Microbiocidal phenylamidine derivatives

Abstract

Compounds of the formula (I), wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined in claim 1. Furthermore, the present invention relates to agrochemical compositions which comprise compounds of formula (I), to preparation of these compositions, and to the use of the compounds or compositions in agriculture or horticulture for combating, preventing or controlling infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular fungi. ##STR00001##

Claims

1. A compound of formula (I): ##STR00118## wherein R.sup.1 and R.sup.2 are each independently selected from C.sub.1-C.sub.4 alkyl and C.sub.3-C.sub.6 cycloalkyl; or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a three to six-membered saturated cyclic group which may optionally contain one oxygen or one sulphur atom; R.sup.3 is hydrogen, halogen, C.sub.1-C.sub.4 alkyl or C.sub.3-C.sub.6 cycloalkyl; R.sup.4 is C.sub.1-C.sub.4 haloalkyl; R.sup.5 is C.sub.3-C.sub.8 cycloalkyl wherein the cycloalkyl is substituted with 1 to 3 substituents independently selected from cyano, halogen, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6 cycloalkyloxy, C.sub.3-C.sub.6 alkenyloxy, C.sub.3-C.sub.6 alkynyloxy, aryloxy, NOR.sup.9; or R.sup.5 is C.sub.3-C.sub.8 cycloalkyl wherein the cyclic group contains one or two non-contiguous oxygen or sulfur atoms or where one of the ring members represents SO or SO.sub.2; or R.sup.5 is C.sub.1-C.sub.6 alkyloxycarbonyl; or R.sup.5 is C.sub.1-C.sub.6 alkyl wherein the alkyl is substituted with 1 or 2 substituents independently selected from cyano, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkoxy(C.sub.1-C.sub.6)alkyloxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6 cycloalkyloxy (wherein the cycloalkyl group optionally contains one or two non-contiguous oxygen or sulfur atoms or where one of the ring members optionally represents SO or SO.sub.2 and wherein the cycloalkyl group is optionally substituted with one to four groups independently selected from halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkyoxy, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy and/or one phenyl (where the phenyl is itself optionally substituted with halogen)), C.sub.3-C.sub.6 cycloalkyl(C.sub.1-C.sub.6)alkyloxy (wherein the cycloalkyl group optionally contains one or two non-contiguous oxygen or sulfur atoms or where one of the ring members optionally represents SO or SO.sub.2 and wherein the cycloalkyl group is optionally substituted with one to four groups independently selected from halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkyoxy, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy and/or one phenyl (where the phenyl is itself optionally substituted with halogen)), benzocyclopentanyloxy, benzocyclohexanyloxy, C.sub.3-C.sub.6 alkenyloxy, C.sub.3-C.sub.6 alkynyloxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4haloalkylthio, C.sub.3-C.sub.6cycloalkylthio, C.sub.1-C.sub.4alkylsulphonyl, arylsulphonyl (wherein the aryl is optionally substituted with one to three R.sup.6 groups), aryl(C.sub.1-C.sub.4)alkylsulphonyl (wherein the aryl is optionally substituted with one to three R.sup.6 groups), arylthio (wherein the aryl is optionally substituted with one to three R.sup.6 groups), aryl(C.sub.1-C.sub.4)alkylthio (wherein the aryl is optionally substituted with one to three R.sup.6 groups), aryloxy (wherein the aryl is optionally substituted with one to three R.sup.6 groups), heteroaryloxy (wherein the heteroaryl is optionally substituted with one to four R.sup.6 groups), Si(C.sub.1-C.sub.4 alkyl).sub.3C.sub.1-C.sub.4alkoxy, aryl(C.sub.1-C.sub.4)alkyloxy (wherein the aryl is optionally substituted with one to three R.sup.6 groups), heteroaryl(C.sub.1-C.sub.4)alkyloxy (wherein the heteroaryl is optionally substituted with one to three R.sup.6 groups), NOR.sup.9, ONC(R.sup.7)(R.sup.8), O(C.sub.1-C.sub.6 alkyl)-ONC(R.sup.7)(R.sup.8), N(OR.sup.9)R.sup.10; or R.sup.5 is CH.sub.2C(NOR.sup.9)C.sub.1-C.sub.2 alkyl or CH.sub.2C(NOR.sup.9)-phenyl; Each R.sup.6 is independently selected from halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6cycloalkyloxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4haloalkylthio, C.sub.3-C.sub.6cycloalkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkenyloxy, C.sub.2-C.sub.6haloalkenyloxy, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkylC.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6alkynyloxy, aryl, aryloxy, heteroaryl, heteroaryloxy; R.sup.7 and R.sup.8 are each independently selected from hydrogen, C.sub.1-C.sub.4alkyl, aryl (wherein the aryl is optionally substituted with one to three R.sup.6 groups) and C.sub.3-C.sub.8cycloalkyl; or R.sup.7 and R.sup.8 together with the carbon atom to which they are attached form a four to eight-membered saturated cyclic group which may optionally contain one oxygen or one sulphur atom; R.sup.9 is C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6alkenyl, C.sub.3-C.sub.6alkynyl, aryl(C.sub.1-C.sub.4)alkyl or C.sub.3-C.sub.8cycloalkyl; and R.sup.10 is C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6alkenyl, C.sub.3-C.sub.6alkynyl, aryl(C.sub.1-C.sub.4)alkyl, aryl or C.sub.3-C.sub.8cycloalkyl; or R.sup.9 and R.sup.10 together with the nitrogen and oxygen atom to which they are attached form a four to six-membered saturated cyclic group; or an enantiomer, salt or N-oxide thereof.

