Pesticidally active heterocyclic derivatives with sulfur containing substituents
11440910 · 2022-09-13
Assignee
Inventors
- Sebastian RENDLER (Stein, CH)
- Andrew Edmunds (Stein, CH)
- Pierre Joseph Marcel Jung (Stein, CH)
- Michel Muehlebach (Stein, CH)
- Girish Rawal (Ilhas Goa, IN)
- Indira Sen (llhas Goa, IN)
- Vikas Sikervar (llhas Goa, IN)
Cpc classification
A01N43/90
HUMAN NECESSITIES
A01N2300/00
HUMAN NECESSITIES
C07D213/78
CHEMISTRY; METALLURGY
A01N43/90
HUMAN NECESSITIES
C07C323/62
CHEMISTRY; METALLURGY
A01N2300/00
HUMAN NECESSITIES
International classification
A01N43/90
HUMAN NECESSITIES
Abstract
Compounds of formula (I), wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides and can be prepared in a manner known per se. ##STR00001##
Claims
1. A compound of formula I, ##STR00114## wherein A is CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl or C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl; G.sub.1 is N or CH; X.sub.1 is O, S or NR.sub.3; wherein R.sub.3 is hydrogen or C.sub.1-C.sub.4alkyl; R.sub.2 is halogen, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl or C.sub.1-C.sub.6haloalkoxy; R.sub.7 is hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.8 is chlorine, bromine, iodine, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula I.
2. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein R.sub.1 is C.sub.1-C.sub.4alkyl or C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl.
3. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein R.sub.2 is halogen, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfinyl or C.sub.1-C.sub.4haloalkylsulfonyl.
4. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein R.sub.7 is hydrogen, fluoro, cyano, C.sub.1-C.sub.4alkoxycarbonyl, C.sub.1-C.sub.4alkyl.
5. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein R.sub.8 is cyano or C.sub.1-C.sub.4alkyl.
6. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein X.sub.1 is NR.sub.3, wherein R.sub.3 is C.sub.1-C.sub.4alkyl.
7. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein X is S or SO.sub.2.
8. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein R.sub.1 is C.sub.1-C.sub.4alkyl or cyclopropylmethyl and R.sub.2 is halogen or C.sub.1-C.sub.3haloalkyl.
9. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein R.sub.7 is hydrogen methyl, ethyl or fluoro and R.sub.8 is methyl or ethyl.
10. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 1 wherein A is CH or N; X is S or SO.sub.2; G.sub.1 is N or CH; X.sub.1 is NCH.sub.3; R.sub.1 is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl; R.sub.2 is C.sub.1-C.sub.2haloalkyl; R.sub.7 is methyl; and R.sub.8 is methyl or ethyl.
11. A compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, of formula I, ##STR00115## wherein A is N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl or C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl; G.sub.1 is N or CH; X.sub.1 is O, S or NR.sub.3; wherein R.sub.3 is hydrogen or C.sub.1-C.sub.4alkyl; R.sub.2 is halogen, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl or C.sub.1-C.sub.6haloalkoxy; R.sub.7 is hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.8 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl.
12. A compound of formula IX, ##STR00116## wherein A is CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl; G.sub.1 is N or CH; R.sub.3 is hydrogen or C.sub.1-C.sub.4alkyl; R.sub.2 is halogen, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl or C.sub.1-C.sub.6haloalkoxy; R.sub.7 is hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.8 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; or a regioisomer thereof, or an isomeric mixture thereof; or a compound of formula XI, ##STR00117## wherein A is CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl; R.sub.7 is hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.8 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; or a compound of formula XII, ##STR00118## wherein A is CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl; R.sub.7 is hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.8 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; or a compound of formula XIII, ##STR00119## wherein A is CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl; R.sub.7 is hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.8 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.LG is C.sub.1-C.sub.4alkyl and wherein the compound is not ##STR00120## or a compound of formula XVI, ##STR00121## wherein A is CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl; R.sub.11 is C.sub.1-C.sub.4alkyl; and R.sub.LG is C.sub.1-C.sub.4alkyl.
13. The compound of claim 12, wherein the compound is the compound of formula IX.
14. The compound of claim 13, wherein A is N; X is S or SO.sub.2; R.sub.1 is ethyl; R.sub.3 is methyl; R.sub.2 is CF.sub.3; R.sub.7 is methyl of fluoro; and R.sub.8 is methyl or fluoro.
15. The compound of claim 12, wherein the compound is the compound of formula XI.
16. The compound of claim 15, wherein A is N; X is S or SO.sub.2; R.sub.1 is ethyl; R.sub.7 is methyl of fluoro; and R.sub.8 is methyl or fluoro.
17. The compound of claim 12, wherein the compound is the compound of formula XVI.
18. The compound of claim 17, wherein A is N; X is S or SO.sub.2; R.sub.1 is ethyl; R.sub.7 is methyl of fluoro; and R.sub.8 is methyl or fluoro.
19. The compound of claim 12, wherein the compound is the compound of formula XIII.
20. The compound of claim 19, wherein A is N; X is S or SO.sub.2; R.sub.1 is ethyl; R.sub.7 is methyl of fluoro; R.sub.8 is methyl or fluoro; and R.sub.LG is methyl or ethyl.
21. The compound of claim 12, wherein the compound is the compound of formula XIII.
22. The compound of claim 21, wherein A is N; X is S or SO.sub.2; R.sub.1 is ethyl; R.sub.11 is methyl or ethyl; and R.sub.LG is methyl or ethyl.
23. A compound of formula I, ##STR00122## wherein A is CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl or C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl; G.sub.1 is N or CH; X.sub.1 is O, S or NR.sub.3; wherein R.sub.3 is hydrogen or C.sub.1-C.sub.4alkyl; R.sub.2 is halogen, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl or C.sub.1-C.sub.6haloalkoxy; R.sub.7 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and R.sub.8 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfanyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfinyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylsulfonyl-C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkyloxycarbonyl; and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula I.
24. A composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of the compound of formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, as defined in claim 23 and, optionally, an auxiliary or diluent.
25. A method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of the pest, or to a plant susceptible to attack by the pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of the compound of formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, as defined in claim 23.
26. 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 the composition according to claim 24.
27. The compound, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, according to claim 23 wherein A is CH or N; X is S or SO.sub.2; G.sub.1 is N or CH; X.sub.1 is NCH.sub.3; R.sub.1 is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl; R.sub.2 is C.sub.1-C.sub.2haloalkyl; R.sub.7 is methyl or fluoro; and R.sub.8 is fluoro, methyl or ethyl.
28. A compound selected from 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanedinitrile; 2-[5-ethylsulfonyl-6-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]-3-pyridyl]-2-methyl-propanenitrile; 2-ethyl-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]butanenitrile; 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]butanenitrile; 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanenitrile; 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanenitrile; 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanedinitrile; 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanedinitrile; ethyl 2-cyano-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanoate; 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-3-methyl-butanenitrile; 2-[3-ethylsulfanyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]-2-methyl-propanenitrile; 2-[3-ethylsulfonyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]-2-methyl-propanenitrile; 2-[3-ethylsulfanyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]propanenitrile; 2-[3-ethylsulfonyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]propanenitrile; 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2,2-difluoro-acetonitrile; 2-[3-ethylsulfanyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]phenyl]-2-methyl-propanenitrile; 2-[3-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]phenyl]-2-methyl-propanenitrile; 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-fluoro-propanenitrile; 2-[6-(6-bromo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-5-ethylsulfonyl-3-pyridyl]-2-methyl-propanenitrile; 2-[5-ethylsulfonyl-6-[3-methyl-6-(1,1,2,2,2-pentafluoroethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanenitrile; ethyl 2-cyano-2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanoate; 2-[5-ethylsulfonyl-6-(6-iodo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-3-pyridyl]-2-methyl-propanenitrile; 2-[6-(6-bromo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-5-ethylsulfanyl-3-pyridyl]-2-methyl-propanenitrile; 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanenitrile; ethyl 2-cyano-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetate; and 2-[5-ethylsulfanyl-6-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]-3-pyridyl]-2-methyl-propanenitrile.
Description
PREPARATORY EXAMPLES
(1) “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.−.
(2) LCMS Methods:
(3) Method 1: Standard 1
(4) Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions, Capillary: 3.00 kV, Cone range: 30 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650 l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment, diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 1.2 min; Flow (ml/min) 0.85.
(5) Method 2: Standard Long
(6) Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 3.00 kV, Cone range: 30V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650 l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment, diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 2.7 min; Flow (ml/min) 0.85.
(7) Method 3: Standard 2 Long
(8) Spectra were recorded on a Mass Spectrometer from Agilent Technologies (6410 Triple Quadruple Mass Spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch, Capillary: 4.00 kV, Fragmentor: 100.00 V, Gas Temperature: 350° C., Gas Flow: 11 L/min, Nebulizer Gas: 45 psi, Mass range: 110-1000 Da, DAD Wavelength range: 210-400 nm). Column: KINETEX EVO C18, length 50 mm, diameter 4.6 mm, particle size 2.6 μm. Column oven temperature 40° C. Solvent gradient: A=Water with 0.1% formic acid: Acetonitrile (95:5 v/v). B=Acetonitrile with 0.1% formic acid. Gradient=0 min 90% A, 10% B; 0.9-1.8 min 0% A, 100% B, 2.2-2.5 min 90% A, 10% B. Flow rate 1.8 mL/min.
(9) Method 4: Standard 2
(10) Spectra were recorded on a Mass Spectrometer from Waters (Acquity SDS Mass Spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch, Capillary: 3.00 kV, Cone Voltage: 41.00 V, Source temperature: 150° C., Desolvation Gas Flow: 1000 L/Hr, Desolvation temperature: 500° C., Gas Flow @Cone: 50 L/hr, Mass range: 110-800 Da, PDA wavelength range: 210-400 nm. Column: Acquity UPLC HSS T3 C18, length 30 mm, diameter 2.1 mm, particle size 1.8 μm. Column oven temperature 40° C. Solvent gradient: A=Water with 0.1% formic acid: Acetonitrile (95:5 v/v). B=Acetonitrile with 0.05% formic acid. Gradient=0 min 90% A, 10% B; 0.2 min 50% A, 50% B; 0.7-1.3 min 0% A, 100% B; 1.4-1.6 min 90% A, 10% B. Flow rate 0.8 mL/min.
Example P1: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanedinitrile (compound P1)
(11) ##STR00021##
(12) Step 1: Preparation of 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanedinitrile (compound P7)
(13) ##STR00022##
(14) A microwave vial was charged with 2-(5-bromo-3-ethylsulfanyl-2-pyridyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine (prepared according to WO16096584) (5.00 g, 12.0 mmol), propanedinitrile (0.830 ml, 13.2 mmol, 1.10 equiv.), potassium hydroxide (2.02 g, 36.0 mmol, 3.00 equiv.) and bis(triphenylphosphine)palladium(II) dichloride (420 mg, 0.60 mmol, 0.05 equiv.) After addition of N-methyl-pyrrolidone (24 mL) the reaction mixture was degassed with argon for 5 min: The vessel was sealed and heated in an oil bath at 130° C. overnight. After cooling to room temperature, the reaction mixture was poured into water, the pH was carefully acidified with 2M HCl, and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed twice with water, and these combined aqueous phases were extracted again three times with dichloromethane. A solid precipitated from the combined dichloromethane phases, which was filtered. Both ethyl acetate and dichloromethane organic phases were combined, dried over sodium sulfate, filtered and concentrated under vacuum. The crude dark brown oil was purified by column chromatography over silica gel, eluting with pure ethyl acetate. The selected fractions were evaporated to yield the title compound as a brown solid. LCMS (method 1): 403 (M+H).sup.+; retention time: 0.86 min.
(15) Step 2: Preparation of 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanedinitrile (compound P8)
(16) ##STR00023##
(17) To a of solution of 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanedinitrile (9.58 g, 10.7 mmol) in N,N-dimethylformamide (32 ml) under argon atmosphere was added potassium carbonate (1.58 g, 11.3 mmol, 1.05 equiv.), followed by dropwise addition of methyl iodide (1.00 ml, 16.1 mmol, 1.50 equiv.). The resulting brown mixture was stirred at 40° C. for 2 hours. Additional potassium carbonate (148 mg, 1.07 mmol, 0.10 equiv.) and methyl iodide (1.00 ml, 16.1 mmol, 1.50 equiv.) were added, and the reaction mixture was heated further 3 hours at 40° C. After completion of the reaction, the reaction mixture was cooled down to room temperature and diluted with water. The aqueous phase was slightly acidified with 2M HCl, and extracted twice with ethyl acetate. The combined organic phases were washed four times with water, dried over sodium sulfate, filtered and concentrated. The residue was subjected to column chromatography over silica gel, eluting with ethyl acetate in dichloromethane to yield the title compound as a tan solid. LCMS (method 1): 417 (M+H).sup.+; retention time: 1.01 min.
(18) Step 3: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanedinitrile (compound P1)
(19) ##STR00024##
(20) To a solution of 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanedinitrile (100 mg, 0.24 mmol) in dichloromethane (30 ml) under argon atmosphere at 0° C. was added 3-chloroperbenzoic acid (91 mg, 0.53 mmol, 2.2 equiv.). After stirring for 30 min at 0° C. then 1 hour at room temperature, the reaction mixture was slowly quenched by pouring into a saturated sodium thiosulfate solution. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude material was first triturated in diisopropyl ether, and the resulting white solid was further purified by column chromatography over silica gel, eluting with ethyl acetate in dichloromethane to give the title compound as a white solid. LCMS (method 1): 449 (M+H).sup.+; retention time: 0.95 min.
Example P2: Preparation of 2-[5-ethylsulfonyl-6-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]-3-pyridyl]-2-methyl-propanenitrile (compound P2)
(21) ##STR00025##
Step 1: Preparation of methyl 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carboxylate
(22) ##STR00026##
(23) Methyl 5-(cyanomethyl)-3-ethylsulfonyl-pyridine-2-carboxylate (prepared according to WO16096584) (1.40 g, 5.22 mmol) was dissolved in DMF (21 ml) under argon. The reaction mixture was cooled to 0° C., and sodium hydride (480 mg, 12.5 mmol, 2.40 equiv.) was added portionwise. The deep red reaction mixture was stirred for 30 min at 0° C. This reaction mixture was added to a solution of methyl iodide (0.78 ml, 12.5 mmol, 2.40 equiv.) in DMF (21 ml) at 0° C. via syringe. The resulting mixture was slowly allowed to warm up to room temperature and stirred overnight. After completion of the reaction, the mixture was poured into a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed four times with water and then brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography over silica gel, eluting with ethyl acetate in cyclohexane to yield the title compound as a white solid. LCMS (method 1): 297 (M+H).sup.+; retention time: 0.77 min.
