Pesticidal Compounds

Abstract

The present invention relates to the compounds of formula (I), and the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof wherein the variables are defined according to the description,

##STR00001##

The compounds of formula (I), as well as the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof, are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

Claims

1-15. (canceled)

16. A compound of the formula I ##STR00139## wherein A is N or CR.sup.A; G is N or CR.sup.B; R, R.sup.A, and R.sup.B are H, halogen, N.sub.3, OH, CN, NO.sub.2, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, tri-C.sub.1-C.sub.6-alkylsilyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkoxy, which are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, OC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, NHC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, SO.sub.2NR.sup.bR.sup.c, or S(O).sub.mR.sup.e, one radical may also be phenyl, phenoxy, phenylcarbonyl, phenylthio, or benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; Q is NR.sup.2, O, or S(O)m, wherein R.sup.2 is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with halogen, C(O)OR.sup.a, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, SO.sub.2NR.sup.bR.sup.c, S(O).sub.mR.sup.e, phenyl, or benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; Ar is phenyl or 5- or 6-membered hetaryl, which are unsubstituted or substituted with R.sup.Ar, wherein R.sup.Ar is halogen, N.sub.3, OH, CN, NO.sub.2, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, tri-C.sub.1-C.sub.6-alkylsilyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, OC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, NHC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, SO.sub.2NR.sup.bR.sup.c, or S(O).sub.mR.sup.e, one radical may also be phenyl, phenoxy, phenylcarbonyl, phenylthio or benzyl, where the rings are unsubstituted or substituted with R.sup.f; R.sup.1 is a moiety of formula XYZ-T-R or XYZ-T-R.sup.12; wherein X is CR.sup.xaR.sup.xb, O, S, NR.sup.xc, CR.sup.xaCR.sup.xb, CR.sup.xaR.sup.xbCR.sup.xaR.sup.xb, OCR.sup.xaR.sup.xb, SCR.sup.xaR.sup.xb, NCR.sup.xa, NR.sup.xcCR.sup.xaR.sup.xb, NR.sup.xcC(S), NC(SR.sup.e), or NR.sup.xcC(O); Y is CR.sup.yaN, wherein the N is bound to Z; NR.sup.ycC(O), wherein C(O) is bound to Z; or NR.sup.ycC(S), wherein C(S) is bound to Z; Z is a single bond; NR.sup.zcC(S), wherein C(S) is bound to T; NR.sup.zcC(O), wherein C(O) is bound to T; NC(SR.sup.za), wherein T is bound to the carbon atom; OC(O), wherein T is bound to the carbon atom; OC(S), wherein T is bound to the carbon atom; or NR.sup.zcC(SR.sup.za), wherein T is bound to the carbon atom; T is O, N or NR.sup.T; R.sup.11 is C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkoxy, which are unsubstituted or substituted with halogen, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, aryl, arylcarbonyl, aryl-C.sub.1-C.sub.4-alkyl, aryloxy-C.sub.1-C.sub.4-alkyl, hetaryl, carbonyl-hetaryl, hetaryl-C.sub.1-C.sub.4-alkyl or hetaryloxy-C.sub.1-C.sub.4-alkyl, where the rings are unsubstituted or substituted with R.sup.g and wherein the hetaryl is a 5- or 6-membered monocyclic hetaryl or a 8-, 9- or 10-membered bicyclic hetaryl; R.sup.12 is a radical of the formula A.sup.1; ##STR00140## wherein # indicates the point of attachment to T; R.sup.121, R.sup.122, R.sup.123 are H, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyloxy, C.sub.2-C.sub.6-alkynyloxy, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.6-alkylcarbonlyoxy, C.sub.1-C.sub.6-haloalkylcarbonlyoxy, C.sub.1-C.sub.6-alkenylcarbonlyoxy, C.sub.3-C.sub.6-cycloalkylcarbonlyoxy, or NR.sup.bR.sup.c, or one of R.sup.121, R.sup.122, R.sup.123 may also be oxo; R.sup.124 is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, or C.sub.2-C.sub.6-alkenyloxy; and wherein R.sup.xa, R.sup.xb, R.sup.ya are H, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkoxy, which are unsubstituted or substituted with halogen, C(O)OR.sup.a, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, SO.sub.2NR.sup.bR.sup.c, S(O).sub.mR.sup.e, phenyl, or benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; R.sup.xc, R.sup.yc, R.sup.zc are H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.4-alkyl-C.sub.1-C.sub.6-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkyl, or C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkoxy, which are unsubstituted or substituted with halogen; R.sup.T is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.4-alkyl-C.sub.1-C.sub.6-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, where the alkyl, which are unsubstituted or substituted with halogen, C(O)OR.sup.a, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, SO.sub.2NR.sup.bR.sup.c, S(O).sub.mR.sup.e, phenyl, or benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; R.sup.zc together with R.sup.T if present, may form C.sub.1-C.sub.6-alkylene or a linear C.sub.2-C.sub.6-alkenylene group, where in the linear C.sub.1-C.sub.6-alkylene and the linear C.sub.2-C.sub.6-alkenylene a CH.sub.2 moiety may be replaced by a carbonyl or a CNR and/or wherein 1 or 2 CH.sub.2 moieties may be replaced by O or S and/or wherein the linear C.sub.1-C.sub.6-alkylene and the linear C.sub.2-C.sub.6-alkenylene may be unsubstituted or substituted with R.sup.h; R.sup.za is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, tri-C.sub.1-C.sub.6-alkylsilyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.4-alkyl-C.sub.1-C.sub.6-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkoxy, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkyl, which are unsubstituted or substituted with halogen, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, phenyl, phenylcarbonyl, or benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; R.sup.za together with R.sup.T if present, may form C.sub.1-C.sub.6-alkylene or a linear C.sub.2-C.sub.6-alkenylene group, where in the linear C.sub.1-C.sub.6-alkylene and the linear C.sub.2-C.sub.6-alkenylene a CH.sub.2 moiety may be replaced by a carbonyl or a CNR and/or wherein 1 or 2 CH.sub.2 moieties may be replaced by O or S and/or wherein the linear C.sub.1-C.sub.6-alkylene and the linear C.sub.2-C.sub.6-alkenylene may be unsubstituted or substituted with R.sup.h; R.sup.a, R.sup.b and R.sup.c independently of each other are H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with halogen, C.sub.1-C.sub.6-alkylen-CN, phenyl, or benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; R.sup.d is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with halogen, phenyl, or benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; R.sup.e is C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with halogen, phenyl and benzyl, wherein the rings are unsubstituted or substituted with R.sup.f; R.sup.f is halogen, N.sub.3, OH, CN, NO.sub.2, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, tri-C.sub.1-C.sub.6-alkylsilyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxyx-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, OC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, NHC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, SO.sub.2NR.sup.bR.sup.c, or S(O).sub.mR.sup.e; R.sup.g is halogen, N3, OH, CN, NO.sub.2, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, tri-C.sub.1-C.sub.6-alkylsilyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, OC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylen-CN, NHC.sub.1-C.sub.6-alkylen-NR.sup.bR.sup.c, C(O)NR.sup.bR.sup.c, C(O)R.sup.d, SO.sub.2NR.sup.bR.sup.c, or S(O).sub.mRe; R.sup.h is halogen, OH, C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl, or CN; m is 0, 1, or 2; or an N-oxide, stereoisomer, tautomer or an agriculturally or veterinarily acceptable salt thereof.

