002 Time Flow rate (minutes) A (%) B (%) (ml/min) 0 90 10 1.8 0.9 0 100 1.8 1.8 0 100 1.8 2.2 90 10 1.8 2.5 90 10 1.8

[0280] 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

[0281]

TABLE-US-00003 Wettable powders a) b) c) active ingredient 25%  50% 75% [compound of formula (I)] sodium lignosulfonate 5%  5% — sodium lauryl sulfate 3% —  5% sodium —  6% 10% diisobutylnaphthalenesulfonate phenol polyethylene glycol ether —  2% — (7-8 mol of ethylene oxide) highly dispersed silicic acid 5% 10% 10% Kaolin 62%  27% —

[0282] 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-00004 Powders for dry seed treatment a) b) c) active ingredient 25% 50% 75% [compound of formula (I)] light mineral oil  5%  5%  5% highly dispersed silicic acid  5%  5% — Kaolin 65% 40% — Talcum — 20%

[0283] 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-00005 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  4% ethylene oxide) Cyclohexanone 30% xylene mixture 50%

[0284] Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

TABLE-US-00006 Dusts a) b) 0) Active ingredient  5%  6%  4% [compound of formula (I)] Talcum 95% — — Kaolin — 94% — mineral filler — — 96%

[0285] 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-00007 Extruder granules Active ingredient [compound of formula (I)] 15% sodium lignosulfonate  2% Carboxymethylcellulose  1% Kaolin 82%

[0286] 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-00008 Coated granules Active ingredient [compound of formula (I)] 8% polyethylene glycol (mol. wt. 200) 3% Kaolin 89% 

[0287] 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-00009 Suspension concentrate active ingredient [compound of formula (I)] 40% propylene glycol 10% nonylphenol polyethylene glycol ether  6% (15 mol of ethylene oxide) Sodium lignosulfonate 10% Carboxymethylcellulose  1% silicone oil (in the form of a 75%  1% emulsion in water) Water 32%

[0288] 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-00010 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 0.5%.sup.  a 20% solution in water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% 0.2%.sup.  emulsionin water) Water 45.3%  

[0289] 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

[0290] 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.

[0291] 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.

[0292] The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

List of Abbreviations

[0293] CDCl.sub.3=chloroform-d [0294] ° C.=degrees Celsius [0295] DCM=dichloromethane [0296] DMF=dimethylformamide [0297] DMSO=dimethyl sulfoxide [0298] d=doublet [0299] EtOAc=ethyl acetate [0300] h=hour(s) [0301] HCl=hydrochloric acid [0302] M=molar [0303] min=minutes [0304] MHz=mega hertz [0305] mp=melting point [0306] Pd.sub.2(dba).sub.3=Tris(dibenzylideneacetone)dipalladium(0) [0307] ppm=parts per million [0308] RT=room temperature [0309] Rt=retention time [0310] rh=relative humidity [0311] s=singlet [0312] =triplet [0313] THF=tetrahydrofuran [0314] LCMS=Liquid Chromatography Mass Spectrometry (description of the apparatus and the [0315] methods used for LC/MS analysis are given above)

PREPARATION EXAMPLES

Example A1: Preparation of methyl (Z)-2-[5-(4-cyclopropyltriazol-2-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (F-8)

Step 1:

[0316] To a solution of 5-bromo-2-methylphenol (53.47 mmol, 10.00 g) and methyl 2-bromoacetate (1.5 equiv., 80.20 mmol, 12.27 g, 7.44 mL) in tetrahydrofuran (0.5 mol/L, 106.9 mL) at room temperature was added potassium carbonate (2 equiv., 106.9 mmol, 14.78 g), and the light brown suspension was heated to 65° C. for 2 h and then allowed to cool down to room temperature overnight. The reaction mixture was diluted with EtOAc and washed with water. The aqueous phase was extracted with EtOAc, and the total combined organic layer was washed with water, brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo to give methyl 2-(5-bromo-2-methyl-phenoxy)acetate (47.22 mmol, 15.89 g, 88% yield) as a brown liquid. The crude oil was slightly contaminated with residual methyl-2-bromoacetate, but was taken directly to the next step without further purification.

[0317] LCMS (Method H), Rt=1.59 min, MS: (M+1)=259, 261; .sup.1H NMR (400 MHz, CDCl3) δ ppm 2.25 (s, 3H) 3.84 (s, 3H) 4.66 (s, 2H) 6.84 (d, 1H) 7.05 (m, 2H)

Step 2:

[0318] Part 1: To a solution of 2-(5-bromo-2-methyl-phenoxy)acetate (20.8 g, 80.3 mmol) and methyl formate (6.0 equiv., 482 mmol, 29.5 g, 30.5 mL) in tetrahydrofuran (0.5 mol/L, 161 mL) at room temperature under argon was added sodium methoxide (20 equiv., 161 mmol, 9.13 g) portionwise. The reaction was slightly exothermic and was kept below 30° C. with the assistance of a room temperature water bath. The reaction mixture was stirred at room temperature for 1 h and quenched by the slow addition of an aqueous saturated solution of NaHCO.sub.3. The two phases were separated and the aqueous phase was extracted with EtOAc. The total combined organic layer was washed with aqueous saturated solution of NaHCO.sub.3, brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo to give methyl-2-(5-bromo-2-methyl-phenoxy)-3-hydroxy-prop-2-enoate, which was taken directly to the next step without further purification.

[0319] LCMS (Method G), Rt=0.80 and 0.90 min, MS: (M+1)=287, 289

[0320] Part 2: To a solution of the crude methyl-2-(5-bromo-2-methyl-phenoxy)-3-hydroxy-prop-2-enoate and dimethyl sulfate (1.2 equiv., 93.2 mmol, 11.8 g, 8.8 mL) in DMF (0.5 mol/L, 155 mL) at room temperature under argon was added potassium carbonate (1.5 equiv., 117 mmol, 16.3 g), and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched by the slow addition of water, and the mixture was extracted with EtOAc. The total combined organic layer was washed with aqueous saturated solution of NaHCO.sub.3, brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane:EtOAc) to give methyl (Z)-2-(5-bromo-2-methyl-phenoxy)-3-methoxy-prop-2-enoate (59.6 mmol, 18.0 g, 75% yield) as an off-white solid. LCMS (Method G), Rt=1.02 min, MS: (M+1)=301, 303; .sup.1H NMR (400 MHz, CDCl3) δ ppm 2.31 (s, 3H) 3.74 (s, 3H) 3.91 (s, 3H) 6.86 (d, 1H) 7.05 (m, 2H) 7.35 (s, 1H)

Step 3:

