PESTICIDALLY ACTIVE HETEROCYCLIC DERIVATIVES WITH SULFUR CONTAINING SUBSTITUENTS

Abstract

Compounds of the formula (I) wherein the substituents are as defined in claim 1. Furthermore, the present invention relates to agrochemical compositions which comprise compounds of formula (I), to preparation of these compositions, and to the use of the compounds or compositions in agriculture or horticulture for combating, preventing or controlling animal pests, including arthropods and in particular insects, nematodes, molluscs or representatives of the order Acarina.

##STR00001##

Claims

1. A compound of formula (I) ##STR00187## wherein G.sub.1 and G.sub.2 are, independently from each other, CH or N; R.sub.2 is C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.4 haloalkylsulfanyl, C.sub.1-C.sub.4 haloalkylsulfinyl, C.sub.1-C.sub.4 haloalkylsulfonyl, C.sub.1-C.sub.6 haloalkoxy or C.sub.1-C.sub.4 haloalkylsulfonyloxy; Q is a radical selected from the group consisting of formula Qa and Qb ##STR00188## wherein the arrow denotes the point of attachment to the nitrogen atom of the bicyclic ring; and wherein, X is S, SO, or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4 alkyl or C.sub.3-C.sub.6 cycloalkyl-C.sub.1-C.sub.4 alkyl; R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are, independently from each other, hydrogen, halogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycloalkyl monosubstituted by cyano, C.sub.1-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6 cyanoalkoxy, C.sub.3-C.sub.6 cyanocycloalkylC.sub.1-C.sub.4 alkoxy, cyano, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.6 haloalkoxy, —N(R.sub.7).sub.2, or —N(R.sub.7)C(═O)R.sub.8; and R.sub.7 and R.sub.8 are, independently from each other, hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.6 haloalkyl, or C.sub.3-C.sub.6 cycloalkyl; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide of a compound of formula I.

2. A compound of formula I according to claim 1, represented by the compounds of formula (I-1) ##STR00189## wherein R.sub.2, G.sub.1, G.sub.2, X, R.sub.1, R.sub.3, R.sub.4, R.sub.7 and R.sub.8 are as defined under formula I are as defined under formula I in claim 1, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof.

3. A compound of formula I according to claim 1, represented by the compounds of formula (I-2) ##STR00190## wherein R.sub.2, G.sub.1, G.sub.2, X, R.sub.1, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are as defined under formula I in claim 1, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof.

4. A compound according to claim 1, wherein either G.sub.1 is N and G.sub.2 is CH, or G.sub.1 is CH and G.sub.2 is N; preferably G.sub.1 is N and G.sub.2 is CH.

5. A compound according to claim 1, wherein either both G.sub.1 and G.sub.2 are N, or both G.sub.1 and G.sub.2 are CH.

6. A compound of formula I according to claim 1, represented by the compounds of formula (I-3) ##STR00191## wherein Q is a radical selected from the group consisting of formula Qa and Qb ##STR00192## wherein the arrow denotes the point of attachment to the nitrogen atom of the bicyclic ring; and R.sub.2, X, R.sub.1, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are as defined under formula I in claim 1, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof.

7. A compound of formula I according to claim 1, represented by the compounds of formula (I-4) ##STR00193## wherein Q is a radical selected from the group consisting of formula Qa and Qb ##STR00194## wherein the arrow denotes the point of attachment to the nitrogen atom of the bicyclic ring; and R.sub.2, X, R.sub.1, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are as defined under formula I in claim 1, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof.

8. A compound of formula I according to claim 1, represented by the compounds of formula (I-5) ##STR00195## wherein Q is a radical selected from the group consisting of formula Qa and Qb ##STR00196## wherein the arrow denotes the point of attachment to the nitrogen atom of the bicyclic ring; and R.sub.2, X, R.sub.1, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are as defined under formula I in claim 1, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof.

9. A compound of formula I according to claim 1, represented by the compounds of formula (I-6) ##STR00197## wherein Q is a radical selected from the group consisting of formula Qa and Qb ##STR00198## wherein the arrow denotes the point of attachment to the nitrogen atom of the bicyclic ring; and R.sub.2, X, R.sub.1, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are as defined under formula I in claim 1, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof.

10. A compound according to claim 1 wherein: X is S or SO.sub.2; preferably X is SO.sub.2; and R.sub.1 is C.sub.1-C.sub.4 alkyl or cyclopropyl-C.sub.1-C.sub.4 alkyl; preferably R.sub.1 is ethyl or cyclopropylmethyl.

11. A compound according to claim 1 wherein: R.sub.2 is C.sub.1-C.sub.2 haloalkyl, C.sub.1-C.sub.2 haloalkylsulfanyl, C.sub.1-C.sub.2 haloalkylsulfinyl, C.sub.1-C.sub.2 haloalkylsulfonyl, C.sub.1-C.sub.2 haloalkoxy or C.sub.1-C.sub.2 haloalkylsulfonyloxy; preferably R.sub.2 is —CF.sub.3, —CF.sub.2CF.sub.3, —SCF.sub.3, —SOCF.sub.3, —SO.sub.2CF.sub.3, —OCHF.sub.2, —OCF.sub.3 or —OSO.sub.2CF.sub.3.

12. A compound according to claim 11 wherein R.sub.2 is —CF.sub.3, —OCHF.sub.2, —OCF.sub.3 or —SO.sub.2CF.sub.3.

13. A compound according to claim 1 wherein: Q is Qa; and R.sub.4 is hydrogen and R.sub.3 is hydrogen, bromo, methyl, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 1-cyano-1-methyl-ethoxy, methoxy, isopropoxy, difluoromethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoroethoxy, or —NHC(O)CH.sub.3; preferably R.sub.3 is bromo, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 1-cyano-1-methyl-ethoxy, methoxy, isopropoxy, difluoromethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoroethoxy, or —NHC(O)CH.sub.3; or R.sub.3 is hydrogen and R.sub.4 is bromo, methyl, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 1-cyano-1-methyl-ethoxy, methoxy, isopropoxy, difluoromethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoroethoxy, or —NHC(O)CH.sub.3; preferably R.sub.4 is bromo, methyl, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, 1-cyanocyclopropyl, methoxy, or 2,2,2-trifluoroethoxy.

14. A compound according to claim 1 wherein: Q is Qb; and R.sub.6 is hydrogen and R.sub.5 is hydrogen, bromo, methyl, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 1-cyano-1-methyl-ethoxy, methoxy, isopropoxy, difluoromethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoroethoxy, or —NHC(O)CH.sub.3; or R.sub.5 is hydrogen and R.sub.6 is bromo, methyl, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 1-cyano-1-methyl-ethoxy, methoxy, isopropoxy, difluoromethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoroethoxy, or —NHC(O)CH.sub.3.

15. A compound of formula I according to claim 1, selected from the group consisting of: 2-[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]-6-(trifluoromethyl)-3H-pyrrolo[3,4-c]pyridin-1-one (compound P1); 6-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P2); 1-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-7-yl]cyclopropanecarbonitrile (compound P3); 6-[3-ethylsulfonyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P4); 1-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethoxy)isoindolin-2-yl]imidazo[1,2-a]pyridin-7-yl]cyclopropanecarbonitrile (compound P5); 2-[3-ethylsulfonyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethoxy)isoindolin-1-one (compound P6); 2-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethoxy)isoindolin-1-one (compound P7); 6-(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P8); 6-(3-ethylsulfonyl-6-isopropoxy-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P9); 6-[6-(difluoromethoxy)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P10); 6-[3-ethylsulfonyl-6-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P11); 6-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P12); 6-(3-ethylsulfonyl-7-methoxy-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P13); 1-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethoxy)isoindolin-2-yl]imidazo[1,2-a]pyridin-6-yl]cyclopropanecarbonitrile (compound P14); 1-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]cyclopropanecarbonitrile (compound P15); 1-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethyl)isoindolin-2-yl]imidazo[1,2-a]pyridin-6-yl]cyclopropanecarbonitrile (compound P16); 2-[6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethoxy)isoindolin-1-one (compound P17); 6-[6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P18); 6-[6-(2,2-difluoroethoxy)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P19); 2-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]oxy-2-methyl-propanenitrile (compound P20); 6-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P21); 6-(7-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P22); 6-(3-ethylsulfonyl-7-methyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P23); 6-(7-cyclopropyl-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P24); 6-[7-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P25); 2-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethoxy)isoindolin-2-yl]imidazo[1,2-a]pyridin-6-yl]oxy-2-methyl-propanenitrile (compound P26); 6-(6-cyclopropyl-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P27); 2-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethoxy)isoindolin-1-one (compound P28); 2-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethoxy)isoindolin-1-one (compound P29); 2-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethylsulfonyl)isoindolin-1-one (compound P30); 1-[[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]oxymethyl]cyclopropanecarbonitrile (compound P31); 2-[3-ethylsulfonyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethylsulfonyl)isoindolin-1-one (compound P32); 2-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethylsulfonyl)isoindolin-1-one (compound P33); 6-(difluoromethoxy)-2-[3-ethylsulfonyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]isoindolin-1-one (compound P34); 2-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]-2-methyl-propanenitrile (compound P35); N-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]acetamide (compound P36); 2-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethylsulfonyl)isoindolin-1-one (compound P37); and 6-[7-(2,2-difluoroethoxy)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P38).

16. A composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, claim 1, optionally, an auxiliary or diluent.

17. 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 a compound of formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, as defined in claim 1.

18. 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 a composition according to claim 16.

19. A compound of formula XVII-Qa-1 ##STR00199## wherein R.sub.2, G.sub.1, G.sub.2, R.sub.3, R.sub.4, R.sub.1 and X are as defined under formula I according to claim 1; and R.sub.a is hydrogen, C.sub.1-C.sub.6 alkyl, benzyl or phenyl.

20. A compound of formula XIX-Qa ##STR00200## wherein R.sub.3, R.sub.4, R.sub.1 and X are as defined under formula I according to claim 1.

21. 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 a compound of formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, or a composition as defined claim 16.

Description

PREPARATORY EXAMPLES

[0553] “Mp” means melting point in ° C. Free radicals represent methyl groups. .sup.1H NMR measurements were recorded on a Brucker 400 MHz spectrometer, chemical shifts are given in ppm relevant to a TMS standard. Spectra measured in deuterated solvents as indicated. Either one of the LCMS methods below was used to characterize the compounds. The characteristic LCMS values obtained for each compound were the retention time (“Rt”, recorded in minutes) and the measured molecular ion (M+H).sup.+ or (M−H).sup.−.

[0554] LCMS Methods:

[0555] Method 1:

[0556] Spectra were recorded on a Mass Spectrometer from Waters (SQD Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Full Scan, Capillary: 3.00 kV, Cone range: 41 V, Source Temperature: 150° C., Desolvation Temperature: 500° C., Cone Gas Flow: 50 L/Hr, Desolvation Gas Flow: 1000 L/Hr, Mass range: 110 to 800 Da) and a H-Class UPLC from Waters: Binary pump, heated column compartment and diode-array detector.

[0557] Column: Waters UPLC HSS T3 C18, 1.8 μm, 30×2.1 mm, Temp: 40° C., DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.05% HCOOH: gradient: 0 min 10% B; 0.-0.2 min 10-50% B; 0.2-0.7 min 50-100% B; 0.7-1.3 min 100% B; 1.3-1.4 min 100-10% B; 1.4-1.6 min 10% B; Flow (mL/min) 0.6.

[0558] Method 2:

[0559] Spectra were recorded on a Mass Spectrometer from Agilent Technologies (6410 Triple Quadrupole mass spectrometer) equipped with an equipped with an electrospray source (Polarity: positive or negative ions, MS2 Scan, Capillary: 4.00 kV, Fragmentor: 100 V, Desolvation Temperature: 350° C., Gas Flow: 11 L/min, Nebulizer Gas: 45 psi, Mass range: 110 to 1000 Da) and a 1200 Series HPLC from Agilent: quaternary pump, heated column compartment and diode-array detector. Column: KINETEX EVO C18, 2.6 μm, 50×4.6 mm, Temp: 40° C., DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.1% HCOOH: gradient: 0 min 0% B, 100% A; 0.9-1.8 min 100% B; Flow (mL/min) 1.8.

[0560] Method 3:

[0561] Spectra were recorded on a Mass Spectrometer from Waters (SQD Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Full Scan, Capillary: 3.00 kV, Cone range: 41 V, Source Temperature: 150° C., Desolvation Temperature: 500° C., Cone Gas Flow: 50 L/Hr, Desolvation Gas Flow: 1000 L/Hr, Mass range: 110 to 800 Da) and a H-Class UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3 C18, 1.8 μm, 30×2.1 mm, Temp: 40° C., DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.1% HCOOH: gradient: 0 min 10% B; 0.-0.2 min 10-50% B; 0.2-0.7 min 50-100% B; Flow (mL/min) 0.8.