2. A compound according to claim 1 wherein R.sup.1 and R.sup.2 are each independently selected from C.sub.1-C.sub.4alkyl and C.sub.3-C.sub.6cycloalkyl.

3. A compound according to claim 1 wherein R.sup.3 is hydrogen, halogen, C.sub.1-C.sub.4alkyl or C.sub.3-C.sub.6cycloalkyl.

4. A compound according to claim 1 wherein R.sup.4 is C.sub.1-C.sub.3haloalkyl.

5. A compound according to claim 1 wherein R.sup.5 is C.sub.3-C.sub.8cycloalkyl wherein the cycloalkyl is substituted with 1 to 3 substituents independently selected from cyano, halogen, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6 cycloalkyloxy, C.sub.3-C.sub.6 alkenyloxy, C.sub.3-C.sub.6 alkynyloxy, phenyloxy, NOR.sup.9; or R.sup.5 is C.sub.1-C.sub.6 alkyl wherein the alkyl is substituted with 1 to 2 substituents independently selected from cyano, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6 cycloalkyloxy, C.sub.3-C.sub.6 alkenyloxy, C.sub.3-C.sub.6 alkynyloxy, phenyloxy (wherein the phenyl is optionally substituted with one to three R.sup.6 groups), pyridinyloxy (wherein the pyridinyl is optionally substituted with one or two R.sup.6 groups), Si(C.sub.1-C.sub.4 alkyl).sub.3C.sub.1-C.sub.4alkoxy, phenyl(C.sub.1-C.sub.4)alkyloxy (wherein the phenyl is optionally substituted with one to three R.sup.6 groups), NOR.sup.9, ONC(R.sup.7)(R.sup.8), N(OR.sup.9)R.sup.10; wherein each R.sup.6 is independently selected from fluoro, chloro, cyano, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.3-C.sub.6cycloalkyloxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3haloalkylthio, C.sub.3-C.sub.6cycloalkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylsulfonyl, C.sub.1-C.sub.3alkylcarbonyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkenyloxy, C.sub.2-C.sub.4haloalkenyloxy, C.sub.2-C.sub.4alkynyl, C.sub.3-C.sub.6cycloalkylC.sub.2-C.sub.4alkynyl, C.sub.2-C.sub.4alkynyloxy, phenyl, phenyloxy; R.sup.7 and R.sup.8 are each independently selected from hydrogen, C.sub.1-C.sub.4alkyl, phenyl (wherein the phenyl is optionally substituted with one or two R.sup.6 groups) and C.sub.3-C.sub.8cycloalkyl or R.sup.7 and R.sup.8 together with the carbon atom to which they are attached form a four- to six-membered saturated cyclic group which may optionally contain one oxygen or one sulphur atom; or R.sup.5 is CH.sub.2C(NOR.sup.9)C.sub.1-C.sub.2 alkyl or CH.sub.2C(NOR.sup.9)-phenyl; R.sup.9 is C.sub.1-C.sub.6 alkyl or phenyl(C.sub.1-C.sub.4)alkyl and R.sup.10 is C.sub.1-C.sub.6 alkyl, pheyl(C.sub.1-C.sub.4)alkyl, phenyl or C.sub.3-C.sub.6 cycloalkyl or R.sup.9 and R.sup.10 together with the nitrogen and oxygen atoms to which they are attached form a five- to six-membered saturated cyclic group.

6. A compound according to claim 1 wherein R.sup.1 and R.sup.2 are each independently selected from methyl, ethyl, propyl or isopropyl.