17. The compound of claim 16, wherein A is CR.sup.A and G is N.

18. The compound of claim 16, wherein A is N and G is CR.sup.B.

19. The compound of claim 16, wherein A is N and G is N.

20. The compound of claim 16, wherein A is CR.sup.A and G is CR.sup.B.

21. The compound of claim 16, wherein Q is NR.sup.2

22. The compound of claim 16, wherein XYZ-T are formulas XYZT-1 to XYZT-19 wherein ##STR00141## denotes attachment to the 6 membered hetaryl and # denotes attachment to R.sup.11 or R.sup.12; ##STR00142## ##STR00143##

23. The compound of claim 16, wherein A is N or CR.sup.A; G is N or CR.sup.B; Q is NH or NCH.sub.3; R is H or C.sub.1-C.sub.6-alkyl; R.sup.A is H or N(CH.sub.3).sub.2; R.sup.B is H or CH.sub.3; Ar is Ar-2; ##STR00144## R.sup.1 is a moiety of formula XYZ-T-R or XYZ-T-R.sup.12; wherein XYZ-T is selected from XYZ-T-1, XYZ-T-2, XYZ-T-3, XYZ-T-4, XYZ-T, XYZ-T-9, XYZ-T-13, XYZ-T-16, XYZ-T-17, XYZ-T-18, and XYZ-T-19; R.sup.11 is R.sup.11-1 or R.sup.11-10; ##STR00145## R.sup.12 is formula A.sup.11-1; ##STR00146##

24. A composition comprising one compound of claim 16, an N-oxide or an agriculturally acceptable salt thereof.

25. The composition of claim 24, comprising additionally a further active substance.

26. A method for combating or controlling invertebrate pests, which method comprises contacting said pest or its food supply, habitat or breeding grounds with a pesticidally effective amount of at least one compound of claim 16.

27. A method for protecting growing plants from attack or infestation by invertebrate pests, which method comprises contacting a plant, or soil or water in which the plant is growing, with a pesticidally effective amount of at least one compound of claim 16.

28. Seed treated with the compound of claim 16, or an enantiomer, diastereomer or salt thereof, in an amount of from 0.1 g to 10 kg per 100 kg of seed.

29. A method for treating or protecting an animal from infestation or infection by invertebrate pests which comprises bringing the animal in contact with a pesticidally effective amount of at least one compound of the formula I of claim 16, a stereoisomer thereof and/or at least one veterinarily acceptable salt thereof.

30. A method for combating or controlling invertebrate pests, which method comprises contacting said pest or its food supply, habitat or breeding grounds with a pesticidally effective amount of the composition of claim 24.

31. A method for protecting growing plants from attack or infestation by invertebrate pests, which method comprises contacting a plant, or soil or water in which the plant is growing, with a pesticidally effective amount of the composition of claim 24.

