PESTICIDALLY ACTIVE DIAZINE-AMIDE COMPOUNDS

Abstract

Compounds of formula I (Formula I) wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides.

##STR00001##

Claims

1. A compound of the formula I ##STR00242## wherein R1 is H, C1-C6alkyl, C1-C6cyanoalkyl, aminocarbonylC1-C6alkyl, hydroxycarbonylC1-C6alkyl, C1-C6nitroalkyl, trimethylsilaneC1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkeny, C2-C6alkynyl, C2-C6haloalkynyl, C3-C4cycloalkylC1-C2alkyl-, C.sub.3-C.sub.4cycloalkylC1-C2alkyl- wherein the C3-C4cycloalkyl group is substituted with 1 or 2 halogen atoms, oxetan-3-yl-CH2-, benzyl or benzyl substituted with halogen or C1-C6haloalkyl; A1 is N or C—R2c; R2c is H, halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, or C1-C3haloalkoxy; R2a is C3-C6cycloalkyl, C3-C6cycloalkoxy, C3-C6cycloalkyl substituted with one to three substituents independently selected from C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, cyano, and halogen, C3-C6cycloalkoxy substituted with one to three substituents independently selected from C1-C3alkyl, C1-C3haloalkyl, cyano, and halogen, C3-C6cycloalkylC1-C4alkyl, C3-C6cycloalkylC1-C4alkoxy, C3-C6cycloalkylC1-C4alkyl substituted with one to five substituents independently selected from C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, cyano, and halogen, C3-C6cycloalkylC1-C4alkoxy substituted with one to five substituents independently selected from C1-C3alkyl, C1-C3haloalkyl, cyano, and halogen, C1-C5cyanoalkyl, C1-C4alkylsulfonyl, C1-C4haloalkylsulfonyl, C1-C4alkylsulfinyl, or C1-C4haloalkylsulfinyl; R2b is H, halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3haloalkylthio, C1-C3alkoxy, C1-C3haloalkoxy, SF5, or CN; R3 is C1-C3alkyl or C1-C3haloalkyl; R4 is pyridine, pyrimidine, pyrazine, pyridazine, or pyridine, pyrimidine, pyrazine and pyridazine, each of which is substituted with one substituent selected from C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C3-C4cycloalkyl, halogen and hydroxy; R5a and R5b are, independently of each other, selected from hydrogen, halogen, CN, C1-C3alkyl, C1-C3haloalkyl, C3-C4cycloalkyl, C1-C3alkoxy, and C1-C3haloalkoxy; or agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula I.

2. The compound according to claim 1 wherein R3 is methyl.

3. The compound according to claim 1, wherein A1 is N.

4. The compound according to claim 1, wherein A1 is C—R2c, where R2c is hydrogen or halogen.

5. The compound according to claim 1, wherein R1 is hydrogen, methyl, ethyl, n-propyl, isobutyl, cyclopropylmethyl or HCH≡CCH2-.

6. The compound according to claim 1, wherein R2a is C3-C6cycloalkyl, C3-C6cycloalkoxy, C3-C6cycloalkyl substituted with one to three substituents independently selected from C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, cyano, and halogen, C3-C6cycloalkylC1-C4alkyl substituted with one to five substituents independently selected from halogen and C1-C3haloalkyl, C1-C5cyanoalkyl, C3-C6cycloalkoxy, C1-C4haloalkylsulfonyl or C1-C4haloalkylsulfinyl.

7. The compound according to claim 1, wherein R2b is halogen, C1-C3haloalkyl, C1-C3haloalkylthio, C1-C3alkoxy, C1-C3haloalkoxy, or CN.

8. The compound according to claim 1, wherein R4 is 2-pyridine, 2-pyrimidine, 2-pyridine substituted with one substituent selected from cyclopropyl or halogen, and 2-pyrimidine substituted with one substituent selected from cyclopropyl or halogen.

9. The compound according to claim 1, wherein R5a and R5b, independent of each other, are selected from hydrogen, bromo, chloro, methyl, and methoxy.

10. A composition comprising a compound as according to claim 1, one or more auxiliaries and diluent, and optionally one more other active ingredient.

11. A method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of the compound according to claim 1, or of a composition comprising said compound, one or more auxiliaries and diluent, and optionally one more other active ingredient.

12. A plant propagation material, comprising, or treated with or adhered thereto, the compound according to claim 1, or of a composition comprising said compound, one or more auxiliaries and diluent, and optionally one more other active ingredient.

13. A compound of formulae IIaa to IIae ##STR00243## wherein R1 is H, C1-C6alkyl, C1-C6cyanoalkyl, aminocarbonylC1-C6alkyl, hydroxycarbonylC1-C6alkyl, C1-C6nitroalkyl, trimethylsilaneC1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkeny, C2-C6alkynyl, C2-C6haloalkynyl, C3-C4cycloalkylC1-C2alkyl-, C3-C4cycloalkylC1-C2alkyl- wherein the C3-C4cycloalkyl group is substituted with 1 or 2 halogen atoms, oxetan-3-yl-CH2-, benzyl or benzyl substituted with halogen or C1-C6 haloalkyl; and R4 is 2-pyridine, 2-pyrimidine, 2-pyridine substituted with one substituent selected from cyclopropyl or halogen, and 2-pyrimidine substituted with one substituent selected from cyclopropyl or halogen.

14. A method for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of the compound according to claim 1, or of a composition comprising said compound, one or more auxiliaries and diluent, and optionally one more other active ingredient.

15. A method of controlling parasites in or on an animal in need thereof comprising administering an effective amount of the compound according to claim 1, or of a composition comprising said compound, one or more auxiliaries and diluent, and optionally one more other active ingredient.

16. The plant propagation material according to claim 12, wherein the plant propagation material is a seed.

17. The compound according to claim 13, wherein R1 is hydrogen, methyl, ethyl, n-propyl, isobutyl, cyclopropylmethyl or HCH≡CCH2-.

Description

PREPARATORY EXAMPLES

LCMS Methods:

Method 1:

[0310] 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 l/h, Desolvation Gas Flow: 650 l/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 2:

[0311] 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 l/h, Desolvation Gas Flow: 650 l/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 3:

[0312] Spectra were recorded on a Mass Spectrometer from Agilent (Single quad mass spectrometer) equipped with an Multimode-Electron Spray and APCI (Polarity: positive and negative ions), Capillary: 4.00 KV, Corona Current 4.0 μA, Charging Voltage, 2.00 kV, Nitrogen Gas Flow: 9.0 L/min, Nebulizer Pressure: 40 psig, Mass range: 100 to 1000 m/z), dry gas temperature 250° C., Vaporizer temperature 200° C. and Spectra were recorded on LCMS from Agilent: quaternary pump, heated column compartment, Variable wave length detector. Column: Eclipse XDB C18, 5.0 μm, 150×4.6 mm, column Temp: Ambient, Wavelength (nm): 220 nm, Solvents: A=0.05% TFA in water, B=0.05% TFA in Acetonitrile. Gradient: time/% B: 0/5, 0.5/5, 3.5/90, 5/90, 5.1/5, 7/5; Flow rate: 1.0 ml/min

Method 4:

[0313] 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: 41 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 5000° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 1000 l/h, Mass range: 110 to 800 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: 40° C., PDA Wavelength range (nm): 200 to 400, Solvent Gradient: A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 1.3 min; Flow (ml/min) 0.6

[0314] Chiral SFC method 1: Spectra were recorded on a SFC from Waters (Waters Acquity UPC.sup.2/QDa) equipped with a PDA Detector Waters Acquity UPC.sup.2. Column: Daicel SFC CHIRALPAK® IC, (3 μm, 0.3 cm×10 cm, 40° C.; Mobile phase: A: CO2 B: MeOH isocratic: 10% B in 2.0 min; ABPR: 1800 psi; Flow rate: 2.0 ml/min; Detection: 220 nm; Sample concentration: 1 mg/mL in ACN; Injection: 1 μL Chiral SFC method 2: Spectra were recorded on a SFC from Waters (Waters Acquity UPC.sup.2/QDa) equipped with a PDA Detector Waters Acquity UPC.sup.2. Column: Daicel SFC CHIRALPAK® IG, (3 μm, 0.3 cm×10 cm, 40° C.; Mobile phase: A: CO2 B: MeOH isocratic: 15% B in 4.8 min; ABPR: 1800 psi; Flow rate: 2.0 ml/min; Detection: 270 nm; Sample concentration: 1 mg/mL in ACN/MeOH (1:1); Injection: 1 μL

Preparation of methyl 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I1)

[0315] ##STR00060##

[0316] Sulfuric acid (2.46 mL, 44.3 mmol, 1.00 equiv.) was added dropwise at room temperature to a solution of 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylic acid (CAS 796090-23-8, 10.0 g, 44.3 mmol) in methanol (266 mL). The reaction mixture was heated up to 65° C. and stirred overnight. After cooling down to room temperature, the reaction mixture was poured over a saturated sodium hydrogenocarbonate aqueous solution and the aqueous phase was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and evaporated to afford the desired product (10.2 g, 42.70 mmol) which was used without further purification.

[0317] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 4.04 (s, 3H) 8.11 (s, 1H) 8.17 (d, J=1.10 Hz, 1H).

Preparation of methyl 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I2) and 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid (intermediate I3)

[0318] ##STR00061##

[0319] Cyclopropylboronic acid (1.43 g, 16.7 mmol, 2.00 equiv.) and sodium hydrogenocarbonate (2.10 g, 25.1 mmol, 3.00 equiv.) were added to a solution of methyl 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I1 prepared as described above) (2.00 g, 8.35 mmol) in 1,4-dioxane (20.9 mL) and water (8.35 mL), and the resulting suspension was flushed with argon for 10 min. [1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium (II) (0.322 g, 0.417 mmol, 0.05 equiv.) was added and the resulting suspension was stirred at 100° C. for 1 hour under argon. After cooling down to room temperature, the reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and evaporated to give of first crude material, which gave after purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) the desired intermediate I2 (0.706 g, 2.88 mmol).

[0320] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 1.04-1.23 (m, 4H) 2.14-2.28 (m, 1H) 4.00 (s, 3H) 7.88 (s, 1H) 7.95 (d, J=1.47 Hz, 1H).

[0321] LC-MS (method 1): retention time 1.12 min, m/z 246 [M+H].sup.+.

[0322] After acidification to pH 1, the aqueous layer was extracted again twice with ethyl acetate, the combined organic phases were dried over sodium sulfate, filtered and evaporated to give a second crude material, which upon purification by flash chromatography over silica gel (methanol in dichloromethane) afforded the intermediate I3 (0.166 g, 0.718 mmol).

[0323] .sup.1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm: 0.94-1.03 (m, 2H) 1.06-1.15 (m, 2H) 2.37-2.46 (m, 1H) 7.88 (d, J=1.10 Hz, 1H) 8.05 (d, J=0.73 Hz, 1H) 13.89-14.33 (m, 1H).

[0324] LC-MS (method 1): retention time 0.94 min, m/z 232 [M+H].sup.+.

Preparation of 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid (intermediate I3)

[0325] ##STR00062##

[0326] Lithium hydroxide monohydrate (0.147 g, 3.43 mmol, 1.20 equiv.) was added to a solution of methyl 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I2 prepared as described above) in a 3:1 tetrahydrofuran/water mixture (24.5 mL). After stirring for 2 hours at room temperature, the reaction mixture was concentrated, and the remaining aqueous phase was acidified to pH 1 by addition of a 1 M hydrochloric acid aqueous solution (3.43 mL). The aqueous layer was extracted three times with ethyl acetate, the combined organic phases were dried over sodium sulfate, filtered and concentrated to afford 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid.

[0327] .sup.1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm: 0.96-1.02 (m, 2H) 1.07-1.15 (m, 2H) 2.40 (tt, J.sub.1=8.12 Hz, J.sub.2=4.72 Hz, 1H) 7.88 (d, J=1.10 Hz, 1H) 8.04 (s, 1H) 13.90-14.36 (m, 1H)

[0328] LC-MS (method 1): retention time 0.94 min, m/z 232 [M+H].sup.+.

Preparation of methyl 3-cyclopropyl-5-(trifluoromethyl)benzoate (intermediate I4)

[0329] ##STR00063##

[0330] A solution of propargyl bromide in toluene (80% weight, 0.89 g, 0.67 mL) was added to a white suspension of 9-BBN dimer (3.0 g, 12 mmol) in 26 mL of dry tetrahydrofuran under argon to give a pale yellow solution. The mixture was refluxed for 2 hours and then cooled to room temperature. A previously degassed sodium hydroxide 4M aqueous solution (4.4 mL, 18 mmol) was added to give a cloudy colorless solution. The mixture obtained was stirred for 1 hour at room temperature under argon. The resulting very pale yellow solution was then added to a previously degassed light yellow solution of methyl 3-bromo-5-(trifluoromethyl)benzoate (187331-46-0, 1.5 g, 5.2 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.30 g, 0.26 mmol) in 52 mL of dry tetrahydrofuran to give a light yellow solution. The resulting mixture was stirred for 19 hours at reflux. The mixture was cooled down at room temperature, diluted with ethyl acetate, quenched with water (+few drops of brine) and the aqueous layer was extracted twice with ethyl acetate. Organic layers were combined, washed once with brine, dried over sodium sulfate, filtered and evaporated under vacuum at 60° C. The crude was purified by chromatography over silica gel to afford methyl 3-cyclopropyl-5-(trifluoromethyl)benzoate as a colorless liquid.

[0331] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 0.76-0.85 (m, 2H) 1.06-1.15 (m, 2H) 2.03 (tt, J.sub.1=8.39 Hz, J.sub.2=5.00 Hz, 1H) 3.96 (s, 3H) 7.52 (s, 1H) 7.91 (s, 1H) 8.08 (d, J=0.73 Hz, 1H).

[0332] .sup.19F NMR (377 MHz, chloroform-d) δ ppm: −62.75 (s, 3 F).

Preparation of 3-cyclopropyl-5-(trifluoromethyl)benzoic acid (intermediate I5)

[0333] ##STR00064##

[0334] Methyl 3-cyclopropyl-5-(trifluoromethyl)benzoate (7.00 g, 28.7 mmol) was dissolved in tetrahydrofuran (57.3 mL) and water (28.7 mL). Then lithium hydroxide (1.21 g, 28.7 mmol) was added and the resulting pale yellow cloudy solution was stirred for 4 hours at room temperature. The reaction mixture was diluted in ethyl acetate and water. The organic phase was washed twice with water. The combined aqueous layers were acidified with 1N aqueous hydrochloric acid until pH 1-2 and extracted three times with ethyl acetate. The combined organic layers were washed once with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure at 60° C. to afford 3-cyclopropyl-5-(trifluoromethyl)benzoic acid, which was used without further purification.

[0335] .sup.1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm: 0.79-0.85 (m, 2H) 1.03-1.10 (m, 2H) 2.12-2.22 (m, 1H) 7.70 (s, 1H) 7.88 (s, 1H) 7.93 (s, 1H) 13.47 (br s, 1H).

[0336] LC-MS (method 1): retention time 0.99 min, m/z 229 [M−H].sup.−.

Preparation of methyl 3-(trifluoromethyl)-5-vinyl-benzoate (intermediate I6)

[0337] ##STR00065##

[0338] In a three neck flask under argon, methyl 3-bromo-5-(trifluoromethyl)benzoate (CAS: 187331-46-0, 20 g, 69.24 mmol) was dissolved in toluene (312 mL). Then Tributyl(vinyl) Tin (25.56 mL, 83.09 mmol) was added and the resulting solution was degassed with argon for 10 min. Tetrakis(triphenylphosphine) palladium(0) (0.816543 g, 0.69 mmol) was added, and the resulting mixture was stirred at 110° C. for 2 hours. After cooling at room temperature, the mixture was diluted with ethyl acetate (100 mL), filtered though a pad of Celite, washed with ethyl acetate and the filtrate was concentrated under vacuum. The crude was purified by chromatography over silica gel to afford methyl 3-(trifluoromethyl)-5-vinyl-benzoate.

[0339] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 3.98 (s, 3H) 5.47 (d, J=11.00 Hz, 1H) 5.93 (d, J=17.61 Hz, 1H) 6.79 (dd, J.sub.1=17.42 Hz, J.sub.2=10.82 Hz, 1H) 7.82 (s, 1H) 8.19 (s, 1H) 8.24-8.29 (m, 1H).

Preparation of diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonate

[0340] ##STR00066##

[0341] In an autoclave, diphenyl sulfide (36.43 mL, 211.1 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (6.207 mL, 42.22 mmol) were mixed. The mixture was stirred for 2 min at room temperature then the autoclave was closed and heated at 150° C. for 20 hours. The reaction was cooled at room temperature and a white precipitate was formed. 75 ml of diethyl ether was added, then the white solid was filtered. It was washed four times with 30 mL of diethyl ether and then dried under reduced pressure to afford diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonate.

[0342] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 5.78 (d, J=8.80 Hz, 2H) 7.89 (d, J=8.07 Hz, 4H) 7.93-8.00 (m, 2H) 8.37 (dd, J.sub.1=8.62 Hz, J.sub.2=1.28 Hz, 4H).

[0343] .sup.19F NMR (377 MHz, chloroform-d) δ ppm: −78.91 (s, 3 F)-61.26 (s, 3 F).

Preparation of methyl 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate (intermediate I7)

[0344] ##STR00067##

[0345] In a vial under argon, 3-(trifluoromethyl)-5-vinyl-benzoate (1.9 g, 8.3 mmol) and cesium fluoride (1.5 g, 9.9 mmol) were dissolved in dimethylacetamide (33 mL) to give a colorless solution which was degassed under argon for 20 min. 5,10,15,20-Tetraphenyl-21H,23H-porphine Iron(III) chloride (0.31 g, 0.41 mmol) was added. The reaction became a green suspension and diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonic acid (3.8 g, 9.1 mmol) was also added portionwise. The reaction was stirred at room temperature overnight. The resulting mixture was diluted with dichloromethane, then water was added. The organic layer was washed four times with water, dried over sodium sulfate, filtered and concentrated under reduced pressure at 40° C. under 160 mbar. The crude was purified by chromatography over silica gel to afford methyl 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate.

[0346] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 1.25-1.34 (m, 1H) 1.48-1.55 (m, 1H) 1.88-2.00 (m, 1H) 2.46-2.53 (m, 1H) 3.98 (s, 3H) 7.60 (s, 1H) 7.98 (s, 1H) 8.19 (s, 1H).

Preparation of 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoic acid (I8)

[0347] ##STR00068##

[0348] 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate (1.43 g, 3.80 mmol) was dissolved in tetrahydrofuran (11.4 mL) and water (7.60 mL). Lithium hydroxide monohydrate (0.322 g, 7.60 mmol) was added and the resulting mixture was stirred 3 hours 30 min at room temperature. The reaction mixture was cooled to 0° C. then it was acidified with a 2M hydrochloric acid solution. The aqueous layer was extracted twice with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoic acid.

[0349] .sup.1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm 1.40-1.47 (m, 2H) 2.53-2.60 (m, 1H) 2.72 (td, J.sub.1=7.70 Hz, J.sub.2=4.77 Hz, 1H) 7.87 (s, 1H) 8.02 (s, 1H) 8.05-8.08 (m, 1H) 13.54 (br s, 1H).

[0350] LC-MS (method 1): retention time 1.04 min, m/z 297 [M−H].sup.−.

Preparation of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfanyl)benzoate (intermediate I9)

[0351] ##STR00069##

[0352] (2,2′-bipyridine)(trifluoromethanethiolato) copper (CAS 1413732-47-4) (3.9 g, 12 mmol, 2.0 equiv.) was added to a solution of methyl 3-iodo-5-(trifluoromethyl)benzoate (2.0 g, 6.1 mmol) in acetonitrile (18 mL) under argon. The reaction mixture was heated up to 90° C. and stirred overnight. After cooling down to room temperature, the reaction mixture was filtered over a pad of Celite and concentrated. The crude material was purified by two flash chromatographies over silica gel (ethyl acetate in cyclohexane) to afford the desired product as a yellow gum (1.5 g, 4.9 mmol).

[0353] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 4.02 (s, 3H), 8.11 (s, 1H), 8.44 (s. 1H), 8.53 (s, 1H).

[0354] LC-MS (method 1): retention time 1.21 min, m/z 279 [M−MeO+H].sup.+.

Preparation of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoate (intermediate I10)

[0355] ##STR00070##

[0356] 3-Chloroperbenzoic acid (2.3 g, 11 mmol, 2.1 equiv.) was added portionwise to a 0° C. cooled solution of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfanyl)benzoate (intermediate I13 prepared as described above) (1.8 g, 5.3 mmol) in dichloromethane (16 mL). After stirring for 1 hour at room temperature, more 3-chloroperbenzoic acid (2.3 g, 11 mmol, 2.1 equiv.) was added and the reaction mixture was stirred overnight. The precipitate formed was filtered. The filtrate was washed with 10% aqueous solution of sodium thiosulfate and with NaHCO.sub.3 sat solution. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude was purified by chromatography over silica gel to afford methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl) benzoate.

[0357] .sup.1H NMR (400 MHz, Chloroform) δ ppm 4.07 (s, 3H) 8.43-8.51 (m, 1H) 8.70-8.80 (m, 1H) 8.84-8.91 (m, 1H).

[0358] .sup.19F NMR (377 MHz, chloroform-d) δ ppm: −77.49 (s, 3 F)-62.96 (s, 3 F)

Preparation of 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoic acid (I11)

[0359] ##STR00071##

[0360] Methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoate (1.8 g, 5.4 mmol) was charged in a flask and dissolved in tetrahydrofuran (16 mL) and water (11 mL). To this mixture was added lithium hydroxide monohydrate (0.26 g, 11 mmol) and the reaction was stirred for 1 hour at room temperature. The reaction mixture was acidified with 1 M hydrochloric acid, and the aqueous phase was extracted with ethyl acetate twice. The combined organic phases were dried over sodium sulfate, filtered and then concentrated to afford 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoic acid which was used without further purification.

[0361] .sup.1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm: 8.68 (s, 2H) 8.71-8.76 (m, 1H) 13.33-15.22 (m, 1H).

Preparation of methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (intermediate I12)

[0362] ##STR00072##

[0363] Methyl 3-iodo-5-(trifluoromethyl)benzoate (10 g, 28.78 mmol) was taken in tetrahydrofuran (115 mL) under argon. The resulting pale brown solution was cooled down to −78° C. with a dry ice/acetone bath. The Turbo-Grignard 1.3 M in tetrahydrofuran solution (31 mL, 40.29 mmol) was added dropwise with a syringe over 20 minutes to give directly a dark solution while maintaining the temperature below −65° C. The resulting mixture was stirred at −78° C. for 15 minutes. Cuprous cyanide (3.125 g, 34.5 mmol) and anhydrous lithium chloride (1.479 g, 34.5 mmol) were added simultaneously at once to give a dark suspension. The resulting mixture was stirred again at −78° C. for 15 minutes. Cyclopropanecarbonyl chloride (5.340 mL, 57.5 mmol) was finally added dropwise over 5 minutes (temperature reached −68° C. maximum). The resulting mixture was stirred at −78° C. for 1 hour, warmed up to room temperature and stirred for 30 minutes to give a brown suspension. The reaction mixture was cooled down to −78° C. and quenched slowly with 20 ml of methanol. The resulting mixture was allowed to reach room temperature and the suspension obtained was filtered over Celite. Saturated aqueous ammonium chloride and ethyl acetate were added to the filtrate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure at 40° C. The crude material was purified by chromatography over silica gel to afford methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate.

[0364] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 1.16-1.22 (m, 2H) 1.35 (quin, J=3.76 Hz, 2H) 2.74 (tt, J.sub.1=7.84 Hz, J.sub.2=4.45 Hz, 1H) 4.02 (s, 3H) 8.45 (d, J=0.73 Hz, 1H) 8.51 (d, J=0.73 Hz, 1H) 8.86 (s, 1H).

Preparation of methyl 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoate (intermediate I13)

[0365] ##STR00073##

[0366] Methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (5.5 g, 20 mmol) was taken in 2,2-difluoro-1,3-dimethyl-imidazolidine (36 mL, 280 mmol) under argon to give a light yellow solution. The resulting mixture was stirred for 5 hours at 110° C. to give a light brown solution. The reaction mixture was cooled down to room temperature and added dropwise to 1.0 L of a vigorously stirred saturated aqueous sodium hydrogenocarbonate solution at 0° C. (temperature was maintained below 10° C.). The resulting mixture (pH 8-9) was then extracted 3 times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure at 50° C. The crude material was purified by chromatography over silica gel to afford methyl 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoate.