7. A compound according to claim 1 wherein R.sup.3 is hydrogen, fluoro, methyl, ethyl, or cyclopropyl.

8. A compound according to claim 1 wherein R.sup.4 is trifluoromethyl, pentafluoroethyl or chlorodifluoromethyl.

9. A compound according to claim 1 wherein R.sup.5 is C.sub.4-C.sub.6 cycloalkyl wherein the cycloalkyl is substituted with 1 or 2 substituents independently selected from cyano, fluoro, chloro, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.3-C.sub.6 cycloalkoxy, C.sub.3-C.sub.4 alkenyloxy, C.sub.3-C.sub.4 alkynyloxy, phenyloxy, NOR.sup.9; or R.sup.5 is C.sub.1-C.sub.3 alkyl wherein the alkyl is substituted with 1 to 2 substituents independently selected from C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.2haloalkoxy, C.sub.3-C.sub.6 cycloalkyloxy, C.sub.3-C.sub.4 alkenyloxy, C.sub.3-C.sub.4 alkynyloxy, phenyloxy (wherein the phenyl is optionally substituted with one or two R.sup.6 groups), phenyl(C.sub.1-C.sub.2)alkyloxy (wherein the phenyl is optionally substituted with one or two R.sup.6 groups), NOR.sup.9, ONC(R.sup.7)(R.sup.8), wherein each R.sup.6 is independently selected from fluoro, chloro, methyl, ethyl, methoxy, ethoxy, trifluoromethoxy, diflouromethoxy, cyclopropyl, methylthio, trifluoromethylthio, methylsulfonyl, and ethynyl; R.sup.7 is selected from C.sub.1-C.sub.4 alkyl, phenyl (wherein the phenyl is optionally substituted with one or two R.sup.6 groups) and C.sub.3-C.sub.8cycloalkyl; R.sup.8 is C.sub.1-C.sub.4 alkyl; or R.sup.7 and R.sup.8 together with the carbon atom to which they are attached form a four- to six-membered saturated cyclic group; or R.sup.5 is CH.sub.2C(NOR.sup.9)C.sub.1-C.sub.2 alkyl or CH.sub.2C(NOR.sup.9)-phenyl; and R.sup.9 is C.sub.1-C.sub.4 alkyl or phenyl(C.sub.1-C.sub.2)alkyl.

10. A compound according to claim 1 wherein R.sup.1 is methyl or ethyl; R.sup.2 is methyl, ethyl, propyl or isopropyl; and R.sup.3 is hydrogen, methyl or ethyl.

11. A compound according to claim 1 wherein R.sup.1 is methyl or ethyl; R.sup.2 is methyl, ethyl, propyl or isopropyl; R.sup.3 is hydrogen, methyl or ethyl; R.sup.4 is trifluoromethyl or chlorodifluoromethyl; R.sup.5 is C.sub.4-C.sub.6 cycloalkyl wherein the cycloalkyl is substituted with 1 substituent selected from fluoro, chloro, methoxy, ethoxy, cyclopropoxy, allyloxy, propargyloxy, NOR.sup.9; or R.sup.5 is C.sub.1-C.sub.3 alkyl wherein the alkyl is substituted with 1 substituent selected from C.sub.1-C.sub.4 alkoxy, trifluoromethoxy, difluoromethoxy, C.sub.3-C.sub.6 cycloalkyloxy, phenyloxy (wherein the phenyl is optionally substituted with one or two R.sup.6 groups), benzyloxy (wherein the phenyl of the benzyl group is optionally substituted with an R.sup.6 group) and NOR.sup.9; Each R.sup.6 is independently selected from fluoro, chloro, methyl, trifluoromethoxy, diflouromethoxy, cyclopropyl and methylthio; or R.sup.5 is CH.sub.2C(NOR.sup.9)C.sub.1-C.sub.2 alkyl or CH.sub.2C(NOR.sup.9)-phenyl; and R.sup.9 is C.sub.1-C.sub.4alkyl or benzyl; or an enantiomer, salt or N-oxide thereof.

12. A compound according to claim 1 wherein R.sup.1 is methyl or ethyl; R.sup.2 is ethyl, propyl or isopropyl; R.sup.3 is hydrogen or methyl; R.sup.4 is trifluoromethyl or chlorodifluoromethyl; R.sup.5 is cyclobutyl or cyclohexyl wherein the cyclobutyl or cyclohexyl is substituted with 1 substituent selected from methoxy, ethoxy, cyclopropoxy, allyloxy, propargyloxy, NOR.sup.9; or R.sup.5 is methyl, ethyl, propyl or isopropyl, wherein the methyl, ethyl, propyl or isopropyl is substituted with 1 substituent selected from C.sub.1-C.sub.4 alkoxy, C.sub.3-C.sub.6 cycloalkyloxy, phenyloxy (wherein the phenyl is optionally substituted with one or two R.sup.6 groups) and benzyloxy (wherein the phenyl of the benzyl group is optionally substituted with an R.sup.6 group); or R.sup.5 is CH.sub.2C(NOR.sup.9)C.sub.1-C.sub.2 alkyl or CH.sub.2C(NOR.sup.9)-phenyl; Each R.sup.6 is independently selected from fluoro, chloro and methyl; and R.sup.9 is C.sub.1-C.sub.4 alkyl or benzyl; or an enantiomer, salt or N-oxide thereof.