[0321] A solution of Tetramethyl-t-BuXphos (0.10 equiv., 0.066 mmol, 0.033 g) and Pd.sub.2(dba).sub.3 (0.05 equiv., 0.033 mmol, 0.031 g) in 1 mL toluene under argon was heated at 110° C. for 3 minutes, and the mixture was then allowed to cool down to room temperature. The pre-formed palladium catalyst was transferred to a mixture of methyl (Z)-2-(5-bromo-2-methyl-phenoxy)-3-methoxy-prop-2-enoate (0.66 mmol, 0.20 g), 4-cyclopropyl-2H-triazole (1.1 equiv., 0.73 mmol, 0.080 g) and potassium carbonate (2.0 equiv., 1.33 mmol, 0.184 g) in toluene (0.2 mol/L, 3.3 mL) at room temperature and the obtained dark brown suspension was heated to 110° C. for 1 h. The reaction mixture was allowed to cool down to room temperature, then EtOAc was added. The organic phase was washed with water, and the aqueous was extracted with EtOAc. The total combined organic layer was washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane:EtOAc) to give methyl (Z)-2-[5-(4-cyclopropyltriazol-2-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (0.23 mmol, 0.075 g, 34% yield).

[0322] LCMS (Method G), Rt=1.07 min, MS: (M+1)=330; .sup.1H NMR (400 MHz, CDCl3) δ ppm 0.88 (m, 2H) 1.04 (m, 2H) 2.03 (m, 1H) 2.40 (s, 3H) 3.74 (s, 3H) 3.91 (s, 3H) 7.24 (d, 1H) 7.40 (s, 1H) 7.41 (d, 1H) 7.46 (s, 1H) 7.58 (dd, 1H)

Example A2: Preparation of methyl (Z)-3-methoxy-2-[2-methyl-5-[3-(trifluoromethyl)pyrazo]-1-yl]phenoxy]prop-2-enoate (E-105)

[0323] A solution of Tetramethyl-t-BuXphos (0.10 equiv., 0.050 mmol, 0.025 g) and Pd.sub.2(dba).sub.3 (0.05 equiv., 0.025 mmol, 0.024 g) in 1 mL toluene under argon was heated at 110° C. for 3 minutes. This mixture was then allowed to cool down to room temperature. The pre-formed active palladium catalyst was transferred to a mixture of methyl (Z)-2-(5-bromo-2-methyl-phenoxy)-3-methoxy-prop-2-enoate (0.50 mmol, 0.15 g), 3-(trifluoromethyl)-1H-pyrazole (1.2 equiv., 0.60 mmol, 0.082 g) and potassium carbonate (2.0 equiv., 1.0 mmol, 0.138 g) in toluene (0.2 mol/L, 2.5 mL) at room temperature and the obtained dark brown suspension was heated to 110° C. for 1 h. The reaction mixture was allowed to cool down to room temperature, then EtOAc was added. The organic phase was washed with water, and the aqueous was extracted with EtOAc. The total combined organic layer was washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane:EtOAc) to give methyl (Z)-3-methoxy-2-[2-methyl-5-[3-(trifluoromethyl)pyrazo]-1-yl]phenoxy]prop-2-enoate (0.28 mmol, 0.10 g, 56% yield) as a white solid.

[0324] mp: 154-156° C.; LCMS (Method G), Rt=1.07 min, MS: (M+1)=357; .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 2.40 (s, 3H) 3.75 (s, 3H) 3.93 (s, 3H) 6.69 (m, 1H) 7.10 (d, 1H) 7.19-7.30 (m, 2H) 7.40 (s, 1H) 7.87 (m, 1H)

Example A3: Preparation of methyl (Z)-2-[5-(3-iodopyrazol-1-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (E-78)

Step 1:

[0325] To a solution of methyl (Z)-2-(5-bromo-2-methyl-phenoxy)-3-methoxy-prop-2-enoate (66.4 mmol, 20.0 g) in 1,4-dioxane (133 mL) at room temperature were added bis(pinacolato)diboron (1.10 equiv., 73.1 mmol, 18.7), potassium acetate (2.00 equiv., 133 mmol, 13.6 g) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.025 equiv., 1.66 mmol, 1.38 g), and the reaction mixture was then heated at 100° C. (inside temperature 94° C.) for 90 min. The dark brown suspension was diluted with EtOAc and water was added. The layers were separated and the aqueous phase was extracted with EtOAc. The total combined organic layer was washed with brine, dried with Na.sub.2SO.sub.4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane:EtOAc) to give a beige wet crystalline solid, which was triturated with a small amount of hexane, filtered and dried in vacuo to give methyl (Z)-3-methoxy-2-[2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]prop-2-enoate (32.6 mmol, 12.0 g, 49% yield) as a white solid.

[0326] LCMS (Method H), Rt=1.82 min, MS: (M+1)=349; .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.34 (s, 12H) 2.39 (s, 3H) 3.72 (s, 3H) 3.89 (s, 3H) 7.12 (s, 1H) 7.19 (d, 1H) 7.34 (s, 1H) 7.39 (d, 1H)

Step 2:

[0327] To a solution of methyl (Z)-3-methoxy-2-[2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]prop-2-enoate (14.4 mmol, 5.00 g) in tetrahydrofuran:water mixture (4:1 V/V, 72 mL) was added sodium periodate (3.00 equiv., 43.1 mmol, 9.31 g) followed by a solution of hydrochloric acid (2.0 M, 0.25 equiv., 3.59 mmol, 1.79 mL). The obtained white suspension was stirred at room temperature for 4 h, then EtOAc and water were added. The layers were separated, and the aqueous phase was extracted with EtOAc. The total combined organic layer was washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo to give [3-[(Z)-2-methoxy-1-methoxycarbonyl-vinyloxy]-4-methyl-phenyl]boronic acid (12.1 mmol, 3.58 g, 84% yield) as a white solid.

[0328] LCMS (Method H), Rt=1.00 min, MS: (M+H)=367; .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 2.23 (s, 3H) 3.64 (s, 3H) 3.85 (s, 3H) 7.12 (m, 2H) 7.33 (d, 1H) 7.54 (s, 1H) 7.96 (brs, 2H)

Step 3:

[0329] To a suspension of [3-[(Z)-2-methoxy-1-methoxycarbonyl-vinyloxy]-4-methyl-phenyl]boronic acid (0.28 mmol, 0.075 g), 3-iodo-1h-pyrazole (1.1 equiv., 0.31 mmol, 0.060 g) and sodium carbonate (1.5 equiv., 0.42 mmol, 0.045 g) in N,N-dimethylacetamide (0.33 mol/L, 0.85 mL) at room temperature under air, were added copper(II) acetate (0.25 equiv., 0.070 mmol, 0.013 g) and pyridine (0.50 equiv., 0.141 mmol, 0.011 g, 0.012 mL), and the reaction mixture was heated at 80° C. overnight. The mixture was diluted with EtOAc and quenched with an aqueous solution of NH.sub.4Cl (2.5 mol/L). The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by flash chromatography to give methyl (Z)-2-[5-(3-iodopyrazol-1-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (0.12 mmol, 0.057 g, 44% yield) as a white solid.