Example H1: Preparation of 2-[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]-6-(trifluoromethyl)-3H-pyrrolo[3,4-c]pyridin-1-one (Compound P1)

[0562] ##STR00060##

Step 1: Preparation of ethyl 3-chloro-6-(trifluoromethyl)benzothiophene-2-carboxylate (intermediate I-2) via 3-chloro-6-(trifluoromethyl)benzothiophene-2-carbonyl Chloride (Intermediate I-1)

[0563] ##STR00061##

[0564] To a solution of (E)-3-[4-(trifluoromethyl)phenyl]prop-2-enoic acid (4.00 g, 19.0 mmol) in N,N-dimethylformamide (1.6 mL) and pyridine (0.80 mL) was added thionyl chloride (6.90 mL, 93.0 mmol) slowly at room temperature. The reaction mixture was heated to 145° C. and stirred for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to afford crude intermediate I-1.

##STR00062##

[0565] To crude intermediate I-1 was added ethanol (48 mL) slowly at 0° C. The reaction mixture was heated to 80° C. and stirred for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (100% cyclohexane) afforded the desired product (2.98 g). .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.46 (t, J=7.2 Hz, 3H), 4.47 (q, J=7.2 Hz, 2H), 7.73 (dd, J=8.5, 1.0 Hz, 1H), 8.07-8.15 (m, 2H).

Step 2: Preparation of ethyl 3-ethylsulfanyl-6-(trifluoromethyl)benzothiophene-2-carboxylate (Intermediate I-3)

[0566] ##STR00063##

[0567] To a solution of ethyl 3-chloro-6-(trifluoromethyl)benzothiophene-2-carboxylate (intermediate I-2 prepared as described above, 76%, 18.8 g, 42.6 mmol) in N,N-dimethylformamide (188 mL) was added sodium ethanethiolate (6.45 g, 76.7 mmol). The reaction mixture was stirred at room temperature for 6 hours, then diluted with water and extracted three times 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 (100% cyclohexane) afforded the desired product (9.20 g). .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.22 (t, 3H), 1.47 (t, 3H), 3.06 (q, 2H), 4.48 (q, 2H), 7.61-7.74 (m, 1H), 8.15 (s, 1H), 8.32 (d, 1H).

Step 3: Preparation of ethyl 3-ethylsulfonyl-6-(trifluoromethyl)benzothiophene-2-carboxylate (Intermediate I-4)

[0568] ##STR00064##

[0569] To a solution of ethyl 3-ethylsulfanyl-6-(trifluoromethyl)benzothiophene-2-carboxylate (intermediate I-3 prepared as described above, 9.20 g, 28.0 mmol) in dichloromethane (140 mL) was added 3-chloro-perbenzoic acid (15.0 g, 61.0 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 hours, then quenched at 0° C. with 2 M sodium hydroxide and extracted two times with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (gradient ethyl acetate in cyclohexane) afforded the desired product (5.50 g). .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.40 (t, 3H), 1.46 (t, 3H), 3.60 (q, J=7.5 Hz, 2H), 4.51 (q, J=7.2 Hz, 2H), 7.77 (dd, J=8.9, 1.3 Hz, 1H), 8.19 (s, 1H), 8.75 (d, J=8.9 Hz, 1H).

Step 4: Preparation of 3-ethylsulfonyl-6-(trifluoromethyl)benzothiophene-2-carboxylic Acid (Intermediate I-5)

[0570] ##STR00065##

[0571] To a solution of ethyl 3-ethylsulfonyl-6-(trifluoromethyl)benzothiophene-2-carboxylate (intermediate I-4 prepared as described above, 5.50 g, 15.0 mmol) in methanol (44 mL) was added a solution of sodium hydroxide (1.20 g, 30.0 mmol) in water (22 mL). The reaction mixture was stirred at room temperature for 6 hours, then acidified with aqueous 2N hydrochloric acid, 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 to afford the desired product (5.20 g), which was used without further purification. .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (t, J=7.3 Hz, 3H), 3.63 (q, J=7.3 Hz, 2H), 7.93 (dd, J=8.9, 1.6 Hz, 1H), 8.59 (d, J=8.9 Hz, 1H), 8.77 (s, 1H).

Step 5: Preparation of tert-butyl N-[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]carbamate (Intermediate I-6)

[0572] ##STR00066##

[0573] To a solution of 3-ethylsulfonyl-6-(trifluoromethyl)benzothiophene-2-carboxylic acid (intermediate I-5 prepared as described above, 5.20 g, 15.0 mmol) in tert-butanol (100 mL) was added triethylamine (3.50 mL, 25.0 mmol). The reaction mixture was heated to 90° C. and stirred for 10 minutes, before adding diphenylphosphoryl azide (5.40 mL, 25.0 mmol) dropwise over 15 minutes. The resulting reaction mixture was stirred at 90° C. for 1 hour and after cooling to room temperature, it was quenched with water and brine and extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (2.50 g). .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.28 (t, 3H), 1.60 (s, 9H), 3.28 (q, J=7.3 Hz, 2H), 7.67 (d, J=8.7 Hz, 1H), 8.02 (s, 1H), 8.14 (d, J=8.7 Hz, 1H), 9.96 (s, 1H).

Step 6: Preparation of 3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-amine (Intermediate I-7)

[0574] ##STR00067##

[0575] To a solution of tert-butyl N-[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]carbamate (intermediate I-6 prepared as described above, 2.30 g, 5.60 mmol) in dichloromethane (23 mL) was added 2,2,2-trifluoroacetic acid (5.20 mL, 67.0 mmol) dropwise. The reaction mixture was stirred at room temperature for 16 hours, then concentrated under reduced pressure. The resulting residue was diluted with water, neutralized with sat. aq. sodium bicarbonate 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 (100% cyclohexane) afforded the desired product (0.600 g). .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.34 (t, 3H), 3.22 (q, J=7.3 Hz, 2H), 6.26 (br s, 2H), 7.58 (d, J=8.6 Hz, 1H), 7.82 (s, 1H), 7.93 (d, J=8.6 Hz, 1H).

Step 7: Preparation of methyl 5-[[[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]amino]methyl]-2-(trifluoromethyl)pyridine-4-carboxylate (Intermediate I-8)

[0576] ##STR00068##

[0577] To a solution of 3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-amine (intermediate I-7 prepared as described above, 0.600 g, 1.94 mmol) in N,N-dimethylformamide (15 mL) was added sodium hydride (60%, 0.116 g, 2.91 mmol) at 0° C. and the reaction mixture was stirred at this temperature for 30 minutes. Then a solution of methyl 5-(bromomethyl)-2-(trifluoromethyl)pyridine-4-carboxylate (intermediate IP-6 prepared as described below; 60%, 1.35 g, 2.72 mmol) in N,N-dimethylformamide (6 mL) was added and the reaction mixture further stirred at 0° C. for 2 hours. The mixture was diluted with water and extracted two times with ethyl acetate. The combined organic layers were concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (gradient ethyl acetate in cyclohexane) afforded the desired product (0.910 g). LCMS (method 1): m/z 527 [M+H].sup.+, retention time Rt=1.24 min.

Step 8: Preparation of 5-[[[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]amino]methyl]-2-(trifluoromethyl)pyridine-4-carboxylic Acid (Intermediate I-9)

[0578] ##STR00069##

[0579] To a suspension of methyl 5-[[[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]amino]methyl]-2-(trifluoromethyl)pyridine-4-carboxylate (intermediate I-8 prepared as described above, 0.800 g, 1.52 mmol) in methanol (16 mL) was added a solution of dihydroxybarium octahydrate (0.959 g, 3.04 mmol) in water (8 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 hours, then diluted with water, acidified with aqueous 2N hydrochloric acid and extracted three times with ethyl acetate. The combined organic layers were concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (gradient methanol in ethyl acetate) afforded the desired product (0.570 g, 0.779 mmol). LCMS (method 1): m/z 513 [M+H].sup.+, retention time Rt=1.12 min.

Step 9: Preparation of 2-[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]-6-(trifluoromethyl)-3H-pyrrolo[3,4-c]pyridin-1-one (Title Compound P1)

[0580] ##STR00070##

[0581] To a solution of 5-[[[3-ethylsulfonyl-6-(trifluoromethyl)benzothiophen-2-yl]amino]methyl]-2-(trifluoromethyl)pyridine-4-carboxylic acid (intermediate I-9 prepared as described above, 0.620 g, 1.21 mmol) in pyridine (3.1 mL) was added phosphorus(V) oxychloride (0.228 mL, 2.42 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 4 hours, then diluted with water, acidified with aqueous 1N hydrochloric acid 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (80 mg). LCMS (method 1): m/z 495 [M+H].sup.+, retention time Rt=1.16 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.42 (t, J=7.5 Hz, 3H), 3.46 (q, J=7.5 Hz, 2H), 5.15 (s, 2H), 7.81 (d, J=8.8 Hz, 1H), 8.21 (m, 2H), 8.52 (d, J=8.8 Hz, 1H), 9.06 (s, 1H).

Example H2: Preparation of 6-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (Compound P2)

[0582] ##STR00071##

Step 1: Preparation of tert-butyl N-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbamate (Intermediate II-1)

[0583] ##STR00072##

[0584] To a solution of 3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid (CAS 2181821-89-4; 2.50 g, 7.76 mmol) in tert-butanol (50 mL) was added triethylamine (1.75 mL, 12.4 mmol). The reaction mixture was heated to 90° C. and stirred for 10 minutes, before adding diphenylphosphoryl azide (2.73 mL, 12.4 mmol) dropwise over 15 minutes. The resulting reaction mixture was stirred at 90° C. for 40 minutes. After cooling to room temperature, the mixture was quenched with water and brine, and extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (0.850 g). .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.27 (t, 3H), 1.48 (s, 9H), 3.66 (q, J=7.34 Hz, 2H), 7.47 (dd, J=7.34, 1.96 Hz, 1H), 8.24 (s, 1H), 8.94 (d, J=7.34 Hz, 1H), 9.57 (s, 1H).

Step 2: Preparation of methyl 2-chloro-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate II-2)

[0585] ##STR00073##

[0586] To a solution of 2-chloro-5-(trifluoromethyl)pyridine-3-carboxylic acid (CAS 505084-59-3; 7.00 g, 31.0 mmol) in N,N-dimethylformamide (70 mL) was added cesium carbonate (12.1 g, 37.2 mmol). The reaction mixture was stirred at room temperature for 5 minutes, before addition of iodomethane (2.90 mL, 46.6 mmol). Stirring was continued at room temperature for 1 hour. The reaction mixture was diluted with ice water and extracted three times with ethyl acetate. The combined organic layers were washed with ice water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the desired product (7.00 g), which was used without further purification. LCMS (method 1): m/z 240/242 [M+H].sup.+, retention time Rt=1.00 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 4.01 (s, 3H), 8.41 (d, 1H), 8.78 (d, 1H).

Step 3: Preparation of methyl 2-methyl-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate II-3)

[0587] ##STR00074##

[0588] A reaction vessel was charged with methylboronic acid (7.73 g, 125 mmol), potassium phosphate tribasic (26.6 g, 125 mmol), tricyclohexylphosphane (1.17 g, 4.17 mmol), followed by toluene (100 mL) and water (13 mL). The flask was purged with nitrogen for 15 minutes. To the reaction mixture were added methyl 2-chloro-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate II-2 prepared as described above, 10.0 g, 41.7 mmol) and palladium(II) acetate (0.469 g, 2.09 mmol). The reaction mixture was first heated to 100° C. and stirred for 2 hours, then at 90° C. overnight. After cooling to room temperature, the mixture was diluted with water and ethyl acetate, and filtered over a Celite pad. The layers were separated, and the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the desired product (5.00 g), which was used without further purification. LCMS (method 1): m/z 220 [M+H].sup.+, retention time Rt=0.93 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 2.92 (s, 3H), 3.97 (s, 3H), 8.44 (d, 1H), 8.87 (m, 1H).

Step 4: Preparation of methyl 2-(bromomethyl)-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate II-4)

[0589] ##STR00075##

[0590] To a solution of methyl 2-methyl-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate II-3 prepared as described above, 3.50 g, 16.0 mmol) in tetrachloromethane (80 mL) were added N-bromosuccinimide (4.00 g, 22.0 mmol) and benzoyl peroxide (70%, 1.40 g, 4.00 mmol). The reaction mixture was heated to 70° C. and stirred for 3 hours. After cooling to room temperature, it was diluted with ice water and extracted three times 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 flash chromatography over silica gel (gradient ethyl acetate in cyclohexane) afforded the desired product (1.40 g). LCMS (method 1): m/z 298/300 [M+H].sup.+, retention time Rt=1.01 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 4.03 (s, 3H) 5.08 (s, 2H), 8.53 (d, J=2.01 Hz, 1H), 8.96 (m, 1H).

[0591] Similarly, ethyl 2-(bromomethyl)-5-(trifluoromethyl)pyridine-3-carboxylate (II-4-a) can be prepared:

##STR00076##

[0592] LCMS (method 1): m/z 312/314 [M+H].sup.+, retention time 1.14 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 1.47 (t, 3H), 4.49 (q, 2H), 5.07 (s, 2H), 8.51 (s, 1H), 8.95 (s, 1H).

[0593] Similarly, methyl 2-(bromomethyl)-5-(trifluoromethyl)benzoate (CAS 875895-66-2; 11-4-b) can be prepared:

##STR00077##

[0594] .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 3.99 (s, 3H), 4.98 (s, 2H), 7.62 (d, J=8.1 Hz, 1H), 7.76 (dd, J=8.1, 1.5 Hz, 1H), 8.24 (d, J=1.5 Hz, 1H).