32. The method of claim 26, wherein A is CR.sup.A and G is N.

33. The method of claim 26, wherein A is N and G is CR.sup.B.

34. The method of claim 26, wherein A is N and G is N.

35. The method of claim 26, wherein A is CR.sup.A and G is CR.sup.B.

36. The method of claim 26, wherein Q is NR.sup.2

37. The method of claim 26, wherein XYZ-T are formulas XYZT-1 to XYZT-19 wherein ##STR00147## denotes attachment to the 6 membered hetaryl and # denotes attachment to R.sup.11 or R.sup.12; ##STR00148## ##STR00149##

38. The method of claim 26, wherein A is N or CR.sup.A; G is N or CR.sup.B; Q is NH or NCH.sub.3; R is H or C.sub.1-C.sub.6-alkyl; R.sup.A is H or N(CH.sub.3).sub.2; R.sup.B is H or CH.sub.3; Ar is Ar-2; ##STR00150## R.sup.1 is a moiety of formula XYZ-T-R or XYZ-T-R.sup.12; wherein XYZ-T is selected from XYZ-T-1, XYZ-T-2, XYZ-T-3, XYZ-T-4, XYZ-T, XYZ-T-9, XYZ-T-13, XYZ-T-16, XYZ-T-17, XYZ-T-18, and XYZ-T-19; R.sup.11 is R.sup.11-1 or R.sup.11-10; ##STR00151## R.sup.12 is formula A.sup.11-1; ##STR00152##

Description

PREPARATION EXAMPLES

[1366] With appropriate modification of the starting materials, the procedures as described in the preparation examples below were used to obtain further compounds of formula I. The compounds obtained in this manner are listed in the table C that follows, together with physical data.

[1367] Compounds can be characterized e.g. by coupled High Performance Liquid Chromatography/mass spectrometry (HPLC/MS), by .sup.1H-NMR and/or by their melting points.

[1368] Analytical HPLC-Method: Agilent Eclipse Plus C18, 504.6 mm, ID 5 m; Elution: A=10 mM Amm. Formate (0.1% Formic Acid), B=Acetonitrile (0.1% Formic Acid), Flow=1.2 ml/min. at 30 C.; Gradient:=10% B to 100% B3 min, hold for 1 min, 1 min10% B. Run Time=5.01 min.

[1369] .sup.1H-NMR: The signals are characterized by chemical shift (ppm, 8 [delta]) vs. tetramethylsilane respectively, CDCl.sub.3 for .sup.13C-NMR, by their multiplicity and by their integral (relative number of hydrogen atoms given). The following abbreviations are used to characterize the multiplicity of the signals: m=multiplet, q=quartet, t=triplet, d=doublet and s=singlet.

[1370] Abbreviations used are: d for day(s), h for hour(s), min for minute(s), r.t./room temperature for 20-25 C., Rt for retention time; DMSO for dimethyl sulfoxide, OAc for acetate, EtOAc for ethyl acetate, TH F for tetrahydrofuran, and t-BuOH for tert-butanol.

Example1: 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[2-[4-(trifluoromethoxy)anilino] pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (C-1)

Step 1: 5-bromo-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1371] To a solution of 5-bromo-2-chloro-pyrimidine (0.1 g) in N,N-Dimethyl formamide (3 mL), was added Potassium carbonate (0.142 g), Copper (I) iodide (0.01 g), 8-hydroxy quinoline (0.08 g) and 4-(trifluoromethoxy) aniline (0.11 g). The mixture was heated at 95 C. for 24 h. The mixture was diluted with water (15 mL) and extracted with Ethyl acetate. The organic extracts were dried over anhydrous Sodium sulfate and evaporated under reduced pressure and the resulting residue was subjected to flash silica gel column chromatography using a gradient of Ethyl acetate and Heptane as eluent to afford the titled compound as a off-white solid (0.05 g). LC/MS: R.sub.t: 1.86 min; MS: m/z=334 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 10.12-9.94 (m, 1H), 8.74-8.56 (m, 2H), 7.89-7.72 (m, 2H), 7.38-7.24 (m, 2H).

Step 2: (E)-2-methyl-3-[2-[4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal

[1372] A solution of 5-bromo-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (0.1 g) was taken up in 1,4-Dioxane (4 mL) and water (1 mL) and the mixture degassed with nitrogen for 15 min. [1,1-Bis(diphenylphosphino)ferrocene]dichloro palladium(II) (0.01 g), Cesium carbonate (0.2 g) and 2-[(E)-3,3-diethoxy-2-methyl-prop-1-enyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.11 g) were added and the mixture degassed with nitrogen for an additional 10 min. The mixture was heated at 95 C. for 4 h and subsequently cooled to ambient temperature. A solution of Hydrochloric acid (1 N) was added and the mixture stirred for 30 min. The mixture was neutralized with solid Sodium bicarbonate and extracted with Ethyl acetate. The organic extracts were dried over anhydrous sodium sulfate and evaporated under reduced pressure and the residue obtained was purified by flash column chromatography eluting with a gradient of Ehyl acetate and Heptane to afford (E)-2-methyl-3-[2-[4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal as a solid (0.03 g). LC/MS: R.sub.t: 1.65 min; MS: m/z=324 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 10.33 (s, 1H), 9.54 (s, 1H), 8.80 (s, 2H), 8.01-7.80 (m, 2H), 7.48-7.34 (m, 2H), 7.32 (s, 1H), 2.02 (s, 3H).