13. A composition comprising a fungicidally effective amount of a compound of formula (I) as defined in claim 1.

14. A composition according to claim 13, wherein the composition further comprises at least one additional active ingredient and/or a diluent, wherein the active ingredient is selected from a pesticide, a plant nutrient, a plant fertilizer, and combinations thereof.

15. A method of combating, preventing or controlling phytopathogenic diseases which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I) as defined in claim 1 or a composition comprising a fungicidally effective amount of a compound of formula (I) as defined in claim 1.

Description

EXAMPLES

(1) The Examples which follow serve to illustrate the invention. Certain 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.

(2) Throughout this description, temperatures are given in degrees Celsius and m.p. means melting point. LC/MS means Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the methods are:

Formulation Examples

(3) TABLE-US-00002 Wettable powders a) b) c) active ingredient [compound of 25% 50% 75% formula (I)] sodium lignosulfonate 5% 5% sodium lauryl sulfate 3% 5% sodium diisobutylnaphthalenesulfonate 6% 10% phenol polyethylene glycol ether 2% (7-8 mol of ethylene oxide) highly dispersed silicic acid 5% 10% 10% Kaolin 62% 27%
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.

(4) TABLE-US-00003 Powders for dry seed treatment a) b) c) active ingredient [compound of 25% 50% 75% formula (I)] light mineral oil 5% 5% 5% highly dispersed silicic acid 5% 5% Kaolin 65% 40% Talcum 20
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.

(5) Emulsifiable Concentrate

(6) TABLE-US-00004 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%
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

(7) TABLE-US-00005 Dusts a) b) c) Active ingredient [compound of 5% 6% 4% formula (I)] talcum 95% Kaolin 94% mineral filler 96%
Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.

(8) Extruder Granules

(9) TABLE-US-00006 Extruder granules Active ingredient [compound of 15% formula (I)] sodium lignosulfonate 2% carboxymethylcellulose 1% Kaolin 82%
The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

(10) Coated Granules

(11) TABLE-US-00007 Coated granules Active ingredient [compound of 8% formula (I)] polyethylene glycol (mol. wt. 200) 3% Kaolin 89%
The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
Suspension Concentrate

(12) TABLE-US-00008 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% emulsion 1% in water) Water 32%
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Flowable Concentrate for Seed Treatment

(13) TABLE-US-00009 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 0.5% of a 20% solution in water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% 0.2% emulsion in water) Water 45.3%
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Slow Release Capsule Suspension
28 parts of a combination of the compound of formula (I) are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

Preparation Examples

(14) Using techniques described above and below, and also in WO 08/101682 and WO 12/146125, together with further techniques generally known to the person skilled in the art, compounds of formula (I) may be prepared.

Preparation of N-ethyl-N-[5-methoxy-2-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(isobutoxymethyl)-ethyl]phenyl]-N-methyl-formamidine

Preparation of 4-bromo-5-methoxy-2-methyl-aniline

(15) N-bromosuccinimide (1.28 g, 7.29 mmol) was added portion wise to an ice-cold (0-5 C.) solution of 5-methoxy-2-methyl-aniline (1.0 g, 7.29 mmol) in CHCl.sub.3 (15 mL). The resulting solution was stirred for 60 minutes at 0 C., warmed to room temperature and diluted with CH.sub.2Cl.sub.2. The mixture was washed with aqueous NaHCO.sub.3 (+2 mL Na.sub.2S20.sub.3 solution), brine and dried over MgSO.sub.4. Solids were removed by filtration and volatiles were removed in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as off white solid.

(16) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.17 (s, 1H), 6.27 (s, 1H), 3.82 (s, 3H), 3.53-3.73 (br. s., 2H), 2.08 (s, 3H).

Preparation of N-(4-bromo-5-methoxy-2-methyl-phenyl)-N-ethyl-N-methyl-formamidine

(17) To a suspension of 4-bromo-5-methoxy-2-methyl-aniline (1.4 g, 6.48 mmol) and p-toluene sulfonic acid (0.05 g, 0.32 mmol) in toluene (13 mL) was added N-(dimethoxymethyl)-N-methyl-ethanamine (1.3 g, 9.7 mmol) at room temperature. The resulting clear solution was warmed to 50 C. and stirred for 24 h at this temperature. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, washed with aqueous NaHCO.sub.3, brine and dried over MgSO.sub.4. Solids were removed by filtration and volatiles were removed in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as light yellow liquid.

(18) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.40 (br. s., 1H), 7.26 (s, 1H), 6.33 (s, 1H), 3.85 (s, 3H), 3.34 (br. s., 2H), 3.00 (s, 3H), 2.16 (s, 3H), 1.22 (t, 3H).