[0367] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 0.73-0.79 (m, 2H) 0.82-0.89 (m, 2H) 1.47-1.60 (m, 1H) 8.00 (d, J=0.73 Hz, 1H) 8.39 (s, 1H) 8.42 (s, 1H). .sup.19F NMR (377 MHz, chloroform-d) δ ppm: −98.40 (s, 3 F)-62.81 (s, 2 F).

Preparation of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (I14)

[0368] ##STR00074##

[0369] Methyl 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoate (4.45 g, 15.1 mmol) was taken in tetrahydrofuran (30.3 mL) and water (15.1 mL). Lithium hydroxide monohydrate (0.833 g, 19.7 mmol) was added and the resulting colourless cloudy solution was stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed twice with water. The combined aqueous layers were acidified with 1N aqueous hydrochloric acid until pH 1-2 and extracted three times with ethyl acetate. The combined organic layers were washed once with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure at 60° C. to afford 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic, which was used without further purification.

[0370] .sup.1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm: 0.62-0.84 (m, 4H) 1.65-1.97 (m, 1H) 7.93-8.23 (m, 1H) 8.23-8.51 (m, 2H) 13.24-14.48 (m, 1H).

[0371] LC-MS (method 1): retention time 1.03 min, m/z 279 [M−H].sup.−.

Preparation of methyl 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I15)

[0372] ##STR00075##

[0373] Methyl 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylate (1.05 g, 4.40 mmol) was dissolved in dimethylsulfoxide (13.2 mL). Then ethyl 2-cyanoacetate (0.702 mL, 6.60 mmol), potassium carbonate (1.535 g, 11.00 mmol) and tetrabutylammonium bromide (0.145 g, 0.440 mmol) were added successively at room temperature. The resulting suspension was stirred 1 hour at 90° C. and then let stirred overnight at room temperature. The reaction mass was diluted with 50 mL of water and 100 mL of ethyl acetate, cooled to O-10° C. and slowly quenched with 1N hydrochloric acid via dropping funnel until pH 3. The aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure at 50° C. The crude material was purified by chromatography over silica gel with ethyl acetate in cyclohexane to afford methyl 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)pyridine-4-carboxylate.

[0374] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 1.36-1.43 (m, 3H) 4.01 (s, 3H) 4.34 (q, J=7.58 Hz, 2H) 7.34 (s, 1H) 8.06 (s, 1H) 14.46-14.67 (m, 1H).

[0375] LC-MS (method 1): retention time 1.01 min, m/z 317 [M+H].sup.+.

Preparation of methyl 2-(cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (I16)

[0376] ##STR00076##

[0377] To a solution of methyl 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (0.800 g, 2.53 mmol) in dimethyl sulfoxide (20 mL) was added sodium chloride (0.299 g, 5.06 mmol) in water (10 mL). The resulting mixture was stirred for 4 hours at 95° C. After cooling down to room temperature, the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3*50 mL). The combined organic layers were dried over sodium sulfate, filtered and contracted under reduced pressure to afford methyl 2-(cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylate which was used without further purification.

[0378] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 4.05 (s, 3H) 4.13 (s, 2H) 8.24 (s, 1H) 8.26 (s, 1H).

[0379] LC-MS (method 1): retention time 0.89 min, m/z 243 [M−H].sup.−.

Preparation of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (I17)

[0380] ##STR00077##

[0381] Methyl 2-(cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (0.05 g, 0.20 mmol) was dissolved in dimethylformamide (2 mL). Sodium hydride (24 mg, 0.61 mmol) was added at room temperature and the colorless solution became a dark purple suspension. After 10 min, 1,2-dibromoethane (0.02 mL, 0.24 mmol) was added and the resulting suspension was stirred for 15 min at room temperature. The reaction mixture was quenched with a saturated ammonium chloride solution at 0-5° C. and diluted with ethyl acetate. The aqueous layer was acidified to pH 2-3 with 1N hydrochloric acid and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and evaporated under reduced pressure. The crude was purified by reverse phase chromatography to afford 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid.

[0382] .sup.1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm: 1.76-1.83 (m, 2H) 1.96-2.03 (m, 2H) 8.07 (d, J=1.10 Hz, 1H) 8.17 (s, 1H) 13.35-15.45 (m, 1H).

[0383] LC-MS (method 1): retention time 0.89 min, m/z 255 [M−H].sup.−.

Preparation of methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate (intermediate I18)

[0384] ##STR00078##

[0385] Methyl 3-bromo-5-(trifluoromethyl)benzoate (0.600 g, 2.08 mmol) was dissolved in N,N-dimethylformamide (4.2 mL). (Trimethylsilyl)acetonitrile (0.862 mL, 6.23 mmol) was added dropwise with a syringe. The solution was degassed under Ar for 5 min. Then ZnF.sub.2 (0.130 g, 1.25 mmol), Xantphos (0.0481 g, 0.0831 mmol) and Pd.sub.2(dba).sub.3 (0.0384 g, 0.0415 mmol) were added. The resulting black suspension was stirred at 100° C. for 22 hours then cooled down to room temperature. The mixture was concentrated under reduced pressure at 50° C. The crude material was purified by chromatography over silica gel with ethyl acetate in cyclohexane to afford methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate.

[0386] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 8.30 (1H, s), 8.23 (1H, s), 7.81 (1H, s), 3.99 (3H, s), 3.90 (2H, s); LC-MS (method 1): retention time 0.92 min, m/z 242 [M−H].sup.−.

Preparation of methyl 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoate (intermediate I19)

[0387] ##STR00079##

[0388] methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate (2.15 g, 7.07 mmol) was dissolved in N,N-dimethylformamide (32.3 mL). Cesium carbonate (7.13 g, 21.2 mmol) was added to the stirred solution and the mixture was stirred at room temperature for 10 min. 1,2-dibromoethane (0.68 mL 7.78 mmol) was added and the mixture was stirred at 60° C. for 3 hours then cooled down to room temperature. Water (30 mL) was added, then the aqueous layer was extracted with ethyl acetate (60 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, ethyl acetate in hexanes) to afford methyl 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoate.

[0389] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 8.23 (1H, s), 8.09 (1H, s), 7.79 (1H, s), 3.98 (3H, s), 1.84-1.92 (2H, m), 1.47-1.57 (m, 2H).

Preparation of 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoic acid (intermediate I20)

[0390] ##STR00080##

[0391] Methyl 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoate (59 mg, 0.22 mmol) was dissolved in tetrahydrofuran (0.66 mL) and water (0.33 ml). Lithium hydroxide monohydrate (9.3 mg, 0.22 mmol) was added and the mixture was stirred at room temperature for 42 hours. 1N hydrochloric acid was added until pH=2. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoic acid.

[0392] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 8.60-9.90 (1H, br s), 8.29 (1H, s), 8.15 (1H, s), 7.84 (1H, s), 1.84-1.93 (2H, m), 1.50-1.60 (2H, m).

[0393] LC-MS (method 1): retention time 0.86 min. m/z 254 [M−H].sup.−.

Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol

[0394] ##STR00081##

[0395] Methyl magnesium bromide (1.00 M in THF, 63.2 mL, 63.2 mmol) was added to a solution of 3-bromo-5-(trifluoromethyl)benzaldehyde (8.00 g, 31.6 mmol) in tetrahydrofuran (100 mL) at 0° C. under nitrogen. resulting brown reaction mixture was stirred at room temperature for 30 min. The reaction mixture was quenched with saturated ammonium chloride solution. The aqueous layer was extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure to obtain 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol as a light yellow liquid. 1H NMR (400 MHz, DMSO-d) δ ppm: 7.78-7.88 (m, 2H), 7.71 (s, 1H), 5.52 (d, 1H), 4.81 (m, 1H), 1.35 (d, 3H).

Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone

[0396] ##STR00082##

[0397] Pyridinium chlorochromate (5.05 g, 23.4 mmol) was added portionwise to a stirred solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol (7.00 g, 15.6 mmol) in dichloromethane (150 mL) at 0° C. The resulting brown colour reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered through celite pad then the filtrate was evaporated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (eluting with ethyl acetate in hexanes) to afford 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone as a colorless oil.

[0398] 1H NMR (400 MHz, DMSO-d) δ ppm: 8.38 (1H, s), 8.26 (1H, s), 8.19 (1H, s), 2.69 (s, 1H).

Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol

[0399] ##STR00083##

[0400] A solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone (5.00 g, 18.3 mmol) in dichloromethane (30 mL) at 0° C. was treated with triethylamine (3.84 mL, 27.5 mmol) and trimethylsilyl trifluoromethanesulfonate (6.12 g, 27.5 mmol). The mixture was stirred for 2 hours at room temperature. The reaction mixture was quenched with saturated sodium bicarbonate solution (100 mL). The aqueous layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude silyl enol ether was dissolved in dichloromethane and cooled down to 0° C. Di-iodomethane (7.37 g, 27.5 mmol) and diethylzinc (1.00 M in hexane, 27.5 mL, 27.5 mmol) were added dropwise and the mixture was stirred for 16 hours at room temperature. The reaction mixture was quenched with saturated ammonium chloride solution. The aqueous layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was dissolved in methanol at 0° C. and potassium carbonate (0.254 g, 1.83 mmol) was added. The resulting light yellow reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel (eluting with ethyl acetate in hexanes) to afford 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol as an off-white solid.

[0401] 1H NMR (400 MHz, chloroform-d) δ ppm: 7.75 (1H, s), 7.65 (1H, s), 7.58 (1H, s), 6.30 (s, 1H), 1.15-1.25 (m, 2H), 1.05-1.15 (m, 2H).

Preparation of 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene (I50)

[0402] ##STR00084##

[0403] A solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol (500 mg, 1.74 mmol) in tetrahydrofuran (2.0 mL) was added dropwise to a suspension of sodium hydride (60% in oil, 139 mg, 3.49 mmol) in tetrahydrofuran (2.0 mL). The mixture was stirred at 0° C. for 10 minutes. Methyl iodide (371 mg, 2.62 mmol) was added dropwise and the resulting mixture was stirred at 0° C. for 1 hour. Saturated ammonium chloride solution was added. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (gradient of ethyl acetate in hexanes) to afford 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene as a colorless liquid.

[0404] 1H NMR (400 MHz, DMSO-d) δ ppm: 7.82 (s, 1H), 7.69 (s, 1H), 7.55 (s, 1H), 3.27 (s, 3H), 1.20-1.28 (m, 2H), 1.09-1.18 (m, 2H).

Preparation of methyl 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoate (I51)

[0405] ##STR00085##

[0406] An autoclave was charged with 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene (1.50 g, 4.83 mmol), triethylamine (1.02 mL, 7.24 mmol) and methanol (30 mL). The reaction mixture was purged with argon. [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (353 mg, 0.483 mmol) was added. The autoclave was placed under carbon monoxide atmosphere (200 psi) and heated to 100° C. for 16 hours. The autoclave was cooled down to room temperature and filled with argon. The reaction mixture was filtered through celite. Water and ethyl acetate were added to the filtrate and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The crude residue was purified by flash chromatography over silica gel (gradient of ethyl acetate in hexanes) to afford methyl 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoate as a pale yellow liquid.

[0407] 1H NMR (400 MHz, chloroform-d) δ ppm: 8.17 (s, 1H), 8.05 (s, 1H), 7.78 (s, 1H), 3.95 (s, 3H), 3.25 (s, 3H), 1.30 (t, 2H), 1.05 (t, 2H).

Preparation of 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid (I52)

[0408] ##STR00086##

[0409] Methyl 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoate (1.00 g, 3.46 mmol) was dissolved in tetrahydrofuran (6.0 mL) and water (3.0 mL). Lithium hydroxide monohydrate (291 mg, 6.93 mmol) was added and the mixture was stirred at room temperature for 3 hours. The mixture was concentrated and 2N hydrochloric acid was added at 0° C. The precipitate that formed was filtered off, washed with water and dried to afford 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid as a white solid.

[0410] 1H NMR (400 MHz, chloroform-d) δ ppm: 13.4-13.7 (br. S, 1H), 8.00-8.10 (m, 2H), 7.72 (s, 1H), 3.19 (s, 3H), 1.25-1.35 (m, 2H), 1.08-1.15 (m, 2H).

Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethenone (I21)

[0411] ##STR00087##

[0412] To a previously degassed solution of 1-(3-chloropyrazin-2-yl)ethanone (8.14 g, 52.0 mmol) in toluene (160 mL) were added tetrakis(triphenylphosphine)palladium(0) (4.72 g, 4.00 mmol), copper(I) iodide (0.777 g, 4.00 mmol) and tributyl(pyrimidin-2-yl)stannane (12.7 mL, 40.0 mmol). The reaction mixture was heated up to reflux and stirred overnight. After cooling down to room temperature, it was filtered though Celite and the filtrate was concentrated under reduced pressure. Two purifications of the crude material by flash chromatography over silica gel (eluting first with ethyl acetate:ethanol 3:1 in dichloromethane, and then with ethyl acetate in cyclohexane) afforded 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethenone.

[0413] LCMS (method 1): retention time 0.37 min, m/z 201 [M+H.sup.+]; .sup.1H-NMR (400 MHz, CDCl.sub.3): δ ppm: 8.89 (d, J=4.77 Hz, 2H) 8.82 (d, J=2.20 Hz, 1H) 8.68 (d, J=2.20 Hz, 1H) 7.37 (t, J=4.95 Hz, 1H) 2.76 (s, 3H).

Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine (I31)

[0414] ##STR00088##

[0415] To a solution of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (0.401 g, 2.01 mmol) in a saturated solution of ammonium acetate in ethanol (32 mL) were added ammonia (7 M in methanol, 14.3 mL) and sodium cyanoborohydride (0.398 g, 6.02 mmol). The reaction mixture was heated up to reflux and stirred for 16.5 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was diluted in 2 M sodium hydroxide (10 mL) and it was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. One purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water), followed by a second purification by flash chromatography over silica gel (eluting methanol in dichloromethane) afforded 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine as a yellow solid.

[0416] LCMS (method 1): retention time 0.19 min, m/z 202 [M+H.sup.+]; .sup.1H-NMR (400 MHz, CDCl.sub.3): δ ppm: 8.97 (d, J=4.77 Hz, 2H), 8.68 (d, J=2.20 Hz, 1H), 8.64 (d, J=2.57 Hz, 1H), 7.41 (t, J=4.95 Hz, 1H), 4.64 (q, J=6.60 Hz, 1H), 2.13 (br s, 2H), 1.48 (d, J=6.60 Hz, 3H).

Preparation of tributyl-(5-cyclopropylpyrimidin-2-yl)stannane

[0417] ##STR00089##

[0418] To a solution of 2-chloro-5-cyclopropyl-pyrimidine (90%, 2.70 g, 15.7 mmol) in toluene (40 mL) were added hexa-n-butylditin (15.9 mL, 31.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.82 g, 1.57 mmol). The reaction mixture was purged with argon for 10 minutes, heated up to 100° C. and stirred for 2 hours. After cooling down to room temperature, it was diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethyl acetate in hexane) afforded tributyl-(5-cyclopropylpyrimidin-2-yl)stannane as a yellow oil. .sup.1H-NMR (400 MHz, CDCl.sub.3): δ ppm: 7.3 (m, 2H), 1.65 (m, 6H), 1.35 (m, 16H), 0.9 (m, 12H).

Preparation of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone (I23)

[0419] ##STR00090##

[0420] To a solution of 1-(3-chloropyrazin-2-yl)ethanone (90%, 2.00 g, 11.5 mmol) in toluene (20 mL) were added tributyl-(5-cyclopropylpyrimidin-2-yl)stannane (6.80 g, 14.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.33 g, 1.15 mmol). The reaction mixture was purged with argon for 10 minutes. Then copper(I) iodide (0.438 g, 2.30 mmol.) was added and the resulting reaction mixture was heated up to 100° C. and stirred for 12 hours. After cooling down to room temperature, it was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethyl acetate in hexane) afforded 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone as a brown solid.

[0421] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ ppm: 8.7 (d, 1H), 8.55 (d, 1H), 8.50 (s, 2H), 2.7 (s, 3H), 1.85 (m, 1H), 1.1 (m, 2H), 0.8 (m, 2H).

Preparation of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanamine (I32)

[0422] ##STR00091##

[0423] To a solution of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone (90%, 1.00 g, 3.75 mmol) in a saturated solution of ammonium acetate in ethanol (75 mL) was added ammonia (30% in water, 30 mL). The reaction mixture was stirred at room temperature for 10 minutes. Then sodium cyanoborohydride (0.706 g, 11.2 mmol) was added and the reaction mixture was heated up to 100° C. and stirred for 12 hours. After cooling down to room temperature, it was concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanamine as a brown oil.

[0424] .sup.1H-NMR (400 MHz, DMSO): δ ppm 8.85 (m, 2H), 8.80 (m, 2H), 5.0 (m, 1H), 3.2 (m, 3H) 2.1 (m, 1H), 1.15 (m, 2H), 1.0 (m, 2H).

Preparation of tert-butyl N-(6-tributylstannyl-3-pyridyl)carbamate

[0425] ##STR00092##

[0426] A solution of tert-butyl N-(6-bromo-3-pyridyl)carbamate (2.50 g, 8.24 mmol) in dry tetrahydrofuran (50 mL) was cooled to −75° C. and n-Butyllithium (2.50 M, 5.77 mL, 14.4 mmol) was added dropwise over 5 min. The reaction mixture was stirred for 1 hour at the same temperature. Then tributyltin chloride (4.69 g, 14.4 mmol) was added to the reaction mixture which was then allowed to stir at room temperature for 3 hours. The reaction mixture was quenched with saturated ammonium chloride solution and it was extracted with ethyl acetate. Combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by chromatography over neutral alumina afforded the desired product.

[0427] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ ppm: 8.5 (m, 1H), 7.85 (br s, 1H), 7.4 (dd, 1H), 6.5 (s, 1H), 1.55 (m, 15H), 1.35 (m, 6H), 1.15 (m, 6H), 0.9 (m, 9H).

Preparation of tert-butyl N-[6-(3-acetylpyrazine-2-yl)-3-pyridyl]carbamate (I28)

[0428] ##STR00093##

[0429] To a solution of tert-butyl N-(6-tributylstannyl-3-pyridyl)carbamate (36.0 g, 70.8 mmol) in toluene (720 mL) were added 1-(3-chloropyrazin-2-yl)ethanone (12.3 g, 70.8 mmol) and copper(I) iodide (2.70 g, 14.2 mmol). The reaction mixture was purged with argon for 20 min and tetrakis(triphenylphosphine)palladium(0) (4.09 g, 3.54 mmol) was added. The reaction was stirred at 100° C. for 5 h. After cooling down at room temperature, the reaction mixture was filtered through celite pad and the filtrate was evaporated under reduced pressure. The residue was diluted with ethyl acetate, washed with water, brine and saturated potassium fluoride solution, over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethylacetate in n-hexane) afforded tert-butyl N-[6-(3-acetylpyrazin-2-yl)-3-pyridyl]carbamate.

[0430] .sup.1H-NMR (400 MHz, DMSO): δ ppm: 9.9 (s, 1H), 8.6-8.9 (m, 3H), 8.1-8.25 (m, 2H), 2.55 (s, 1H), 1.5 (s, 9H).

Preparation of 1-[3-(5-amino-2-pyridyl)pyrazin-2-yl]ethanone (I29)

[0431] ##STR00094##

[0432] HCl in 1,4-dioxane (4.00 M, 73.0 mL, 0.292 mol) was added as dropwise to a solution of tert-butyl N-[6-(3-acetylpyrazin-2-yl)-3-pyridyl]carbamate (17.0 g, 0.0487 mol) in dichloromethane (510 mL) cooled to 0° C. The mixture was stirred for 10 min then allowed to stir at room temperature for 16 hours. The reaction mixture was concentrated in vacuo and poured into a mixture of ice-cold water and dichloromethane. The pH was adjusted to 12 with 2N sodium hydroxide solution. The aqueous layer was extracted with dichloromethane three times. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification of the crude material by flash chromatography over silica gel (eluting with methanol in dichloromethane) afforded 1-[3-(5-amino-2-pyridyl)pyrazin-2-yl]ethenone as a yellow solid.

[0433] LC-MS (method 3): retention time 1.41 min, m/z 215.1 [M+H].sup.+

Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanone (125)

[0434] ##STR00095##

[0435] A solution of 1-[3-(5-amino-2-pyridyl)pyrazin-2-yl]ethanone (3.00 g, 12.6 mmol) in acetonitrile (200 mL) was cooled to 0° C. Copper (11) chloride (3.39 g, 25.2 mmol) was added, followed by tert-butyl nitrite (2.17 mL, 25.2 mmol) dropwise. The reaction mixture was stirred for 16 hours at room temperature. The reaction mixture was quenched with saturated ammonium chloride solution, stirred for 15 min and concentrated under reduced pressure. Purification of the crude material by reverse phase chromatography (C18; eluting with acetonitrile in water) afforded 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanone. .sup.1H-NMR (400 MHz, DMSO): δ ppm: 8.9 (s, 1H), 8.8 (d, 1H), 8.7 (s, 1H), 8.2 (m, 2H), 2.6 (s, 3H).

Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (I35)

[0436] ##STR00096##

[0437] To a solution of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanone (3.20 g, 11.0 mmol) in a saturated solution of ammonium acetate in ethanol (150 mL) were added at room temperature sodium cyanoborohydride (2.04 g, 32.9 mmol) and ammonia (30% in water, 100 mL). The reaction mixture was stirred at 90° C. for 12 hours. After cooling down to room temperature, it was concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine.

[0438] LCMS (method 3): retention time 2.7 min, m/z=235 [M+H.sup.+]

Preparation of tert-butyl N-[2-(3-acetylpyrazin-2-yl)pyrimidin-5-yl]carbamate (I53)

[0439] ##STR00097##

[0440] To a solution of tert-butyl N-(2-tributylstannylpyrimidin-5-yl)carbamate (600 mg, 0.867 mmol) in toluene (20 mL) were added 1-(3-chloropyrazin-2-yl)ethanone (151 mg, 0.867 mmol) and copper(I) iodide (33 mg, 0.173 mmol). The reaction mixture was purged with argon for 5 min and tetrakis(triphenylphosphine)palladium(0) (50.1 mg, 0.0434 mmol) was added. The reaction was stirred at 90° C. for 3 hours. After cooling down at room temperature, the reaction mixture was filtered through celite pad and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography over silica gel (eluting with ethylacetate in n-hexane) afforded tert-butyl N-[2-(3-acetylpyrazin-2-yl)pyrimidin-5-yl]carbamate as a brown gum.

[0441] LCMS (method 3): retention time 1.04 min, m/z=216.1 [M+H.sup.+]

Preparation of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanone (I54)

[0442] ##STR00098##

[0443] A solution of 1-[3-(5-aminopyrimidin-2-yl)pyrazin-2-yl]ethanone (2.80 g, 11.7 mmol) in acetonitrile (50 mL) was cooled to 0° C. Isoamyl nitrite (2.74 g, 23.4 mmol) was added followed by cupric bromide (5.23 g, 23.4 mmol). The reaction mixture was stirred for 6 hours at room temperature. The reaction mixture was quenched with saturated ammonium chloride solution, stirred for 15 min and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethylacetate in n-hexane) afforded 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethenone as a brown solid.

[0444] .sup.1H-NMR (400 MHz, DMSO): δ ppm: 9.15 (s, 2H), 8.95 (m, 1H), 8.88 (m, 1H), 2.63 (s, 3H).

[0445] LCMS (method 3): retention time 3.54 min, m/z=279/281 [M+H]+(bromo pattern)

Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (I55)

[0446] ##STR00099##

[0447] To a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanone (495 mg, 1.60 mmol) in aqueous ammonia (30% in water, 4.3 mL) was added a saturated solution of ammonium acetate in ethanol (10.8 mL) followed by sodium cyanoborohydride (301 mg, 4.79 mmol). The reaction mixture was stirred at 90° C. for 12 hours. After cooling down to room temperature, it was concentrated under reduced pressure to afford 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine.

[0448] .sup.1H-NMR (400 MHz, DMSO): δ ppm: 9.22 (s, 2H), 8.70-9.00 (m, 2H), 4.50-4.80 (m, 1H), 1.42 (d, 3H).

Preparation of 3,5-dichloro-2-pyrimidin-2-yl-pyrazine

[0449] ##STR00100##

[0450] To a solution of 3,5-dichloro-2-iodo-pyrazine (0.500 g, 1.81 mmol) in dioxane (5 mL) was added at room temperature tributyl(pyrimidin-2-yl)stannane (CAS 153435-63-3, 0.671 g, 1.81 mmol followed tetrakis(triphenylphosphine)palladium (0.211 g, 0.181 mmol). The reaction mixture was heated to 180° C. for 2 hours in microwave. After cooling down to room temperature, the reaction mixture was concentrated under reduced pressure to afford crude mass which was purified by flash column chromatography over silica gel (ethyl acetate in cyclohexane) to afford 3,5-dichloro-2-pyrimidin-2-yl-pyrazine as a brown solid.