(24) Step 2: Preparation of 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid
(25) ##STR00027##
(26) Methyl 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carboxylate (1.40 g, 4.72 mmol) was dissolved in tetrahydrofurane (40 ml) and water (13 ml). Lithium hydroxide (170 mg, 7.09 mmo, 1.50 equiv.) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the pH of the aqueous residue was adjusted to pH 1 with 1M HCl. The resulting white suspension was filtered, the solid washed with a minimum of cold water and dried under vacuum, giving the desired product. The compound was used directly in the next step without further purification. LCMS (method 1): 283 (M+H).sup.+; retention time: 0.42 min.
(27) Step 3: Preparation of 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carbonyl chloride
(28) ##STR00028##
(29) 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid (1.02 g, 3.61 mmol) was dissolved in dichloromethane (24 ml) under argon, along with a catalytic amount of N,N-dimethylformamide. Oxalyl chloride (0.47 ml, 5.42 mmol, 1.50 equiv.) was added dropwise via syringe. The reaction mixture was then heated at reflux for 3 hours. After cooling down to room temperature, the reaction mixture was evaporated to dryness. The resulting brown oil was used in the next step directly.
(30) Step 4: Preparation of 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-N-[3-(methylamino)-6-(trifluoromethyl)pyridazin-4-yl]pyridine-2-carboxamide
(31) ##STR00029##
(32) N-3-methyl-6-(trifluoromethyl)pyridazine-3,4-diamine (prepared according to WO2016/116338) (150 mg, 0.78 mmol) was dissolved in tetrahydrofuran (5.0 ml) along with N,N′-diisopropylethylamine. The reaction mixture was cooled to 0° C., and a solution of 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carbonyl chloride (258 mg, 1.1 equiv.) in tetrahydrofuran (5.0 ml) was added dropwise. The reaction mixture was slowly warmed up to room temperature and stirred overnight. The reaction was slowly quenched by addition of a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with water, brine, dried over sodium sulfate, filtered and concentrated. The crude material was used in the next step directly without purification. LCMS (method 1): 425 (M+H).sup.+; retention time: 1.03 min.
(33) Step 5: Preparation of 2-[5-ethylsulfonyl-6-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]-3-pyridyl]-2-methyl-propanenitrile
(34) ##STR00030##
(35) 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfonyl-N-[3-(methylamino)-6-(trifluoromethyl)pyridazin-4-yl]pyridine-2-carboxamide (250 mg, 0.55 mmol) was dissolved in acetic acid (1.64 ml) and the reaction mixture was heated to 100° C. for 5 hours. The reaction mixture was concentrated, and the residue was evaporated with toluene to remove the excess of acetic acid. The crude material was purified by column chromatography over silica gel, eluting with ethyl acetate in cyclohexane followed by trituration in diethyl ether to yield the title compound as a white solid. LCMS (method 1): 439 (M+H).sup.+; retention time: 0.93 min.
Example P3: Preparation of 2-ethyl-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]butanenitrile (compound P3)
(36) ##STR00031##
Step 1: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetonitrile
(37) ##STR00032##
(38) A microwave vial was charged with a solution of 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine (prepared according to WO16096584) (6.00 g, 13.4 mmol) in N,N-dimethylformamide (27 ml). To this solution under argon atmosphere, trimethylsilyl acetonitrile (2.77 ml, 20.0 mmol, 1.50 equiv.), zinc fluoride (837 mg, 8.01 mmol, 0.60 equiv.), xantphos (315 mg, 0.53 mmol, 0.04 equiv.) and Pd.sub.2(dba).sub.3 (250 mg, 0.27 mmol, 0.02 equiv.) were added. The vial was sealed and heated at 140° C. for 30 min in the microwave. The reaction mixture was diluted with ethyl acetate, washed three times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography over silica gel, eluting with methanol in dichloromethane, to yield the title compound as a white solid. LCMS (method 1): 410 (M+H).sup.+; retention time: 0.86 min.
(39) Step 2: Preparation of 2-ethyl-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]butanenitrile
(40) ##STR00033##
(41) 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetonitrile (500 mg, 1.22 mmol) was dissolved in N,N-dimethylformamide (5 ml) under argon. The reaction mixture was cooled down to 0° C. Sodium hydride (66 mg, 1.71 mmol, 1.40 equiv.) was added carefully portionwise. The deep red reaction mixture was stirred at 0° C. for 30 min. The obtained solution was added to a solution of ethyl iodide (0.137 ml, 1.71 mmol, 1.40 equiv.) in DMF (5 ml) under argon at 0° C. via syringe. The resulting mixture was slowly warmed up to room temperature and stirred overnight. The mixture was then poured slowly into a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed four times with water then brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography over silica gel, eluting with ethyl acetate in cyclohexane to yield the title compound as a white solid. LCMS (method 1): 466 (M+H).sup.+; retention time: 1.02 min.
Example P4: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]butanenitrile (compound P4)
(42) ##STR00034##
(43) 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetonitrile (prepared as described in step 1 of EXAMPLE P3) (500 mg, 1.22 mmol) was dissolved in N,N-dimethylformamide (5 ml) under argon. The reaction mixture was cooled down to 0° C. Sodium hydride (66 mg, 1.71 mmol, 1.40 equiv.) was added carefully portionwise. The deep red reaction mixture was stirred at 0° C. for 30 min. The obtained reaction mixture was added dropwise to a solution of ethyl iodide (0.137 ml, 1.71 mmol, 1.40 equiv.) in DMF (5 ml) under argon at 0° C. The resulting mixture was slowly warmed up to room temperature and stirred overnight. The mixture was then poured slowly into a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed four times with water then brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography over silica gel, eluting with ethyl acetate in cyclohexane to yield the title compound as a white solid. LCMS (method 1): 438 (M+H).sup.+; retention time: 0.94 min.
Example P5: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanenitrile (compound P5)
(44) ##STR00035##
(45) 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetonitrile (prepared as described in step 1 of EXAMPLE P3) (400 mg, 0.98 mmol) was dissolved in N,N-dimethylformamide (4 ml) under argon. The reaction mixture was cooled down to 0° C. Sodium hydride (52 mg, 1.37 mmol, 1.40 equiv.) was added carefully portionwise. The deep red reaction mixture was stirred at 0° C. for 30 min. The obtained mixture was added to a solution of methyl iodide (0.085 ml, 1.37 mmol, 1.40 equiv.) in DMF (4 ml) under argon at 0° C. The resulting mixture was slowly warmed up to room temperature and stirred overnight. The mixture was then poured slowly into a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed four times with water then brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography over silica gel, eluting with ethyl acetate in cyclohexane to yield the title compound as a white solid. LCMS (method 1): 438 (M+H).sup.+; retention time: 0.93 min.
Example P6: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanenitrile (compound P6)
(46) ##STR00036##
(47) 22-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetonitrile (prepared as described in step 1 of EXAMPLE P3) (400 mg, 0.98 mmol) was dissolved in N,N-dimethylformamide (4 ml) under argon. The reaction mixture was cooled down to 0° C. Sodium hydride (52 mg, 1.37 mmol, 1.40 equiv.) was added carefully portionwise. The deep red reaction mixture was stirred at 0° C. for 30 min. The obtained mixture was added to a solution of methyl iodide (0.085 ml, 1.37 mmol, 1.40 equiv.) in DMF (4 ml) under argon at 0° C. The resulting mixture was slowly warmed up to room temperature and stirred overnight. The mixture was then poured slowly into a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed four times with water then brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography over silica gel, eluting with ethyl acetate in cyclohexane to yield the title compound as a white solid. LCMS (method 1): 424 (M+H).sup.+; retention time: 1.32 min.
(48) Alternative procedure for the preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanenitrile (compound P6):
(49) To a solution of ethyl 2-cyano-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanoate (compound P9) (250 mg, 0.505 mmol, 1.00 equiv.) in DMSO (2.0 mL) was added sodium chloride (298 mg, 5.05 mmoL, 10.0 equiv.) in water (1.0 mL) and the obtained reaction mixture was heated to 120° C. for 2 h. After cooling to room temp. the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered and concentrated in vacuo to give the crude product. Purification by flash chromatography (SiO2, 30% ethyl acetate/cyclohexane) furnished the desired product. LCMS (method 4): 424 (M+H).sup.+; retention time: 0.91 min.
Example P9: Preparation of ethyl 2-cyano-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[. 4,5-c]pyridin-2-yl]-3-pyridyl]propanoate (compound P9)
(50) ##STR00037##
Step 1: Preparation of ethyl 2-cyano-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetate (compound P25):
(51) ##STR00038##
(52) To a solution of 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine (prepared according to WO16096584) (5.40 g, 11.1 mmol, 1.00 equiv.) in DMSO (50 mL) was added ethyl 2-cyanoacetate (3.85 g, 33.3 mmol, 3.00 equiv.) followed by potassium carbonate (3.89 g, 27.8 mmol, 2.50 equiv.), L-proline (261 mg, 2.23 mmol, 0.200 equiv.) and copper(I) iodide (212 mg, 1.11 mmol, 0.100 equiv.). The raction mixture was heated to 150° C. for 3.5 h. After cooling to room temp. the reaction mixture was acidified with 2N HCl solution (50 mL), extracted with ethyl acetate (3×100 mL) and the combined organic layers were washed with brine, dried (sodium sulfate), filtered and contracted under reduced pressure to obtain the desired product. LCMS (method 4): 482 (M+H).sup.+; retention time: 0.95 min.
(53) Step 2: Preparation of ethyl 2-cyano-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]propanoate (corn pound P9)
(54) ##STR00039##
(55) To a solution of ethyl 2-cyano-2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetate (500 mg, 1.04 mmol, 1.00 equiv.) in DMF (6.0 mL) was added potassium carbonate (175 mg, 1.25 mmol, 1.20 equiv.) and iodomethane (78 μL, 180 mg, 1.25 mmol, 1.20 equiv.). The obtained reaction mixture was stirred at room temp. overnight. Subsequently, the reaction mixture was diluted with water (30 mL), extracted with ethyl acetate (3×30 mL) and the combined organic layers were dried over sodium sulfate, filtered and contracted under reduced pressure. The crude product was purified by flash chromatography (30% ethyl acetate/cyclohexane) to afford the title compound. LCMS (method 4): 496 (M+H).sup.+; retention time: 1.00 min.
Example P11: Preparation of 2-[3-ethylsulfanyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]-2-methyl-propanenitrile (compound P11)
(56) ##STR00040##
Step 1: Preparation of 4-bromo-2-ethylsulfanyl-N-[3-(methylamino)-6-(trifluoromethyl)pyridazin-4-yl]benzamide
(57) ##STR00041##
(58) To a solution of N-3-methyl-6-(trifluoromethyl)pyridazine-3,4-diamine (800 mg, 4.16 mmol, 1.00 equiv.) and in tetrahydrofuran (15 mL) was added N,N-diisopropylethylamine (1.07 mL, 807 mg, 6.25 mmol, 1.50 equiv.). The reaction mixture was cooled to 0° C. and a solution of 4-bromo-2-ethylsulfanyl-benzoyl chloride (prepared according to WO2016/026848) (1.28 g, 4.58 mmol, 1.10 equiv.) in tetrahydrofuran (15 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature and stirred overnight. The reaction was slowly quenched by addition of a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with water, brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography (SiO.sub.2, ethyl acetate/cyclohexane) to afford the title compound. LCMS (method 1): 435 (M+H).sup.+; retention time: 1.05 min.
(59) Step 2: Preparation of 6-(4-bromo-2-ethylsulfanyl-phenyl)-7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazine
(60) ##STR00042##
(61) A round bottom flask equipped with reflux condenser and stir bar was charged with a solution of 4-bromo-2-ethylsulfanyl-N-[3-(methylamino)-6-(trifluoromethyl)pyridazin-4-yl]benzamide (4.40 g, 10.1 mmol, 1.00 equiv.) in glacial acetic acid (30 mL) and the reaction mixture was heated to 100° C. for 5 h. After cooling to room temp. the reaction mixture was concentrated in vacuo and remaining acetic acid was removed by repeated azeotropic distillation with toluene. The obtained crude product was purified by flash chromatography (SiO2, ethyl acetate/cyclohexane) to furnish the title compound. LCMS (method 1): 417 (M+H).sup.+; retention time: 1.09 min.
(62) Step 3: Preparation of 2-[3-ethylsulfanyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]acetonitrile
(63) ##STR00043##
(64) Under an argon atmosphere, a 3-neck-flask equipped with stir bar and reflux condenser was charged with a solution of 6-(4-bromo-2-ethylsulfanyl-phenyl)-7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazine (1.30 g, 3.12 mmol, 1.00 equiv.) in N,N-dimethylacetamide (16 mL). To this solution, trimethylsilyl acetonitrile (1.32 mL, 9.35 mmol, 3.00 equiv.), zinc fluoride (193 mg, 1.87 mmol, 0.60 equiv.), Xantphos (73.6 mg, 0.125 mmol, 0.0400 equiv.) and Pd.sub.2(dba).sub.3 (44.6 mg, 0.046 mmol, 0.015 equiv.) were added. The reaction mixture was heated to 100° C. for 7 h. After cooling to room temp., the reaction mixture was diluted with ethyl acetate, filtered through a plug of Celite and washed three times with water and once with brine. The organic layers were dried over sodium sulfate, filtered and concentrated. The crude material was purified by flash column chromatography (SiO.sub.2, ethyl acetate/cyclohexane) to furnish the title compound. LCMS (method 1): 378 (M+H).sup.+; retention time: 0.96 min.
(65) Step 4: Preparation of 2-[3-ethylsulfanyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]-2-methyl-propanenitrile (compound P11)
(66) ##STR00044##
(67) A solution of 2-[3-ethylsulfanyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]acetonitrile (192 mg, 0.509 mmol, 1.00 equiv.) in N,N-dimethylformamide (4 mL) under argon atmosphere was cooled to at 0° C. At this temperature, sodium hydride (60 wt-% in mineral oil, 273 mg, 0.712 mmol, 1.40 equiv.) was added portionwise. The deep red reaction mixture was stirred at 0° C. for 30 min. The obtained mixture was added via syringe to a solution of methyl iodide (44 μl, 101 mg, 0.712 mmol, 1.40 equiv.) in DMF (4 mL) under argon at 0° C. The resulting mixture was slowly warmed up to room temperature and stirred overnight. The mixture was then poured slowly into a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed four times with water then brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography over silica gel, eluting with ethyl acetate in cyclohexane to yield the title compound. LCMS (method 1): 406 (M+H).sup.+; retention time: 1.03 min.