[0330] mp: 156-159° C.; LCMS (Method H), Rt=1.69 min, MS: (M+1)=415; .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 2.39 (s, 3H) 3.74 (s, 3H) 3.92 (s, 3H) 6.60 (d, 1H) 7.06 (d, 1H) 7.14 (dd, 1H) 7.22 (d, 1H) 7.38 (s, 1H) 7.66 (d, 1H)

Example A4: Preparation of methyl (Z)-2-[5-(3-cyclohexylpyrazol-1-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (E-36)

Step 1:

[0331] Procedure: To a solution of methyl (Z)-2-[5-(3-iodopyrazol-1-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (0.18 mmol, 0.075 g), cesium carbonate (2.5 equiv., 0.45 mmol, 0.148 g) and cyclohex-1-en-1-ylboronic acid (1.75 equiv., 0.32 mmol, 0.040 g) in 1,4-dioxane (0.25 mol/L, 0.73 mL) and water (0.40 mL/mmol, 0.072 mL) at room temperature was added CATACXIUM-A® Pd-G3 (0.10 equiv., 0.018 mmol, 0.014 g), and the reaction mixture was heated at 100° C. for 80 min. The reaction mixture was allowed to cool down to room temperature, filtered over a pad of Na.sub.2SO.sub.4. The pad was washed with EtOAc, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography to give methyl (Z)-2-[5-[3-(cyclohexen-1-yl)pyrazol-1-yl]-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (0.10 mmol, 0.040 g, 57% yield) as a beige solid.

[0332] mp: 108-110° C.; LCMS (Method H), Rt=2.05 min, MS: (M+1)=369; .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.69 (m, 2H) 1.78 (m, 2H) 2.23 (m, 2H) 2.36 (s, 3H) 2.52 (m, 2H) 3.72 (s, 3H) 3.90 (s, 3H) 6.40 (m, 1H) 6.46 (d, 1H) 7.09 (s, 1H) 7.19 (m, 2H) 7.36 (s, 1H) 7.74 (d, 1H)

Step 2:

[0333] To a solution of methyl (Z)-2-[5-[3-(cyclohexen-1-yl)pyrazol-1-yl]-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (0.060 mmol, 0.022 g) in ethyl acetate (0.1 mol/L, 0.60 mL) and n-hexane (0.1 mol/L, 0.60 mL) at room temperature was added Pd/C (5% wt, 0.05 equiv., 0.006 g). The reaction mixture was purged with hydrogen gas using a balloon. The reaction mixture was stirred at room temperature until no more starting material was observed by LCMS. The black suspension was filtered through a pad of celite and silica and washed with EtOAc. The filtrate was concentrated in vacuo to give methyl (Z)-2-[5-(3-cyclohexylpyrazol-1-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate (0.049 mmol, 0.020 g, 81% yield) as a beige solid.

[0334] mp: 85-89° C.; LCMS (Method H), Rt=2.06 min, MS: (M+1)=371; .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.39-1.50 (m, 4H) 1.54-1.59 (m, 1H) 1.72-1.79 (m, 1H) 1.80-1.88 (m, 2H) 2.02 (m, 2H) 2.37 (s, 3H) 2.71-2.82 (m, 1H) 3.73 (s, 3H) 3.91 (s, 3H) 6.24 (d, 1H) 7.05 (s, 1H) 7.19 (m, 2H) 7.37 (s, 1H) 7.72 (d, 1H)

