Pesticidally active heterocyclic derivatives with sulphur containing sustitutents

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 ##STR00244## wherein Y is O or S; R.sub.2 is hydrogen, halogen, C.sub.1-C.sub.6haloalkyl or C.sub.1-C.sub.6alkyl; or R.sub.2 is C.sub.1-C.sub.6haloalkylsulfanyl, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.4haloalkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, SF.sub.5, cyano, C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.4alkyl or C(O)C.sub.1-C.sub.6haloalkyl; or R.sub.2 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from R.sub.6; R.sub.4 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, or is C.sub.3-C.sub.6cycloalkyl which can be mono- or poly-substituted by R.sub.20; or is C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by R.sub.20; or R.sub.4 is C.sub.1-C.sub.4alkyl substituted by R.sub.7; or R.sub.4 is C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.4alkoxy C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfanyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.1-C.sub.6haloalkylsulfinyl, amine or hydroxyl; or R.sub.4 is C.sub.2-C.sub.6alkenyl substituted by R.sub.7, or is C.sub.2-C.sub.6alkynyl substituted by R.sub.7; R.sub.5 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or C.sub.1-C.sub.4alkyl substituted by C.sub.1-C.sub.4alkylsulfanyl; R.sub.6 and R.sub.20, independently from each other, are selected from the group consisting of cyano, halogen, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.4haloalkyl; R.sub.7 is cyano, halogen, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4 alkoxy or phenyl which itself can be mono- or polysubstituted by substituents selected from R.sub.8; R.sub.8 is halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl or C.sub.1-C.sub.4alkoxy; R.sub.3 is a radical selected from the group consisting of formula Q.sub.1, Q.sub.2, Q.sub.3, Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, Q.sub.8, Q.sub.9, Q.sub.10, Q.sub.11, Q.sub.12, Q.sub.13 and Q.sub.14; ##STR00245## ##STR00246## wherein the arrow denotes the point of attachment to the imidazole ring; A represents CH or N; X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4haloalkyl; or R.sub.1 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.1 is C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; R.sub.9 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, hydroxyl, C.sub.1-C.sub.6alkoxy or S(O)m.sub.1R.sub.21; or R.sub.9 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.9 is C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.9 is C.sub.3-C.sub.6 cycloalkylcarbonyl; R.sub.10 is hydrogen, C.sub.1-C.sub.6alkyl, cyano, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6alkenyl, amino, NHCN, N(C.sub.1-C.sub.4alkyl)amino, N(C.sub.1-C.sub.4 alkyl)N(C.sub.1-C.sub.4 alkyl)amino, N(C.sub.3-C.sub.6cycloalkyl)amino, N(C.sub.1-C.sub.4alkyl)N(C.sub.3-C.sub.6cycloalkyl)amino, N(C.sub.1-C.sub.4alkylcarbonyl)amino, N(C.sub.1-C.sub.4alkyl)N(C.sub.1-C.sub.4alkylcarbonyl)amino, N(C.sub.1-C.sub.4alkyl)N(C.sub.3-C.sub.6cycloalkylcarbonyl)amino, N(C.sub.3-C.sub.6cycloalkylcarbonyl)amino, N(C.sub.1-C.sub.4alkylcarbonyl)N(C.sub.3-C.sub.6cycloalkyl)amino or S(O)mR.sub.13; or R.sub.10 is C.sub.1-C.sub.4alkyl mono- or polysubstituted by substituents independently selected from the group Z; or R.sub.10 is a five- to six-membered aromatic or heteroaromatic ring system, said aromatic or heteroaromatic ring system can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, with the proviso that each ring system cannot contain more than 2 oxygen atoms and more than 2 sulfur atoms, said five- to six-membered ring system can be mono- or polysubstituted by substituents independently selected from the group V; R.sub.11 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6 haloalkoxy, amino, NC.sub.1-C.sub.4alkylamino, N(C.sub.1-C.sub.4 alkyl)N(C.sub.3-C.sub.6 cycloalkyl)amino, N(C.sub.3-C.sub.6cycloalkyl)amino or N(C.sub.1-C.sub.4alkyl)N(C.sub.1-C.sub.4alkyl)amino; or R.sub.11 is C.sub.1-C.sub.4alkyl mono- or polysubstituted by substituents independently selected from the group Z; or R.sub.11 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.11 is C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.11 is a five- to six-membered aromatic or heteroaromatic ring system, said aromatic or heteroaromatic ring system can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, with the proviso that each ring system cannot contain more than 2 oxygen atoms and more than 2 sulfur atoms, said five- to six-membered aromatic or heteroaromatic ring system can be mono- or polysubstituted by substituents independently selected from the group V; R.sub.12 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6alkoxy, hydroxy or C.sub.1-C.sub.6haloalkoxy; or R.sub.12 is C.sub.1-C.sub.4alkyl mono- or polysubstituted by substituents independently selected from the group Z; or R.sub.12 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.12 is C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; R.sub.13 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, NC.sub.1-C.sub.4alkylamino, N,N(C.sub.1-C.sub.4 alkyl).sub.2amino or phenyl; said phenyl can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4alkyl, cyano, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkoxy; or R.sub.13 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.13 is C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; R.sub.21 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, NC.sub.1-C.sub.4alkylamino, N,N(C.sub.1-C.sub.4 alkyl).sub.2amino or phenyl; said phenyl can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4alkyl, cyano, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkoxy; or R.sub.21 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.21 is C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; m is 0, 1 or 2; m.sub.1 is 0, 1 or 2; R.sub.14 is hydrogen or C.sub.1-C.sub.6 alkyl; R.sub.15 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6 haloalkoxy, amino, NC.sub.1-C.sub.4alkylamino or N,N(C.sub.1-C.sub.4 alkyl).sub.2amino; or R.sub.15 is C.sub.1-C.sub.4alkyl mono- or polysubstituted by substituents independently selected from the group Z; or R.sub.15 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.15 is C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; p is 0 or 1; R.sub.16 is hydrogen or C.sub.1-C.sub.6 alkyl; R.sub.17 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy or C.sub.1-C.sub.6 haloalkoxy; or R.sub.17 is amino which can be mono- or disubstituted by substituents selected from the group consisting of cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.3-C.sub.6cycloalkyl and C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, said C.sub.3-C.sub.6cycloalkyl and C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl groups itself can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.17 is C.sub.1-C.sub.4alkyl mono- or polysubstituted by substituents independently selected from Z; or R.sub.17 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.17 is C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; or R.sub.17 is a five- to six-membered ring aromatic or heteroaromatic ring system, said aromatic or heteroaromatic ring system can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, with the proviso that each ring system cannot contain more than 2 oxygen atoms and more than 2 sulfur atoms, said five- to six-membered aromatic or heteroaromatic ring system can be mono- to polysubstituted by substituents independently selected from V; R.sub.18 is hydrogen, halogen, amino, cyano, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl or C.sub.3-C.sub.6cycloalkyl substituted by cyano, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 alkyl and halogen; R.sub.19 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl; Z is cyano, halogen, hydroxy, SH, amino, nitro, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl or phenyl; said phenyl can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4 alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl, cyano, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkyl; or Z is pyridyl; said pyridyl can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4 alkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl, cyano, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkyl; or Z is pyrimidyl; said pyrimidyl can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl, cyano, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkyl; and V is cyano, halogen, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl or C.sub.1-C.sub.4haloalkylsulfonyl; and agrochemically acceptable salts, stereoismers, enantiomers, tautomers and N-oxides of the compounds of formula I.

2. A compound of formula I according to claim 1, wherein Y is O; X is S, SO or SO.sub.2; and R.sub.1 is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl.

3. A compound of formula I according to claim 2, wherein R.sub.4 is methyl, ethyl, cyclopropyl.

4. A compound of formula I according to claim 2, wherein R.sub.5 is methyl.

5. A compound of formula I according to claim 2, wherein A is N; X is S or SO.sub.2; and R.sub.1 is ethyl.

6. A compound of formula I according to claim 2, wherein R.sub.3 is selected from the group Q consisting of Q.sub.1 to Q.sub.6 ##STR00247## wherein R.sub.18 is hydrogen; X is S, SO or SO.sub.2; and R.sub.1 is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl.

7. A compound of formula I according to claim 2, wherein R.sub.2 is C.sub.1-C.sub.4haloalkyl; R.sub.4 is C.sub.1-C.sub.4 alkyl or C.sub.3-C.sub.6 cycloalkyl; R.sub.5 is C.sub.1-C.sub.4 alkyl; R.sub.3 is selected from the group consisting of Q.sub.1 to Q.sub.6 ##STR00248## wherein R.sub.1 is C.sub.1-C.sub.4 alkyl; X is S, SO or SO.sub.2; R.sub.18 is hydrogen; and A is N or CH.

8. A compound of formula I according to claim 2, wherein A is N or CH; R.sub.2 is C.sub.1-C.sub.4haloalkyl; X is S, SO or SO.sub.2; R.sub.3 is selected from the group consisting of Q.sub.1 to Q.sub.6 ##STR00249## wherein R.sub.18 is hydrogen; R.sub.1 is C.sub.1-C.sub.4 alkyl; R.sub.4 is C.sub.1-C.sub.4 alkyl or C.sub.3-C.sub.6 cycloalkyl; R.sub.5 is C.sub.1-C.sub.4 alkyl; R.sub.9 is hydrogen or C.sub.1-C.sub.4alkyl; or R.sub.9 is C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl; R.sub.10 is hydrogen, C.sub.1-C.sub.6alkyl, cyano, N(C.sub.1-C.sub.4 alkyl)N(C.sub.3-C.sub.6cycloalkylcarbonyl)amino, NC.sub.3-C.sub.6cycloalkylcarbonylamino or S(O).sub.2R.sub.13; or R.sub.10 is C.sub.1-C.sub.4alkyl mono- or disubstituted by a group selected from cyano and halogen; or R.sub.10 is phenyl, pyridinyl or pyrazolyl; said phenyl, pyridinyl or pyrazolyl can be mono to polysubstituted by substituents independently selected from C.sub.1-C.sub.4haloalkyl and halogen; and R.sub.11 is C.sub.1-C.sub.4alkyl, NC.sub.1-C.sub.4alkylamino or N,N(C.sub.1-C.sub.4alkyl).sub.2amino.

9. A compound of formula I according to claim 2, wherein A is N or CH; R.sub.2 is C.sub.1-C.sub.4haloalkyl; X is S, SO or SO.sub.2; R.sub.3 is selected from the group consisting of Q.sub.1 to Q.sub.6 ##STR00250## wherein R.sub.18 is hydrogen; R.sub.1 is C.sub.1-C.sub.4 alkyl; R.sub.4 is C.sub.1-C.sub.4 alkyl or C.sub.3-C.sub.6 cycloalkyl; R.sub.5 is C.sub.1-C.sub.4 alkyl; R.sub.9 is hydrogen, C.sub.1-C.sub.4alkyl or C.sub.3-C.sub.6cycloalkyl; R.sub.10 is hydrogen or C.sub.1-C.sub.6alkyl; and R.sub.11 is C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.6cycloalkyl, or is C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.6cycloalkyl mono- or polysubstituted by substituents selected from the group consisting of halogen, C.sub.1-C.sub.4haloalkyl, cyano and C.sub.1-C.sub.4alkyl.

10. A compound of formula I according to claim 2, wherein Y is O; R.sub.2 is C.sub.1-C.sub.2 haloalkyl; R.sub.4 is C.sub.1-C.sub.3 alkyl or cyclopropyl; R.sub.5 is C.sub.1-C.sub.3 alkyl; R.sub.3 is selected from the group consisting of Q.sub.1 to Q.sub.7, Q.sub.9, Q.sub.10 and Q.sub.11 ##STR00251## ##STR00252## X is S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.3 alkyl; A is N or CH; R.sub.9 is hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, hydroxyl or C.sub.1-C.sub.6alkoxy; or R.sub.9 is cyclopropylcarbonyl, cyclopropyl, cyclopropyl monosubstituted by cyano, or is S(O).sub.2C.sub.1-C.sub.2alkyl; R.sub.10 is hydrogen, C.sub.1-C.sub.6alkyl, S(O).sub.2C.sub.1-C.sub.2alkyl, S(O).sub.2cyclopropyl, amino, N(C.sub.1-C.sub.2alkyl)amino or N(C.sub.1-C.sub.2alkyl)N-(cyclopropylcarbonyl)amino; R.sub.10 is C.sub.1-C.sub.4alkyl monosubstituted by cyano; R.sub.11 is C.sub.1-C.sub.6alkoxy or cyclopropyl which can be substituted by cyano; R.sub.12 is hydroxyl and C.sub.1-C.sub.4 alkyl; R.sub.14 is C.sub.1-C.sub.4 alkyl; R.sub.15 is cyclopropyl; p is 1; R.sub.18 is hydrogen, C.sub.1-C.sub.3 alkyl, halogen, cyclopropyl or cyano and R.sub.19 is C.sub.1-C.sub.4alkoxy.

11. A pesticidal composition, which comprises at least one compound of formula I according to claim 1 or a tautomer thereof, in each case in free form or in agrochemically utilizable salt form, as active ingredient and at least one auxiliary.

12. A method for controlling pests, which comprises applying a composition according to claim 11 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.

13. A method for the protection of plant propagation material from the attack by pests, which comprises treating the propagation material or a site, where the propagation material is planted, with a composition according to claim 11.

14. A plant propagation material treated with at least one compound of formula I according to claim 1.

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. Common abbreviations: aq=aqueous, min=minute, h=hour, sat=saturated, RT=retention time, mCPBA=meta-chloroperoxybenzoic acid, MeOH=methanol, EtOH=ethanol, NaHCO.sub.3=sodium hydrogen carbonate, Na.sub.2CO.sub.3=sodium carbonate, HCl=hydrogen chloride, CH.sub.2Cl.sub.2=dichloromethane, Et.sub.3N=triethylamine, DMF=N,N-dimethylformamide. Either one of the LCMS and/or GCMS 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.+.

(2) LCMS and GCMS Methods:

(3) Method AStandard:

(4) Spectra were recorded on a Mass Spectrometer from Waters (SQD or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150 C., Desolvation Temperature: 350 C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 m, 302.1 mm, Temp: 60 C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH: gradient: gradient: 0 min 0% B, 100% A; 1.2-1.5 min 100% B; Flow (ml/min) 0.85.

(5) Method BStandard Long:

(6) Spectra were recorded on a Mass Spectrometer from Waters (SQD or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150 C., Desolvation Temperature: 350 C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 m, 302.1 mm, Temp: 60 C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH: gradient: gradient: 0 min 0% B, 100% A; 2.7-3.0 min 100% B; Flow (ml/min) 0.85

(7) Method CUnpolar:

(8) Spectra were recorded on a Mass Spectrometer from Waters (SQD or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150 C., Desolvation Temperature: 350 C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 m, 302.1 mm, Temp: 60 C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH: gradient: gradient: 0 min 40% B, 60% A; 1.2-1.5 min 100% B; Flow (ml/min) 0.85

Example I1: 4-amino-1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(9) ##STR00048##

Step A: 1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(10) ##STR00049##

(11) To a solution of 3-amino-1-ethyl-6-(trifluoromethyl)pyridin-2-one (5.00 g, 24.3 mmol, Commercially available or synthesised by analogy with literature, for example, Synthesis 2005, No. 8, pp 1269-1278 and Synthesis 2011, No. 7, pp 1149-1156) in acetonitrile (150 mL) was added formaldehyde (37 mass %) in aqueous solution (14.5 ml, 194 mmol) and acetic acid (6.96 ml, 121 mmol). The resulting suspension stirred for 1 hour, then sodium cyanoborohydride (6.42 g, 97.0 mmol) was added in 5 portions over 3 hours and the mixture was stirred for 18 hours. The solution was diluted with water and extracted with ethyl acetate (3). The combined organic layer was dried over Sodium sulfate, filtered, concentrated and purified by column chromatography using cyclohexane-ethyl acetate (100-200 silica gel) to give the desired compound as a white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 6.70 (d, 1H), 6.04 (d, 1H), 5.44 (sb, 1H), 4.15 (q, 2H), 2.85 (s, 3H), 1.32 (t, 3H).

Step B: 1-ethyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one

(12) ##STR00050##

(13) A solution of 1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one (14.3 g, 64.9 mmol) sulfuric acid (195 mL, 356 mmol) was cooled with an ice bath at 0 C. Then, Ice (71.5 g, 397 mmol) and nitric acid (6.30 g, 4.53 mL, 64.9 mmol) were added. After 15 min at 0-10 C., the brown thick solution was poured into iced water. The orange precipitate form was filtrated off, rinsing with water and drying under vacuum to give an orange solid. The water phase was extracted 3 times with ethyl acetate and the orange solid, obtained before, was added to the combinated organic phase. The combinated organic phase was washed with a saturated solution of sodium hydrogenocarbonate, water and brine, dried over magnesium sulfate and concentrated under vacuum to give yield the title compound (4.0 g). The compound was used without extra purification for the next step. LC-MS (Method A): RT 0.98, 276 (M+H.sup.+).

Step C: 4-amino-1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(14) ##STR00051##

(15) To a solution of 1-ethyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one (12.3 g, 46.4 mmol) in propan-2-ol (500 mL, 6500 mmol) was added tin(II) chloride dihydrate (32.0 g, 167 mmol) followed by hydrogen chloride (50 mL, 610 mmol, 37% aq. solution). The resulting solution was stirred at 70 C. for one hour, and, then allowed to cool down to ambient temperature. The reaction mixture was poured into water, and pH was adjusted to 10-12 with a concentrated aqueous solution of sodium hydroxide (30%).

(16) The aqueous phase was extracted three times with ethyl acetate; the organic phases were combinated, dried over magnesium sulfate and concentrated under vacuum. The residue was subjected to column chromatography over silica gel, eluting with ethyl acetate/cyclohexane. The selected fractions were evaporated to yield the title compound (8.43 g). LC-MS (Method A): RT 0.47, 236 (M+H.sup.+).

Example I2: Preparation of 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylic Acid

(17) ##STR00052##

Step A: Preparation of 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylic Acid

(18) ##STR00053##

(19) To a solution of methyl 5-bromo-3-chloro-pyridine-2-carboxylate (0.100 g, 0.399 mmol) (commercial product) in tetrahydrofuran, stirred at 0 C., was added ethylsulfanylsodium (0.034 g, 1 equiv.). After 1 hour at that temperature, the ice bath was removed and stirring was continued for 20 hours. The reaction mixture was then poured onto water (15 ml) and extracted twice with ethyl acetate. The organic phases were dried over sodium sulfate and the solvent was removed. The residue was submitted to flash chromatography over silica gel and the selected fractions evaporated to yield methyl 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate as a colorless solid. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.46 (s, 1H); 7.79 (s, 1H); 4.00 (s, 3H); 2.94 (q, J=7.4 Hz, 2H); 1.42 (t, J=7.4 Hz, 3H).

Step B: Preparation of 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylic Acid

(20) ##STR00054##

(21) A solution of methyl 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate (3.900 g, 14.12 mmol) (preparation described here above) in a mixture of methyl alcohol (75 ml) and water (20 ml) stirred at 20 C. was treated with 2N aqueous sodium hydroxide solution (7.04 ml, 1.05 equiv.). The mixture was stirred for two hours, and then most of the alcohol was eliminated under reduced pressure. The residue was then treated with 2N aqueous hydrochloric acid solution and the resulting precipitate was filtered off, washed with water and dried under vacuum. The title compound was obtained as a colorless solid. .sup.1H NMR (400 MHz, d6-DMSO) ppm: 13.4 (s, 1H); 8.50 (s, 1H); 8.07 (s, 1H); 3.04 (q, 2H); 1.27 (t, 3H).

Example I3: Preparation of 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(22) ##STR00055##

Step A: Preparation of 5-bromo-N-[1-ethyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-4-pyridyl]-3-ethylsulfanyl-pyridine-2-carboxamide and N-[4-amino-1-ethyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]-5-bromo-3-ethylsulfanyl-N-methyl-pyridine-2-carboxamide

(23) ##STR00056##

(24) To a suspension of 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylic acid (2.61 g, 9.95 mmol) in dichloromethane (25 ml) was added one drop of N,N-dimethylformamide, followed by oxalyl chloride (2.93 g, 2.01 mL, 22.6 mmol). After the end of gas evolution, the reaction mixture was a pale red solution. The latter was evaporated under reduced pressure at a bath temperature of 60 C. The residue formed dark red crystals of 5-bromo-3-ethylsulfanyl-pyridine-2-carbonyl chloride and the residue was redissolved in a mixture ethyl acetate (20 mL) and dichloromethane (15 mL).

(25) To a solution of 4-amino-1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one (prepared in Example I1, 2.00 g, 9.04 mmol) in ethyl acetate (100 ml) was added N,N-diethylethanamine (2.31 g, 3.18 mL, 22.6 mmol) then the resulting solution was cooled with an ice bath, before slow addition of the previous acid chloride solution. The resulting mixture was stirred 1 hour at 0 C. The solution was neutralized by addition of a saturated aqueous solution of sodium bicarbonate and the product was extracted twice with ethyl acetate. The organic solution was dried over sodium sulfate and evaporated under reduced pressure to yield the crude product. A mixture 70:30 of 5-bromo-N-[1-ethyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-4-pyridyl]-3-ethylsulfanyl-pyridine-2-carboxamide and N-[4-amino-1-ethyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]-5-bromo-3-ethylsulfanyl-N-methyl-pyridine-2-carboxamide was obtained and used without extra purification for the next step. LC-MS (Method A): RT 0.86, 467.1 (M+H.sup.+), 465.1 (MH.sup.+).

Step B: Preparation of 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(26) ##STR00057##

(27) To a solution of 5-bromo-N-[1-ethyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-4-pyridyl]-3-ethylsulfanyl-pyridine-2-carboxamide and N-[4-amino-1-ethyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]-5-bromo-3-ethylsulfanyl-N-methyl-pyridine-2-carboxamide (9.7 g, 20 mmol) in glacial acetic acid (49 mL, 850 mmol) was refluxed for 12 hours. The dark brown solution was allowed to cool down, and was poured into water.