Step 3: 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[2-[4-(trifluoromethoxy)anilino] pyrimidin-5-yl]prop-2-enylidene]amino]thiourea

[1373] A mixture of (E)-2-methyl-3-[2-[4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.2 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.130 g) in Ethanol (3 mL) was heated at 80 C. for 3 h. The mixture was cooled to ambient temperature and the precipitated solid was filtered and washed with cold Ethanol and n-pentane to afford the titled compound (0.2 g). LC/MS: R.sub.t: 1.96 min; MS: m/z=515 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 11.74 (s, 1H), 10.10 (s, 1H), 9.72 (s, 1H), 8.69 (s, 2H), 7.96 (s, 1H), 7.91-7.88 (m, 2H), 7.36-7.19 (m, 6H), 6.69 (s, 1H), 3.14-3.05 (m, 1H), 2.14 (s, 3H), 1.19-1.17 (m, 6H).

Example 2: Synthesis of 1-(2,6-dimethylphenyl)-3-[(E)-[(E)-2-methyl-3-[2-[4-(trifluoromethoxy) anilino]pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (C-2)

[1374] A mixture of (E)-2-methyl-3-[2-[4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.2 g) and 1-amino-3-(2,6-dimethylphenyl)thiourea (0.12 g) in Ethanol (3 mL) was heated at 80 C. for 3 h. The mixture was subsequently cooled to ambient temperature, the suspended solids filtered, washed sequentially with cold ethanol, pentane and dried to afford the title compound (0.2 g). LC/MS: R.sub.t: 1.89 min; MS: m/z=501 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 11.67 (s, 1H), 10.09 (s, 1H), 9.61 (s, 1H), 8.69 (s, 2H), 7.94 (s, 1H), 7.91-7.80 (m, 2H), 7.42-7.22 (m, 2H), 7.21-7.02 (m, 3H), 6.67 (s, 1H), 2.21 (s, 3H), 2.18 (s, 6H).

Example 3: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[(E)-2-methyl-3-[2-[4-(trifluoromethoxy) anilino]pyrimidin-5-yl]prop-2-enylidene]hydrazono]thiazolidin-4-one (C-3)

[1375] To a stirred solution of 1-(2-isopropylphenyl)-3-[(2-methyl-3-[2-[4-(trifluoromethoxy) anilino]pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (0.170 g) in Ethanol (3 mL) was added Sodium acetate (0.082 g) and Methyl bromoacetate (0.25 g). The mixture was stirred at room temperature for 30 h and subsequently diluted with water and extracted with Ethyl acetate. The organic extracts were separated, dried over anhydrous Sodium sulfate and evaporated under reduced pressure. The residue obtained was subjected to flash silica gel column chromatography eluting with a gradient of Ethylacetate-Heptane to afford the title compound as a solid (0.16 g). LC/MS: R.sub.t: 1.99 min; MS: m/z=555 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 10.14 (s, 1H), 8.61 (s, 2H), 8.02 (s, 1H), 7.96-7.78 (m, 2H), 7.57-7.40 (m, 2H), 7.40-7.27 (m, 3H), 7.27-7.19 (m, 1H), 6.78 (s, 1H), 4.33-3.99 (m, 2H), 2.85-2.67 (m, 1H), 2.01 (s, 3H), 1.14-1.12 (m, 6H).

Example 4: Synthesis of (2Z)-3-(2,6-dimethylphenyl)-2-[(2-methyl-3-[2-[4-(trifluoromethoxy) anilino]pyrimidin-5-yl] prop-2-enylidene]hydrazono]thiazolidin-4-one (C-4)

[1376] A mixture of 1-(2,6-dimethylphenyl)-3-[2-methyl-3-[2-[4(trifluoromethoxy)anilino] pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (0.19 g), Sodium acetate (0.094 g) and Methyl bromoacetate (0.29 g) in Ethanol (4 mL) was stirred at r.t. for 24 h. The mixture was subsequently diluted with water and extracted with Ethyl acetate. The organic extracts were dried over anhydrous Sodium sulfate and evaporated under reduced pressure and the residue obtained was subjected to silica gel flash column chromatography, eluting with a gradient of Ethyl acetate-Heptane to obtain the title compound (0.170 g). LC/MS: R.sub.t: 1.95 min; MS: m/z=541 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 10.11 (s, 1H), 8.61 (s, 2H), 8.02 (s, 1H), 7.95-7.75 (m, 2H), 7.38-7.28 (m, 2H), 7.28-7.24 (m, 1H), 7.24-7.16 (m, 2H), 6.78 (s, 1H), 4.22 (s, 2H), 2.14 (s, 3H), 2.08 (s, 6H).

Example 5: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[(E)-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enylidene]hydrazono]thiazolidin-4-one (C-5)

Step 1: 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1377] To a stirred solution of 5-bromo-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (0.1 g) in N, N-Dimethylformamide (3 mL) at 0 C. was added sodium hydride (0.01 g). Methyl iodide (0.064 g) was added and the mixture stirred at r.t. for 12 h. The mixture was diluted with saturated Ammonium chloride solution, extracted with Ethyl acetate, the organic extracts dried over anhydrous Sodium sulfate and concentrated under reduced pressure. The residue obtained was subjected to silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to afford the desired product (0.05 g). LC/MS: R.sub.t: 2.262 min; MS: m/z=348 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.53 (s, 2H), 7.54-7.43 (m, 2H), 7.43-7.32 (m, 2H), 3.44 (s, 3H), 1.20 (d, J=19.4 Hz, 2H).