Preparation of N-ethyl-N-[5-methoxy-2-methyl-4-(2,2,2-trifluoroacetyl)phenyl]-N-methyl-formamidine

(19) A solution of N-(4-bromo-5-methoxy-2-methyl-phenyl)-N-ethyl-N-methyl-formamidine (0.94 g, 3.30 mmol) in THF (7 mL) under inert atmosphere was cooled to 78 C. and n-butyl lithium (2.5 M in hexanes, 2.5 mL, 3.96 mmol) was added drop wise. The resulting solution was aged for 30 min at 78 C., then ethyl 2,2,2-trifluoroacetate (1.40 g, 9.89 mmol) was added, the flask was removed from the cooling bath and was allowed to reach room temperature. The mixture was quenched with aq. NH.sub.4Cl and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO.sub.4, filtrated and concentrated in vacuo to yellow oil. Purification by flash chromatography on silica gel to afford the title compound as light yellow solid.

(20) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.55 (s, 1H), 7.36-7.54 (m, 1H), 6.32 (s, 1H), 3.89 (s, 3H), 3.27-3.64 (m, 2H), 3.05 (s, 3H), 2.20 (s, 3H), 1.16-1.35 (m, 3H).

Preparation of N-ethyl-N-[5-methoxy-2-methyl-4-[2-(trifluoromethyl)oxiran-2-yl]phenyl]-N-methyl-formamidine

(21) Trimethyl sulfonium iodide (0.52 g, 2.48 mmol) was added in small portions to an ice-cold suspension of sodium hydride (60% in oil, 0.11 g, 2.48 mmol) in tetrahydrofuran (8 mL) and dimethylsulfoxide (6 mL). The cooling bath was removed and the mixture was stirred for 30 min at room temperature. A solution of N-ethyl-N-[5-methoxy-2-methyl-4-(2,2,2-trifluoroacetyl)phenyl]-N-methyl-formamidine (0.50 g, 1.65 mmol) in tetrahydrofuran (5 mL) was added and the reaction was stirred at room temperature until HPLC indicated full conversion of the starting material. The mixture was cooled with an ice bath, carefully quenched with aq. NH.sub.4Cl solution and was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO.sub.4, filtrated and concentrated in vacuo to a light brown solid which was purified by flash chromatography on silica gel to afford the title compound as light brown solid

(22) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.43 (br.s, 1H), 7.20 (s, 1H), 6.31 (s, 1H), 3.81 (s, 3H), 3.40 (d, 1H), 3.15-3.66 (m, 2H), 3.00 (s, 3H), 2.95-2.93 (m, 1H), 2.18 (s, 3H), 1.21 (t, 3H).

Preparation of N-ethyl-N-[5-methoxy-2-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(isobutoxymethyl)-ethyl]phenyl]-N-methyl-formamidine

(23) 2-methylpropan-1-ol (0.11 g, 1.52 mmol) was added slowly to a suspension of sodium hydride (60%, 0.04 g, 1.0 mmol) in DMF (1 mL) at 0 C. and the mixture was aged for 5 min at 0 C. A solution of N-ethyl-N-[5-methoxy-2-methyl-4-[2-(trifluoromethyl)oxiran-2-yl]phenyl]-N-methyl-formamidine (0.20 g, 0.51 mmol) in DMF (1 mL) was added, the resulting solution was warmed to 65 C. and stirred at this temperature until HPLC indicated full conversion of the starting material. The reaction was cooled to room temperature, diluted with aq. NH.sub.4Cl solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO.sub.4, filtrated and concentrated in vacuo to brown oil. Purification by flash chromatography on silica gel to afford the title compound as light yellow liquid.

(24) .sup.1H NMR (400 MHz, CDCl.sub.3-d) 7.43 (br.s, 1H), 7.31 (s, 1H), 6.34 (s, 1H), 5.49 (s, 1H), 4.13 (d, 1H), 3.89 (d, 1H), 3.83 (s, 3H), 3.17-3.59 (m, 4H), 3.00 (s, 3H), 2.19 (s, 3H), 1.81-1.98 (m, 1H), 1.21 (t, 3H), 0.88 (dd, 6H).

(25) Table E: Physical data of compounds of formula (I)

(26) The compounds of formula (I) in Table E were prepared using techniques analogous to those described above and/or common synthetic techniques generally known to the person skilled in the art, as well as those described in WO 12/146125 and WO 08/101682.