Example P12: Preparation of 2-[3-ethylsulfonyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]-2-methyl-propanenitrile (compound P12)
(68) ##STR00045##
(69) To a solution of 2-[3-ethylsulfanyl-4-[7-methyl-3-(trifluoromethyl)imidazo[4,5-c]pyridazin-6-yl]phenyl]-2-methyl-propanenitrile (compound P11) (74.0 mg, 0.183 mmol, 1.00 equiv.) in dichloromethane (2.0 mL) was added 3-chloroperbenzoic acid (75 wt-%, 92.4 mg, 0.384 mmol, 2.10 equiv) at room temperature. Stirring was continued for 18 h at room temperature before addition of a saturated solution of sodium thiosulfate (10 mL) and saturated NaHCO.sub.3 (10 mL). The reaction mixture was diluted with dichloromethane (50 mL), and the mixture was stirred for 20 min. After separation of the aqueous layer, extraction with dichloromethane (3×20 mL), the combined organic layers were washed with water and brine, dried (Na.sub.2SO.sub.4), and concentrated under reduced pressure. The obtained crude material was purified by flash chromatography (SiO.sub.2, ethyl acetate/cyclohexane) to furnish the title compound. LCMS (method 1): 438 (M+H).sup.+; retention time: 0.93 min.
Example P15: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2,2-difluoro-acetonitrile (compound P15)
(70) ##STR00046##
(71) To a solution of 2-[5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]acetonitrile (see example P3, step 1) (409 mg, 1.00 mmol, 1.00 equiv.) in tetrahydrofuran (6.0 mL), was added Cs.sub.2CO.sub.3 (391 mg, 1.20 mmol, 1.00 equiv.) followed by N-Fluorobenzenesulfonimide (315 mg, 1.00 mmol, 1.00 equiv.) under nitrogen. The reaction mixture was stirred at room temp. for 1 h. The obtained reaction mixture was diluted ethyl acetate (30 mL) and water (30 mL). After extraction with ethyl acetate (3×30 mL), the combined organic layers were washed with water (2×30 mL) and dried with sodium sulfate. Concentration under reduced pressure and purification by flash chromatography (SiO.sub.2, ethyl acetate/cyclohexane) furnished the title compound as a white solid. LCMS (method 4): 446 (M+H).sup.+; retention time: 1.05 min.
Example P16: Preparation of 2-[3-ethylsulfanyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]phenyl]-2-methyl-propanenitrile (compound P16)
(72) ##STR00047##
(73) A microwave vial was charged with 2-(4-bromo-2-ethylsulfanyl-phenyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine (prepared according to WO2016/026848) (500 mg, 1.20 mmol, 1.00 equiv.), rac-BINAP (77.1 mg, .0120 mmol, 0.10 equiv.), and Pd.sub.2(dba).sub.3 (56.7 mg, 0.0600 mmol, 0.0500 equiv.). After flushing with argon, tetrahydrofuran (THF) (1.20 mL) and cyclopentylmethylether (CPME) (1.20 mL) followed by isobutyronitrile (119 μL, 91.7 mg, 1.32 mmol, 1.10 equiv.) were added. The vial was capped under argon atmosphere and the obtained solution was cooled to −25° C. After stirring for 25 min, LiHMDS (1M solution in THF, 1.32 mL, 1.32 mmol, 1.10 equiv.) was added dropwise over 5 min. The obtained solution was allowed to warm to room temperature before heating to 80° C. for 4 h. After cooling to room temp. the reaction mixture was quenched with water, filtered through a plug of celite and rinsed with ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×), and the combined organic layers were washed with water and brine. Drying over sodium sulfate, filtration and concentration in vacuo furnished the crude material which was purified by flash chromatography (SiO.sub.2, ethyl acetate/cyclohexane) to furnish the title compound. LCMS (method 1): 405 (M+H).sup.+; retention time: 1.02 min.
Example P17: Preparation of 2-[3-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]phenyl]-2-methyl-propanenitrile (compound P17)
(74) ##STR00048##
(75) To a solution of 2-[3-ethylsulfanyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]phenyl]-2-methyl-propanenitrile (compound P16) (88.8 mg, 0.220 mmol, 1.00 equiv.) in dichloromethane (1.0 mL) was added 3-chloroperbenzoic acid (75 wt-%, 103 mg, 0.461 mmol, 2.10 equiv) at room temperature. Stirring was continued for 18 h at room temperature before addition of a saturated solution of sodium thiosulfate (5 mL) and saturated NaHCO.sub.3 (5 mL). The reaction mixture was diluted with dichloromethane (15 mL), and the mixture was stirred for 20 min. After separation of the aqueous layer, extraction with dichloromethane (3×10 mL), the combined organic layers were washed with water and brine, dried (Na.sub.2SO.sub.4), and concentrated under reduced pressure. The obtained crude material was purified by flash chromatography (SiO.sub.2, MeOH/dichloromethane) to furnish the title compound. LCMS (method 1): 437 (M+H).sup.+; retention time: 0.90 min.
Example P19: Preparation of 2-[6-(6-bromo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-5-ethylsulfonyl-3-pyridyl]-2-methyl-propanenitrile (compound P19)
(76) ##STR00049##
Step 1: Preparation of methyl 5-(1-cyano-2-ethoxy-2-oxo-ethyl)-3-ethylsulfanyl-pyridine-2-carboxylate
(77) ##STR00050##
(78) To a solution of methyl 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate (prepared according to WO2017/055147) (32.0 g, 116 mmol, 1.00 equiv.) in DMSO (350 mL) was added ethyl 2-cyanoacetate (18.5 mL, 19.7 g, 174 mmol, 1.50 equiv.), K.sub.2CO.sub.3 (40.4 g, 290 mmol, 2.50 equiv.) and tetrabutylammonium bromide (3.81 g, 11.6 mmol, 0.100 equiv.). The resulting suspension was heated to 90° C. overnight. After cooling to room temp., the reaction mixture was diluted with water (150 mL) and ethyl acetate (300 mL) and cooled to 0° C. To the stirred mixture, 2M HCl (200 mL) was added slowly (exothermic reaction) until pH 4-5 was reached. The aqueous layer was separated and extracted with ethyl acetate (3×500 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo to obtain the crude material. Recrystallization from ethanol furnished the title compound as a tan solid. LCMS (method 1): 309 (M+H).sup.+; retention time: 0.86 min.
(79) Step 2: Preparation of methyl 5-(cyanomethyl)-3-ethylsulfanyl-pyridine-2-carboxylate
(80) ##STR00051##
(81) In a 3-neck-flask equipped with magnetic stir bar and reflux condenser and gas exhaust, to a solution of methyl 5-(1-cyano-2-ethoxy-2-oxo-ethyl)-3-ethylsulfanyl-pyridine-2-carboxylate (21.1 g, 68.4 mmol, 1.00 equiv.) in DMSO (210 mL) was first added sodium chloride (40.0 g, 684 mmol, 10.0 equiv.) followed by water (105 mL). The reaction mixture was heated to 125° C. internal temperature at which temperature strong gas evolution set in. Stirring was continued for 3 h. After cooling to room temp. the reaction mixture was diluted with water (50 mL) and ethyl acetate (100 mL) was added. The aqueous layer was separated, extracted with ethyl acetate (3×200 mL) and the combined organic layers were washed with water, dried (Na.sub.2SO.sub.4) and concentrated in vacuo to afford the crude material. The crude product was directly used as obtained. LCMS (method 1): 237 (M+H).sup.+; retention time: 0.72 min
(82) Step 3: Preparation of 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfanyl-pyridine-2-carboxylic acid
(83) ##STR00052##
(84) To a solution of methyl 5-(cyanomethyl)-3-ethylsulfanyl-pyridine-2-carboxylate (20.0 g, 84.6 mmol, 1.00 equiv.) in 1,4-dioxane (170 mL) was added benzyltrimethylammonium chloride (998 mg, 4.23 mmol, 0.0500 equiv.) and the obtained solution was cooled to 0° C. This this solution, aqueous NaOH (30 wt %, 59 mL, 590 mmol, 7.0 equiv.) was added slowly followed by dropwise addition of iodomethane (10.5 mL, 24.0 g, 169 mmol, 2.00 equiv.) while maintaining the temperature between 0 and 5° C. Stirring at 0° C. was continued for 5 h before quenching the reaction mixture by slow addition of 2M HCl until pH 5 was reached. After addition of ethyl acetate (250 mL) and stirring for 30 min, the layers were separated and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried (Na.sub.2SO.sub.4) and evaporated. The crude material was purified by flash chromatography (SiO.sub.2, ethyl acetate/cyclohexane) to furnish the title compound. LCMS (method 1): 251 (M+H).sup.+; retention time: 0.71 min.
(85) Step 4: Preparation of N-[2-bromo-5-(methylamino)-4-pyridyl]-5-(1-cyano-1-methyl-ethyl)-3-ethylsulfanyl-pyridine-2-carboxamide
(86) ##STR00053##
(87) To a solution of 5-(1-cyano-1-methyl-ethyl)-3-ethylsulfanyl-pyridine-2-carboxylic acid (10.0 g, 40.0 mmol, 1.00 equiv.) and a catalytic amount of N,N-dimethylformamide in dichloromethane (24 mL) under argon was added oxalyl chloride (5.23 mL, 7.61 g, 59.9 mmol, 1.50 equiv.) dropwise via syringe. The reaction mixture was then heated to reflux for 3 h. After cooling to room temperature, the reaction mixture was evaporated to dryness. The resulting brown oil was dissolved in THF (190 mL) and slowly added at 0° C. via dropping funnel to a solution of 6-bromo-N3-methyl-pyridine-3,4-diamine (prepared according to WO2016/107831) (8.43 g, 41.7 mmol, 1.04 equiv.) and N,N-diisopropylethylamine (16.7 mL, 12.4 g, 94.9 mmol, 2.54 equiv.) in THF (300 mL). The reaction was allowed to warm to room temp. and stirring was continued for 20 h. The reaction was slowly quenched by addition of a saturated aqueous ammonium chloride solution, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with water, brine, dried over sodium sulfate, filtered and concentrated to furnish the title compound as a crude product. LCMS (method 1): 434 (M+H).sup.+; retention time: 0.82 min.
(88) Step 5: Preparation of 2-[6-(6-bromo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-5-ethylsulfanyl-3-pyridyl]-2-methyl-propanenitrile (compound P23)
(89) ##STR00054##
(90) A round bottom flask equipped with reflux condenser and stir bar was charged with a solution of N-[2-bromo-5-(methylamino)-4-pyridyl]-5-(1-cyano-1-methyl-ethyl)-3-ethylsulfanyl-pyridine-2-carboxamide (13.0 g, 29.9 mmol, 1.00 equiv) in glacial acetic acid (90 mL) and the reaction mixture was heated to 100° C. for 5 h. After cooling to room temp. the reaction mixture was concentrated in vacuo and remaining acetic acid was removed by repeated azeotropic distillation with toluene. The obtained crude product was purified by flash chromatography (SiO.sub.2, ethyl acetate/cyclohexane) to furnish the title compound. LCMS (method 1): 416 (M+H).sup.+; retention time: 0.94 min.
(91) Step 6: Preparation of 2-[6-(6-bromo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-5-ethylsulfonyl-3-pyridyl]-2-methyl-propanenitrile (compound P19)
(92) ##STR00055##
(93) To a solution of 2-[6-(6-bromo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-5-ethylsulfanyl-3-pyridyl]-2-methyl-propanenitrile (compound P23) (7.10 g, 17.1 mmol, 1.00 equiv.) in dichloromethane (171 mL) was added 3-chloroperbenzoic acid (75 wt-%, 8.04 g, 35.0 mmol, 2.05 equiv) in small portions (exothermic reaction) at 0° C. The reaction mixture was allowed to warm to room temperature and stirring was continued for 18 h at room temperature before addition of a saturated solution of sodium thiosulfate (100 mL) and saturated NaHCO.sub.3 (100 mL). The reaction mixture was diluted with dichloromethane (150 mL), and the mixture was stirred for 20 min. After separation of the aqueous layer, extraction with dichloromethane (3×10 mL), the combined organic layers were washed with of saturated sodium thiosulfate (50 mL), saturated NaHCO.sub.3 (50 mL), followed by water (50 mL) and brine (50 mL). Drying (Na.sub.2SO.sub.4) and concentration under reduced pressure yielded a crude material which was purified by flash chromatography (SiO.sub.2, MeOH/dichloromethane) to furnish the title compound. LCMS (method 1): 448 (M+H).sup.+; retention time: 0.88 min.
Example P20: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(1,1,2,2,2-pentafluoroethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanenitrile (compound P20)
(94) ##STR00056##
Step 1: Preparation of 2-[5-ethylsulfonyl-6-(6-iodo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-3-pyridyl]-2-methyl-propanenitrile (compound P22)
(95) ##STR00057##
(96) To a solution of 2-[6-(6-bromo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-5-ethylsulfonyl-3-pyridyl]-2-methyl-propanenitrile (compound P19) (1.00 g, 2.23 mmol, 1.00 equiv.) in 1,4-dioxane (11 mL) was added Nal (689 mg, 4.46 mmol, 2.00 equiv.), Cul (224 mg, 1.12 mmol, 0500 equiv.) and N,N′-dimethylethylendiamine (DMEDA) (0.29 mL, 0.24 g, 2.7 mmol, 1.2 equiv.). The reaction mixture was heated to 100° C. for 40 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL) and a 1M aqueous solution of NH.sub.3 was added. The aqueous layer was separated and extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with sat. NaHCO.sub.3, water and brine, and dried (Na.sub.2SO.sub.4). Concentration under reduced pressure furnished the title compound. LCMS (method 1): 496 (M+H).sup.+; retention time: 0.90 min.
(97) Step 2: Preparation of 2-[5-ethylsulfonyl-6-[3-methyl-6-(1,1,2,2,2-pentafluoroethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanenitrile (compound P20)
(98) ##STR00058##
(99) To a solution of 2-[5-ethylsulfonyl-6-(6-iodo-3-methyl-imidazo[4,5-c]pyridin-2-yl)-3-pyridyl]-2-methyl-propanenitrile (compound P22) (900 mg, 1.82 mmol, 1.00 equiv.) in DMF (6.5 mL) under an argon atmosphere was added (phen)CuC.sub.2F.sub.5 [1360806-59-2]. The stirred reaction mixture was heated to 90° C. for 2 h. After cooling to room temperature, the reaction mixture filtered over Celite and rinsed with ethyl acetate. The filtrate was washed with 28% aqueous ammonia (20 mL), sat. NaHCO.sub.3 (20 mL), water (20 mL) and brine (20 mL). Drying over sodium sulfate, filtration and concentration under reduced pressure furnished the crude product. Purification by flash chromatography (SiO.sub.2, ethyl acetate/cyclohexane) yielded the title compound as a white solid. LCMS (method 1): 488 (M+H).sup.+; retention time: 1.00 min.