Step 2: (E)-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal

[1378] A mixture of 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl] pyrimidin-2-amine (0.5 g) in 1,4-Dioxane (8 mL) and water (2 mL) was degassed with nitrogen gas for 15 min. [1,1-Bis(diphenylphosphino)ferrocene]dichloro palladium(II) (0.055 g), Cesium carbonate (1 g) and 2-[(E)-3,3-diethoxyprop-1-enyl]-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (0.7 g) were added and the mixture heated at 95 C. for 3 h. The reaction mixture was cooled to ambient temperature, acidified with 1N HCl solution and stirred at r.t. for 30 min. The mixture was neutralized with solid Sodium bicarbonate, extracted with ethyl acetate, the organic layers dried over Sodium sulfate and evaporated under reduced pressure. The resulting residue was subjected to silica gel flash column chromatography eluting with a gradient of Ethyl acetate and heptane to obtain the title compound as a solid (150 mg). LC/MS: R.sub.t: 1.98 min; MS: m/z=324.2 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 9.59 (d, J=7.8 Hz, 1H), 8.79 (s, 2H), 7.59 (d, J=16.0 Hz, 1H), 7.56-7.48 (m, 2H), 7.42 (d, J=8.6 Hz, 2H), 6.84 (dd, J=16.0, 7.8 Hz, 1H), 3.53 (s, 3H).

Step 3: 1-(2-isopropylphenyl)-3-[[3-[2-[N-methyl-4-(trifluoromethoxy)anilino] pyrimidin-5-yl]prop-2-enylidene]amino]thiourea

[1379] A mixture of (E)-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.09 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.058 g) in Ethanol (3 mL) was heated at 80 C. for 2 h. The mixture was subsequently cooled to ambient temperature, the suspended solids filtered and washed with cold Ethanol to afford the title compound (0.08 g). LC/MS: R.sub.t: 1.90 min; MS: m/z=515 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.64 (s, 2H), 8.00-7.87 (m, 1H), 7.57-7.43 (m, 2H), 7.45-7.35 (m, 2H), 7.35-7.29 (m, 1H), 7.29-7.22 (m, 1H), 7.22-7.12 (m, 2H), 6.99-6.82 (m, 2H), 3.50 (s, 3H), 3.15-2.94 (m, 1H), 1.15 (d, J=6.9 Hz, 6H).

Step 4: (2Z)-3-(2-isopropylphenyl)-2-[[3-[2-[N-methyl-4-(trifluoromethoxy)anilino] pyrimidin-5-yl]prop-2-enylidene]hydrazono]thiazolidin-4-one

[1380] A mixture of 1-(2-isopropylphenyl)-3-[(E)-[(E)-3-[2-[N-methyl-4-(trifluoromethoxy)aniline]pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (0.08 g), Sodium acetate (0.039 g) and Methyl bromo acetate (0.120 g) in Ethanol (3 mL) was stirred at r.t. for 12 h. The reaction mixture was subsequently diluted with water and extracted with Ethyl acetate. The organic extracts were dried over anhydrous Sodium sulfate and evaporated under reduced pressure and the residue obtained subjected to silica gel flash column chromatograph eluting with a gradient of Ethyl acetate-Heptane to afford the title compound (0.04 g). LC/MS: R.sub.t: 1.97 min; MS: m/z=555 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.65 (s, 2H), 8.00 (d, J=9.3 Hz, 1H), 7.55-7.44 (m, 4H), 7.44-7.35 (m, 2H), 7.35-7.27 (m, 1H), 7.26-7.19 (m, 1H), 7.12-6.99 (m, 1H), 6.99-6.85 (m, 1H), 4.29-3.99 (m, 2H), 3.50 (s, 3H), 2.82-2.64 (m, 1H), 1.21-1.00 (m, 6H).

Example 6: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[2-[N-methyl-4-(trifluoro methoxy)anilino]pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (C-6)

Step 1: (E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal

[1381] A mixture of 5-bromo-N-methyl-N-[4-(trifluoromethoxy) phenyl] pyrimidin-2-amine (0.4 g) in 1,4 Dioxane (6 mL) and water (1.5 mL) was degassed with nitrogen gas for 15 min. [1,1-Bis(diphenylphosphino)ferrocene]dichloro palladium(II) (0.042 g), Cesium carbonate (0.751 g) and 2-[(E)-3, 3-diethoxyprop-1-enyl]-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (0.590 g) were added and the mixture heated at 95 C. for 4 h. The reaction mixture was cooled to ambient temperature, acidified with 1N HCl solution and stirred at r.t. for 30 min. The mixture was neutralized with solid Sodium bicarbonate, extracted with ethyl acetate, the organic layers dried over Sodium sulfate and evaporated under reduced pressure. The resulting residue was subjected to silica gel flash column chromatography eluting with a gradient of Ethyl acetate and heptane to obtain the title compound as a solid (0.2 g). LC/MS: R.sub.t: 2.15 min; MS: m/z=338.2 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 9.51 (s, 1H), 8.71 (s, 2H), 7.60-7.47 (m, 2H), 7.47-7.37 (m, 2H), 7.33 (s, 1H), 3.54 (s, 3H), 1.97 (s, 3H).