TABLE-US-00011 TABLE E Physical data of compounds of formula (I) Mass Rt charge LCMS mp Entry Structure Name (min) [M + H] Method (° C.) E-1 [00025] methyl (Z)-2-[5-[3-(2- cyclopropylethynyl)pyra- zol-1-yl]-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.57 353 J .sup.  158- 162 E-2 [00026] methyl (Z)-3-methoxy- 2-[2-methyl-5-(3-prop- 1-ynylpyrazol-1- yl)phenoxy]prop-2- enoate 1.51 327 J .sup.  175- 179 E-3 [00027] methyl (Z)-2-[3-fluoro- 2-methyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.58 375 J .sup.  133- 135 E-4 [00028] methyl (Z)-2-[5-[3-(1- ethylpropyl)pyrazol-1- yl]-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.18 359 G .sup.  108- 111 E-5 [00029] methyl (Z)-2-[5-(3- cyclopentylpyrazol-1- yl)-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.16 357 G E-6 [00030] methyl (Z)-2-[5-(4- chloro-3-propyl- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.19 365 G E-7 [00031] methyl (Z)-2-[3-fluoro- 5-(3-isopropylpyrazol- 1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.59 349 J .sup.  114- 116 E-9 [00032] methyl (Z)-3-methoxy- 2-[3-(3-methylpyrazol- 1-yl)phenoxy]prop-2- enoate 0.90 289 G E-10 [00033] methyl (Z)-2-[5-(4- bromo-3-cyclohexyl- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.32 451 G .sup.  120- 126 E-11 [00034] methyl (Z)-2-[5-(4- chloro-3-isopropyl- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.20 365 G  .sup.  95- 100 E-12 [00035] methyl (Z)-2-[5-(4- chloro-3-isopropoxy- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.17 381 G .sup.  104- 107 E-13 [00036] methyl (Z)-3-methoxy- 2-[2-methyl-5-(3- propoxypyrazol-1- yl)phenoxy]prop-2- enoate 1.56 347 J  .sup.  85-  87 E-14 [00037] methyl (Z)-2-[3-(3- cyclopropylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 0.98 315 G E-15 [00038] methyl (Z)-3-methoxy- 2-[3-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.02 343 G E-16 [00039] methyl (Z)-2-[2,4- dimethyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.56 371 J  .sup.  96-  98 E-17 [00040] methyl (Z)-2-[2,4- dimethyl-5-(3- methylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 1.42 317 J .sup.  123- 124 E-18 [00041] methyl (Z)-2-[5-(3- cyclobutylpyrazol-1-yl)- 4-fluoro-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.89 361 H E-19 [00042] methyl (Z)-2-[2,3- dimethyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.56 371 J .sup.  144- 146 E-20 [00043] methyl (Z)-2-[5-(3- isopropylpyrazol-1-yl)- 2,3-dimethyl-phenoxy]- 3-methoxy-prop-2- enoate 1.56 345 J .sup.  103- 105 E-21 [00044] methyl (Z)-2-[5-(3- isopropylpyrazol-1-yl)- 3-methoxy-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.56 361 J  .sup.  90-  92 E-22 [00045] methyl (Z)-3-methoxy- 2-[3-methoxy-2-methyl- 5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.53 387 J .sup.  153- 156 E-23 [00046] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3-(2,2,2- trifluoro-1-methyl- ethyl)pyrazol-1- yl]phenoxy]prop-2- enoate 1.82 385 H .sup.  119- 122 E-24 [00047] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3-[1- (trifluoromethyl)vinyl] pyrazol-1- yl]phenoxy]prop-2- enoate 1.87 383 H E-25 [00048] methyl (Z)-2-[5-(3- isopropylpyrazol-1-yl)- 2,4-dimethyl-phenoxy]- 3-methoxy-prop-2- enoate 1.54 345 J  .sup.  96-  98 E-26 [00049] methyl (Z)-2-[5-[3-(2,2- difluorocyclopropyl) pyrazol-1-yl]-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.68 365 H E-27 [00050] methyl (Z)-2-[4-chloro- 2-methyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.59 391 J E-28 [00051] methyl (Z)-2-[4-chloro- 2-methyl-5-(3- methylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 1.48 337 J E-29 [00052] methyl (Z)-2-[4-chloro- 5-(3-isopropylpyrazol- 1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.58 365 J  .sup.  96-  98 E-30 [00053] methyl (Z)-3-methoxy- 2-[5-[3-(N-methoxy-C- methyl- carbonimidoyl)pyrazol- 1-yl]-2-methyl- phenoxy]prop-2-enoate 1.72 1.75 360 H .sup.  130- 133 E-31 [00054] methyl (Z)-2-[5-(3- isopropylpyrazol-1-yl)- 4-methoxy-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.56 361 J E-32 [00055] methyl (Z)-3-methoxy- 2-[4-methoxy-2-methyl- 5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.54 387 J .sup.  130- 133 E-33 [00056] methyl (Z)-2-[5-[3- (cyanomethyl)pyrazol- 1-yl]-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.38 328 H .sup.  120- 123 E-34 [00057] methyl (Z)-3-methoxy- 2-[3-methyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.54 357 J E-35 [00058] methyl (Z)-2-[3-(3- isopropylpyrazol-1-yl)- 5-methyl-phenoxy]-3- methoxy-prop-2-enoate 1.54 331 J E-36 [00059] methyl (Z)-2-[5-(3- cyclohexylpyrazol-1-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate 2.06 371 H  .sup.  85-  89 E-37 [00060] methyl (Z)-3-methoxy- 2-[4-methoxy-2-methyl- 5-(3-methylpyrazol-1- yl)phenoxy]prop-2- enoate 1.40 333 J  .sup.  99- 101 E-38 [00061] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3-[(E)- prop-1-enyl]pyrazol-1- yl]phenoxy]prop-2- enoate 1.72 328 H .sup.  110- 112 E-39 [00062] methyl (Z)-2-[5-[3- (cyclohexen-1- yl)pyrazol-1-yl]-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 2.05 369 H .sup.  108- 110 E-40 [00063] methyl (Z)-3-methoxy- 2-[2-methyl-5-(3- propylpyrazol-1- yl)phenoxy]prop-2- enoate 1.77 331 H  .sup.  91-  94 E-41 [00064] methyl (Z)-2-[4-fluoro- 5-(3-isopropylpyrazol- 1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.58 349 J E-42 [00065] methyl (Z)-2-[4-fluoro- 2-methyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.54 375 J .sup.  104- 108 E-43 [00066] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3-[(E)-1- methylprop-1- enyl]pyrazol-1- yl]phenoxy]prop-2- enoate 1.90 343 H .sup.  115- 118 E-44 [00067] methyl (Z)-3-methoxy- 2-[2-methyl-5-(3-sec- butylpyrazol-1- yl)phenoxy]prop-2- enoate 1.90 345 H .sup.  110- 113 E-45 [00068] methyl (Z)-3-methoxy- 2-[2-methyl-5-(3- vinylpyrazol-1- yl)phenoxy]prop-2- enoate 1.61 315 H .sup.  114- 117 E-46 [00069] methyl (Z)-2-[5-(4- fluoro-3-isopropyl- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.92 349 H .sup.  111- 113 E-47 [00070] methyl (Z)-2-[5-(4- bromopyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.65   366.97 I E-48 [00071] methyl (Z)-2-[5-(4- ethynylpyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.54   313.06 I E-49 [00072] methyl (Z)-2-[5-(4-tert- butylpyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.83   345.13 I E-50 [00073] methyl (Z)-2-[5-(4- cyclopropylpyrazol-1- yl)-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.64   329.10 I E-51 [00074] methyl (Z)-3-methoxy- 2-[5-[4- (methoxymethyl)pyrazol- 1-yl]-2-methyl- phenoxy]prop-2-enoate 1.37   333.09 I E-52 [00075] methyl (Z)-2-[5-(4- ethoxypyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.54   333.07 I E-53 [00076] methyl (Z)-2-[5-(4- isopropylsulfanylpyrazol- 1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.81   363.08 I E-54 [00077] methyl (Z)-2-[5-(4- chloropyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.62   322.07 I E-55 [00078] methyl (Z)-2-[5-(4- cyanopyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.42   314.07 I E-56 [00079] methyl (Z)-2-[5-(4- ethylpyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.63   317.08 I E-57 [00080] methyl (Z)-2-[5-(4- isopropylpyrazol-1-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate 1.74   331.11 I E-58 [00081] methyl (Z)-2-[5-(4- cyclopentylpyrazol-1- yl)-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.90   357.11 I E-59 [00082] methyl (Z)-3-methoxy- 2-[2-methyl-5-(4- methylpyrazol-1- yl)phenoxy]prop-2- enoate 1.50   303.03 I E-60 [00083] methyl (Z)-2-[5-(4- iodopyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.69   414.98 I E-61 [00084] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3- (trifluoromethylsulfanyl) pyrazol-1- yl]phenoxy]prop-2- enoate 1.88 389 H .sup.  137- 139 E-64 [00085] methyl (Z)-2-[4-fluoro- 2-methyl-5-(3- methylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 1.43 321 J .sup.  134- 138 E-65 [00086] methyl (Z)-2-[5-(3- isopropenylpyrazol-1- yl)-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.81 329 H  .sup.  80-  84 E-66 [00087] methyl (Z)-2-[5-[3- (difluoromethoxy)pyrazol- 1-yl]-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.67 355 H .sup.  123- 126 E-67 [00088] methyl (Z)-2-[5-[3-(1- fluorocyclopropyl)pyrazol- 1-yl]-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.73 347 H .sup.  128- 131 E-68 [00089] methyl (Z)-2-[5-[3-(1,1- difluoroethyl)pyrazol-1- yl]-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.74 353 H .sup.  119- 121 E-69 [00090] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3- (1,1,2,2,2- pentafluoroethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.94 407 H .sup.  117- 120 E-70 [00091] methyl (Z)-2-[5-(3- isopropoxypyrazol-1- yl)-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.78 347 H  .sup.  94-  97 E-75 [00092] methyl (Z)-3-methoxy- 2-[2-methyl-5-[4- methyl-3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.88 371 H .sup.  131- 134 E-76 [00093] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3- (methylsulfanylmethyl) pyrazol-1- yl]phenoxy]prop-2- enoate 1.61 349 H  .sup.  78-  80 E-77 [00094] methyl (Z)-3-methoxy- 2-[5-[3- (methoxymethyl)pyrazol- 1-yl]-2-methyl- phenoxy]prop-2-enoate 1.41 333 H .sup.  107- 110 E-78 [00095] methyl (Z)-2-[5-(3- iodopyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.69 415 H .sup.  156- 159 E-80 [00096] methyl (Z)-2-[5-(4- cyclobutylpyrazol-1-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate 1.82 343 H E-81 [00097] methyl (Z)-3-methoxy- 2-[2-methyl-5-[4- (trifluoromethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.75 357 H .sup.  102- 105 E-82 [00098] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3-(1- methylcyclopropyl)pyra- zol-1-yl]phenoxy]prop- 2-enoate 1.85 343 H  .sup.  83-  86 E-83 [00099] methyl (Z)-2-[5-(3- bromopyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.64 367/369 H .sup.  106- 110 E-84 [00100] methyl (Z)-2-[2-bromo- 5-(3-bromopyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 1.04 431/433/ 435 G E-85 [00101] methyl (Z)-2-[2-bromo- 5-(3-chloropyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 1.03 387/389 G E-86 [00102] methyl (Z)-2-[2-bromo- 5-[3- (difluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.01 403/405 G E-87 [00103] methyl (Z)-2-[2-bromo- 5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.08 421/423 G E-88 [00104] methyl (Z)-2-[5-(3- cyclobutylpyrazol-1-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate 1.76   343.25 I  .sup.  91-  94 E-89 [00105] methyl (Z)-2-[5-(3- cyanopyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.47   314.2 I E-90 [00106] methyl (Z)-2-[5-(3- isobutylpyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.82   345.27 I  .sup.  76-  80 E-91 [00107] methyl (Z)-2-[5-(3- ethylpyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.57   317.24 I E-92 [00108] methyl (Z)-2-[5-(3- isopropylpyrazol-1-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate 1.72   331.26 I  .sup.  88-  91 E-94 [00109] methyl (Z)-2-[5-(3- ethoxypyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.59   333.23 I  .sup.  94-  96 E-95 [00110] methyl (Z)-3-methoxy- 2-[5-(3- methoxypyrazol-1-yl)-2- methyl-phenoxy]prop- 2-enoate 1.47   319.21 I .sup.  120- 123 E-96 [00111] methyl (Z)-2-[5-[3- (difluoromethyl)pyrazol- 1-yl]-2-methyl- phenoxy]-3-methoxy- prop-2-enoate 1.53   339.19 I E-97 [00112] methyl (Z)-2-[2-bromo- 5-(3- cyclopropylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 1.01 393/395 G E-98 [00113] methyl (Z)-2-[2-chloro- 5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate 1.06 377/379 G E-99 [00114] methyl (Z)-2-[2-chloro- 5-(3- cyclopropylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate 1.03 349/351 G E-100 [00115] methyl (Z)-2-[5-(3- chloropyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.02 323/325 G .sup.  150- 152 E-101 [00116] methyl (Z)-2-[5-(3- cyclopropylpyrazol-1- yl)-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate 1.03 329 G .sup.  115- 118 E-103 [00117] methyl (Z)-2-[5-(3-tert- butylpyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate 1.13 345 G E-104 [00118] methyl (Z)-3-methoxy- 2-[2-methyl-5-(3- methylpyrazol-1- yl)phenoxy]prop-2- enoate 0.95 303 G E-105 [00119] methyl (Z)-3-methoxy- 2-[2-methyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]prop-2- enoate 1.07 357 G .sup.  154- 156 E-106 [00120] methyl (Z)-2-[2- cyclopropyl-5-(3- methylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate .sup.  189- 191 E-107 [00121] methyl (Z)-2-[2-ethyl-5- (3-methylpyrazol-1- yl)phenoxy]-3-methoxy- prop-2-enoate .sup.  169- 171 E-108 [00122] methyl (Z)-2-[2- cyclopropyl-5-[3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate .sup.  130- 132 E-109 [00123] methyl (Z)-2-[2-ethyl-5- [3- (trifluoromethyl)pyrazol- 1-yl]phenoxy]-3- methoxy-prop-2-enoate .sup.  135- 137 E-110 [00124] methyl (Z)-2-[5-(3- cyclohexylpyrazol-1-yl)- 2,3-dimethyl-phenoxy]- 3-methoxy-prop-2- enoate  .sup.  90-  93 E-111 [00125] methyl (Z)-2-[5-(3,4- dichloropyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate .sup.  140- 144 E-112 [00126] methyl (Z)-2-[5-(4- chloro-3-cyclohexyl- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate .sup.  150- 152 E-113 [00127] methyl (Z)-2-[5-(3- cyclohexyl-4-methyl- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate .sup.  145- 148 E-114 [00128] methyl (Z)-2-[5-(3- cyclohexylpyrazol-1-yl)- 4-fluoro-2-methyl- phenoxy]-3-methoxy- prop-2-enoate E-115 [00129] methyl (Z)-2-[4-chloro- 5-(3-cyclohexylpyrazol- 1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate .sup.  127- 129 E-116 [00130] methyl (Z)-2-[5-(3,4- dimethylpyrazol-1-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate .sup.  155- 157 E-117 [00131] methyl (Z)-2-[5-(4- bromo-3-methyl- pyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy- prop-2-enoate .sup.  120- 122 E-118 [00132] methyl (Z)-2-[5-[3- [chloro(difluoro)methyl] pyrazol-1-yl]-2-methyl- phenoxy]-3-methoxy- prop-2-enoate .sup.  146- 148