(27) TABLE-US-00010 [M + H] IUPAC RT (meas- Meth- MP Entry name STRUCTURE (min) ured) od C. E.001 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-[(5-methyl-2-propyl- 1,3-dioxan-5-yl) methoxymethyl]ethyl]phenyl]- N-methyl-formamidine 1.34 492 A E.002 N-[4-[1-(ethoxymethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 1.08 363 A E.003 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-[(3,3,5,5- tetramethylcyclohexoxy)methyl] ethyl]phenyl]-N-methyl- formamidine 1.64 473 A E.004 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-[(4- methylcyclohexoxy)methyl] ethyl]phenyl]-N-methyl- formamidine 0 1.47 431 A E.005 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(indan-1- yloxymethyl)ethyl]phenyl]-N- methyl-formamidine 1.34 452 A E.006 N-[4-[1-[(3,5- dimethylcyclohexoxy)methyl]- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 1.50 446 A E.007 N-[4-[1-[[1-(4- chlorophenyl)cyclopropyl] methoxymethyl]-2,2,2-triuoro- 1-hydroxy-ethyl]-5-methoxy-2- methyl-phenyl]-N-ethyl-N- methyl-formamidine 1.44 499 A E.008 N-[4-[1-(2,2- dimethylpropoxymethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 1.37 406 A E.009 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(2- naphthylmethoxymethyl)ethyl] phenyl]-N-methyl-formamidine 1.37 476 A E.010 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(indan-2- yloxymethyl)ethyl]phenyl]-N- methyl-formamidine 1.35 452 A E.011 N-[4-[1- (cyclobutylmethoxymethyl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 1.30 404 A E.012 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(2- methoxyethoxymethyl)ethyl] phenyl]-N-methyl-formamidine 0.99 393 A E.013 N-[4-[1-(butoxymethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 1.26 392 A E.014 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (propoxymethyl)ethyl]phenyl]- N-methyl-formamidine 0 1.16 377 A E.015 N-[4-[1-[(3-tert-butoxy-2,2- dimethyl-propoxy)methyl]- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 1.54 478 A E.016 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-[2- (isopropylideneamino) oxyethoxymethyl]ethyl]phenyl]- N-methyl-formamidine 1.12 435 A E.017 N-ethyl-N-[4-[1-[(2-ethyl-5- methyl-1,3-dioxan-5- yl)methoxymethyl]-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 1.29 478 A E.018 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-[(3-methyloxetan-3- yl)methoxymethyl]ethyl]phenyl]- N-methyl-formamidine 1.05 420 A E.019 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-[(3-methoxy-3- methyl- butoxy)methyl]ethyl]phenyl]- N-methyl-formamidine 1.18 436 A E.020 N-[4-[1-(2- ethoxyethoxymethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 1.08 408 A E.021 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(2- phenylethoxymethyl)ethyl] phenyl]-N-methyl- formamidine 1.30 440 A E.022 N-[4-[1-[2-(3,4- dimethoxyphenyl)ethoxymethyl]- 2,2,2-trifluoro-1-hydroxy- ethyl]-5-methoxy-2-methyl- phenyl]-N-ethyl-N-methyl- formamidine 1.24 500 A E.023 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1-(2- furylmethoxymethyl)-1- hydroxy-ethyl]phenyl]-N- methyl-formamidine 1.14 416 A E.024 N-ethyl-N-[4-[1-(1- ethylpropoxymethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 0 1.40 405 A E.025 N-[4-[1-(cyclobutoxymethyl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 1.18 389 A E.026 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1-[2- (4-fluorophenyl)ethoxymethyl]- 1-hydroxy-ethyl]phenyl]-N- methyl-formamidine 1.30 458 A E.027 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(p- tolylmethoxymethyl)ethyl] phenyl]-N-methyl-formamidine 1.31 440 A E.028 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(1- phenylethoxymethyl)ethyl] phenyl]-N-methyl-formamidine 1.31 440 A E.029 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(o- tolylmethoxymethyl)ethyl] phenyl]-N-methyl-formamidine 1.30 440 A E.030 N-[4-[1-(2- allyloxyethoxymethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 1.13 420 A E.031 N-[4-[1-[(2,2- difluorocyclopropyl) methoxymethyl]-2,2,2-trifluoro- 1-hydroxy-ethyl]-5- methoxy-2-methyl- phenyl]-N-ethyl-N-methyl- formamidine 1.14 426 A E.032 N-[4-[1-(cyclopentoxymethyl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 1.33 403 A E.033 N-ethyl-N-[4-[1-[(4- ethylcyclohexoxy)methyl]- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-methyl-formamidine 1.50 446 A E.034 N-ethyl-N-[4-[1-[(3- ethyloxetan-3- yl)methoxymethyl]-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 0 1.15 433 A E.035 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(m- tolylmethoxymethyl)ethyl] phenyl]-N-methyl-formamidine 1.32 440 A E.036 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- [(isopropylideneamino) oxymethyl]ethyl]phenyl]-N- methyl-formamidine 0.76 390 B E.037 N-[4-[1- [(cyclohexylideneamino) oxymethyl]-2,2,2-trifluoro-1- hydroxy-ethyl]-5-methoxy-2- methyl-phenyl]-N-ethyl-N- methyl-formamidine 0.87 430 B E.038 N-[4-[1-[(4,4- dimethylcyclohexoxy)methyl]- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 0.96 445 B E.039 N-[4-[1-(cyclohexoxymethyl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 0.89 417 B E.040 