Step 2: 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy) anilino]pyrimidin-5-yl]prop-2-enylidene]amino]thiourea

[1382] A mixture of (E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl] prop-2-enal (0.83 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.51 g) in Ethanol (6 mL) was heated at 85 C. for 3 h. The mixture was cooled to ambient temperature and the precipitated solid was filtered and washed with cold ethanol and n-pentane and dried to afford the desired product (0.850 g). LC/MS: R.sub.t: 2.37 min; MS: m/z=529.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 11.71 (s, 1H), 9.69 (s, 1H), 8.59 (s, 2H), 7.94 (s, 1H), 7.53-7.50 (m, 2H), 7.41-7.38 (m, 2H), 7.35-7.15 (m, 4H), 6.64 (s, 1H), 3.52 (s, 3H), 3.14-3.01 (m, 1H), 2.16 (s, 3H), 1.17 (d, J=6.9 Hz, 6H).

Example 7: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[(E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enylidene]hydrazono]thiazolidin-4-one (C-7)

[1383] 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy)anilino] pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (0.67 g) was taken up in Ethanol (15 mL). Ethyl-2-bromo acetate (0.97 g) and Sodium acetate (0.31 g) added and the mixture stirred a r.t. for 24 h. The reaction mixture was diluted with water and extracted with Ethyl acetate, the organic extracts dried over anhydrous Sodium sulfate and evaporated under reduced pressure. The residue obtained was purified by silica gel flash column chromatography using a gradient of Ethyl acetate and Heptane to afford the desired product. (0.59 g). LC/MS: R.sub.t: 2.49 min; MS: m/z=569.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.51 (s, 2H), 7.99 (s, 1H), 7.62-7.47 (m, 3H), 7.44 (dd, J=8.1, 1.5 Hz, 1H), 7.42-7.36 (m, 2H), 7.32 (ddd, J=8.6, 6.8, 2.0 Hz, 1H), 7.23 (dd, J=7.9, 1.3 Hz, 1H), 6.74 (s, 1H), 4.29-3.95 (m, 2H), 3.51 (s, 3H), 2.84-2.66 (m, 1H), 2.10 (s, 3H), 1.13 (t, J=6.3 Hz, 6H).

Example 8: Synthesis of 1-[(E)-[(E)-3-[5-(dimethylamino)-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]-2-methyl-prop-2-enylidene]amino]-3-(2-isopropylphenyl)thiourea (C-8)

Step 1: Synthesis of 5-bromo-3-nitro-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine

[1384] To a solution of 5-bromo-2-chloro-3-nitro pyridine (12 g, 0.050 mol) in n-butanol (100 mL) were added Triethyl amine (6.13 g, 0.060 mol) and 4-Trifluoromethoxy aniline (10.74 g, 0.060 mol). The mixture was heated at 125 C. for 2 h. The mixture was subsequently cooled to ambient temperature and the precipitated solids were filtered and dried under vacuum to obtain the desired product as a brown solid (12.1 g, 63.3% yield. LC/MS: Rt: 1.938 min; MS: m/z=378 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6); 8.69 (d, J=2.3 Hz, OH), 8.60 (d, J=2.3 Hz, OH), 7.71 (d, J=9.0 Hz, 1H), 7.37 (d, J=8.6 Hz, 1H).

Step 2: Synthesis of 5-bromo-N2-[4-(trifluoromethoxy)phenyl]pyridine-2,3-diamine

[1385] To a stirred solution of 5-bromo-3-nitro-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine (1.33 g) in Ethyl acetate (15 mL) was added Tin chloride dihydrate (3.1 g) and the mixture was heated at 80 C. for 2 h. The mixture was subsequently cooled to ambient temperature and Sodium bicarbonate solution was added and the resultant mixture was filtered through a Celite bed. The organic layer was separated, washed with saturated Sodium chloride solution and water and dried over anhydrous Sodium sulphate. The organic layer was then evaporated under reduced pressure to get the desired product as a light brown solid (0.63 g, 53% yield). LC/MS: Rt: 1.723 min; MS: m/z=348.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6); 8.08 (s, 1H), 7.68 (d, J=9.0 Hz, 2H), 7.52 (d, J=2.2 Hz, 1H), 7.24 (d, J=8.6 Hz, 2H), 7.07 (d, J=2.2 Hz, 1H), 5.45 (s, 2H).

Step 3: Synthesis of 5-bromo-N2,N3,N3-trimethyl-N2-[4-(trifluoromethoxy)phenyl]pyridine-2,3-diamine

[1386] To a solution of 5-bromo-N2-[4-(trifluoromethoxy)phenyl]pyridine-2,3-diamine (3.8 g) in N, N-Dimethyl formamide (30 mL) was added Sodium hydride, 60% suspension in mineral oil, (1 g) at 0 C. and stirred for 15 minutes. Methyl iodide (7 g) was added drop-wise. The mixture was stirred at ambient temperature for 12 h and subsequently a saturated solution of Ammonium chloride was added and the mixture extracted with Ethyl acetate. The Ethyl acetate extracts were dried over anhydrous Sodium sulfate and evaporated under reduced pressure and the resultant solids subjected to flash column chromatography on Silica gel using a gradient of Ethyl acetate/Heptane as eluent to afford the desired product as a brown solid (1.33 g, 31%). LC/MS: Rt: 2.441 min; MS: m/z=390.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6); 8.04 (d, J=2.2 Hz, 1H), 7.51 (d, J=2.2 Hz, 1H), 7.21 (d, J=8.1 Hz, 1H), 6.84 (d, J=9.1 Hz, 2H), 3.29 (s, 3H), 2.65 (s, 6H).