Example P23: Preparation of 2-[5-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-3-pyridyl]-2-methyl-propanenitrile (compound P23)
(100) ##STR00059##
(101) A three-neck flask equipped with dropping funnel and argon inlet was charged with isobutyronitrile (4.30 mL, 3.31 g, 47.9 mmol, 2.00 equiv) and cooled to −25° C. At this temperature, LiHMDS (1.0M solution in THF, 72 mL, 64 g, 72 mmol, 3.0 equiv.) was added dropwise over 30 min while the stirred reaction mixture was kept at −25° C. Stirring at this temperature was continued for another 15 min. The obtained solution was then added dropwise to a stirred solution of 2-(5-bromo-3-ethylsulfanyl-2-pyridyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine (prepared according to WO2016/026848) (10.0 g, 24.0 mmol, 1.00 equiv.) in THF (50 mL) at −25° C. over a period of 1.5 h. Stirring at this temperature was continued for an additional 30 min before allowing to warm up to room temperature. After further 1 h at this temperature, the reaction mixture was quenched by slow addition of water (50 mL) and ethyl acetate (100 mL). The aqueous layer was separated and extracted with ethyl acetate (2×50 mL) and the combined organic layers were washed with brine and dried over sodium sulfate. Concentration in vacuo and purification by flash chromatography furnished the desired title compound. LCMS (method 1): 406 (M+H).sup.+; retention time: 0.99 min.
(102) TABLE-US-00012 TABLE 4 Examples of compounds of formula (I) Compound Melting No. IUPAC Name Structure Point MS/NMR P1 2-[5-ethylsulfonyl-6-[3- methyl-6- (trifluoromethyl)imidazo [4,5-c]pyridin-2-yl]-3- pyridyl]-2-methyl- propanedinitrile
(103) TABLE-US-00013 TABLE I1 Examples of novel intermediate compounds of formula (XVI), (XIV), (XII), (XI), (XIII), (IX), and (II): Compound Melting No. IUPAC Name Structure Point MS/NMR XVI-1 5-(1-cyano-1-methyl- ethyl)-3-ethylsulfonyl- pyridine-2-carboxylic acid
(104) 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 1-4 of the present invention”):
(105) an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628)+TX,
(106) an acaricide selected from the group of substances consisting of 1,1-bis(4-chlorophenyl)-2-ethoxyethanol (IUPAC name) (910)+TX, 2,4-dichlorophenyl benzenesulfonate (IUPAC/Chemical Abstracts name) (1059)+TX, 2-fluoro-N-methyl-N-1-naphthylacetamide (IUPAC name) (1295)+TX, 4-chlorophenyl phenyl sulfone (IUPAC name) (981)+TX, abamectin (1)+TX, acequinocyl (3)+TX, acetoprole [CCN]+TX, acrinathrin (9)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, alpha-cypermethrin (202)+TX, amidithion (870)+TX, amidoflumet [CCN]+TX, amidothioate (872)+TX, amiton (875)+TX, amiton hydrogen oxalate (875)+TX, amitraz (24)+TX, aramite (881)+TX, arsenous oxide (882)+TX, AVI 382 (compound code)+TX, AZ 60541 (compound code)+TX, azinphos-ethyl (44)+TX, azinphos-methyl (45)+TX, azobenzene (IUPAC name) (888)+TX, azocyclotin (46)+TX, azothoate (889)+TX, benomyl (62)+TX, benoxafos (alternative name) [CCN]+TX, benzoximate (71)+TX, benzyl benzoate (IUPAC name) [CCN]+TX, bifenazate (74)+TX, bifenthrin (76)+TX, binapacryl (907)+TX, brofenvalerate (alternative name)+TX, bromo-cyclen (918)+TX, bromophos (920)+TX, bromophos-ethyl (921)+TX, bromopropylate (94)+TX, buprofezin (99)+TX, butocarboxim (103)+TX, butoxycarboxim (104)+TX, butylpyridaben (alternative name)+TX, calcium polysulfide (IUPAC name) (111)+TX, camphechlor (941)+TX, carbanolate (943)+TX, carbaryl (115)+TX, carbofuran (118)+TX, carbophenothion (947)+TX, CGA 50′439 (development code) (125)+TX, chinomethionat (126)+TX, chlorbenside (959)+TX, chlordimeform (964)+TX, chlordimeform hydrochloride (964)+TX, chlorfenapyr (130)+TX, chlorfenethol (968)+TX, chlorfenson (970)+TX, chlorfensulfide (971)+TX, chlorfenvinphos (131)+TX, chlorobenzilate (975)+TX, chloromebuform (977)+TX, chloromethiuron (978)+TX, chloropropylate (983)+TX, chlorpyrifos (145)+TX, chlorpyrifos-methyl (146)+TX, chlorthiophos (994)+TX, cinerin I (696)+TX, cinerin II (696)+TX, cinerins (696)+TX, clofentezine (158)+TX, closantel (alternative name) [CCN]+TX, coumaphos (174)+TX, crotamiton (alternative name) [CCN]+TX, crotoxyphos (1010)+TX, cufraneb (1013)+TX, cyanthoate (1020)+TX, cyflumetofen (CAS Reg. No.: 400882-07-7)+TX, cyhalothrin (196)+TX, cyhexatin (199)+TX, cypermethrin (201)+TX, DCPM (1032)+TX, DDT (219)+TX, demephion (1037)+TX, demephion-O (1037)+TX, demephion-S (1037)+TX, demeton (1038)+TX, demeton-methyl (224)+TX, demeton-O (1038)+TX, demeton-O-methyl (224)+TX, demeton-S (1038)+TX, demeton-S-methyl (224)+TX, demeton-S-methylsulfon (1039)+TX, diafenthiuron (226)+TX, dialifos (1042)+TX, diazinon (227)+TX, dichlofluanid (230)+TX, dichlorvos (236)+TX, dicliphos (alternative name)+TX, dicofol (242)+TX, dicrotophos (243)+TX, dienochlor (1071)+TX, dimefox (1081)+TX, dimethoate (262)+TX, dinactin (alternative name) (653)+TX, dinex (1089)+TX, dinex-diclexine (1089)+TX, dinobuton (269)+TX, dinocap (270)+TX, dinocap-4 [CCN]+TX, dinocap-6 [CCN]+TX, dinocton (1090)+TX, dinopenton (1092)+TX, dinosulfon (1097)+TX, dinoterbon (1098)+TX, dioxathion (1102)+TX, diphenyl sulfone (IUPAC name) (1103)+TX, disulfiram (alternative name) [CCN]+TX, disulfoton (278)+TX, DNOC (282)+TX, dofenapyn (1113)+TX, doramectin (alternative name) [CCN]+TX, endosulfan (294)+TX, endothion (1121)+TX, EPN (297)+TX, eprinomectin (alternative name) [CCN]+TX, ethion (309)+TX, ethoate-methyl (1134)+TX, etoxazole (320)+TX, etrimfos (1142)+TX, fenazaflor (1147)+TX, fenazaquin (328)+TX, fenbutatin oxide (330)+TX, fenothiocarb (337)+TX, fenpropathrin (342)+TX, fenpyrad (alternative name)+TX, fenpyroximate (345)+TX, fenson (1157)+TX, fentrifanil (1161)+TX, fenvalerate (349)+TX, fipronil (354)+TX, fluacrypyrim (360)+TX, fluazuron (1166)+TX, flubenzimine (1167)+TX, flucycloxuron (366)+TX, flucythrinate (367)+TX, fluenetil (1169)+TX, flufenoxuron (370)+TX, flumethrin (372)+TX, fluorbenside (1174)+TX, fluvalinate (1184)+TX, FMC 1137 (development code) (1185)+TX, formetanate (405)+TX, formetanate hydrochloride (405)+TX, formothion (1192)+TX, formparanate (1193)+TX, gamma-HCH (430)+TX, glyodin (1205)+TX, halfenprox (424)+TX, heptenophos (432)+TX, hexadecyl cyclopropanecarboxylate (IUPAC/Chemical Abstracts name) (1216)+TX, hexythiazox (441)+TX, iodomethane (IUPAC name) (542)+TX, isocarbophos (alternative name) (473)+TX, isopropyl O-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473)+TX, ivermectin (alternative name) [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX, jodfenphos (1248)+TX, lindane (430)+TX, lufenuron (490)+TX, malathion (492)+TX, malonoben (1254)+TX, mecarbam (502)+TX, mephosfolan (1261)+TX, mesulfen (alternative name) [CCN]+TX, methacrifos (1266)+TX, methamidophos (527)+TX, methidathion (529)+TX, methiocarb (530)+TX, methomyl (531)+TX, methyl bromide (537)+TX, metolcarb (550)+TX, mevinphos (556)+TX, mexacarbate (1290)+TX, milbemectin (557)+TX, milbemycin oxime (alternative name) [CCN]+TX, mipafox (1293)+TX, monocrotophos (561)+TX, morphothion (1300)+TX, moxidectin (alternative name) [CCN]+TX, naled (567)+TX, NC-184 (compound code)+TX, NC-512 (compound code)+TX, nifluridide (1309)+TX, nikkomycins (alternative name) [CCN]+TX, nitrilacarb (1313)+TX, nitrilacarb 1:1 zinc chloride complex (1313)+TX, NNI-0101 (compound code)+TX, NNI-0250 (compound code)+TX, omethoate (594)+TX, oxamyl (602)+TX, oxydeprofos (1324)+TX, oxydisulfoton (1325)+TX, pp′-DDT (219)+TX, parathion (615)+TX, permethrin (626)+TX, petroleum oils (alternative name) (628)+TX, phenkapton (1330)+TX, phenthoate (631)+TX, phorate (636)+TX, phosalone (637)+TX, phosfolan (1338)+TX, phosmet (638)+TX, phosphamidon (639)+TX, phoxim (642)+TX, pirimiphos-methyl (652)+TX, polychloroterpenes (traditional name) (1347)+TX, polynactins (alternative name) (653)+TX, proclonol (1350)+TX, profenofos (662)+TX, promacyl (1354)+TX, propargite (671)+TX, propetamphos (673)+TX, propoxur (678)+TX, prothidathion (1360)+TX, prothoate (1362)+TX, pyrethrin I (696)+TX, pyrethrin II (696)+TX, pyrethrins (696)+TX, pyridaben (699)+TX, pyridaphenthion (701)+TX, pyrimidifen (706)+TX, pyrimitate (1370)+TX, quinalphos (711)+TX, quintiofos (1381)+TX, R-1492 (development code) (1382)+TX, RA-17 (development code) (1383)+TX, rotenone (722)+TX, schradan (1389)+TX, sebufos (alternative name)+TX, selamectin (alternative name) [CCN]+TX, SI-0009 (compound code)+TX, sophamide (1402)+TX, spirodiclofen (738)+TX, spiromesifen (739)+TX, SSI-121 (development code) (1404)+TX, sulfiram (alternative name) [CCN]+TX, sulfluramid (750)+TX, sulfotep (753)+TX, sulfur (754)+TX, SZI-121 (development code) (757)+TX, tau-fluvalinate (398)+TX, tebufenpyrad (763)+TX, TEPP (1417)+TX, terbam (alternative name)+TX, tetrachlorvinphos (777)+TX, tetradifon (786)+TX, tetranactin (alternative name) (653)+TX, tetrasul (1425)+TX, thiafenox (alternative name)+TX, thiocarboxime (1431)+TX, thiofanox (800)+TX, thiometon (801)+TX, thioquinox (1436)+TX, thuringiensin (alternative name) [CCN]+TX, triamiphos (1441)+TX, triarathene (1443)+TX, triazophos (820)+TX, triazuron (alternative name)+TX, trichlorfon (824)+TX, trifenofos (1455)+TX, trinactin (alternative name) (653)+TX, vamidothion (847)+TX, vaniliprole [CCN] and YI-5302 (compound code)+TX,
(107) an algicide selected from the group of substances consisting of bethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX, copper sulfate (172)+TX, cybutryne [CCN]+TX, dichlone (1052)+TX, dichlorophen (232)+TX, endothal (295)+TX, fentin (347)+TX, hydrated lime [CCN]+TX, nabam (566)+TX, quinoclamine (714)+TX, quinonamid (1379)+TX, simazine (730)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX,
(108) an anthelmintic selected from the group of substances consisting of abamectin (1)+TX, crufomate (1011)+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,
(109) 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,
(110) 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 (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,
(111) a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537)+TX,
(112) 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,
(113) 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,
(114) 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,