N-[4-[1-(but-2-ynoxymethyl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 0.75 387 B E.041 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(prop-2- ynoxymethyl)ethyl]phenyl]-N- methyl-formamidine 0.69 373 B E.042 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-[(4- methylcyclohexoxy)methyl] ethyl]phenyl]-N-methyl- formamidine 0.92 431 B E.043 N-[4-[1-(benzyloxymethyl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 0.81 425 B E.044 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1-[(4- fluorophenyl)methoxymethyl]- 1-hydroxy-ethyl]phenyl]-N- methyl-formamidine 0 0.82 443 B E.045 N-[4-[1-[(3,5- difluorophenoxy)methyl]-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.82 447 B 86- 89 E.046 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (isobutoxymethyl)ethyl] phenyl]-N-methyl-formamidine 0.82 391 B E.047 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (phenoxymethyl)ethyl]phenyl]- N-methyl-formamidine 0.83 411 B E.048 ethyl 2-[4- [[ethyl(methyl)amino] methyleneamino]-2-methoxy- 5-methyl-phenyl]- 3,3,3-trifluoro-2- hydroxy-propanoate 1.03 377 B E.049 N-[4-[3-but-2-ynoxy-1- hydroxy-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.78 401 B E.050 N-ethyl-N-[4-[1-hydroxy-3- prop-2-ynoxy-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 0.73 397 B E.051 N-[4-[3-benzyloxy-1-hydroxy- 1-(trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.86 439 B E.052 N-ethyl-N-[4-[1-hydroxy-3- propoxy-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 391 E.053 N-ethyl-N-[4-[3-(4- fluorophenoxy)-1-hydroxy-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 0.84 443 B E.054 N-ethyl-N-[4-[1-hydroxy-3- phenoxy-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 0 0.83 425 B E.055 N-ethyl-N-[5-methoxy-2- methyl-4-(2,2,2-trifluoro-1- hydroxy-1-tetrahydropyran-4- yl-ethyl)phenyl]-N-methyl- formamidine 0.70 389 B E.056 N-[4-[(3E)-3-ethoxyimino-1- hydroxy-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.76 390 B E.057 N-[4-[(3E)-3-ethoxyimino-1- hydroxy-1- (trifluoromethyl)butyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.81 404 B E.058 N-[4-[(3Z)-3-ethoxyimino-1- hydroxy-3-phenyl-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.90 466 B E.059 N-ethyl-N-[4-[(3Z)-1-hydroxy- 3-methoxyimino-3-phenyl-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 0.86 452 B 105- 107 E.060 N-[4-[2-cyano-1-hydroxy-2- methyl-1- (trifluoromethyl)propyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.74 372 B 90- 93 E.061 N-[4-[1-(cyanomethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 0.61 344 B 86- 88 E.062 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (propylsulfanylmethyl)ethyl] phenyl]-N-methyl-formamidine 0.80 393 B E.063 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (isopropylsulfonylmethyl)ethyl] phenyl]-N-methyl-formamidine 425 E.064 N-[4-[1- (benzylsulfonylmethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 00 0.76 473 B 56- 58 E.065 N-[4-[1- (benzenesulfonylmethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 01 0.73 459 B 103- 105 E.066 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (methylsulfonylmethyl)ethyl] phenyl]-N-methyl-formamidine 02 0.59 397 B E.067 N-ethyl-N-[4-[1- (ethylsulfonylmethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 03 411 E.068 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1-[(4- fluorophenyl)sulfanylmethyl]-1- hydroxy-ethyl]phenyl]-N- methyl-formamidine 04 0.84 445 B E.069 N-[4-[1- (benzylsulfanylmethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- ethyl-N-methyl-formamidine 05 0.86 441 B E.070 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (methylsulfanylmethyl)ethyl] phenyl]-N-methyl-formamidine 06 0.70 365 B E.071 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (isopropylsulfanylmethyl)ethyl] phenyl]-N-methyl-formamidine 07 0.78 393 B E.072 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1- (phenylsulfanylmethyl)ethyl] phenyl]-N-methyl-formamidine 08 0.81 427 B E.073 N-ethyl-N-[4-[1- (ethylsulfanylmethyl)-2,2,2- trifluoro-1-hydroxy-ethyl]-5- methoxy-2-methyl-phenyl]-N- methyl-formamidine 09 0.74 379 B 81- 83 E.074 N-[4-[1-(3,4-dihydro-2H-pyran- 5-yl)-2,2,2-trifluoro-1-hydroxy- ethyl]-5-methoxy-2-methyl- phenyl]-N-ethyl-N-methyl- formamidine 0 0.75 387 B 115- 116.6 E.075 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(4- methoxycyclohexyl)ethyl] phenyl]-N-methyl- formamidine 0.76 417 B E.076 N-[4-[1-(1,1-dioxothian-4-yl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 0.62 437 B E.077 N-ethyl-N-[5-methoxy-2- methyl-4-(2,2,2-trifluoro-1- hydroxy-1-tetrahydrothiopyran- 4-yl-ethyl)phenyl]-N-methyl- formamidine 0.78 405 B E.078 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(4- isopropoxycyclohexyl)ethyl] phenyl]-N-methyl-formamidine 0.86, 0.90 446 B E.079 N-ethyl-N-[5-methoxy-2- methyl-4-[2,2,2-trifluoro-1- hydroxy-1-(4- propoxycyclohexyl)ethyl] phenyl]-N-methyl-formamidine 0.87, 0.91 446 B E.080 N-[4-[1-(4-ethoxycyclohexyl)- 2,2,2-trifluoro-1-hydroxy-ethyl]- 5-methoxy-2-methyl-phenyl]- N-ethyl-N-methyl-formamidine 0.81, 0.86 431 B E.081 0.86 466 B
HPLC Method Used