Step 4: Synthesis of (E)-3-[5-(dimethylamino)-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]-2-methyl-prop-2-enal

[1387] A mixture of 5-bromo-N2,N3,N3-trimethyl-N2-[4-(trifluoromethoxy)phenyl]pyridine-2,3-diamine (0.130 g) in 1,4 Dioxane (4 mL) and water (1 mL) was degassed with Nitrogen gas for 15 minutes. [1,1 -Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.012 g), Cesium carbonate (0.217 g,) and 2-[(E)-3,3-diethoxy-2-methyl-prop-1-enyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.171 g) were added and the mixture heated at 95 C. for 4 h. 1N Hydrochloric acid solution was subsequently added and the mixture was neutralized with solid Sodium bicarbonate and extracted with Ethyl acetate. The Ethyl acetate extracts were separated and filtered through Celite, dried over anhydrous Sodium sulphate and evaporated under reduced pressure. The residue obtained was subjected to Silica gel flash column chromatography using a gradient of Ethyl acetate/Heptane as eluent to afford the desired product as a pale yellow solid (0.090 g, 71%, yield). LC/MS: Rt: 2.302 min; MS: m/z=380.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6); 9.57 (s, 1H), 8.22 (d, J=2.0 Hz, 1H), 7.69-7.39 (m, 2H), 7.29-7.10 (m, 2H), 6.91 (d, J=9.1 Hz, 2H), 3.37 (s, 3H), 2.57 (s, 6H).

Step 5: Synthesis of 1-[(E)-[(E)-3-[5-(dimethylamino)-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]-2-methyl-prop-2-enyl idene]amino]-3-(2-isopropylphenyl)thiourea

[1388] To a solution of (E)-3-[5-(dimethylamino)-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]-2-methyl-prop-2-enal (0.420 g) in Ethanol (5 mL) was added 1-amino-3-(2-isopropyl phenyl)thiourea (0.231 g) and the mixture heated at 85 C. for 2 h. The reaction mixture was cooled to ambient temperature and the resulting precipitate was filtered, washed with cold Ethanol and n-Pentane to get the desired product as yellow solid (0.5 g, 78.3%, yield). LC/MS: Rt: 2.49 min; MS: m/z=571.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6); 11.75 (s, 1H), 9.71 (s, 1H), 8.11 (d, J=1.9 Hz, 1H), 7.98 (d, J=1.2 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.38-7.20 (m, 4H), 7.20-7.13 (m, 2H), 6.83 (d, J=9.3 Hz, 3H), 3.31 (s, 3H), 3.19-2.95 (m, 1H), 2.60 (s, 6H), 2.29-2.17 (m, 3H), 1.19 (d, J=6.9 Hz, 6H).

Example 9: Synthesis of (2Z)-2-[(E)-[(E)-3-[5-(dimethylamino)-6-[N-methyl-4-(trifluoromethoxy) anilino]-3-pyridyl]-2-methyl-prop-2-enylidene]hydrazono]-3-(2-isopropylphenyl)thiazolidin-4-one (C-9

[1389] To a stirred solution of 1-[(E)-[(E)-3-[5-(dimethylamino)-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]-2-methyl-prop-2-enylidene]amino]-3-(2-isopropylphenyl)thiourea (0.370 g) in Ethanol (5 mL) was added Sodium acetate (0.160 g) and Methyl-2-bromo acetate (0.496 g). The mixture was stirred for 12 h, Water was added and the mixture was subsequently extracted with Ethyl acetate, the organic extracts dried over anhydrous Sodium sulfate and evaporated under reduced pressure. The residue obtained was subjected to flash column chromatography using a gradient of Ethyl acetate/Heptane as eluent to obtain the desired product as a yellow solid (0.170 g, 42%). LC/MS: Rt: 2.550 min; MS: m/z=611.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6); 8.04 (d, J=2.1 Hz, 2H), 7.59-7.41 (m, 2H), 7.39-7.27 (m, 2H), 7.24 (dd, J=7.9, 1.3 Hz, 1H), 7.16 (d, J=8.7 Hz, 2H), 6.91 (s, 1H), 6.83 (d, J=9.1 Hz, 2H), 4.56-3.86 (m, 2H), 3.33 (s, 4H), 2.76 (dd, J=13.4, 6.5 Hz, 1H), 2.58 (s, 6H), 2.17 (d, J=1.2 Hz, 3H), 1.14 (t, J=6.9 Hz, 6H).

Example 10: Synthesis of (2E)-2-[(Z)-[3-(2-isopropylphenyl)-4-oxo-thiazolidin-2-ylidene]hydrazono]-N-methyl-N-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]acetamide (C-10)

Step 1: 5-bromo-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1390] To a stirred solution of 5-bromo-2-chloro-pyrimidine (0.1 g) in N,N-Dimethylformamide (3 mL) were added Potassium carbonate (0.142 g), Copper(I)iodide (0.01 g), 8-hydroxy quinoline (0.08 g) and 4-(trifluoromethoxy) aniline (0.11 g). The mixture was heated at 95 C. for 24 h, cooled to ambient temperature, diluted with Water and extracted with Ethyl acetate. The Ethyl acetate extracts were dried over anhydrous Sodium sulfate and concentrated under reduced pressure. The residue obtained was purified by silica gel flash column chromatography using a gradient of Ethyl acetate and Heptane as eluent to afford the desired compound as yellow solid (0.05 g, 27% yield). LC/MS: Rt: 1.80 min; MS: m/z=336 (M+1)+.