[0451] LC-MS (method 4): retention time 1.23 min, m/z 228 [M+H.sup.+]; .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 8.99 (d, 2H), 8.68 (s, 1H), 7.46 (t, 1H).

Preparation of 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine

[0452] ##STR00101##

[0453] To a solution of 3,5-dichloro-2-pyrimidin-2-yl-pyrazine (0.100 g, 0.440 mmol) in methanol (1 mL), was added sodium methoxide (0.0099 mL, 0.044 mmol) at 0° C. and the reaction mass was stirred for 2 hours at room temperature. The reaction mixture was quenched in acetic acid and water (20 mL), extracted three times with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine as a white solid.

[0454] LC-MS (method 4): retention time 0.37 min, m/z 223 [M+H.sup.+]; .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 8.95 (d, 2H) 8.29 (s, 1H) 7.37 (t, 1H) 4.07 (s, 3H)

Preparation of 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine

[0455] ##STR00102##

[0456] To a solution of 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine (0.060 g, 0.269 mmol) in dioxane (1 mL) was added at room temperature tributyl (1-ethoxyvinyl) stannane (0.140 mL, 0.404 mmol) and tetrakis(triphenylphosphine)palladium (0.013 g, 0.026 mmol). The reaction mixture was heated to 150° C. and stirred for 1 hour in the microwave. After cooling down to room temperature, the reaction mixture was concentrated under reduced pressure and purified by flash column chromatography over silica gel (ethyl acetate in cyclohexane) to afford 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine as a brown solid.

[0457] LC-MS (method 4): retention time 1.11 min, m/z 259 [M+H.sup.+].

Preparation of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethenone (I47)

[0458] ##STR00103##

[0459] To a solution of 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine (0.10 g, 0.387 mmol) in acetonitrile (1 mL), acetic acid (1 mL) and water (1 mL) were added at room temperature and the reaction mixture was heated at 50° C. for 2 hours. The reaction mixture was quenched with water (20 mL), extracted three times with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethenone as a white solid.

[0460] LC-MS (method 4): retention time 1.07 min, m/z 231 [M+H.sup.+].

Preparation of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethanamine (I48)

[0461] ##STR00104##

[0462] To a solution of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethanone (0.060 g, 0.260 mmol) in methanol (5 mL), ammonium acetate (0.209 g, 2.60 mmol) was added at room temperature and the reaction mixture was stirred for 1 hour at room temperature. To this reaction mixture, sodium cyanoborohydride (0.051 g, 0.781 mmol) was added and the reaction mixture was heated at 50° C. for 2 hours. The reaction mixture was diluted in water (40 mL) extracted three times with 20% in methanol in chloroform. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethanamine as a brown solid.

[0463] LC-MS (method 4): retention time 0.35 min, m/z 232 [M+H.sup.+].

Preparation of 1-(3-chloropyrazin-2-yl)ethanamine

[0464] ##STR00105##

[0465] To a of 1-(3-chloropyrazin-2-yl)ethanone (0.200 g, 1.28 mmol) in methanol (4.5 mL) were added at room temperature ammonium acetate (0.995 g, 12.8 mmol) and sodium cyanoborohydride (0.0591 g, 0.894 mmol). The resulting suspension was stirred at room temperature for 18 hours, then concentrated in vacuo. The crude material was purified by reverse phase chromatography (C18 column, gradient of acetonitrile in water) to afford 1-(3-chloropyrazin-2-yl)ethanamine.

[0466] .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 8.49 (d, 1H), 8.26 (d, 1H), 4.56 (q, 1H), 1.95 (br s, 2H), 1.44 (d, 3H)

Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethanamine (I45)

[0467] ##STR00106##

[0468] To a solution if 1-(3-chloropyrazin-2-yl)ethanamine (202.2 mg, 1.20 mmol) in tert-butyl methyl ether (11 mL) was added Novozym® 435 (240 mg), followed by ethyl methoxyacetate (1.44 mL, 12.0 mmol) at room temperature. The mixture was stirred at 40° C. for 5.5 hours. The reaction mixture was diluted with dichloromethane and filtered. The filtrate was concentrated in vacuo. The crude material was purified by flash chromatography over silica gel (eluting with a gradient of methanol in dichloromethane) to afford (1S)-1-(3-chloropyrazin-2-yl)ethanamine.

[0469] .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 8.49 (d, 1H), 8.27 (d, 1H), 4.56 (q, 1H), 1.73 (br s, 2H), 1.44 (d, 3H); [α].sub.D.sup.20: −32.3° (c: 1.157, CHCl.sub.3)

Preparation of (1R)-1-(3-chloropyrazin-2-yl)ethanol (I44)

[0470] ##STR00107##

[0471] 1-(3-chloropyrazin-2-yl)ethanone (157 mg, 1.00 mmol) was dissolved in dichloromethane (10.0 mL) and the flask was evacuated and backfilled with argon three times. Then RuBF.sub.4[(R,R)-TsDPEN](p-cymene) (0.0362 g, 0.0526 mmol) was added. A cooled solution of triethylamine (0.348 mL, 2.50 mmol.) and formic acid (0.160 mL, 4.29 mmol) was added dropwise to the reaction mixture, which was stirred at room temperature for 4 hours. The reaction mixture was concentrated in vacuo. The crude material was purified by flash chromatography over silica gel (eluting with a gradient of ethyl acetate in cyclohexane) to afford (1R)-1-(3-chloropyrazin-2-yl)ethanol.

[0472] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ ppm 8.49 (d, 1H), 8.34 (d, 1H), 5.18 (m, 1H), 3.81 (d, 1H), 1.52 (d, 3H) Chiral SFC (method 2): 1.98 min (minor enantiomer), 2.55 min (major enantiomer); ee=85%

Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethanamine (I45)

[0473] ##STR00108##

[0474] (1R)-1-(3-chloropyrazin-2-yl)ethanol (87.8 mg, 0.554 mmol) was dissolved in tetrahydrofuran (1.9 mL). Then, 1,8-diazabicyclo[5.4.0]undec-7-ene (0.10 mL, 0.66 mmol) was added dropwise to the reaction mixture followed by diphenylphosphine azide (0.130 mL, 0.585 mmol). The reaction mixture was stirred at rt for 19 hours.

[0475] Tetrahydrofuran (1.4 mL) was added, followed by triphenylphosphine (179.4 mg, 0.677 mmol). The reaction mixture was stirred at room temperature for 2 hours. Water (0.15 mL) was added, and the reaction mixture was stirred at room temperature for 46 hours.

[0476] The reaction mixture was concentrated to a volume of 1 mL then diluted with dichloromethane. 1 M hydrochloric acid was added, then the aqueous layer was washed with dichloromethane. The aqueous layer was basified to pH=14 with 4 M sodium hydroxide solution and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography over silica gel (eluting with a gradient of methanol in dichloromethane) to afford (1S)-1-(3-chloropyrazin-2-yl)ethanamine.

[0477] .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 8.49 (d, 1H), 8.27 (d, 1H), 4.56 (q, 1H), 1.84 (s, 2H), 1.44 (d, 3H) [α].sub.D.sup.20: −26.0° (c: 0.960, CHCl.sub.3)

Preparation of (2R)—N-[(1S)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide

[0478] ##STR00109##

[0479] To a solution of 1-(3-chloropyrazin-2-yl)ethanamine;hydrochloride (700 mg, 3.61 mmol) in dichloromethane (18 mL) were added (R)-(−)-mandelic acid (610 mg, 3.97 mmol), N-ethyldiisopropylamine (1.26 mL, 7.21 mmol), 1-hydroxybenzotriazole (50.8 mg, 0.361 mmol) and N,N′-dicyclohexylcarbodiimide (844 mg, 3.97 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with saturated aqueous sodium carbonate solution and extracted with dichloromethane. The organic layers were dried over magnesium sulfate and concentrated in vacuo. Purification of the crude material by flash chromatography over silica gel (eluting with methanol in dichloromethane) afforded (2R)—N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide and (2R)—N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide. The relative stereochemistry of (2R)—N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide was determined by X-ray crystallography (crystallized from acetonitrile/water).

[0480] Analytical data for (2R)—N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide: LCMS (method 1): retention time 0.74 min, m/z=291 [M+H.sup.+]

Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethanamine;hydrochloride

[0481] ##STR00110##

[0482] A solution of (2R)—N-[(1S)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide (0.93 g, 3.2 mmol) in hydrochloric acid (32% in water, 13 mL) was heated up to reflux and stirred for 2 hours. After cooling down to room temperature, the reaction mixture was basified with 3 N sodium hydroxide and diluted and extracted with ethyl acetate. The aqueous layer was freeze-dried overnight and the resulting solid was suspended in acetone. The suspension was filtered and the filtrate was concentrated under reduced pressure. The resulting oil was dissolved in ethyl acetate and 1 N hydrochloric acid was added. A precipitate appeared, it was filtered and dried under reduced pressure to afford the desired product. LCMS (method 1): retention time 0.19 min, m/z=158 [M+H+].

Preparation of (1S)-1-(3-chloropyrazin-2-yl)-N-(cyclopropylmethyl)ethanamine (I46)

[0483] ##STR00111##

[0484] Sodium triacetoxyborohydride (59.4 mg, 0.267 mmol) was added to a stirred solution of (1S)-1-(3-chloropyrazin-2-yl)ethanamine (30.0 mg, 0.190 mmol), cyclopropanecarboxyladehyde (15.0 mg, 0.209 mmol) and acetic acid (0.0109 mL, 0.190 mmol) in 1,2-dichloroethane (0.95 mL). The mixture was stirred at room temperature for 4 hours. Saturated aqueous sodium carbonate solution was added, the aqueous layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography over silica gel (eluting with ethyl acetate in cyclohexane) to afford (1S)-1-(3-chloropyrazin-2-yl)-N-(cyclopropylmethyl)ethanamine.

[0485] .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm −0.03-0.10 (m, 2H) 0.38-0.52 (m, 2H) 0.83-1.00 (m, 1H) 1.40 (d, 3H) 2.07 (dd, 1H) 2.15-2.29 (m, 1H) 2.53 (dd, 1H) 4.39 (q, 1H) 8.26 (d, 1H) 8.51 (d, 1H); [α].sub.D.sup.20=−540 (c 0.327, CHCl.sub.3)

Preparation of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamate

[0486] ##STR00112##

[0487] In a round-bottomed flask was prepared a solution of tert-butyl N-[(1S)-1-methyl-2-oxo-ethyl]carbamate (CAS 79069-50-4, 1.07 g, 6.18 mmol) in dichloromethane (12 mL). The flask was evacuated and refilled with argon three times. Then, 2-(3-benzyl-4-methyl-thiazol-3-ium-5-yl)ethanol;bromide (0.388 g, 1.24 mmol), 5-bromopyridine-2-carbaldehyde (CAS 31181-90-5, 1.81 g, 9.27 mmol) and dichloromethane (6 mL) were added successively, followed by N,N-diisopropylethylamine (2.16 mL, 12.4 mmol). The reaction mixture was stirred for 1 hour at room temperature. It was quenched with ammonium chloride sat. aq. and extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethyl acetate in cyclohexane) afforded tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamate as an orange gum.

[0488] LCMS (method 1): retention time 0.98 min, m/z=359-361[M+H+] (Bromo pattern); 1H-NMR (400 MHz, CDCl3) δ ppm: 1.37-1.40 (m, 3H) 1.43-1.44 (m, 9H) 4.34-4.69 (m, 2H) 5.22-5.36 (m, 1H) 7.86-8.08 (m, 2H) 8.73 (d, J=2.20 Hz, 1H).

Preparation of tert-butyl N-[(1 S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate

[0489] ##STR00113##

[0490] To a solution of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamate (15.2 g, 42.3 mmol) in dichloromethane (100 mL) and dimethyl sulfoxide (20 mL) were added at 0° C. N,N-diisopropylethylamine (21.8 mL, 127 mmol, 3.00 equiv.) and in two portions sulfur trioxide pyridine complex (13.9 g, 84.6 mmol, 2.00 equiv.). The reaction mixture was stirred at 0° C. for 1 hour. It was quenched water and diluted with dichloromethane and 1 N hydrochloric acid. The aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethyl acetate in cyclohexane) afforded tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate as an orange oil.

[0491] 1H-NMR (400 MHz, CDCl3) δ ppm: 1.36-1.41 (m, 9H) 1.45-1.48 (m, 3H) 4.82-4.96 (m, 1H) 5.10 (br s, 1H) 7.91-8.00 (m, 1H) 8.01-8.11 (m, 1H) 8.79 (d, J=1.83 Hz, 1H).

Preparation of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (I42)

[0492] ##STR00114##

[0493] To a solution of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate (2.00 g, 5.60 mmol) in ethanol (22 mL) was added ethylenediamine (1.91 mL, 28.0 mmol). The reaction mixture was stirred at room temperature for 60 h in the presence of air. It was concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethyl acetate in cyclohexane) afforded tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate as a colorless gum.

[0494] LCMS (method 1): Retention time 1.09 min, m/z=379-381 [M+H+] (Bromo pattern);

[0495] 1H-NMR (400 MHz, CDCl.sub.3) δ ppm: 1.33-1.45 (m, 9H) 1.52-1.56 (m, 3H) 5.65-5.83 (m, 2H) 7.96-8.02 (m, 2H) 8.53-8.60 (m, 2H) 8.79 (dd, J=2.20, 1.10 Hz, 1H);

[0496] Chiral SFC (method 1): 1.80 min (major enantiomer), 1.11 min (minor enantiomer); ee=92%

Preparation of tert-butyl N-[(1S)-1-[6-amino-3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (149)

[0497] ##STR00115##

[0498] 2-aminoacetamide dihydrobromide (1.21 g, 4.11 mmol) was added to a mixture of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate (500 mg, 0.894 mmol) in 2-propanol (13.4 mL). Potassium acetate (266 mg, 2.68 mmol) was added, and the mixture was stirred at room temperature for 2.5 hours. Water was added, the aqueous layer was extracted with ethyl acetate, the organic layer was washed with brine, dried over magnesium sulfate and concentrated. The crude mixture was purified by reverse-phase chromatography (C18 column, gradient of acetonitrile in water) to give tert-butyl N-[(1S)-1-[6-amino-3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate.

[0499] LCMS (method 1): Retention time 1.04 min, m/z=394-396 [M+H.sup.+] (Bromo pattern); .sup.1H NMR (600 MHz, CDCl3) δ ppm: 1.45-1.47 (m, 12H) 4.84 (br s, 2H) 5.66-5.74 (m, 1H) 5.89 (br s, 1H) 7.86-7.88 (m, 1H) 7.89 (br d, 1H) 7.90 (s, 1H) 8.72 (s, 1H).

Preparation of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate

[0500] ##STR00116##

[0501] 1,2-diaminopropane (16.4 mL, 190 mmol) was added in 4 portions over 36 hours to a mixture of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate (1.130 g, 3.16 mmol) in ethanol (12.7 mL). Water was added, the aqueous layer was extracted with ethyl acetate, the organic layer was washed with brine, dried over magnesium sulfate and concentrated. The crude mixture was purified by chromatography over silica gel (gradient of ethyl acetate in cyclohexane) to give a mixture of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate.

[0502] LCMS (method 1): Retention time 1.14 and 1.15 min, m/z=393-395 [M+H.sup.+] (Bromo pattern); .sup.1H NMR (600 MHz, CDCl3) δ ppm (mixture): 1.45-1.47 (m, 24H) 4.84 (br s, 4H) 5.66-5.74 (m, 2H) 5.89 (br s, 2H) 7.86-7.88 (m, 2H) 7.89 (br d, 2H) 7.90 (s, 1H) 8.72 (s, 2H).

Preparation of (1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethanamine and (1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethanamine

[0503] ##STR00117##

[0504] Trifluoroacetic acid (2.00 mL, 25.2 mmol) was added in two portions to a solution of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate (550 mg, 1.40 mmol) in dichloromethane (9.0 mL) at 0° C. The reaction was stirred at room temperature for 28 hours. The reaction mixture was poured in sat. aq. Sodium bicarbonate. The aqueous layer was extracted with dichloromethane, the organic layer was dried with magnesium sulfate and concentrated to give a mixture of (1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethanamine and (1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethanamine as a brown oil.

[0505] LCMS (method 1): Retention time 0.54 min, m/z=293-295 [M+H.sup.+] (Bromo pattern); .sup.1H NMR (400 MHz, CDCl3) δ ppm: 1.40-1.46 (m, 6H) 2.55-2.62 (m, 6H) 4.56-4.73 (m, 2H) 7.86-8.02 (m, 4H) 7.93-7.93 (m, 1H) 8.34-8.48 (m, 2H) 8.72-8.78 (m, 2H)

Preparation of (1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine (I43)

[0506] ##STR00118##

[0507] To a solution of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (1.14 g, 3.00 mmol) in dichloromethane (27 mL) was added at 0° C. trifluoroacetic acid (5.40 mL, 68.0 mmol). The reaction mixture was stirred at room temperature overnight. It was added dropwise to a saturated solution of sodium carbonate. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford (1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine as a yellow oil.

[0508] LCMS (method 1): Retention time 0.54, m/z=279-281 [M+H+] (Bromo pattern); 1H-NMR (400 MHz, CDCl3) δ ppm: 1.47 (d, J=6.60 Hz, 3H) 2.09 (s, 2H) 4.67-4.76 (m, 1H) 7.90-7.94 (m, 1H) 7.96-8.03 (m, 1H) 8.51 (d, J=2.20 Hz, 1H) 8.60 (d, J=2.57 Hz, 1H) 8.77 (dd, J=2.20, 0.73 Hz, 1H).

Preparation of 2-(1-cyanocyclopropyl)-N-[1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethyl]-6-(trifluoromethyl)pyridine-4-carboxamide (P32)

[0509] ##STR00119##

[0510] To a solution of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanamine (20.7 mg, 85.9 μmol) in N,N-dimethylformamide (1 mL) were added at 0° C. 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (22 mg, 85.9 μmol), N,N-diisopropylethylamine (44.9 μL, 0.258 mmol) and propanephosphonic acid anhydride (78.1 μL, 0.172 mmol). The reaction mixture was stirred at room temperature for 6 hours. It was then poured on ice water and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (eluting with ethyl acetate in hexane) afforded 2-(1-cyanocyclopropyl)-N-[1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethyl]-6-(trifluoromethyl)pyridine-4-carboxamide as a light brown solid.

[0511] .sup.1H-NMR (400 MHz, DMSO): δ ppm: 9.4 (d, 1H), 8.75 (m, 1H), 8.7 (m, 3H), 8.1 (s, 1H), 7.95 (s, 1H), 5.65 (m, 1H), 2.0 (m, 1H), 1.95 (m, 2H), 1.75 (m, 2H), 1.6 (m, 3H), 1.1 (m, 2H), 0.85 (m, 2H).

Preparation of N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzamide (P17)

[0512] ##STR00120##

[0513] To a solution of 3-[cyano(cyclopropyl)methyl]-5-(trifluoromethyl)benzoic acid (130 mg, 0.484 mmol) in toluene (20 mL) was added dropwise at 0° C. thionyl chloride (0.141 mL, 1.94 mmol). The reaction mixture was stirred at 90° C. for 20 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added at 0° C. to a solution of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (139 mg, 0.532 mmol) and triethylamine (0.272 mL, 1.94 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzamide.

[0514] 1H-NMR (400 MHz, DMSO): δ ppm: 9.25 (d, 1H), 8.8 (m, 1H), 8.75 (m, 1H), 8.65 (m, 1H), 8.15 (m, 1H), 8.05 (s, 1H), 8 (d, 1H), 7.95 (m, 1H), 7.75 (s, 1H), 5.8 (m, 1H), 1.8 (m, 2H), 1.65 (m, 5H).

Preparation of N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide (P16)

[0515] ##STR00121##

[0516] To a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (130 mg, 0.482 mmol) in toluene (20 mL) was added dropwise at 0° C. thionyl chloride (0.141 mL, 1.94 mmol). The reaction mixture was stirred at 90° C. for 2 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added at 0° C. to a solution of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (138 mg, 0.530 mmol) and triethylamine (0.271 mL, 1.93 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid.

[0517] .sup.1H-NMR (400 MHz, DMSO): δ ppm: 9.55 (d, 1H), 8.60-8.80 (m, 3H), 8.12 (m, 1H), 8.01 (m, 2H), 7.95 (s, 1H), 5.83 (m, 1H), 1.92 (m, 2H), 1.75 (m, 2H), 1.67 (d, 3H).

Preparation of N-[1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide (P28)

[0518] ##STR00122##

[0519] To a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (100 mg, 0.371 mmol) in toluene (15 mL) was added dropwise at 0° C. thionyl chloride (0.108 mL, 1.48 mmol). The reaction mixture was stirred at 90° C. for 2.5 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added at 0° C. to a solution of 1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine (108 mg, 0.371 mmol) and triethylamine (0.208 mL, 1.48 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 3 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded N-[1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid.

[0520] .sup.1H-NMR (400 MHz, DMSO): δ ppm: 9.53 (d, 1H), 8.80-8.90 (m, 1H), 8.60-8.80 (m, 2H), 8.20-8.30 (m, 1H), 8.12 (m, 1H), 7.97 (m, 2H), 5.79-5.90 (m, 1H), 1.93 (m, 2H), 1.70-1.80 (m, 2H), 1.65 (d, 3H); .sup.19F-NMR (377 MHz, DMSO): δ ppm: −66.69.

Preparation of 3-cyclopropyl-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)-benzamide (P41)

[0521] ##STR00123##

[0522] A mixture of 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic (0.10 g, 0.43 mmol, 1.0 equiv.), 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine trifluoroacetate salt (1.6 g, 0.52 mmol, 1.2 equiv.), and HATU (0.17 g, 1.3 mmol, 3.0 equiv.) in N,N-dimethylformamide (2.9 mL) was stirred at room temperature 1 hour. The reaction mixture was then diluted with ethyl acetate and the organic phase was washed with water (5 times), brine, dried over magnesium sulfate, filtered and concentrated. The crude material was purified by chromatography over silica gel to afford the title compound as an off-white solid.

[0523] .sup.1H NMR (400 MHz, chloroform-d) δ ppm: 0.79 (q, J=5.14 Hz, 2H), 1.03-1.11 (m, 2H), 1.64 (d, J=6.6 Hz, 3H), 1.97-2.05 (m, 1H), 6.22-6.29 (m, 1H), 7.42 (s, 1H), 7.46 (t, J=4.9 Hz, 1H), 7.64-7.72 (m, 2H), 7.77 (s, 1H), 8.72 (s, 1H), 8.76 (s, 1H), 9.04 (d, J=5.1 Hz, 2H)

[0524] .sup.19F NMR (376 MHz, chloroform-d) δ/ppm −62.58 (s, 3 F) LC-MS (method 1): retention time 0.97 min, m/z 414 [M+H].sup.+

Preparation of 3-[cyclopropyl(difluoro)methyl]-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide (P30)

[0525] ##STR00124##

[0526] To a solution of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine (50 mg, 0.22 mmol) in N,N-dimethylformamide (2 mL) were added at 0° C. 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (84 mg, 0.27 mmol), 1-propanephosphonic acid cyclic anhydride (0.21 g, 0.67 mmol) and N,N-diisopropylethylamine (87 mg, 0.67 mmol). The reaction mixture was stirred at room temperature for 5 hours. It was then diluted with water and extracted twice with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded 3-[cyclopropyl(difluoro)methyl]-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide as an off-white solid.

[0527] .sup.1H-NMR (400 MHz, DMSO-d6): δ ppm: 9.3 (m, 1H) 8.95 (m, 2H) 8.75 (m, 2H) 8.2 (m, 2H), 8.0 (m, 1H) 7.55 (m, 1H) 5.6 (m, 1H) 1.8 (m, 1H) 1.6 (m, 3H) 0.7 (m, 4H).

Preparation of 3-(1-methoxycyclopropyl)-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide (P47)

[0528] ##STR00125##

[0529] To a solution of 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid (130 mg, 0.490 mmol) in toluene (3 mL) was added dropwise at 0° C. thionyl chloride (0.107 mL, 1.47 mmol). The reaction mixture was stirred at 90° C. for 2 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (2 mL) and added at 0° C. to a solution of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine (201 mg, 0.979 mmol) and triethylamine (0.206 mL, 1.47 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded 3-(1-methoxycyclopropyl)-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide as an off-white solid.