(28) The resulting beige suspension was filtered, washed with water, and solid was redissolved into ethyl acetate (250 mL), dried over Magnesium sulfate and concentrated under vacuum to give 2-(5-bromo-3-ethylsulfanyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one. LC-MS (method A): RT 1.14, 462 (M+H). .sup.1H NMR (400 MHz, CDCl3) ppm 1.37 (m, 6H) 2.95 (m, 2H) 4.20 (s, 3H) 4.25 (s, 2H) 7.36 (s, 1H) 7.86 (d, 1H) 8.56 (d, 1H).

Step C: Preparation of 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(29) ##STR00058##

(30) To a solution of 2-(5-bromo-3-ethylsulfanyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (Prepared in Step B, 6.46 g, 14.0 mmol) in dichloromethane (150 mL, 2330 mmol) was added meta-chloroperbenzoic acid (6.61 g, 28.7 mmol). The yellow solution was stirred at room temperature for an hour. After this time, the reaction mixture was diluted with aqueous sodium thiosulfate solution and extracted with dichloromethane, the combined organic fractions washed with sodium carbonate, dried over magnesium sulfate, and concentrated in vacuo. The crude product was dissolved in dichloromethane and adsorbed on TEFLON BULK SORBENTS, and purified over a silica gel cartridge (TORENT) eluting with heptane/ethyl acetate and then dichloromethane/methanol. This gave the title product as the first eluting product. LC-MS (method A): RT 1.05, 493 (M+H). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.38 (m, 6H) 3.82 (q, 2H) 4.09 (s, 3H) 4.25 (q, 2H) 7.22 (s, 1H) 8.64 (d, 1H) 9.03 (d, 1H).

(31) 2-(5-bromo-3-ethylsulfinyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one was prepared by using the same protocol with only one equivalent of m-CPBA: .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 8.84 (s, 1H), 8.74 (s, 1H), 7.22 (s, 1H), 4.57 (s, 3H), 4.30 (q, 2H), 3.63 (m, 1H), 3.05 (m, 1H), 1.48-1.308 (m, 6H).

(32) ##STR00059##

Example I4: 4-amino-1-methyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(33) ##STR00060##

Step A: 1-methyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(34) ##STR00061##

(35) To a solution of 3-amino-1-methyl-6-(trifluoromethyl)pyridin-2-one (1.00 g, 5.20 mmol, Commercially available or synthesized as described for example in Synthesis 2005, No. 8, pp 1269-1278, Synthesis 2011, No. 7, pp 1149-1156) in 1,4-dioxane (62.5 mL, 726 mmol) and pyridine (1.49 mL, 18.2 mmol) under argon was added diacetoxycopper (2.39 g, 13.0 mmol). The mixture was stirred for 15 min before addition of methyl boronic acid (0.803 g, 13.0 mmol). The resulting green/blue suspension was refluxed for 5 hours. After cooling, the solution was filtered through a Celite pad. The dark green solution was concentrated under vacuum and was subjected to column chromatography over silica gel, eluting with ethyl acetate/cyclohexane. The selected fractions were evaporated to yield the title compound (0.71 g). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 7.27 (s, 1H); 6.72 (d, 1H); 6.04 (d, 2H), 5.46 (bs, 1H), 3.68 (s, 3H), 2.88 (d, 3H).

Step A: Alternative

(36) To a solution of 3-amino-1-methyl-6-(trifluoromethyl)pyridin-2-one (5 g, 26.023 mmol) in acetonitrile (133 g, 169.15 mL,) was added formaldehyde (37 mass %) in aq. solution (16.894 g, 15.60 mL, 208.2 mmol) and acetic acid (7.83 g, 7.46 mL, 130.11 mmol). The reaction was stirred at room temperature for 1 hour then sodium cyanoborohydride (6.89 g, 104.1 mmol) was added in fives portions over 3 hours and the mixture was stirred overnight. The white cloudy solution was extracted with ethyl acetate/water. the organic phase was washed with brine, dried over magnesium sulfate, and concentrated under vacuum. the residue was purified by Flash chromatography to give 1-methyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one (4.32 g) as a white solid.

Step B: 1-methyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one

(37) ##STR00062##

(38) A solution of 1-methyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one (4.00 g, 19.4 mmol) sulfuric acid (58.2 mL) was cooled with an ice bath at 0 C. Then, Ice (20.0 g) and nitric acid (1.88 g, 1.35 mL, 19.4 mmol) were added. After 15 min at 0-10 C., the brown thick solution was poured into iced water. The orange precipitate form was filtrated off, rinsing with water and drying under vacuum to give an orange solid. The water phase was extracted 3 times with Ethyl acetate and the orange solid, obtained before, was added to the combinated organic phase. The combinated organic phase was washed with a saturated solution of sodium hydrogen carbonate, water and brine, dried over magnesium sulfate and concentrated under vacuum to give yield the title compound (4.0 g). The compound was used without extra purification for the next step. LC-MS (Method A): RT 0.91, 252 (M+H.sup.+), 250 (MH.sup.+).

Step C: 4-amino-1-methyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(39) ##STR00063##

(40) To a solution of 1-methyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one (3.0 g, 11.9 mmol) in propan-2-ol (98.1 g, 125 mL, 1620 mmol) was added Tin dichloride (8.24 g, 43.0 mmol) followed by hydrogen chloride (10 mL, 120 mmol, 37%). The resulting solution was stirred at 70 C. for one hour, and, then allowed to cool down to ambient temperature. The reaction mixture was poured into water, and pH was adjusted to 10-12 with a concentrated aqueous solution of sodium hydroxide (30%). The aqueous phase was extracted three times with ethyl acetate; the organic phases were combinated, dried over magnesium sulfate and concentrated under vacuum. subjected to column chromatography over silica gel, eluting with ethyl acetate/cyclohexane. The selected fractions were evaporated to yield the title compound (2.15 g). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 6.30 (s, 1H); 4.15 (bs, 2H), 3.8 (bs, 1H), 3.60 (s, 3H), 2.64 (s, 3H).

Example I5: 6-chloro-3-ethylsulfanyl-pyridine-2-carboxylic Acid

(41) ##STR00064##

Step A: methyl 3,6-dichloropyridine-2-carboxylate

(42) ##STR00065##

(43) To a suspension of 3,6-dichloropyridine-2-carboxylic acid (22.3 g, 116 mmol) (commercial product) in methanol (223 mL) was added sulfuric acid (12.0 g, 6.55 mL, 116 mmol) at ambient temperature. The resulting mixture was stirred four hours at 65 C. The reaction mixture was concentrated under reduce pressure. The crude was dissolved in dichloromethane and with a saturated solution of sodium hydrogen carbonate solution. Then washed with sodium chloride and the organic layer were dried over magnesium sulfate and concentrated under vacuum. Methyl 3,6-dichloropyridine-2-carboxylate was obtained as a white crystal was obtained. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 4.00 (s, 3H), 7.42 (d, 1H), 7.76 (d, 1H).

Step B: Preparation of methyl 6-chloro-3-ethylsulfanyl-pyridine-2-carboxylate

(44) ##STR00066##

(45) A solution of methyl 3,6-dichloropyridine-2-carboxylate (20 g, 97.073 mmol, commercial compound) in tetrahydrofuran (200 mL) was treated with catalytic quantities of 18-crown-6-ether (ca. 300 mg) followed by sodium ethoxide (9.073 g, 97.073 mmol) in 3 portions. The reaction was the allowed to stir at ambient temperature for 1 hour. LCMS analysis after this time showed consumption of starting materials and the formation of three new products. The reaction mixture was poured on 100 ml saturated ammonium chloride aqueous solution, extracted with 2 100 ml Ethyl acetate, and the combined organic layers washed with 2 50 ml saturated aqueous ammonium chloride aqueous solution, 3 100 ml water, dried over Sodium sulfate, filtered and concentrated in vacuum. The crude product was purified by combi flash chromatography with a column of 220 g and a gradient cyclohexane+0-10% Ethyl acetate. This gave as the first eluting product methyl 3,6-bis(ethylsulfanyl)pyridine-2-carboxylate (Method A, retention time 1.04 mins, (MH+)=258). The second product to elute was methyl 3-chloro-6-ethylsulfanyl-pyridine-2-carboxylate (Method A, retention time 0.99 min, (MH+)=232). The final product to elute was the major product and desired title product, as white crystals. LC-MS (method A): RT 0.88 mins, 232 (MH+). .sup.1H NMR (400 MHz, chloroform-d) ppm 1.40 (t, 3H) 2.95 (q, 2H) 4.00 (s, 3H) 7.41 (d, 1H) 7.66 (d, 1H).

Step C: 6-chloro-3-ethylsulfanyl-pyridine-2-carboxylic Acid

(46) ##STR00067##

(47) A solution of methyl 6-chloro-3-ethylsulfanyl-pyridine-2-carboxylate (3.900 g, 14.12 mmol) (preparation described here above) in a mixture of methyl alcohol (75 ml) and water (20 ml) stirred at 20 C. was treated with 2N aqueous sodium hydroxide solution (7.04 ml, 1.05 equiv.). The mixture was stirred for two hours, and then most of the alcohol was eliminated under reduced pressure. The residue was then treated with 2N aqueous hydrochloric acid solution and the resulting precipitate was filtered off, washed with water and dried under vacuum. The title compound was obtained as a colorless solid. .sup.1H NMR (400 MHz, DMSO) ppm 1.23 (d, 3H) 2.99 (q, 2H) 7.64 (d, 1H) 7.95 (d, 1H).

Example I6: 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(48) ##STR00068##

Step A: 6-chloro-3-ethylsulfanyl-N-[1-methyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-4-pyridyl]pyridine-2-carboxamide and N-[4-amino-1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]-6-chloro-3-ethylsulfanyl-N-methyl-pyridine-2-carboxamide

(49) ##STR00069##

(50) Prepared from intermediate 4-amino-1-methyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one and 6-chloro-3-ethylsulfanyl-pyridine-2-carboxylic acid, using a similar protocol as described in Example I3 Step A. LC-MS (Method A): RT 0.86, 421 (M+H.sup.+).

Step B: 2-(6-chloro-3-ethylsulfanyl-2-pyridyl)-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(51) ##STR00070##

(52) Prepared from intermediate 2-(6-chloro-3-ethylsulfanyl-2-pyridyl)-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one, using a similar protocol as described in Example I3 Step B: LC-MS (Method A) RT 1.07, 403 (MH+). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.32 (t, 3H), 2.92 (q, 2H), 3.73 (d, 3H), 4.23 (s, 3H), 7.31 (s, 1H), 7.40 (d, 1H), 7.72 (d, 1H).

Step C: 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(53) ##STR00071##

(54) Prepared from intermediate 2-(6-chloro-3-ethylsulfanyl-2-pyridyl)-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one, using a similar protocol as described in Example I3 Step C: LC-MS (Method A) RT 0.99, 435 (MH+). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.34 (t, 3H), 3.75 (s, 3H), 3.78 (q, 2H), 4.12 (s, 3H), 7.20 (s, 1H), 7.70 (d, 1H), 8.44 (d, 1H).

Example I7: 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(55) ##STR00072##

Step A: 1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(56) ##STR00073##

(57) To a solution of 3-amino-1-ethyl-6-(trifluoromethyl)pyridin-2-one (5.00 g, 24.3 mmol, Commercially available or synthesised by analogy with literature, for example, Synthesis 2005, No. 8, pp 1269-1278 and Synthesis 2011, No. 7, pp 1149-1156) in acetonitrile (150 mL) was added formaldehyde (37 mass %) in aqueous solution (14.5 ml, 194 mmol) and acetic acid (6.96 ml, 121 mmol). The resulting suspension stirred for 1 hour, then sodium cyanoborohydride (6.42 g, 97.0 mmol) was added in 5 portions over 3 hours and the mixture was stirred for 18 hours. The solution was diluted with water and extracted with ethyl acetate (3). The combined organic layer was dried over Sodium sulfate, filtered, concentrated and purified by column chromatography using cyclohexane-ethyl acetate (100-200 silica gel) to give the desired compound as a white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 6.70 (d, 1H), 6.04 (d, 1H), 5.44 (sb, 1H), 4.15 (q, 2H), 2.85 (s, 3H), 1.32 (t, 3H).

Step B: 1-ethyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one

(58) ##STR00074##

(59) A solution of 1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one (14.3 g, 64.9 mmol) sulfuric acid (195 mL, 3560 mmol) was cooled with an ice bath at 0 C. Then, Ice (71.5 g, 3970 mmol) and nitric acid (6.30 g, 4.53 mL, 64.9 mmol) were added. After 15 min at 0-10 C., the brown thick solution was poured into iced water. The orange precipitate form was filtrated off, rinsing with water and drying under vacuum to give an orange solid. The water phase was extracted 3 times with ethyl acetate and the orange solid, obtained before, was added to the combinated organic phase. The combinated organic phase was washed with a saturated solution of sodium hydrogenocarbonate, water and brine, dried over magnesium sulfate and concentrated under vacuum to give yield the title compound (4.0 g). The compound was used without extra purification for the next step. LC-MS (Method A): RT 0.98, 276 (M+H.sup.+).

Step C: 4-amino-1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(60) ##STR00075##

(61) To a solution of 1-ethyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one (12.3 g, 46.4 mmol) in propan-2-ol (500 mL, 6500 mmol) was added tin(II) chloride dihydrate (32.0 g, 167 mmol) followed by hydrogen chloride (50 mL, 610 mmol, 37%). The resulting solution was stirred at 70 C. for one hour, and, then allowed to cool down to ambient temperature. The reaction mixture was poured into water, and pH was adjusted to 10-12 with a concentrated solution of sodium hydroxide (30%).

(62) The aqueous phase was extracted three times with ethyl acetate; the organic phases were combinated, dried over magnesium sulfate and concentrated under vacuum. The residue was subjected to column chromatography over silica gel, eluting with ethyl acetate/cyclohexane. The selected fractions were evaporated to yield the title compound (8.43 g). LC-MS (Method A): RT 0.47, 236 (M+H.sup.+).

Step D: 6-chloro-N-[1-ethyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-4-pyridyl]-3-ethylsulfanyl-pyridine-2-carboxamide and N-[4-amino-1-ethyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]-6-chloro-3-ethylsulfanyl-N-methyl-pyridine-2-carboxamide

(63) ##STR00076##

(64) Under argon, 6-chloro-3-ethylsulfanyl-pyridine-2-carboxylic acid (as prepared in Example I5) (4.2 g, 19 mmol) was dissolved in dichloromethane (39 mL) with oxalyl dichloride (5.0 g, 39 mmol) and N,N-dimethylformamide (1 drop). The mixture was stirred for 30 min at room temperature then at reflux for 30 min. Then the solvent was removed and dried under vacuum, 6-chloro-3-ethylsulfanyl-pyridine-2-carbonyl chloride (4.2 g, 18 mmol) was diluted with 5 ml of tetrahydrofuran and a solution of 4-amino-1-ethyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one (4.6 g, 20 mmol) in tetrahydrofuran (36 mL) and pyridine (4.2 g, 4.3 mL) was added. The mixture was stirred at reflux for 3 hours, then the brown suspension was poured into a saturated solution of sodium bicarbonate, extracted with ethyl acetate, organic phase was washed with a solution of Hydrogen chloride (1N), brine, dried over MgSO.sub.4 and concentrated under vacuum to give a mixture of 6-chloro-N-[1-ethyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-4-pyridyl]-3-ethylsulfanyl-pyridine-2-carboxamide and N-[4-amino-1-ethyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]-6-chloro-3-ethylsulfanyl-N-methyl-pyridine-2-carboxamide (7 g, 90%) as a brown solid. LC-MS (Method A): RT 0.91, 436 (M+H.sup.+), 433 (MH.sup.+).

Step E: 2-(6-chloro-3-ethylsulfanyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(65) ##STR00077##

(66) 6-chloro-N-[1-ethyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-4-pyridyl]-3-ethylsulfanyl-pyridine-2-carboxamide and N-[4-amino-1-ethyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]-6-chloro-3-ethylsulfanyl-N-methyl-pyridine-2-carboxamide (7.0 g, 16 mmol) were dissolved in acetic acid (50 mL) and refluxed for 24 hours. The reaction was concentrated under reduced pressure to remove all acetic acid, and then dissolved in dichloromethane and purified by combiflash to give 2-(6-chloro-3-ethylsulfanyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (5 g, 75%) as an slightly yellow solid. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.72 (d, 1H), 7.40 (d, 1H), 7.32 (s, 1H), 4.29-4.21 (m, 5H), 2.93 (q, 2H), 1.42-1.28 (m, 6H).

Step F: 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(67) ##STR00078##

(68) To a solution of 2-(6-chloro-3-ethylsulfanyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (4.6 g, 11 mmol) in dichloromethane (50 mL) was added 3-chlorobenzenecarboperoxoic acid (5.2 g, 23 mmol). The mixture was allowed to stand over night at room temperature. It was quenched with a solution of sodium thiosulfate (100 ml) and The reaction was diluted with 1N NaOH (100 ml), extracted with dichloromethane (350 ml). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (4.6 g, 93%). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.43 (d, 1H), 7.69 (d, 1H), 7.20 (s, 1H), 4.25 (q, 2H), 4.13 (s, 3H), 3.78 (m, 2H), 1.45-1.31 (m, 6H).

Example I8: 4-amino-1-cyclopropyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(69) ##STR00079##

Step A: 1-cyclopropyl-3-(amino)-6-(trifluoromethyl)pyridin-2-one

(70) ##STR00080##

(71) A sealed bomb was charged with N-[2-oxo-6-(trifluoromethyl)pyran-3-yl]benzamide (commercially available, CAS Registry Number 312615-59-1, 30 g, 105.9 mmol), tetrahydrofuran (132.4 mL, 1620 mmol) and cyclopropylamine (8.24 mL, 116.5 mmol). The mixture was stirred for overnight at 70 C. The sealed vial was cooled and the reaction mixture was dissolved with water and ethyl acetate (250 ml/250 ml). The aqueous phase was extracted with ethyl acetate (3) and the combined organic layer was dried over sodium sulfate, filtered, concentrated under vacuum. The residue was purified by column chromatography using cyclohexane-ethyl acetate to give the starting material and 23 g of N-[1-cyclopropyl-2-hydroxy-6-oxo-2-(trifluoromethyl)-3H-pyridin-5-yl]benzamide. The N-[1-cyclopropyl-2-hydroxy-6-oxo-2-(trifluoromethyl)-3H-pyridin-5-yl]benzamide was dissolved in hydrogen chloride (563 g, 473.1 mL, 5710 mmol) and the mixture was stirred at 100 C. for Over Night. The precipitate of Benzoic acid was filtered off and the filtrate was basified to pH 7-8 with a solution of sodium hydroxyl conc. Then the water phase was extracted (3) with AcOEt and the combined organic layers were dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by column chromatography using cyclohexane-ethyl acetate to give 12 g of 1-cyclopropyl-3-(amino)-6-(trifluoromethyl)pyridin-2-one. LC-MS (Method A): RT 0.79, 219 (M.sup.+H.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 6.59 (d, 1H), 6.33 (d, 1H), 4.60 (sb, 2H), 3.07 (m, 1H), 1.24 (m, 2H), 1.02 (m, 2H).

Step B: 1-cyclopropyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(72) ##STR00081##

(73) The 1-cyclopropyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one was prepared as for Example I4, step A. LC-MS (Method A): RT 0.93, 233 (M+H.sup.+).

Step C: 1-cyclopropyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one

(74) ##STR00082##

(75) The 1-cyclopropyl-3-(methylamino)-4-nitro-6-(trifluoromethyl)pyridin-2-one was prepared as for Example I2, step C. LC-MS (Method A): RT 0.98, 278 (M+H.sup.+).

Step D: 4-amino-1-cyclopropyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one

(76) ##STR00083##

(77) The 4-amino-1-cyclopropyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one was prepared as for Example I2, step D. LC-MS (Method A): RT 0.52, 247 (M+H.sup.+). Alternatively, the 4-amino-1-cyclopropyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2-one could be prepared via hydrogenation in presence of Pd/C in ethanol using classical reaction. 1H NMR (400 MHz, CDCl3) ppm 6.28 (s, 1H), 4.08 (sb, 2H), 3.81 (sb, 1H), 2.97 (m, 1H), 2.63 (s, 3H), 1.18 (m, 2H), 0.98 (m, 2H).

Example I9: 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(78) ##STR00084##

(79) 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one was prepared as described for Example I7 using the appropriate intermediates.

(80) 2-(6-chloro-3-ethylsulfanyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one: .sup.1H NMR (400 MHz, DMSO) ppm 8.08 (d, 1H), 7.70 (d, 1H), 7.34 (s, 1H), 4.02 (s, 3H), 3.08 (m, 1H), 3.04 (q, 2H), 1.18 (m, 5H), 0.96 (m, 2H).

(81) 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one: .sup.1H NMR (400 MHz, DMSO) ppm 8.52 (d, 1H), 8.08 (d, 1H), 7.38 (s, 1H), 3.91 (s, 3H), 3.74 (q, 2H), 3.08 (m, 1H), 1.18 (m, 5H), 0.98 (m, 2H).