[0595] Similarly, methyl 2-(bromomethyl)-5-(difluoromethoxy)benzoate (CAS 944718-50-7; 11-4-c) can be prepared from methyl 5-(difluoromethoxy)-2-methyl-benzoate (CAS 1190320-23-0):

##STR00078##

[0596] .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 3.98 (s, 3H), 4.96 (s, 2H), 6.57 (t, 1H), 7.28 (dd, 1H), 7.50 (d, 1H), 7.74 (d, 1H).

Step 5: Preparation of methyl 2-[[tert-butoxycarbonyl-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate II-5)

[0597] ##STR00079##

[0598] To a solution of tert-butyl N-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbamate (intermediate II-1 prepared as described above, 0.450 g, 1.14 mmol) in acetonitrile (10 mL) were added methyl 2-(bromomethyl)-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate II-4 prepared as described above, 0.443 g, 1.49 mmol) and cesium carbonate (0.560 g, 1.72 mmol). The reaction mixture was heated to 50° C. and stirred for 2 hours. After cooling to room temperature, it was quenched with ice water and extracted two times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (0.510 g). LCMS (method 1): m/z 611 [M+H].sup.+, retention time Rt=1.25 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.37 (s, 9H), 1.47 (t, 3H), 3.71 (br q, 2H), 3.98 (s, 3H), 5.55 (s, 2H), 7.14 (br d, 1H), 7.81 (s, 1H), 8.58 (s, 1H), 8.92 (br d, 1H), 8.97 (s, 1H).

Step 6: Preparation of methyl 2-[[[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate II-6)

[0599] ##STR00080##

[0600] To a solution methyl 2-[[tert-butoxycarbonyl-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate II-5 prepared as described above, 0.510 g, 0.835 mmol) in dichloromethane (10 mL) was added 2,2,2-trifluoroacetic acid (0.673 mL, 8.35 mmol) dropwise at 0° C. The reaction mixture was stirred at room temperature overnight, then quenched with sat. aq. sodium bicarbonate 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 to afford the desired product (0.400 g), which was used without further purification. LCMS (method 1): m/z 511 [M+H].sup.+, retention time Rt=1.17 min. .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.19 (t, 3H), 3.43 (q, J=7.34 Hz, 2H), 3.96 (s, 3H), 5.17 (d, J=5.5 Hz, 2H), 7.05 (t, J=5.5 Hz, 1H), 7.31 (dd, J=7.09, 1.83 Hz, 1H), 7.95 (s, 1H), 8.55 (d, J=1.83 Hz, 1H), 8.71 (d, J=7.09 Hz, 1H), 9.14 (s, 1H).

Step 7: Preparation of 2-[[[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylic Acid (Intermediate II-7)

[0601] ##STR00081##

[0602] To a solution of methyl 2-[[[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate II-6 prepared as described above, 0.400 g, 0.784 mmol) in methanol (8 mL) and water (4 mL) was added dihydroxybarium octahydrate (0.494 g, 1.57 mmol). The reaction mixture was stirred at room temperature for 16 hours, then acidified with aqueous 2N hydrochloric acid and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the desired product (0.380 g). LCMS (method 1): m/z 497 [M+H].sup.+, retention time Rt=1.04 min. .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.18 (t, 3H), 3.43 (q, 2H), 5.19 (d, J=5.4 Hz, 2H), 7.12 (t, J=5.4 Hz, 1H), 7.31 (dd, J=7.1, 1.9 Hz, 1H), 7.98 (s, 1H), 8.53 (d, J=1.9 Hz, 1H), 8.70 (d, J=7.1 Hz, 1H), 9.12 (s, 1H).

Step 8: Preparation of 6-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (Title Compound P2)

[0603] ##STR00082##

[0604] To a solution of 2-[[[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylic acid (intermediate II-7 prepared as described above, 0.300 g, 0.604 mmol) in pyridine (6 mL) was added phosphorus(V) oxychloride (0.114 mL, 1.21 mmol) at 0° C. The reaction mixture was slowly allowed to reach room temperature and stirred for 1 hour, then acidified with aqueous 1N hydrochloric acid and extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (0.187 g). LCMS (method 1): m/z 479 [M+H].sup.+, retention time Rt=1.06 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.53 (t, J=7.46 Hz, 3H), 3.84 (q, J=7.46 Hz, 2H), 5.25 (s, 2H), 7.29 (d, J=7.34 Hz, 1H), 8.04 (s, 1H), 8.48 (s, 1H), 9.03 (d, J=7.34 Hz, 1H), 9.13 (s, 1H).

Example H3: Preparation of 2-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethylsulfonyl)isoindolin-1-one (Compound P33)

[0605] ##STR00083##

Step 1: Preparation of 4-(2,2,2-trifluoroethoxy)pyridin-2-amine (Intermediate III-1)

[0606] ##STR00084##

[0607] To a solution of 2-aminopyridin-4-ol (15.0 g, 136 mmol) in DMSO (150 mL) were added potassium carbonate (95.5 g, 681 mmol) and 2-iodo-1,1,1-trifluoroethane (72.2 g, 341 mmol) and the reaction mixture was heated to 100° C. and stirred for 12 hours. After cooling to room temperature, the reaction mixture was extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (14.0 g). LCMS (method 1): m/z 193 [M+H].sup.+, retention time Rt=0.19 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 4.73 (q, 2H), 5.93 (s, 2H), 6.02 (d, 1H), 6.24 (dd, 1H), 7.79 (d, 1H).

Step 2: Preparation of ethyl 7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (Intermediate III-2)

[0608] ##STR00085##

[0609] To a solution of 4-(2,2,2-trifluoroethoxy)pyridin-2-amine (intermediate III-1 prepared as described above, 14.0 g, 72.9 mmol) in ethanol (140 mL) were added ethyl 3-bromo-2-oxo-propanoate (17.1 g, 87.4 mmol, 11.0 mL) and sodium bicarbonate (12.2 g, 146 mmol). The reaction mixture was heated to 85° C. and stirred for 7 hours. After cooling to room temperature, the reaction mixture was diluted with water, and extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (11.0 g). LCMS (method 1): m/z 289 [M+H].sup.+, retention time Rt=1.19 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 1.31 (t, 3H), 4.29 (q, 2H), 6.75 (dd, 1H), 7.02 (d, 1H), 8.07 (d, 1H), 8.11 (s, 1H).

Step 3: Preparation of ethyl 3-chloro-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (Intermediate III-3)

[0610] ##STR00086##

[0611] To a solution of ethyl 7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (intermediate III-2 prepared as described above, 12.0 g, 41.6 mmol) in acetonitrile (120 mL) was added 1-chloropyrrolidine-2,5-dione (6.67 g, 50.0 mmol) and the reaction mixture was stirred at room temperature for 16 hours. Ice cold water was added to the reaction mixture, the precipitated compound was filtered and dried to afford the desired product (10.5 g), which was used without further purification. LCMS (method 2): m/z 323/325 [M+H].sup.+, retention time Rt=2.32 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.48 (t, 3H), 4.40-4.54 (m, 4H), 6.88 (dd, 1H), 7.01 (d, 1H), 8.08 (d, 1H).

Step 4: Preparation of ethyl 3-ethylsulfanyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (Intermediate III-4)

[0612] ##STR00087##

[0613] To a solution of ethyl 3-chloro-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (intermediate III-3 prepared as described above, 9.60 g, 30.0 mmol) in methylsulfinylmethane (96.0 mL) at 15-20° C. was added sodium ethanethiolate (5.00 g, 60.0 mmol) portionwise, and the reaction mixture was stirred at room temperature for 2 hours. Ice cold water was added to the reaction mixture, the precipitated compound was filtered and dried to afford the desired product (9.60 g), which was used without further purification. LCMS (method 1): m/z 349 [M+H].sup.+, retention time Rt=1.47 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 1.05 (t, 3H), 1.34 (t, 3H), 2.85 (q, 2H), 4.33 (q, 2H), 4.94 (q, 2H), 6.97 (dd, 1H), 7.28 (d, 1H), 8.56 (d, 1H).

Step 5: Preparation of ethyl 3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (Intermediate III-5)

[0614] ##STR00088##

[0615] To a solution of ethyl 3-ethylsulfanyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (intermediate III-4 prepared as described above, 9.60 g, 28.0 mmol) in trifluoromethylbenzene (96.0 mL) was added 3-chlorobenzenecarboperoxoic acid (18.4 g, 74.9 mmol) at 0° C. The reaction mixture was stirred at room temperature for 24 hours, then quenched with water and aqueous 2 M sodium hydroxide, and the product extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (gradient ethyl acetate in cyclohexane) afforded the desired product (8.10 g). LCMS (method 1): m/z 381 [M+H].sup.+, retention time Rt=0.96 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.36 (t, 3H), 1.48 (t, 3H), 3.73 (q, 2H), 4.42-4.56 (m, 4H), 6.90 (dd, 1H), 7.06 (d, 1H), 9.16 (d, 1H).

Step 6: Preparation of 3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylic Acid (Intermediate III-6)

[0616] ##STR00089##

[0617] To a solution of ethyl 3-ethylsulfonyl-6-(trifluoromethyl)benzothiophene-2-carboxylate (intermediate III-5 prepared as described above, 8.10 g, 21.0 mmol) in tetrahydrofuran (81 mL) was added a solution of lithium hydroxide (0.77 g, 32.0 mmol) in water (32 mL) at 0-5° C. The reaction mixture was stirred at room temperature for 16 hours, then acidified with aqueous 2N hydrochloric acid. The precipitate formed was filtered and dried to afford the desired product (6.00 g), which was used without further purification. LCMS (method 1): m/z 353 [M+H].sup.+, retention time Rt=0.83 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 1.21 (t, 3H), 3.64 (q, 3H), 5.00 (q, 2H), 7.15 (dd, 1H), 7.46 (d, 1H), 8.87 (d, 1H).

Step 7: Preparation of tert-butyl N-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]carbamate (Intermediate III-7)

[0618] ##STR00090##

[0619] To a solution of 3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylic acid (intermediate III-6 prepared as described above, 3.50 g, 9.90 mmol) in tert-butanol (70 mL) was added triethylamine (2.20 mL, 16.0 mmol). The reaction mixture was heated to 90° C. and stirred for 10 minutes before adding diphenylphosphoryl azide (3.50 mL, 16.0 mmol) dropwise over 15 minutes. The resulting reaction mixture was stirred at 90° C. for 30 minutes and after cooling to room temperature, it was quenched with water and brine and the product extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (2.90 g). LCMS (method 1): m/z 424 [M+H].sup.+, retention time Rt=1.03 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.32 (t, 3H), 1.56 (s, 9H), 3.22 (q, 2H), 4.41 (q, 2H), 6.79 (dd, 1H), 7.05 (d, 1H), 8.16 (s, 1H), 8.51 (d, 1H).

Step 8: Preparation of methyl 2-[[tert-butoxycarbonyl-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy) imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethylsulfonyl)benzoate (Intermediate III-8)

[0620] ##STR00091##

[0621] To a solution of tert-butyl N-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]carbamate (intermediate III-7 prepared as described above, 1.00 g, 2.4 mmol) in acetonitrile (15 mL) were added cesium carbonate (1.20 g, 3.50 mmol), then a solution of methyl 2-(bromomethyl)-5-(trifluoromethylsulfonyl)benzoate (prepared according to WO 20/174,094, 1.80 g, 3.50 mmol) in acetonitrile (2 mL) dropwise. The reaction mixture was heated to 50° C. and stirred for 2 hours. After cooling to room temperature, it was diluted with water and the product extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (gradient ethyl acetate in cyclohexane) afforded the desired product (2.10 g). LCMS (method 2): m/z 704 [M+H].sup.+, retention time Rt=1.68 min.

Step 9: Preparation of methyl 2-[[[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethylsulfonyl)benzoate (Intermediate III-9)

[0622] ##STR00092##

[0623] To a solution of methyl 2-[[tert-butoxycarbonyl-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethylsulfonyl)benzoate (intermediate III-8 prepared as described above, 2.70 g, 3.80 mmol) in benzotrifluoride (14.0 mL) was added 2,2,2-trifluoroacetic acid (5.90 mL, 77.0 mmol). The reaction mixture was stirred at room temperature for 4 hours, then diluted with water and the product extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (gradient ethyl acetate in cyclohexane) afforded the desired product (1.30 g). LCMS (method 2): m/z 604 [M+H].sup.+, retention time Rt=1.60 min.

Step 10: Preparation of 2-[[[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethylsulfonyl)benzoic Acid (Intermediate III-10)

[0624] ##STR00093##

[0625] To a solution of methyl 2-[[[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethylsulfonyl)benzoate (intermediate III-9 prepared as described above, 0.70 g, 1.16 mmol) in NMP (14.0 mL) was added lithium chloride (0.34 g, 8.12 mmol) and the reaction mixture was stirred in the microwave at 150° for 1.5 hour. The mixture was diluted with water, then acidified with aqueous 2N hydrochloric acid. The formed precipitate was filtered and dried to afford the desired product (0.35 g), which was used without further purification. LCMS (method 2): m/z 590 [M+H].sup.+, retention time Rt=1.51 min.