[0530] .sup.1H-NMR (400 MHz, DMSO-d6): δ ppm: 9.1 (m, 1H) 8.95 (m, 2H) 8.77 (m, 1H) 8.66 (m, 1H), 7.92 (m, 1H), 7.78 (m, 1H), 7.64 (m, 1H), 7.50-7.60 (m, 1H), 5.55-5.65 (m, 1H), 3.12 (s, 3H), 1.61 (d, 3H), 1.20-1.30 (m, 2H), 1.00-1.13 (m, 2H)

Preparation of N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethyl)benzamide (P58)

[0531] ##STR00126##

[0532] To a solution of 3-cyclopropyl-5-(trifluoromethyl)benzoic acid (60 mg, 0.248 mmol) in toluene (8 mL) was added dropwise at 0° C. thionyl chloride (0.723 mL, 9.91 mmol). The reaction mixture was stirred at 90° C. for 2.5 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added at 0° C. to a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanamine (217 mg, 0.310 mmol) and triethylamine (0.139 mL, 0.991 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 3 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethyl)benzamide as an off-white solid.

[0533] .sup.1H-NMR (400 MHz, DMSO-d6): δ ppm: 9.12 (m, 2H) 9.00 (m, 1H) 8.76 (m, 1H) 8.68 (m, 1H), 7.77 (m, 1H), 7.58 (m, 2H), 5.52-5.61 (m, 1H), 2.05-2.12 (m, 1H), 1.60 (d, 3H), 0.98-1.08 (m, 2H), 0.75-0.82 (m, 2H)

Preparation of N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide (P55)

[0534] ##STR00127##

[0535] To a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (60 mg, 0.222 mmol) in toluene (10 mL) was added dropwise at 0° C. thionyl chloride (0.162 mL, 2.22 mmol). The reaction mixture was stirred at 90° C. for 2 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added at 0° C. to a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanamine (78 mg, 0.222 mmol) and triethylamine (0.125 mL, 0.890 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid.

[0536] .sup.1H-NMR (400 MHz, DMSO-d6): δ ppm: 9.44 (m, 1H) 9.16 (s, 2H) 8.80 (m, 1H) 8.71 (m, 1H), 8.05 (m, 1H), 7.95 (m, 1H), 5.55-5.65 (m, 1H), 1.90-2.00 (m, 2H), 1.70-1.80 (m, 2H) 1.61 (d, 3H)

Preparation of N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide (P53)

[0537] ##STR00128##

[0538] To a solution of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (90 mg, 0.305 mmol) in toluene (10 mL) was added dropwise at 0° C. thionyl chloride (0.089 mL, 1.22 mmol). The reaction mixture was stirred at 90° C. for 2.5 hours. After cooling down to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added at 0° C. to a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanamine (321 mg, 0.458 mmol) and triethylamine (0.172 mL, 1.22 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 3 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (eluting acetonitrile in water) afforded N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide as a brown solid.

[0539] .sup.1H-NMR (400 MHz, DMSO-d6): δ ppm: 9.29 (d, 1H) 9.14 (s, 2H) 8.81 (m, 1H) 8.70 (m, 1H), 8.15-8.25 (m, 2H), 8.00 (m, 1H), 5.58-5.68 (m, 1H), 1.70-1.90 (m, 1H), 1.61 (d, 3H), 0.65-0.75 (m, 4H)

Preparation of N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide (P42)

[0540] ##STR00129##

[0541] Oxalyl chloride (0.0281 mL, 0.321 mmol) was added to a solution of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (0.0600 g, 0.214 mmol) in dichloromethane (0.65 mL) containing one drop of N,N-dimethylformamide. After 30 minutes, the reaction mixture was concentrated in vacuo. The crude acyl chloride was dissolved in ethyl acetate (0.86 mL), and (1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine (0.0598 g, 0.214 mmol) and aqueous sodium bicarbonate (1N, 0.86 mL) were added. The mixture was stirred at room temperature for 45 minutes. The layers were separated, the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. Purification of the crude material by flash chromatography over silica gel (eluting with ethyl acetate in cyclohexane) afforded N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide.

[0542] .sup.1H-NMR (400 MHz, chloroform-d): δ ppm: 0.71-0.80 (m, 2H) 0.81-0.88 (m, 2H) 1.47-1.61 (m, 1H) 1.68 (d, J=6.97 Hz, 3H) 6.25-6.35 (m, 1H) 7.83 (br d, J=8.07 Hz, 1H) 7.93 (s, 1H) 8.02-8.07 (m, 1H) 8.07-8.11 (m, 1H) 8.12 (s, 1H) 8.18 (s, 1H) 8.61-8.67 (m, 2H) 8.87 (dd, J=2.20, 0.73 Hz, 1H); [α].sub.D.sup.20+1150 (c: 0.580, CHCl.sub.3)

[0543] Compounds described in table P were prepared by methods similar to those described for the examples above:

TABLE-US-00013 TABLE P Examples of prepared compounds of formula I [M + H] RT (mea- Meth- Entry IUPAC name STRUCTURE (min) sured) od MP° C. P1 2-chloro-N-[1-(3-pyrimidin- 2-ylpyrazin-2-yl)ethyl]-6- (trifluoromethyl)pyridine-4- carboxamide [00130] 0.88 409 1 P2 2-(1-cyanocyclopropyl)-N- [1-[3- (5-methylpyrimidin-2-yl) pyrazin- 2-yl]ethyl]-6- (trifluoromethyl)pyridine-4- carboxamide [00131] 200-205 P3 3-(1-cyanocyclopropyl)- N-[1-[3- (5-cyclopropylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-5- (trifluoromethyl) benzamide [00132] 170-180 P4 N-[1-[3-(5-chloro-2- pyridyl)pyrazin-2-yl]ethyl]- 3-[cyclopropyl(difluoro) methyl]-5- (trifluoromethyl) benzamide [00133] 105-110 P5 3-(1-cyano-1-methyl-ethyl)- N-[1-[3-(5-fluoro-2- pyridyl)pyrazin-2-yl]ethyl]- 5-(trifluoromethyl) benzamide [00134] 210-220 P6 3-(1-cyano-1-methyl-ethyl)- N-[1-[3-(5- cyclopropylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-5- (trifluoromethyl) benzamide [00135] 130-140 P7 3-(1-cyano-1-methyl-ethyl)- N-[1-[3-(2-pyridyl)pyrazin- 2-yl]ethyl]-5- (trifluoromethyl) benzamide [00136] 150-160 P8 N-[1-[3-(5-chloro-2- pyridyl)pyrazin-2-yl]ethyl]- 3-(1-cyano-1-methyl-ethyl)- 5-(trifluoromethyl) benzamide [00137] 120-125 P9 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl]ethyl]- 3-(1-cyano-1-methyl-ethyl)- 5-(trifluoromethyl) benzamide [00138] 130-135 P10 3-cyclopropylsulfonyl-N- [1-(3-pyrimidin-2- ylpyrazin-2-yl)ethyl]-5- (trifluoromethyl) benzamide [00139] 0.85 478 1 P11 N-[1-[3-(5- cyclopropylpyrimidin- 2-yl)pyrazin-2-yl]ethyl]-3- (trifluoromethyl)-5- (trifluoromethylsulfonyl) benzamide [00140] 195-200 P12 N-[1-[3-(5-fluoro-2- pyridyl)pyrazin-2-yl] ethyl]-3- (trifluoromethyl)-5- (trifluoromethylsulfonyl) benzamide [00141] 145-150 P13 N-[1-[3-(2-pyridyl) pyrazin-2- yl]ethyl]-3- (trifluoromethyl)- 5-(trifluoromethylsulfonyl) benzamide [00142] 170-180 P14 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl] ethyl]-3- (trifluoromethyl)-5- (trifluoromethylsulfonyl) benzamide [00143] 190-195 P15 N-[1-[3-(5-chloro-2- pyridyl)pyrazin-2-yl]ethyl]- 3-(trifluoromethyl)-5- (trifluoromethylsulfonyl) benzamide [00144] 190-195 P16 N-[1-[3-(5-chloro-2- pyridyl)pyrazin-2-yl]ethyl]- 2-(1-cyanocyclopropyl)-6- (trifluoromethyl)pyridine-4- carboxamide [00145] 165-170 P17 N-[1-[3-(5-chloro-2- pyridyl)pyrazin-2-yl]ethyl]- 3-(1-cyanocyclopropyl)-5- (trifluoromethyl)benzamide [00146] 170-175 P18 N-[1-[3-(5-chloro-2- pyridyl)pyrazin-2-yl]ethyl]- 3-cyclopropyl-5- (trifluoromethyl)benzamide [00147] 155-160 P19 N-[1-(3-pyrimidin-2- ylpyrazin-2- yl)ethyl]-3- (trifluoromethyl)-5- (trifluoromethylsulfonyl) benzamide [00148] 215-220 P20 3-[cyclopropyl (difluoro)methyl]- N-[1-[3-(2-pyridyl)pyrazin- 2-yl]ethyl]-5- (trifluoromethyl) benzamide [00149] 130-140 P21 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl]ethyl]- 3-[cyclopropyl(difluoro) methyl]-5- (trifluoromethyl) benzamide [00150] 130-135 P22 3-(1-cyanocyclopropyl)- N-[1-[3- (2-pyridyl)pyrazin-2-yl] ethyl]-5- (trifluoromethyl) benzamide [00151] 130-140 P23 3-(1-cyanocyclopropyl)- N-[1-[3- (5-fluoro-2-pyridyl) pyrazin-2-yl]ethyl]-5- (trifluoromethyl) benzamide [00152] 175-180 P24 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl] ethyl]-3-(1- cyanocyclopropyl)-5- (trifluoromethyl)benzamide [00153] 125-130 P25 3-(1-cyanocyclopropyl)- N-[1-(3- pyrimidin-2-ylpyrazin-2- yl)ethyl]-5- (trifluoromethyl)benzamide [00154] 178-182 P26 2-(1-cyanocyclopropyl)- N-[1-[3- (2-pyridyl)pyrazin-2-yl] ethyl]-6- (trifluoromethyl)pyridine-4- carboxamide [00155] 120-130 P27 2-(1-cyanocyclopropyl)- N-[1-[3- (5-fluoro-2-pyridyl)pyrazin- 2-yl]ethyl]-6- (trifluoromethyl)pyridine-4- carboxamide [00156] 185-190 P28 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl]ethyl]- 2-(1-cyanocyclopropyl)-6- (trifluoromethyl)pyridine-4- carboxamide [00157] 120-125 P29 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl]ethyl]- 3-cyclopropyl-5- (trifluoromethyl)benzamide [00158] 120-125 P30 3-[cyclopropyl(difluoro) methyl]- N-[1-(3-pyrimidin-2- ylpyrazin-2- yl)ethyl]-5- (trifluoromethyl)benzamide [00159] 152-155 P31 2-cyclopropyl-N- [1-(3-pyrimidin- 2-ylpyrazin-2-yl)ethyl]-6- (trifluoromethyl)pyridine- 4-carboxamide [00160] 165-168 P32 2-(1-cyanocyclopropyl)-N- [1-(3-pyrimidin-2-ylpyrazin- 2-yl)ethyl]-6- (trifluoromethyl)pyridine-4- carboxamide [00161] 160-165 P33 3-cyclopropyl-N-[1-[3-(2- pyridyl)pyrazin-2-yl] ethyl]-5- (trifluoromethyl)benzamide [00162] 130-140 P34 3-cyclopropyl-N-[1-[3-[5- (difluoromethoxy)pyrimidin- 2-yl]pyrazin-2-yl]ethyl]-5- (trifluoromethyl)benzamide [00163] 90-95 P35 3-cyclopropyl-N-[1-[3-(5- cyclopropylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-5- (trifluoromethyl)benzamide [00164] 75-80 P36 2-(1-cyanocyclopropyl)- N-[1-[3- (5-cyclopropylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-6- (trifluoromethyl)pyridine-4- carboxamide [00165] 230-232 P37 N-[1-(3-pyrimidin-2- ylpyrazin-2- yl)ethyl]-3- (trifluoromethyl)-5-[2- (trifluoromethyl) cyclopropyl] benzamide [00166] 115-120 P38 3-[cyclopropyl (difluoro)methyl]- N-[1-[3-(5-fluoro-2- pyridyl)pyrazin-2- yl]ethyl]-5- (trifluoromethyl)benzamide [00167] 63-66 P39 3-[cyclopropyl(difluoro) methyl]-N-[1-[3-(5- cyclopropylpyrimidin- 2-yl)pyrazin-2-yl]ethyl]-5- (trifluoromethyl)benzamide [00168] 85-90 P40 3-cyclopropyl-N- [1-[3-(5-fluoro- 2-pyridyl)pyrazin- 2-yl]ethyl]-5- (trifluoromethyl)benzamide [00169] 152-160 P41 3-cyclopropyl-N-[1- (3-pyrimidin- 2-ylpyrazin-2-yl)ethyl]-5- (trifluoromethyl)benzamide [00170] 0.97 414 1 P42 N-[(1S)-1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl]ethyl]- 3-[cyclopropyl(difluoro) methyl]-5- (trifluoromethyl)benzamide [00171] 1.23 541-543 1 P43 2-(cyclopropylmethoxy)-N- [1-(3-pyrimidin-2- ylpyrazin-2- yl)ethyl]-6- (trifluoromethyl)pyridine-4- carboxamide [00172] 123-134 P44 3-(1-cyanocyclopropyl)-5- (difluoromethoxy)-N-[1-(3- pyrimidin-2-ylpyrazin-2- yl)ethyl]benzamide [00173] 120-130 P45 3-(difluoromethoxy)-N-[1- (3-pyrimidin-2-ylpyrazin-2- yl)ethyl]-5- (trifluoromethylsulfonyl) benzamide [00174] 225-230 P46 3-(1-cyanocyclopropyl)- N-[1-(3- pyrimidin-2-ylpyrazin-2- yl)ethyl]-5- (trifluoromethoxy) benzamide [00175] 150-160 P47 3-(1- methoxycyclopropyl)-N-[1- (3-pyrimidin-2-ylpyrazin-2- yl)ethyl]-5- (trifluoromethyl)benzamide [00176] 140-150 P48 3-(1-cyano-1-methyl- ethyl)-N-[1-[3-(5- methylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-5- (trifluoromethyl)benzamide [00177] 175-180 P49 N-[1-[3-(5-bromopyrimidin- 2-yl)pyrazin-2-yl]ethyl]-3- (1-cyano-1-methyl-ethyl)-5- (trifluoromethyl)benzamide [00178] 170-175 P50 3-(1-cyano-1-methyl- ethyl)-N- [1-(3-pyrimidin-2- ylpyrazin-2-yl) ethyl]-5- (trifluoromethyl)benzamide [00179] 160-165 P51 3-cyclopropyl-N-[1-[3-(5- methylpyrimidin-2-yl) pyrazin-2-yl]ethyl]-5- (trifluoromethyl)benzamide [00180] 135-140 P52 3-[cyclopropyl (difluoro)methyl]- N-[1-[3-(5- methylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-5- (trifluoromethyl)benzamide [00181] 140-145 P53 N-[1-[3-(5-bromopyrimidin- 2-yl)pyrazin-2-yl]ethyl]-3- [cyclopropyl(difluoro) methyl]-5- (trifluoromethyl)benzamide [00182] 130-135 P54 3-(1-cyanocyclopropyl)- N-[1-[3- (5-methylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-5- (trifluoromethyl)benzamide [00183] 150-155 P55 N-[1-[3-(5- bromopyrimidin-2- yl)pyrazin-2-yl]ethyl]-2-(1- cyanocyclopropyl)-6- (trifluoromethyl)pyridine-4- carboxamide [00184] 175-185 P56 N-[1-[3-(5- methylpyrimidin-2- yl)pyrazin-2-yl]ethyl]-3- (trifluoromethyl)-5- (trifluoromethylsulfonyl) benzamide [00185] 200-205 P57 N-[1-[3-(5- bromopyrimidin-2- yl)pyrazin-2-yl]ethyl]-3- (trifluoromethyl)-5- (trifluoromethylsulfonyl) benzamide [00186] 185-190 P58 N-[1-[3-(5- bromopyrimidin-2- yl)pyrazin-2-yl]ethyl]-3- cyclopropyl-5- (trifluoromethyl) benzamide [00187] 130-140

TABLE-US-00014 TABLE I Table of Intermediates RT m/z Index IUPAC name STRUCTURE (min) (measured) Method NMR I1 methyl 2-chloro-6- (trifluoromethyl)pyridine- 4-carboxylate [00188] .sup.1) I2 methyl 2-cyclopropyl-6- (trifluoromethyl)pyridine- 4-carboxylate [00189] 1.12 246 [M + H].sup.+ 1 I3 2-cyclopropyl-6- (trifluoromethyl)pyridine- 4-carboxylic acid [00190] 0.94 232 [M + H].sup.+ 1 I4 methyl 3-cyclopropyl-5- (trifluoromethyl)benzoate [00191] .sup.2) I5 3-cyclopropyl-5- (trifluoromethyl)benzoic acid [00192] 0.99 229 [M − H].sup.− 1 I6 methyl 3- (trifluoromethyl)-5-vinyl- benzoate [00193] .sup.3) I7 methyl 3- (trifluoromethyl)-5-[2- (trifluoromethyl)cyclo- propyl]benzoate [00194] .sup.4) I8 3-(trifluoromethyl)-5-[2- (trifluoromethyl)cyclo- propyl]benzoic acid [00195] 1.04 297 [M − H].sup.− 1 I9 methyl 3- (trifluoromethyl)-5- (trifluoromethyl- sulfanyl)benzoate [00196] .sup.5) I10 methyl 3- (trifluoromethyl)-5- (trifluoromethyl- sulfonyl)benzoate [00197] .sup.6) I11 3-(trifluoromethyl)-5- (trifluoromethyl- sulfonyl)benzoic acid [00198] .sup.7) I12 methyl 3- (cyclopropanecarbonyl)- 5- (trifluoromethyl)benzoate [00199] .sup.8) I13 methyl 3-[cyclo- propyl(difluoro)methyl]-5- (trifluoromethyl)benzoate [00200] .sup.9) I14 3-[cyclo- propyl(difluoro)methyl]-5- (trifluoromethyl)benzoic acid [00201] 1.03 279 [M − H].sup.− 1 I15 methyl 2-(1-cyano-2- ethoxy-2-oxo-ethyl)-6- (trifluoromethyl)pyridine- 4-carboxylate [00202] 1.01 317 [M + H].sup.+ 1 I16 methyl 2-(cyanomethyl)- 6- (trifluoromethyl)pyridine- 4-carboxylate [00203] .sup.10) I17 2-(1-cyanocyclopropyl)- 6- (trifluoromethyl)pyridine- 4-carboxylic acid [00204] 0.89 255 [M − H].sup.− 1 I18 methyl 3-(cyanomethyl)- 5- (trifluoromethyl)benzoate [00205] .sup.11) I19 methyl 3-(1- cyanocyclopropyl)-5- (trifluoromethyl)benzoate [00206] .sup.12) I20 3-(1-cyanocyclopropyl)- 5- (trifluoromethyl)benzoic acid [00207] .sup.13) I21 1-(3-pyrimidin-2- ylpyrazin-2-yl)ethanone [00208] 0.39 201.0 [M + H].sup.+ 1 I22 1-[3-(5-methylpyrimidin- 2-yl)pyrazin-2- yl]ethanone [00209] .sup.14) I23 1-[3-(5- cyclopropylpyrimidin-2- yl)pyrazin-2-yl]ethanone [00210] .sup.15) I24 1-[3-(2-pyridyl)pyrazin-2- yl]ethanone [00211] 0.35 200.3 [M + H].sup.+ 1 I25 1-[3-(5-chloro-2- pyridyl)pyrazin-2- yl]ethanone [00212] .sup.16) I26 1-[3-(5-bromo-2- pyridyl)pyrazin-2- yl]ethanone [00213] 3.64 278.0/280.0 [M + H].sup.+ (bromo pattern) 3 I27 1-[3-(5-fluoro-2- pyridyl)pyrazin-2- yl]ethanone [00214] 0.69 218.3 [M + H].sup.+ 1 I28 tert-butyl N-[6-(3- acetylpyrazin-2-yl)-3- pyridyl]carbamate [00215] .sup.17) I29 1-[3-(5-amino-2- pyridyl)pyrazin-2- yl]ethanone [00216] 1.41 215.1 [M + H].sup.+ 3 I30 1-(6-methyl-3-pyrimidin- 2-yl-pyrazin-2- yl)ethanone [00217] 0.56 215.0 1 I31 1-(3-pyrimidin-2- ylpyrazin-2- yl)ethanamine [00218] 0.17 202 [M + H].sup.+ 1 I32 1-[3-(5- cyclopropylpyrimidin-2- yl)pyrazin-2- yl]ethanamine [00219] .sup.18) I34 1-[3-(2-pyridyl)pyrazin-2- yl]ethanamine [00220] 0.53 201.1 [M + H].sup.+ I35 1-[3-(5-chloro-2- pyridyl)pyrazin-2- yl]ethanamine [00221] 2.7 235 [M + H].sup.+ 3 I36 1-[3-(5-bromo-2- pyridyl)pyrazin-2- yl]ethanamine [00222] 0.53 279/281 [M + H].sup.+ (bromo pattern) 1 I37 1-[3-(5-fluoro-2- pyridyl)pyrazin-2- yl]ethanamine [00223] 0.18 219.3 [M + H].sup.+ 1 I38 tert-butyl N-[6-[3-(1- aminoethyl)pyrazin-2-yl]- 3-pyridyl]carbamate [00224] .sup.19) I39 1-(6-methyl-3-pyrimidin- 2-yl-pyrazin-2- yl)ethanamine [00225] 0.19 216 [M + H].sup.+ 1 I40 (1R)-1-(3-pyrimidin-2- ylpyrazin-2-yl)ethanol [00226] 0.25 203.1 [M + H].sup.+ 1 I41 (1S)-1-(3-pyrimidin-2- ylpyrazin-2- yl)ethanamine [00227] 0.17 202 [M + H].sup.+ 1 I42 tert-butyl N-[(1S)-1-[3-(5- bromo-2-pyridyl)pyrazin- 2-yl]ethyl]carbamate [00228] 1.09 379/381 [M + H].sup.+ (bromo pattern) 1 I43 (1S)-1-[3-(5-bromo-2- pyridyl)pyrazin-2- yl]ethanamine [00229] 0.53 279/281 [M + H].sup.+ (bromo pattern) 1 I44 (1R)-1-(3-chloropyrazin- 2-yl)ethanol [00230] 0.40 159/160 [M + H].sup.+ I45 (1S)-1-(3-chloropyrazin- 2-yl)ethanamine [00231] 0.17 158 [M + H].sup.+ 1 I46 (1S)-1-(3-chloropyrazin- 2-yl)-N-(cyclopropyl- methyl)ethanamine [00232] 0.26 212 [M + H].sup.+ 2 I47 1-(6-methoxy-3- pyrimidin-2-yl-pyrazin-2- yl)ethanone [00233] 1.07 231 [M + H].sup.+ 4 I48 1-(6-methoxy-3- pyrimidin-2-yl-pyrazin-2- yl)ethanamine [00234] 0.35 232 [M + H].sup.+ 4 I49 tert-butyl N-[(1S)-1-[6- amino-3-(5-bromo-2- pyridyl)pyrazin-2- yl]ethyl]carbamate [00235] 1.04 394/396 [M + H].sup.+ (bromo pattern) 1 I50 1-bromo-3-(1- methoxycyclopropyl)-5- (trifluoromethyl)benzene [00236] .sup.21) I51 methyl 3-(1- methoxycyclopropyl)-5- (trifluoromethyl)benzoate [00237] .sup.22) I52 3-(1 methoxycyclopropyl)-5- (trifluoromethyl)benzoic acid [00238] .sup.23) I53 tert-butyl N-[2-(3- acetylpyrazin-2- yl)pyrimidin-5- yl]carbamate [00239] 1.04 216.1 3 I54 1-[3-(5-bromopyrimidin- 2-yl)pyrazin-2- yl]ethanone [00240] 3.54 279/281 [M + H].sup.+ (bromo pattern) 3 I55 1-[3-(5-bromopyrimidin- 2-yl)pyrazin-2- yl]ethanamine [00241] .sup.24) .sup.1) 1H NMR (400 MHz, chloroform-d) δ ppm: 4.04 (s, 3 H) 8.11 (s, 1 H) 8.17 (d, J = 1.10 Hz, 1 H). .sup.2) 1H NMR (400 MHz, chloroform-d) δ ppm: 0.76-0.85 (m, 2 H) 1.06-1.15 (m, 2 H) 2.03 (tt, J.sub.1 = 8.39 Hz, J.sub.2 = 5.00 Hz, 1 H 3.96 (s, 3 H) 7.52 (s, 1 H) 7.91 (s, 1 H) 8.08 (d, J = 0.73 Hz, 1 H); .sup.19F NMR (377 MHz, chloroform-d) δ ppm: −62.75 (s, 3 F). .sup.3) 1H NMR (400 MHz, chloroform-d) δ ppm: 3.98 (s, 3 H) 5.47 (d, J = 11.00 Hz, 1 H) 5.93 (d, J = 17.61 Hz, 1 H) 6.79 (dd, J.sub.1 = 17.42 Hz, J.sub.2 = 10.82 Hz, 1 H) 7.82 (s, 1 H) 8.19 (s, 1 H) 8.24-8.29 (m, 1 H). .sup.4) 1H NMR (400 MHz, chloroform-d) δ ppm: 1.25-1.34 (m, 1 H) 1.48-1.55 (m, 1 H) 1.88-2.00 (m, 1 H) 2.46-2.53 (m, 1 H) 3.98 (s, 3 H) 7.60 (s, 1 H) 7.98 (s, 1 H) 8.19 (s, 1 H). .sup.5) 1H NMR (400 MHz, chloroform-d) δ ppm: 4.02 (s, 3 H), 8.11 (s, 1 H), 8.44 (s, 1H), 8.53 (s, 1 H). .sup.6) 1H NMR (400 MHz, Chloroform) δ ppm 4.07 (s, 3 H) 8.43-8.51 (m, 1 H) 8.70-8.80 (m, 1 H) 8.84-8.91 (m, 1 H); .sup.19F NMR (377 MHz, chloroform-d) δ ppm: −77.49 (s, 3 F) −62.96 (s, 3 F) .sup.7) 1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm: 8.68 (s, 2 H) 8.71-8.76 (m, 1 H) 13.33-15.22 (m, 1 H). .sup.8) 1H NMR (400 MHz, chloroform-d) δ ppm: 1.16-1.22 (m, 2 H) 1.35 (quin, J = 3.76 Hz, 2 H) 2.74 (tt, J.sub.1 = 7.84 Hz, J.sub.2 = 4.45 Hz, 1 H) 4.02 (s, 3 H) 8.45 (d, J = 0.73 Hz, 1 H) 8.51 (d, J = 0.73 Hz, 1 H) 8.86 (s, 1 H). .sup.9) 1H NMR (400 MHz, chloroform-d) δ ppm: 0.73-0.79 (m, 2 H) 0.82-0.89 (m, 2 H) 1.47-1.60 (m, 1 H) 8.00 (d, J = 0.73 Hz, 1 H) 8.39 (s, 1 H) 8.42 (s, 1 H); .sup.19F NMR (377 MHz, chloroform-d) δ ppm: −98.40 (s, 3 F) −62.81 (s, 2 F). .sup.10) 1H NMR (400 MHz, chloroform-d) δ ppm: 4.05 (s, 3 H) 4.13 (s, 2 H) 8.24 (s, 1 H) 8.26 (s, 1 H). .sup.11) 1H NMR (400 MHz, chloroform-d) δ ppm: 8.30 (1 H, s), 8.23 (1 H, s), 7.81 (1 H, s), 3.99 (3 H, s), 3.90 (2 H, s). .sup.12) 1H NMR (400 MHz, chloroform-d) δ ppm: 8.23 (1 H, s), 8.09 (1 H, s), 7.79 (1 H, s), 3.98 (3 H, s), 1.84-1.92 (2 H, m), 1.47-1.57 (m, 2H). .sup.13) 1H NMR (400 MHz, chloroform-d) δ ppm: 8.60-9.90 (1 H, br s), 8.29 (1H, s), 8.15 (1H, s), 7.84 (1H, s), 1.84-1.93 (2 H, m), 1.50-1.60 (2 H, m) .sup.14) 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.93 (d, 1H), 8.84 (d, 1H), 8.78 (m, 2H), 2.64 (s, 3H), 2.36 (s, 3H) .sup.15) 1H-NMR (400 MHz, CDCl3): δ ppm 8.7 (d, 1H), 8.55 (d, 1H), 8.50 (s, 2H), 2.7 (s, 3H), 1.85 (m, 1H), 1.1 (m, 2H), 0.8 (m, 2H). .sup.16) 1H-NMR (400 MHz, DMSO): δ ppm 8.9 (s, 1H), 8.8 (d, 1H), 8.7 (s, 1H), 8.2 (m, 2H), 2.6 (s, 3H) .sup.17) 1H-NMR (400 MHz, DMSO): δ ppm 9.9 (s, 1H), 8.6-8.9 (m, 3H), 8.1-8.25 (m, 2H), 2.55 (s, 1H), 1.5 (s, 9H) .sup.18) 1H-NMR (400 MHz, DMSO): δ ppm 8.85 (m, 2H), 8.80 (m, 2H), 5.0 (m, 1H), 3.2 (m, 3H) 2.1 (m, 1H), 1.15 (m, 2H), 1.0 (m, 2H) .sup.19) 1H-NMR (400 MHz, DMSO): δ ppm 9.9 (s, 1H), 8.6-8.9 (m, 3H), 8.1-8.25 (m, 2H), 2.55 (s, 1H), 1.5 (s, 9H) .sup.20) 1H-NMR (400 MHz, chloroform-d) δ ppm 8.49 (d, 1H), 8.34 (d, 1H), 5.18 (m, 1H), 3.81 (d, 1H), 1.52 (d, 3H) .sup.21) 1H NMR (400 MHz, DMSO-d) δ ppm: 7.82 (s, 1H), 7.69 (s, 1H), 7.55 (s, 1H), 3.27 (s, 3H), 1.20-1.28 (m, 2H), 1.09-1.18 (m, 2H). .sup.22) 1H NMR (400 MHz, chloroform-d) δ ppm: 8.17 (s, 1H), 8.05 (s, 1H), 7.78 (s, 1H), 3.95 (s, 3H), 3.25 (s, 3H), 1.30 (t, 2H), 1.05 (t, 2H). .sup.23) 1H NMR (400 MHz, chloroform-d) δ ppm: 13.4-13.7 (br. s, 1H), 8.00-8.10 (m, 2H), 7.72 (s, 1H), 3.19 (s, 3H), 1.25-1.35 (m, 2H), 1.08-1.15 (m, 2H). .sup.24) 1H-NMR (400 MHz, DMSO): δ ppm: 9.22 (s, 2H), 8.70-9.00 (m, 2H), 4.50-4.80 (m, 1H), 1.42 (d, 3H).