Example P1: Preparation of 2-[6-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A1

(82) ##STR00085##

(83) To a solution of 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (Prepared 13 step C, 500 mg, 1.0136 mmol), cyclopropylamine (63.66 mg, 0.077 mL), cesium carbonate (1155.87 mg, 3.55 mmol) and (5-diphenylphosphanyl-9,9-dimethyl-xanthen-4-yl)-diphenyl-phosphane (30.2438 mg, 0.0507 mmol) in 1,4-dioxane (9.914 g, 9.588 mL, 112 mmol) was added (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium (9.5349 mg, 0.0101 mmol) under argon atmosphere at room temperature. The mixture was heated at 95 C. stirred for Overnight. The reaction mixture was poured to a mixture of water and ethyl acetate. The organic phase was separated, dried on magnesium sulfate and concentrated under vacuum. The crude product was dissolved in dichloromethane, adsorbed onto TEFLON BULK SORBENTS, and then purified over a silica gel cartridge (Rf200), eluting with dichloromethane/methanol to give the title compound (55.4 mg, 11.6%). LC-MS (Method A) RT 1.00, 470 (MH+) 468 (MH). .sup.1H NMR (400 MHz, CDCl3) ppm 0.63 (m, 2H), 0.93 (m, 2H), 1.36 (m, 6H), 2.60 (m, 1H), 3.71 (q, 2H), 4.02 (s, 3H), 4.25 (m, 2H), 7.19 (s, 1H), 7.73 (d, 1H), 8.40 (d, 1H)

Example P2: Preparation of 2-[6-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A2

(84) ##STR00086##

(85) To a solution of 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-3,5-dimethyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (200 mg, 0.46 mmol) and triethylamine (3.0 equiv., 0.194 mL, 0.1410 g) in tetrahydrofuran (1.0 equiv., 2 mL) was added cyclopropylamine (1.5 equiv., 0.0488 mL). The mixture was stirred at 70 C. for 1 h. The reaction was not complete; cyclopropylamine (1.5 equiv., 0.0488 mL, 0.04020 g) was added and stirred overnight at 70 C. to complete conversion. The mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered and evaporated to yield a pale brown solid. LC-MS (Method A) RT 0.95, 456 (MH+) 454 (MH). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.63 (m, 2H), 0.93 (m, 2H), 1.30 (t, 3H), 3.5 (q, 2H), 3.70 (s, 3H), 4.00 (s, 3H), 5.70 (s, 1H), 6.9 (d, 1H), 8.10 (d, 1H).

Example P3: Preparation of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxylic Acid A3

(86) ##STR00087##

Step A: Preparation of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonitrile

(87) ##STR00088##

(88) 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (Prepared 13 step C, 0.1 g, 0.2 mmol) was dissolved in N,N-dimethyl acetamide (1 mL). To this reaction mixture was added zinc dust (0.02 mmol, 0.002 g) and 1,1-bis(diphenylphosphino)ferrocene (0.008 mmol, 0.004 g) and then purged with N.sub.2 gas for 10 min with constant stirring. zinc cyanide (0.1 mmol, 0.01 g) and (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium (0.004 mmol, 0.004 g) were then added to the above reaction mixture and heated at 130 C. for 1 h. After completion, the reaction mixture was quenched in 2 M NH.sub.4OH solution (5 mL), extracted with ethyl acetate (15 mL3), organic layer was then washed with water (10 ml3), brine solution, dried and concentrated. The crude was purified by combiflash using 10% Ethyl acetate-Cyclohexane solvent system to give 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonitrile (0.07 g, 80%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.38 (m, 6H) 3.91 (m, 2H) 4.16 (s, 3H) 4.26 (m, 2H), 7.21 (s, 1H) 8.78 (d, 1H) 9.19 (d, 1H).

Step B: Preparation of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxylic Acid A3

(89) ##STR00089##

(90) 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonitrile (7 g, 15.93 mmol) in HCl 32% (80 mL) was heated to 60 C. and stirred for 10 hour. After completion, the reaction mixture was cooled to 05 C., treated with NaOH 30% sol. until pH11 and extracted with methyl tert-butyl ether. The water phase was acidified with 10% aqueous HCl to pH4. The solid was filtrated, washed with water and diethyl ether and dried in vacuo to give 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxylic acid 7 g, 95%). .sup.1H NMR (400 MHz, DMSO-d6) ppm 1.19 (m, 3H) 1.30 (m, 3H) 3.81 (m, 3H) 3.97 (s, 3H) 4.11-4.23 (m, 2H) 7.47 (s, 1H) 8.81 (d, 1H) 9.48 (d, 1H).

Example P4: Preparation of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carboxylic Acid A4

(91) ##STR00090##

Step A: Preparation of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carbonitrile

(92) ##STR00091##

(93) 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (11.14 mmol, 5 g) was dissolved in methylsulfinylmethane (40 mL) in a round bottom flask. To this reaction mixture, 1,4-diazabicyclo[2.2.2]octane (0.56 mmol, 0.0625 g, 0.0613 mL) was added at room temperature under nitrogen and stirred for 10 mins. Sodium cyanide (13.37 mmol, 0.655 g) dissolved in water (5 mL) was added to the reaction mixture and heated at 50 C. for 6 hrs. The reaction was quenched with water (100 ml) and diluted with Ethyl acetate (50 ml). Organic layer was separated and the aqueous layer was further extracted with Ethyl acetate (250 ml). Combined organic extract was washed with brine, dried over sodium sulfate and concentrated to get crude compound. the purification was done by chromatography and pure compound eluted in 30%-Ethyl acetate/Cyclohexane to give 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carbonitrile (7.5 mmol, 3.3 g) in 45% yield. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.36 (m, 6H) 3.85 (m, 2H) 4.15 (s, 3H) 4.23 (m, 2H), 7.21 (s, 1H) 8.05 (d, 1H) 8.68 (d, 1H).

Step B: Preparation of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carboxylic Acid A4

(94) ##STR00092##

(95) A round bottom flask was charged with 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carbonitrile (3.10 mmol, 1.36 g) and concentrated hydrogen chloride (17 mL) was added at room temperature. The reaction was heated at 80 C. for 8 h, then cooled to room temperature and basified till pH 8 with a solution of saturated sodium hydroxide. The aqueous layer was washed with TBME (3100 ml) to remove non polar impurities. Then, the aqueous layer was acidified till pH-4 when white solid precipitated out. It was then extracted in Ethyl acetate (100 ml). The aqueous layer was further extracted with Ethyl acetate (2100 ml). Combined organic extract was washed with brine, dried with sodium sulfate, evaporated under vacuum and concentrated to get pure 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carboxylic acid (2.8 mmol, 1.3 g) in 92% yield. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.43-1.36 (m, 6H) 3.67 (q, 2H) 3.97 (s, 3H) 4.27 (q, 2H) 7.21 (s, 1H) 8.54 (d, 1H) 8.71 (d, 1H)

Example P5: Preparation of 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A5

(96) ##STR00093##

Step A: tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]carbamate

(97) ##STR00094##

(98) 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (Cas: 1879051-82-7) (1 g, 2.027 mmol) was dissolved in anhydrous 1,4-dioxane (10 mL) and cesium carbonate (0.926 g, 2.838 mmol) was added under nitrogen followed by the addition of palladium (II) acetate (0.0137 g, 0.061 mmol) and tert-butyl carbamate (0.2850 g, 2.433 mmol). The reaction mixture was degassed with nitrogen for 15-20 mins, X-PHOS (0.182 mmol, 0.0888 g) was added and the reaction mixture was heated at 110 C. in a preheated oil bath for 14 hours. The solution was filtered through celite bed and washed with Ethyl acetate (20 ml). Organic layer was taken in a separating funnel and washed with water (30 ml), brine, dried over sodium sulfate, filtered and concentrated to get crude product. Column purification done and pure compound eluted in 30% Ethyl acetate/Cyclohexane to give tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]carbamate (0.893 g, 83%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.37 (m, 6H) 1.57 (s, 9H) 3.74 (q, 2H) 4.04 (s, 3H) 4.25 (m, 2H) 6.97 (s, 1H) 7.21 (s, 1H) 8.59 (d, 1H) 8.97 (d, 1H).

Step B: 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(99) ##STR00095##

(100) Hydrochloric acid (4M in Dioxane) (1 mL, 4 mmol) was added to a solution of tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]carbamate (100 mg, 0.1889 mmol) in 1,4-dioxane (1 mL) and the pale yellow solution was stirred at room temperature for overnight and then heated at 50 C. for 6 hours. The reaction was quenched by adding of a saturated aqueous solution of Sodium bicarbonate, and extracted with ethyl acetate. Combined organic layer was evaporated on rotavap and the crude was purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to give 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (69 mg, 85%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.33 (t, 3H) 1.38 (t, 3H) 3.71 (q, 2H) 4.01 (s, 3H) 4.24 (q, 2H) 4.47 (br. s., 2H) 7.20 (s, 1H) 7.67 (d, 1H) 8.33 (d, 1H).

Example P6: Preparation of 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A6

(101) ##STR00096##

Step A: tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate

(102) ##STR00097##

(103) In a round bottom flask was added 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (I7) (15 g, 33.42 mmol), tert-butyl carbamate (4.69 g, 40.11 mmol), cesium carbonate (15.3 g, 46.79 mmol), XPHOS (1.478 g, 3.00 mmol), and 1,4-dioxane (150 mL). The reaction was purged with nitrogen for 10 mins followed by addition of Palladium (II) acetate (237 mg, 1.00 mmol) and then heated at 110 C. for overnight. The reaction was diluted with water (150 ml), extracted with ethyl acetate. The combined organic layers were washed successively with water and brine, dried over Sodium sulfate and concentrated in vacuo. Crude compound was purified by column chromatography gradient cyclohexane+0-30% Ethyl acetate to give tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate (14 g, 79%). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.38 (d, 1H), 8.30 (d, 1H), 7.52 (s, 1H), 7.21 (s, 1H), 4.25 (q, 2H), 4.03 (s, 3H), 3.62 (m, 2H), 1.56 (s, 9H), 1.39 (t, 3H), 1.32 (t, 3H).

Step B: 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(104) ##STR00098##

(105) To a solution of tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate (9.0 g, 17 mmol) in 1,4-dioxane (45 mL) was added 4M Dioxane solution of hydrogen chloride (4 mol/L, 45 mL). The reaction was stirred at 50 C. for 8 hour and then neutralized with saturated aqueous solution of sodium bicarbonate (100 ml) and aqueous layer was extracted with ethyl acetate, combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was dried under high-vacuum to give 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (7.0 g, 96%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.10 (d, 1H), 7.20 (s, 1H), 6.69 (d, 1H), 5.25 (s, 2H), 4.24 (q, 2H), 4.04 (s, 3H), 3.53 (q, 2H), 1.38 (t, 3H), 1.29 (t, 3H).

Example P7: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxamide A7

(106) ##STR00099##

(107) In a one neck round bottom flask, 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (300 mg, 0.6986 mmol) was dissolved in dichloromethane (5 mL) and N,N-diethylethanamine (2.096 mmol, 0.30 ml) was added. The mixture was stirred at 0 C. for 5 min, followed by addition of cyclopropane carbonyl chloride (0.8384 mmol, 0.08 ml) dropwise and the mixture was stirring for 3 hours at room temperature. The reaction was quenched by addition of 10 ml of water and additional 15 ml of dichloromethane was added. Organic layer was separated in separating funnel, washed with brine, concentrated and crude was purified by column chromatography gradient cyclohexane+0-40% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxamide (209 mg, 60%) as a crystalline-white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) =9.32 (s., 1H), 8.63 (d, 1H), 8.33 (brs, 1H), 7.21 (s, 1H), 4.25 (q, 2H), 4.06 (s, 3H), 3.79 (q, 2H), 1.65-1.59 (m, 1H), 1.48-1.32 (m, 6H), 1.22-1.11 (m, 2H), 1.03-0.92 (m, 2H).

Example P8: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]cyclopropanecarboxamide A8

(108) ##STR00100##

(109) In one neck round bottom flask, 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (300 mg, 0.6986 mmol) was dissolved in dichloromethane (4 mL) and to it was added N,N-diethylethanamine (0.2121 g, 2.096 mmol) and reaction mixture was stirred at 0 C. under ice bath. After 5 min, cyclopropane carbonyl chloride (0.8384 mmol, 0.08764 g) was added dropwise under ice bath and stirred for 6 Hours at room temperature. and the reaction mixture was then quenched by adding 10 ml of water and 15 ml of dichloromethane. Organic and aqueous layer were separated in separating funnel, aqueous layer re-extracted with dichloromethane (215 mL). Combined org layer was washed with brine and concentrated under reduced pressure. The crude product was purified by column chromatography gradient cyclohexane+0-50% Ethyl acetate and further with reverse phase column chromatography to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]cyclopropanecarboxamide (71 mg, 10%) as a crystalline-white solid. Mp=103-105 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.96-1.01 (m, 2H) 1.16-1.20 (m, 2H) 1.30 (t, 3H) 1.38 (t, 3H) 1.65-1.70 (m, 1H) 3.58 (q, 2H) 4.01 (s, 3H) 4.24 (q, 2H) 7.20 (s, 1H) 8.40 (d, 1H) 8.55 (d, 1H) 8.74 (s, 1H).

Example P9: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-cyclopropanecarboxamide A9

(110) ##STR00101##

Step A: tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]carbamate A64

(111) ##STR00102##

(112) 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (Cas: 1879051-82-7) (1 g, 2.027 mmol) was dissolved in anhydrous 1,4-dioxane (10 mL) and to it cesium carbonate (0.926 g, 2.838 mmol) was added under nitrogen followed by the addition of palladium (II) acetate (0.01366 g, 0.06081 mmol) and tert-butyl carbamate (0.2850 g, 2.433 mmol). The reaction mixture was degassed with nitrogen for 15-20 mins, X-PHOS (0.1824 mmol, 0.0888 g) was added and the reaction mixture was heated at 110 C. in a preheated oil bath for 14 hours. The solution was filtered through celite bed and washed with Ethyl acetate (20 ml). Organic layer was washed with water (30 ml), brine, dried over sodium sulfate, filtered and concentrated to get crude product. Column purification was done and pure compound was eluted in 30% Ethyl acetate/Cyclohexane to give tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]carbamate (0.893 g, 83%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.37 (m, 6H) 1.57 (s, 9H) 3.74 (q, 2H) 4.04 (s, 3H) 4.25 (m, 2H) 6.97 (s, 1H) 7.21 (s, 1H) 8.59 (d, 1H) 8.97 (d, 1H).

Step B: tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-carbamate. A65

(113) ##STR00103##

(114) To a solution of tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]carbamate (50 mg, 0.0944 mmol) in N,N-dimethylformamide (1 mL) under N.sub.2 at room temperature, dipotassium carbonate (0.5665 mmol, 78 mg) and iodomethane (0.2833 mmol, 0.02 ml) were added. The mixture was stirred at room temperature for 3 hours and then quenched with water. The aqueous phase was extracted in ethyl acetate. Combined organic layer was washed with brine, dried over sodium sulfate and concentrated to give tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-carbamate (50 mg, 97%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.96 (d, 1H), 8.41 (d, 1H), 7.21 (s, 1H), 4.25 (q, 2H), 4.08 (m, 3H), 3.78 (q, 2H), 3.44 (s, 3H), 1.55 (s, 9H), 1.44-1.32 (m, 6H).

Step C: 5-ethyl-2-[3-ethylsulfonyl-5-(methylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(115) ##STR00104##

(116) The hydrochloric acid (4M in Dioxane) (45 mL) was added to a solution of tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-carbamate (4.45 g, 8.19 mmol) in 1,4-dioxane (45 mL) and the pale yellow solution was then heated at 50 C. for 9 hour. The reaction was cooled down to 0 C. and quenched by addition of saturated aqueous Sodium bicarbonate solution and 20 ml water. The solution was extracted with 60 ml ethyl acetate, combined organic layer was evaporated on rotavap and crude product was purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to give 5-ethyl-2-[3-ethylsulfonyl-5-(methylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (3.2 g, 88%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.30-1.43 (m, 6H) 3.01 (d, 3H) 3.65-3.77 (m, 2H) 4.01 (s, 3H) 4.24 (q, 2H) 4.56 (br. s., 1H) 7.20 (s, 1H) 7.51 (d, 1H) 8.26 (d, 1H).

Step D: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-cyclopropanecarboxamide A9

(117) ##STR00105##

(118) In a 25 ml RB, to a 0 C. cooled solution of 5-ethyl-2-[3-ethylsulfonyl-5-(methylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (300 mg, 0.6766 mmol) and N,N-diethylethanamine (1.353 mmol) (0.2 ml) in dichloromethane (4 mL) was added cyclopropane carbonyl chloride (1.015 mmol, 0.1 ml). The reaction was slowly allowed to warm to room temperature, stirred for 3 hours. After this mixture was quenched with 10 ml of water and extracted with 15 ml of dichloromethane. Combined dichloromethane layer was evaporated on rotavap to get crude product and purified by column chromatography gradient cyclohexane+0-50% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-cyclopropanecarboxamide (270 mg, 78%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.96 (d, 1H), 8.43 (d, 1H), 7.21 (s, 1H), 4.24 (m, 2H), 4.12 (s, 3H), 3.82 (q, 2H), 3.53 (s, 3H), 1.56 (m, 1H), 1.44-1.33 (m, 6H), 1.22-1.15 (m, 2H), 0.94-0.85 (m, 2H).

Example P10: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-methyl-cyclopropanecarboxamide A10

(119) ##STR00106##

Step A: tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate A66

(120) ##STR00107##

(121) In a round bottom flask was added 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (I7) (15 g, 33.42 mmol), tert-butyl carbamate (4.69 g, 40.11 mmol), cesium carbonate (15.3 g, 46.79 mmol), XPHOS (1.478 g, 3.00 mmol), and 1,4-dioxane (150 mL). The reaction was purged with nitrogen for 10 mins followed by addition of Palladium (II) acetate (237 mg, 1.00 mmol) and then heated at 110 C. for overnight. The reaction was diluted with water (150 ml), extracted with ethyl acetate. The combined organic layers were washed successively with water and brine, dried over Sodium sulfate and concentrated in vacuo. Crude compound was purified by column chromatography gradient cyclohexane+0-30% Ethyl acetate to give tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate (14 g, 79%).

(122) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.38 (d, 1H), 8.30 (d, 1H), 7.52 (s, 1H), 7.21 (s, 1H), 4.25 (q, 2H), 4.03 (s, 3H), 3.62 (m, 2H), 1.56 (s, 9H), 1.39 (t, 3H), 1.32 (t, 3H).

Step B: tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-methyl-carbamate A67

(123) ##STR00108##

(124) In a 25 ml flask, at 0 C. cooled suspension of sodium hydride (1.700 mmol, 0.06798 g) in tetrahydrofuran (2 mL) was added dropwise a clear solution of tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate (600 mg, 1.133 mmol) in tetrahydrofuran (6 ml). The reaction was stirred at 0 C. for 30 mins followed by addition of iodomethane (3.399 mmol, 0.4825 g) (0.22 ml) and N,N-dimethylformamide (1 ml). The reaction mixture was allowed to warm to room temperature over 3 hours and then heated at 40 C. for 15 min. The reaction was neutralized with 2N HCl, diluted with 10 ml water, extracted with ethyl acetate (315 ml). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Crude product was purified by column chromatography gradient cyclohexane+0-30% Ethyl acetate to give tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-methyl-carbamate (530 mg, 86%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.29-1.41 (m, 6H) 1.58 (s, 9H) 3.44 (s, 3H) 3.61-3.72 (m, 2H) 4.07 (s, 3H) 4.24 (q, 2H) 7.21 (s, 1H) 8.32 (m, 2H).

Step C: 5-ethyl-2-[3-ethylsulfonyl-6-(methylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A62

(125) ##STR00109##

(126) The hydrochloric acid (4M in dioxane) (5 mL, 20 mmol) was added to a solution of tert-butyl N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-methyl-carbamate (500 mg, 0.9198 mmol) in 1,4-dioxane (5 mL) and the clear solution was then heated at 50 C. for 8 Hours. The reaction went to completion and was cooled to 0 C., quenched with saturated aqueous solution of Sodium bicarbonate and 10 ml water. The aqueous phase was extracted in 20 ml ethyl acetate, combined organic layer was evaporated on rotavap and the crude was purified by Column chromatography gradient cyclohexane+0-70% Ethyl acetate to give 5-ethyl-2-[3-ethylsulfonyl-6-(methylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (340 mg, 83%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.26-1.31 (m, 3H) 1.37 (t, 3H) 2.95 (m, 3H) 3.54 (q, 2H) 4.04 (s, 3H) 4.23 (q, 2H) 5.47 (br. s., 1H) 6.56 (d, 1H) 7.20 (s, 1H) 8.04 (d, 1H).

Step D: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-methyl-cyclopropanecarboxamide A10

(127) ##STR00110##

(128) In one neck round bottle flask, 5-ethyl-2-[3-ethylsulfonyl-6-(methylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (330 mg, 0.7442 mmol) was dissolved in dichloromethane (4 mL) and N,N-diethylethanamine (0.22 ml) was added to it. The mixture was stirred at 0 C. under ice bath and after 5 min cyclopropane carbonyl chloride (1.116 mmol, 0.1167 g) was added dropwise. The reaction was stirred for 40 hours at room temperature. 10 ml Water followed by 15 ml dichloromethane were added to the reaction mixture, organic layer was separated in separating funnel, aqueous layer re-extracted with dichloromethane (215 mL). Organic layer was washed with brine, concentrated and crude product was purified by column chromatography gradient cyclohexane+0-40% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-methyl-cyclopropanecarboxamide (140 mg, 77%) as a crystalline-white solid. Mp=177-179 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.99 (m, 2H) 1.20-1.24 (m, 2H) 1.35 (t, 3H) 1.40 (t, 3H) 1.98 (m, 1H) 3.65 (s, 3H) 3.70 (q, 2H) 4.09 (s, 3H) 4.26 (m, 2H) 7.22 (s, 1H) 8.13 (d, 1H) 8.38 (d, 1H).