(115) an insecticide selected from the group of substances consisting of 1-dichloro-1-nitroethane (IUPAC/Chemical Abstracts name) (1058)+TX, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (IUPAC name) (1056), +TX, 1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062)+TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063)+TX, 1-bromo-2-chloroethane (IUPAC/Chemical Abstracts name) (916)+TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate (IUPAC name) (1451)+TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate (IUPAC name) (1066)+TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate (IUPAC/Chemical Abstracts name) (1109)+TX, 2-(2-butoxyethoxy)ethyl thiocyanate (IUPAC/Chemical Abstracts name) (935)+TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate (IUPAC/Chemical Abstracts name) (1084)+TX, 2-(4-chloro-3,5-xylyloxy)ethanol (IUPAC name) (986)+TX, 2-chlorovinyl diethyl phosphate (IUPAC name) (984)+TX, 2-imidazolidone (IUPAC name) (1225)+TX, 2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate (IUPAC name) (1284)+TX, 2-thiocyanatoethyl laurate (IUPAC name) (1433)+TX, 3-bromo-1-chloroprop-1-ene (IUPAC name) (917)+TX, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate (IUPAC name) (1283)+TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate (IUPAC name) (1285)+TX, 5,5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate (IUPAC name) (1085)+TX, abamectin (1)+TX, acephate (2)+TX, acetamiprid (4)+TX, acethion (alternative name) [CCN]+TX, acetoprole [CCN]+TX, acrinathrin (9)+TX, acrylonitrile (IUPAC name) (861)+TX, alanycarb (15)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, aldrin (864)+TX, allethrin (17)+TX, allosamidin (alternative name) [CCN]+TX, allyxycarb (866)+TX, alpha-cypermethrin (202)+TX, alpha-ecdysone (alternative name) [CCN]+TX, aluminium phosphide (640)+TX, amidithion (870)+TX, amidothioate (872)+TX, aminocarb (873)+TX, amiton (875)+TX, amiton hydrogen oxalate (875)+TX, amitraz (24)+TX, anabasine (877)+TX, athidathion (883)+TX, AVI 382 (compound code)+TX, AZ 60541 (compound code)+TX, azadirachtin (alternative name) (41)+TX, azamethiphos (42)+TX, azinphos-ethyl (44)+TX, azinphos-methyl (45)+TX, azothoate (889)+TX, Bacillus thuringiensis delta endotoxins (alternative name) (52)+TX, barium hexafluorosilicate (alternative name) [CCN]+TX, barium polysulfide (IUPAC/Chemical Abstracts name) (892)+TX, barthrin [CCN]+TX, Bayer 22/190 (development code) (893)+TX, Bayer 22408 (development code) (894)+TX, bendiocarb (58)+TX, benfuracarb (60)+TX, bensultap (66)+TX, beta-cyfluthrin (194)+TX, beta-cypermethrin (203)+TX, bifenthrin (76)+TX, bioallethrin (78)+TX, bioallethrin S-cyclopentenyl isomer (alternative name) (79)+TX, bioethanomethrin [CCN]+TX, biopermethrin (908)+TX, bioresmethrin (80)+TX, bis(2-chloroethyl) ether (IUPAC name) (909)+TX, bistrifluron (83)+TX, borax (86)+TX, brofenvalerate (alternative name)+TX, bromfenvinfos (914)+TX, bromocyclen (918)+TX, bromo-DDT (alternative name) [CCN]+TX, bromophos (920)+TX, bromophos-ethyl (921)+TX, bufencarb (924)+TX, buprofezin (99)+TX, butacarb (926)+TX, butathiofos (927)+TX, butocarboxim (103)+TX, butonate (932)+TX, butoxycarboxim (104)+TX, butylpyridaben (alternative name)+TX, cadusafos (109)+TX, calcium arsenate [CCN]+TX, calcium cyanide (444)+TX, calcium polysulfide (IUPAC name) (111)+TX, camphechlor (941)+TX, carbanolate (943)+TX, carbaryl (115)+TX, carbofuran (118)+TX, carbon disulfide (IUPAC/Chemical Abstracts name) (945)+TX, carbon tetrachloride (IUPAC name) (946)+TX, carbophenothion (947)+TX, carbosulfan (119)+TX, cartap (123)+TX, cartap hydrochloride (123)+TX, cevadine (alternative name) (725)+TX, chlorbicyclen (960)+TX, chlordane (128)+TX, chlordecone (963)+TX, chlordimeform (964)+TX, chlordimeform hydrochloride (964)+TX, chlorethoxyfos (129)+TX, chlorfenapyr (130)+TX, chlorfenvinphos (131)+TX, chlorfluazuron (132)+TX, chlormephos (136)+TX, chloroform [CCN]+TX, chloropicrin (141)+TX, chlorphoxim (989)+TX, chlorprazophos (990)+TX, chlorpyrifos (145)+TX, chlorpyrifos-methyl (146)+TX, chlorthiophos (994)+TX, chromafenozide (150)+TX, cinerin I (696)+TX, cinerin 11 (696)+TX, cinerins (696)+TX, cis-resmethrin (alternative name)+TX, cismethrin (80)+TX, clocythrin (alternative name)+TX, cloethocarb (999)+TX, closantel (alternative name) [CCN]+TX, clothianidin (165)+TX, copper acetoarsenite [CCN]+TX, copper arsenate [CCN]+TX, copper oleate [CCN]+TX, coumaphos (174)+TX, coumithoate (1006)+TX, crotamiton (alternative name) [CCN]+TX, crotoxyphos (1010)+TX, crufomate (1011)+TX, cryolite (alternative name) (177)+TX, CS 708 (development code) (1012)+TX, cyanofenphos (1019)+TX, cyanophos (184)+TX, cyanthoate (1020)+TX, cyclethrin [CCN]+TX, cycloprothrin (188)+TX, cyfluthrin (193)+TX, cyhalothrin (196)+TX, cypermethrin (201)+TX, cyphenothrin (206)+TX, cyromazine (209)+TX, cythioate (alternative name) [CCN]+TX, d-limonene (alternative name) [CCN]+TX, d-tetramethrin (alternative name) (788)+TX, DAEP (1031)+TX, dazomet (216)+TX, DDT (219)+TX, decarbofuran (1034)+TX, deltamethrin (223)+TX, demephion (1037)+TX, demephion-O (1037)+TX, demephion-S (1037)+TX, demeton (1038)+TX, demeton-methyl (224)+TX, demeton-O (1038)+TX, demeton-O-methyl (224)+TX, demeton-S (1038)+TX, demeton-S-methyl (224)+TX, demeton-S-methylsulphon (1039)+TX, diafenthiuron (226)+TX, dialifos (1042)+TX, diamidafos (1044)+TX, diazinon (227)+TX, dicapthon (1050)+TX, dichlofenthion (1051)+TX, dichlorvos (236)+TX, dicliphos (alternative name)+TX, dicresyl (alternative name) [CCN]+TX, dicrotophos (243)+TX, dicyclanil (244)+TX, dieldrin (1070)+TX, diethyl 5-methylpyrazol-3-yl phosphate (IUPAC name) (1076)+TX, diflubenzuron (250)+TX, dilor (alternative name) [CCN]+TX, dimefluthrin [CCN]+TX, dimefox (1081)+TX, dimetan (1085)+TX, dimethoate (262)+TX, dimethrin (1083)+TX, dimethylvinphos (265)+TX, dimetilan (1086)+TX, dinex (1089)+TX, dinex-diclexine (1089)+TX, dinoprop (1093)+TX, dinosam (1094)+TX, dinoseb (1095)+TX, dinotefuran (271)+TX, diofenolan (1099)+TX, dioxabenzofos (1100)+TX, dioxacarb (1101)+TX, dioxathion (1102)+TX, disulfoton (278)+TX, dithicrofos (1108)+TX, DNOC (282)+TX, doramectin (alternative name) [CCN]+TX, DSP (1115)+TX, ecdysterone (alternative name) [CCN]+TX, EI 1642 (development code) (1118)+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, EMPC (1120)+TX, empenthrin (292)+TX, endosulfan (294)+TX, endothion (1121)+TX, endrin (1122)+TX, EPBP (1123)+TX, EPN (297)+TX, epofenonane (1124)+TX, eprinomectin (alternative name) [CCN]+TX, esfenvalerate (302)+TX, etaphos (alternative name) [CCN]+TX, ethiofencarb (308)+TX, ethion (309)+TX, ethiprole (310)+TX, ethoate-methyl (1134)+TX, ethoprophos (312)+TX, ethyl formate (IUPAC name) [CCN]+TX, ethyl-DDD (alternative name) (1056)+TX, ethylene dibromide (316)+TX, ethylene dichloride (chemical name) (1136)+TX, ethylene oxide [CCN]+TX, etofenprox (319)+TX, etrimfos (1142)+TX, EXD (1143)+TX, famphur (323)+TX, fenamiphos (326)+TX, fenazaflor (1147)+TX, fenchlorphos (1148)+TX, fenethacarb (1149)+TX, fenfluthrin (1150)+TX, fenitrothion (335)+TX, fenobucarb (336)+TX, fenoxacrim (1153)+TX, fenoxycarb (340)+TX, fenpirithrin (1155)+TX, fenpropathrin (342)+TX, fenpyrad (alternative name)+TX, fensulfothion (1158)+TX, fenthion (346)+TX, fenthion-ethyl [CCN]+TX, fenvalerate (349)+TX, fipronil (354)+TX, flonicamid (358)+TX, flubendiamide (CAS. Reg. No.: 272451-65-7)+TX, flucofuron (1168)+TX, flucycloxuron (366)+TX, flucythrinate (367)+TX, fluenetil (1169)+TX, flufenerim [CCN]+TX, flufenoxuron (370)+TX, flufenprox (1171)+TX, flumethrin (372)+TX, fluvalinate (1184)+TX, FMC 1137 (development code) (1185)+TX, fonofos (1191)+TX, formetanate (405)+TX, formetanate hydrochloride (405)+TX, formothion (1192)+TX, formparanate (1193)+TX, fosmethilan (1194)+TX, fospirate (1195)+TX, fosthiazate (408)+TX, fosthietan (1196)+TX, furathiocarb (412)+TX, furethrin (1200)+TX, gamma-cyhalothrin (197)+TX, gamma-HCH (430)+TX, guazatine (422)+TX, guazatine acetates (422)+TX, GY-81 (development code) (423)+TX, halfenprox (424)+TX, halofenozide (425)+TX, HCH (430)+TX, HEOD (1070)+TX, heptachlor (1211)+TX, heptenophos (432)+TX, heterophos [CCN]+TX, hexaflumuron (439)+TX, HHDN (864)+TX, hydramethylnon (443)+TX, hydrogen cyanide (444)+TX, hydroprene (445)+TX, hyquincarb (1223)+TX, imidacloprid (458)+TX, imiprothrin (460)+TX, indoxacarb (465)+TX, iodomethane (IUPAC name) (542)+TX, IPSP (1229)+TX, isazofos (1231)+TX, isobenzan (1232)+TX, isocarbophos (alternative name) (473)+TX, isodrin (1235)+TX, isofenphos (1236)+TX, isolane (1237)+TX, isoprocarb (472)+TX, isopropyl O-(methoxy-aminothiophosphoryl)salicylate (IUPAC name) (473)+TX, isoprothiolane (474)+TX, isothioate (1244)+TX, isoxathion (480)+TX, ivermectin (alternative name) [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX, jodfenphos (1248)+TX, juvenile hormone I (alternative name) [CCN]+TX, juvenile hormone II (alternative name) [CCN]+TX, juvenile hormone III (alternative name) [CCN]+TX, kelevan (1249)+TX, kinoprene (484)+TX, lambda-cyhalothrin (198)+TX, lead arsenate [CCN]+TX, lepimectin (CCN)+TX, leptophos (1250)+TX, lindane (430)+TX, lirimfos (1251)+TX, lufenuron (490)+TX, lythidathion (1253)+TX, m-cumenyl methylcarbamate (IUPAC name) (1014)+TX, magnesium phosphide (IUPAC name) (640)+TX, malathion (492)+TX, malonoben (1254)+TX, mazidox (1255)+TX, mecarbam (502)+TX, mecarphon (1258)+TX, menazon (1260)+TX, mephosfolan (1261)+TX, mercurous chloride (513)+TX, mesulfenfos (1263)+TX, metaflumizone (CCN)+TX, metam (519)+TX, metam-potassium (alternative name) (519)+TX, metam-sodium (519)+TX, methacrifos (1266)+TX, methamidophos (527)+TX, methanesulfonyl fluoride (IUPAC/Chemical Abstracts name) (1268)+TX, methidathion (529)+TX, methiocarb (530)+TX, methocrotophos (1273)+TX, methomyl (531)+TX, methoprene (532)+TX, methoquin-butyl (1276)+TX, methothrin (alternative name) (533)+TX, methoxychlor (534)+TX, methoxyfenozide (535)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, methylchloroform (alternative name) [CCN]+TX, methylene chloride [CCN]+TX, metofluthrin [CCN]+TX, metolcarb (550)+TX, metoxadiazone (1288)+TX, mevinphos (556)+TX, mexacarbate (1290)+TX, milbemectin (557)+TX, milbemycin oxime (alternative name) [CCN]+TX, mipafox (1293)+TX, mirex (1294)+TX, monocrotophos (561)+TX, morphothion (1300)+TX, moxidectin (alternative name) [CCN]+TX, naftalofos (alternative name) [CCN]+TX, naled (567)+TX, naphthalene (IUPAC/Chemical Abstracts name) (1303)+TX, NC-170 (development code) (1306)+TX, NC-184 (compound code)+TX, nicotine (578)+TX, nicotine sulfate (578)+TX, nifluridide (1309)+TX, nitenpyram (579)+TX, nithiazine (1311)+TX, nitrilacarb (1313)+TX, nitrilacarb 1:1 zinc chloride complex (1313)+TX, NNI-0101 (compound code)+TX, NNI-0250 (compound code)+TX, nornicotine (traditional name) (1319)+TX, novaluron (585)+TX, noviflumuron (586)+TX, O-5-dichloro-4-iodophenyl 0-ethyl ethylphosphonothioate (IUPAC name) (1057)+TX, O,O-diethyl O-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate (IUPAC name) (1074)+TX, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate (IUPAC name) (1075)+TX, O,O,O′,O′-tetrapropyl dithiopyrophosphate (IUPAC name) (1424)+TX, oleic acid (IUPAC name) (593)+TX, omethoate (594)+TX, oxamyl (602)+TX, oxydemeton-methyl (609)+TX, oxydeprofos (1324)+TX, oxydisulfoton (1325)+TX, pp'-DDT (219)+TX, para-dichlorobenzene [CCN]+TX, parathion (615)+TX, parathion-methyl (616)+TX, penfluron (alternative name) [CCN]+TX, pentachlorophenol (623)+TX, pentachlorophenyl laurate (IUPAC name) (623)+TX, permethrin (626)+TX, petroleum oils (alternative name) (628)+TX, PH 60-38 (development code) (1328)+TX, phenkapton (1330)+TX, phenothrin (630)+TX, phenthoate (631)+TX, phorate (636)+TX, phosalone (637)+TX, phosfolan (1338)+TX, phosmet (638)+TX, phosnichlor (1339)+TX, phosphamidon (639)+TX, phosphine (IUPAC name) (640)+TX, phoxim (642)+TX, phoxim-methyl (1340)+TX, pirimetaphos (1344)+TX, pirimicarb (651)+TX, pirimiphos-ethyl (1345)+TX, pirimiphos-methyl (652)+TX, polychlorodicyclopentadiene isomers (IUPAC name) (1346)+TX, polychloroterpenes (traditional name) (1347)+TX, potassium arsenite [CCN]+TX, potassium thiocyanate [CCN]+TX, prallethrin (655)+TX, precocene I (alternative name) [CCN]+TX, precocene II (alternative name) [CCN]+TX, precocene Ill (alternative name) [CCN]+TX, primidophos (1349)+TX, profenofos (662)+TX, profluthrin [CCN]+TX, promacyl (1354)+TX, promecarb (1355)+TX, propaphos (1356)+TX, propetamphos (673)+TX, propoxur (678)+TX, prothidathion (1360)+TX, prothiofos (686)+TX, prothoate (1362)+TX, protrifenbute [CCN]+TX, pymetrozine (688)+TX, pyraclofos (689)+TX, pyrazophos (693)+TX, pyresmethrin (1367)+TX, pyrethrin I (696)+TX, pyrethrin II (696)+TX, pyrethrins (696)+TX, pyridaben (699)+TX, pyridalyl (700)+TX, pyridaphenthion (701)+TX, pyrimidifen (706)+TX, pyrimitate (1370)+TX, pyriproxyfen (708)+TX, quassia (alternative name) [CCN]+TX, quinalphos (711)+TX, quinalphos-methyl (1376)+TX, quinothion (1380)+TX, quintiofos (1381)+TX, R-1492 (development code) (1382)+TX, rafoxanide (alternative name) [CCN]+TX, resmethrin (719)+TX, rotenone (722)+TX, RU 15525 (development code) (723)+TX, RU 25475 (development code) (1386)+TX, ryania (alternative name) (1387)+TX, ryanodine (traditional name) (1387)+TX, sabadilla (alternative name) (725)+TX, schradan (1389)+TX, sebufos (alternative name)+TX, selamectin (alternative name) [CCN]+TX, SI-0009 (compound code)+TX, SI-0205 (compound code)+TX, SI-0404 (compound code)+TX, SI-0405 (compound code)+TX, silafluofen (728)+TX, SN 72129 (development code) (1397)+TX, sodium arsenite [CCN]+TX, sodium cyanide (444)+TX, sodium fluoride (IUPAC/Chemical Abstracts name) (1399)+TX, sodium hexafluorosilicate (1400)+TX, sodium pentachlorophenoxide (623)+TX, sodium selenate (IUPAC name) (1401)+TX, sodium thiocyanate [CCN]+TX, sophamide (1402)+TX, spinosad (737)+TX, spiromesifen (739)+TX, spirotetrmat (CCN)+TX, sulcofuron (746)+TX, sulcofuron-sodium (746)+TX, sulfluramid (750)+TX, sulfotep (753)+TX, sulfuryl fluoride (756)+TX, sulprofos (1408)+TX, tar oils (alternative name) (758)+TX, tau-fluvalinate (398)+TX, tazimcarb (1412)+TX, TDE (1414)+TX, tebufenozide (762)+TX, tebufenpyrad (763)+TX, tebupirimfos (764)+TX, teflubenzuron (768)+TX, tefluthrin (769)+TX, temephos (770)+TX, TEPP (1417)+TX, terallethrin (1418)+TX, terbam (alternative name)+TX, terbufos (773)+TX, tetrachloroethane [CCN]+TX, tetrachlorvinphos (777)+TX, tetramethrin (787)+TX, theta-cypermethrin (204)+TX, thiacloprid (791)+TX, thiafenox (alternative name)+TX, thiamethoxam (792)+TX, thicrofos (1428)+TX, thiocarboxime (1431)+TX, thiocyclam (798)+TX, thiocyclam hydrogen oxalate (798)+TX, thiodicarb (799)+TX, thiofanox (800)+TX, thiometon (801)+TX, thionazin (1434)+TX, thiosultap (803)+TX, thiosultap-sodium (803)+TX, thuringiensin (alternative name) [CCN]+TX, tolfenpyrad (809)+TX, tralomethrin (812)+TX, transfluthrin (813)+TX, transpermethrin (1440)+TX, triamiphos (1441)+TX, triazamate (818)+TX, triazophos (820)+TX, triazuron (alternative name)+TX, trichlorfon (824)+TX, trichlormetaphos-3 (alternative name) [CCN]+TX, trichloronat (1452)+TX, trifenofos (1455)+TX, triflumuron (835)+TX, trimethacarb (840)+TX, triprene (1459)+TX, vamidothion (847)+TX, vaniliprole [CCN]+TX, veratridine (alternative name) (725)+TX, veratrine (alternative name) (725)+TX, XMC (853)+TX, xylylcarb (854)+TX, YI-5302 (compound code)+TX, zeta-cypermethrin (205)+TX, zetamethrin (alternative name)+TX, zinc phosphide (640)+TX, zolaprofos (1469) and ZXI 8901 (development code) (858)+TX, cyantraniliprole [736994-63-19+TX, chlorantraniliprole [500008-45-7]+TX, cyenopyrafen [560121-52-0]+TX, cyflumetofen [400882-07-7]+TX, pyrifluquinazon [337458-27-2]+TX, spinetoram [187166-40-1+187166-15-0]+TX, spirotetramat [203313-25-1]+TX, sulfoxaflor [946578-00-3]+TX, flufiprole [704886-18-0]+TX, meperfluthrin [915288-13-0]+TX, tetramethylfluthrin [84937-88-2]+TX, triflumezopyrim (disclosed in WO 2012/092115)+TX, fluxametamide (WO 2007/026965)+TX, epsilon-metofluthrin [240494-71-7]+TX, epsilon-momfluorothrin [1065124-65-3]+TX, fluazaindolizine [1254304-22-7]+TX, chloroprallethrin [399572-87-3]+TX, fluxametamide [928783-29-3]+TX, cyhalodiamide [1262605-53-7]+TX, tioxazafen [330459-31-9]+TX, broflanilide [1207727-04-5]+TX, flufiprole [704886-18-0]+TX, cyclaniliprole [1031756-98-5]+TX, tetraniliprole [1229654-66-3]+TX, guadipyr (described in WO2010/060231)+TX, cycloxaprid (described in WO 2005/077934)+TX, spiropidion+TX, Afidopyropen+TX, flupyrimin+TX, Momfluorothrin+TX, kappa-bifenthrin+TX, kappa-tefluthrin+TX, Dichloromezotiaz+TX, Tetrachloraniliprole+TX, benzpyrimoxan+TX;
(116) a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913)+TX, bromoacetamide [CCN]+TX, calcium arsenate [CCN]+TX, cloethocarb (999)+TX, copper acetoarsenite [CCN]+TX, copper sulfate (172)+TX, fentin (347)+TX, ferric phosphate (IUPAC name) (352)+TX, metaldehyde (518)+TX, methiocarb (530)+TX, niclosamide (576)+TX, niclosamide-olamine (576)+TX, pentachlorophenol (623)+TX, sodium pentachlorophenoxide (623)+TX, tazimcarb (1412)+TX, thiodicarb (799)+TX, tributyltin oxide (913)+TX, trifenmorph (1454)+TX, trimethacarb (840)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX, pyriprole [394730-71-3]+TX, a nematicide selected from the group of substances consisting of AKD-3088 (compound code)+TX, 1,2-dibromo-3-chloropropane (IUPAC/Chemical Abstracts name) (1045)+TX, 1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062)+TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063)+TX, 1,3-dichloropropene (233)+TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC/Chemical Abstracts name) (1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPAC name) (1286)+TX, 6-isopentenylaminopurine (alternative name) (210)+TX, abamectin (1)+TX, acetoprole [CCN]+TX, alanycarb (15)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, AZ 60541 (compound code)+TX, benclothiaz [CCN]+TX, benomyl (62)+TX, butylpyridaben (alternative name)+TX, cadusafos (109)+TX, carbofuran (118)+TX, carbon disulfide (945)+TX, carbosulfan (119)+TX, chloropicrin (141)+TX, chlorpyrifos (145)+TX, cloethocarb (999)+TX, cytokinins (alternative name) (210)+TX, dazomet (216)+TX, DBCP (1045)+TX, DCIP (218)+TX, diamidafos (1044)+TX, dichlofenthion (1051)+TX, dicliphos (alternative name)+TX, dimethoate (262)+TX, doramectin (alternative name) [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin (alternative name) [CCN]+TX, ethoprophos (312)+TX, ethylene dibromide (316)+TX, fenamiphos (326)+TX, fenpyrad (alternative name)+TX, fensulfothion (1158)+TX, fosthiazate (408)+TX, fosthietan (1196)+TX, furfural (alternative name) [CCN]+TX, GY-81 (development code) (423)+TX, heterophos [CCN]+TX, iodomethane (IUPAC name) (542)+TX, isamidofos (1230)+TX, isazofos (1231)+TX, ivermectin (alternative name) [CCN]+TX, kinetin (alternative name) (210)+TX, mecarphon (1258)+TX, metam (519)+TX, metam-potassium (alternative name) (519)+TX, metam-sodium (519)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, milbemycin oxime (alternative name) [CCN]+TX, moxidectin (alternative name) [CCN]+TX, Myrothecium verrucaria composition (alternative name) (565)+TX, NC-184 (compound code)+TX, oxamyl (602)+TX, phorate (636)+TX, phosphamidon (639)+TX, phosphocarb [CCN]+TX, sebufos (alternative name)+TX, selamectin (alternative name) [CCN]+TX, spinosad (737)+TX, terbam (alternative name)+TX, terbufos (773)+TX, tetrachlorothiophene (IUPAC/Chemical Abstracts name) (1422)+TX, thiafenox (alternative name)+TX, thionazin (1434)+TX, triazophos (820)+TX, triazuron (alternative name)+TX, xylenols [CCN]+TX, YI-5302 (compound code) and zeatin (alternative name) (210)+TX, fluensulfone [318290-98-1]+TX, fluopyram+TX,
(117) a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580)+TX,
(118) 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,
(119) a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, alpha-chlorohydrin [CCN]+TX, aluminium phosphide (640)+TX, antu (880)+TX, arsenous oxide (882)+TX, barium carbonate (891)+TX, bisthiosemi (912)+TX, brodifacoum (89)+TX, bromadiolone (91)+TX, bromethalin (92)+TX, calcium cyanide (444)+TX, chloralose (127)+TX, chlorophacinone (140)+TX, cholecalciferol (alternative name) (850)+TX, coumachlor (1004)+TX, coumafuryl (1005)+TX, coumatetralyl (175)+TX, crimidine (1009)+TX, difenacoum (246)+TX, difethialone (249)+TX, diphacinone (273)+TX, ergocalciferol (301)+TX, flocoumafen (357)+TX, fluoroacetamide (379)+TX, flupropadine (1183)+TX, flupropadine hydrochloride (1183)+TX, gamma-HCH (430)+TX, HCH (430)+TX, hydrogen cyanide (444)+TX, iodomethane (IUPAC name) (542)+TX, lindane (430)+TX, magnesium phosphide (IUPAC name) (640)+TX, methyl bromide (537)+TX, norbormide (1318)+TX, phosacetim (1336)+TX, phosphine (IUPAC name) (640)+TX, phosphorus [CCN]+TX, pindone (1341)+TX, potassium arsenite [CCN]+TX, pyrinuron (1371)+TX, scilliroside (1390)+TX, sodium arsenite [CCN]+TX, sodium cyanide (444)+TX, sodium fluoroacetate (735)+TX, strychnine (745)+TX, thallium sulfate [CCN]+TX, warfarin (851) and zinc phosphide (640)+TX,
(120) 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,
(121) an animal repellent selected from the group of substances consisting of anthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX, copper oxychloride (171)+TX, diazinon (227)+TX, dicyclopentadiene (chemical name) (1069)+TX, guazatine (422)+TX, guazatine acetates (422)+TX, methiocarb (530)+TX, pyridin-4-amine (IUPAC name) (23)+TX, thiram (804)+TX, trimethacarb (840)+TX, zinc naphthenate [CCN] and ziram (856)+TX, a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN]+TX,
(122) a wound protectant selected from the group of substances consisting of mercuric oxide (512)+TX, octhilinone (590) and thiophanate-methyl (802)+TX,
(123) and biologically active compounds selected from the group consisting of azaconazole (60207-31-0]+TX, bitertanol [70585-36-3]+TX, bromuconazole [116255-48-2]+TX, cyproconazole [94361-06-5]+TX, difenoconazole [119446-68-3]+TX, diniconazole [83657-24-3]+TX, epoxiconazole [106325-08-0]+TX, fenbuconazole [114369-43-6]+TX, fluquinconazole [136426-54-5]+TX, flusilazole [85509-19-9]+TX, flutriafol [76674-21-0]+TX, hexaconazole [79983-71-4]+TX, imazalil [35554-44-0]+TX, imibenconazole [86598-92-7]+TX, ipconazole [125225-28-7]+TX, metconazole [125116-23-6]+TX, myclobutanil [88671-89-0]+TX, pefurazoate [101903-30-4]+TX, penconazole [66246-88-6]+TX, prothioconazole [178928-70-6]+TX, pyrifenox [88283-41-4]+TX, prochloraz [67747-09-5]+TX, propiconazole [60207-90-1]+TX, simeconazole [149508-90-7]+TX, tebuconazole [107534-96-3]+TX, tetraconazole [112281-77-3]+TX, triadimefon [43121-43-3]+TX, triadimenol [55219-65-3]+TX, triflumizole [99387-89-0]+TX, triticonazole [131983-72-7]+TX, ancymidol [12771-68-5]+TX, fenarimol [60168-88-9]+TX, nuarimol [63284-71-9]+TX, bupirimate [41483-43-6]+TX, dimethirimol [5221-53-4]+TX, ethirimol [23947-60-6]+TX, dodemorph [1593-77-7]+TX, fenpropidine [67306-00-7]+TX, fenpropimorph [67564-91-4]+TX, spiroxamine [118134-30-8]+TX, tridemorph [81412-43-3]+TX, cyprodinil [121552-61-2]+TX, mepanipyrim [110235-47-7]+TX, pyrimethanil [53112-28-0]+TX, fenpiclonil [74738-17-3]+TX, fludioxonil [131341-86-1]+TX, benalaxyl [71626-11-4]+TX, furalaxyl [57646-30-7]+TX, meta-laxyl [57837-19-1]+TX, R-metalaxyl [70630-17-0]+TX, ofurace [58810-48-3]+TX, oxadixyl [77732-09-3]+TX, benomyl [17804-35-2]+TX, carbendazim [10605-21-7]+TX, debacarb [62732-91-6]+TX, fuberidazole [3878-19-1]+TX, thiabendazole [148-79-8]+TX, chlozolinate [84332-86-5]+TX, dichlozoline [24201-58-9]+TX, iprodione [36734-19-7]+TX, myclozoline [54864-61-8]+TX, procymidone [32809-16-8]+TX, vinclozoline [50471-44-8]+TX, boscalid [188425-85-6]+TX, carboxin [5234-68-4]+TX, fenfuram [24691-80-3]+TX, flutolanil [66332-96-5]+TX, mepronil [55814-41-0]+TX, oxycarboxin [5259-88-1]+TX, penthiopyrad [183675-82-3]+TX, thifluzamide [130000-40-7]+TX, guazatine [108173-90-6]+TX, dodine [2439-10-3] [112-65-2] (free base)+TX, iminoctadine [13516-27-3]+TX, azoxystrobin [131860-33-8]+TX, dimoxystrobin [149961-52-4]+TX, enestroburin {Proc. BCPC, Int. Congr., Glasgow, 2003, 1, 93}+TX, fluoxastrobin [361377-29-9]+TX, kresoxim-methyl [143390-89-0]+TX, metominostrobin [133408-50-1]+TX, trifloxystrobin [141517-21-7]+TX, orysastrobin [248593-16-0]+TX, picoxystrobin [117428-22-5]+TX, pyraclostrobin [175013-18-0]+TX, ferbam [14484-64-1]+TX, mancozeb [8018-01-7]+TX, maneb [12427-38-2]+TX, metiram [9006-42-2]+TX, propineb [12071-83-9]+TX, thiram [137-26-8]+TX, zineb [12122-67-7]+TX, ziram [137-30-4]+TX, captafol [2425-06-1]+TX, captan [133-06-2]+TX, dichlofluanid [1085-98-9]+TX, fluoroimide [41205-21-4]+TX, folpet [133-07-3]+TX, tolylfluanid [731-27-1]+TX, bordeaux mixture [8011-63-0]+TX, copperhydroxid [20427-59-2]+TX, copperoxychlorid [1332-40-7]+TX, coppersulfat [7758-98-7]+TX, copperoxid [1317-39-1]+TX, mancopper [53988-93-5]+TX, oxine-copper [10380-28-6]+TX, dinocap [131-72-6]+TX, nitrothal-isopropyl [10552-74-6]+TX, edifenphos [17109-49-8]+TX, iprobenphos [26087-47-8]+TX, isoprothiolane [50512-35-1]+TX, phosdiphen [36519-00-3]+TX, pyrazophos [13457-18-6]+TX, tolclofos-methyl [57018-04-9]+TX, acibenzo-lar-S-methyl [135158-54-2]+TX, anilazine [101-05-3]+TX, benthiavalicarb [413615-35-7]+TX, blasticidin-S [2079-00-7]+TX, chinomethionat [2439-01-2]+TX, chloroneb [2675-77-6]+TX, chlorothalonil [1897-45-6]+TX, cyflufenamid [180409-60-3]+TX, cymoxanil [57966-95-7]+TX, dichlone [117-80-6]+TX, diclocymet [139920-32-4]+TX, diclomezine [62865-36-5]+TX, dicloran [99-30-9]+TX, diethofencarb [87130-20-9]+TX, dimethomorph [110488-70-5]+TX, SYP-L190 (Flumorph) [211867-47-9]+TX, dithianon [3347-22-6]+TX, ethaboxam [162650-77-3]+TX, etridiazole [2593-15-9]+TX, famoxadone [131807-57-3]+TX, fenamidone [161326-34-7]+TX, fenoxanil [115852-48-7]+TX, fentin [668-34-8]+TX, ferimzone [89269-64-7]+TX, fluazinam [79622-59-6]+TX, fluopicolide [239110-15-7]+TX, flusulfamide [106917-52-6]+TX, fenhexamid [126833-17-8]+TX, fosetyl-aluminium [39148-24-8]+TX, hymexazol [10004-44-1]+TX, iprovalicarb [140923-17-7]+TX, IKF-916 (Cyazofamid) [120116-88-3]+TX, kasugamycin [6980-18-3]+TX, methasulfocarb [66952-49-6]+TX, metrafenone [220899-03-6]+TX, pencycuron [66063-05-6]+TX, phthalide [27355-22-2]+TX, polyoxins [11113-80-7]+TX, probenazole [27605-76-1]+TX, propamocarb [25606-41-1]+TX, proquinazid [189278-12-4]+TX, pyroquilon [57369-32-1]+TX, quinoxyfen [124495-18-7]+TX, quintozene [82-68-8]+TX, sulfur [7704-34-9]+TX, tiadinil [223580-51-6]+TX, triazoxide [72459-58-6]+TX, tricyclazole [41814-78-2]+TX, triforine [26644-46-2]+TX, validamycin [37248-47-8]+TX, zoxamide (RH7281) [156052-68-5]+TX, mandipropamid [374726-62-2]+TX, isopyrazam [881685-58-1]+TX, sedaxane [874967-67-6]+TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide (disclosed in WO 2007/048556)+TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3′,4′,5′-trifluoro-biphenyl-2-yl)-amide (disclosed in WO 2006/087343)+TX, [(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5,6,6a,12,12a, 12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)-2H,11Hnaphtho[2,1-b]pyrano[3,4-e]pyran-4-yl]methyl-cyclopropanecarboxylate [915972-17-7]+TX and 1,3,5-trimethyl-N-(2-methyl-1-oxopropyl)-N-[3-(2-methylpropyl)-4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole-4-carboxamide [926914-55-8]+TX; and
(124) microbials including: Acinetobacter lwoffii+TX, Acremonium alternatum+TX+TX, Acremonium cephalosporium+TX+TX, Acremonium diospyri+TX, Acremonium obclavatum+TX, Adoxophyes orana granulovirus (AdoxGV) (Capex®)+TX, Agrobacterium radiobacter strain K84 (Galltrol-A®)+TX, Alternaria alternate+TX, Alternaria cassia+TX, Alternaria destruens (Smolder®)+TX, Ampelomyces quisqualis (AQ10®)+TX, Aspergillus flavus AF36 (AF36®)+TX, Aspergillus flavus NRRL 21882 (Aflaguard®)+TX, Aspergillus spp.+TX, Aureobasidium pullulans+TX, Azospirillum+TX, (MicroAZ®+TX, TAZO B®)+TX, Azotobacter+TX, Azotobacter chroocuccum (Azotomeal®)+TX, Azotobacter cysts (Bionatural Blooming Blossoms®)+TX, Bacillus amyloliquefaciens+TX, Bacillus cereus+TX, Bacillus chitinosporus strain CM-1+TX, Bacillus chitinosporus strain AQ746+TX, Bacillus licheniformis strain HB-2 (Biostart™ Rhizoboost®)+TX, Bacillus licheniformis strain 3086 (EcoGuard®+TX, Green Releaf®)+TX, Bacillus circulans+TX, Bacillus firmus (BioSafe®+TX, BioNem-WP®+TX, VOTiVO®)+TX, Bacillus firmus strain 1-1582+TX, Bacillus macerans+TX, Bacillus marismortui+TX, Bacillus megaterium+TX, Bacillus mycoides strain AQ726+TX, Bacillus papillae (Milky Spore Powder®)+TX, Bacillus pumilus spp.+TX, Bacillus pumilus strain GB34 (Yield Shield®)+TX, Bacillus pumilus strain AQ717+TX, Bacillus pumilus strain QST 2808 (Sonata®+TX, Ballad Plus®)+TX, Bacillus spahericus (VectoLex®)+TX, Bacillus spp.+TX, Bacillus spp. strain AQ175+TX, Bacillus spp. strain AQ177+TX, Bacillus spp. strain AQ178+TX, Bacillus subtilis strain QST 713 (CEASE®+TX, Serenade®+TX, Rhapsody®)+TX, Bacillus subtilis strain QST 714 (JAZZ®)+TX, Bacillus subtilis strain AQ153+TX, Bacillus subtilis strain AQ743+TX, Bacillus subtilis strain QST3002+TX, Bacillus subtilis strain QST3004+TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 (Taegro®+TX, Rhizopro®)+TX, Bacillus thuringiensis Cry 2Ae+TX, Bacillus thuringiensis Cry1Ab+TX, Bacillus thuringiensis aizawai GC 91 (Agree®)+TX, Bacillus thuringiensis israelensis (BMP123®+TX, Aquabac®+TX, VectoBac®)+TX, Bacillus thuringiensis kurstaki (Javelin®+TX, Deliver®+TX, CryMax®+TX, Bonide®+TX, Scutella WP®+TX, Turilav WP®+TX, Astuto®+TX, Dipel WP®+TX, Biobit®+TX, Foray®)+TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®)+TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF/3P®)+TX, Bacillus thuringiensis strain BD #32+TX, Bacillus thuringiensis strain AQ52+TX, Bacillus thuringiensis var. aizawai (XenTari®+TX, DiPel®)+TX, bacteria spp. (GROWMEND®+TX, GROWSWEET@+TX, Shootup®)+TX, bacteriophage of Clavipacter michiganensis (AgriPhage®)+TX, Bakflor®+TX, Beauveria bassiana (Beaugenic®+TX, Brocaril WP®)+TX, Beauveria bassiana GHA (Mycotrol ES®+TX, Mycotrol O®+TX, BotaniGuard®)+TX, Beauveria brongniartii (Engerlingspilz®+TX, Schweizer Beauveria®+TX, Melocont®)+TX, Beauveria spp.+TX, Botrytis cineria+TX, Bradyrhizobium japonicum (TerraMax®)+TX, Brevibacillus brevis+TX, Bacillus thuringiensis tenebrionis (Novodor®)+TX, BtBooster+TX, Burkholderia cepacia (Deny®+TX, Intercept®+TX, Blue Circle®)+TX, Burkholderia gladii+TX, Burkholderia gladioli+TX, Burkholderia spp.+TX, Canadian thistle fungus (CBH Canadian Bioherbicide®)+TX, Candida butyri+TX, Candida famata+TX, Candida fructus+TX, Candida glabrata+TX, Candida guilliermondii+TX, Candida melibiosica+TX, Candida oleophila strain O+TX, Candida parapsilosis+TX, Candida pelliculosa+TX, Candida pulcherrima+TX, Candida reukaufii+TX, Candida saitoana (Bio-Coat®+TX, Biocure®)+TX, Candida sake+TX, Candida spp.+TX, Candida tenius+TX, Cedecea dravisae+TX, Cellulomonas flavigena+TX, Chaetomium cochliodes (Nova-Cide®)+TX, Chaetomium globosum (Nova-Cide®)+TX, Chromobacterium subtsugae strain PRAA4-1T (Grandevo®)+TX, Cladosporium cladosporioides+TX, Cladosporium oxysporum+TX, Cladosporium chlorocephalum+TX, Cladosporium spp.+TX, Cladosporium tenuissimum+TX, Clonostachys rosea (EndoFine®)+TX, Colletotrichum acutatum+TX, Coniothyrium minitans (Cotans WG®)+TX, Coniothyrium spp.+TX, Cryptococcus albidus (YIELDPLUS®)+TX, Cryptococcus humicola+TX, Cryptococcus infirmo-miniatus+TX, Cryptococcus laurentii+TX, Cryptophlebia leucotreta granulovirus (Cryptex®)+TX, Cupriavidus campinensis+TX, Cydia pomonella granulovirus (CYD-X®)+TX, Cydia pomonella granulovirus (Madex®+TX, Madex Plus®+TX, Madex Max/Carpovirusine®)+TX, Cylindrobasidium laeve (Stumpout®)+TX, Cylindrocladium+TX, Debaryomyces hansenii+TX, Drechslera hawaiinensis+TX, Enterobacter cloacae+TX, Enterobacteriaceae+TX, Entomophtora virulenta (Vektor®)+TX, Epicoccum nigrum+TX, Epicoccum purpurascens+TX, Epicoccum spp.+TX, Filobasidium floriforme+TX, Fusarium acuminatum+TX, Fusarium chlamydosporum+TX, Fusarium oxysporum (Fusaclean®/Biofox C®)+TX, Fusarium proliferatum+TX, Fusarium spp.+TX, Galactomyces geotrichum+TX, Gliocladium catenulatum (Primastop®+TX, Prestop®)+TX, Gliocladium roseum+TX, Gliocladium spp. (SoilGard®)+TX, Gliocladium virens (Soilgard®)+TX, Granulovirus (Granupom®)+TX, Halobacillus halophilus+TX, Halobacillus litoralis+TX, Halobacillus trueperi+TX, Halomonas spp.+TX, Halomonas subglaciescola+TX, Halovibrio variabilis+TX, Hanseniaspora uvarum+TX, Helicoverpa armigera nucleopolyhedrovirus (Helicovex®)+TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar®)+TX, Isoflavone-formononetin (Myconate®)+TX, Kloeckera apiculata+TX, Kloeckera spp.+TX, Lagenidium giganteum (Laginex®)+TX, Lecanicillium longisporum (Vertiblast®)+TX, Lecanicillium muscarium (Vertikil®)+TX, Lymantria Dispar nucleopolyhedrosis virus (Disparvirus®)+TX, Marinococcus halophilus+TX, Meira geulakonigii+TX, Metarhizium anisopliae (Met52®)+TX, Metarhizium anisopliae (Destruxin WP®)+TX, Metschnikowia fruticola (Shemer®)+TX, Metschnikowia pulcherrima+TX, Microdochium dimerum (Antibot®)+TX, Micromonospora coerulea+TX, Microsphaeropsis ochracea+TX, Muscodor albus 620 (Muscudor®)+TX, Muscodor roseus strain A3-5+TX, Mycorrhizae spp. (AMykor®+TX, Root Maximizer®)+TX, Myrothecium verrucaria strain AARC-0255 (DiTera®)+TX, BROS PLUS®+TX, Ophiostoma piliferum strain D97 (Sylvanex®)+TX, Paecilomyces farinosus+TX, Paecilomyces fumosoroseus (PFR-97®+TX, PreFeRal®)+TX, Paecilomyces linacinus (Biostat WP®)+TX, Paecilomyces lilacinus strain 251 (MeloCon WG®)+TX, Paenibacillus polymyxa+TX, Pantoea agglomerans (BlightBan 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 aureofasciens (Spot-Less Biofungicide®)+TX, Pseudomonas cepacia+TX, Pseudomonas chlororaphis (AtEze®)+TX, Pseudomonas corrugate+TX, Pseudomonas fluorescens strain A506 (BlightBan A506®)+TX, Pseudomonas putida+TX, Pseudomonas reactans+TX, Pseudomonas spp.+TX, Pseudomonas syringae (Bio-Save®)+TX, Pseudomonas viridiflava+TX, Pseudomons 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, Rhanella aquatilis+TX, Rhanella 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, Virgibaclillus marismortui+TX, Xanthomonas campestris pv. Poae (Camperico®)+TX, Xenorhabdus bovienii+TX, Xenorhabdus nematophilus; and
(125) 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 (NemaC.sub.20)+TX, Reynoutria sachalinensis (Regalia®+TX, Sakalia®)+TX, rotenone (Eco Roten®)+TX, Rutaceae plant extract (Soleo®)+TX, soybean oil (Ortho ecosense®)+TX, tea tree oil (Timorex Gold®)+TX, thymus oil+TX, AGNIQUE® MMF+TX, BugOil®+TX, mixture of rosemary sesame pepermint thyme and cinnamon extracts (EF 300®)+TX, mixture of clove rosemary and peppermint extract (EF 400®)+TX, mixture of clove pepermint garlic oil and mint (Soil Shot®)+TX, kaolin (Screen®)+TX, storage glucam of brown algae (Laminarin®); and
(126) pheromones including: blackheaded fireworm pheromone (3M Sprayable Blackheaded Fireworm Pheromone®)+TX, Codling Moth Pheromone (Paramount dispenser-(CM)/Isomate C-Plus®)+TX, Grape Berry Moth Pheromone (3M MEC-GBM Sprayable Pheromone®)+TX, Leafroller pheromone (3M MEC—LR Sprayable Pheromone®)+TX, Muscamone (Snip7 Fly Bait®+TX, Starbar Premium Fly Bait®)+TX, Oriental Fruit Moth Pheromone (3M oriental fruit moth sprayable pheromone®)+TX, Peachtree Borer Pheromone (Isomate-P®)+TX, Tomato Pinworm Pheromone (3M Sprayable pheromone®)+TX, Entostat powder (extract from palm tree) (Exosex CM®)+TX, (E+TX,Z+TX,Z)-3+TX,8+TX,11 Tetradecatrienyl acetate+TX, (Z+TX,Z+TX,E)-7+TX,11+TX,13-Hexadecatrienal+TX, (E+TX,Z)-7+TX,9-Dodecadien-1-yl acetate+TX, 2-Methyl-1-butanol+TX, Calcium acetate+TX, Scenturion®+TX, Biolure®+TX, Check-Mate®+TX, Lavandulyl senecioate; and