[0544] The activity of the compositions according to the invention can be broadened considerably, and adapted to prevailing circumstances, by adding other insecticidally, acaricidally and/or fungicidally active ingredients. The mixtures of the compounds of formula I with other insecticidally, acaricidally and/or fungicidally active ingredients may also have further surprising advantages which can also be described, in a wider sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different development stages or better behaviour during their production, for example during grinding or mixing, during their storage or during their use.

[0545] Suitable additions to active ingredients here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.

[0546] The following mixtures of the compounds of formula I with active ingredients are preferred (where the abbreviation “TX” means “one compound selected from the compounds defined in the Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21 and E-1 to E-21, and Table P”): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628)+TX,

an insect control active substance selected from Abamectin+TX, Acequinocyl+TX, Acetamiprid+TX, Acetoprole+TX, Acrinathrin+TX, Acynonapyr+TX, Afidopyropen+TX, Afoxalaner+TX, Alanycarb+TX, Allethrin+TX, Alpha-Cypermethrin+TX, Alphamethrin+TX, Amidoflumet+TX, Aminocarb+TX, Azocyclotin+TX, Bensultap+TX, Benzoximate+TX, Benzpyrimoxan+TX, Betacyfluthrin+TX, Beta-cypermethrin+TX, Bifenazate+TX, Bifenthrin+TX, Binapacryl+TX, Bioallethrin+TX, Bioallethrin S)-cyclopentylisomer+TX, Bioresmethrin+TX, Bistrifluron+TX, Broflanilide+TX, Brofluthrinate+TX, Bromophos-ethyl+TX, Buprofezine+TX, Butocarboxim+TX, Cadusafos+TX, Carbaryl+TX, Carbosulfan+TX, Cartap+TX, CAS number: 1472050-04-6+TX, CAS number: 1632218-00-8+TX, CAS number: 1808115-49-2+TX, CAS number: 2032403-97-5+TX, CAS number: 2044701-44-0+TX, CAS number: 2128706-05-6+TX, CAS number: 2249718-27-0+TX, Chlorantraniliprole+TX, Chlordane+TX, Chlorfenapyr+TX, Chloroprallethrin+TX, Chromafenozide+TX, Clenpirin+TX, Cloethocarb+TX, Clothianidin+TX, 2-chlorophenyl N-methylcarbamate (CPMC)+TX, Cyanofenphos+TX, Cyantraniliprole+TX, Cyclaniliprole+TX, Cyclobutrifluram+TX, Cycloprothrin+TX, Cycloxaprid+TX, Cycloxaprid+TX, Cyenopyrafen+TX, Cyetpyrafen (or Etpyrafen)+TX, Cyflumetofen+TX, Cyfluthrin+TX, Cyhalodiamide+TX, Cyhalothrin+TX, Cypermethrin+TX, Cyphenothrin+TX, Cyromazine+TX, Deltamethrin+TX, Diafenthiuron+TX, Dialifos+TX, Dibrom+TX, Dicloromezotiaz+TX, Diflovidazine+TX, Diflubenzuron+TX, dimpropyridaz+TX, Dinactin+TX, Dinocap+TX, Dinotefuran+TX, Dioxabenzofos+TX, Emamectin+TX, Empenthrin+TX, Epsilon-momfluorothrin+TX, Epsilon-metofluthrin+TX, Esfenvalerate+TX, Ethion+TX, Ethiprole+TX, Etofenprox+TX, Etoxazole+TX, Famphur+TX, Fenazaquin+TX, Fenfluthrin+TX, Fenitrothion+TX, Fenobucarb+TX, Fenothiocarb+TX, Fenoxycarb+TX, Fenpropathrin+TX, Fenpyroxymate+TX, Fensulfothion+TX, Fenthion+TX, Fentinacetate+TX, Fenvalerate+TX, Fipronil+TX, Flometoquin+TX, Flonicamid+TX, Fluacrypyrim+TX, Fluazaindolizine+TX, Fluazuron+TX, Flubendiamide+TX, Flubenzimine+TX, Flucitrinate+TX, Flucycloxuron+TX, Flucythrinate+TX, Fluensulfone+TX, Flufenerim+TX, Flufenprox+TX, Flufiprole+TX, Fluhexafon+TX, Flumethrin+TX, Fluopyram+TX, Flupentiofenox+TX, Flupyradifurone+TX, Flupyrimin+TX, Fluralaner+TX, Fluvalinate+TX, Fluxametamide+TX, Fosthiazate+TX, Gamma-Cyhalothrin+TX, Gossyplure™+TX, Guadipyr+TX, Halofenozide+TX, Halofenozide+TX, Halofenprox+TX, Heptafluthrin+TX, Hexythiazox+TX, Hydramethylnon+TX, Imicyafos+TX, Imidacloprid+TX, Imiprothrin+TX, Indoxacarb+TX, Iodomethane+TX, Iprodione+TX, Isocycloseram+TX, Isothioate+TX, Ivermectin+TX, Kappa-bifenthrin+TX, Kappa-tefluthrin+TX, Lambda-Cyhalothrin+TX, Lepimectin+TX, Lufenuron+TX, Metaflumizone+TX, Metaldehyde+TX, Metam+TX, Methomyl+TX, Methoxyfenozide+TX, Metofluthrin+TX, Metolcarb+TX, Mexacarbate+TX, Milbemectin+TX, Momfluorothrin+TX, Niclosamide+TX, Nitenpyram+TX, Nithiazine+TX, Omethoate+TX, Oxamyl+TX, Oxazosufyl+TX, Parathion-ethyl+TX, Permethrin+TX, Phenothrin+TX, Phosphocarb+TX, Piperonylbutoxide+TX, Pirimicarb+TX, Pirimiphos-ethyl+TX, Polyhedrosis virus+TX, Prallethrin+TX, Profenofos+TX, Profenofos+TX, Profluthrin+TX, Propargite+TX, Propetamphos+TX, Propoxur+TX, Prothiophos+TX, Protrifenbute+TX, Pyflubumide+TX, Pymetrozine+TX, Pyraclofos+TX, Pyrafluprole+TX, Pyridaben+TX, Pyridalyl+TX, Pyrifluquinazon+TX, Pyrimidifen+TX, Pyrimostrobin+TX, Pyriprole+TX, Pyriproxyfen+TX, Resmethrin+TX, Sarolaner+TX, Selamectin+TX, Silafluofen+TX, Spinetoram+TX, Spinosad+TX, Spirodiclofen+TX, Spiromesifen+TX, Spiropidion+TX, Spirotetramat+TX, Sulfoxaflor+TX, Tebufenozide+TX, Tebufenpyrad+TX, Tebupirimiphos+TX, Tefluthrin+TX, Temephos+TX, Tetrachloraniliprole+TX, Tetradiphon+TX, Tetramethrin+TX, Tetramethylfluthrin+TX, Tetranactin+TX, Tetraniliprole+TX, Theta-cypermethrin+TX, Thiacloprid+TX, Thiamethoxam+TX, Thiocyclam+TX, Thiodicarb+TX, Thiofanox+TX, Thiometon+TX, Thiosultap+TX, Tioxazafen+TX, Tolfenpyrad+TX, Toxaphene+TX, Tralomethrin+TX, Transfluthrin+TX, Triazamate+TX, Triazophos+TX, Trichlorfon+TX, Trichloronate+TX, Trichlorphon+TX, Triflumezopyrim+TX, Tyclopyrazoflor+TX, Zeta-Cypermethrin+TX, Extract of seaweed and fermentation product derived from melasse+TX, Extract of seaweed and fermentation product derived from melasse comprising urea+TX, amino acids+TX, potassium and molybdenum and EDTA-chelated manganese+TX, Extract of seaweed and fermented plant products+TX, Extract of seaweed and fermented plant products comprising phytohormones+TX, vitamins+TX, EDTA-chelated copper+TX, zinc+TX, and iron+TX, Azadirachtin+TX, Bacillus aizawai+TX, Bacillus chitinosporus AQ746 (NRRL Accession No B-21 618)+TX, Bacillus firmus+TX, Bacillus kurstaki+TX, Bacillus mycoides AQ726 (NRRL Accession No. B-21664)+TX, Bacillus pumilus (NRRL Accession No B-30087)+TX, Bacillus pumilus AQ717 (NRRL Accession No. B-21662)+TX, Bacillus sp. AQ178 (ATCC Accession No. 53522)+TX, Bacillus sp. AQ175 (ATCC Accession No. 55608)+TX, Bacillus sp. AQ177 (ATCC Accession No. 55609)+TX, Bacillus subtilis unspecified+TX, Bacillus subtilis AQ153 (ATCC Accession No. 55614)+TX, Bacillus subtilis AQ30002 (NRRL Accession No. B-50421)+TX, Bacillus subtilis AQ30004 (NRRL Accession No. B-50455)+TX, Bacillus subtilis AQ713 (NRRL Accession No. B-21661)+TX, Bacillus subtilis AQ743 (NRRL Accession No. B-21665)+TX, Bacillus thuringiensis AQ52 (NRRL Accession No. B-21619)+TX, Bacillus thuringiensis BD #32 (NRRL Accession No B-21530)+TX, Bacillus thuringiensis subspec. kurstaki BMP 123+TX, Beauveria bassiana+TX, D-limonene+TX, Granulovirus+TX, Harpin+TX, Helicoverpa armigera Nucleopolyhedrovirus+TX, Helicoverpa zea Nucleopolyhedrovirus+TX, Heliothis virescens Nucleopolyhedrovirus+TX, Heliothis punctigera Nucleopolyhedrovirus+TX, Metarhizium spp.+TX, Muscodor albus 620 (NRRL Accession No. 30547)+TX, Muscodor roseus A3-5 (NRRL Accession No. 30548)+TX, Neem tree based products+TX, Paecilomyces fumosoroseus+TX, Paecilomyces lilacinus+TX, Pasteuria nishizawae+TX, Pasteuria penetrans+TX, Pasteuria ramosa+TX, Pasteuria thornei+TX, Pasteuria usgae+TX, P-cymene+TX, Plutella xylostella Granulosis virus+TX, Plutella xylostella Nucleopolyhedrovirus+TX, Polyhedrosis virus+TX, pyrethrum+TX, QRD 420 (a terpenoid blend)+TX, QRD 452 (a terpenoid blend)+TX, QRD 460 (a terpenoid blend)+TX, Quillaja saponaria+TX, Rhodococcus globerulus AQ719 (NRRL Accession No B-21663)+TX, Spodoptera frugiperda Nucleopolyhedrovirus+TX, Streptomyces galbus (NRRL Accession No. 30232)+TX, Streptomyces sp. (NRRL Accession No. B-30145)+TX, Terpenoid blend+TX, and Verticillium spp., an algicide selected from the group of substances consisting of bethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX, copper sulfate (172)+TX, cybutryne [CCN]+TX, dichlone (1052)+TX, dichlorophen (232)+TX, endothal (295)+TX, fentin (347)+TX, hydrated lime [CCN]+TX, nabam (566)+TX, quinoclamine (714)+TX, quinonamid (1379)+TX, simazine (730)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX,
an anthelmintic selected from the group of substances consisting of abamectin (1)+TX, crufomate (1011)+TX, Cyclobutrifluram+TX, doramectin (alternative name) [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin (alternative name) [CCN]+TX, ivermectin (alternative name) [CCN]+TX, milbemycin oxime (alternative name) [CCN]+TX, moxidectin (alternative name) [CCN]+TX, piperazine [CCN]+TX, selamectin (alternative name) [CCN]+TX, spinosad (737) and thiophanate (1435)+TX,
an avicide selected from the group of substances consisting of chloralose (127)+TX, endrin (1122)+TX, fenthion (346)+TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745)+TX, a bactericide selected from the group of substances consisting of 1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222)+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, 8-hydroxyquinoline sulfate (446)+TX, bronopol (97)+TX, copper dioctanoate (IUPAC name) (170)+TX, copper hydroxide (IUPAC name) (169)+TX, cresol [CCN]+TX, dichlorophen (232)+TX, dipyrithione (1105)+TX, dodicin (1112)+TX, fenaminosulf (1144)+TX, formaldehyde (404)+TX, hydrargaphen (alternative name) [CCN]+TX, kasugamycin (483)+TX, kasugamycin hydrochloride hydrate (483)+TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308)+TX, nitrapyrin (580)+TX, octhilinone (590)+TX, oxolinic acid (606)+TX, oxytetracycline (611)+TX, potassium hydroxyquinoline sulfate (446)+TX, probenazole (658)+TX, streptomycin (744)+TX, streptomycin sesquisulfate (744)+TX, tecloftalam (766)+TX, and thiomersal (alternative name) [CCN]+TX,
a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12)+TX, Agrobacterium radiobacter (alternative name) (13)+TX, Amblyseius spp. (alternative name) (19)+TX, Anagrapha falcifera NPV (alternative name) (28)+TX, Anagrus atomus (alternative name) (29)+TX, Aphelinus abdominalis (alternative name) (33)+TX, Aphidius colemani (alternative name) (34)+TX, Aphidoletes aphidimyza (alternative name) (35)+TX, Autographa californica NPV (alternative name) (38)+TX, Bacillus firmus (alternative name) (48)+TX, Bacillus sphaericus Neide (scientific name) (49)+TX, Bacillus thuringiensis Berliner (scientific name) (51)+TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51)+TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51)+TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51)+TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51)+TX, Bacillus thuringiensis subsp. tenebrionis (scientific name) (51)+TX, Beauveria bassiana (alternative name) (53)+TX, Beauveria brongniartii (alternative name) (54)+TX, Chrysoperla carnea (alternative name) (151)+TX, Cryptolaemus montrouzieri (alternative name) (178)+TX, Cydia pomonella GV (alternative name) (191)+TX, Dacnusa sibirica (alternative name) (212)+TX, Diglyphus isaea (alternative name) (254)+TX, Encarsia formosa (scientific name) (293)+TX, Eretmocerus eremicus (alternative name) (300)+TX, Helicoverpa zea NPV (alternative name) (431)+TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433)+TX, Hippodamia convergens (alternative name) (442)+TX, Leptomastix dactylopii (alternative name) (488)+TX, Macrolophus caliginosus (alternative name) (491)+TX, Mamestra brassicae NPV (alternative name) (494)+TX, Metaphycus helvolus (alternative name) (522)+TX, Metarhizium anisopliae var. acridum (scientific name) (523)+TX, Metarhizium anisopliae var. anisopliae (scientific name) (523)+TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575)+TX, Orius spp. (alternative name) (596)+TX, Paecilomyces fumosoroseus (alternative name) (613)+TX, Phytoseiulus persimilis (alternative name) (644)+TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741)+TX, Steinernema bibionis (alternative name) (742)+TX, Steinernema carpocapsae (alternative name) (742)+TX, Steinernema feltiae (alternative name) (742)+TX, Steinernema glaseri (alternative name) (742)+TX, Steinernema riobrave (alternative name) (742)+TX, Steinernema riobravis (alternative name) (742)+TX, Steinernema scapterisci (alternative name) (742)+TX, Steinernema spp. (alternative name) (742)+TX, Trichogramma spp. (alternative name) (826)+TX, Typhlodromus occidentalis (alternative name) (844) and Verticillium lecanii (alternative name) (848)+TX,
a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537)+TX,
a chemosterilant selected from the group of substances consisting of apholate [CCN]+TX, bisazir (alternative name) [CCN]+TX, busulfan (alternative name) [CCN]+TX, diflubenzuron (250)+TX, dimatif (alternative name) [CCN]+TX, hemel [CCN]+TX, hempa [CCN]+TX, metepa [CCN]+TX, methiotepa [CCN]+TX, methyl apholate [CCN]+TX, morzid [CCN]+TX, penfluron (alternative name) [CCN]+TX, tepa [CCN]+TX, thiohempa (alternative name) [CCN]+TX, thiotepa (alternative name) [CCN]+TX, tretamine (alternative name) [CCN] and uredepa (alternative name) [CCN]+TX,
an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (IUPAC name) (222)+TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829)+TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541)+TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate (IUPAC name) (779)+TX, (Z)-dodec-7-en-1-yl acetate (IUPAC name) (285)+TX, (Z)-hexadec-11-enal (IUPAC name) (436)+TX, (Z)-hexadec-11-en-1-yl acetate (IUPAC name) (437)+TX, (Z)-hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438)+TX, (Z)-icos-13-en-10-one (IUPAC name) (448)+TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782)+TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783)+TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283)+TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780)+TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781)+TX, 14-methyloctadec-1-ene (IUPAC name) (545)+TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (IUPAC name) (544)+TX, alpha-multistriatin (alternative name) [CCN]+TX, brevicomin (alternative name) [CCN]+TX, codlelure (alternative name) [CCN]+TX, codlemone (alternative name) (167)+TX, cuelure (alternative name) (179)+TX, disparlure (277)+TX, dodec-8-en-1-yl acetate (IUPAC name) (286)+TX, dodec-9-en-1-yl acetate (IUPAC name) (287)+TX, dodeca-8+TX, 10-dien-1-yl acetate (IUPAC name) (284)+TX, dominicalure (alternative name) [CCN]+TX, ethyl 4-methyloctanoate (IUPAC name) (317)+TX, eugenol (alternative name) [CCN]+TX, frontalin (alternative name) [CCN]+TX, gossyplure (alternative name) (420)+TX, grandlure (421)+TX, grandlure I (alternative name) (421)+TX, grandlure II (alternative name) (421)+TX, grandlure III (alternative name) (421)+TX, grandlure IV (alternative name) (421)+TX, hexalure [CCN]+TX, ipsdienol (alternative name) [CCN]+TX, ipsenol (alternative name) [CCN]+TX, japonilure (alternative name) (481)+TX, lineatin (alternative name) [CCN]+TX, litlure (alternative name) [CCN]+TX, looplure (alternative name) [CCN]+TX, medlure [CCN]+TX, megatomoic acid (alternative name) [CCN]+TX, methyl eugenol (alternative name) (540)+TX, muscalure (563)+TX, octadeca-2,13-dien-1-yl acetate (IUPAC name) (588)+TX, octadeca-3,13-dien-1-yl acetate (IUPAC name) (589)+TX, orfralure (alternative name) [CCN]+TX, oryctalure (alternative name) (317)+TX, ostramone (alternative name) [CCN]+TX, siglure [CCN]+TX, sordidin (alternative name) (736)+TX, sulcatol (alternative name) [CCN]+TX, tetradec-11-en-1-yl acetate (IUPAC name) (785)+TX, trimedlure (839)+TX, trimedlure A (alternative name) (839)+TX, trimedlure B.sub.1 (alternative name) (839)+TX, trimedlure B.sub.2 (alternative name) (839)+TX, trimedlure C (alternative name) (839) and trunc-call (alternative name) [CCN]+TX,
an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591)+TX, butopyronoxyl (933)+TX, butoxy(polypropylene glycol) (936)+TX, dibutyl adipate (IUPAC name) (1046)+TX, dibutyl phthalate (1047)+TX, dibutyl succinate (IUPAC name) (1048)+TX, diethyltoluamide [CCN]+TX, dimethyl carbate [CCN]+TX, dimethyl phthalate [CCN]+TX, ethyl hexanediol (1137)+TX, hexamide [CCN]+TX, methoquin-butyl (1276)+TX, methylneodecanamide [CCN]+TX, oxamate [CCN] and picaridin [CCN]+TX,
a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913)+TX, bromoacetamide [CCN]+TX, calcium arsenate [CCN]+TX, cloethocarb (999)+TX, copper acetoarsenite [CCN]+TX, copper sulfate (172)+TX, fentin (347)+TX, ferric phosphate (IUPAC name) (352)+TX, metaldehyde (518)+TX, methiocarb (530)+TX, niclosamide (576)+TX, niclosamide-olamine (576)+TX, pentachlorophenol (623)+TX, sodium pentachlorophenoxide (623)+TX, tazimcarb (1412)+TX, thiodicarb (799)+TX, tributyltin oxide (913)+TX, trifenmorph (1454)+TX, trimethacarb (840)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX, pyriprole [394730-71-3]+TX,
a nematicide selected from the group of substances consisting of AKD-3088 (compound code)+TX, 1,2-dibromo-3-chloropropane (IUPAC/Chemical Abstracts name) (1045)+TX, 1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062)+TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063)+TX, 1,3-dichloropropene (233)+TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC/Chemical Abstracts name) (1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPAC name) (1286)+TX, 6-isopentenylaminopurine (alternative name) (210)+TX, abamectin (1)+TX, acetoprole [CCN]+TX, alanycarb (15)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, AZ 60541 (compound code)+TX, benclothiaz [CCN]+TX, benomyl (62)+TX, butylpyridaben (alternative name)+TX, cadusafos (109)+TX, carbofuran (118)+TX, carbon disulfide (945)+TX, carbosulfan (119)+TX, chloropicrin (141)+TX, chlorpyrifos (145)+TX, cloethocarb (999)+TX, Cyclobutrifluram+TX, cytokinins (alternative name) (210)+TX, dazomet (216)+TX, DBCP (1045)+TX, DCIP (218)+TX, diamidafos (1044)+TX, dichlofenthion (1051)+TX, dicliphos (alternative name)+TX, dimethoate (262)+TX, doramectin (alternative name) [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin (alternative name) [CCN]+TX, ethoprophos (312)+TX, ethylene dibromide (316)+TX, fenamiphos (326)+TX, fenpyrad (alternative name)+TX, fensulfothion (1158)+TX, fosthiazate (408)+TX, fosthietan (1196)+TX, furfural (alternative name) [CCN]+TX, GY-81 (development code) (423)+TX, heterophos [CCN]+TX, iodomethane (IUPAC name) (542)+TX, isamidofos (1230)+TX, isazofos (1231)+TX, ivermectin (alternative name) [CCN]+TX, kinetin (alternative name) (210)+TX, mecarphon (1258)+TX, metam (519)+TX, metam-potassium (alternative name) (519)+TX, metam-sodium (519)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, milbemycin oxime (alternative name) [CCN]+TX, moxidectin (alternative name) [CCN]+TX, Myrothecium verrucaria composition (alternative name) (565)+TX, NC-184 (compound code)+TX, oxamyl (602)+TX, phorate (636)+TX, phosphamidon (639)+TX, phosphocarb [CCN]+TX, sebufos (alternative name)+TX, selamectin (alternative name) [CCN]+TX, spinosad (737)+TX, terbam (alternative name)+TX, terbufos (773)+TX, tetrachlorothiophene (IUPAC/Chemical Abstracts name) (1422)+TX, thiafenox (alternative name)+TX, thionazin (1434)+TX, triazophos (820)+TX, triazuron (alternative name)+TX, xylenols [CCN]+TX, YI-5302 (compound code) and zeatin (alternative name) (210)+TX, fluensulfone [318290-98-1]+TX, fluopyram+TX,
a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580)+TX, a plant activator selected from the group of substances consisting of acibenzolar (6)+TX, acibenzolar-S-methyl (6)+TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720)+TX,
a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, alpha-chlorohydrin [CCN]+TX, aluminium phosphide (640)+TX, antu (880)+TX, arsenous oxide (882)+TX, barium carbonate (891)+TX, bisthiosemi (912)+TX, brodifacoum (89)+TX, bromadiolone (91)+TX, bromethalin (92)+TX, calcium cyanide (444)+TX, chloralose (127)+TX, chlorophacinone (140)+TX, cholecalciferol (alternative name) (850)+TX, coumachlor (1004)+TX, coumafuryl (1005)+TX, coumatetralyl (175)+TX, crimidine (1009)+TX, difenacoum (246)+TX, difethialone (249)+TX, diphacinone (273)+TX, ergocalciferol (301)+TX, flocoumafen (357)+TX, fluoroacetamide (379)+TX, flupropadine (1183)+TX, flupropadine hydrochloride (1183)+TX, gamma-HCH (430)+TX, HCH (430)+TX, hydrogen cyanide (444)+TX, iodomethane (IUPAC name) (542)+TX, lindane (430)+TX, magnesium phosphide (IUPAC name) (640)+TX, methyl bromide (537)+TX, norbormide (1318)+TX, phosacetim (1336)+TX, phosphine (IUPAC name) (640)+TX, phosphorus [CCN]+TX, pindone (1341)+TX, potassium arsenite [CCN]+TX, pyrinuron (1371)+TX, scilliroside (1390)+TX, sodium arsenite [CCN]+TX, sodium cyanide (444)+TX, sodium fluoroacetate (735)+TX, strychnine (745)+TX, thallium sulfate [CCN]+TX, warfarin (851) and zinc phosphide (640)+TX,
a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934)+TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903)+TX, farnesol with nerolidol (alternative name) (324)+TX, MB-599 (development code) (498)+TX, MGK 264 (development code) (296)+TX, piperonyl butoxide (649)+TX, piprotal (1343)+TX, propyl isomer (1358)+TX, S421 (development code) (724)+TX, sesamex (1393)+TX, sesasmolin (1394) and sulfoxide (1406)+TX,
an animal repellent selected from the group of substances consisting of anthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX, copper oxychloride (171)+TX, diazinon (227)+TX, dicyclopentadiene (chemical name) (1069)+TX, guazatine (422)+TX, guazatine acetates (422)+TX, methiocarb (530)+TX, pyridin-4-amine (IUPAC name) (23)+TX, thiram (804)+TX, trimethacarb (840)+TX, zinc naphthenate [CCN] and ziram (856)+TX,
a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN]+TX,