Example P11: Preparation of 2-[5-[cyclopropyl(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A11

(129) ##STR00111##

Step A: 2-[5-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(130) ##STR00112##

(131) 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (Cas: 1879051-82-7) (2.027 mmol, 1 g) was dissolved in anhydrous toluene (10 mL) and to it cesium carbonate (3.041 mmol, 0.992 g) was added under nitrogen. The mixture was purged with nitrogen for 15 mins. tris(dibenzylideneacetone)dipalladium (0) (0.04054 mmol, 0.03750 g), (+/)-BINAP (0.0811 mmol, 0.0521 g) and cyclopropyl amine (2.433 mmol, 0.1389 g) were successively added to the mixture and it was heated at 110 C. for 16 hours. Pd.sub.2(dba).sub.3 (0.01 eq), BINAP (0.02 eq), cesium carbonate (0.75 eq.) and cyclopropylamine (0.6 eq.) were further added to the mixture and heating continued for another 5 hours. The reaction was complete and was filtered through celite bed and the bed was washed with ethyl acetate (20 ml). Organic layer was evaporated and directly subjected to column purification gradient cyclohexane+0-40% Ethyl acetate to give 2-[5-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.523 g, 55%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.62-0.68 (m, 2H) 0.91-0.99 (m, 2H) 1.31-1.42 (m, 6H) 2.57-2.65 (m, 1H) 3.72 (q, 2H) 4.03 (s, 3H) 4.20-4.29 (m, 2H) 4.81 (s, 1H) 7.21 (s, 1H) 7.74 (d, 1H) 8.40 (d, 1H).

Step B: 2-[5-[cyclopropyl(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A11

(132) ##STR00113##

(133) 2-[5-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (1.114 mmol, 0.523 g) was dissolved in dry N,N-dimethylformamide (5 mL) and sodium hydride (1.448 mmol, 0.0579 g) was added under nitrogen at 0 C. The mixture was stirred at 0 C. for 10 mins, iodomethane (1.225 mmol, 0.1739 g) was added to the mixture and stirring continued for 2 hours at room temperature. After the completion of the reaction it was quenched in water and diluted with ethyl acetate (10 ml). Organic layer was separated. Aqueous layer was further extracted with ethyl acetate (215 ml). Combined organic layer was washed with brine, dried over sodium sulfate and concentrated under vacuum to get crude product. Column purification done in combiflash gradient cyclohexane+0-30% Ethyl acetate to give 2-[5-[cyclopropyl(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A11 (0.2875 mmol, 0.139 g, 25%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.60 (d, 1H), 7.82 (d, 1H), 7.20 (s, 1H), 4.24 (q, 2H), 4.03 (s, 3H), 3.72 (q, 2H), 3.17 (s, 3H), 2.70 (m, 1H), 1.42-1.31 (m, 6H), 1.09-1.00 (m, 2H), 0.79-0.71 (m, 2H).

Example P12: Preparation of 2-[6-[cyclopropyl(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A12

(134) ##STR00114##

(135) In a microwave vial was added 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (I7) (235 mg, 0.5236 mmol), dipotassium carbonic acid (1.047 mmol), N-methylcyclopropyl amine hydrochloride (84.50 mg, 0.7854 mmol) and N,N-DIMETHYLFORMAMIDE (3 mL). The reaction was subjected to microwave heating at 130 C. for 1 hour. The reaction was diluted with water (10 ml), extracted with ethyl acetate and combined organic layer was dried over sodium sulfate, concentrated under reduced pressure. The residue was purified by CombiFlash column chromatography gradient cyclohexane+0-50% Ethyl acetate to give 2-[6-[cyclopropyl(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (90 mg, 35%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.09 (d, 1H), 7.22 (s, 1H), 7.13 (d, 1H), 4.24 (q, 2H), 4.07 (s, 3H), 3.58 (q, 2H), 3.17 (s, 3H), 2.76-2.65 (m, 1H), 1.42-1.35 (m, 3H), 1.31 (t, 3H), 1.06-0.97 (m, 2H), 0.81-0.73 (m, 2H).

Example P13: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]l-N-methyl-methanesulfonamide A13

(136) ##STR00115##

Step A: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methylsulfonyl-methanesulfonamide

(137) ##STR00116##

(138) In a stirring solution of 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A5 (1.5 g, 3.5 mmol) in dichloromethane (15 mL) was added N,N-diethylethanamine (3.145 mmol, 0.93 ml) then was added methane sulfonyl chloride (0.88 g, 7.7 mmol) and reaction was stirred at room temperature for 1 hour. The reaction was washed with sodium bicarbonate solution and dichloromethane layer was concentrated to get crude product which was purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methylsulfonyl-methanesulfonamide (1.4 g, 68%). Mp=260 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.25-1.41 (m, 6H) 3.51 (s, 6H), 3.80 (q, 2H) 4.16 (s, 3H) 4.26 (q, 2H) 7.23 (s, 1H) 8.50 (d. 1H). 8.94 (d, 1H).

Step B: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]methanesulfonamide A15

(139) ##STR00117##

(140) In a stirring solution of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methylsulfonyl-methanesulfonamide (1.3 g, 2.2 mmol) in methanol (20 ml) was added sodium hydroxide (88 mg, 2.2 mmol) dissolved in 4 ml of water and reaction was stirred at room temperature for 1 hour. The reaction was quenched by adding 2N HCl and extracted with Ethyl acetate. Ethyl acetate layer was concentrated and purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]methanesulfonamide (600 mg, 46%). Mp=251-253 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.33-1.47 (m, 6H) 3.23 (s, 3H) 3.82 (q, 2H) 4.10 (s, 3H) 4.27 (q, 2H) 7.24 (s, 1H) 8.32 (d, 1H) 8.72 (m, 1H), 8.85 (d, 1H).

Step C: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-methanesulfonamide

(141) ##STR00118##

(142) In a stirring solution of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]methanesulfonamide (0.3941 mmol, 0.2 g) in dichloromethane (10 mL) was added sodium hydride (0.7882 mmol, 0.0315252 g) at room temperature and to this solution was added methyl iodide (0.7882 mmol, 0.112 g). The reaction was stirred at room temperature for 12 hours and then quenched by addition of water (50 ml). Product was extracted by ethyl acetate, organic layer was concentrated to get crude product and purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-methanesulfonamide (70 mg, 34%)._Mp=223-225 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.40 (q, 6H) 3.05 (s, 3H) 3.52 (s, 3H) 3.84 (q, 2H) 4.13 (s, 3H) 4.27 (q, 2H) 7.23 (s, 1H) 8.43 (d, 1H) 9.03 (d, 1H).

Example P14: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-methanesulfonamide A14

(143) ##STR00119##

(144) To a solution of sodium hydride (1.034 mmol, 60 mass %) in tetrahydrofuran (2 ml) was added a solution of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]methanesulfonamide (Prepared using procedure as descripted in Example I3 Step A and B) (350 mg, 0.6897 mmol) in tetrahydrofuran (3 ml). The reaction was stirred at room temperature for 30 mins. To this was then added iodomethane (2.069 mmol). The reaction was stirred at 50 C. for 5 hours, monitored by TLC. The reaction was neutralized with 2N HCl (10 ml), aqueous layer was extracted with ethyl acetate, combined organic layer was dried over sodium sulfate, concentrated under reduced pressure. Crude product was purified by column chromatography gradient cyclohexane+0-50% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-methanesulfonamide A14 (170 mg, 47%). .sup.1H NMR (400 MHz, DMSO) =8.44 (d, 1H), 7.71 (d, 1H), 7.22 (s, 1H), 4.26 (q, 2H), 4.11 (s, 3H), 3.73 (q, 2H), 3.52 (s, 3H), 3.19 (s, 3H), 1.38 (m, 6H).

Example P15: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]methanesulfonamide A15

(145) ##STR00120##

(146) See Example P13 Step A and B.

Example P16: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]methanesulfonamide A16

(147) ##STR00121##

(148) In a microwave vial was taken 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (600 mg, 1.337 mmol), dipotassium carbonic acid (2.674 mmol, 0.3749 g), methane sulfonamide (2.005 mmol, 0.1907 g) in N,N-dimethylformamide (90.1 mmol, 6.61 g). The reaction was subjected to microwave heating at 150 C. for 1 hour. The reaction was neutralized with 1N HCl (5 ml), diluted with water (10 ml). Aqueous layer was extracted with ethyl acetate. Combined organic layer was dried over sodium sulfate, concentrated under reduced pressure. Crude product was purified by column chromatography gradient cyclohexane+0-30% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]methanesulfonamide (520 mg, 76%). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.43 (d, 1H), 8.15 (br. s., 1H), 7.38 (d, 1H), 7.22 (s, 1H), 4.26 (q, 2H), 4.10 (s, 3H), 3.72 (q, 2H), 3.32 (s, 3H), 1.46-1.31 (m, 6H).

Example P17: Preparation of N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-N-methyl-pyridine-3-carboxamide A17

(149) ##STR00122##

Step A: 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonyl Chloride

(150) ##STR00123##

(151) In a stirring solution of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxylic acid (1500 mg, 3.272 mmol) in dichloromethane (20 mL) was added, oxalyl dichloride (6.545 mmol, 0.6 ml) followed by N,N-dimethylformamide and reaction was stirred at ice cold condition for 2 hour. The mixture was concentrated to get 1500 mg crude acid chloride and used immediately for amide coupling.

Step B: N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-N-methyl-pyridine-3-carboxamide A17

(152) ##STR00124##

(153) In a stirring solution of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonyl chloride (500 mg, 1.048 mmol) in dichloromethane (20 mL) was added N,N-diethylethanamine (4.194 mmol, 0.0.6 ml) then was added HCl salt of N-methylcyclopropyl amine (2.097 mmol, 225 mg) and reaction was stirred at room temperature for 12 hour. The reaction was washed by sodium bicarbonate solution and dichloromethane layer was concentrated to get crude product which was purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to get N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-N-methyl-pyridine-3-carboxamide (250 mg, 46%). Mp=200-202 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.57 (br. s., 2H) 0.78 (br. s., 2H) 1.34-1.47 (m, 6H) 2.90-3.00 (m, 1H) 3.21 (br. s., 3H) 3.83 (m, 2H) 4.12 (s, 3H) 4.27 (q, 2H) 7.23 (s, 1H) 8.66 (br. s., 1H) 9.13 (s, 1H).

Example P18: Preparation of N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-N-methyl-pyridine-2-carboxamide A18

(154) ##STR00125##

(155) A solution of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[45-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonyl chloride (Prepared from 17 using same procedure for Example P17 Step A) dissolved in dry dichloromethane (7 ml) was added dropwise to a mixture of N-methylcyclopropyl amine hydrochloride (1.3089 mmol, 0.1408 g), N,N-diethylethanamine (4.3629 mmol, 0.4415 g, 0.608 mL) and dichloromethane (5 ml) under nitrogen at 0 C. The mixture was stirred at room temperature for 3 hours and then quenched with water (20 ml) and diluted with dichloromethane (20 ml). Organic layer was separated, aqueous layer was further extracted with dichloromethane. Combined Organic extract was washed with brine, dried with sodium sulfate, evaporated under vacuum and concentrated to get crude compound which was purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to give N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-N-methyl-pyridine-2-carboxamide (0.211 g, 37%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.59 (d, 1H), 7.90 (d, 1H), 7.21 (s, 1H), 4.25 (q, 2H), 4.05 (s, 3H), 3.74 (q, 2H), 3.19 (s, 3H), 2.99-2.91 (m, 1H), 1.42-1.32 (m, 6H), 0.63-0.53 (m, 2H), 0.51-0.41 (m, 2H).

Example P19: Preparation of N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide A19

(156) ##STR00126##

(157) In a stirring solution of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonyl chloride (Prepared as descripted for A17 Step A)

(158) (500 mg, 1.048 mmol) in dichloromethane (5 mL) was added N,N-diethylethanamine (3.145 mmol, 0.6 ml) followed by cyclopropyl amine (2.097 mmol, 0.16 ml) and reaction was stirred at room temperature for 2 hour. The reaction was washed by sodium bicarbonate solution and dichloromethane layer was concentrated to get crude product which was purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to get N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide (210 mg, 40%). Mp=215-217 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.61-0.69 (m, 2H) 0.84-0.93 (m, 2H) 1.26-1.36 (m, 6H) 2.88-2.96 (m, 1H) 3.76 (q, 2H) 4.02 (s, 3H) 4.18 (q, 2H) 6.52 (br. s., 1H) 7.14 (s, 1H) 8.51 (m, 1H) 9.28 (d, 1H).

Example P20: Preparation of N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carboxamide A20

(159) ##STR00127##

(160) Prepared as descripted in Example A18 using cyclopropyl amine to give N-cyclopropyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-2-carboxamide (0.132 g, 60%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.68-8.64 (m, 1H), 8.59-8.55 (m, 1H), 7.79 (d, J=3.1 Hz, 1H), 7.22 (s, 1H), 4.26 (q, 2H), 4.03 (s, 3H), 3.68 (q, 2H), 2.96 (m, 1H), 1.40 (t, 3H), 1.33 (t, 3H), 0.94-0.87 (m, 2H), 0.68-0.61 (m, 2H)

Example P21: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methylsulfonyl-cyclopropanecarboxamide A21

(161) ##STR00128##

(162) In a stirring solution of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]methanesulfonamide A15 (200 mg, 0.3941 mmol) in dichloromethane (15 mL) was added N,N-diethylethanamine (3.145 mmol, 0.11 ml) then was added cyclopropyl carbonyl chloride (0.7882 mmol, 0.0.07 ml) and the reaction was stirred at room temperature for 2 hour. The reaction was washed by sodium bicarbonate solution and dichloromethane layer was concentrated to get crude product which was purified by column chromatography gradient cyclohexane+0-70% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methylsulfonyl-cyclopropanecarboxamide (130 mg, 57%). Mp: 232-234 C.

(163) .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.00-1.06 (m, 2H) 1.33 (m, 2H) 1.41 (m, 7H) 3.56 (s, 3H) 3.90 (q, 2H) 4.18 (s, 3H) 4.27 (q, 2H) 7.23 (s, 1H) 8.51 (d, 1H) 8.97 (d, 1H).

Example P22: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N,N-dimethyl-cyclopropanecarbohydrazide A22

(164) ##STR00129##

Step A: 2-[5-(2-benzhydrylidenehydrazino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(165) ##STR00130##

(166) 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (4.054 mmol, 2 g) was dissolved in degassed (20 mins with nitrogen) 2-methylbutan-2-ol (4 mL) and to it sodium hydroxide (5.676 mmol, 0.2270 g) was added under nitrogen in a microwave vial. The mixture was heated at 110 C. In another round flask, palladium (ii) acetate (0.2027 mmol, 0.04553 g) and me-phos (0.4054 mmol, 0.1508 g) were taken together and stirred under nitrogen for 20 mins. This active catalyst was then transferred to the mixture followed by portion wise addition of diphenylmethanone hydrazone (4.054 mmol, 0.7955 g) under nitrogen. The mixture was heated at 110 C. for 5 hours. The mixture was filtered through celite bed and the bed was washed with ethyl acetate (10 ml). Organic layer was evaporated under vacuum and directly subjected to column purification gradient cyclohexane+0-30% Ethyl acetate to give 2-[5-(2-benzhydrylidene hydrazino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (2 g, 81%). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.78 (d, 1H), 8.01 (d, 1H), 7.84 (s, 1H), 7.70-7.60 (m, 5H), 7.42-7.35 (m, 5H), 7.21 (s, 1H), 4.24 (q, 2H), 4.04 (s, 3H), 3.75 (q, 2H), 1.37 (m, 6H).

Step B: 2-[5-[(benzhydrylideneamino)-methyl-amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(167) ##STR00131##

(168) 2-[5-[(benzhydrylideneamino)-methyl-amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.1606 mmol, 0.1 g) was dissolved in dry tetrahydrofuran (1 mL) and to it sodium hydride (0.2465 mmol, 0.009858 g) was added under nitrogen at 0 C. The mixture was stirred at 0 C. for 15 mins and then iodomethane (0.1972 mmol, 0.02799 g) was added. The mixture was stirred at room temperature for 1 hour and then quenched with water and extracted in ethyl acetate (10 ml). Aqueous layer was further extracted in ethyl acetate (210 ml), combined organic layer was washed with brine, dried over sodium sulfate, concentrated under vacuum to get crude product which was subjected to column purification gradient cyclohexane+0-50% Ethyl acetate to give 2-[5-[(benzhydrylideneamino)-methyl-amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (100 mg, 97%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.75 (d, 1H), 7.92 (d, 1H), 7.68-7.62 (m, 2H), 7.54-7.33 (m, 8H), 7.22 (s, 1H), 4.29-4.21 (m, 2H), 4.06 (s, 3H), 3.76 (q, 2H), 2.99 (s, 3H), 1.38 (m, 8H).

Step C: 2-[5-[amino(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A56

(169) ##STR00132##

(170) 2-[5-[(benzhydrylideneamino)-methyl-amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.2 mmol, 0.1 g) was dissolved in ethanol (0.02 mL) and to it conc. hydrogen chloride (0.176 mL) was added and heated at 50 C. overnight. The mixture was diluted with ethyl acetate (10 ml) and neutralized with sodium hydroxide solution until pH 8. Organic layer separated. Aqueous layer was further extracted with ethyl acetate (210 ml). Combined organic layer was washed with brine, dried over sodium sulfate, concentrated under vacuum to get crude product which was subjected to column purification gradient cyclohexane+0-90% Ethyl acetate to give 2-[5-[amino(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (23 mg, 30%).

(171) .sup.1H NMR (400 MHz, DMSO) =8.57 (d, 1H), 7.86 (d, 1H), 7.39 (s, 1H), 4.93 (s, 2H), 4.15 (m, 2H), 3.87 (s, 3H), 3.70 (m, 2H), 3.26 (s, 3H), 1.29 (t, 3H), 1.15 (t. 3H)

Step D: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-cyclopropanecarbohydrazide

(172) ##STR00133##

(173) In a stirring solution of 2-[5-[amino(methyl)amino]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (650 mg, 1.418 mmol) in N,N-dimethylformamide (20 mL) under nitrogen was added N-ethyl-N-isopropyl-propan-2-amine (4.253 mmol, 0.5497 g) followed by cyclopropyl carboxylic acid (1.559 mmol, 0.1343 g) and HATU (2.126 mmol, 0.81 g) and reaction was stirred at that temp for two hours. The mixture was then poured into water and extracted with ethyl acetate. The combined extracts were washed with brine, dried over NaSO.sub.4, filtered and evaporated under reduced pressure to give the crude product. The crude was purified via flash chromatography to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-cyclopropanecarbohydrazide (250 mg, 33%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.83-0.90 (m, 2H) 0.99-1.04 (m, 2H) 1.23-1.34 (m, 6H) 1.48 (m, 1H) 3.36 (s, 3H) 3.62-3.70 (m, 2H) 3.96 (s, 3H) 4.12-4.22 (m, 2H) 7.16 (s, 1H) 7.63-7.67 (m, 1H) 7.76 (s, 1H) 8.36-8.39 (m, 1H)

Step E: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N,N-dimethyl-cyclopropanecarbohydrazide

(174) ##STR00134##

(175) In a stirring solution of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-cyclopropanecarbohydrazide (250 mg, 0.4748 mmol) in N,N-dimethylacetamide (5 mL) was added sodium hydride (0.7123 mmol, 60 mass %). The reaction was stirred 15 min and then methyl iodide (0.6648 mmol, 99.5 mass %) was added and the reaction mixture was stirred at room temperature for 8 hour. The reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layers were washed with water, brine solution, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography using ethyl acetate/cyclohexane to get the desired product N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N,N-dimethyl-cyclopropane carbohydrazide (47 mg, 18%). .sup.1H NMR (400 MHz, CHLOROFORM-d) ppm 0.66-0.85 (m, 2H) 0.95-1.05 (m, 2H) 1.24-1.36 (m, 6H) 1.82-1.92 (m, 1H) 3.08 (s, 3H) 3.33 (s, 3H) 3.63-3.74 (m, 2H) 3.98 (s, 3H) 4.17 (m, 2H) 7.07 (s, 1H) 7.64 (d, 1H) 8.35 (d, 1H).

Example P23: Preparation of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-N-methylsulfonyl-pyridine-3-carboxamide A23

(176) ##STR00135##

(177) To a 10 C. cooled solution of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxylic acid (300 mg, 0.6545 mmol) and methane sulfonamide (0.7853 mmol, 0.07470 g) in pyridine (3 mL) was added phosphorous oxychloride (0.7853 mmol, 0.1204 g) and was stirred at room temperature for 1.5 hours. The reaction was neutralized with 2N HCl (10 ml) and extracted with ethyl acetate. Combined organic layer was dried over sodium sulfate, concentrated under reduced pressure. The crude product was triturated with cyclohexane (10 ml). The solid obtained was purified by reverse phase preparative HPLC to give 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-N-methylsulfonyl-pyridine-3-carboxamide (30 mg, 8.5%). .sup.1H NMR (400 MHz, CDCl.sub.3) =9.49 (d, 1H), 8.98 (d, 1H), 7.22 (s, 1H), 4.26 (q, 2H), 4.14 (s, 3H), 3.93 (q, 2H), 3.53 (s, 3H), 1.45-1.35 (m, 6H).

Example P24: Preparation of 1-[[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]amino]cyclopropanecarbonitrile A24

(178) ##STR00136##

(179) 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.6081 mmol, 0.3 g) was dissolved in anhydrous 1,4-dioxane (3 mL) and to it cesium carbonate (0.8514 mmol, 0.278 g) was added under nitrogen followed by palladium (II) acetate (0.0365 mmol, 0.0082 g) and 1-cyanocyclopropyl)ammonium chloride (0.9122 mmol, 0.1082 g). The mixture was purged with nitrogen for 15-20 mins, X-PHOS (0.1095 mmol, 0.05325 g) was then added and the reaction mixture was heated at 110 C. in a preheated oil bath for 26 hours. The reaction was quenched in water (15 ml) and diluted with ethyl acetate (30 ml). Organic layer was separated and washed with brine, dried over sodium sulfate, filtered and concentrated to get crude product. Crude product was purified by column purification with gradient cyclohexane+0-80% Ethyl acetate to give 1-[[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]amino]cyclopropanecarbonitrile (0.079 g, 26%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.33-1.45 (m, 8H) 1.67-1.80 (m, 2H) 3.77 (q, 2H) 4.05 (s, 3H) 4.25 (q, 2H) 5.46 (s, 1H) 7.21 (s, 1H) 7.86 (d, 1H) 8.53 (d, 1H).