TABLE-US-00012 TABLE F Physical data of compounds of formula (I) Mass Rt charge LCMS mp Entry Structure Name (min) [M + H] Method (° C.) F-1 methyl (Z)-2-[5-(4- bromotriazol-2-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate [00133] 1.10 368, 370 G F-2 methyl (Z)-3-methoxy-2- [2-methyl-5-(4- propyltriazol-2- yl)phenoxy]prop-2- enoate [00134] 1.15 332 G F-3 methyl (Z)-2-[5-(4- butyltriazol-2-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate [00135] 68- 70 F-4 methyl (Z)-2-[5-(4- isopropyltriazol-2-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate [00136] 1.14 332 G F-5 methyl (Z)-2-[5-(4- cyclopentyltriazol-2-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate [00137] 1.22 358 G F-6 methyl (Z)-3-methoxy-2- [2-methyl-5-[4- (trifluoromethyl)triazol- 2-yl]phenoxy]prop-2- enoate [00138] 107- 109 F-7 methyl (Z)-2-[5-(4- cyclohexyltriazol-2-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate [00139] 120- 122 F-8 methyl (Z)-2-[5-(4- cyclopropyltriazol-2-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate [00140] 1.07 30 G F-9 methyl (Z)-2-[3-(4- cyclopropyltriazol-2- yl)phenoxy]-3-methoxy- prop-2-enoate [00141] 1.01 316 G F-10 methyl (Z)-2-[5-(4,5- dibromotriazol-2-yl)-2- methyl-phenoxy]-3- methoxy-prop-2-enoate [00142] 1.20 446, 448, 450 G F-11 methyl (Z)-2-[5-(4- isopropenyltriazol-2-yl)- 2-methyl-phenoxy]-3- methoxy-prop-2-enoate [00143] 1.15 330 G F-12 methyl (Z)-2-[5-[4-(N- ethoxy-C-methyl- carbonimidoyl)triazol-2- yl]-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate [00144] 113- 116 F-13 methyl (Z)-2-[5-[4-(N- hydroxy-C-methyl- carbonimidoyl)triazol-2- yl]-2-methyl-phenoxy]- 3-methoxy-prop-2- enoate [00145] 146- 150