Step 11: Preparation of 2-[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]-6-(trifluoromethylsulfonyl)isoindolin-1-one (Compound P33)

[0626] ##STR00094##

[0627] To a solution of 2-[[[3-ethylsulfonyl-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethylsulfonyl)benzoic acid (intermediate III-10 prepared as described above, 0.80 g, 1.36 mmol) in pyridine (4.00 mL) was added phosphorus oxychloride (0.26 mL, 2.71 mmol) at 0° C. and the reaction mixture was stirred at room temperature for 10 minutes. The mixture was diluted with water, then acidified with aqueous 1N hydrochloric acid, and the product extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (0.29 g). LCMS (method 2): m/z 572 [M+H].sup.+, retention time Rt=1.53 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.50 (t, 3H), 3.79 (q, 2H), 4.48 (q, 2H), 5.21 (s, 2H), 6.90 (dd, 1H), 6.97 (d, 1H), 7.88 (d, 1H), 8.31 (dd, 1H), 8.63 (s, 1H), 8.78 (d, 1H).

Example H4: Preparation of N-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]acetamide (Compound P36)

[0628] ##STR00095##

Step 1: Preparation of ethyl 2-[[(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-tert-butoxycarbonyl-amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate IV-1)

[0629] ##STR00096##

[0630] To a solution of tert-butyl N-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)carbamate (intermediate IQ-8 prepared in analogy to intermediate III-7 described above, 0.84 g, 2.08 mmol) in acetonitrile (13.0 mL) was added cesium carbonate (1.02 g, 3.12 mmol). The reaction mixture was stirred at room temperature for 5 minutes, then a solution of ethyl 2-(bromomethyl)-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate II-4-a prepared in analogy to intermediate II-4 described above, 0.84 g, 2.70 mmol) in acetonitrile (8.4 mL) was added dropwise and the resulting mixture stirred at 50° C. for 2 hours. After cooling to room temperature, ice cold water was added and the product extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduce pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (0.95 g). LCMS (method 1): m/z 635/637 [M+H].sup.+, retention time 1.26 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 9.15 (s, 1H), 8.88 (s, 1H), 8.57 (br s, 1H), 7.72 (br d, 1 h), 7.64 (br d, 1H), 5.38 (br s, 2H), 4.36 (q, 2H), 3.68-3.80 (m, 2H), 1.29-1.40 (t, 6H), 1.27 (s, 9H).

Step 2: Preparation of ethyl 2-[[(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate IV-2)

[0631] ##STR00097##

[0632] To a solution of ethyl 2-[[(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-tert-butoxycarbonyl-amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate IV-1 prepared as described above, 0.95 g, 1.50 mmol) in benzotrifluoride (4.8 mL) was added 2,2,2-trifluoroacetic acid (2.29 mL, 29.9 mmol). The reaction mixture was stirred at room temperature for 4 hours, then diluted with water and extracted with ethyl acetate. The organic phase was washed with an aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (0.75 g). LCMS (method 1): m/z 535/537 [M+H].sup.+, retention time 1.18 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 9.14 (d, 1H), 8.60 (d, 1H), 8.52 (d, 1H), 7.61 (dd, 1H), 7.44 (d, 1H), 6.90 (br s, 1H), 5.13 (s, 2H), 4.41 (q, 2H), 3.43 (d, 2H), 1.39 (t, 3H), 1.13-1.23 (t, 3H).

Step 3: Preparation of 2-[[(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylic Acid (Intermediate IV-3)

[0633] ##STR00098##

[0634] To a suspension of ethyl 2-[[(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate IV-2 prepared as described above, 0.90 g, 1.68 mmol) in methanol (18 mL) was added dihydroxybarium octahydrate (1.33 g, 4.20 mmol) in water (9 mL). The reaction mixture was stirred at room temperature for 18 hours, then concentrated under reduce pressure. To the residue was added water and the mixture was acidified with aqueous 2N hydrochloric acid. The formed precipitate was filtered and dried under reduce pressure to afford the desired product which was used without further purification (0.68 g). LCMS (method 1): m/z 507/509 [M+H].sup.+, retention time 1.01 min.

Step 4: Preparation of 6-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (Compound P21)

[0635] ##STR00099##

[0636] To a solution of 2-[[(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylic acid (intermediate IV-3 prepared as described above, 4.3 g, 8.5 mmol) in pyridine (22 mL) was added phosphorus oxychloride (1.6 mL, 17 mmol) at 0° C., and the mixture stirred at room temperature for 10 minutes. To the reaction mixture was added water, it was acidified with aqueous 1N hydrochloric acid, and the product extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane). The purified product was dissolved in acetonitrile and water was added. The precipitate formed was filtered and dried to afford the desired product (2.6 g). LCMS (method 1): m/z 489/491 [M+H].sup.+, retention time 1.11 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 9.32 (d, 1H), 8.97 (t, 1H), 8.74 (d, 1H), 7.87 (d, 2H), 5.26 (s, 2H), 3.89 (q, 2H), 1.35 (t, 3H).

Step 5: Preparation of tert-butyl N-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]carbamate (Intermediate IV-4)

[0637] ##STR00100##

[0638] To a solution of 6-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P21 prepared as described above, 0.5 g, 1.02 mmol) in toluene (5 mL) were added tert-butyl carbamate (0.14 g, 1.23 mmol) and dicyclohexyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane (0.58 g, 1.23 mmol). The mixture was degassed with argon, then cesium carbonate (0.54 g, 1.64 mmol) and palladium diacetate (23 mg, 0.10 mmol) were added. The reaction mixture was stirred at 110° C. for 2 hours. After cooling, the reaction mixture was poured into water and the product extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered through a pad of Celite, and the filtrate concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (0.12 g). LCMS (method 1): m/z 526 [M+H].sup.+, retention time 1.10 min.

Step 6: Preparation of 6-(6-amino-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (Intermediate IV-5)

[0639] ##STR00101##

[0640] To a solution of tert-butyl N-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]carbamate (intermediate IV-4 prepared as described above, 0.12 g, 0.23 mmol) in benzotrifluoride (0.6 mL) was added 2,2,2-trifluoroacetic acid (0.35 mL, 4.57 mmol). The reaction mixture was stirred at room temperature for 16 hours, then diluted with water and the product extracted with ethyl acetate. The organic phase was washed with aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the desired product (23 mg), which was used without further purification. LCMS (method 1): m/z 426 [M+H].sup.+, retention time 0.95 min.

Step 7: Preparation of N-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]acetamide (P36)

[0641] ##STR00102##

[0642] To a solution of 6-(6-amino-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (intermediate IV-5 prepared as described above, 23 mg, 0.054 mmol) in acetonitrile (0.23 mL) was added triethylamine (0.023 mL, 0.16 mmol). The solution was cooled to 0-5° C., then acetyl chloride (0.004 mL, 0.054 mmol) was added dropwise. The reaction mixture was stirred at 25° C. for 1 hour, diluted with water, and the product extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated under reduce pressure. The crude was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (13 mg). LCMS (method 2): m/z 468 [M+H].sup.+, retention time 1.25 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 9.49 (s, 1H), 9.11 (s, 1H), 8.47 (s, 1H), 7.64 (d, 1H), 7.43-7.49 (m, 2H), 5.2 (s, 2H), 3.76 (q, 2H), 2.26 (s, 3H), 1.53 (t, 3H).

Example H5: Preparation of 2-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethoxy)isoindolin-2-yl]imidazo[1,2-a]pyridin-6-yl]oxy-2-methyl-propanenitrile (Compound P26)

[0643] ##STR00103##

Step 1: Preparation of methyl 2-[[tert-butoxycarbonyl-(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethoxy)benzoate (Intermediate V-1)

[0644] ##STR00104##

[0645] To a solution of tert-butyl N-(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)carbamate (intermediate IQ-5 prepared in analogy to intermediate III-7 described above, 1.0 g, 2.8 mmol) in acetonitrile (15.0 mL) was added cesium carbonate (1.4 g, 4.2 mmol). The reaction mixture was stirred at room temperature for 5 minutes, then a solution of methyl 2-(bromomethyl)-5-(trifluoromethoxy)-benzoate (prepared according to WO 20/174,094, 1.3 g, 4.2 mmol) in acetonitrile (2 mL) was added dropwise. The reaction mixture was stirred at 50° C. for 2 hours, allowed to cool, diluted with ice cold water, and the product was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduce pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (1.9 g). LCMS (method 1): m/z 588 [M+H].sup.+, retention time 1.24 min.

Step 2: Preparation of methyl 2-[[(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethoxy)benzoate (Intermediate V-2)

[0646] ##STR00105##

[0647] To a solution of methyl 2-[[tert-butoxycarbonyl-(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethoxy)benzoate (intermediate V-1 prepared as described above, 1.9 g, 3.2 mmol) in benzotrifluoride (9.5 mL) was added 2,2,2-trifluoroacetic acid (4.9 mL, 65 mmol). The reaction mixture was stirred at room temperature for 4 hours, then diluted with water and extracted with ethyl acetate. The organic phase was washed with an aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (0.75 g). LCMS (method 1): m/z 488 [M+H].sup.+, retention time 1.15 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 8.06 (d, 1H), 7.73-7.8 (m, 1H), 7.65 (d, 1H), 7.59 (br d, 1H), 7.39 (d, 1H), 7.27 (dd, 1H), 6.61 (br t, 1H), 4.85 (br d, 2H), 3.91 (s, 3H), 3.83 (m, 3H), 3.30-3.42 (m, 2H), 1.09 (t, 3H).

Step 3: Preparation of 2-[[(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethoxy)benzoic Acid (Intermediate V-3)

[0648] ##STR00106##

[0649] To a suspension of methyl 2-[[(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethoxy)benzoate (intermediate V-2 prepared as described above, 1.0 g, 2.1 mmol) in methanol (20 mL) was added dihydroxybarium octahydrate (1.6 g, 5.1 mmol) in water (10 mL). The reaction mixture was stirred at room temperature for 18 hours, then concentrated under reduce pressure. To the residue was added water, then the mixture was acidified with aqueous 2N hydrochloric acid, and the formed precipitate filtered and dried under reduce pressure to afford the desired product which was used without further purification (0.84 g). LCMS (method 1): m/z 474 [M+H].sup.+, retention time 1.10 min.

Step 4: Preparation of 2-(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethoxy)isoindolin-1-one (Intermediate V-4)

[0650] ##STR00107##

[0651] To a solution of 2-[[(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)amino]methyl]-5-(trifluoromethoxy)benzoic acid (intermediate V-3 prepared as described above, 0.9 g, 1.90 mmol) in pyridine (4.5 mL) was added phosphorus oxychloride (0.36 mL, 3.8 mmol, 2 equiv.) at 0° C. The mixture was stirred at room temperature for 10 minutes, quenched by addition of water, acidified with aqueous 1N hydrochloric acid, and the product extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane). The purified product was dissolved in acetonitrile and water was added. The precipitate formed was filtered and dried to afford the desired product (0.7 g). LCMS (method 2): m/z 456 [M+H].sup.+, retention time 1.48 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 8.35 (d, 1H), 7.87 (d, 1H), 7.74-7.82 (m, 3H), 7.52 (dd, 1H), 5.08 (s, 2H), 3.90 (s, 3H), 3.82 (q, 2H), 1.34 (t, 3H).

Step 5: Preparation of 2-(3-ethylsulfonyl-6-hydroxy-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethoxy)isoindolin-1-one (Intermediate V-5)

[0652] ##STR00108##

[0653] To 2-(3-ethylsulfonyl-6-methoxy-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethoxy)isoindolin-1-one (intermediate V-4 prepared as described above, 0.65 g, 1.43 mmol) was added a solution of tribromoborane 1 M in dichloromethane (14.3 mL, 14.3 mmol) at 0° C. and the reaction mixture was stirred at room temperature for 2 hours. The mixture was slowly poured into ice and extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduce pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (0.59 g). LCMS (method 2): m/z 442 [M+H].sup.+, retention time 1.43 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 10.22 (s, 1H), 8.4 (d, 1H), 7.86 (d, 1H), 7.70-7.80 (m, 3H), 7.37 (dd, 1H), 5.05 (s, 2H), 3.73 (q, 2H), 1.32 (t, 3H).

[0654] Similarly, 6-(3-ethylsulfonyl-6-hydroxy-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (V-5-a) can be prepared:

##STR00109##

[0655] LCMS (method 1): m/z 427 [M+H].sup.+, retention time 0.99 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 1.31 (t, 3H), 3.72 (q, 2H), 5.19 (s, 2H), 7.38 (dd, 1H), 7.74 (d, 1H), 8.39 (d, 1H), 8.71 (d, 1H), 9.32 (d, 1H), 10.26 (s, 1H).

Step 6: Preparation of 2-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethoxy)isoindolin-2-yl]imidazo[1,2-a]pyridin-6-yl]ox-2-methyl-propanamide (Intermediate V-6)

[0656] ##STR00110##

[0657] To a solution of 2-(3-ethylsulfonyl-6-hydroxy-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethoxy)isoindolin-1-one (intermediate V-5 prepared as described above, 0.58 g, 1.31 mmol) in acetonitrile (12.0 mL) was added cesium carbonate (0.86 g, 2.63 mmol). The reaction mixture was stirred at room temperature for 5 minutes, then 2-bromo-2-methyl-propanamide (0.44 g, 2.63 mmol) was added, and stirring continued at 60° C. for 12 hours. The mixture was concentrated under reduce pressure and taken up with water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduce pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (0.32 g). LCMS (method 2): m/z 527 [M+H].sup.+, retention time 1.40 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 8.51 (d, 1H), 7.87 (d, 1H), 7.76-7.83 (m, 3H), 7.73 (s, 1H), 7.51 (dd, 1H), 7.42 (s, 1H), 5.09 (s, 2H), 3.76 (q, 2H), 1.49 (s, 6H), 1.34 (t, 3H).