Example P25: Preparation of N-(1-cyanocyclopropyl)-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl) imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide A25

(180) ##STR00137##

(181) In a stirring solution of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonyl chloride (prepared as in example P17 Step A, 500 mg, 1.048 mmol) in dichloromethane (10 mL) was added N,N-diethylethanamine (3.145 mmol, 0.6 ml) followed by 1-aminocyclopropanecarbonitrile (2.097 mmol, 250 mg) and reaction mixture was stirred at room temperature for 2 hour. The mixture was washed with sodium bicarbonate solution and dichloromethane layer was concentrated to get crude product which was purified by column purification with gradient cyclohexane+0-70% Ethyl acetate to give N-(1-cyanocyclopropyl)-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide (330 mg, 60%). Mp=250 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.25-1.41 (m, 8H) 1.62 (s, 2H) 3.80 (q, 2H) 4.02 (s, 3H) 4.18 (q, 2H) 7.15 (s, 1H) 7.71 (s, 1H) 8.72 (d, 1H) 9.36 (d, 1H)

Example P26: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methoxy-formamidine A26

(182) ##STR00138##

(183) A solution of 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (450 mg, 1.048 mmol), 1,1-dimethoxy-N,N-dimethyl-methanamine (1.258 mmol) in acetonitrile (5 mL) was refluxed for 1 hour. The reaction was concentrated under reduced pressure to obtain N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N,N-dimethyl-formamidine (400 mg, 0.8256 mmol).

(184) To a solution of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N,N-dimethyl-formamidine (400 mg, 0.8256 mmol) in methanol (2 mL) was added O-methyl hydroxylamine hydrochloride (1.258 mmol, 0.1050 g). The reaction was refluxed for 1 hour and monitored by TLC. The reaction was quenched with water (5 ml), extracted with ethyl acetate, combined organic layer was dried over sodium sulfate, concentrated under reduced pressure and was purified by column purification with gradient cyclohexane+0-100% Ethyl acetate to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methoxy-formamidine (220 mg, 43%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.64 (d, 1H), 8.28 (d, 1H), 8.00 (d, 1H), 7.36 (d, 1H), 7.18 (s, 1H), 4.21 (q, 2H), 4.01 (s, 3H), 3.92 (s, 3H), 3.74 (q, 2H), 1.40-1.28 (m, 6H).

Example P27: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methoxy-N-methyl-formamidine A27

(185) ##STR00139##

(186) To a solution of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methoxy-formamidine (300 mg, 0.6166 mmol) in N,N-dimethylformamide (3 mL) was added dipotassium carbonate (129 mg, 0.925 mmol) followed by iodomethane (0.060 ml, 0.925 mmol), The reaction was stirred at room temperature for overnight. The reaction was neutralized with 2N HCl (5 ml), diluted with water (10 ml) and extracted with ethyl acetate. The combined organic layers were washed successively with water and brine, dried over Sodium sulfate and concentrated in vacuo. Crude compound was purified by column chromatography with gradient cyclohexane+0-50% Ethyl acetate_N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methoxy-N-methyl-formamidine (120 mg, 39%). .sup.1H NMR (400 MHz, CDCl.sub.3) =8.70 (d, 1H), 8.45 (s, 1H), 8.04 (d, 1H), 7.21 (s, 1H), 4.25 (q, 2H), 4.06 (s, 3H), 3.85 (s, 3H), 3.77 (m, 2H), 3.46 (s, 3H), 1.44-1.33 (m, 6H).

Example P28: Preparation of N-(cyanomethyl)-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide A28

(187) ##STR00140##

(188) In a stirring solution of 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonyl chloride (prepared as in example P17 Step A, 500 mg, 1.048 mmol) in dichloromethane (10 mL) was added N,N-diethylethanamine (3.145 mmol, 0.6 ml) then was added HCl salt of 2-aminoacetonitrile (2.097 mmol, 193 mg) and reaction was stirred at room temperature for 2 hour. The reaction was washed with sodium bicarbonate solution and dichloromethane layer was concentrated to get crude product which was purified by column chromatography with gradient cyclohexane+0-70% Ethyl acetate to get N-(cyanomethyl)-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide (250 mg, 48%). Mp=213-215 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.26-1.37 (m, 6H) 3.87 (q, 2H) 4.13 (s, 3H) 4.24 (m, 2H) 4.42 (d, 2H) 7.23 (s, 1H) 7.80 (m, 1H) 8.91 (s, 1H) 9.48 (d, 1H).

Example P29: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methylsulfonyl-methanesulfonamide A29

(189) ##STR00141##

(190) In a stirring solution of 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (1.5 g, 3.5 mmol) in dichloromethane (15 mL) was added N,N-diethylethanamine (3.145 mmol, 0.93 ml) then was added methane sulfonyl chloride (7.7 mmol, 0.0.36 ml) and reaction was stirred at room temperature for 1 hour. NMR confirms the desired product and reaction was washed with sodium bicarbonate solution and dichloromethane layer was concentrated to get crude product which was purified by column chromatography with gradient cyclohexane+0-70% Ethyl acetate to get N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methylsulfonyl-methanesulfonamide (1.4 g, 68%). Mp=260 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.25-1.41 (m, 6H) 3.51 (s, 6H), 3.80 (q, 2H) 4.16 (s, 3H) 4.26 (m, 2H) 7.23 (s, 1H) 8.50 (d, 1H) 8.94 (d, 1H).

Example P30: Preparation of 2-[6-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A30

(191) ##STR00142##

(192) 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (4.456 mmol, 2 g) was dissolved in anhydrous toluene (20 mL) and to it cesium carbonate (6.684 mmol, 2.18 g) was added under nitrogen. The mixture was degassed with nitrogen for 15 mins, tris(dibenzylideneacetone)dipalladium (0) (0.089 mmol, 0.0824 g), (+/)-BINAP (0.1783 mmol, 0.1144 g) and cyclopropyl amine (5.348 mmol, 0.3053 g, 0.371 mL) were added to the reaction mixture and it was heated at 110 C. for 16 hours. The reaction was diluted with water (30 ml) and extracted with ethyl acetate. The combined organic layers were washed successively with water and brine, dried over Sodium sulfate, filtered and concentrated in vacuum. The crude compound was purified by column chromatography with gradient cyclohexane+0-30% Ethyl acetate to give 2-[6-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (1.2 g, 57%). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.16 (d, 1H), 7.20 (s, 1H), 6.93 (m, 1H), 5.69 (br. s., 1H), 4.23 (m, 2H), 4.03 (s, 3H), 3.53 (q, 2H), 2.63 (m, 1H), 1.43-1.34 (m, 3H), 1.28 (t, 3H), 0.97-0.88 (m, 2H), 0.69-0.61 (m, 2H).

Example P31: Preparation of 2-[5-chloro-6-(cyclopropylamino)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A31

(193) ##STR00143##

(194) Copper-II-acetate (0.479 g, 2.61 mmol) was added to a solution of 2-(6-amino-5-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A38 (0.303 g, 0.653 mmol) in 1,4-Dioxane (7.83 mL) and Pyridine (0.160 mL) under argon. The mixture was stirred for 5 minutes before addition of Cyclopropylboronic acid (0.234 g, 2.61 mmol). Then, the mixture was heated at reflux for 6 h at 110 C. The mixture was cooled to RT, quenched with a saturated solution of Sodium bicarbonate. The aqueous phase was extracted three times with DCM, washed with aqueous Sodium bicarbonate, dried with sodium sulfate, filtered, and 2 g Isolute was added. After evaporation of the solvent, the residue was purified by chromatography with DCM:EA 0-40% over 12 g silica gel to give the tittle compound (79.8 mg, 24% yield) and the starting material (183.2 mg). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.14 (s, 1H), 7.20 (s, 1H), 5.82 (s.b., 1H), 4.24 (q, 2H), 4.12 (s, 3H), 3.70 (q, 2H), 2.84 (m, 1H), 1.30-1.38 (m, 6H), 0.85 (m, 2H), 0.6 (m, 2H).

Example P32: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide A32

(195) ##STR00144##

(196) In one neck 25 ml round flask, 5-ethyl-2-[3-ethylsulfonyl-6-(2,2,2-trifluoroethylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (110 mg, 0.2151 mmol) was dissolved in dichloromethane (2 mL), N,N-diethylethanamine (0.4302 mmol, 0.04353 g) was added. The mixture was stirred at 0 C. under ice bath, after 5 min, cyclopropane carbonyl chloride (0.3226 mmol, 0.03373 g) was added dropwise under ice bath stirred for 8 Hours at room temperature. Then dichloromethane (1 ml), cyclopropane carbonyl chloride (0.04 ml), N,N-diethylethanamine (0.08 ml) and N,N-dimethylpyridin-4-amine (0.2151 mmol, 0.02654 g) was added to reaction mixture and reaction mixture was heated at 50 C. for overnight. Desired product mass was observed, the reaction mixture was quenched in 10 ml of water, added 15 ml dichloromethane, separate organic layer in separating funnel, aqueous layer extracted with 15 ml dichloromethane two times, organic layer washed with brine, concentrated, crude was purified by combiflash to get N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide as a yellow gummy mass ((100 mg, 80%). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.02-1.06 (m, 2H) 1.29 (m, 2H) 1.39 (m, 6H) 1.80-1.85 (m, 1H) 3.73 (q, 2H) 4.05 (s, 3H) 4.26 (q, 2H) 4.89 (q, 2H) 7.22 (s, 1H) 7.89 (d, 1H) 8.50 (d, 1H)

Example P33: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide A33

(197) ##STR00145##

(198) In a 25 ml round flask, to a 0 C. cooled suspension of sodium hydride (0.2738 mmol, 0.01095 g) in N,N-dimethylformamide (0.4 mL) was added dropwise a clear solution of 5-ethyl-2-[3-ethylsulfonyl-6-(2,2,2-trifluoroethylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.1955 mmol, 0.1 g) in N,N-dimethylformamide (0.6 ml). The reaction was stirred at 0 C. for 30 mins, to this was added iodomethane (0.2542 mmol, 0.03608 g), and reaction was stirred at room temperature for 2 hours. After this TLC was checked, LCMS shows product mass, reaction went to completion.

(199) The reaction was quenched in 10 ml of water extracted with ethyl acetate. Combined organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure.

(200) The title compound was purified by combiflash silica column chromatography to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide (99 mg, 96%) Mp=171-173 C. .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.32 (t, 3H) 1.40 (t, 3H) 3.27 (s, 3H) 3.62 (q, 2H) 4.03 (s, 3H) 4.25 (q, 2H) 4.37 (q, 2H) 6.83 (d, 1H) 7.21 (s, 1H) 8.22 (d, 1H).

Example P34: Preparation of 5-ethyl-2-[3-ethylsulfonyl-6-(2,2,2-trifluoroethylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A34

(201) ##STR00146##

(202) In a 15 ml reaction tube sealed with rubber stopper, 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (1.114 mmol, 0.5 g) was dissolved in anhydrous toluene (4 ml) and to it cesium carbonate (4.456 mmol, 1.45 g) and 2,2,2-trifluoroethylammonium chloride (1.671 mmol, 0.2265 g) was added under nitrogen. The mixture was degassed with nitrogen for 15 mins, tris(dibenzylideneacetone)dipalladium (0) (0.0223 mmol, 0.0206 g) and (+/)-BINAP (0.0446 mmol, 0.0286 g) was further added to the reaction mixture and it was heated at 110 C. for 16 hours. The reaction was diluted with water (30 ml), extracted with ethyl acetate, the combined organic layers were washed successively with water and brine, dried over Sodium sulfate and concentrated in vacuo. The title compound was purified by combiflash to give 5-ethyl-2-[3-ethylsulfonyl-6-(2,2,2-trifluoroethylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (298 mg, 52%) as a white crystalline solid.

(203) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.13 (d, 1H), 7.21 (s, 1H), 6.75 (d, 1H), 5.62 (t, 1H), 4.24 (q, 2H), 4.20-4.13 (m, 2H), 4.03 (s, 3H), 3.60 (q, 2H), 1.39 (t, 3H), 1.31 (t, 3H).

Example P35: Preparation of N-cyclopropylsulfonyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide A35

(204) ##STR00147##

(205) In a stirring solution of dichloromethane (20 mL) was added N,N-diethylethanamine (3.489 mmol) and cyclopropanesulfonamide (1.047 mmol, 0.1268 g). Then in ice cold conditions is added 6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carbonyl chloride (500 mg, 1.048 mmol) and reaction was stirred at room temperature for 12 hour. The reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layers were washed with water, brine solution, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by reverse chromatography to get the desired product N-cyclopropylsulfonyl-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-pyridine-3-carboxamide (120 mg, 24%). .sup.1H NMR (400 MHz, MeOH-d4) ppm 0.85-0.90 (m, 2H) 1.06-1.10 (m, 2H) 1.17-1.23 (m, 4H) 1.26-1.31 (m, 3H) 2.86-3.05 (m, 1H) 3.46-3.65 (m, 2H) 4.09-4.23 (m, 2H) 7.19-7.29 (m, 1H) 8.81-9.01 (m, 1H) 9.31-9.52 (m, 1H).

Example P36: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]cyclopropanesulfonamide A36

(206) ##STR00148##

(207) In a stirring solution of pyridine (3.493 mmol, 0.2763 g) under nitrogen was added 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (500 mg, 1.164 mmol) followed by cyclopropane sulfonyl chloride (1.747 mmol, 0.2456 g) and the reaction mixture was stirred at 80 C. for 12 hr. The reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layers were washed with water, brine solution, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using ethyl acetate/cyclohexane (6:4) to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]cyclopropanesulfonamide A36 (420 mg, 0.7873 mmol, 67.61% Yield) as a white solid. 1H NMR (400 MHz, CDCl.sub.3) ppm 1.14-1.22 (m, 2H) 1.36-1.44 (m, 8H) 2.63-2.75 (m, 1H) 3.82 (m, 2H) 4.10 (s, 3H) 4.27 (m, 2H) 7.23 (s, 1H) 7.31 (s, 1H) 8.35 (d, 1H) 8.85 (d, 1H)

Example P37: N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]-N-methyl-cyclopropanesulfonamide A37

(208) ##STR00149##

(209) In a stirring solution of tetrahydrofuran (5 mL, 61.6 mmol) was added potassium carbonate (0.3749 mmol, 0.05181 g) followed by N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]cyclopropanesulfonamide (100 mg, 0.1874 mmol) and The mixture was stirred at room temperature for 2 hr. Then 1 ml of DMF was added and The mixture stirred for 4 hrs.

(210) The mixture was poured in a separating funnel containing Ethyl acetate and water. Organic layer was separated, washed with water and brine, dried over Sodium sulfate, filtered, and concentrated to give crude product which was purified by column chromatography using ethyl acetate/cyclohexane (4:6). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.08-1.16 (m, 2H) 1.23-1.27 (m, 2H) 1.39 (m, 6H) 2.45 (m, 1H) 3.54 (s, 3H) 3.83 (m, 2H) 4.12 (s, 3H) 4.27 (m, 2H) 7.23 (s, 1H) 8.47 (d, 1H) 9.05 (d, 1H)

Example P38: Preparation of 2-(6-amino-5-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A38

(211) ##STR00150##

(212) To a 0 C. cooled solution of 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.6986 mmol, 0.3 g) in N,N-dimethylformamide (3.0 mL) was added 1-chloropyrrolidine-2,5-dione (0.7685 mmol, 0.1026 g) in two portions. The reaction was stirred at 0 C. for 1 hour, then at room temperature for 4 hours, monitored by TLC. The reaction was diluted with water (10 ml), extracted with ethyl acetate and combined organic layer was dried over sodium sulfate, concentrated under reduced pressure. Crude product was purified by combiflash to afford 2-(6-amino-5-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.3665 mmol, 0.17 g). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.21 (s, 1H), 7.20 (s, 1H), 5.60 (s, 2H), 4.24 (q, 2H), 4.05 (s, 3H), 3.59 (q, 2H), 1.38 (t, 3H), 1.33 (t, 3H).

Example P39: Preparation of 2-(6-amino-5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A39

(213) ##STR00151##

(214) To a 0 C. cooled solution of 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.6986 mmol, 0.3 g) in N,N-dimethylformamide (3.0 mL) was added 1-bromopyrrolidine-2,5-dione (0.8384 mmol, 0.1492 g) in two portions. The reaction was stirred at 0 C. for 1 hour, then at room temperature for 4 hours, monitored by TLC. The reaction was diluted with water (10 ml), extracted with ethyl acetate. Combined organic layer was dried over sodium sulfate, concentrated under reduced pressure. Crude product was purified by combiflash to afford 2-(6-amino-5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.3935 mmol, 0.2 g).sup.1H NMR (400 MHz, CDCl.sub.3) 8.37 (s, 1H), 7.21 (s, 1H), 5.64 (s, 2H), 4.24 (q, 2H), 4.05 (s, 3H), 3.59 (q, 2H), 1.42-1.29 (m, 6H).

Example P40: Preparation of N-[3-chloro-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-(cyclopropanecarbonyl)cyclopropanecarboxamide A40

(215) ##STR00152##

(216) To a flask, 2-(6-amino-5-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A38 (0.2 g, 0.431 mmol) was dissolved in dichloromethane (6 mL), then Triethylamine (0.0661 mL) was added to this solution. The solution was cooled to 0 C., and a solution of cyclopropyl carbonyl chloride (0.046 g, 0.04 mL) in dichloromethane (3 mL) was added dropwise at this temperature. The solution was stirred for 15 minutes at 0 C., then at room temperature. After 1 h at room temperature, additional quantities of Triethylamine (0.0661 mL) and cyclopropyl carbonyl chloride (0.04 mL) were added. After 2.5 h at room temperature, additional quantities of Triethylamine (0.0661 mL) and cyclopropyl carbonyl chloride (0.04 mL) were added. After 2 h at room temperature, additional quantities of Triethylamine (0.0661 mL) and cyclopropyl carbonyl chloride (0.04 mL) were added and, finally after 1 h at room temperature, additional Triethylamine (1 mL) and cyclopropyl carbonyl chloride (0.2 mL) were added. The mixture was quenched with a saturated solution of Sodium bicarbonate, and the aqueous phase was extracted twice with dichloromethane. The combinated organic phases were washed with a saturated solution of Sodium bicarbonate, dried with sodium sulfate, filtered. 1.5 g Isolute was added to the filtrate before evaporation of solvent. The residue was purified by chromatography over 12 g silica gel with dichloromethane:ethyl acetate=0-20% to give the title compound in 97% yield. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.64 (s, 1H), 7.18 (s, 1H), 4.24 (q, 2H), 4.10 (s, 3H), 3.88 (q, 2H), 2.0 (m, 2H), 1.30-1.40 (m, 6H), 1.22 (m, 4H), 1.0 (m, 4H).

Example P41: Preparation of N-[3-chloro-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]cyclopropanecarboxamide A41

(217) ##STR00153##

(218) To a colorless solution of N-[3-chloro-6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]-N-(cyclopropanecarbonyl)cyclopropanecarboxamide A40 (0.14 g, 0.233 mmol) in tetrahydrofuran (14 mL) was added Sodium hydroxide (1N, 2.33 mL, 2.33 mmol). The mixture was stirred 1.5 h at room temperature and the reaction was quenched by addition of 2 ml of a aqueous solution of HCl (1N). The aqueous phase was extracted twice with EA. The combinated organic phases were washed with a saturated solution of Sodium bicarbonate, dried with sodium sulfate, filtered. 1.5 g Isolute was added to the filtrate before evaporation of solvent. The residue was purified by chromatography over 12 g silica gel with cyclohexane:ethyl acetate (0-60%) to give the title compound in 81% yield. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.48 (s, 1H), 8.25 (s, 1H), 7.20 (s, 1H), 4.24 (q, 2H), 4.18 (s, 3H), 3.84 (q, 2H), 2.28 (m, 1H), 1.30-1.40 (m, 6H), 1.22 (m, 2H), 0.96 (m, 2H)

Example P42: Preparation of 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A42

(219) ##STR00154##

(220) 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A42 was prepared by similar reactions as described for Example P6 using the appropriate intermediates via the Tert-butyl N-[6-[5-cyclopropyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate A63 as intermediate.

(221) ##STR00155##

(222) Tert-butyl N-[6-[5-cyclopropyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-2-pyridyl]carbamate A63: LC-MS (Method A): RT 1.11, 542 (M+H.sup.+), 540 (MH.sup.+).

(223) 2-(6-amino-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A42: .sup.1H NMR (400 MHz, CDCl.sub.3) 8.10 (d, 1H), 7.17 (s, 1H), 6.69 (d, 1H), 5.13 (s, 2H), 4.00 (s, 3H), 3.52 (q, 2H), 3.07 (m, 1H), 1.23-1.33 (m, 5H), 1.05 (m, 2H).

Example P43: Preparation of 5-cyclopropyl-2-(3-ethylsulfonyl-6-hydrazino-2-pyridyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A45

(224) ##STR00156##

(225) To a flask, Hydrazine hydrate (0.1521 g, 3.04 mmol) was dissolved in tetrahydrofuran (1.823 mL) at room temperature. Then 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl) imidazo[4,5-c]pyridin-4-one (see example 19, 0.28 g, 0.608 mmol) was added portion wise. The reaction was stirred at room temperature for 2.5 h. 2 g Isolute was added to the reaction, before evaporation of solvent. The residue was purified by chromatography over 12 g silica gel with dichloromethane:ethyl acetate to give the title compound in 80% yield. LC-MS (Method A): RT 0.82, 457 (M+H.sup.+), 455 (MH.sup.+).