Example B: Biological Examples/Test Methods

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

[0335] 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 (relative humidity) 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).

[0336] 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:

[0337] E-1, E-15, E-16, E-17, E-21, E-27, E-29, E-30, E-34, E-36, E-39, E-57, E-58, E-60, E-64, E-67, E-68, E-70, E-80, E-82, E-83, E-85, E-88, E-98, E-99, E-105, E-113, F-1, F-2, F-4, F-5, F-10, F-13

Example B2: Botryotinia fuckeliana (Botrytis cinerea)/Liquid Culture (Gray Mould)

[0338] 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.

[0339] The following compounds 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:

[0340] E-5, E-6, E-16, E-23, E-24, E-25, 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-42, E-43, E-44, E-46, E-47, E-48, E-49, E-50, E-51, E-52, E-53, E-54, E-55, E-57, E-58, E-59, E-60, E-61, E-64, E-65, E-66, E-75, E-80, E-81, E-82, E-85, E-86, E-87, E-88, E-90, E-91, E-92, E-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-116, F-8

Example B3: Glomerella lagenarium (Colletotrichum lagenarium)/Liquid Culture (Anthracnose)

[0341] 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.

[0342] 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:

[0343] E-5, E-6, E-7, E-12, E-14, E-15, E-16, E-18, E-19, E-20, E-21, 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-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-57, E-58, E-59, E-60, E-61, E-64, E-65, E-66, E-67, E-68, E-69, E-70, E-77, E-78, E-80, E-81, E-82, E-83, E-84, E-85, E-86, E-87, E-88, E-90, E-91, E-92, E-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-110, E-111, E-112, E-113, E-114, E-115, E-116, E-117, E-118, 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

Example B4: Blumeria Graminis f. Sp. tritici (Erysiphe graminis f. Sp. tritici)/Wheat/Leaf Disc Preventative (Powdery Mildew on Wheat)

[0344] 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).

[0345] 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:

[0346] E-3, E-4, E-7, E-15, E-16, E-17, E-18, E-19, E-22, E-24, E-25, E-26, E-27, E-28, E-29, E-32, E-34, E-35, E-38, E-39, E-40, E-41, E-42, E-44, E-45, E-47, E-48, E-50, E-51, E-54, E-57, E-58, E-59, E-60, E-61, E-64, E-66, E-67, E-68, E-69, E-70, E-75, E-77, E-78, E-80, E-81, E-82, E-83, E-84, E-85, E-86, E-87, E-88, E-90, E-91, E-92, E-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-108, E-109, E-111, E-114, E-115, E-116, E-117, E-118, F-1, F-4, F-5, F-6, F-7, F-8, F-9, F-10, F-11, F-12, F-13

Example B5: Fusarium culmorum/Wheat/Spikelet Preventative (Head Blight)

[0347] 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).

[0348] The following compounds 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:

[0349] E-68, E-92, E-103, E-117

Example B6: Phaeosphaeria Nodorum (Septoria nodorum)/Wheat/Leaf Disc Preventative (Glume Blotch)

[0350] 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 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).

[0351] 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:

[0352] E-1, E-2, E-3, E-4, E-6, E-7, E-11, E-19, E-20, E-24, E-26, E-29, E-30, E-31, E-32, E-36, E-40, E-42, E-44, E-45, E-47, E-48, E-49, E-50, E-53, E-54, E-57, E-58, E-59, E-60, E-65, E-66, E-67, E-68, E-70, E-75, E-78, E-81, E-82, E-83, E-84, E-85, E-86, E-88, E-90, E-92, E-94, E-96, E-99, E-100, E-101, E-103, E-104, E-105, E-110, E-111, E-112, E-113, E-114, E-118, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-10, F-11, F-12, F-13

Example B7: Monographella nivalis (Microdochium Nivale)/Liquid Culture (Foot Rot Cereals)

[0353] 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.

[0354] 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:

[0355] E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-9, E-10, E-11, E-12, 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-57, E-58, E-59, E-60, E-61, E-64, E-65, E-66, E-67, E-68, E-69, E-70, E-75, E-76, E-77, E-78, 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-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-108, E-109, E-110, E-111, E-112, E-113, E-114, E-115, E-116, E-117, E-118, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-9, F-11, F-12, F-13

Example B8: Mycosphaerella arachidis (Cercospora arachidicola)/Liquid Culture (Early Leaf Spot)

[0356] 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.