[0658] Similarly, 2-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]oxy-2-methyl-propanamide (V-6-a) can be prepared:

##STR00111##

[0659] LCMS (method 1): m/z 512 [M+H].sup.+, retention time 1.02 min.

Step 7: Preparation of 2-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethoxy)isoindolin-2-yl]imidazo[1,2-a]pyridin-6-yl]oxy-2-methyl-propanenitrile (Compound P26)

[0660] ##STR00112##

[0661] To a solution of 2-[3-ethylsulfonyl-2-[1-oxo-6-(trifluoromethoxy)isoindolin-2-yl]imidazo[1,2-a]pyridin-6-yl]oxy-2-methyl-propanamide (intermediate V-6 prepared as described above, 0.32 g, 0.61 mmol) in tetrahydrofuran was added triethylamine (2.43 mmol, 4 equiv.) at 0° C., followed by trifluoroacetic anhydride (2.43 mmol, 4 equiv.) dropwise, at 0° C. The reaction mixture was stirred at room temperature for 3 hours, then carefully quenched and basified with an aqueous sodium bicarbonate solution. The aqueous phase was extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduce pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (0.25 g). LCMS (method 2): m/z 509 [M+H].sup.+, retention time 1.52 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 8.89 (s, 1H), 7.82 (s, 1H), 7.70 (d, 1H), 7.61 (d, 1H), 7.51 (br d, 2H), 5.10 (s, 2H), 3.83 (q, 2H), 1.82 (s, 6H), 1.52 (t, 3H).

Example H6: Preparation of 2-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]-2-methyl-propanenitrile (Compound P35)

[0662] ##STR00113##

Step 1: Preparation of 2-(6-chloro-3-pyridyl)-2-methyl-propanenitrile (Intermediate VI-1)

[0663] ##STR00114##

[0664] To a solution of 2-(6-chloro-3-pyridyl)acetonitrile (5.00 g, 33.0 mmol) in tetrahydrofuran (50 mL) was added sodium hydride (60% mass in oil) (3.30 g, 82.0 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes, then iodomethane (5.10 mL, 82 mmol) was added at 0° C. The reaction mixture stirred at room temperature for 2 hours, diluted with ice cold water and the product extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was used without further purification. This reaction was done on 6 batches to afford the desired product (35.0 g). LCMS (method 1): m/z 180 [M+H].sup.+, retention time 0.99 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.77 (s, 6H), 7.38 (d, 1H), 7.78 (dd, 1H), 8.52 (d, 1H).

Step 2: Preparation of 2-(6-chloro-3-pyridyl)-2-methyl-propanenitrile tert-butyl N-[5-(1-cyano-1-methyl-ethyl)-2-pyridyl]carbamate (Intermediate VI-2)

[0665] ##STR00115##

[0666] To a solution of 2-(6-chloro-3-pyridyl)-2-methyl-propanenitrile (intermediate VI-1 prepared as described above, 20.0 g, 110 mmol) in 1,4-dioxane (400 mL) were added tert-butyl carbamate (19.5 g, 166 mmol) and cesium carbonate (54.2 g, 166 mmol). The reaction mixture was purged with argon for 15 minutes, then 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos, 16.2 g, 33.2 mmol) and palladium(II) acetate (3.73 g, 16.7 mmol) were added and the reaction mixture was stirred at 110° C. for 3 hours. After cooling to room temperature, the mixture was diluted with cold water and the product extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was used without further purification (30.0 g). LCMS (method 1): m/z 262 [M+H].sup.+, retention time 1.08 min.

Step 3: Preparation 2-(6-amino-3-pyridyl)-2-methyl-propanenitrile (Intermediate VI-3)

[0667] ##STR00116##

[0668] To a solution of tert-butyl N-[5-(1-cyano-1-methyl-ethyl)-2-pyridyl]carbamate (intermediate VI-2 prepared as described above, 28.0 g, 107 mmol) in benzotrifluoride (140 mL) was added 2,2,2-trifluoroacetic acid (164 mL, 2143 mmol). The reaction mixture was stirred at room temperature for 16 hours, then diluted with water and the product extracted with ethyl acetate. The organic phase was washed with an aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (21.0 g). LCMS (method 1): m/z 162 [M+H].sup.+, retention time 0.17 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.72 (s, 6H), 6.92 (d, 1H), 7.80 (d, 1H), 7.88 (dd, 1H).

Step 4: Preparation ethyl 6-(1-cyano-1-methyl-ethyl)imidazo[1,2-a]pyridine-2-carboxylate (Intermediate VI-4)

[0669] ##STR00117##

[0670] To a solution of 2-(6-amino-3-pyridyl)-2-methyl-propanenitrile (intermediate VI-3 prepared as described above, 15.0 g, 93.1 mmol) in ethanol (150 mL) were added NaHCO.sub.3 (15.6 g, 186 mmol) and ethyl 3-bromo-pyruvate (40.3 g, 186 mmol). The reaction mixture was stirred at 85° C. for 4 hours, then allowed to cool to room temperature. The mixture was diluted with cold water and the product extracted with ethyl acetate. The organic phase was washed with an aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (13.2 g). LCMS (method 1): m/z 258 [M+H].sup.+, retention time 1.08 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.43 (t, 3H), 1.78 (s, 6H), 4.46 (q, 2H), 7.24-7.31 (m, 1H), 7.72 (d, 1H), 8.21 (s, 1H), 8.30-8.33 (m, 1H).

Step 5: Preparation ethyl 3-chloro-6-(1-cyano-1-methyl-ethyl)imidazo[1,2-a]pyridine-2-carboxylate (Intermediate VI-5)

[0671] ##STR00118##

[0672] To a solution of ethyl 6-(1-cyano-1-methyl-ethyl)imidazo[1,2-a]pyridine-2-carboxylate (intermediate VI-4 prepared as described above, 13.2 g, 51.3 mmol) in acetonitrile (264 mL) was added N-chlorosuccinimide (8.22 g, 61.6 mmol). The reaction mixture was stirred at 50° C. for 4 hours. The reaction mixture was diluted with cold water and extracted with ethyl acetate. The organic phase was washed with an aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was used without further purification (11.0 g). LCMS (method 1): m/z 292 [M+H].sup.+, retention time 1.31 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.48 (t, 3H), 1.84 (s, 6H), 4.52 (q, 2H), 7.50 (dd, 1H), 7.90 (d, 1H), 8.31 (m, 1H).

Step 6: Preparation ethyl 6-(1-cyano-1-methyl-ethyl)-3-ethylsulfanyl-imidazo[1,2-a]pyridine-2-carboxylate (Intermediate VI-6)

[0673] ##STR00119##

[0674] To a solution of ethyl 3-chloro-6-(1-cyano-1-methyl-ethyl)imidazo[1,2-a]pyridine-2-carboxylate (intermediate VI-5 prepared as described above, 11.0 g, 37.7 mmol) in dimethylsulfoxide (110 mL) was added sodium ethanethiolate (6.34 g, 75.4 mmol) portionwise. The reaction mixture was stirred at room temperature for 1 hour, then it was diluted with cold water and the formed precipitate filtered and dried to afford the desired product (8.00 g). LCMS (method 1): m/z 318 [M+H].sup.+, retention time 1.07 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.21 (t, 3H), 1.47 (t, 3H), 1.82 (s, 6H), 2.97 (q, 2H), 4.50 (q, 2H), 7.40 (s, 1H), 7.74 (d, 1H), 8.69 (d, 1H). LCMS (method 1): m/z 318 [M+H].sup.+, retention time 1.07 min.

Step 7: Preparation of ethyl 6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (Intermediate VI-7)

[0675] ##STR00120##

[0676] To a solution of ethyl 6-(1-cyano-1-methyl-ethyl)-3-ethylsulfanyl-imidazo[1,2-a]pyridine-2-carboxylate (intermediate VI-6 prepared as described above, 8.00 g, 25.0 mmol) in trifluoromethylbenzene (120 mL) was added 3-chlorobenzenecarboperoxoic acid (16.0 g, 63.0 mmol) portionwise. The reaction mixture was stirred at room temperature for 24 hours. After dilution with an aqueous saturated sodium bicarbonate solution, the formed precipitate was filtered and dried. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (6.70 g). LCMS (method 1): m/z 350 [M+H].sup.+, retention time 1.01 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.40 (t, 3H), 1.49 (t, 3H), 1.83 (s, 6H), 3.76 (q, 2H), 4.54 (q, 2H), 7.66 (dd, 1H), 7.89 (d, 1H), 9.41 (d, 1H).

Step 8: Preparation of 6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylic Acid (Intermediate VI-8)

[0677] ##STR00121##

[0678] To a solution of ethyl 6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (intermediate VI-7 prepared as described above, 6.7 g, 19.0 mmol) in tetrahydrofuran (67 mL) and water (27 mL) was added lithium hydroxide (1.60 g, 38.0 mmol) in water (32 mL) portionwise at 0-5° C. The reaction mixture was stirred at room temperature for 5 hours, then acidified with aqueous 2N hydrochloric acid, diluted with water and the product extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was used without further purification (5.30 g). LCMS (method 1): m/z 322 [M+H].sup.+, retention time 0.89 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 1.25 (t, 3H), 1.78 (s, 6H), 3.72 (q, 2H), 7.89 (dd, 1H), 7.96 (d, 1H), 9.12 (s, 1H), 13.79-14.02 (m, 1H).

Step 9: Preparation of tert-butyl N-[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]carbamate (Intermediate VI-9)

[0679] ##STR00122##

[0680] To a solution of 6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylic acid (intermediate VI-8 prepared as described above, 5.30 g, 16.0 mmol) in tert-butanol (27 mL) and toluene (53 mL) were added triethylamine (3.00 mL, 21.0 mmol), followed by diphenylphosphoryl azide (4.70 mL, 21.0 mmol) dropwise. The reaction mixture was stirred at 80° C. for 30 minutes, then cooled to room temperature. The mixture was diluted with ice and the product extracted with ethyl acetate, the organic phase dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography over silica gel (gradient ethyl acetate in cyclohexane) to afford the desired product (1.80 g). LCMS (method 1): m/z 393 [M+H].sup.+, retention time 1.04 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 1.26 (t, 3H), 1.47 (s, 9H), 1.77 (s, 6H), 3.65 (q, 2H), 7.77-7.84 (m, 2H), 8.79 (s, 1H), 9.40 (s, 1H).

Step 10: Preparation of ethyl 2-[[tert-butoxycarbonyl-[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate VI-10)

[0681] ##STR00123##

[0682] To a solution of tert-butyl N-[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]carbamate (intermediate VI-9 prepared as described above, 0.50 g, 1.27 mmol) in acetonitrile (7.50 mL) were added cesium carbonate (0.63 g, 1.91 mmol), followed by a solution of ethyl 2-(bromomethyl)-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate II-4-a prepared in analogy to intermediate II-4 described above, 0.52 g, 1.66 mmol) in acetonitrile (7.50 mL) dropwise. The reaction mixture was heated to 50° C. and stirred for 2 hours. After cooling to room temperature, it was diluted with water and the product extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was used without further purification (0.60 g). LCMS (method 1): m/z 624 [M+H].sup.+, retention time 1.52 min.

Step 11: Preparation of ethyl 2-[[[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (Intermediate VI-11)

[0683] ##STR00124##

[0684] To a solution of ethyl 2-[[tert-butoxycarbonyl-[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate VI-10 prepared as described above, 0.60 g, 0.96 mmol) in benzotrifluoride (3.00 mL) was added 2,2,2-trifluoroacetic acid (1.47 mL, 19.2 mmol). The reaction mixture was stirred at room temperature for 16 hours, then diluted with water and the product extracted with ethyl acetate. The combined organic layers were washed with an aqueous saturated sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was used without further purification (0.48 g). LCMS (method 1): m/z 524 [M+H].sup.+, retention time 1.12 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 1.18 (t, 3H), 1.39 (t, 3H), 1.74 (s, 6H), 3.41 (q, 2H), 4.42 (q, 2H), 5.14 (br d, 2H), 6.90 (br t, 1H), 7.53 (d, 1H), 7.67 (dd, 1H), 8.53 (d, 1H), 8.56 (d, 1H), 9.13 (m, 1H).

Step 12: Preparation of 2-[[[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylic Acid (Intermediate VI-12)

[0685] ##STR00125##

[0686] To a solution of ethyl 2-[[[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylate (intermediate VI-11 prepared as described above, 0.48 g, 0.92 mmol) in methanol (9.60 mL) was added dihydroxybarium octahydrate (0.72 g, 2.29 mmol) dissolved in water (4.8 mL). The reaction mixture was stirred at room temperature for 4 hours, then the volatiles were removed under reduced pressure. The residue was acidified with aqueous 2N hydrochloric acid, the formed precipitate filtered and dried to afford the desired product (0.41 g). LCMS (method 1): m/z 496 [M+H].sup.+, retention time 1.02 min. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm: 1.18 (t, 3H), 1.74 (s, 6H), 3.42 (q, 2H), 5.16 (br d, 2H), 6.98 (t, 1H), 7.55 (d, 1H), 7.67 (dd, 1H), 8.52 (d, 1H), 8.57 (s, 1H), 9.11-9.13 (m, 1H).