(28) Method A:

(29) Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, 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), DAD Wavelength range (nm): 210 to 400, and an Acquity UPLC from Waters: Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 m, 302.1 mm, Temp: 60 C., DAD Wavelength range (nm): 210 to 500, 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

(30) Method B:

(31) Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters 10 (SQD, SQDII or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150 C., Desolvation Temperature: 350 C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. 15 Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 mm, 302.1 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

Biological Examples

(32) Blumeria graminis f. sp. tritici (Erysiphe graminis f. sp. tritici)/Wheat/Leaf Disc Preventative (Powdery Mildew on Wheat)

(33) 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).

(34) 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:

(35) E.001, E.002, E.005, E.006, E.007, E.008, E.009, E.010, E.011, E.012, E.013, E.014, E.015, E.016, E.017, E.018, E.019, E.020, E.021, E.022, E.023, E.025, E.026, E.027, E.028, E.029, E.030, E.031, E.033, E.034, E.035, E.036, E.037, E.038, E.039, E.040, E.041, E.042, E.043, E.0044, E.045, E.046, E.047, E.049, E.050, E.051, E.052, E.053, E.054, E.0055, E.056, E.057, E.058, E.059, E.060, E.061, E.062, E.063, E.064, E.065, E.067, E.068, E.069, E.070, E.071, E.072, E.073, E.074, E.075, E.078, E.079, E.080, E.081

(36) Phakopsora pachyrhizi/Soybean/Preventative (Soybean Rust)

(37) 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).

(38) 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:

(39) E.002, E.004, E.006, E.011, E.013, E.014, E.020, E.021, E.024, E.027, E.028, E.032, E.036, E.037, E.039, E.040, E.041, E.042, E.043, E.044, E.045, E.046, E.047, E.049, E.050, E.051, E.052, E.053, E.054, E.055, E.056, E.057, E.059, E.060, E.068, E.069, E.072, E.075, E.078, E.079, E.080, E.081

(40) Puccinia recondita f. Sp. Tritici/Wheat/Leaf Disc Curative (Brown Rust)

(41) 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).

(42) 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:

(43) E.001, E.002, E.005, E.006, E.007, E.008, E.009, E.010, E.011, E.012, E.013, E.014, E.015, E.016, E.017, E.018, E.019, E.020, E.021, E.022, E.023, E.025, E.026, E.027, E.028, E.029, E.030, E.031, E.033, E.034, E.035, E.036, E.037, E.038, E.039, E.040, E.041, E.042, E.046, E.047, E.049, E.050, E.051, E.052, E.053, E.054, E.055, E.056, E.057, E.058, E.059, E.060, E.061, E.062, E.063, E.064, E.065, E.067, E.068, E.069, E.074, E.0075, E.076, E.078, E.079, E.080, E.081

(44) Puccinia recondita f. Sp. Tritici/Wheat/Leaf Disc Preventative (Brown Rust)

(45) 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).

(46) 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:

(47) E.001, E.002, E.005, E.006, E.007, E.008, E.009, E.010, E.011, E.012, E.013, E.014, E.015, E.016, E.017, E.018, E.019, E.020, E.021, E.023, E.025, E.026, E.027, E.028, E.029, E.030, E.031, E.033, E.034, E.035, E.036, E.037, E.038, E.039, E.040, E.041, E.042, E.043, E.044, E.045, E.046, E.047, E.049, E.050, E.051, E.052, E.053, E.054, E.055, E.056, E.057, E.058, E.059, E.060, E.061, E.063, E.064, E.065, E.067, E.068, E.069, E.070, E.071, E.072, E.073, E.074, E.075, E.078, E.079, E.080, E.081