[0357] 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:

[0358] E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-9, E-10, E-11, E-12, 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-57, E-58, E-59, E-60, E-61, E-64, E-65, E-66, E-67, E-68, E-69, E-70, E-75, E-76, E-77, E-78, E-80, E-81, E-82, E-83, E-84, E-85, E-86, E-87, E-88, E-90, E-91, E-92, E-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-108, E-109, E-110, E-111, E-112, E-113, E-114, E-115, E-116, E-117, E-118, 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

Example B9: Phakopsora pachyrhizi/Soybean/Preventative (Soybean Rust)

[0359] Soybean leaf disks are placed on agar in multiwell plates (24-well format) and sprayed with test solutions. After drying, the leaf disks are inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound is assessed approx. 12 dpi (days after inoculation) as preventive fungicidal activity.

[0360] 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:

[0361] E-1, E-5, E-11, E-26, E-29, E-31, E-32, E-36, E-38, E-40, E-41, E-42, E-44, E-45, E-46, E-48, E-54, E-60, E-66, E-67, E-68, E-69, E-70, E-75, E-78, E-83, E-88, E-90, E-92, E-94, E-95, E-96, E-100, E-101, E-104, E-105, E-110, E-111, E-112, E-113, E-114, E-115, E-118, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8

[0362] The following compounds gave at least 50% control of Phakopsora pachyrhizi at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

[0363] E-1, E-2, E-3, E-4, E-5, E-7, E-11, E-20, E-26, E-27, E-29, E-30, E-31, E-32, E-35, E-36, E-37, E-38, E-40, E-41, E-42, E-44, E-45, E-46, E-47, E-48, E-50, E-51, E-52, E-54, E-57, E-58, E-59, E-60, E-61, E-64, E-66, E-67, E-68, E-69, E-70, E-75, E-77, E-78, E-80, E-81, E-82, E-83, E-84, E-85, E-87, E-88, E-89, E-90, E-91, E-92, E-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-110, E-111, E-112, E-113, E-114, E-115, E-118, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8

Example B10: Phytophthora infestans/Tomato/Leaf Disc Preventative (Late Blight)

[0364] Tomato leaf disks are placed on water 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 disks are incubated at 16° C. and 75% 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 disks (5-7 days after application).

[0365] The following compounds gave at least 80% control of Phytophthora infestans at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

[0366] E-1, E-3, E-4, E-5, E-6, E-7, E-12, E-18, E-19, E-20, E-21, E-22, E-23, E-24, E-25, E-26, E-29, E-30, E-31, E-32, E-34, E-35, E-36, E-38, E-39, E-40, E-43, E-44, E-45, E-46, E-47, E-48, E-49, E-50, E-52, E-53, E-54, E-57, E-58, E-59, E-60, E-61, E-67, E-70, E-76, E-78, E-80, E-81, E-82, E-83, E-87, E-88, E-90, E-92, E-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-110, E-113, E-114, E-116, E-118, F-1, F-2, F-4, F-5, F-6, F-8, F-9, F-10, F-11, F-12, F-13

Example B11: Plasmopara viticola/Grape/Leaf Disc Preventative (Late Blight)

[0367] Grape vine leaf disks are placed on water 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 disks are incubated at 19° C. and 80% 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 (6-8 days after application).

[0368] The following compounds gave at least 80% control of Plasmopara viticola at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

[0369] E-1, E-2, E-3, E-5, E-6, E-7, E-11, E-12, E-18, E-19, E-20, E-21, 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-57, E-58, E-59, E-60, E-61, E-64, E-65, E-66, E-67, E-68, E-69, E-70, E-75, E-76, E-77, E-78, E-80, E-81, E-82, E-83, E-84, E-85, E-87, E-88, E-89, E-90, E-92, E-94, E-95, E-96, E-98, E-99, E-100, E-101, E-103, E-105,

[0370] E-106, E-109, E-110, E-111, E-112, E-113, E-114, E-116, E-117, E-118, 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

Example B12: Puccinia recondita f. Sp. tritici/Wheat/Leaf Disc Curative (Brown Rust)

[0371] Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are inoculated with a spore suspension of the fungus. Plates are stored in darkness at 19° C. and 75% rh. The formulated test compound diluted in water is applied 1 day after inoculation. The 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 (6-8 days after application).

[0372] 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:

[0373] E-5, E-7, E-11, E-15, E-16, E-17, E-18, E-20, E-21, E-23, E-24, E-25, E-26, E-27, E-28, E-29, E-30, E-31, E-32, E-35, E-36, E-37, E-38, E-39, E-40, E-41, E-42, E-43, E-45, E-46, E-47, E-48, E-49, E-51, E-57, E-58, E-60, E-64, E-65, E-66, E-67, E-68, E-69, E-70, E-77, E-80, E-82, E-88, E-90, E-92, E-94, E-95, E-96, E-99, E-101, E-103, E-110, E-112, E-114, E-115, E-116, E-117, E-118, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8, F-9, F-11, F-12, F-13

Example B13: Puccinia recondita f. Sp. Tritici/Wheat/Leaf Disc Preventative (Brown Rust)

[0374] 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).

[0375] 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:

[0376] E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-11, E-12, 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-57, E-58, E-59, E-60, E-61, E-65, E-66, E-67, E-68, E-69, E-70, E-75, E-76, E-77, E-78, 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-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-106, E-107, E-108, E-109, E-110, E-113, E-114, E-115, E-116, E-117, E-118, 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

Example B14: Magnaporthe grisea (Pyricularia oryzae)/Rice/Leaf Disc Preventative (Rice Blast)

[0377] 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).

[0378] 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:

[0379] E-1, E-2, E-5, E-6, E-7, E-10, E-11, E-12, E-18, E-19, E-20, E-24, E-25, E-26, E-27, E-29, E-30, E-31, E-32, E-34, E-35, E-36, E-38, E-39, E-40, E-41, E-42, E-43, E-44, E-45, E-46, E-47, E-49, E-50, E-51, E-52, E-53, E-57, E-58, E-59, E-60, E-61, E-64, E-65, E-68, E-69, E-70, E-76, E-78, E-80, E-81, E-82, E-83, E-85, E-86, E-88, E-90, E-92, E-98, E-99, E-100, E-103, E-104, E-105, E-110, E-112, E-113, E-114, E-118, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-10, F-11, F-12, F-13

Example B15: Pyrenophora teres/Barley/Leaf Disc Preventative (Net Blotch)

[0380] 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).

[0381] 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:

[0382] E-1, E-2, E-12, E-34, E-36, E-38, E-39, E-42, E-44, E-45, E-54, E-67, E-70, E-75, E-78, E-81, E-82, E-83, E-89, E-105, E-108, E-109, E-112, E-114, E-118, F-1, F-2, F-4, F-5, F-7, F-10, F-11, F-12, F-13

[0383] Example B16: Pythium ultimum/Liquid Culture (Seedling Damping Off)

[0384] Mycelia fragments and oospores 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 mycelia/spore mixture is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 2-3 days after application.