(127) 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 califomicus (Amblyline®+TX, Spical®)+TX, Amblyseius cucumeris (Thripex®+TX, Bugline cucumeris®)+TX, Amblyseius fallacis (Fallacis®)+TX, Amblyseius swirskii (Bugline swirskii®+TX, Swirskii-Mite®)+TX, Amblyseius womersleyi (WomerMite®)+TX, Amitus hesperidum+TX, Anagrus atomus+TX, Anagyrus fusciventris+TX, Anagyrus kamali+TX, Anagyrus loecki+TX, Anagyrus pseudococci (Citripar®)+TX, Anicetus benefices+TX, Anisopteromalus calandrae+TX, Anthocoris nemoralis (Anthocoris-System®)+TX, Aphelinus abdominalis (Apheline®+TX, Aphiline®)+TX, Aphelinus asychis+TX, Aphidius colemani (Aphipar®)+TX, Aphidius ervi (Ervipar®)+TX, Aphidius gifuensis+TX, Aphidius matricariae (Aphipar-M®)+TX, Aphidoletes aphidimyza (Aphidend®)+TX, Aphidoletes aphidimyza (Aphidoline®)+TX, Aphytis lingnanensis+TX, Aphytis melinus+TX, Aprostocetus hagenowii+TX, Atheta coriaria (Staphyline®)+TX, Bombus spp.+TX, Bombus terrestris (Natupol Beehive®)+TX, Bombus terrestris (Beeline®+TX, Tripol®)+TX, Cephalonomia stephanoderis+TX, Chilocorus nigritus+TX, Chrysoperla carnea (Chrysoline®)+TX, Chrysoperla carnea (Chrysopa®)+TX, Chrysoperla rufilabris+TX, Cirrospilus ingenuus+TX, Cirrospilus quadristriatus+TX, Citrostichus phyllocnistoides+TX, Closterocerus chamaeleon+TX, Closterocerus spp.+TX, Coccidoxenoides perminutus (Planopar®)+TX, Coccophagus cowperi+TX, Coccophagus lycimnia+TX, Cotesia flavipes+TX, Cotesia plutellae+TX, Cryptolaemus montrouzieri (Cryptobug®+TX, Cryptoline®)+TX, Cybocephalus nipponicus+TX, Dacnusa sibirica+TX, Dacnusa sibirica (Minusa®)+TX, Diglyphus isaea (Diminex®)+TX, Delphastus catalinae (Delphastus®)+TX, Delphastus pusillus+TX, Diachasmimorpha krausii+TX, Diachasmimorpha longicaudata+TX, Diaparsis jucunda+TX, Diaphorencyrtus aligarhensis+TX, Diglyphus isaea+TX, Diglyphus isaea (Miglyphus®+TX, Digline®)+TX, Dacnusa sibirica (DacDigline®+TX, Minex®)+TX, Diversinervus spp.+TX, Encarsia citrina+TX, Encarsia formosa (Encarsia max®+TX, Encarline®+TX, En-Strip®)+TX, Eretmocerus eremicus (Enermix®)+TX, Encarsia guadeloupae+TX, Encarsia haitiensis+TX, Episyrphus balteatus (Syrphidend®)+TX, Eretmoceris siphonini+TX, Eretmocerus califomicus+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 dactylopfi (Leptopar®)+TX, Leptomastix epona+TX, Lindorus lophanthae+TX, Lipolexis oregmae+TX, Lucilia caesar (Natufly®)+TX, Lysiphlebus testaceipes+TX, Macrolophus caliginosus (Mirical-N®+TX, Macroline c®+TX, Mirical®)+TX, Mesoseiulus longipes+TX, Metaphycus flavus+TX, Metaphycus lounsburyi+TX, Micromus angulatus (Milacewing®)+TX, Microterys flavus+TX, Muscidifurax raptorellus and Spalangia cameroni (Biopar®)+TX, Neodryinus typhlocybae+TX, Neoseiulus californicus+TX, Neoseiulus cucumeris (THRYPEX®))+TX, Neoseiulus fallacis+TX, Nesideocoris tenuis (NesidioBug®+TX, Nesibug®)+TX, Ophyra aenescens (Biofly®)+TX, Orius insidiosus (Thripor-I®+TX, Oriline i®)+TX, Orius laevigatus (Thripor-L®+TX, Oriline I®)+TX, Orius majusculus (Oriline m®)+TX, Orius strigicollis (Thripor-S®)+TX, Pauesia juniperorum+TX, Pediobius foveolatus+TX, Phasmarhabditis hermaphrodita (Nemaslug®)+TX, Phymastichus coffea+TX, Phytoseiulus macropilus+TX, Phytoseiulus persimilis (Spidex®+TX, Phytoline p®)+TX, Podisus maculiventris (Podisus®)+TX, Pseudacteon curvatus+TX, Pseudacteon obtusus+TX, Pseudacteon tricuspis+TX, Pseudaphycus maculipennis+TX, Pseudleptomastix mexicana+TX, Psyllaephagus pilosus+TX, Psyttalia concolor (complex)+TX, Quadrastichus spp.+TX, Rhyzobius lophanthae+TX, Rodolia cardinalis+TX, Rumina decollate+TX, Semielacher petiolatus+TX, Sitobion avenae (Ervibank®)+TX, Steinernema carpocapsae (Nematac C®+TX, Millenium®+TX, BioNem C®+TX, NemAttack®+TX, Nemastar®+TX, Capsanem®)+TX, Steinernema feltiae (NemaShield®+TX, Nemasys F®+TX, BioNem F®+TX, Steinernema-System®+TX, NemAttack®+TX, Nemaplus®+TX, Exhibitline sf®+TX, Scia-rid®+TX, Entonem®)+TX, Steinernema kraussei (Nemasys L®+TX, BioNem L®+TX, Exhibitline srb®)+TX, Steinernema riobrave (BioVector®+TX, BioVektor®)+TX, Steinernema scapterisci (Nematac S®)+TX, Steinernema spp.+TX, Steinernematid spp. (Guardian Nematodes®)+TX, Stethorus punctillum (Stethorus®)+TX, Tamarixia radiate+TX, Tetrastichus setifer+TX, Thripobius semiluteus+TX, Torymus sinensis+TX, Trichogramma brassicae (Tricholine b®)+TX, Trichogramma brassicae (Tricho-Strip®)+TX, Trichogramma evanescens+TX, Trichogramma minutum+TX, Trichogramma ostriniae+TX, Trichogramma platneri+TX, Trichogramma pretiosum+TX, Xanthopimpla stemmator; and
(128) other biologicals including: abscisic acid+TX, bioSea®+TX, Chondrostereum purpureum (Chontrol Paste®)+TX, Colletotrichum gloeosporioides (Callego®)+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;
(129) or a biologically active compound or agent selected from: Brofluthrinate+TX, Diflovidazine+TX, Flometoquin+TX, Fluhexafon+TX, Plutella xylostella Granulosis virus+TX, Cydia pomonella Granulosis virus+TX, Imicyafos+TX, Heliothis virescens Nucleopolyhedrovirus+TX, Heliothis punctigera Nucleopolyhedrovirus+TX, Helicoverpa zea Nucleopolyhedrovirus+TX, Spodoptera frugiperda Nucleopolyhedrovirus+TX, Plutella xylostella Nucleopolyhedrovirus+TX, p-cymene+TX, Pyflubumide+TX, Pyrafluprole+TX, QRD 420+TX, QRD 452+TX, QRD 460+TX, Terpenoid blends+TX, Terpenoids+TX, Tetraniliprole+TX, and α-terpinene+TX; or an active substance referenced by a code+TX, such as code AE 1887196 (BSC-BX60309)+TX, code NNI-0745 GR+TX, code IKI-3106+TX, code JT-L001+TX, code ZNQ-08056+TX, code IPPA152201+TX, code HNPC-A9908 (CAS: [660411-21-2])+TX, code HNPC-A2005 (CAS: [860028-12-2])+TX, code JS118+TX, code ZJ0967+TX, code ZJ2242+TX, code JS7119 (CAS: [929545-74-4])+TX, code SN-1172+TX, code HNPC-A9835+TX, code HNPC-A9955+TX, code HNPC-A3061+TX, code Chuanhua 89-1+TX, code IPP-10+TX, code ZJ3265+TX, code JS9117+TX, code ZJ3757+TX, code ZJ4042+TX, code ZJ4014+TX, code ITM-121+TX, code DPX-RAB55 (DKI-2301)+TX, code NA-89+TX, code MIE-1209+TX, code MCI-8007+TX, code BCS-CL73507+TX, code S-1871+TX, code DPX-RDS63+TX, and code AKD-1193+TX.
(130) 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.
(131) 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.
(132) The active ingredient mixture of the compounds of formula I selected from Tables 1-4 with active ingredients described above comprises a compound selected from Tables 1-4 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.
(133) 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.
(134) The mixtures comprising a compound of formula I selected from Tables 1-4 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 1-4 and the active ingredients as described above is not essential for working the present invention.
(135) The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
(136) 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.
(137) 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.
(138) 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.
(139) 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.
(140) 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.
(141) 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).
(142) 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
(143) 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, 25 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm, 0.2 ppm or 0.05 ppm.
Example B1: Spodoptera Littoralis (Egyptian Cotton Leaf Worm)
(144) 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.
(145) The following compounds resulted in at least 80% control at an application rate of 200 ppm: P2, P5.
Example B2: Spodoptera Littoralis (Egyptian Cotton Leaf Worm)
(146) Test compounds were applied by pipette from 10′000 ppm DMSO stock solutions into 24-well plates and mixed with agar. Lettuce seeds were placed onto the agar and the multi well plate was closed by another plate which contained also agar. After 7 days the compound was absorbed by the roots and the lettuce grew into the lid plate. The lettuce leaves were then cut off into the lid plate. Spodoptera eggs were pipetted through a plastic stencil onto a humid gel blotting paper and the lid plate was closed with it. The samples were assessed for mortality, anti-feedant effect and growth inhibition in comparison to untreated samples 6 days after infestation.
(147) The following compounds gave an effect of at least 80% in at least one of the three categories (mortality, anti-feeding, or growth inhibition) at a test rate of 12.5 ppm: P2.
Example B3: Plutella Xylostella (Diamond Back Moth)
(148) 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 (10 to 15 per well). The samples were assessed for mortality and growth inhibition in comparison to untreated samples 5 days after infestation.
(149) 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: P2, P3, P4, P5, P9, P10, P12 and P17.
Example B4: Diabrotica Balteata (Corn Root Worm)
(150) 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.
(151) 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: P2, P3, P4, P5, P6, P10, P11, P12, P15, P16 and P17.
Example B5: Myzus Persicae (Green Peach Aphid)
(152) 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.
(153) The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P2, P4, P5, P10, P12, P15 and P17.
Example B6: Myzus Persicae (Green Peach Aphid)
(154) Roots of pea seedlings infested with an aphid population of mixed ages were placed directly into aqueous test solutions prepared from 10′000 DMSO stock solutions. The samples were assessed for mortality 6 days after placing seedlings into test solutions.
(155) The following compounds resulted in at least 80% mortality at a test rate of 24 ppm: P2, P5, P6, P10, P12, P15, P17 and P19.
Example B7: Bemisia Tabaci (Cotton White Fly)
(156) 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.
(157) The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P2, P5, P11, P12 and P17.
Example B8: Euschistus Heros (Neotropical Brown Stink Bug)
(158) 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.
(159) 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: P2, P5, P6, P9, P11, P12, P13, P15, P16, P17 and P19.
Example B10: Tetranychus Urticae (Two-Spotted Spider Mite)
(160) 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.
Example B11: Thrips Tabaci (Onion Thrips)
(161) 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 thrips population of mixed ages. The samples were assessed for mortality 6 days after infestation.
Example B12: Frankliniella Occidentalis (Western Flower Thrips)
(162) Sunflower leaf discs were placed on agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10′000 DMSO stock solutions. After drying the leaf discs were infested with a Frankliniella population of mixed ages. The samples were assessed for mortality 7 days after infestation.
Example B13: Comparison of the Insecticidal Activity of Compound P17 According to the Invention with the Structurally Most Closely Comparable Compound from the State of the Art
(163) Activity of compound P17 according to the present invention and of compound P15 from WO2016/026848 against Euschistus heros is summarized in Table B13.
(164) TABLE-US-00014 TABLE B13 Concentration Mortality Compound (ppm) Insect (%) Compound No. P15, known from 3 Euschistus heros 65 WO2016/026848
Test Description:
(165) 2 week old soybean plants were sprayed with diluted aqueous test solutions. Afterwards plants were infested with 10 stink bug nymphs (N2). Soybean seeds were added as additional food source to the test system. 5 days after treatment the samples were assessed for mortality.