Example P44: Preparation of 5-cyclopropyl-2-[3-ethylsulfonyl-6-(methoxyamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A46

(226) ##STR00157##

(227) To a vial, 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (see example 19, 0.25 g, 0.5424 mmol) was dissolved in ethanol (1.2 mL) and tetrahydrofuran (1.2 mL), then o-methyl hydroxylamine hydrochloride (0.093 g, 1.09 mmol) and sodium hydrogenocarbonate (0.0914 g, 1.09 mmol) were added to this solution. The solution was stirred overnight at room temperature and extra o-methyl hydroxylamine hydrochloride (0.093 g, 1.09 mmol) and sodium hydrogenocarbonate (0.0914 g, 1.09 mmol) were added. The solution was stirred overnight at room temperature, then 3 h at 40 C. and additional 20 h at 60 C. Then, two time, o-methyl hydroxylamine hydrochloride (0.093 g, 1.09 mmol) and sodium hydrogenocarbonate (0.0914 g, 1.09 mmol) were added and the reaction was heated at 60 C. for 20 h. Then, two time, o-methyl hydroxylamine hydrochloride (0.093 g, 1.09 mmol) and sodium hydrogenocarbonate (0.0914 g, 1.09 mmol) were added, in addition, extra solvent ethanol (1.2 mL) was added and the reaction was heated at 60 C. for 20 h. Extra o-methyl hydroxylamine hydrochloride (0.093 g, 1.09 mmol) and sodium hydrogenocarbonate (0.0914 g2) were added and the reaction was at 60 C. for 20 h. The mixture was quenched in dichloromethane and with a saturated solution of Sodium bicarbonate. The aqueous phase was extracted twice with dichloromethane. All of the organic phases were combinated, dried with sodium sulfate and filtered. 2 g Isolute was added to the organic phase before evaporation of solvent. The residue was purified by chromatography over 4 g silica gel with dichloromethane:ethyl acetate to give the title compound in 59% yield. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.32 (d, 1H), 7.90 (s, 1H), 7.14 (m, 2H), 3.98 (s, 3H), 3.86 (s, 3H), 3.58 (q, 2H), 3.10 (m, 1H), 1.28 (m, 5H), 1.05 (m, 2H).

Example P45: Preparation of 5-cyclopropyl-2-[3-ethylsulfonyl-6-(hydroxyamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A47

(228) ##STR00158##

(229) To a flask, 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (see example 19, 0.25 g, 0.5424 mmol) was dissolved in DMSO (0.6 mL), then sodium hydrogen carbonate (0.093 g, 1.09 mmol) and hydroxylamine hydrochloride (0.0762 g, 1.09 mmol) were added to this solution. The solution was heated for 1 h at 90 C. The mixture was dissolved in dichloromethane and the organic phase was washed with a saturated solution of Sodium bicarbonate (2). The combinated aqueous phase was extracted twice with dichloromethane. All of the organic phases were combinated, dried with sodium sulfate and filtered. 1.5 g Isolute was added to the organic phase before evaporation of solvent. The residue was purified by chromatography over 12 g silica gel with dichloromethane:ethyl acetate to give the title compound in 58% yield. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.52 (s, 1H), 8.18 (d, 1H), 7.18 (s, 1H), 7.06 (d, 1H), 3.92 (s, 3H), 3.42 (q, 2H), 3.10 (m, 1H), 1.30 (m, 5H), 1.05 (m, 2H).

Example P46: Preparation of 2-(6-amino-5-cyclopropyl-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A48

(230) ##STR00159##

(231) A solution of 2-(6-amino-5-bromo-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A44 (preparation described before, 0.13 g, 0.25 mmol) in a mixture of water (1.7 mL) and toluene (1.7 mL) was added potassium phosphate tribasic (0.33 g, 1.50 mmol), cyclopropylboronic acid, (0.081 g, 0.90 mmol) in a vial. The vial was flushed with argon and tetrakis(triphenylphosphine) palladium(0) (0.029 g, 0.025 mmol) was added. The reaction mixture was stirred at reflux for 3.5 hours, then 20 minutes in Microwave at 130 C. Then, cyclopropylboronic acid (0.081 g, 0.90 mmol) and 1,1-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichloromethane complex (0.0215 g, 0.025 mmol) were added and the vial was flushed with argon. The reaction was heated 20 minutes in Microwave at 130 C. The mixture was quenched in dichloromethane and with a 1N solution of sodium hydroxide. The aqueous phase was extracted twice with dichloromethane. All of the organic phases were combinated, watched with a solution of Na.sub.2HCO.sub.3, dried with sodium sulfate and filtered. 1 g Isolute was added to the organic phase before evaporation of solvent. The residue was chromatographed over 4 g silica gel with dichloromethane:ethyl acetate to give the title compound in 32% yield. LC-MS (Method A): RT 0.96, 482 (M+H.sup.+).

Example P47: Preparation of 2-(6-amino-5-methyl-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A49

(232) ##STR00160##

(233) A solution of 2-(6-amino-5-bromo-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl) imidazo[4,5-c]pyridin-4-one A44 (preparation described before, 0.12 g, 0.23 mmol) in a mixture of water (0.12 mL) and dioxane (1.1 mL) was added potassium carbonate (0.0.095 g, 0.63 mmol), trimethylboroxine (0.030 g, 0.239 mmol) in a vial. The vial was flushed with argon and bis[cyclopentyl(diphenyl)phosphaniumyl]palladium; iron; dihydrochloride (0.0167 g, 0.0228 mmol) was added. The reaction mixture was heated at 100 C. for 3 hours. The mixture was quenched in dichloromethane and with a 1N solution of sodium hydroxide. The aqueous phase was extracted twice with dichloromethane. All of the organic phases were combinated, washed with a solution of Na.sub.2HCO.sub.3, dried with sodium sulfate and filtered. 1.5 g Isolute was added to the organic phase before evaporation of solvent. The residue was purified by chromatography over 4 g silica gel with dichloromethane:ethyl acetate to give the title compound in 76% yield. LC-MS (Method A): RT 0.88, 454 (MH.sup.+), 456 (M+H.sup.+).

Example P48: Preparation of 2-(6-amino-5-cyano-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A50

(234) ##STR00161##

(235) A vial was charged with 2-(6-amino-5-bromo-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl) imidazo[4,5-c]pyridin-4-one A44 (preparation described before, 0.12 g) in dimethylformamide (2.16 mL). To this solution was added Pd.sub.2(dba).sub.3 (0.010 g), zinc cyanide (0.22 g) and S-Phos (0.011 g). The reaction mixture was purged with N.sub.2 gas for 25 min. Then, the mixture was heated in the microwave 30 at 150 C. The mixture was quenched with ethyl acetate and with a solution of sodium hydroxide (0.1M). The aqueous phase was extracted twice with ethyl acetate. All of the organic phases were combinated, washed with a solution of sodium hydroxide (0.1M), dried with sodium sulfate and filtered. 1 g Isolute was added to the organic phase before evaporation of solvent. The residue was purified by chromatography over 4 g silica gel with dichloromethane:ethyl acetate to give the title compound in 88% yield. LC-MS (Method A): RT 0.92, 465 (MH.sup.+), 466 (M+H.sup.+).

Example P49: Preparation of 5-cyclopropyl-2-[3-ethylsulfonyl-6-(methylamino)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A51

(236) ##STR00162##

(237) A flask was charged with 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (see example 19, 0.25 g, 0.542 mmol) in methylamine (in THF 2M, 2 mL, 4.00 mmol). The reaction was stirred at RT for 1 h. The mixture was quenched in dichloromethane and with a saturated solution of Sodium bicarbonate. The aqueous phase was extracted twice with dichloromethane. All of the organic phases were combinated, dried with sodium sulfate and filtered. The solvent was evaporated to give the title compound in quantitative yield. LC-MS (Method A): RT 0.93, 457 (M+H.sup.+).

Example P50: Preparation of 1-cyano-N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxamide A55

(238) ##STR00163##

(239) 2-(5-amino-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (100 mg, 0.233 mmol) and 1-cyanocyclopropanecarboxylic acid (26 mg, 0.233 mmol, 1 eq) were dissolved in pyridine (1 ml) at room temperature under nitrogen. The reaction mixture was cooled to 10 C. and phosphorus oxychloride (0.02 ml, 0.279 mmol) was added dropwise under nitrogen. The mixture was stirred at 10 C. and warmed to 0 C. over 30 mins. It was then quenched in water and diluted with Ethyl acetate (10 ml). Organic layer was separated. Aqueous layer was further washed with Ethyl acetate (10 ml). Combined organic extract was washed with brine, dried over sodium sulfate, filtered and concentrated to get crude product which was purified by column chromatography with gradient cyclohexane+0-50% Ethyl acetate to give 1-cyano-N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxamide (94 mg) in 79% yield.

(240) 1H NMR (400 MHz, CDCl.sub.3) ppm 1.34-1.45 (m, 6H) 1.74-1.80 (m, 2H) 1.89-1.95 (m, 2H) 3.78 (m, 2H) 4.08 (s, 3H) 4.25 (m, 2H) 7.21 (s, 1H) 8.58 (s, 1H) 8.73 (d, 1H) 9.21 (d, 1H)

Example P51: Preparation of 1-[[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfinyl-3-pyridyl]amino]cyclopropanecarbonitrile A57

(241) ##STR00164##

(242) 2-(5-bromo-3-ethylsulfinyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (prepared as described in Example I3step C, 250 mg, 0.5238 mmol) was dissolved in anhydrous 1,4-dioxane (5 mL) and to it cesium carbonate (2.095 mmol, 0.683 g) was added under nitrogen followed by the addition of palladium (II) acetate (0.03143 mmol, 0.00706 g) and (1-cyanocyclopropyl)ammonium chloride (0.7857 mmol, 0.09315 g). The mixture was purged with nitrogen for 15 minutes. X-PHOS (0.09428 mmol, 0.04586 g) was then added and the mixture was heated at 110 C. in a preheated oil bath for 14 hrs. The mixture was filtered through celite bed and bed was washed with Ethyl acetate (20 ml). Organic layer was evaporated and purified by column chromatography using 60% Ethyl acetate/cyclohexane to give 1-[[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfinyl-3-pyridyl]amino]cyclopropanecarbonitrile (20 mg, 0.04180 mmol, 8% Yield). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.28-1.34 (m, 2H) 1.37-1.50 (m, 6H) 2.98-3.10 (m, 1H) 3.56-3.67 (m, 1H) 4.23-4.30 (m, 2H) 4.55 (s, 3H) 5.63-5.78 (m, 1H) 7.23 (s, 1H) 8.07 (d, 1H) 8.46 (d, 1H).

Example P52: Preparation of 2-[5-(cyclopropylamino)-3-ethylsulfinyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A58

(243) ##STR00165##

(244) In a 25 ml vial, under nitrogen was taken 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (220 mg, 0.4460 mmol) in anhydrous toluene (5 mL) and to it cesium carbonate (0.6914 mmol, 0.225 g) was added under nitrogen. The mixture was purged with nitrogen for 5 mins. tris(dibenzylideneacetone)dipalladium (0) (0.009219 mmol, 0.008527 g) and (+/)-BINAP (0.01844 mmol, 0.01184 g) were added to the above The mixture was purged with nitrogen for 5 min. Cyclopropyl amine (0.5531 mmol, 0.03158 g, 0.0383 mL) was finally added to the above reaction mixture and heated at 110 C. for 16 hrs. The mixture was filtered through celite bed and the bed was washed with Ethyl acetate (20 ml). The mixture was poured in a separating funnel containing Ethyl acetate and water. Organic layer was separated, washed with water and brine, dried over Sodium sulfate, filtered, and concentrated to give crude product which was purified by column chromatography using ethyl acetate/cyclohexane (4:6) to give 2-[5-(cyclopropylamino)-3-ethylsulfinyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (54 mg, 0.1191 mmol, 26% Yield). .sup.1H NMR (400 MHz, METHANOL-d4) ppm 0.53-0.61 (m, 2H) 0.84-0.94 (m, 2H) 1.38 (m, 6H) 2.57 (m, 1H) 2.92-3.02 (m, 1H) 3.50 (m, 1H) 4.25 (m, 2H) 4.43 (s, 3H) 7.29 (s, 1H) 7.79 (d, 1H) 8.30 (d, 1H)

Example P53: Preparation of N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfanyl-3-pyridyl]cyclopropanecarboxamide A59

(245) ##STR00166##

(246) 2-(5-amino-3-ethylsulfanyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (See A69, 0.4529 mmol, 0.18 g) was dissolved in dry dichloromethane (2 mL) and to it N,N-diethylethanamine (1.359 mmol, 0.1375 g, 0.189 mL) was added at room temperature under nitrogen. The reaction mixture was cooled to 0 C. and cyclopropane carbonyl chloride (0.4982 mmol, 0.05209 g, 0.04521 mL) was added dropwise under nitrogen. The mixture was stirred at 0 C. to room temperature for 1 h and then quenched in water and diluted with DCM (10 ml). Organic layer was separated. Aqueous layer was further washed with DCM (10 ml). Combined organic extract was washed with brine, dried over sodium sulfate and concentrated to get crude product. Crude compound was purified by column chromatography using 60% Ethyl acetate/Cyclohexane to give N-[6-[5-ethyl-3-methyl-4-oxo-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl]-5-ethylsulfanyl-3-pyridyl]cyclopropanecarboxamide (0.3631 mmol, 0.169 g) in 80% yield. 1H NMR (400 MHz, CDCl.sub.3) ppm 8.78 (br. s., 1H), 8.44 (d, 1H), 8.37 (s, 1H), 7.33 (s, 1H), 4.26 (m, 2H), 4.15 (s, 3H), 2.95 (m, 2H), 1.75 (m, 1H), 1.42-1.36 (m, 3H), 1.31 (t, 3H), 1.16-1.10 (m, 2H), 0.96-0.90 (m, 2H).

Example P54: Preparation of 2-[6-[cyclopropyl(methyl)sulfoximine]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A60

(247) ##STR00167##

(248) A solution of 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.3 g, 0.7 mmol), Cyclopropyl(methyl)sulfoximine (Commercially available, CAS 1609964-41-1, 0.7 mmol, 0.09 g), dicesium carbonic acid (1 mmol, 0.4 g), and (5-diphenylphosphanyl-9,9-dimethyl-xanthen-4-yl)-diphenyl-phosphane (0.1 mmol, 0.08 g) in 1,4-dioxane (5.0 mL) was purged with nitrogen for 10 min. To this was then added (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one palladium (0.07 mmol, 0.06 g) and reaction mixture was heated in microwave at 110 C. for 60 min. The reaction was diluted with water (10 ml), extracted with ethyl acetate (330 ml). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Crude product was purified by column chromatography using 50% EA-cyclohexane to give 2-[6-[cyclopropyl(methyl)sulfoximine]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (120 mg, 30% yield). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 8.16 (d, 1H), 7.21 (s, 1H), 6.98 (s, 1H), 4.22 (m, 2H), 4.09 (s, 3H), 3.73-3.52 (m, 2H), 3.37 (s, 3H), 2.77-2.65 (m, 1H), 1.50-1.29 (m, 8H), 1.11 (m, 2H)

Example P55: Preparation of 2-[5-[cyclopropyl(methyl)sulfoximine]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A61

(249) ##STR00168##

(250) A solution of 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (0.6081 mmol, 0.3 g), Cyclopropyl(methyl)sulfoximine (Commercially available, CAS 1609964-41-1, 0.6690 mmol, 0.07973 g), dicesium carbonic acid (1.216 mmol, 0.3987 g) and (5-diphenylphosphanyl-9,9-dimethyl-xanthen-4-yl)-diphenyl-phosphane (0.1216 mmol, 0.07255 g) in 1,4-dioxane (5.0 mL) was purged with nitrogen for 10 min. To this was then added (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium (0.06081 mmol, 0.05569 g) and The mixture was heated in microwave at 110 C. for 60 min. The reaction was diluted with water (10 ml), extracted with ethyl acetate (330 ml). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude was purified by combiflash (silica gel, 50% ethyl acetate-cyclohexane) to gave 2-[5-[Cyclopropyl(methyl)sulfoximine]-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl) imidazo[4,5-c]pyridin-4-one (0.376 mmol, 0.2 g, 62% yield). .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 8.63 (d, 1H), 8.06 (d, 1H), 7.20 (s, 1H), 4.24 (m, 2H), 4.05 (s, 3H), 3.70 (m, 2H), 3.26 (s, 3H), 2.67-2.60 (m, 1H), 1.41-1.32 (m, 6H), 1.31-1.19 (m, 4H).

Example P56: Preparation of 2-(6-acetyl-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A70

(251) ##STR00169##

Step A: Preparation of 2-[6-(1-ethoxyvinyl)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one

(252) ##STR00170##

(253) In 30 mL vial, 2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (5.3 mmol, 2400 mg) and tributyl(1-ethoxyvinyl)stannane (5.6 mmol, 2000 mg) were dissolved in 1,4-dioxane (27 mL), then this yellow suspension was degazzed with an nitrogen for 20 minutes. Pd(PPh3)4 (0.27 mmol, 310 mg) was added at room temperature and the suspension was stirred at 80 C. for 2 hr under microwave irradiation. After completion, the reaction was neutralysed with sodium bicarbonate 10% solution (30 ml), and resultant solution was extracted with ehylacetate (20 ml3). The combined organic layer was washed with aqueous saturated sodium chloride solution (30 ml), dried over anhydrous sodium sulfate, and concentrated of under reduced pressure. The residue was subjected to silica gel column chromatography (30% Ethylacetate hexane and 12 g silica cartage) to obtain tittle compound. This compound was used without any extra purification in the next step.

Step B: Preparation of 2-(6-acetyl-3-ethylsulfonyl-2-pyridyl)-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one A70

(254) a solution of hydrochloride (20 ml) was added to a solution of 2-[6-(1-ethoxyvinyl)-3-ethylsulfonyl-2-pyridyl]-5-ethyl-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-4-one (1 mmol, 500 mg) in dichloromethane (30 ml). The reaction was stirred at 50 C. for 2 h. After completion, the reaction was neutralysed with sodium by carbonate 10% solution (30 ml) at 0 C., and resultant solution was extracted with dichloromethane (20 ml3). The combined organic layer was washed with aqueous saturated sodium chloride solution (30 ml), dried over anhydrous sodium sulfate, and concentrated of under reduced pressure. The residue was subjected to silica gel column chromatography (30% Ethylacetate/hexane and 12 g silica cartage was used) to obtain the desired compound. .sup.1H NMR (400 MHz, CDCl3) ppm 1.34-1.43 (m, 6H) 2.75 (s, 3H) 3.82 (q, 2H) 4.15 (s, 3H) 4.27 (q, 2H) 7.24 (s, 1H), 8.36 (d, 1H) 8.66 (d, 1H).

(255) TABLE-US-00026 TABLE P1 Examples of compounds of formula (I) Compound No. Structures Analytic Method A1 See experimental part above A2 See experimental part above A3 See experimental part above A4 See experimental part above A5 See experimental part above A6 See experimental part above A7 See experimental part above A8 See experimental part above A9 See experimental part above A10 0 See experimental part above A11 See experimental part above A12 See experimental part above A13 See experimental part above A14 See experimental part above A15 .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.33-1.47 (m, 6 H), 3.23 (s, 3 H), 3.82 (q, 2 H), 4.10 (s, 3 H), 4.27 (q, 2 H), 7.24 (s, 1 H), 8.12 (br. s., 1 H), 8.32 (d, 1 H), 8.85 (d, 1 H). A16 See experimental part above A17 See experimental part above A18 See experimental part above A19 .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 0.61-0.69 (m, 2 H), 0.84-0.93 (m, 2 H), 1.26-1.36 (m, 6 H), 2.88-2.96 (m, 1 H), 3.76 (q, 2 H), 4.02 (s, 3 H), 4.18 (q, 2 H), 6.52 (br. s., 1 H), 7.14 (s, 1 H), 8.51-8.77 (m, 1 H), 9.28 (d, 1 H). A20 0 See experimental part above A21 See experimental part above A22 See experimental part above A23 See experimental part above A24 See experimental part above A25 See experimental part above A26 See experimental part above A27 See experimental part above A28 See experimental part above A29 See experimental part above A30 00 See experimental part above A31 01 See experimental part above A32 02 See experimental part above A33 03 See experimental part above A34 04 See experimental part above A35 05 See experimental part above A36 06 See experimental part above A37 07 See experimental part above A38 08 See experimental part above A39 09 See experimental part above A40 0 See experimental part above A41 See experimental part above A42 See experimental part above A43 2-(6-amino-5-chloro-3-ethylsulfonyl-2- pyridyl)-5-cyclopropyl-3-methyl-6- (trifluoromethyl)imidazo[4,5-c]pyridin-4- one was synthesised as described example P38: LC-MS (Method A): RT 0.93, 476 (M + H.sup.+), 474 (M H.sup.+). A44 2-(6-amino-5-bromo-3-ethylsulfonyl-2- pyridyl)-5-cyclopropyl-3-methyl-6- (trifluoromethyl)imidazo[4,5-c]pyridin-4- one was synthesised as described in example P39: LC-MS (Method A): RT 0.95, 522 (M + H.sup.+), 520 (M H.sup.+). A45 See experimental part above A46 See experimental part above A47 See experimental part above A48 See experimental part above A49 See experimental part above A50 0 See experimental part above A51 See experimental part above A52 2-[5-bromo-3-ethylsulfonyl-6- (methylamino)-2-pyridyl]-5-cyclopropyl- 3-methyl-6-(trifluoromethyl)imidazo[4,5- c]pyridin-4-one was synthesised as described in example P39: LC-MS (Method A): RT 1.05, 536 (M + H.sup.+), 534 (M H.sup.+). A53 2-(5-amino-6-chloro-3-ethylsulfonyl-2- pyridyl)-5-ethyl-3-methyl-6- (trifluoromethyl)imidazo[4,5-c]pyridin-4- onewas synthesised as described in example P38: .sup.1H NMR (400 MHz, CDCl.sub.3) 7.74 (s, 1H), 7.19 (s, 1H), 4.77 (s, 2H), 4.24 (q, 2H), 4.07 (s, 3H), 3.74 (q, 2H), 1.36 (m, 6H). A54 2-(5-amino-6-bromo-3-ethylsulfonyl-2- pyridyl)-5-ethyl-3-methyl-6- (trifluoromethyl)imidazo[4,5-c]pyridin-4- onewas synthesised as described in example P39: .sup.1H NMR (400 MHz, CDCl.sub.3) 7.68 (s, 1H), 7.19 (s, 1H), 4.82 (s, 2H), 4.24 (q, 2H), 4.07 (s, 3H), 3.74 (q, 2H), 1.36 (m, 6H). A55 See experimental part above A56 See experimental part above A57 See experimental part above A58 See experimental part above A59 See experimental part above A60 0 See experimental part above A61 See experimental part above A62 See experimental part above A63 See experimental part above A64 See experimental part above A65 See experimental part above A66 See experimental part above A67 See experimental part above A68 A68 was prepared by analogy with Example P9, step A: .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 1.36 (m, 6H), 1.56 (s, 9 H), 2.98 (q, 2 H), 4.17 (s, 3 H), 4.25 (q, 2 H), 6.80 (s, 1 H), 7.33 (s, 1 H), 8.20 (br. s., 1 H), 8.25 (br. s., 1 H). A69 A69 was prepared by deprotecting A68 using the same protocol that described in step C example P9: .sup.1H NMR (400 MHz, CDCl.sub.3) 7.95 (s, 1H), 7.31 (s, 1H), 6.98 (s, 1H), 4.24 (q, 2H), 4.15 (s, 3H), 2.88 (q, 2H), 1.38 (t, 3H), 1.31 (t, 3H) A70 0 See experimental part above A71 A71 was prepared using similar protocoles that A48/A50,: .sup.1H NMR (400 MHz, CDCl.sub.3) 0.75 (m, 2 H), 1.08 (m, 2 H), 1.27 (m, 3 H), 1.38 (m, 3 H), 1.70 (m, 1 H), 3.50 (m, 2 H), 4.03 (s, 3 H), 4.23 (m, 2 H), 5.41 (s, 2 H), 7.19 (s, 1 H), 7.90 (s, 1 H). A72 A72 was prepared using similar protocoles that A48/A50: .sup.1H NMR (400 MHz, CDCl.sub.3) 1.33-1.43 (m, 6 H), 3.65 (m, 2 H), 4.09 (s, 3 H), 4.23 (m, 2 H), 5.89 (s, 2 H), 7.20 (s, 1 H), 8.46 (s, 1 H). A73 A73 was prepared using similar protocoles that A52: .sup.1H NMR (400 MHz, CDCl.sub.3) 1.33 (t, 3 H), 1.40 (m, 3 H), 3.08 (m, 3 H), 3.60-3.67 (m, 2 H), 4.09 (s, 3 H), 4.21-4.27 (m, 2 H), 5.76-5.80 (m, 1 H), 7.21-7.23 (m, 1 H), 8.19-8.32 (m, 1 H).