Step 13: Preparation of 2-[3-ethylsulfonyl-2-[5-oxo-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-6-yl]imidazo[1,2-a]pyridin-6-yl]-2-methyl-propanenitrile (P35)

[0687] ##STR00126##

[0688] To a solution of 2-[[[6-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]amino]methyl]-5-(trifluoromethyl)pyridine-3-carboxylic acid (intermediate VI-12 prepared as described above, 0.40 g, 0.81 mmol) in pyridine (2.00 mL) was added phosphorus oxychloride (0.15 mL, 1.65 mmol) at 0° C. The reaction mixture was stirred at room temperature for 10 minutes, then diluted with water, acidified with aqueous 1N hydrochloric acid, and the product extracted three times 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 (gradient ethyl acetate in cyclohexane) afforded the desired product (0.25 g). LCMS (method 1): m/z 478 [M+H].sup.+, retention time 1.04 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm: 1.55 (t, 3H), 1.86 (s, 6H), 3.83 (q, 2H), 5.23 (s, 2H), 7.66 (dd, 1H), 7.79 (d, 1H), 8.49 (s, 1H), 9.04 (s, 1H), 9.13 (s, 1H).

Example H7: Preparation of 6-[6-(2,2-difluoroethoxy)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (Compound P19)

[0689] ##STR00127##

[0690] To a solution of 6-(3-ethylsulfonyl-6-hydroxy-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (intermediate V-5-a prepared as described above) (40 mg, 0.094 mmol) in acetonitrile (0.8 mL) were added potassium carbonate (3 equiv., 0.281 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate (1.3 equiv., 0.122 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, then added to water (10 mL) and the product extracted twice with ethyl acetate (2×8 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated under vacuum. The crude residue was purified by combiflash chromatography (50-60% ethyl acetate in cyclohexane) to afford the desired product (32 mg). LCMS (method 1): m/z 491 [M+H].sup.+, retention time 1.09 min.

Example H8: Preparation of 6-[6-(difluoromethoxy)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (Compound P10)

[0691] ##STR00128##

[0692] To a solution of 6-(3-ethylsulfonyl-6-hydroxy-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (intermediate V-5-a prepared as described above) (0.1 g, 0.235 mmol) and potassium carbonate (1.5 equiv., 0.352 mmol) in N,N-dimethylformamide (3 mL) was added sodium 2-chloro-2,2-difluoro-acetate (2.0 equiv., 0.469 mmol). The reaction mixture was stirred at 60° C. for 5 hours, then diluted with water (20 mL) and the product extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude was purified by combiflash (silica gel, 30% ethyl acetate in cyclohexane) to afford the desired product (26 mg). LCMS (method 1): m/z 477 [M+H].sup.+, retention time 1.00 min.

Example H9: Preparation of 6-(7-cyclopropyl-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (Compound P24)

[0693] ##STR00129##

[0694] To 6-(7-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-7H-pyrrolo[3,4-b]pyridin-5-one (compound P22) (240 mg, 0.40 mmol) in toluene (4 mL) and water (0.8 mL) were added potassium carbonate (3 equiv.), cyclopropylboronic acid (2 equiv.) and the solution was flushed with nitrogen for 10 minutes. 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.05 equiv.) was added and the solution further flushed with nitrogen for 5 minutes, then heated in the microwave at 110° for 1.5 hours. After cooling to room temperature, the mixture was diluted with water and the product extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by combiflash column chromatography (0-30% ethyl acetate in cyclohexane) to afford the desired product (133 mg) as a solid. LCMS (method 2): m/z 451 [M+H].sup.+, retention time 1.48 min.

TABLE-US-00015 TABLE P Examples of compounds of formula (I) LCMS R.sub.t [M + H].sup.+ Mp No. IUPAC name Structures (min) (measured) Method (° C.) P1 2-[3-ethylsulfonyl-6- (trifluoromethyl) benzothiophen-2-yl]- 6-(trifluoromethyl)- 3H-pyrrolo[3,4-c] pyridin-1-one [00130] 1.16 495 1 — P2 6-[3-ethylsulfonyl-7- (trifluoromethyl) imidazo[1,2-a] pyridin-2-yl]-3- (trifluoromethyl)- 7H-pyrrolo[3,4-b] pyridin-5-one [00131] 1.06 479 1 207- 209 P3 1-[3-ethylsulfonyl-2- [5-oxo-3- (trifluoromethyl)-7H- pyrrolo[3,4-b] pyridin-6-yl]imidazo [1,2-a]pyridin-7-yl] cyclopropane- carbonitrile [00132] 0.99 476 1 211- 213 P4 6-[3-ethylsulfonyl-6- (trifluoromethyl) imidazo[1,2-a] pyridin-2-yl]-3- (trifluoromethyl)- 7H-pyrrolo[3,4-b] pyridin-5-one [00133] 1.05 479 1 195- 197 P5 1-[3-ethylsulfonyl-2- [1-oxo-6- (trifluoromethoxy) isoindolin-2-yl] imidazo[1,2-a] pyridin-7-yl] cyclopropane- carbonitrile [00134] 1.06 491 1 189- 191 P6 2-[3-ethylsulfonyl-6- (trifluoromethyl) imidazo[1,2-a] pyridin-2-yl]-6- (trifluoromethoxy) isoindolin-1-one [00135] 1.12 494 1 158- 160 P7 2-[3-ethylsulfonyl-7- (trifluoromethyl) imidazo[1,2-a] pyridin-2-yl]-6- (trifluoromethoxy) isoindolin-1-one [00136] 1.13 494 1 198- 200 P8 6-(3-ethylsulfonyl-6- methoxy-imidazo [1,2-a]pyridin-2-yl)- 3-(trifluoromethyl)- 7H-pyrrolo[3,4-b] pyridin-5-one [00137] 1.06 441 1 214- 216 P9 6-(3-ethylsulfonyl-6- isopropoxy-imidazo [1,2-a]pyridin-2-yl)- 3-(trifluoromethyl)- 7H-pyrrolo[3,4-b] pyridin-5-one [00138] 1.05 469 1 185- 187 P10 6-[6- (difluoromethoxy)- 3-ethylsulfonyl- imidazo[1,2-a] pyridin-2-yl]-3- (trifluoromethyl)- 7H-pyrrolo[3,4-b] pyridin-5-one [00139] 1.00 477 1 196- 198 P11 6-[3-ethylsulfonyl-6- (2,2,2-trifluoroethoxy) imidazo[1,2-a]pyridin- 2-yl]-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00140] 1.04 509 1 188- 190 P12 6-[3-ethylsulfonyl-7- (2,2,2-trifluoroethoxy) imidazo[1,2-a]pyridin- 2-yl]-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00141] 1.03 509 1 120- 122 P13 6-(3-ethylsulfonyl-7- methoxy-imidazo [1,2-a]pyridin-2-yl)- 3-(trifluoromethyl)- 7H-pyrrolo[3,4-b] pyridin-5-one [00142] 1.31 441 2 106- 109 P14 1-[3-ethylsulfonyl-2- [1-oxo-6- (trifluoromethoxy) isoindolin-2-yl] imidazo[1,2-a] pyridin-6-yl] cyclopropane- carbonitrile [00143] 1.04 491 1 90- 92 P15 1-[3-ethylsulfonyl-2- [5-oxo-3- (trifluoromethyl)-7H- pyrrolo[3,4-b] pyridin-6-yl]imidazo [1,2-a]pyridin-6-yl] cyclopropane- carbonitrile [00144] 0.98 476 1 224- 226 P16 1-[3-ethylsulfonyl-2- [1-oxo-6- (trifluoromethyl) isoindolin-2-yl] imidazo[1,2-a] pyridin-6-yl] cyclopropane- carbonitrile [00145] 1.03 475 1 212- 214 P17 2-[6-(1,1-difluoroethyl)- 3-ethylsulfonyl- imidazo[1,2-a]pyridin- 2-yl]-6- (trifluoromethoxy) isoindolin-1-one [00146] 1.09 490 1 164- 166 P18 6-[6-(1,1-difluoroethyl)- 3-ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl]-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00147] 1.10 475 1 187- 190 P19 6-[6-(2,2- difluoroethoxy)-3- ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl]-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00148] 1.09 491 1 188- 190 P20 2-[3-ethylsulfonyl-2- [5-oxo-3- (trifluoromethyl)-7H- pyrrolo[3,4-b] pyridin-6-yl]imidazo [1,2-a]pyridin-6-yl] oxy-2-methyl- propanenitrile [00149] 1.10 494 1 149- 151 P21 6-(6-bromo-3- ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00150] 1.11 489/491 1 218- 220 P22 6-(7-bromo-3- ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00151] 1.05 489/491 1 225- 227 P23 6-(3-ethylsulfonyl-7- methyl-imidazo[1,2-a] pyridin-2-yl)-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00152] 1.43 425 2 166- 168 P24 6-(7-cyclopropyl-3- ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00153] 1.48 451 2 190- 192 P25 6-[7-(1,1-difluoroethyl)- 3-ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl]-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00154] 1.11 475 1 215- 217 P26 2-[3-ethylsulfonyl-2-[1- oxo-6- (trifluoromethoxy) isoindolin-2-yl] imidazo[1,2-a]pyridin- 6-yl]oxy-2-methyl- propanenitrile [00155] 1.52 509 2 186- 188 P27 6-(6-cyclopropyl-3- ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00156] 1.05 451 1 210- 212 P28 2-[3-ethylsulfonyl-7- (2,2,2- trifluoroethoxy) imidazo[1,2-a] pyridin-2-yl]-6- (trifluoromethoxy) isoindolin-1-one [00157] 1.45 524 2 208- 210 P29 2-(6-bromo-3- ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl)-6- (trifluoromethoxy) isoindolin-1-one [00158] 1.15 504/506 1 217- 219 P30 2-(6-bromo-3- ethylsulfonyl- imidazo[1,2-a] pyridin-2-yl)-6- (trifluoromethyl- sulfonyl) isoindolin-1-one [00159] 1.14 552/554 1 251- 253 P31 1-[[3-ethylsulfonyl-2- [5-oxo-3- (trifluoromethyl)-7H- pyrrolo[3,4-b] pyridin-6-yl]imidazo [1,2-a]pyridin-6-yl] oxymethyl] cyclopropane- carbonitrile [00160] 1.06 506 1 238- 240 P32 2-[3-ethylsulfonyl-6- (trifluoromethyl) imidazo[1,2-a] pyridin-2-yl]-6- (trifluoromethyl- sulfonyl) isoindolin-1-one [00161] 1.13 542 1 264- 266 P33 2-[3-ethylsulfonyl-7- (2,2,2-trifluoroethoxy) imidazo[1,2-a]pyridin- 2-yl]-6- (trifluoromethyl- sulfonyl) isoindolin-1-one [00162] 1.53 572 2 215- 217 P34 6-(difluoromethoxy)-2- [3-ethylsulfonyl-6- (trifluoromethyl) imidazo[1,2-a]pyridin- 2-yl]isoindolin-1-one [00163] 1.09 476 1 169- 171 P35 2-[3-ethylsulfonyl-2- [5-oxo-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 6-yl]imidazo[1,2-a] pyridin-6-yl]-2- methyl-propanenitrile [00164] 1.04 478 1 209- 211 P36 N-[3-ethylsulfonyl-2- [5-oxo-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 6-yl]imidazo[1,2-a] pyridin-6-yl]acetamide [00165] 1.25 468 2 248- 250 P37 2-[3-ethylsulfonyl-7- (trifluoromethyl) imidazo[1,2-a] pyridin-2-yl]-6- (trifluoromethyl- sulfonyl) isoindolin-1-one [00166] 1.15 542 1 114- 116 P38 6-[7-(2,2- difluoroethoxy)-3- ethylsulfonyl-imidazo [1,2-a]pyridin-2-yl]-3- (trifluoromethyl)-7H- pyrrolo[3,4-b]pyridin- 5-one [00167] 1.06 491 1 188- 190

Intermediate Preparation

Example I1: Preparation of ethyl 5-(bromomethyl)-2-(trifluoromethyl)pyridine-4-carboxylate (Intermediate IP-5)

[0695] ##STR00168##

Step A1: Preparation of 5-chloro-2-(trifluoromethyl)pyridine-4-carboxylic acid (Intermediate IP-1) and 2,2,6,6-tetramethylpiperidin-1-ium 5-chloro-2-(trifluormethyl)pyridine-4-carboxylate (Intermediate IP-2)

[0696] ##STR00169##

[0697] A 2.0 M butyllithium solution in tetrahydrofuran (165 mL, 330 mmol, 4.00 equiv.) was added dropwise to a −78° C. cooled solution of 2,2,6,6-tetramethylpiperidine (35.0 g, 248 mmol, 3.00 equiv.) in tetrahydrofuran (500 mL). After complete addition, the reaction mixture was stirred for 30 min at −50° C. and cooled again to −78° C. before adding a solution of 5-chloro-2-(trifluoromethyl)pyridine (15.0 g, 82.6 mmol) in tetrahydrofuran (100 mL). The reaction mixture was stirred for 30 min at −78° C. before being added via cannula to a CO.sub.2 saturated solution of tetrahydrofuran cooled at −78° C. Once the addition was complete, the reaction mixture was warmed up to room temperature, and quenched by addition of a saturated ammonium chloride aqueous solution (200 mL). The aqueous phase was extracted twice with ethyl acetate (200 mL), the combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure to give 2,2,6,6-tetramethylpiperidin-1-ium 5-chloro-2-(trifluoromethyl)pyridine-4-carboxylate (intermediate IP-2). The aqueous phase was acidified to pH 3 by addition of a 2 M hydrochloric acid aqueous solution and extracted twice with a 90/10 mixture of dichloromethane/methanol (200 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure to give 5-chloro-2-(trifluoromethyl)pyridine-4-carboxylic acid (intermediate IP-1). Both crude materials were used in the next step without further purification. LCMS (method 1): m/z 226 [M+H].sup.+, retention time 0.67 min. .sup.1H NMR (400 MHz, DMSO-d6) δ/ppm: 8.18 (s, 1H), 8.98 (s, 1H) for 5-chloro-2-(trifluoromethyl)pyridine-4-carboxylic acid (IP-1).