[0385] The following compounds gave at least 80% control of Pythium ultimum at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

[0386] E-5, E-7, E-21, E-68, E-80, E-92, E-103, F-9

[0387] Example B17: Thanatephorus cucumeris (Rhizoctonia solani)/Liquid Culture (Foot Rot, Damping-Off)

[0388] 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 the test compounds 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 Thanatephorus cucumeris at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

[0389] E-23, E-24, E-30, E-31, E-32, E-34, E-35, E-36, E-38, E-39, E-40, E-41, E-42, E-43, E-44, E-45, E-46, E-48, E-50, E-52, E-53, E-57, E-58, E-59, E-60, E-65, E-67, E-68, E-69, E-98, E-101

Example B18: Sclerotinia sclerotiorum/Liquid Culture (Cottony Rot)

[0390] 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:

[0391] E-18, E-19, E-20, E-23, E-24, E-36, E-67, E-68, E-69, E-117, F-3, F-7

Example B19: Mycosphaerella graminicola (Septoria tritici)/Liquid Culture (Septoria Blotch)

[0392] 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.

[0393] 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:

[0394] E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-9, E-10, E-11, E-12, 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-57, E-58, E-59, E-60, E-61, E-64, E-65, E-66, E-67, E-68, E-69, E-70, E-75, E-76, E-77, E-78, 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-94, E-95, E-96, E-97, E-98, E-99, E-100, E-101, E-103, E-104, E-105, E-107, E-108, E-109, E-110, E-113, E-114, E-115, E-116, E-117, E-118, 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

Comparative Data:

[0395] The biological activity of compounds E-15, E-40, E-42, E-70, E-92, E-105, F-8, F-9, of the invention are compared to the reference compounds X-1. Reference compound X-1 is specifically disclosed on page 13 of EP 0 212 859 as compound no. 140.

[0396] The data are presented as the percentage of disease control of each compound for the biological tests against G. lagenarium (Example B3), P. recondita preventative (Example B13), P. teres (Example B15) and M. graminicola (Example B19) as described above. The testing rates of each biological test is specifically described in table C1 below.

TABLE-US-00013 TABLE C1 Comparative Data Concentration Disease Compound (ppm) Pathogen (test method) control (%) [00146]  20  60 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19) 100 100  0  90 [00147]  20  60  20  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19) 100 100  50 100 [00148]  20  60 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19) 100 100  90 100 [00149]  20  60 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19) 100 100   0 100 [00150]  20  60 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19) 100 100  90 100 [00151]  20  60 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19) 100  70 — 100 [00152]  20  60 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19)  90 100  90 100 [00153]  20 200 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19)  20  90  50  70 [00154]  20 200 200  6 G. lagenarium (B3) P. recondita prev (B13) P. teres (B15) M. graminicola (B19)  0  0  0  20

Example D: Comparative Photostability Data

[0397] The photostability data of compounds E-40, E-41, E-42, E-44, E-67, E-68, E-70, E-88, E-90, E-92, E-101 and E-105 of the invention are compared to the reference compound X-1.

[0398] The testing method to measure the photostability data of each compound in table is D1 is as specifically described below. The objective of the photostability assay was to determine the stability of the individual test compounds in a strictly controlled and reproducible environment allowing a comparison of their photostability.

[0399] Method: Compounds were dissolved in methanol (HPLC grade) to give 1 g/L stock solutions. Compound stock solution (2 μl) was spotted onto microscope slides in a 3D printed holder and put into the Atlas Suntest. The spectral output power of the Suntest was set to 750 W/m.sup.2, which is considered typical of the daily maximum (noon) irradiance level on a very bright British Summer day. At specific time points slides were removed from the Suntest and placed in 4D vials. Wash solvent made up of 50:40:10 H.sub.2O:MeCN:THF (1 mL) is then added to the vials and whirlimixed. The resulting solution is then subsampled to an HPLC vial to be analysed. A Waters UPLC system with Photodiode Array was used with a Waters reverse phase column (BEH C18, 100×2.1 mm×1.7 μm) and acetonitrile (HPLC grade) acidified water (0.2% formic acid) mobile phase at a flow rate of 0.6 mL/min. Peak detection was at the optimum wavelength and peak areas were used for quantification

[0400] Initial and subsequent measurements of peak area attributable to the test compound were used to provide a % parent remaining at 3 hours.

TABLE-US-00014 TABLE D1 Photostability data Compound Structure % Parent Remaining @ 3 hrs X-1 [00155] 9 E-105 [00156] 74 E-101 [00157] 38 E-92 [00158] 33 E-40 [00159] 65 E-90 [00160] 42 E-88 [00161] 34 E-67 [00162] 37 E-68 [00163] 40 E-44 [00164] 69 E-70 [00165] 25 E-41 [00166] 28 E-42 [00167] 24

Example E: Comparative Biological Activity Against Phakopsora pachyrhizi (Soybean Rust)

[0401] The biological activity of compounds E-40, E-92, E-105, F-2, and F-6 of the invention are compared to the reference compounds X-1, X-2, and X-3. Reference compounds X-1 is specifically disclosed on page 13 of EP0212859 as compound 140 and reference compound X-3 is specifically disclosed on page 61 of WO01/00562 as Compound 1-91.

[0402] Method: Soybean leaf disks are placed on agar in multiwell plates (24-well format) and sprayed with test solutions. After drying, the leaf disks are inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound is assessed approx. 12 dpi (days after inoculation) as preventive fungicidal activity.

[0403] The data are presented as the percentage of disease control of each compound for the biological tests and testing rates described below in table E1.

TABLE-US-00015 TABLE E1 Biological activity against Phakopsora pachyrhizi (Soybean rust): Concentration Compound Compound structure (ppm) control (%) Compound E-40 [00168] 200  60  20  6  2    0.6 100 100  95  90  35  10 Compound E-92 [00169] 200  60  20  6  2    0.6 100 100  90  35  0  0 Compound E-105 [00170] 200  60  20  6  2    0.6 100 100  95  20  0  0 Compound F-2 [00171] 200  60  20  6  2    0.6 100 100  90  50  20  0 Compound F-6 [00172] 200  60  20  6  2    0.6 100 100  80  20  0  0 Reference X-1 (Compound 140 of EP 0 212 859) [00173] 200  60  20  6  2    0.6  45  10  10  0  0  0 Reference Compound X-2 [00174] 200  60  20  6  2    0.6 100  70  0  0  0  0 Reference X-3 (Compound I-91 of WO 2001000562) [00175] 200  60  20  6  2    0.6  85  50  10  0  0  0