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

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

(258) 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 to 42 and P1 of the present invention):

(259) an adjuvant selected from the group of substances consisting of petroleum oils (628)+TX,

(260) 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 [CCN]+TX, benzoximate (71)+TX, benzyl benzoate (IUPAC name) [CCN]+TX, bifenazate (74)+TX, bifenthrin (76)+TX, binapacryl (907)+TX, brofenvalerate+TX, bromocyclen (918)+TX, bromophos (920)+TX, bromophos-ethyl (921)+TX, bromopropylate (94)+TX, buprofezin (99)+TX, butocarboxim (103)+TX, butoxycarboxim (104)+TX, butylpyridaben+TX, calcium polysulfide (IUPAC name) (111)+TX, camphechlor (941)+TX, carbanolate (943)+TX, carbaryl (115)+TX, carbofuran (118)+TX, carbophenothion (947)+TX, CGA 50439 (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 [CCN]+TX, coumaphos (174)+TX, crotamiton [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+TX, dicofol (242)+TX, dicrotophos (243)+TX, dienochlor (1071)+TX, dimefox (1081)+TX, dimethoate (262)+TX, dinactin (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 [CCN]+TX, disulfoton (278)+TX, DNOC (282)+TX, dofenapyn (1113)+TX, doramectin [CCN]+TX, endosulfan (294)+TX, endothion (1121)+TX, EPN (297)+TX, eprinomectin [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+TX, fen-pyroximate (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 (473)+TX, isopropyl O-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473)+TX, ivermectin [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 [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 [CCN]+TX, mipafox (1293)+TX, monocrotophos (561)+TX, morphothion (1300)+TX, moxidectin [CCN]+TX, naled (567)+TX, NC-184 (compound code)+TX, NC-512 (compound code)+TX, nifluridide (1309)+TX, nikkomycins [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 (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 (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+TX, selamectin [CCN]+TX, SI-0009 (compound code)+TX, sophamide (1402)+TX, spirodiclofen (738)+TX, spiromesifen (739)+TX, SSI-121 (development code) (1404)+TX, sulfiram [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+TX, tetrachlorvinphos (777)+TX, tetradifon (786)+TX, tetranactin (653)+TX, tetrasul (1425)+TX, thiafenox+TX, thiocarboxime (1431)+TX, thiofanox (800)+TX, thiometon (801)+TX, thioquinox (1436)+TX, thuringiensin [CCN]+TX, triamiphos (1441)+TX, triarathene (1443)+TX, triazophos (820)+TX, triazuron+TX, trichlorfon (824)+TX, trifenofos (1455)+TX, trinactin (653)+TX, vamidothion (847)+TX, vaniliprole [CCN] and YI-5302 (compound code)+TX,
an algicide selected from the group of substances consisting of bethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX, copper sulfate (172)+TX, cybutryne [CCN]+TX, dichlone (1052)+TX, dichlorophen (232)+TX, endothal (295)+TX, fentin (347)+TX, hydrated lime [CCN]+TX, nabam (566)+TX, quinoclamine (714)+TX, quinonamid (1379)+TX, simazine (730)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX, an anthelmintic selected from the group of substances consisting of abamectin (1)+TX, crufomate (1011)+TX, doramectin [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin [CCN]+TX, ivermectin [CCN]+TX, milbemycin oxime [CCN]+TX, moxidectin [CCN]+TX, piperazine [CCN]+TX, selamectin [CCN]+TX, spinosad (737) and thiophanate (1435)+TX,
an avicide selected from the group of substances consisting of chloralose (127)+TX, endrin (1122)+TX, fenthion (346)+TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745)+TX,
a bactericide selected from the group of substances consisting of 1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222)+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, 8-hydroxyquinoline sulfate (446)+TX, bronopol (97)+TX, copper dioctanoate (IUPAC name) (170)+TX, copper hydroxide (IUPAC name) (169)+TX, cresol [CCN]+TX, dichlorophen (232)+TX, dipyrithione (1105)+TX, dodicin (1112)+TX, fenaminosulf (1144)+TX, formaldehyde (404)+TX, hydrargaphen [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 [CCN]+TX,
a biological agent selected from the group of substances consisting of Adoxophyes orana GV (12)+TX, Agrobacterium radiobacter (13)+TX, Amblyseius spp. (19)+TX, Anagrapha falcifera NPV (28)+TX, Anagrus atomus (29)+TX, Aphelinus abdominalis (33)+TX, Aphidius colemani (34)+TX, Aphidoletes aphidimyza (35)+TX, Autographa californica NPV (38)+TX, Bacillus firmus (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 (53)+TX, Beauveria brongniartii (54)+TX, Chrysoperla carnea (151)+TX, Cryptolaemus montrouzieri (178)+TX, Cydia pomonella GV (191)+TX, Dacnusa sibirica (212)+TX, Diglyphus isaea (254)+TX, Encarsia formosa (scientific name) (293)+TX, Eretmocerus eremicus (300)+TX, Helicoverpa zea NPV (431)+TX, Heterorhabditis bacteriophora and H. megidis (433)+TX, Hippodamia convergens (442)+TX, Leptomastix dactylopii (488)+TX, Macrolophus caliginosus (491)+TX, Mamestra brassicae NPV (494)+TX, Metaphycus helvolus (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 (575)+TX, Orius spp. (596)+TX, Paecilomyces fumosoroseus (613)+TX, Phytoseiulus persimilis (644)+TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741)+TX, Steinernema bibionis (742)+TX, Steinernema carpocapsae (742)+TX, Steinernema feltiae (742)+TX, Steinernema glaseri (742)+TX, Steinernema riobrave (742)+TX, Steinernema riobravis (742)+TX, Steinernema scapterisci (742)+TX, Steinernema spp. (742)+TX, Trichogramma spp. (826)+TX, Typhlodromus occidentalis (844) and Verticillium lecanii (848)+TX,
a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537)+TX,
a chemosterilant selected from the group of substances consisting of apholate [CCN]+TX, bisazir [CCN]+TX, busulfan [CCN]+TX, diflubenzuron (250)+TX, dimatif [CCN]+TX, hemel [CCN]+TX, hempa [CCN]+TX, metepa [CCN]+TX, methiotepa [CCN]+TX, methyl apholate [CCN]+TX, morzid [CCN]+TX, penfluron [CCN]+TX, tepa [CCN]+TX, thiohempa [CCN]+TX, thiotepa [CCN]+TX, tretamine [CCN] and uredepa [CCN]+TX,
an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (IUPAC name) (222)+TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829)+TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541)+TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate (IUPAC name) (779)+TX, (Z)-dodec-7-en-1-yl acetate (IUPAC name) (285)+TX, (Z)-hexadec-11-enal (IUPAC name) (436)+TX, (Z)-hexadec-11-en-1-yl acetate (IUPAC name) (437)+TX, (Z)-hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438)+TX, (Z)-icos-13-en-10-one (IUPAC name) (448)+TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782)+TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783)+TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283)+TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780)+TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781)+TX, 14-methyloctadec-1-ene (IUPAC name) (545)+TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (IUPAC name) (544)+TX, alpha-multistriatin [CCN]+TX, brevicomin [CCN]+TX, codlelure [CCN]+TX, codlemone (167)+TX, cuelure (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 [CCN]+TX, ethyl 4-methyloctanoate (IUPAC name) (317)+TX, eugenol [CCN]+TX, frontalin [CCN]+TX, gossyplure (420)+TX, grandlure (421)+TX, grandlure I (421)+TX, grandlure II (421)+TX, grandlure III (421)+TX, grandlure IV (421)+TX, hexalure [CCN]+TX, ipsdienol [CCN]+TX, ipsenol [CCN]+TX, japonilure (481)+TX, lineatin [CCN]+TX, litlure [CCN]+TX, looplure [CCN]+TX, medlure [CCN]+TX, megatomoic acid [CCN]+TX, methyl eugenol (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 [CCN]+TX, oryctalure (317)+TX, ostramone [CCN]+TX, siglure [CCN]+TX, sordidin (736)+TX, sulcatol [CCN]+TX, tetradec-11-en-1-yl acetate (IUPAC name) (785)+TX, trimedlure (839)+TX, trimedlure A (839)+TX, trimedlure B.sub.1 (839)+TX, trimedlure B.sub.2 (839)+TX, trimedlure C (839) and trunc-call [CCN]+TX,
an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591)+TX, butopyronoxyl (933)+TX, butoxy(polypropylene glycol) (936)+TX, dibutyl adipate (IUPAC name) (1046)+TX, dibutyl phthalate (1047)+TX, dibutyl succinate (IUPAC name) (1048)+TX, diethyltoluamide [CCN]+TX, dimethyl carbate [CCN]+TX, dimethyl phthalate [CCN]+TX, ethyl hexanediol (1137)+TX, hexamide [CCN]+TX, methoquin-butyl (1276)+TX, methylneodecanamide [CCN]+TX, oxamate [CCN] and picaridin [CCN]+TX,
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 [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 [CCN]+TX, allyxycarb (866)+TX, alpha-cypermethrin (202)+TX, alpha-ecdysone [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 (41)+TX, azamethiphos (42)+TX, azinphos-ethyl (44)+TX, azinphos-methyl (45)+TX, azothoate (889)+TX, Bacillus thuringiensis delta endotoxins (52)+TX, barium hexafluorosilicate [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 (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+TX, bromfenvinfos (914)+TX, bromocyclen (918)+TX, bromo-DDT [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+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 (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 1 (696)+TX, cinerin 11 (696)+TX, cinerins (696)+TX, cis-resmethrin+TX, cismethrin (80)+TX, clocythrin+TX, cloethocarb (999)+TX, closantel [CCN]+TX, clothianidin (165)+TX, copper acetoarsenite [CCN]+TX, copper arsenate [CCN]+TX, copper oleate [CCN]+TX, coumaphos (174)+TX, coumithoate (1006)+TX, crotamiton [CCN]+TX, crotoxyphos (1010)+TX, crufomate (1011)+TX, cryolite (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 [CCN]+TX, d-limonene [CCN]+TX, d-tetramethrin (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+TX, dicresyl [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 [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 [CCN]+TX, DSP (1115)+TX, ecdysterone [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 [CCN]+TX, esfenvalerate (302)+TX, etaphos [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 (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+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 (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 [CCN]+TX, jasmolin 1 (696)+TX, jasmolin 11 (696)+TX, jodfenphos (1248)+TX, juvenile hormone I [CCN]+TX, juvenile hormone II [CCN]+TX, juvenile hormone III [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 (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 (533)+TX, methoxychlor (534)+TX, methoxyfenozide (535)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, methylchloroform [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 [CCN]+TX, mipafox (1293)+TX, mirex (1294)+TX, monocrotophos (561)+TX, morphothion (1300)+TX, moxidectin [CCN]+TX, naftalofos [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 O-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 [CCN]+TX, pentachlorophenol (623)+TX, pentachlorophenyl laurate (IUPAC name) (623)+TX, permethrin (626)+TX, petroleum oils (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 [CCN]+TX, precocene II [CCN]+TX, precocene III [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 1 (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 [CCN]+TX, quinalphos (711)+TX, quinalphos-methyl (1376)+TX, quinothion (1380)+TX, quintiofos (1381)+TX, R-1492 (development code) (1382)+TX, rafoxanide [CCN]+TX, resmethrin (719)+TX, rotenone (722)+TX, RU 15525 (development code) (723)+TX, RU 25475 (development code) (1386)+TX, ryania (1387)+TX, ryanodine (traditional name) (1387)+TX, sabadilla (725)+TX, schradan (1389)+TX, sebufos+TX, selamectin [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 (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+TX, terbufos (773)+TX, tetrachloroethane [CCN]+TX, tetrachlorvinphos (777)+TX, tetramethrin (787)+TX, theta-cypermethrin (204)+TX, thiacloprid (791)+TX, thiafenox+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 [CCN]+TX, tolfenpyrad (809)+TX, tralomethrin (812)+TX, transfluthrin (813)+TX, transpermethrin (1440)+TX, triamiphos (1441)+TX, triazamate (818)+TX, triazophos (820)+TX, triazuron+TX, trichlorfon (824)+TX, trichlormetaphos-3 [CCN]+TX, trichloronat (1452)+TX, trifenofos (1455)+TX, triflumuron (835)+TX, trimethacarb (840)+TX, triprene (1459)+TX, vamidothion (847)+TX, vaniliprole [CCN]+TX, veratridine (725)+TX, veratrine (725)+TX, XMC (853)+TX, xylylcarb (854)+TX, YI-5302 (compound code)+TX, zeta-cypermethrin (205)+TX, zetamethrin+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 WO2005/077934)+TX,
a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913)+TX, bromoacetamide [CCN]+TX, calcium arsenate [CCN]+TX, cloethocarb (999)+TX, copper acetoarsenite [CCN]+TX, copper sulfate (172)+TX, fentin (347)+TX, ferric phosphate (IUPAC name) (352)+TX, metaldehyde (518)+TX, methiocarb (530)+TX, niclosamide (576)+TX, niclosamide-olamine (576)+TX, pentachlorophenol (623)+TX, sodium pentachlorophenoxide (623)+TX, tazimcarb (1412)+TX, thiodicarb (799)+TX, tributyltin oxide (913)+TX, trifenmorph (1454)+TX, trimethacarb (840)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX, pyriprole [394730-71-3]+TX,
a nematicide selected from the group of substances consisting of AKD-3088 (compound code)+TX, 1,2-dibromo-3-chloropropane (IUPAC/Chemical Abstracts name) (1045)+TX, 1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062)+TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063)+TX, 1,3-dichloropropene (233)+TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC/Chemical Abstracts name) (1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPAC name) (1286)+TX, 6-isopentenylaminopurine (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+TX, cadusafos (109)+TX, carbofuran (118)+TX, carbon disulfide (945)+TX, carbosulfan (119)+TX, chloropicrin (141)+TX, chlorpyrifos (145)+TX, cloethocarb (999)+TX, cytokinins (210)+TX, dazomet (216)+TX, DBCP (1045)+TX, DCIP (218)+TX, diamidafos (1044)+TX, dichlofenthion (1051)+TX, dicliphos+TX, dimethoate (262)+TX, doramectin [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin [CCN]+TX, ethoprophos (312)+TX, ethylene dibromide (316)+TX, fenamiphos (326)+TX, fenpyrad+TX, fensulfothion (1158)+TX, fosthiazate (408)+TX, fosthietan (1196)+TX, furfural [CCN]+TX, GY-81 (development code) (423)+TX, heterophos [CCN]+TX, iodomethane (IUPAC name) (542)+TX, isamidofos (1230)+TX, isazofos (1231)+TX, ivermectin [CCN]+TX, kinetin (210)+TX, mecarphon (1258)+TX, metam (519)+TX, metam-potassium (519)+TX, metam-sodium (519)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, milbemycin oxime [CCN]+TX, moxidectin [CCN]+TX, Myrothecium verrucaria composition (565)+TX, NC-184 (compound code)+TX, oxamyl (602)+TX, phorate (636)+TX, phosphamidon (639)+TX, phosphocarb [CCN]+TX, sebufos+TX, selamectin [CCN]+TX, spinosad (737)+TX, terbam+TX, terbufos (773)+TX, tetrachlorothiophene (IUPAC/Chemical Abstracts name) (1422)+TX, thiafenox+TX, thionazin (1434)+TX, triazophos (820)+TX, triazuron+TX, xylenols [CCN]+TX, YI-5302 (compound code) and zeatin (210)+TX, fluensulfone [318290-98-1]+TX,
a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580)+TX,
a plant activator selected from the group of substances consisting of acibenzolar (6)+TX, acibenzolar-S-methyl (6)+TX, probenazole (658) and Reynoutria sachalinensis extract (720)+TX,
a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, alpha-chlorohydrin [CCN]+TX, aluminium phosphide (640)+TX, antu (880)+TX, arsenous oxide (882)+TX, barium carbonate (891)+TX, bisthiosemi (912)+TX, brodifacoum (89)+TX, bromadiolone (91)+TX, bromethalin (92)+TX, calcium cyanide (444)+TX, chloralose (127)+TX, chlorophacinone (140)+TX, cholecalciferol (850)+TX, coumachlor (1004)+TX, coumafuryl (1005)+TX, coumatetralyl (175)+TX, crimidine (1009)+TX, difenacoum (246)+TX, difethialone (249)+TX, diphacinone (273)+TX, ergocalciferol (301)+TX, flocoumafen (357)+TX, fluoroacetamide (379)+TX, flupropadine (1183)+TX, flupropadine hydrochloride (1183)+TX, gamma-HCH (430)+TX, HCH (430)+TX, hydrogen cyanide (444)+TX, iodomethane (IUPAC name) (542)+TX, lindane (430)+TX, magnesium phosphide (IUPAC name) (640)+TX, methyl bromide (537)+TX, norbormide (1318)+TX, phosacetim (1336)+TX, phosphine (IUPAC name) (640)+TX, phosphorus [CCN]+TX, pindone (1341)+TX, potassium arsenite [CCN]+TX, pyrinuron (1371)+TX, scilliroside (1390)+TX, sodium arsenite [CCN]+TX, sodium cyanide (444)+TX, sodium fluoroacetate (735)+TX, strychnine (745)+TX, thallium sulfate [CCN]+TX, warfarin (851) and zinc phosphide (640)+TX,
a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934)+TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903)+TX, farnesol with nerolidol (324)+TX, MB-599 (development code) (498)+TX, MGK 264 (development code) (296)+TX, piperonyl butoxide (649)+TX, piprotal (1343)+TX, propyl isomer (1358)+TX, S421 (development code) (724)+TX, sesamex (1393)+TX, sesasmolin (1394) and sulfoxide (1406)+TX,
an animal repellent selected from the group of substances consisting of anthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX, copper oxychloride (171)+TX, diazinon (227)+TX, dicyclopentadiene (chemical name) (1069)+TX, guazatine (422)+TX, guazatine acetates (422)+TX, methiocarb (530)+TX, pyridin-4-amine (IUPAC name) (23)+TX, thiram (804)+TX, trimethacarb (840)+TX, zinc naphthenate [CCN] and ziram (856)+TX,
a virucide selected from the group of substances consisting of imanin [CCN] and ribavirin [CCN]+TX,
a wound protectant selected from the group of substances consisting of mercuric oxide (512)+TX, octhilinone (590) and thiophanate-methyl (802)+TX,
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, tebucon-azole [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, metalaxyl [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, acibenzolar-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-LI90 (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, 11H naphtho[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; lancotrione [1486617-21-3], florpyrauxifen [943832-81-3], ipfentrifluconazole[1417782-08-1], mefentrifluconazole [1417782-03-6], quinofumelin [861647-84-9], chloroprallethrin [399572-87-3], cyhalodiamide [1262605-53-7], fluazaindolizine [1254304-22-7], fluxametamide [928783-29-3], epsilon-metofluthrin [240494-71-7], epsilon-momfluorothrin [1065124-65-3], pydiflumetofen [1228284-64-7], kappa-bifenthrin [439680-76-9], broflanilide [1207727-04-5], dicloromezotiaz [1263629-39-5], dipymetitrone [16114-35-5], pyraziflumid [942515-63-1] and kappa-tefluthrin [391634-71-2]; and
microbials including: Acinetobacter Iwoffii+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, Melocont)+TX, Beauveria spp.+TX, Botrytis cineria+TX, Bradyrhizobium japonicum (TerraMax)+TX, Brevibacillus brevis+TX, Bacillus thuringiensis tenebrionis (Novodor)+TX, BtBooster+TX, Burkholderia cepacia (Deny+TX, Intercept+TX, Blue Circle)+TX, Burkholderia gladii+TX, Burkholderia gladioli+TX, Burkholderia spp.+TX, Canadian thistle fungus (CBH Canadian Bioherbicide)+TX, Candida butyri+TX, Candida famata+TX, Candida fructus+TX, Candida glabrata+TX, Candida guilliermondii+TX, Candida melibiosica+TX, Candida oleophila strain O+TX, Candida parapsilosis+TX, Candida pelliculosa+TX, Candida pulcherrima+TX, Candida reukaufii+TX, Candida saitoana (Bio-Coat+TX, Biocure)+TX, Candida sake+TX, Candida spp.+TX, Candida tenius+TX, Cedecea dravisae+TX, Cellulomonas flavigena+TX, Chaetomium cochliodes (Nova-Cide)+TX, Chaetomium globosum (Nova-Cide)+TX, Chromobacterium subtsugae strain PRAA4-1T (Grandevo)+TX, Cladosporium cladosporioides+TX, Cladosporium oxysporum+TX, Cladosporium chlorocephalum+TX, Cladosporium spp.+TX, Cladosporium tenuissimum+TX, Clonostachys rosea (EndoFine)+TX, Colletotrichum acutatum+TX, Coniothyrium minitans (Cotans WG)+TX, Coniothyrium spp.+TX, Cryptococcus albidus (YIELDPLUS)+TX, Cryptococcus humicola+TX, Cryptococcus infirmo-miniatus+TX, Cryptococcus laurentii+TX, Cryptophlebia leucotreta granulovirus (Cryptex)+TX, Cupriavidus campinensis+TX, Cydia pomonella granulovirus (CYD-X)+TX, Cydia pomonella granulovirus (Madex+TX, Madex Plus+TX, Madex Max/Carpovirusine)+TX, Cylindrobasidium laeve (Stumpout)+TX, Cylindrocladium+TX, Debaryomyces hansenii+TX, Drechslera hawaiinensis+TX, Enterobacter cloacae+TX, Enterobacteriaceae+TX, Entomophtora virulenta (Vektor)+TX, Epicoccum nigrum+TX, Epicoccum purpurascens+TX, Epicoccum spp.+TX, Filobasidium floriforme+TX, Fusarium acuminatum+TX, Fusarium chlamydosporum+TX, Fusarium oxysporum (Fusaclean/Biofox C)+TX, Fusarium proliferatum+TX, Fusarium spp.+TX, Galactomyces geotrichum+TX, Gliocladium catenulatum (Primastop+TX, Prestop)+TX, Gliocladium roseum+TX, Gliocladium spp. (SoilGard)+TX, Gliocladium virens (Soilgard)+TX, Granulovirus (Granupom)+TX, Halobacillus halophilus+TX, Halobacillus litoralis+TX, Halobacillus trueperi+TX, Halomonas spp.+TX, Halomonas subglaciescola+TX, Halovibrio variabilis+TX, Hanseniaspora uvarum+TX, Helicoverpa armigera nucleopolyhedrovirus (Helicovex)+TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar)+TX, Isoflavone-formononetin (Myconate)+TX, Kloeckera apiculata+TX, Kloeckera spp.+TX, Lagenidium giganteum (Laginex)+TX, Lecanicillium longisporum (Vertiblast)+TX, Lecanicillium muscarium (Vertikil)+TX, Lymantria Dispar nucleopolyhedrosis virus (Disparvirus)+TX, Marinococcus halophilus+TX, Meira geulakonigii+TX, Metarhizium anisopliae (Met52)+TX, Metarhizium anisopliae (Destruxin WP)+TX, Metschnikowia fruticola (Shemer)+TX, Metschnikowia pulcherrima+TX, Microdochium dimerum (Antibot)+TX, Micromonospora coerulea+TX, Microsphaeropsis ochracea+TX, Muscodor albus 620 (Muscudor)+TX, Muscodor roseus strain A3-5+TX, Mycorrhizae spp. (AMykor+TX, Root Maximizer)+TX, Myrothecium verrucaria strain AARC-0255 (DiTera)+TX, BROS PLUS+TX, Ophiostoma piliferum strain D97 (Sylvanex)+TX, Paecilomyces farinosus+TX, Paecilomyces fumosoroseus (PFR-97+TX, PreFeRal)+TX, Paecilomyces linacinus (Biostat WP)+TX, Paecilomyces lilacinus strain 251 (MeloCon WG)+TX, Paenibacillus polymyxa+TX, Pantoea agglomerans (BlightBan C9-1)+TX, Pantoea spp.+TX, Pasteuria spp. (Econem)+TX, Pasteuria nishizawae+TX, Penicillium aurantiogriseum+TX, Penicillium billai (Jumpstart+TX, TagTeam)+TX, Penicillium brevicompactum+TX, Penicillium frequentans+TX, Penicillium griseofulvum+TX, Penicillium purpurogenum+TX, Penicillium spp.+TX, Penicillium viridicatum+TX, Phlebiopsis gigantean (Rotstop)+TX, phosphate solubilizing bacteria (Phosphomeal)+TX, Phytophthora cryptogea+TX, Phytophthora palmivora (Devine)+TX, Pichia anomala+TX, Pichia guilermondii+TX, Pichia membranaefaciens+TX, Pichia onychis+TX, Pichia stipites+TX, Pseudomonas aeruginosa+TX, Pseudomonas aureofasciens (Spot-Less Biofungicide)+TX, Pseudomonas cepacia+TX, Pseudomonas chlororaphis (AtEze)+TX, Pseudomonas corrugate+TX, Pseudomonas fluorescens strain A506 (BlightBan A506)+TX, Pseudomonas putida+TX, Pseudomonas reactans+TX, Pseudomonas spp.+TX, Pseudomonas syringae (Bio-Save)+TX, Pseudomonas viridiflava+TX, 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
Plant extracts including: pine oil (Retenol)+TX, azadirachtin (Plasma Neem Oil+TX, AzaGuard+TX, MeemAzal+TX, Molt-X+TX, Botanical IGR (Neemazad+TX, Neemix)+TX, canola oil (Lilly Miller Vegol)+TX, Chenopodium ambrosioides near ambrosioides (Requiem)+TX, Chrysanthemum extract (Crisant)+TX, extract of neem oil (Trilogy)+TX, essentials oils of Labiatae (Botania)+TX, extracts of clove rosemary peppermint and thyme oil (Garden Insect Killer)+TX, Glycinebetaine (Greenstim)+TX, garlic+TX, lemongrass oil (GreenMatch)+TX, neem oil+TX, Nepeta cataria (Catnip oil)+TX, Nepeta catarina+TX, nicotine+TX, oregano oil (MossBuster)+TX, Pedaliaceae oil (Nematon)+TX, pyrethrum+TX, Quillaja saponaria (NemaQ)+TX, Reynoutria sachalinensis (Regalia+TX, Sakalia)+TX, rotenone (Eco Roten)+TX, Rutaceae plant extract (Soleo)+TX, soybean oil (Ortho Ecosense)+TX, tea tree oil (Timorex Gold)+TX, thymus oil+TX, AGNIQUE MMF+TX, BugOil+TX, mixture of rosemary sesame peppermint thyme and cinnamon extracts (EF 300)+TX, mixture of clove rosemary and peppermint extract (EF 400)+TX, mixture of clove peppermint garlic oil and mint (Soil Shot)+TX, kaolin (Screen)+TX, storage glucam of brown algae (Laminarin); and
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 MECLR 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
Macrobials including: Aphelinus abdominalis+TX, Aphidius ervi (Aphelinus-System)+TX, Acerophagus papaya+TX, Adalia bipunctata (Adalia-System)+TX, Adalia bipunctata (Adaline)+TX, Adalia bipunctata (Aphidalia)+TX, Ageniaspis citricola+TX, Ageniaspis fuscicollis+TX, Amblyseius andersoni (Anderline+TX, Andersoni-System)+TX, Amblyseius californicus (Amblyline+TX, Spical)+TX, Amblyseius cucumeris (Thripex+TX, Bugline cucumeris)+TX, Amblyseius fallacis (Fallacis)+TX, Amblyseius swirskii (Bugline swirskii+TX, Swirskii-Mite)+TX, Amblyseius womersleyi (WomerMite)+TX, Amitus hesperidum+TX, Anagrus atomus+TX, Anagyrus fusciventris+TX, Anagyrus kamali+TX, Anagyrus loecki+TX, Anagyrus pseudococci (Citripar)+TX, Anicetus benefices+TX, Anisopteromalus calandrae+TX, Anthocoris nemoralis (Anthocoris-System)+TX, Aphelinus abdominalis (Apheline+TX, Aphiline)+TX, Aphelinus asychis+TX, Aphidius colemani (Aphipar)+TX, Aphidius ervi (Ervipar)+TX, Aphidius gifuensis+TX, Aphidius matricariae (Aphipar-M)+TX, Aphidoletes aphidimyza (Aphidend)+TX, Aphidoletes aphidimyza (Aphidoline)+TX, Aphytis lingnanensis+TX, Aphytis melinus+TX, Aprostocetus hagenowii+TX, Atheta coriaria (Staphyline)+TX, Bombus spp.+TX, Bombus terrestris (Natupol Beehive)+TX, Bombus terrestris (Beeline+TX, Tripol)+TX, Cephalonomia stephanoderis+TX, Chilocorus nigritus+TX, Chrysoperla carnea (Chrysoline)+TX, Chrysoperla carnea (Chrysopa)+TX, Chrysoperla rufilabris+TX, Cirrospilus ingenuus+TX, Cirrospilus quadristriatus+TX, Citrostichus phyllocnistoides+TX, Closterocerus chamaeleon+TX, Closterocerus spp.+TX, Coccidoxenoides perminutus (Planopar)+TX, Coccophagus cowperi+TX, Coccophagus lycimnia+TX, Cotesia flavipes+TX, Cotesia plutellae+TX, Cryptolaemus montrouzieri (Cryptobug+TX, Cryptoline)+TX, Cybocephalus nipponicus+TX, Dacnusa sibirica+TX, Dacnusa sibirica (Minusa)+TX, Diglyphus isaea (Diminex)+TX, Delphastus catalinae (Delphastus)+TX, Delphastus pusillus+TX, Diachasmimorpha krausii+TX, Diachasmimorpha longicaudata+TX, Diaparsis jucunda+TX, Diaphorencyrtus aligarhensis+TX, Diglyphus isaea+TX, Diglyphus isaea (Miglyphus+TX, Digline)+TX, Dacnusa sibirica (DacDigline+TX, Minex)+TX, Diversinervus spp.+TX, Encarsia citrina+TX, Encarsia formosa (Encarsia Max+TX, Encarline+TX, En-Strip)+TX, Eretmocerus eremicus (Enermix)+TX, Encarsia guadeloupae+TX, Encarsia haitiensis+TX, Episyrphus balteatus (Syrphidend)+TX, Eretmoceris siphonini+TX, Eretmocerus californicus+TX, Eretmocerus eremicus (Ercal+TX, Eretline e)+TX, Eretmocerus eremicus (Bemimix)+TX, Eretmocerus hayati+TX, Eretmocerus mundus (Bemipar+TX, Eretline m)+TX, Eretmocerus siphonini+TX, Exochomus quadripustulatus+TX, Feltiella acarisuga (Spidend)+TX, Feltiella acarisuga (Feltiline)+TX, Fopius arisanus+TX, Fopius ceratitivorus+TX, Formononetin (Wirless Beehome)+TX, Franklinothrips vespiformis (Vespop)+TX, Galendromus occidentalis+TX, Goniozus legneri+TX, Habrobracon hebetor+TX, Harmonia axyridis (HarmoBeetle)+TX, Heterorhabditis spp. (Lawn Patrol)+TX, Heterorhabditis bacteriophora (NemaShield HB+TX, Nemaseek+TX, Terranem-Nam+TX, Terranem+TX, Larvanem+TX, B-Green+TX, NemAttack+TX, Nematop)+TX, Heterorhabditis megidis (Nemasys H+TX, BioNem H+TX, Exhibitline hm+TX, Larvanem-M)+TX, Hippodamia convergens+TX, Hypoaspis aculeifer (Aculeifer-System+TX, Entomite-A)+TX, Hypoaspis miles (Hypoline m+TX, Entomite-M)+TX, Lbalia leucospoides+TX, Lecanoideus floccissimus+TX, Lemophagus errabundus+TX, Leptomastidea abnormis+TX, Leptomastix dactylopii (Leptopar)+TX, Leptomastix epona+TX, Lindorus lophanthae+TX, Lipolexis oregmae+TX, Lucilia caesar (Natufly)+TX, Lysiphlebus testaceipes+TX, Macrolophus caliginosus (Mirical-N+TX, Macroline c+TX, Mirical)+TX, Mesoseiulus longipes+TX, Metaphycus flavus+TX, Metaphycus lounsburyi+TX, Micromus angulatus (Milacewing)+TX, Microterys flavus+TX, Muscidifurax raptorellus and Spalangia cameroni (Biopar)+TX, Neodryinus typhlocybae+TX, Neoseiulus californicus+TX, Neoseiulus cucumeris (THRYPEX)+TX, Neoseiulus fallacis+TX, Nesideocoris tenuis (NesidioBug+TX, Nesibug)+TX, Ophyra aenescens (Biofly)+TX, Orius insidiosus (Thripor-I+TX, Oriline i)+TX, Orius laevigatus (Thripor-L+TX, Oriline I)+TX, Orius majusculus (Oriline m)+TX, Orius strigicollis (Thripor-S)+TX, Pauesia juniperorum+TX, Pediobius foveolatus+TX, Phasmarhabditis hermaphrodita (Nemaslug)+TX, Phymastichus coffea+TX, Phytoseiulus macropilus+TX, Phytoseiulus persimilis (Spidex+TX, Phytoline p)+TX, Podisus maculiventris (Podisus)+TX, Pseudacteon curvatus+TX, Pseudacteon obtusus+TX, Pseudacteon tricuspis+TX, Pseudaphycus maculipennis+TX, Pseudleptomastix mexicana+TX, Psyllaephagus pilosus+TX, Psyttalia concolor (complex)+TX, Quadrastichus spp.+TX, Rhyzobius lophanthae+TX, Rodolia cardinalis+TX, Rumina decollate+TX, Semielacher petiolatus+TX, Sitobion avenae (Ervibank)+TX, Steinernema carpocapsae (Nematac C+TX, Millenium+TX, BioNem C+TX, NemAttack+TX, Nemastar+TX, Capsanem)+TX, Steinernema feltiae (NemaShield+TX, Nemasys F+TX, BioNem F+TX, Steinernema-System+TX, NemAttack+TX, Nemaplus+TX, Exhibitline sf+TX, Scia-rid+TX, Entonem)+TX, Steinernema kraussei (Nemasys L+TX, BioNem L+TX, Exhibitline srb)+TX, Steinernema riobrave (BioVector+TX, BioVektor)+TX, Steinernema scapterisci (Nematac S)+TX, Steinernema spp.+TX, Steinernematid spp. (Guardian Nematodes)+TX, Stethorus punctillum (Stethorus)+TX, Tamarixia radiate+TX, Tetrastichus setifer+TX, Thripobius semiluteus+TX, Torymus sinensis+TX, Trichogramma brassicae (Tricholine b)+TX, Trichogramma brassicae (Tricho-Strip)+TX, Trichogramma evanescens+TX, Trichogramma minutum+TX, Trichogramma ostriniae+TX, Trichogramma platneri+TX, Trichogramma pretiosum+TX, Xanthopimpla stemmator and
other biologicals including: abscisic acid+TX, bioSea+TX, Chondrostereum purpureum (Chontrol Paste)+TX, Colletotrichum gloeosporioides (Collego)+TX, Copper Octanoate (Cueva)+TX, Delta traps (Trapline d)+TX, Erwinia amylovora (Harpin) (ProAct+TX, Ni-HIBIT Gold CST)+TX, Ferri-phosphate (Ferramol)+TX, Funnel traps (Trapline y)+TX, Gallex+TX, Grower's Secret+TX, Homo-brassonolide+TX, Iron Phosphate (Lilly Miller Worry Free Ferramol Slug & Snail Bait)+TX, MCP hail trap (Trapline f)+TX, Microctonus hyperodae+TX, Mycoleptodiscus terrestris (Des-X)+TX, BioGain+TX, Aminomite+TX, Zenox+TX, Pheromone trap (Thripline ams)+TX, potassium bicarbonate (MilStop)+TX, potassium salts of fatty acids (Sanova)+TX, potassium silicate solution (Sil-Matrix)+TX, potassium iodide+potassiumthiocyanate (Enzicur)+TX, SuffOil-X+TX, Spider venom+TX, Nosema locustae (Semaspore Organic Grasshopper Control)+TX, Sticky traps (Trapline YF+TX, Rebell Amarillo)+TX and Traps (Takitrapline y+b)+TX.