a wound protectant selected from the group of substances consisting of mercuric oxide (512)+TX, octhilinone (590) and thiophanate-methyl (802)+TX, a biologically active substance selected from 1,1-bis(4-chloro-phenyl)-2-ethoxyethanol+TX, 2,4-dichlorophenyl benzenesulfonate+TX, 2-fluoro-N-methyl-N-1-naphthylacetamide+TX, 4-chlorophenyl phenyl sulfone+TX, acetoprole+TX, aldoxycarb+TX, amidithion+TX, amidothioate+TX, amiton+TX, amiton hydrogen oxalate+TX, amitraz+TX, aramite+TX, arsenous oxide+TX, azobenzene+TX, azothoate+TX, benomyl+TX, benoxa-fos+TX, benzyl benzoate+TX, bixafen+TX, brofenvalerate+TX, bromo-cyclen+TX, bromophos+TX, bromopropylate+TX, buprofezin+TX, butocarboxim+TX, butoxycarboxim+TX, butylpyridaben+TX, calcium polysulfide+TX, camphechlor+TX, carbanolate+TX, carbophenothion+TX, cymiazole+TX, chino-methionat+TX, chlorbenside+TX, chlordimeform+TX, chlordimeform hydrochloride+TX, chlorfenethol+TX, chlorfenson+TX, chlorfensulfide+TX, chlorobenzilate+TX, chloromebuform+TX, chloromethiuron+TX, chloropropylate+TX, chlorthiophos+TX, cinerin I+TX, cinerin II+TX, cinerins+TX, closantel+TX, coumaphos+TX, crotamiton+TX, crotoxyphos+TX, cufraneb+TX, cyanthoate+TX, DCPM+TX, DDT+TX, demephion+TX, demephion-O+TX, demephion-S+TX, demeton-methyl+TX, demeton-O+TX, demeton-O-methyl+TX, demeton-S+TX, demeton-S-methyl+TX, demeton-S-methylsulfon+TX, dichlofluanid+TX, dichlorvos+TX, dicliphos+TX, dienochlor+TX, dimefox+TX, dinex+TX, dinex-diclexine+TX, dinocap-4+TX, dinocap-6+TX, dinocton+TX, dino-penton+TX, dinosulfon+TX, dinoterbon+TX, dioxathion+TX, diphenyl sulfone+TX, disulfiram+TX, DNOC+TX, dofenapyn+TX, doramectin+TX, endothion+TX, eprinomectin+TX, ethoate-methyl+TX, etrimfos+TX, fenazaflor+TX, fenbutatin oxide+TX, fenothiocarb+TX, fenpyrad+TX, fen-pyroximate+TX, fenpyrazamine+TX, fenson+TX, fentrifanil+TX, flubenzimine+TX, flucycloxuron+TX, fluenetil+TX, fluorbenside+TX, FMC 1137+TX, formetanate+TX, formetanate hydrochloride+TX, formparanate+TX, gamma-HCH+TX, glyodin+TX, halfenprox+TX, hexadecyl cyclopropanecarboxylate+TX, isocarbophos+TX, jasmolin I+TX, jasmolin II+TX, jodfenphos+TX, lindane+TX, malonoben+TX, mecarbam+TX, mephosfolan+TX, mesulfen+TX, methacrifos+TX, methyl bromide+TX, metolcarb+TX, mexacarbate+TX, milbemycin oxime+TX, mipafox+TX, monocrotophos+TX, morphothion+TX, moxidectin+TX, naled+TX, 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one+TX, nifluridide+TX, nikkomycins+TX, nitrilacarb+TX, nitrilacarb 1:1 zinc chloride complex+TX, omethoate+TX, oxydeprofos+TX, oxydisulfoton+TX, pp′-DDT+TX, parathion+TX, permethrin+TX, phenkapton+TX, phosalone+TX, phosfolan+TX, phosphamidon+TX, polychloroterpenes+TX, polynactins+TX, proclonol+TX, promacyl+TX, propoxur+TX, prothidathion+TX, prothoate+TX, pyrethrin I+TX, pyrethrin II+TX, pyrethrins+TX, pyridaphenthion+TX, pyrimitate+TX, quinalphos+TX, quintiofos+TX, R-1492+TX, phosglycin+TX, rotenone+TX, schradan+TX, sebufos+TX, selamectin+TX, sophamide+TX, SSI-121+TX, sulfiram+TX, sulfluramid+TX, sulfotep+TX, sulfur+TX, diflovidazin+TX, tau-fluvalinate+TX, TEPP+TX, terbam+TX, tetradifon+TX, tetrasul+TX, thiafenox+TX, thiocarboxime+TX, thiofanox+TX, thiometon+TX, thioquinox+TX, thuringiensin+TX, triamiphos+TX, triarathene+TX, triazophos+TX, triazuron+TX, trifenofos+TX, trinactin+TX, vamidothion+TX, vaniliprole+TX, bethoxazin+TX, copper dioctanoate+TX, copper sulfate+TX, cybutryne+TX, dichlone+TX, dichlorophen+TX, endothal+TX, fentin+TX, hydrated lime+TX, nabam+TX, quinoclamine+TX, quinonamid+TX, simazine+TX, triphenyltin acetate+TX, triphenyltin hydroxide+TX, crufomate+TX, piperazine+TX, thiophanate+TX, chloralose+TX, fenthion+TX, pyridin-4-amine+TX, strychnine+TX, 1-hydroxy-1H-pyridine-2-thione+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide+TX, 8-hydroxyquinoline sulfate+TX, bronopol+TX, copper hydroxide+TX, cresol+TX, dipyrithione+TX, dodicin+TX, fenaminosulf+TX, formaldehyde+TX, hydrargaphen+TX, kasugamycin+TX, kasugamycin hydrochloride hydrate+TX, nickel bis(dimethyldithiocarbamate)+TX, nitrapyrin+TX, octhilinone+TX, oxolinic acid+TX, oxytetracycline+TX, potassium hydroxyquinoline sulfate+TX, probenazole+TX, streptomycin+TX, streptomycin sesquisulfate+TX, tecloftalam+TX, thiomersal+TX, Adoxophyes orana GV+TX, Agrobacterium radiobacter+TX, Amblyseius spp.+TX, Anagrapha falcifera NPV+TX, Anagrus atomus+TX, Aphelinus abdominalis+TX, Aphidius colemani+TX, Aphidoletes aphidimyza+TX, Autographa californica NPV+TX, Bacillus sphaericus Neide+TX, Beauveria brongniartii+TX, Chrysoperla carnea+TX, Cryptolaemus montrouzieri+TX, Cydia pomonella GV+TX, Dacnusa sibirica+TX, Diglyphus isaea+TX, Encarsia formosa+TX, Eretmocerus eremicus+TX, Heterorhabditis bacteriophora and H. megidis+TX, Hippodamia convergens+TX, Leptomastix dactylopii+TX, Macrolophus caliginosus+TX, Mamestra brassicae NPV+TX, Metaphycus helvolus+TX, Metarhizium anisopliae var. acridum+TX, Metarhizium anisopliae var. anisopliae+TX, Neodiprion sertifer NPV and N. lecontei NPV+TX, Orius spp.+TX, Paecilomyces fumosoroseus+TX, Phytoseiulus persimilis+TX, Steinernema bibionis+TX, Steinernema carpocapsae+TX, Steinernema feltiae+TX, Steinernema glaseri+TX, Steinernema riobrave+TX, Steinernema riobravis+TX, Steinernema scapterisci+TX, Steinernema spp.+TX, Trichogramma spp.+TX, Typhlodromus occidentalis+TX, Verticillium lecanii+TX, apholate+TX, bisazir+TX, busulfan+TX, dimatif+TX, hemel+TX, hempa+TX, metepa+TX, methiotepa+TX, methyl apholate+TX, morzid+TX, penfluron+TX, tepa+TX, thiohempa+TX, thiotepa+TX, tretamine+TX, uredepa+TX, (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol+TX, (E)-tridec-4-en-1-yl acetate+TX, (E)-6-methylhept-2-en-4-ol+TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate+TX, (Z)-dodec-7-en-1-yl acetate+TX, (Z)-hexadec-11-enal+TX, (Z)-hexadec-11-en-1-yl acetate+TX, (Z)-hexadec-13-en-11-yn-1-yl acetate+TX, (Z)-icos-13-en-10-one+TX, (Z)-tetradec-7-en-1-al+TX, (Z)-tetradec-9-en-1-ol+TX, (Z)-tetradec-9-en-1-yl acetate+TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate+TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate+TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate+TX, 14-methyloctadec-1-ene+TX, 4-methylnonan-5-ol with 4-methylnonan-5-one+TX, alpha-multistriatin+TX, brevicomin+TX, codlelure+TX, codlemone+TX, cuelure+TX, disparlure+TX, dodec-8-en-1-yl acetate+TX, dodec-9-en-1-yl acetate+TX, dodeca-8+TX, 10-dien-1-yl acetate+TX, dominicalure+TX, ethyl 4-methyloctanoate+TX, eugenol+TX, frontalin+TX, grandlure+TX, grandlure I+TX, grandlure II+TX, grandlure III+TX, grandlure IV+TX, hexalure+TX, ipsdienol+TX, ipsenol+TX, japonilure+TX, lineatin+TX, litlure+TX, looplure+TX, medlure+TX, megatomoic acid+TX, methyl eugenol+TX, muscalure+TX, octadeca-2,13-dien-1-yl acetate+TX, octadeca-3,13-dien-1-yl acetate+TX, orfralure+TX, oryctalure+TX, ostramone+TX, siglure+TX, sordidin+TX, sulcatol+TX, tetradec-11-en-1-yl acetate+TX, trimedlure+TX, trimedlure A+TX, trimedlure B.sub.1+TX, trimedlure B.sub.2+TX, trimedlure C+TX, trunc-call+TX, 2-(octylthio)-ethanol+TX, butopyronoxyl+TX, butoxy(polypropylene glycol)+TX, dibutyl adipate+TX, dibutyl phthalate+TX, dibutyl succinate+TX, diethyltoluamide+TX, dimethyl carbate+TX, dimethyl phthalate+TX, ethyl hexanediol+TX, hexamide+TX, methoquin-butyl+TX, methylneodecanamide+TX, oxamate+TX, picaridin+TX, 1-dichloro-1-nitroethane+TX, 1,1-dichloro-2,2-bis(4-ethylphenyl)-ethane+TX, 1,2-dichloropropane with 1,3-dichloropropene+TX, 1-bromo-2-chloroethane+TX, 2,2,2-trichloro-1-(3,4-dichloro-phenyl)ethyl acetate+TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate+TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate+TX, 2-(2-butoxyethoxy)ethyl thiocyanate+TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate+TX, 2-(4-chloro-3,5-xylyloxy)ethanol+TX, 2-chlorovinyl diethyl phosphate+TX, 2-imidazolidone+TX, 2-isovalerylindan-1,3-dione+TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate+TX, 2-thiocyanatoethyl laurate+TX, 3-bromo-1-chloroprop-1-ene+TX, 3-methyl-1-phenylpyrazol-5-yl dimethyl-carbamate+TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate+TX, 5,5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate+TX, acethion+TX, acrylonitrile+TX, aldrin+TX, allosamidin+TX, allyxycarb+TX, alpha-ecdysone+TX, aluminium phosphide+TX, aminocarb+TX, anabasine+TX, athidathion+TX, azamethiphos+TX, Bacillus thuringiensis delta endotoxins+TX, barium hexafluorosilicate+TX, barium polysulfide+TX, barthrin+TX, Bayer 22/190+TX, Bayer 22408+TX, beta-cyfluthrin+TX, beta-cypermethrin+TX, bioethanomethrin+TX, biopermethrin+TX, bis(2-chloroethyl) ether+TX, borax+TX, bromfenvinfos+TX, bromo-DDT+TX, bufencarb+TX, butacarb+TX, butathiofos+TX, butonate+TX, calcium arsenate+TX, calcium cyanide+TX, carbon disulfide+TX, carbon tetrachloride+TX, cartap hydrochloride+TX, cevadine+TX, chlorbicyclen+TX, chlordane+TX, chlordecone+TX, chloroform+TX, chloropicrin+TX, chlorphoxim+TX, chlorprazophos+TX, cis-resmethrin+TX, cismethrin+TX, clocythrin+TX, copper acetoarsenite+TX, copper arsenate+TX, copper oleate+TX, coumithoate+TX, cryolite+TX, CS 708+TX, cyanofenphos+TX, cyanophos+TX, cyclethrin+TX, cythioate+TX, d-tetramethrin+TX, DAEP+TX, dazomet+TX, decarbofuran+TX, diamidafos+TX, dicapthon+TX, dichlofenthion+TX, dicresyl+TX, dicyclanil+TX, dieldrin+TX, diethyl 5-methylpyrazol-3-yl phosphate+TX, dilor+TX, dimefluthrin+TX, dimetan+TX, dimethrin+TX, dimethylvinphos+TX, dimetilan+TX, dinoprop+TX, dinosam+TX, dinoseb+TX, diofenolan+TX, dioxabenzofos+TX, dithicrofos+TX, DSP+TX, ecdysterone+TX, EI 1642+TX, EMPC+TX, EPBP+TX, etaphos+TX, ethiofencarb+TX, ethyl formate+TX, ethylene dibromide+TX, ethylene dichloride+TX, ethylene oxide+TX, EXD+TX, fenchlorphos+TX, fenethacarb+TX, fenitrothion+TX, fenoxacrim+TX, fenpirithrin+TX, fensulfothion+TX, fenthion-ethyl+TX, flucofuron+TX, fosmethilan+TX, fospirate+TX, fosthietan+TX, furathiocarb+TX, furethrin+TX, guazatine+TX, guazatine acetates+TX, sodium tetrathiocarbonate+TX, halfenprox+TX, HCH+TX, HEOD+TX, heptachlor+TX, heterophos+TX, HHDN+TX, hydrogen cyanide+TX, hyquincarb+TX, IPSP+TX, isazofos+TX, isobenzan+TX, isodrin+TX, isofenphos+TX, isolane+TX, isoprothiolane+TX, isoxathion+TX, juvenile hormone I+TX, juvenile hormone II+TX, juvenile hormone III+TX, kelevan+TX, kinoprene+TX, lead arsenate+TX, leptophos+TX, lirimfos+TX, lythidathion+TX, m-cumenyl methylcarbamate+TX, magnesium phosphide+TX, mazidox+TX, mecarphon+TX, menazon+TX, mercurous chloride+TX, mesulfenfos+TX, metam+TX, metam-potassium+TX, metam-sodium+TX, methanesulfonyl fluoride+TX, methocrotophos+TX, methoprene+TX, methothrin+TX, methoxychlor+TX, methyl isothiocyanate+TX, methylchloroform+TX, methylene chloride+TX, metoxadiazone+TX, mirex+TX, naftalofos+TX, naphthalene+TX, NC-170+TX, nicotine+TX, nicotine sulfate+TX, nithiazine+TX, nornicotine+TX, O-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate+TX, O,O-diethyl O-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate+TX, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate+TX, O,O,O′,O′-tetrapropyl dithiopyrophosphate+TX, oleic acid+TX, para-dichlorobenzene+TX, parathion-methyl+TX, pentachlorophenol+TX, pentachlorophenyl laurate+TX, PH 60-38+TX, phenkapton+TX, phosnichlor+TX, phosphine+TX, phoxim-methyl+TX, pirimetaphos+TX, polychlorodicyclopentadiene isomers+TX, potassium arsenite+TX, potassium thiocyanate+TX, precocene I+TX, precocene II+TX, precocene III+TX, primidophos+TX, profluthrin+TX, promecarb+TX, prothiofos+TX, pyrazophos+TX, pyresmethrin+TX, quassia+TX, quinalphos-methyl+TX, quinothion+TX, rafoxanide+TX, resmethrin+TX, rotenone+TX, kadethrin+TX, ryania+TX, ryanodine+TX, sabadilla)+TX, schradan+TX, sebufos+TX, SI-0009+TX, thiapronil+TX, sodium arsenite+TX, sodium cyanide+TX, sodium fluoride+TX, sodium hexafluorosilicate+TX, sodium pentachlorophenoxide+TX, sodium selenate+TX, sodium thiocyanate+TX, sulcofuron+TX, sulcofuron-sodium+TX, sulfuryl fluoride+TX, sulprofos+TX, tar oils+TX, tazimcarb+TX, TDE+TX, tebupirimfos+TX, temephos+TX, terallethrin+TX, tetrachloroethane+TX, thicrofos+TX, thiocyclam+TX, thiocyclam hydrogen oxalate+TX, thionazin+TX, thiosultap+TX, thiosultap-sodium+TX, tralomethrin+TX, transpermethrin+TX, triazamate+TX, trichlormetaphos-3+TX, trichloronat+TX, trimethacarb+TX, tolprocarb+TX, triclopyricarb+TX, triprene+TX, veratridine+TX, veratrine+TX, XMC+TX, zetamethrin+TX, zinc phosphide+TX, zolaprofos+TX, and meperfluthrin+TX, tetramethylfluthrin+TX, bis(tributyltin) oxide+TX, bromoacetamide+TX, ferric phosphate+TX, niclosamide-olamine+TX, tributyltin oxide+TX, pyrimorph+TX, trifenmorph+TX, 1,2-dibromo-3-chloropropane+TX, 1,3-dichloropropene+TX, 3,4-dichlorotetrahydrothio-phene 1,1-dioxide+TX, 3-(4-chlorophenyl)-5-methylrhodanine+TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid+TX, 6-isopentenylaminopurine+TX, 2-fluoro-N-(3-methoxyphenyl)-9H-purin-6-amine+TX, benclothiaz+TX, cytokinins+TX, DCIP+TX, furfural+TX, isamidofos+TX, kinetin+TX, Myrothecium verrucaria composition+TX, tetrachlorothiophene+TX, xylenols+TX, zeatin+TX, potassium ethylxanthate+TX, acibenzolar+TX, acibenzolar-S-methyl+TX, Reynoutria sachalinensis extract+TX, alpha-chlorohydrin+TX, antu+TX, barium carbonate+TX, bisthiosemi+TX, brodifacoum+TX, bromadiolone+TX, bromethalin+TX, chlorophacinone+TX, cholecalciferol+TX, coumachlor+TX, coumafuryl+TX, coumatetralyl+TX, crimidine+TX, difenacoum+TX, difethialone+TX, diphacinone+TX, ergocalciferol+TX, flocoumafen+TX, fluoroacetamide+TX, flupropadine+TX, flupropadine hydrochloride+TX, norbormide+TX, phosacetim+TX, phosphorus+TX, pindone+TX, pyrinuron+TX, scilliroside+TX, -sodium fluoroacetate+TX, thallium sulfate+TX, warfarin+TX, -2-(2-butoxyethoxy)ethyl piperonylate+TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone+TX, farnesol with nerolidol+TX, verbutin+TX, MGK 264+TX, piperonyl butoxide+TX, piprotal+TX, propyl isomer+TX, S421+TX, sesamex+TX, sesasmolin+TX, sulfoxide+TX, anthraquinone+TX, copper naphthenate+TX, copper oxychloride+TX, dicyclopentadiene+TX, thiram+TX, zinc naphthenate+TX, ziram+TX, imanin+TX, ribavirin+TX, mercuric oxide+TX, thiophanate-methyl+TX, azaconazole+TX, bitertanol+TX, bromuconazole+TX, cyproconazole+TX, difenoconazole+TX, diniconazole-+TX, epoxiconazole+TX, fenbuconazole+TX, fluquinconazole+TX, flusilazole+TX, flutriafol+TX, furametpyr+TX, hexaconazole+TX, imazalil-+TX, imiben-conazole+TX, ipconazole+TX, metconazole+TX, myclobutanil+TX, paclobutrazole+TX, pefurazoate+TX, penconazole+TX, prothioconazole+TX, pyrifenox+TX, prochloraz+TX, propiconazole+TX, pyrisoxazole+TX, -simeconazole+TX, tebucon-azole+TX, tetraconazole+TX, triadimefon+TX, triadimenol+TX, triflumizole+TX, triticonazole+TX, ancymidol+TX, fenarimol+TX, nuarimol+TX, bupirimate+TX, dimethirimol+TX, ethirimol+TX, dodemorph+TX, fenpropidine+TX, fenpropimorph+TX, spiroxamine+TX, tridemorph+TX, cyprodinil+TX, mepanipyrim+TX, pyrimethanil+TX, fenpiclonil+TX, fludioxonil+TX, benalaxyl+TX, furalaxyl+TX, -metalaxyl-+TX, Rmetalaxyl+TX, ofurace+TX, oxadixyl+TX, carbendazim+TX, debacarb+TX, fuberidazole-+TX, thiabendazole+TX, chlozolinate+TX, dichlozoline+TX, myclozoline-+TX, procymidone+TX, vinclozoline+TX, boscalid+TX, carboxin+TX, fenfuram+TX, flutolanil+TX, mepronil+TX, oxycarboxin+TX, penthiopyrad+TX, thifluzamide+TX, dodine+TX, iminoctadine+TX, azoxystrobin+TX, dimoxystrobin+TX, enestroburin+TX, fenaminstrobin+TX, flufenoxystrobin+TX, fluoxastrobin+TX, kresoxim-methyl+TX, metominostrobin+TX, trifloxystrobin+TX, orysastrobin+TX, picoxystrobin+TX, pyraclostrobin+TX, pyrametostrobin+TX, pyraoxystrobin+TX, ferbam+TX, mancozeb+TX, maneb+TX, metiram+TX, propineb+TX, zineb+TX, captafol+TX, captan+TX, fluoroimide+TX, folpet+TX, tolylfluanid+TX, bordeaux mixture+TX, copper oxide+TX, mancopper+TX, oxine-copper+TX, nitrothal-isopropyl+TX, edifenphos+TX, iprobenphos+TX, phosdiphen+TX, tolclofos-methyl+TX, anilazine+TX, benthiavalicarb+TX, blasticidin-S+TX, chloroneb-+TX, chloro-tha-lonil+TX, cyflufenamid+TX, cymoxanil+TX, cyclobutrifluram+TX, diclocymet+TX, diclomezine-+TX, dicloran+TX, diethofencarb+TX, dimethomorph-+TX, flumorph+TX, dithianon+TX, ethaboxam+TX, etridiazole+TX, famoxadone+TX, fenamidone+TX, fenoxanil+TX, ferimzone+TX, fluazinam+TX, fluopicolide+TX, flusulfamide+TX, fluxapyroxad+TX, -fenhexamid+TX, fosetyl-aluminium-+TX, hymexazol+TX, iprovalicarb+TX, cyazofamid+TX, methasulfocarb+TX, metrafenone+TX, pencycuron+TX, phthalide+TX, polyoxins+TX, propamocarb+TX, pyribencarb+TX, proquinazid+TX, pyroquilon+TX, pyriofenone+TX, quinoxyfen+TX, quintozene+TX, tiadinil+TX, triazoxide+TX, tricyclazole+TX, triforine+TX, validamycin+TX, valifenalate+TX, zoxamide+TX, mandipropamid+TX, flubeneteram+TX, isopyrazam+TX, sedaxane+TX, benzovindiflupyr+TX, pydiflumetofen+TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3′,4′,5′-trifluoro-biphenyl-2-yl)-amide+TX, isoflucypram+TX, isotianil+TX, dipymetitrone+TX, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithiino[1,2-c]isothiazole-3-carbonitrile+TX, 2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide+TX, 4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine-3-carbonitrile+TX, (R)-3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide+TX, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine+TX, 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1, 3-dimethyl-1H-pyrazol-5-amine+TX, fluindapyr+TX, coumethoxystrobin (jiaxiangjunzhi)+TX, Ivbenmixianan+TX, dichlobentiazox+TX, mandestrobin+TX, 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone+TX, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolyl)oxy]phenyl]propan-2-ol+TX, oxathiapiprolin+TX, tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate+TX, pyraziflumid+TX, inpyrfluxam+TX, trolprocarb+TX, mefentrifluconazole+TX, ipfentrifluconazole+TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide+TX, N′-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine+TX, N′-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine+TX, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chloro-phenyl] methanesulfonate+TX, but-3-ynyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate+TX, methyl N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate+TX, 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine+TX, pyridachlometyl+TX, 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide+TX, 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one+TX, 1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazol-5-one+TX, aminopyrifen+TX, ametoctradin+TX, amisulbrom+TX, penflufen+TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide+TX, florylpicoxamid+TX, fenpicoxamid+TX, tebufloquin+TX, ipflufenoquin+TX, quinofumelin+TX, isofetamid+TX, N-[2-[2,4-dichloro-phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide+TX, N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide+TX, benzothiostrobin+TX, phenamacril+TX, 5-amino-1,3,4-thiadiazole-2-thiol zinc salt (2:1)+TX, fluopyram+TX, flutianil+TX, fluopimomide+TX, pyrapropoyne+TX, picarbutrazox+TX, 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide+TX, 2-(difluoromethyl)-N-((3R)-1, 1, 3-trimethylindan-4-yl) pyridine-3-carboxamide+TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile+TX, metyltetraprole+TX, 2-(difluoromethyl)-N-((3R)-1, 1, 3-trimethylindan-4-yl) pyridine-3-carboxamide+TX, α-(1, 1-dinethylethyl)-α-[4′-(trifluoromethoxy) [1, 1′-biphenyl]-4-yl]-5-pyrimidinemethanol+TX, fluoxapiprolin+TX, enoxastrobin+TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile+TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile+TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile+TX, trinexapac+TX, coumoxystrobin+TX, zhongshengmycin+TX, thiodiazole copper+TX, zinc thiazole+TX, amectotractin+TX, iprodione+TX; N′-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX, N′-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX, N′-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX, N′-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX, N′-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-isopropyl-N-methyl-formamidine+TX (these compounds may be prepared from the methods described in WO2015/155075); N′-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX (this compound may be prepared from the methods described in IPCOM000249876D); N-isopropyl-N′-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine+TX, N′-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine+TX (these compounds may be prepared from the methods described in WO2018/228896); N-ethyl-N′-[5-methoxy-2-methyl-4-[2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine+TX, N-ethyl-N′-[5-methoxy-2-methyl-4-[2-trifuoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine+TX (these compounds may be prepared from the methods described in WO2019/110427); N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide+TX, 8-fluoro-N-[1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide+TX, N-(1-benzyl-1,3-dimethyl-butyl)-8-fluoro-quinoline-3-carboxamide+TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide+TX, N-(1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide+TX (these compounds may be prepared from the methods described in WO2017/153380); 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline+TX, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline+TX, 4,4-difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline+TX, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline+TX, 1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline+TX (these compounds may be prepared from the methods described in WO2017/025510); 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline+TX, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline+TX, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline+TX, 4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline+TX, 3-(4,4-difluoro-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole+TX (these compounds may be prepared from the methods described in WO2016/156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide+TX, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide+TX, N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide+TX, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX, 1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX, 3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX, N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide+TX, 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one+TX, 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one+TX, ethyl 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylate+TX, N,N-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-1,2,4-triazol-3-amine+TX. The compounds in this paragraph may be prepared from the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol+TX (this compound may be prepared from the methods described in WO 2017/029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol+TX (this compound may be prepared from the methods described in WO 2017/029179); 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile+TX (this compound may be prepared from the methods described in WO 2016/156290); 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile+TX (this compound may be prepared from the methods described in WO 2016/156290); (4-phenoxyphenyl)methyl 2-amino-6-methyl-pyridine-3-carboxylate+TX (this compound may be prepared from the methods described in WO 2014/006945); 2,6-Dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c′]dipyrrole-1,3,5,7(2H,6H)-tetrone+TX (this compound may be prepared from the methods described in WO 2011/138281); N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzenecarbothioamide+TX; N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX; (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide+TX (this compound may be prepared from the methods described in WO 2018/153707); N′-(2-chloro-5-methyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine+TX; N′-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N-ethyl-N-methyl-formamidine+TX (this compound may be prepared from the methods described in WO 2016/202742); 2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide+TX (this compound may be prepared from the methods described in WO 2014/095675); (5-methyl-2-pyridyl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone+TX, (3-methylisoxazol-5-yl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone+TX (these compounds may be prepared from the methods described in WO 2017/220485); 2-oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide+TX (this compound may be prepared from the methods described in WO 2018/065414); ethyl 1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylate+TX (this compound may be prepared from the methods described in WO 2018/158365); 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide+TX, N-[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX, N—[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX, N—[N-methoxy-C-methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX (these compounds may be prepared from the methods described in WO 2018/202428);