Step A2: Preparation of ethyl 5-chloro-2-(trifluoromethyl)pyridine-4-carboxylate (Intermediate IP-3)

[0698] ##STR00170##

[0699] A mixture of 5-chloro-2-(trifluoromethyl)pyridine-4-carboxylic acid (intermediate IP-1) prepared as described above) (1.00 g, 4.43 mmol) and concentrated sulfuric acid (1.00 mL) in ethanol (30 mL) was heated at reflux overnight. After cooling to room temperature, the reaction mixture was concentrated and the residue was diluted with iced water (50 mL). The aqueous phase was extracted twice with ethyl acetate (2×30 mL), the combined organic phases were washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated. The crude material was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to give the desired compound as a yellow liquid. LCMS (method 1): m/z 254 [M+H].sup.+, retention time 1.10 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 1.45 (t, J=7.12 Hz, 3H), 4.49 (q, J=7.12 Hz, 2H), 8.04 (s, 1H), 8.82 (s, 1H).

Step A3: Preparation of ethyl 5-methyl-2-(trifluoromethyl)pyridine-4-carboxylate (Intermediate IP-4)

[0700] ##STR00171##

[0701] Tripotassium phosphate (4.5 g, 21.3 mmol, 3.0 equiv.) and tricyclohexylphosphine (0.2 g, 0.71 mmol, 0.10 equiv.) were added to a mixture of ethyl 5-chloro-2-(trifluoromethyl)pyridine-4-carboxylate (intermediate IP-3 prepared as described above) (1.8 g, 7.1 mmol) and methyl-boronic acid (1.3 g, 21.3 mmol, 3.0 equiv.) in toluene (50 mL) and water (5.0 mL). The mixture was purged with nitrogen for 10 min before adding palladium acetate (0.08 g, 0.035 mmol, 0.05 equiv.). Purging was continued for 10 min and the reaction mixture was heated at 100° C. for 2 hours. After cooling down to room temperature, the mixture was diluted with water (50 mL) and ethyl acetate (50 mL), and filtered over Celite (washed with ethyl acetate). The phases were separated, the aqueous phase was extracted with ethyl acetate, the combined organic phases were dried over sodium sulfate, filtered and concentrated. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired compound as a pale yellow liquid. LCMS (method 1): m/z 234 [M+H].sup.+, retention time 1.08 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 1.44 (t, J=7.16 Hz, 3H), 2.66 (s, 3H), 4.44 (q, J=7.16 Hz, 2H), 8.08 (s, 1H), 8.68 (s, 1H).

Step A4: Preparation of ethyl 5-(bromomethyl)-2-(trifluoromethyl)pyridine-4-carboxylate (Intermediate IP-5)

[0702] ##STR00172##

[0703] N-bromosuccinimide (1.40 g, 7.80 mmol, 1.40 equiv.) and benzoyl peroxide (0.42 g, 1.70 mmol, 0.30 equiv.) were added to a solution of ethyl 5-methyl-2-(trifluoromethyl)pyridine-4-carboxylate (intermediate IP-4 prepared as described above) (1.30 g, 5.60 mmol) in tetrachloromethane (45 mL). The reaction mixture was heated at 70° C. overnight. After cooling down to room temperature, the reaction mixture was diluted with iced water (20 mL), and the aqueous phase was extracted twice with ethyl acetate (10 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude material was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to give the desired product. LCMS (method 1): m/z 312/314 [M+H].sup.+, retention time 1.12 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 1.44 (t, J=7.15 Hz, 3H), 4.50 (q, J=7.15 Hz, 2H), 4.94 (s, 2H), 7.27 (s, 1H), 8.14 (s, 1H), 8.85 (s, 1H).

[0704] Similarly, methyl 5-(bromomethyl)-2-(trifluoromethyl)pyridine-4-carboxylate (IP-6) can be prepared:

##STR00173##

[0705] LCMS (method 1): m/z 298/300 [M+H].sup.+, retention time 1.06 min. .sup.1H NMR (400 MHz, CDCl.sub.3) δ/ppm: 4.04 (s, 3H), 4.95 (s, 2H), 8.15 (s, 1H), 8.87 (s, 1H).

Example 12: Preparation of tert-butyl N-[6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]carbamate (Intermediate IQ-7)

[0706] ##STR00174##

Step 1: Preparation of ethyl 6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (Intermediate IP-7)

[0707] ##STR00175##

[0708] Obtained from ethyl 6-bromo-3-ethylsulfanyl-imidazo[1,2-a]pyridine-2-carboxylate (CAS 2093460-48-9) by following procedure Example H3/step 5. LCMS (method 1): m/z 361/363 [M+H].sup.+, retention time Rt=0.93 min.

Step 2: Preparation of ethyl 6-(1-ethoxyvinyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (Intermediate IP-8)

[0709] ##STR00176##

[0710] To a solution of ethyl 6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (intermediate IP-7 prepared as described above) (5 g, 13.15 mmol) in N,N-dimethylformamide (52.6 mL) was added tributyl(1-ethoxyvinyl)tin (6.0 g, 15.78 mmol, 5.61 mL). The reaction mixture was flushed with nitrogen for 15 minutes, then bis(triphenylphosphine)palladium(II) dichloride (0.466 g, 0.657 mmol) was added. The resulting mixture was heated at 80° C. for 3 hours, then cooled to room temperature and used directly in the next step.

Step 3: Preparation of ethyl 6-acetyl-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (Intermediate IP-9)

[0711] ##STR00177##

[0712] To the crude solution of ethyl 6-(1-ethoxyvinyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (intermediate IP-8) obtained above was added an aqueous 2N hydrochloric acid solution (20 mL) and stirring continued at room temperature for 60 minutes. The mixture was diluted with water (100 mL) and the product extracted with ethyl acetate (100 mL). The organic layer was filtered through Celite, the Celite bed washed using ethyl acetate (20 mL), the combined organic layers washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated under vacuum. The crude material was purified by combiflash (silicagel, 30-60% ethyl acetate in cyclohexane) to afford the desired product. LCMS (method 1): m/z 325 [M+H].sup.+, retention time Rt=0.96 min.

Step 4: Preparation of ethyl 6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (Intermediate IP-10)

[0713] ##STR00178##

[0714] To a solution of ethyl 6-acetyl-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (intermediate IP-9 prepared as described above) (2.6 g, 7.6 mmol) in toluene (26 mL) under nitrogen was added bis(2-methoxyethyl)aminosulfur trifluoride (13 g, 30 mmol, 11 mL) dropwise. The reaction mixture was stirred at 80° C. for 12 hours, cooled and quenched carefully by adding an aqueous saturated sodium carbonate solution. After further dilution with ice-cold water (100 mL), the product was extracted with ethyl acetate (3×75 mL), the combined organic phases dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by combiflash (20-50% ethyl acetate in cyclohexane) to afford the desired product. LCMS (method 1): m/z 347 [M+H].sup.+, retention time Rt=1.04 min.

Step 5: Preparation of 6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylic Acid (Intermediate IP-11)

[0715] ##STR00179##

[0716] Obtained from ethyl 6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylate (intermediate IP-10) by following procedure Example H3/step 6. LCMS (method 1): m/z 319 [M+H].sup.+, retention time Rt=0.92 min.

Step 6: Preparation of tert-butyl N-[6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl]carbamate (Intermediate IQ-7)

[0717] ##STR00180##

[0718] Obtained from 6-(1,1-difluoroethyl)-3-ethylsulfonyl-imidazo[1,2-a]pyridine-2-carboxylic acid (intermediate IP-11) by following procedure Example H3/step 7. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 9.47 (s, 1H), 8.85 (d, 1H), 7.84 (d, 1H), 7.77 (dd, 1H), 3.68 (q, 2H), 2.08 (t, J=19.07 Hz, 3H), 1.48 (s, 9H), 1.26 (t, 3H).

TABLE-US-00016 TABLE Q Examples of intermediate compounds of formula (XIX-Qa-1) (XIX-Qa-1) [00181] No. R.sub.3 R.sub.4 .sup.1H NMR IQ-1 CF.sub.3 H .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.36 (t, 3 H) 1.56 (s, 9 H) 3.28 (q, 2 H) 7.59-7.64 (m, 1 H) 7.85 (d, 1 H) 8.24 (s, 1 H) 8.97 (s, 1 H). II-1 H CF.sub.3 .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.27 (t, 3 H) 1.48 (s, 9 H) 3.66 (q, 2 H) 7.47 (dd, 1 H) 8.24 (s, 1 H) 8.94 (d, 1 H) 9.57 (s, 1 H). IQ-2 H [00182] .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.33 (t, 3 H) 1.50- 1.55 (m, 2 H) 1.56 (s, 9 H) 1.87-1.96 (m, 2 H) 3.24 (q, 2 H) 7.05 (dd, 1 H) 7.55 (s, 1 H) 8.19 (s, 1 H) 8.61 (dd, 1 H). IQ-3 [00183] H .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.36 (t, 3 H) 1.44- 1.50 (m, 2 H) 1.57 (s, 9 H) 1.80-1.85 (m, 2 H) 3.24- 3.31 (m, 2 H) 7.42 (dd, 1 H) 7.75 (d, 1 H) 8.23 (s, 1 H) 8.65 (s, 1 H). IQ-4 H OCH.sub.3 .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (t, 3 H) 1.47 (s, 9 H) 3.54 (q, 2 H) 3.89 (s, 3 H) 6.89 (dd, 1 H) 7.12 (d, 1 H) 8.55 (d, 1 H) 9.24 (s, 1 H). IQ-5 OCH.sub.3 H .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.34 (t, 3 H) 1.56 (s, 9 H) 3.24 (q, 2 H) 3.88 (s, 3 H) 7.23 (dd, 1 H) 7.64 (d, 1 H) 8.16 (s, 1 H) 8.20 (d, 1 H). IQ-6 H Br .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.32 (t, 3 H) 1.55 (s, 9 H) 3.23 (q, 2 H) 7.13 (dd, 1 H) 7.91 (dd, 1 H) 8.19 (s, 1 H) 8.48 (dd, 1 H). IQ-7 CF.sub.2CH.sub.3 H .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 9.47 (s, 1H), 8.85 (d, 1H), 7.84 (d, 1H), 7.77 (dd, 1H), 3.68 (q, 2H), 2.08 (t, J = 19.07 Hz, 3H), 1.48 (s, 9H), 1.26 (t, 3H). III-7 H OCH.sub.2CF.sub.3 .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.32 (t, 3 H) 1.56 (s, 9 H) 3.22 (q, 2 H) 4.41 (q, 2 H) 6.79 (dd, 1 H) 7.05 (d, 1 H) 8.16 (s, 1 H) 8.51 (d, 1 H). IQ-8 Br H .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.25 (t, 3 H) 1.46 (s, 9 H) 3.66 (q, 2 H) 7.70 (d, 1 H) 7.74 (d, 1 H) 8.83 (s, 1 H) 9.43 (s, 1 H). VI-9 [00184] H .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.26 (t, 3 H) 1.47 (s, 9 H) 1.77 (s, 6 H) 3.65 (q, 2 H) 7.77-7.84 (m, 2H) 8.79 (s, 1 H) 9.40 (s, 1 H). IQ-9 H CF.sub.2CH.sub.3 .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (t, 3 H) 1.48 (s, 9 H) 1.98-2.12 (m, 3 H) 3.63 (q, 2 H) 7.36 (dd, 1 H) 7.92 (s, 1 H) 8.85 (d, 1 H) 9.48 (s, 1 H). IQ-10 [00185] H .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 0.69-0.80 (m, 2 H) 1.01-1.10 (m, 2 H) 1.33 (t, 3 H) 1.56 (s, 9 H) 1.92- 2.00 (m, 1 H) 3.24 (q, 2 H) 7.15 (dd, 1 H) 7.64 (d, 1 H) 8.23 (s, 1 H) 8.42 (s, 1 H).