(261) 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 ManualA 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.

(262) 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. CAS Reg. No means the Chemical Abstracts Registry Number.

(263) The active ingredient mixture of the compounds of formula I selected from Tables 1 to 42 with active ingredients described above comprises a compound selected from Tables 1 to 42 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.

(264) 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.

(265) The mixtures comprising a compound of formula I selected from Tables 1 to 42 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 to 42 and the active ingredients as described above is not essential for working the present invention.

(266) 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.

(267) 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.

(268) 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 pouringwhich are to be selected to suit the intended aims of the prevailing circumstancesand 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.

(269) 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.

(270) 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.

(271) 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.

(272) 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).

(273) 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

Example B1: Bemisia tabaci (Cotton White Fly): Feeding/Contact Activity

(274) 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.

(275) The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

(276) A6, A7, A8, A9, A10, A12, A18, A20, A30, A31, A37, A38, A39, A40, A42, A43, A44, A47, A48, A49, A51, A52, A63, A64, A66 and A71.

Example B2: Diabrotica balteata (Corn Root Worm)

(277) 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.

(278) 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:

(279) A1, A2, A5, A6, A8, A10, A11, A12, A24, A26, A30, A31, A32, A33, A34, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A56, A57, A58, A59, A63, A66 and A71.

Example B3: Euschistus heros(Neotropical Brown Stink Bug)

(280) 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.

(281) 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:

(282) A1, A2, A6, A7, A8, A9, A10, A11, A12, A13, A17, A19, A20, A22, A24, A25, A26, A28, A30, A31, A37, A38, A39, A40, A41, A42, A43, A44, A46, A47, A48, A50, A51, A52, A56, A64, A71 and A72.

Example B4: Frankliniella occidentalis (Western Flower Thrips):Feeding/Contact Activity

(283) 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.

(284) The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

(285) A1, A8, A10, A11, A43, A48 and, A50.

Example B5: Myzus persicae (Green Peach Aphid):Feeding/Contact Activity

(286) 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.

(287) The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

(288) A1, A2, A5, A6, A7, A8, A9, A10, A11, A12, A13, A18, A20, A28, A30, A36, A38, A39, A40, A41, A42, A43, A44, A45, A47, A48, A49, A50, A51, A52, A53, A55, A56, A59 and A71.

Example B6: Myzus persicae (Green Peach Aphid). Systemic Activity

(289) 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.

(290) The following compounds resulted in at least 80% mortality at a test rate of 24 ppm:

(291) A2, A6, A7, A9, A10, A17, A18, A19, A20, A22, A28, A30, A42, A43, A45, A47, A48, A49, A50, A51, A55, A71 and A72.

Example B7: Myzus persicae (Green Peach Aphid). Intrinsic Activity

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

(293) The following compound resulted in at least 80% mortality at a test rate of 12 ppm:

(294) A59

Example B8: Plutella xylostella (Diamond Back Moth)

(295) 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.

(296) 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:

(297) A1, A2, A5, A6, A7, A8, A9, A10, A11, A12, A13, A17, A18, A19, A20, A22, A24, A26, A27, A28, A30, A31, A32, A33, A34, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A59, A63, A64, A66, A70, A71 and A72.

Example B9: Spodoptera littoralis (Egyptian Cotton Leaf Worm)

(298) 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.

(299) The following compounds resulted in at least 80% control at an application rate of 200 ppm:

(300) A1, A2, A5, A6, A7, A8, A9, A10, A11, A12, A13, A18, A20, A22, A24, A25, A26, A27, A30, A31, A32, A33, A34, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A59, A63, A64, A66, A71 and A72.

Example B10: Spodoptera littoralis (Egyptian Cotton Leaf Worm)

(301) 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.

(302) 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:

(303) A2, A6, A8, A9, A10, A11, A20, A26, A31, A38, A39, A40, A41, A42, A43, A44, A45, A50, A51, A52, A53, A56 and A66.

Example B11: Tetranychus urticae (Two-Spotted Spider Mite):Feeding/Contact Activity

(304) 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.

(305) The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

(306) A1, A2, A4, A1, A13, A19, A24, A30, A32, A34, A42, A48, A64, A66 and A71.

Example B12: Thrips tabaci (Onion Thrips) Feeding/Contact Activity

(307) 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.

(308) The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

(309) A44 and A52.

Example B13: Aedes Aegypti (Yellow Fever Mosquito)

(310) Test solutions, at an application rate of 200 ppm in ethanol, were applied to 12 well tissue culture plates. Once the deposits were dry, five, two to five day old adult female Aedes aegypti were added to each well, and sustained with a 10% sucrose solution in a cotton wool plug. Assessment of knockdown was made one hour after introduction, and mortality was assessed at 24 and 48 hours after introduction.

(311) The following compounds gave at least 80% control of Aedes aegypti after 48 h and/or 24 h:

(312) A1, A2, A5, A6, A11, A12, A30, A38 and A39.

Example B14: Anopheles stephensi (Indian Malaria Mosquito)

(313) Test solutions, at an application rate of 200 ppm in ethanol, were applied to 12 well tissue culture plates. Once the deposits were dry, five, two to five day old adult female Anopheles stephensi were added to each well, and sustained with a 10% sucrose solution in a cotton wool plug. Assessment of knockdown was made one hour after introduction, and mortality was assessed at 24 and 48 hours after introduction.

(314) The following compounds gave at least 80% control of Anopheles stephensi after 48 h and/or 24 h:

(315) A2 and A30.