microbials including: Acinetobacter lwoffii+TX, Acremonium alternatum+TX+TX, Acremonium cephalosporium+TX+TX, Acremonium diospyri+TX, Acremonium obclavatum+TX, Adoxophyes orana granulovirus (AdoxGV) (Capex®)+TX, Agrobacterium radiobacter strain K84 (Galltrol-A®)+TX, Alternaria alternate+TX, Alternaria cassia+TX, Alternaria destruens (Smolder®)+TX, Ampelomyces quisqualis (AQ10®)+TX, Aspergillus flavus AF36 (AF36®)+TX, Aspergillus flavus NRRL 21882 (Aflaguard®)+TX, Aspergillus spp.+TX, Aureobasidium pullulans+TX, Azospirillum+TX, (MicroAZ®+TX, TAZO B®)+TX, Azotobacter+TX, Azotobacter chroocuccum (Azotomeal®)+TX, Azotobacter cysts (Bionatural Blooming Blossoms®)+TX, Bacillus amyloliquefaciens+TX, Bacillus cereus+TX, Bacillus chitinosporus strain CM-1+TX, Bacillus chitinosporus strain AQ746+TX, Bacillus licheniformis strain HB-2 (Biostart™ Rhizoboost®)+TX, Bacillus licheniformis strain 3086 (EcoGuard®+TX, Green Releaf®)+TX, Bacillus circulans+TX, Bacillus firmus (BioSafe®+TX, BioNem-WP®+TX, VOTiVO®)+TX, Bacillus firmus strain 1-1582+TX, Bacillus macerans+TX, Bacillus marismortui+TX, Bacillus megaterium+TX, Bacillus mycoides strain AQ726+TX, Bacillus papillae (Milky Spore Powder®)+TX, Bacillus pumilus spp.+TX, Bacillus pumilus strain GB34 (Yield Shield®)+TX, Bacillus pumilus strain AQ717+TX, Bacillus pumilus strain QST 2808 (Sonata®+TX, Ballad Plus®)+TX, Bacillus spahericus (VectoLex®)+TX, Bacillus spp.+TX, Bacillus spp. strain AQ175+TX, Bacillus spp. strain AQ177+TX, Bacillus spp. strain AQ178+TX, Bacillus subtilis strain QST 713 (CEASE®+TX, Serenade®+TX, Rhapsody®)+TX, Bacillus subtilis strain QST 714 (JAZZ®)+TX, Bacillus subtilis strain AQ153+TX, Bacillus subtilis strain AQ743+TX, Bacillus subtilis strain QST3002+TX, Bacillus subtilis strain QST3004+TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 (Taegro®+TX, Rhizopro®)+TX, Bacillus thuringiensis Cry 2Ae+TX, Bacillus thuringiensis Cry1Ab+TX, Bacillus thuringiensis aizawai GC 91 (Agree®)+TX, Bacillus thuringiensis israelensis (BMP123®+TX, Aquabac®+TX, VectoBac®)+TX, Bacillus thuringiensis kurstaki (Javelin®+TX, Deliver®+TX, CryMax®+TX, Bonide®+TX, Scutella WP®+TX, Turilav WP®+TX, Astuto®+TX, Dipel WP®+TX, Biobit®+TX, Foray®)+TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®)+TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF/3P®)+TX, Bacillus thuringiensis strain BD #32+TX, Bacillus thuringiensis strain AQ52+TX, Bacillus thuringiensis var. aizawai (XenTari®+TX, DiPel®)+TX, bacteria spp. (GROWMEND®+TX, GROWSWEET®+TX, Shootup®)+TX, bacteriophage of Clavipacter michiganensis (AgriPhage®)+TX, Bakflor®+TX, Beauveria bassiana (Beaugenic®+TX, Brocaril WP®)+TX, Beauveria bassiana GHA (Mycotrol ES®+TX, Mycotrol O®+TX, BotaniGuard®)+TX, Beauveria brongniartii (Engerlingspilz®+TX, Schweizer Beauveria®+TX, Melocont®)+TX, Beauveria spp.+TX, Botrytis cineria+TX, Bradyrhizobium japonicum (TerraMax®)+TX, Brevibacillus brevis+TX, Bacillus thuringiensis tenebrionis (Novodor®)+TX, BtBooster+TX, Burkholderia cepacia (Deny®+TX, Intercept®+TX, Blue Circle®)+TX, Burkholderia gladii+TX, Burkholderia gladioli+TX, Burkholderia spp.+TX, Canadian thistle fungus (CBH Canadian Bioherbicide®)+TX, Candida butyri+TX, Candida famata+TX, Candida fructus+TX, Candida glabrata+TX, Candida guilliermondii+TX, Candida melibiosica+TX, Candida oleophila strain O+TX, Candida parapsilosis+TX, Candida pelliculosa+TX, Candida pulcherrima+TX, Candida reukaufii+TX, Candida saitoana (Bio-Coat®+TX, Biocure®)+TX, Candida sake+TX, Candida spp.+TX, Candida tenius+TX, Cedecea dravisae+TX, Cellulomonas flavigena+TX, Chaetomium cochliodes (Nova-Cide®)+TX, Chaetomium globosum (Nova-Cide®)+TX, Chromobacterium subtsugae strain PRAA4-1T (Grandevo®)+TX, Cladosporium cladosporioides+TX, Cladosporium oxysporum+TX, Cladosporium chlorocephalum+TX, Cladosporium spp.+TX, Cladosporium tenuissimum+TX, Clonostachys rosea (EndoFine®)+TX, Colletotrichum acutatum+TX, Coniothyrium minitans (Cotans WG®)+TX, Coniothyrium spp.+TX, Cryptococcus albidus (YIELDPLUS®)+TX, Cryptococcus humicola+TX, Cryptococcus infirmo-miniatus+TX, Cryptococcus laurentii+TX, Cryptophlebia leucotreta granulovirus (Cryptex®)+TX, Cupriavidus campinensis+TX, Cydia pomonella granulovirus (CYD-X®)+TX, Cydia pomonella granulovirus (Madex®+TX, Madex Plus®+TX, Madex Max/Carpovirusine®)+TX, Cylindrobasidium laeve (Stumpout®)+TX, Cylindrocladium+TX, Debaryomyces hansenii+TX, Drechslera hawaiinensis+TX, Enterobacter cloacae+TX, Enterobacteriaceae+TX, Entomophtora virulenta (Vektor®)+TX, Epicoccum nigrum+TX, Epicoccum purpurascens+TX, Epicoccum spp.+TX, Filobasidium floriforme+TX, Fusarium acuminatum+TX, Fusarium chlamydosporum+TX, Fusarium oxysporum (Fusaclean®/Biofox C®)+TX, Fusarium proliferatum+TX, Fusarium spp.+TX, Galactomyces geotrichum+TX, Gliocladium catenulatum (Primastop®+TX, Prestop®)+TX, Gliocladium roseum+TX, Gliocladium spp. (SoilGard®)+TX, Gliocladium virens (Soilgard®)+TX, Granulovirus (Granupom®)+TX, Halobacillus halophilus+TX, Halobacillus litoralis+TX, Halobacillus trueperi+TX, Halomonas spp.+TX, Halomonas subglaciescola+TX, Halovibrio variabilis+TX, Hanseniaspora uvarum+TX, Helicoverpa armigera nucleopolyhedrovirus (Helicovex®)+TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar®)+TX, Isoflavone-formononetin (Myconate®)+TX, Kloeckera apiculata+TX, Kloeckera spp.+TX, Lagenidium giganteum (Laginex®)+TX, Lecanicillium longisporum (Vertiblast®)+TX, Lecanicillium muscarium (Vertikil®)+TX, Lymantria Dispar nucleopolyhedrosis virus (Disparvirus®)+TX, Marinococcus halophilus+TX, Meira geulakonigii+TX, Metarhizium anisopliae (Met52®)+TX, Metarhizium anisopliae (Destruxin WP®)+TX, Metschnikowia fruticola (Shemer®)+TX, Metschnikowia pulcherrima+TX, Microdochium dimerum (Antibot®)+TX, Micromonospora coerulea+TX, Microsphaeropsis ochracea+TX, Muscodor albus 620 (Muscudor®)+TX, Muscodor roseus strain A3-5+TX, Mycorrhizae spp. (AMykor®+TX, Root Maximizer®)+TX, Myrothecium verrucaria strain AARC-0255 (DiTera®)+TX, BROS PLUS®+TX, Ophiostoma piliferum strain D97 (Sylvanex®)+TX, Paecilomyces farinosus+TX, Paecilomyces fumosoroseus (PFR-97®+TX, PreFeRal®)+TX, Paecilomyces linacinus (Biostat WP®)+TX, Paecilomyces lilacinus strain 251 (MeloCon WG®)+TX, Paenibacillus polymyxa+TX, Pantoea agglomerans (BlightBan C9-1®)+TX, Pantoea spp.+TX, Pasteuria spp. (Econem®)+TX, Pasteuria nishizawae+TX, Penicillium aurantiogriseum+TX, Penicillium billai (Jumpstart®+TX, TagTeam®)+TX, Penicillium brevicompactum+TX, Penicillium frequentans+TX, Penicillium griseofulvum+TX, Penicillium purpurogenum+TX, Penicillium spp.+TX, Penicillium viridicatum+TX, Phlebiopsis gigantean (Rotstop®)+TX, phosphate solubilizing bacteria (Phosphomeal®)+TX, Phytophthora cryptogea+TX, Phytophthora palmivora (Devine®)+TX, Pichia anomala+TX, Pichia guilermondii+TX, Pichia membranaefaciens+TX, Pichia onychis+TX, Pichia stipites+TX, Pseudomonas aeruginosa+TX, Pseudomonas aureofasciens (Spot-Less Biofungicide®)+TX, Pseudomonas cepacia+TX, Pseudomonas chlororaphis (AtEze®)+TX, Pseudomonas corrugate+TX, Pseudomonas fluorescens strain A506 (BlightBan A506®)+TX, Pseudomonas putida+TX, Pseudomonas reactans+TX, Pseudomonas spp.+TX, Pseudomonas syringae (Bio-Save®)+TX, Pseudomonas viridiflava+TX, Pseudomonas fluorescens (Zequanox®)+TX, Pseudozyma flocculosa strain PF-A22 UL (Sporodex L®)+TX, Puccinia canaliculata+TX, Puccinia thlaspeos (Wood Warrior®)+TX, Pythium paroecandrum+TX, Pythium oligandrum (Polygandron®+TX, Polyversum®)+TX, Pythium periplocum+TX, Rahnella aquatilis+TX, Rahnella spp.+TX, Rhizobia (Dormal®+TX, Vault®)+TX, Rhizoctonia+TX, Rhodococcus globerulus strain AQ719+TX, Rhodosporidium diobovatum+TX, Rhodosporidium toruloides+TX, Rhodotorula spp.+TX, Rhodotorula glutinis+TX, Rhodotorula graminis+TX, Rhodotorula mucilagnosa+TX, Rhodotorula rubra+TX, Saccharomyces cerevisiae+TX, Salinococcus roseus+TX, Sclerotinia minor+TX, Sclerotinia minor (SARRITOR®)+TX, Scytalidium spp.+TX, Scytalidium uredinicola+TX, Spodoptera exigua nuclear polyhedrosis virus (Spod-X®+TX, Spexit®)+TX, Serratia marcescens+TX, Serratia plymuthica+TX, Serratia spp.+TX, Sordaria fimicola+TX, Spodoptera littoralis nucleopolyhedrovirus (Littovir®)+TX, Sporobolomyces roseus+TX, Stenotrophomonas maltophilia+TX, Streptomyces ahygroscopicus+TX, Streptomyces albaduncus+TX, Streptomyces exfoliates+TX, Streptomyces galbus+TX, Streptomyces griseoplanus+TX, Streptomyces griseoviridis (Mycostop®)+TX, Streptomyces lydicus (Actinovate®)+TX, Streptomyces lydicus WYEC-108 (ActinoGrow®)+TX, Streptomyces violaceus+TX, Tilletiopsis minor+TX, Tilletiopsis spp.+TX, Trichoderma asperellum (T34 Biocontrol®)+TX, Trichoderma gamsii (Tenet®)+TX, Trichoderma atroviride (Plantmate®)+TX, Trichoderma hamatum TH 382+TX, Trichoderma harzianum rifai (Mycostar®)+TX, Trichoderma harzianum T-22 (Trianum-P®+TX, PlantShield HCO+TX, RootShield®+TX, Trianum-G®)+TX, Trichoderma harzianum T-39 (Trichodex®)+TX, Trichoderma inhamatum+TX, Trichoderma koningii+TX, Trichoderma spp. LC 52 (Sentinel®)+TX, Trichoderma lignorum+TX, Trichoderma longibrachiatum+TX, Trichoderma polysporum (Binab T®)+TX, Trichoderma taxi+TX, Trichoderma virens+TX, Trichoderma virens (formerly Gliocladium virens GL-21) (SoilGuard®)+TX, Trichoderma viride+TX, Trichoderma viride strain ICC 080 (Remedier®)+TX, Trichosporon pullulans+TX, Trichosporon spp.+TX, Trichothecium spp.+TX, Trichothecium roseum+TX, Typhula phacorrhiza strain 94670+TX, Typhula phacorrhiza strain 94671+TX, Ulocladium atrum+TX, Ulocladium oudemansii (Botry-Zen®)+TX, Ustilago maydis+TX, various bacteria and supplementary micronutrients (Natural II®)+TX, various fungi (Millennium Microbes®)+TX, Verticillium chlamydosporium+TX, Verticillium lecanii (Mycotal®+TX, Vertalec®)+TX, Vip3Aa20 (VIPtera®)+TX, Virgibaclillus marismortui+TX, Xanthomonas campestris pv. Poae (Camperico®)+TX, Xenorhabdus bovienii+TX, Xenorhabdus nematophilus;
Plant extracts including: pine oil (Retenol®)+TX, azadirachtin (Plasma Neem Oil®+TX, AzaGuard®+TX, MeemAzal®+TX, Molt-X®+TX, Botanical IGR (Neemazad®+TX, Neemix®)+TX, canola oil (Lilly Miller Vegol®)+TX, Chenopodium ambrosioides near ambrosioides (Requiem®)+TX, Chrysanthemum extract (Crisant®)+TX, extract of neem oil (Trilogy®)+TX, essentials oils of Labiatae (Botania®)+TX, extracts of clove rosemary peppermint and thyme oil (Garden insect Killer®)+TX, Glycinebetaine (Greenstim®)+TX, garlic+TX, lemongrass oil (GreenMatch®)+TX, neem oil+TX, Nepeta cataria (Catnip oil)+TX, Nepeta catarina+TX, nicotine+TX, oregano oil (MossBuster®)+TX, Pedaliaceae oil (Nematon®)+TX, pyrethrum+TX, Quillaja saponaria (NemaQ®)+TX, Reynoutria sachalinensis (Regalia®+TX, Sakalia®)+TX, rotenone (Eco Roten®)+TX, Rutaceae plant extract (Soleo®)+TX, soybean oil (Ortho Ecosense®)+TX, tea tree oil (Timorex Gold®)+TX, thymus oil+TX, AGNIQUE® MMF+TX, BugOil®+TX, mixture of rosemary sesame pepermint thyme and cinnamon extracts (EF 300®)+TX, mixture of clove rosemary and peppermint extract (EF 400®)+TX, mixture of clove pepermint garlic oil and mint (Soil Shot®)+TX, kaolin (Screen®)+TX, storage glucam of brown algae (Laminarin®);
pheromones including: blackheaded fireworm pheromone (3M Sprayable Blackheaded Fireworm Pheromone®)+TX, Codling Moth Pheromone (Paramount dispenser-(CM)/Isomate C-Plus®)+TX, Grape Berry Moth Pheromone (3M MEC-GBM Sprayable Pheromone®)+TX, Leafroller pheromone (3M MEC-LR Sprayable Pheromone®)+TX, Muscamone (Snip7 Fly Bait®+TX, Starbar Premium Fly Bait®)+TX, Oriental Fruit Moth Pheromone (3M oriental fruit moth sprayable Pheromone®)+TX, Peachtree Borer Pheromone (Isomate-P®)+TX, Tomato Pinworm Pheromone (3M Sprayable Pheromone®)+TX, Entostat powder (extract from palm tree) (Exosex CM®)+TX, (E+TX,Z+TX,Z)-3+TX,8+TX,11 Tetradecatrienyl acetate+TX, (Z+TX,Z+TX,E)-7+TX,11+TX,13-Hexadecatrienal+TX, (E+TX,Z)-7+TX,9-Dodecadien-1-yl acetate+TX, 2-Methyl-1-butanol+TX, Calcium acetate+TX, Scenturion®+TX, Biolure®+TX, Check-Mate®+TX, Lavandulyl senecioate;
Macrobials including: Aphelinus abdominalis+TX, Aphidius ervi (Aphelinus-System®)+TX, Acerophagus papaya+TX, Adalia bipunctata (Adalia-System®)+TX, Adalia bipunctata (Adaline®)+TX, Adalia bipunctata (Aphidalia®)+TX, Ageniaspis citricola+TX, Ageniaspis fuscicollis+TX, Amblyseius andersoni (Anderline®+TX, Andersoni-System®)+TX, Amblyseius californicus (Amblyline®+TX, Spical®)+TX, Amblyseius cucumeris (Thripex®+TX, Bugline Cucumeris®)+TX, Amblyseius fallacis (Fallacis®)+TX, Amblyseius swirskii (Bugline Swirskii®+TX, Swirskii-Mite®)+TX, Amblyseius womersleyi (WomerMite®)+TX, Amitus hesperidum+TX, Anagrus atomus+TX, Anagyrus fusciventris+TX, Anagyrus kamali+TX, Anagyrus loecki+TX, Anagyrus pseudococci (Citripar®)+TX, Anicetus benefices+TX, Anisopteromalus calandrae+TX, Anthocoris nemoralis (Anthocoris-System®)+TX, Aphelinus abdominalis (Apheline®+TX, Aphiline®)+TX, Aphelinus asychis+TX, Aphidius colemani (Aphipar®)+TX, Aphidius ervi (Ervipar®)+TX, Aphidius gifuensis+TX, Aphidius matricariae (Aphipar-M®)+TX, Aphidoletes aphidimyza (Aphidend®)+TX, Aphidoletes aphidimyza (Aphidoline®)+TX, Aphytis lingnanensis+TX, Aphytis melinus+TX, Aprostocetus hagenowii+TX, Atheta coriaria (Staphyline®)+TX, Bombus spp.+TX, Bombus terrestris (Natupol Beehive®)+TX, Bombus terrestris (Beeline®+TX, Tripol®)+TX, Cephalonomia stephanoderis+TX, Chilocorus nigritus+TX, Chrysoperla carnea (Chrysoline®)+TX, Chrysoperla carnea (Chrysopa®)+TX, Chrysoperla rufilabris+TX, Cirrospilus ingenuus+TX, Cirrospilus quadristriatus+TX, Citrostichus phyllocnistoides+TX, Closterocerus chamaeleon+TX, Closterocerus spp.+TX, Coccidoxenoides perminutus (Planopar®)+TX, Coccophagus cowperi+TX, Coccophagus lycimnia+TX, Cotesia flavipes+TX, Cotesia plutellae+TX, Cryptolaemus montrouzieri (Cryptobug®+TX, Cryptoline®)+TX, Cybocephalus nipponicus+TX, Dacnusa sibirica+TX, Dacnusa sibirica (Minusa®)+TX, Diglyphus isaea (Diminex®)+TX, Delphastus catalinae (Delphastus®)+TX, Delphastus pusillus+TX, Diachasmimorpha krausii+TX, Diachasmimorpha longicaudata+TX, Diaparsis jucunda+TX, Diaphorencyrtus aligarhensis+TX, Diglyphus isaea+TX, Diglyphus isaea (Miglyphus®+TX, Digline®)+TX, Dacnusa sibirica (DacDigline®+TX, Minex®)+TX, Diversinervus spp.+TX, Encarsia citrina+TX, Encarsia formosa (Encarsia Max®+TX, Encarline®+TX, En-Strip®)+TX, Eretmocerus eremicus (Enermix®)+TX, Encarsia guadeloupae+TX, Encarsia haitiensis+TX, Episyrphus balteatus (Syrphidend®)+TX, Eretmoceris siphonini+TX, Eretmocerus californicus+TX, Eretmocerus eremicus (Ercal®+TX, Eretline E®)+TX, Eretmocerus eremicus (Bemimix®)+TX, Eretmocerus hayati+TX, Eretmocerus mundus (Bemipar®+TX, Eretline M®)+TX, Eretmocerus siphonini+TX, Exochomus quadripustulatus+TX, Feltiella acarisuga (Spidend®)+TX, Feltiella acarisuga (Feltiline®)+TX, Fopius arisanus+TX, Fopius ceratitivorus+TX, Formononetin (Wirless Beehome®)+TX, Franklinothrips vespiformis (Vespop®)+TX, Galendromus occidentalis+TX, Goniozus legneri+TX, Habrobracon hebetor+TX, Harmonia axyridis (HarmoBeetle®)+TX, Heterorhabditis spp. (Lawn Patrol®)+TX, Heterorhabditis bacteriophora (NemaShield HB®+TX, Nemaseek®+TX, Terranem-Nam®+TX, Terranem®+TX, Larvanem®+TX, B-Green®+TX, NemAttack®+TX, Nematop®)+TX, Heterorhabditis megidis (Nemasys H®+TX, BioNem H®+TX, Exhibitline Hm®+TX, Larvanem-M®)+TX, Hippodamia convergens+TX, Hypoaspis aculeifer (Aculeifer-System®+TX, Entomite-A®)+TX, Hypoaspis miles (Hypoline M®+TX, Entomite-M®)+TX, Lobalia leucospoides+TX, Lecanoideus floccissimus+TX, Lemophagus errabundus+TX, Leptomastidea abnormis+TX, Leptomastix dactylopii (Leptopar®)+TX, Leptomastix epona+TX, Lindorus lophanthae+TX, Lipolexis oregmae+TX, Lucilia caesar (Natufly®)+TX, Lysiphlebus testaceipes+TX, Macrolophus caliginosus (Mirical-N®+TX, Macroline c®+TX, Mirical®)+TX, Mesoseiulus longipes+TX, Metaphycus flavus+TX, Metaphycus lounsburyi+TX, Micromus angulatus (Milacewing®)+TX, Microterys flavus+TX, Muscidifurax raptorellus and Spalangia cameroni (Biopar®)+TX, Neodryinus typhlocybae+TX, Neoseiulus californicus+TX, Neoseiulus cucumeris (THRYPEX®)+TX, Neoseiulus fallacis+TX, Nesideocoris tenuis (NesidioBug®+TX, Nesibug®)+TX, Ophyra aenescens (Biofly®)+TX, Orius insidiosus (Thripor-I®+TX, Oriline I®)+TX, Orius laevigatus (Thripor-L®+TX, Oriline I®)+TX, Orius majusculus (Oriline m®)+TX, Orius strigicollis (Thripor-S®)+TX, Pauesia juniperorum+TX, Pediobius foveolatus+TX, Phasmarhabditis hermaphrodita (Nemaslug®)+TX, Phymastichus coffea+TX, Phytoseiulus macropilus+TX, Phytoseiulus persimilis (Spidex®+TX, Phytoline P®)+TX, Podisus maculiventris (Podisus®)+TX, Pseudacteon curvatus+TX, Pseudacteon obtusus+TX, Pseudacteon tricuspis+TX, Pseudaphycus maculipennis+TX, Pseudleptomastix mexicana+TX, Psyllaephagus pilosus+TX, Psyttalia concolor (complex)+TX, Quadrastichus spp.+TX, Rhyzobius lophanthae+TX, Rodolia cardinalis+TX, Rumina decollate+TX, Semielacher petiolatus+TX, Sitobion avenae (Ervibank®)+TX, Steinernema carpocapsae (Nematac C®+TX, Millenium®+TX, BioNem C®+TX, NemAttack®+TX, Nemastar®+TX, Capsanem®)+TX, Steinernema feltiae (NemaShield®+TX, Nemasys F®+TX, BioNem F®+TX, Steinernema-System®+TX, NemAttack®+TX, Nemaplus®+TX, Exhibitline Sf®+TX, Scia-rid®+TX, Entonem®)+TX, Steinernema kraussei (Nemasys L®+TX, BioNem L®+TX, Exhibitline Srb®)+TX, Steinernema riobrave (BioVector®+TX, BioVektor®)+TX, Steinernema scapterisci (Nematac S®)+TX, Steinernema spp.+TX, Steinernematid spp. (Guardian Nematodes®)+TX, Stethorus punctillum (Stethorus®)+TX, Tamarixia radiate+TX, Tetrastichus setifer+TX, Thripobius semiluteus+TX, Torymus sinensis+TX, Trichogramma brassicae (Tricholine B®)+TX, Trichogramma brassicae (Tricho-Strip®)+TX, Trichogramma evanescens+TX, Trichogramma minutum+TX, Trichogramma ostriniae+TX, Trichogramma platneri+TX, Trichogramma pretiosum+TX, Xanthopimpla stemmator; and
other biologicals including: abscisic acid+TX, bioSea®+TX, Chondrostereum purpureum (Chontrol Paste®)+TX, Colletotrichum gloeosporioides (Collego®)+TX, Copper Octanoate (Cueva®)+TX, Delta traps (Trapline D®)+TX, Erwinia amylovora (Harpin) (ProAct®+TX, Ni-HIBIT Gold CST®)+TX, Ferri-phosphate (Ferramol®)+TX, Funnel traps (Trapline Y®)+TX, Gallex®+TX, Grower's Secret®+TX, Homo-brassonolide+TX, Iron Phosphate (Lilly Miller Worry Free Ferramol Slug & Snail Bait®)+TX, MCP hail trap (Trapline F®)+TX, Microctonus hyperodae+TX, Mycoleptodiscus terrestris (Des-X®)+TX, BioGain®+TX, Aminomite®+TX, Zenox®+TX, Pheromone trap (Thripline Ams®)+TX, potassium bicarbonate (MilStop®)+TX, potassium salts of fatty acids (Sanova®)+TX, potassium silicate solution (Sil-Matrix®)+TX, potassium iodide+potassiumthiocyanate (Enzicur®)+TX, SuffOil-X®+TX, Spider venom+TX, Nosema locustae (Semaspore Organic Grasshopper Control®)+TX, Sticky traps (Trapline YF®+TX, Rebell Amarillo®)+TX and Traps (Takitrapline y+b®)+TX.