TABLE-US-00017 TABLE R Examples of intermediate compounds of formula (X-Qa-1) (X-Qa-1) [00186] LCMS R.sub.t [M − H].sup.− No. R.sub.3 R.sub.4 G.sub.1 G.sub.2 R.sub.2 (min) (measured) Method IR-1 H CF.sub.3 N CH CF.sub.3 1.04 495 1 (II-7) IR-2 H 1-CNCyPr N CH CF.sub.3 0.96 492 1 IR-3 CF.sub.3 H N CH CF.sub.3 1.51 495 2 IR-4 H 1-CNCyPr CH CH OCF.sub.3 1.04 507 1 IR-5 CF.sub.3 H CH CH OCF.sub.3 1.10 510 1 IR-6 H CF.sub.3 CH CH OCF.sub.3 1.11 510 1 IR-7 OCH.sub.3 H N CH CF.sub.3 0.94 457 1 IR-8 OCH(CH.sub.3).sub.2 H N CH CF.sub.3 — — — IR-9 OCHF.sub.2 H N CH CF.sub.3 — — — IR-10 OCH.sub.2CF.sub.3 H N CH CF.sub.3 — — IR-11 H OCH.sub.2CF.sub.3 N CH CF.sub.3 1.02 525 1 IR-12 H OCH.sub.3 N CH CF.sub.3 0.93 457 1 IR-13 1-CNCyPr H CH CH OCF.sub.3 1.01 507 1 IR-14 1-CNCyPr H N CH CF.sub.3 0.95 492 1 IR-15 1-CNCyPr H CH CH CF.sub.3 1.00 491 1 IR-16 CF.sub.2CH.sub.3 H CH CH OCF.sub.3 1.06 506 1 IR-17 CF.sub.2CH.sub.3 H N CH CF.sub.3 1.09 491 1 IR-18 OCH.sub.2CHF.sub.2 H N CH CF.sub.3 — — — IR-19 OC(CH.sub.3).sub.2(CN) H N CH CF.sub.3 — — — IR-20 Br H N CH CF.sub.3 1.01 505/507 1 (IV-3) IR-21 H Br N CH CF.sub.3 1.48 505/507 2 IR-22 H CH.sub.3 N CH CF.sub.3 — — — IR-23 H CyPr N CH CF.sub.3 — — — IR-24 H CF.sub.2CH.sub.3 N CH CF.sub.3 1.09 491 1 IR-25 OC(CH.sub.3).sub.2(CN) H CH CH OCF.sub.3 — — — IR-26 CyPr H N CH CF.sub.3 — — — IR-27 H OCH.sub.2CF.sub.3 CH CH OCF.sub.3 1.09 540 1 IR-28 Br H CH CH OCF.sub.3 1.14 520/522 1 IR-29 Br H CH CH S(O.sub.2)CF.sub.3 1.10 568/570 1 IR-30 OCH.sub.2(1-CNCyPr) H N CH CF.sub.3 — — — IR-31 CF.sub.3 H CH CH S(O.sub.2)CF.sub.3 1.10 558 1 IR-32 H OCH.sub.2CF.sub.3 CH CH S(O.sub.2)CF.sub.3 1.51 588 2 (III-10) IR-33 CF.sub.3 H CH CH OCHF.sub.2 1.09 492 1 IR-34 C(CH.sub.3).sub.2CN H N CH CF.sub.3 1.02 494 1 (VI-12) IR-35 NH(CO)CH.sub.3 H N CH CF.sub.3 — — — IR-36 H CF.sub.3 CH CH S(O.sub.2)CF.sub.3 1.13 558 1 IR-37 OCH.sub.3 H CH CH OCF.sub.3 1.09 472 1 (V-3) wherein CyPr = cyclopropyl and 1-CNCyPr = 1-cyanocyclopropyl

[0719] 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. 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.

[0720] The following mixtures of the compounds of formula I with active ingredients are preferred (the abbreviation “TX” means “one compound selected from the group consisting of the compounds described in Tables A-1 to A-12, B-1 to B-12, C-1 to C-18, D-1 to D-18, E-1 to E-12, F-1 to F-12, G-1 to G-18, and H-1 to H-18, and Table P of the present invention”): 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, Afoxolaner+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: 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: 2246757-58-2 (or 2249718-27-0)+TX, CAS number: 907187-07-9+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+TX, Cyflumetofen+TX, Cyfluthrin+TX, Cyhalodiamide+TX, Cyhalothrin+TX, Cypermethrin+TX, Cyphenothrin+TX, Cyproflanilide+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 (or Emamectin Benzoate)+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, Halfenprox+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, Nicofluprole+TX; Nitenpyram+TX, Nithiazine+TX, Omethoate+TX, Oxamyl+TX, Oxazosulfyl+TX, Parathion-ethyl+TX, Permethrin+TX, Phenothrin+TX, Phosphocarb+TX, Piperonylbutoxide+TX, Pirimicarb+TX, Pirimiphos-ethyl+TX, Pirimiphos-methyl+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, Pyriminostrobin+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, Tetrachlorantraniliprole+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 algaecide 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, chloethocarb (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, DClP (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;

[0721] a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580)+TX;

[0722] 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;

[0723] 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 (including alpha-bromadiolone)+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;

[0724] a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN]+TX;

[0725] a wound protectant selected from the group of substances consisting of mercuric oxide (512)+TX, octhilinone (590) and thiophanate-methyl (802)+TX;

[0726] 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, DClP+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, chloroinconazide+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, fenpropidin+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-dimethylethyl)-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-octyl-N′-[2-(octylamino)ethyl]ethane-1,2-diamine+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-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide+TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide+TX, 8-fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide+TX, 8-fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]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-((1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide+TX, N-((1S)-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 sphaericus (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 Cry1 Ab+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 lilacinus (Biostat WP®)+TX, Paecilomyces lilacinus strain 251 (MeloCon WG®)+TX, Paenibacillus polymyxa+TX, Pantoea agglomerans (BlightBan C.sub.9-1®)+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 aerofaciens (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 HC+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, Virgibacillus 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 peppermint thyme and cinnamon extracts (EF 300®)+TX, mixture of clove rosemary and peppermint extract (EF 400®)+TX, mixture of clove peppermint garlic oil and mint (Soil Shot®)+TX, kaolin (Screen®)+TX, storage glucam of brown algae (Laminarin®); pheromones including: blackheaded fireworm pheromone (3 M Sprayable Blackheaded Fireworm Pheromone®)+TX, Codling Moth Pheromone (Paramount dispenser-(CM)/Isomate C-Plus®)+TX, Grape Berry Moth Pheromone (3 M MEC-GBM Sprayable Pheromone®)+TX, Leafroller pheromone (3 M MEC-LR Sprayable Pheromone®)+TX, Muscamone (Snip7 Fly Bait®+TX, Starbar Premium Fly Bait®)+TX, Oriental Fruit Moth Pheromone (3 M oriental fruit moth sprayable Pheromone®)+TX, Peachtree Borer Pheromone (Isomate-P®)+TX, Tomato Pinworm Pheromone (3 M 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, Cynocephalus 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, Lbalia 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, Nesidiocoris 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, Rhodiola 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; 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; and a safener, such as benoxacor+TX, cloquintocet (including cloquintocet-mexyl)+TX, cyprosulfamide+TX, dichlormid+TX, fenchlorazole (including fenchlorazole-ethyl)+TX, fenclorim+TX, fluxofenim+TX, furilazole+TX, isoxadifen (including isoxadifen-ethyl)+TX, mefenpyr (including mefenpyr-diethyl)+TX, metcamifen+TX and oxabetrinil+TX.

[0727] 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.

[0728] 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.

[0729] The active ingredient mixture of the compounds of formula I selected from Tables A-1 to A-12, B-1 to B-12, C-1 to C-18, D-1 to D-18, E-1 to E-12, F-1 to F-12, G-1 to G-18, and H-1 to H-18, and Table P with active ingredients described above comprises a compound selected from Tables A-1 to A-12, B-1 to B-12, C-1 to C-18, D-1 to D-18, E-1 to E-12, F-1 to F-12, G-1 to G-18, and H-1 to H-18, and Table P 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.

[0730] 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.

[0731] The mixtures comprising a compound of formula I selected from Tables A-1 to A-12, B-1 to B-12, C-1 to C-18, D-1 to D-18, E-1 to E-12, F-1 to F-12, G-1 to G-18, and H-1 to H-18, and Table P 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 selected from Tables A-1 to A-12, B-1 to B-12, C-1 to C-18, D-1 to D-18, E-1 to E-12, F-1 to F-12, G-1 to G-18, and H-1 to H-18, and Table P and the active ingredients as described above is not essential for working the present invention.

[0732] 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, nematicides, plant activators, molluscicides or herbicides.

[0733] 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.

[0734] 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.

[0735] 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.

[0736] The compounds 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.

[0737] 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.

[0738] 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).

[0739] 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.

BIOLOGICAL EXAMPLES

[0740] The Examples which follow serve to illustrate the invention. Certain compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.

Example B1: Activity Against Bemisia tabaci (Cotton White Fly)

[0741] Cotton leaf discs were placed on 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 adult white flies. The samples were checked for mortality 6 days after incubation.

[0742] The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P1, P3, P4, P5, P6, P7, P10, P14, P15, P16, P17, P20, P26, P33, P35, P37.

Example B2: Activity Against Diabrotica balteata (Corn Root Worm)

[0743] 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.

[0744] The following compounds gave an effect of at least 80% 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, P10, P11, P12, P13, P14, P15, P16, P17, P19, P20, P21, P22, P23, P24, P26, P27, P29, P30, P31, P32, P33, P34, P35, P36, P37.

Example B3: Activity Against Euschistus heros (Neotropical Brown Stink Bug)

[0745] 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.

[0746] The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm: P1, P3, P4, P5, P6, P8, P10, P12, P14, P15, P16, P17, P19, P21, P24, P27, P33, P35, P37.

Example B4: Activity Against Frankliniella occidentalis (Western Flower Thrips)

[0747] Sunflower leaf discs were placed on 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 a Frankliniella population of mixed ages. The samples were assessed for mortality 7 days after infestation.

[0748] The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P3, P5, P10, P14, P15, P17, P27, P33, P35, P37.

Example B5: Activity Against Plutella xylostella (Diamond Back Moth)

[0749] 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.

[0750] The following compounds gave an effect of at least 80% 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, P10, P11, P12, P13, P14, P15, P16, P17, P19, P20, P21, P22, P23, P24, P26, P27, P29, P30, P31, P32, P33, P34, P35, P36.

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

[0751] 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.

[0752] The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P1, P2, P3, P4, P5, P6, P7, P10, P11, P12, P13, P14, P15, P16, P17, P19, P20, P21, P22, P23, P24, P26, P27, P29, P33, P34, P35, P36, P37.

Example B7: Activity Against Spodoptera littoralis (Egyptian Cotton Leaf Worm)

[0753] 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.

[0754] The following compounds resulted in at least 80% control at an application rate of 200 ppm: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12, P13, P14, P15, P16, P17, P19, P20, P21, P22, P23, P24, P26, P27, P29, P30, P31, P32, P33, P34, P35, P36, P37.

Example B8: Activity Against Myzus persicae (Green Peach Aphid) Systemic Activity

[0755] Roots of pea seedlings infested with an aphid population of mixed ages were placed directly into aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. The samples were assessed for mortality 6 days after placing seedlings into test solutions.

[0756] The following compounds resulted in at least 80% mortality at a test rate of 24 ppm: P13, P23, P36.

Example B9: Activity Against Tetranychus urticae (Two-Spotted Spider Mite)

[0757] Bean leaf discs on agar in 24-well microtiter plates were sprayed with aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. After drying the leaf discs were infested with a mite population of mixed ages. The samples were assessed for mortality on mixed population (mobile stages) 8 days after infestation.

[0758] The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P10, P14, P15, P16, P17, P35.

Example B10: Activity Against Chilo suppressalis (Striped Rice Stemborer)

[0759] 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.

[0760] The following compounds resulted in at least 80% control at an application rate of 200 ppm: P10, P11, P12, P17, P19, P20, P21, P22, P23, P24, P26, P27, P29, P30, P31, P32, P33, P34, P35, P36, P37.

Example B11: Activity Against Carpocapsa (Cydia) Pomonella (Codling Moth)

[0761] Diet cubes coated with paraffin were sprayed with diluted test solutions in an application chamber. After drying off the treated cubes (10 replicates) were infested with 1 L1 larvae. Samples were incubated at 26-27° C. and checked 14 days after infestation for mortality and growth inhibition. The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 12.5 ppm: P1, P2, P3, P4, P5, P6, P10, P11, P12, P14, P15, P16, P17, P19, P20, P21, P22, P24, P27, P29, P30, P33, P34, P35.

Example B12: Activity Against Diabrotica Balteata (Corn Root Worm)

[0762] Three corn seedlings were placed on wetted filter paper in plastic cups, and 3 ml of diluted test solutions were pipetted onto them. The cups were infested with 10 L2 larva and checked for mortality and growth regulation 5 days after treatment.

[0763] The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 3 ppm: P1, P2, P3, P4, P5, P6, P7, P10, P11, P12, P14, P15, P16, P17, P18, P19, P20, P21, P22, P24, P26, P27, P28, P29, P30, P32, P33, P34, P35, P37.