[0547] The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in “The Pesticide Manual” [The Pesticide Manual—A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound “abamectin” is described under entry number (1). Where “[CCN]” is added hereinabove to the particular compound, the compound in question is included in the “Compendium of Pesticide Common Names”, which is accessible on the internet [A. Wood; Compendium of Pesticide Common Names, Copyright © 1995-2004]; for example, the compound “acetoprole” is described under the internet address http://www.alanwood.net/pesticides/acetoprole.html.

[0548] Most of the active ingredients described above are referred to hereinabove by a so-called “common name”, the relevant “ISO common name” or another “common name” being used in individual cases. If the designation is not a “common name”, the nature of the designation used instead is given in round brackets for the particular compound; in that case, the IUPAC name, the IUPAC/Chemical Abstracts name, a “chemical name”, a “traditional name”, a “compound name” or a “development code” is used or, if neither one of those designations nor a “common name” is used, an “alternative name” is employed. “CAS Reg. No” means the Chemical Abstracts Registry Number.

[0549] The active ingredient mixture of the compounds of formula I selected from the compounds defined in the Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21 and E-1 to E-21 and with active ingredients described above comprises a compound selected from one compound defined in the Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21 and E-1 to E-21 and an active ingredient as described above preferably in a mixing ratio of from 100:1 to 1:6000, especially from 50:1 to 1:50, more especially in a ratio of from 20:1 to 1:20, even more especially from 10:1 to 1:10, very especially from 5:1 and 1:5, special preference being given to a ratio of from 2:1 to 1:2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750. Those mixing ratios are by weight.

[0550] The mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.

[0551] The mixtures comprising a compound of formula I selected from the compounds defined in the Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21 and E-1 to E-21 and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the compounds of formula I and the active ingredients as described above is not essential for working the present invention.

[0552] The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.

[0553] The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries). These processes for the preparation of the compositions and the use of the compounds I for the preparation of these compositions are also a subject of the invention.

[0554] The application methods for the compositions, that is the methods of controlling pests of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring—which are to be selected to suit the intended aims of the prevailing circumstances—and the use of the compositions for controlling pests of the abovementioned type are other subjects of the invention. Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient. The rate of application per hectare is generally 1 to 2000 g of active ingredient per hectare, in particular 10 to 1000 g/ha, preferably 10 to 600 g/ha.

[0555] A preferred method of application in the field of crop protection is application to the foliage of the plants (foliar application), it being possible to select frequency and rate of application to match the danger of infestation with the pest in question. Alternatively, the active ingredient can reach the plants via the root system (systemic action), by drenching the locus of the plants with a liquid composition or by incorporating the active ingredient in solid form into the locus of the plants, for example into the soil, for example in the form of granules (soil application). In the case of paddy rice crops, such granules can be metered into the flooded paddy-field.

[0556] The compounds of formula I of the invention and compositions thereof are also be suitable for the protection of plant propagation material, for example seeds, such as fruit, tubers or kernels, or nursery plants, against pests of the abovementioned type. The propagation material can be treated with the compound prior to planting, for example seed can be treated prior to sowing. Alternatively, the compound can be applied to seed kernels (coating), either by soaking the kernels in a liquid composition or by applying a layer of a solid composition. It is also possible to apply the compositions when the propagation material is planted to the site of application, for example into the seed furrow during drilling. These treatment methods for plant propagation material and the plant propagation material thus treated are further subjects of the invention. Typical treatment rates would depend on the plant and pest/fungi to be controlled and are generally between 1 to 200 grams per 100 kg of seeds, preferably between 5 to 150 grams per 100 kg of seeds, such as between 10 to 100 grams per 100 kg of seeds.

[0557] The term seed embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like and means in a preferred embodiment true seeds.

[0558] The present invention also comprises seeds coated or treated with or containing a compound of formula I. The term “coated or treated with and/or containing” generally signifies that the active ingredient is for the most part on the surface of the seed at the time of application, although a greater or lesser part of the ingredient may penetrate into the seed material, depending on the method of application. When the said seed product is (re)planted, it may absorb the active ingredient. In an embodiment, the present invention makes available a plant propagation material adhered thereto with a compound of formula I. Further, it is hereby made available, a composition comprising a plant propagation material treated with a compound of formula I.

[0559] Seed treatment comprises all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking and seed pelleting. The seed treatment application of the compound formula I can be carried out by any known methods, such as spraying or by dusting the seeds before sowing or during the sowing/planting of the seeds.

[0560] In each aspect and embodiment of the invention, “consisting essentially” and inflections thereof are a preferred embodiment of “comprising” and its inflections, and “consisting of” and inflections thereof are a preferred embodiment of “consisting essentially of” and its inflections.

[0561] The disclosure in the present application makes available each and every combination of embodiments disclosed herein.

[0562] It should be noted that the disclosure herein in respect of a compound of formula I applies equally in respect of a compound of each of formulae I*, I′a, I-A, I′-A, and Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21 and E-1 to E-21. Further the preferred enantiomer of formula I′a or I′-A applies also to compounds of Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21 and E-1 to E-21 and Table P. Also, made available herein is an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and/or N-oxide of the compound of formula formulae I*, I′a, I-A, I′-A, and Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21 and E-1 to E-21 and Table P.

[0563] The compounds of the invention can be distinguished from other similar compounds by virtue of greater efficacy at low application rates and/or different pest control, which can be verified by the person skilled in the art using the experimental procedures, using lower concentrations if necessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300, 200 or 100, mg of A1 per m.sup.2. The greater efficacy can be observed by an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability).

BIOLOGICAL EXAMPLES

[0564] 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, 24 ppm, 12.5 ppm, δ ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.

Example B1: Diabrotica balteata (Corn Root Worm)

[0565] Maize sprouts placed onto an agar layer in 24-well microtiter plates were treated with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions by spraying. After drying, the plates were infested with L2 larvae (6 to 10 per well). The samples were assessed for mortality and growth inhibition in comparison to untreated samples 4 days after infestation.

[0566] The following compounds gave an effect of at least 80% control in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:

P1, P6, P7, P8, P9, P13, P16, P17, P19, P20, P22, P24, P25, P26, P28, P30, P31, P32, P33, P34, P35, P36, P37, P39, P40, P41, P42, P44, P46, P49, P50, P53, P55, P57, P58.

Example B2: Euschistus heros (Neotropical Brown Stink Bug)

[0567] Soybean leaves on agar in 24-well microtiter plates were sprayed with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions. After drying the leaves were infested with N2 nymphs. The samples were assessed for mortality and growth inhibition in comparison to untreated samples 5 days after infestation.

[0568] The following compounds gave an effect of at least 80% control in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:

P1, P2, P3, P10, P21, P25, P30, P31, P32, P44, P46, P48, P50, P55

Example B3: Frankliniella occidentalis (Western Flower Thrips): Feeding/Contact Activity

[0569] Sunflower leaf discs were placed on agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10′000 DMSO stock solutions. After drying the leaf discs were infested with a Frankliniella population of mixed ages. The samples were assessed for mortality 7 days after infestation.

[0570] The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

P10, P31, P32, P44

Example B4: Chilo suppressalis (Striped Rice Stemborer)

[0571] 24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions by pipetting. After drying, the plates were infested with L2 larvae (6-8 per well). The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 6 days after infestation. Control of Chilo suppressalis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.

[0572] The following compounds resulted in at least 80% control in at least one of the three categories (mortality, anti-feedant or growth inhibition) at an application rate of 200 ppm:

P1, P2, P3, P4, P6, P7, P8, P9, P10, P11, P12, P13, P16, P17, P18, P19, P20, P22, P24, P25, P26, P27, P28, P30, P31, P32, P33, P34, P35, P36, P37, P39, P40, P41, P42, P43, P44, P45, P46, P47, P48, P49, P50, P53, P54, P55, P56, P57, P58

Example B5: Plutella xylostella (Diamond Back Moth)

[0573] 24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions by pipetting. After drying, Plutella eggs were pipetted through a plastic stencil onto a gel blotting paper and the plate was closed with it. The samples were assessed for mortality and growth inhibition in comparison to untreated samples 8 days after infestation.

[0574] The following compounds gave an effect of at least 80% control in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:

P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P13, P16, P17, P18, P19, P20, P21, P22, P23, P24, P25, P26, P27, P28, P29, P30, P31, P32, P33, P34, P35, P36, P37, P38, P39, P40, P41, P42, P43, P44, P45, P46, P47, P48, P49, P50, P51, P52, P53, P54, P55, P56, P57, P58.

Example B6: Myzus persicae (Green Peach Aphid): Feeding/Contact Activity

[0575] Sunflower leaf discs were placed onto agar in a 24-well microtiter plate and sprayed with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions. After drying, the leaf discs were infested with an aphid population of mixed ages. The samples were assessed for mortality 6 days after infestation.

[0576] The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

P44, P45, P46

Example B7: Myzus persicae (Green Peach Aphid): Systemic Activity

[0577] Roots of pea seedlings infested with an aphid population of mixed ages were placed directly into aqueous test solutions prepared from 10′000 DMSO stock solutions. The samples were assessed for mortality 6 days after placing seedlings into test solutions.

[0578] The following compounds resulted in at least 80% mortality at a test rate of 24 ppm:

P10, P25, P44, P46, P50

Example B8: Myzus persicae (Green Peach Aphid): Intrinsic Activity

[0579] Test compounds prepared from 10′000 ppm DMSO stock solutions were applied by pipette into 24-well microtiter plates and mixed with sucrose solution. The plates were closed with a stretched Parafilm. A plastic stencil with 24 holes was placed onto the plate and infested pea seedlings were placed directly on the Parafilm. The infested plate was closed with a gel blotting paper and another plastic stencil and then turned upside down. The samples were assessed for mortality 5 days after infestation.

[0580] The following compounds resulted in at least 80% mortality at a test rate of 12 ppm:

P10, P19, P25, P30, P31, P32, P37, P41, P44, P46, P50, P55.

Example B9: Spodoptera littoralis (Egyptian Cotton Leaf Worm)

[0581] Cotton leaf discs were placed onto agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions. After drying the leaf discs were infested with five L1 larvae. The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 3 days after infestation. Control of Spodoptera littoralis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.

[0582] The following compounds resulted in at least 80% control in at least one of the three categories (mortality, anti-feedant or growth inhibition) at an application rate of 200 ppm:

P2, P3, P4, P6, P7, P8, P9, P11, P13, P16, P17, P19, P20, P22, P24, P25, P26, P28, P30, P31, P32, P34, P35, P36, P37, P39, P40, P41, P42, P44, P45, P46, P48, P49, P50, P51, P52, P53, P54, P55, P56, P57, P58.

Example B10: Spodoptera littoralis (Egyptian Cotton Leaf Worm)

[0583] Test compounds were applied by pipette from 10′000 ppm DMSO stock solutions into 24-well plates and mixed with agar. Lettuce seeds were placed onto the agar and the multi well plate was closed by another plate which contained also agar. After 7 days the compound was absorbed by the roots and the lettuce grew into the lid plate. The lettuce leaves were then cut off into the lid plate. Spodoptera eggs were pipetted through a plastic stencil onto a humid gel blotting paper and the lid plate was closed with it. The samples were assessed for mortality, anti-feedant effect and growth inhibition in comparison to untreated samples 6 days after infestation.

[0584] The following compounds gave an effect of at least 80% control in at least one of the three categories (mortality, anti-feedant, or growth inhibition) at a test rate of 12.5 ppm:

P39

Example B11: Myzus persicae (Green Peach Aphid)

[0585] Test compounds prepared from 10′000 ppm DMSO stock solutions were applied by a liquid handling robot into 96-well microtiter plates and mixed with a sucrose solution. Parafilm was stretched over the 96-well microtiter plate and a plastic stencil with 96 holes was placed onto the plate. Aphids were sieved into the wells directly onto the Parafilm. The infested plates were closed with a gel blotting card and a second plastic stencil and then turned upside down. The samples were assessed for mortality 5 days after infestation.

[0586] The following compounds resulted in at least 80% mortality at an application rate of 50 ppm:

P19, P22, P23, P25, P26

Example B12: Plutella xylostella (Diamondback Moth)

[0587] 96-well microtiter plates containing artificial diet were treated with aqueous test solutions, prepared from 10′000 ppm DMSO stock solutions, by a liquid handling robot. After drying, eggs (˜30 per well) were infested onto a netted lid which was suspended above the diet. The eggs hatch and L1 larvae move down to the diet. The samples were assessed for mortality 9 days after infestation.

[0588] The following compounds gave an effect of at least 80% mortality at an application rate of 500 ppm:

P11, P12, P13, P14, P15, P16, P17, P18, P19, P20, P21, P22, P23, P24, P25, P26, P27, P28, P29, P33, P34, P35, P36, P37, P38, P39, P40, P42