Step 2: 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1391] To a solution of 5-bromo-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (2.5 g) in N, N-Dimethylformamide (10 mL) at 0 C. was added Sodium Hydride (60% dispersion in mineral oil) (0.449g) portion wise. Methyl iodide (0.7 mL) was added and the mixture stirred at ambient temperature for 12 h. The mixture was poured into ice and the precipitated solids were filtered and dried to get the desired product (2.5 g, 96%). LC/MS: Rt: 2.25 min; MS: m/z=348.15 (M+1)+.

Step 3: N2,N5-dimethyl-N2-[4-(trifluoromethoxy)phenyl]pyrimidine-2,5-diamine

[1392] To a solution of 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (0.5 g) in N-Methyl Pyrrolidone (6 mL) in a sealed tube was added Cu (I) oxide (0.021g) and a 40% solution of Methylamine in water (6 mL). The mixture was heated at 80 C. for 12 h and water (20 mL) followed by Ethyl acetate (20 mL) were added. The mixture was filtered through a Celite bed, the organic layer separated, dried over anhydrous Sodium sulphate and evaporated to dryness under reduced pressure. The reside was purified by Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to afford the desired product (0.3 g, 70%) as a beige solid. LC/MS: Rt: 1.88 min; MS: m/z=288.3 (M-1); .sup.1H NMR (300 MHz, DMSO-d6) 7.91 (s, 2H), 7.45-7.33 (m, 2H), 7.33-7.24 (m, 2H), 5.41 (q, J=5.3 Hz, 1H), 3.42 (s, 3H), 2.67 (d, J=5.3 Hz, 3H).

Step 4: (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]acetic acid

[1393] To a solution of 1-amino-3-(2-isopropylphenyl)thiourea (1 g) in Methanol (20 mL) was added Glyoxylic acid monohydrate (0.44 g) and the mixture stirred at ambient temperature for 2 h. The mixture was evaporated under reduced pressure and the residue was washed with n-Pentane to get the desired product (1.2g, 95%) as a off white solid. LC/MS: Rt: 1.439 min; MS: m/z=264 (M-1); .sup.1H NMR (300 MHz, DMSO-d6) 12.34 (s, 1H), 10.32 (s, 1H), 7.44-7.37 (m, 2H), 7.33 (td, J=7.8, 7.4, 1.7 Hz, 1H), 7.24 (td, J=7.4, 1.8 Hz, 1H), 7.17 (dd, J=7.8, 1.6 Hz, 1H), 3.05 (p, J=6.9 Hz, 1H), 1.17 (d, J=6.9 Hz, 6H).

Step 5: (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]-N-methyl-N-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]acetamide

[1394] To a solution of N2,N5-dimethyl-N2-[4-(trifluoromethoxy)phenyl]pyrimidine-2,5-diamine (0.2 g, 0.67 mmol) and (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]acetic acid (0.196 g) in Dichloromethane (20 mL) was added Diisopropylethylamine (0.25 mL) and a 50% solution of Propylphosphonic anhydride in Ethyl acetate (0.835g). The mixture was stirred for 12 h and subsequently poured into Water (30 mL) and extracted with Ethyl acetate (220 mL). The organic extracts were dried over anhydrous Sodium suphate and evaporated under reduced pressure and the residue obtained was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to get the desired product and a yellow solid (0.32 g, 87% yield). LC/MS: Rt: 1.178 min; MS: m/z=546 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.77 (s, 1H), 9.43 (s, 1H), 8.48 (s, 2H), 7.60 (s, 1H), 7.48-7.27 (m, 8H), 7.27-7.07 (m, 4H), 3.45 (s, 5H), 3.24 (s, 5H), 2.58-2.50 (m, 120H), 1.13 (t, J=6.1 Hz, 11H).

Step 6: (2E)-2-[(Z)-[3-(2-isopropylphenyl)-4-oxo-thiazolidin-2-ylidene]hydrazono]-N-methyl-N-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]acetamide

[1395] A mixture of (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]-N-methyl-N-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]acetamide (0.15 g), Sodium acetate (0.26 g, 2.75 mmol) and Methyl bromoacetate (0.11 mL) in Ethanol (20 mL) was stirred at 40 C. for 12 h. The mixture was cooled to ambient temperature and Water (50 mL) was added and the mixture extracted with Ethyl acetate (250 mL). The combined organic extracts were dried over anhydrous Sodium sulphate and evaporated invacuo to a residue which was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to afford the desired product (0.1 g, 62%). LC/MS: Rt: 2.10 min; MS: m/z=586.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.34 (s, 2H), 7.66-7.09 (m, 9H), 4.40-4.00 (m, 2H), 3.47 (s, 4H), 2.62 (d, J=6.9 Hz, 1H), 1.03 (dd, J=22.9, 6.8 Hz, 6H).

Example 11: Synthesis of (2E)-2-[(Z)-[3-(2-isopropylphenyl)-4-oxo-thiazolidin-2-ylidene]hydrazono]-N-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]acetamide (C-11)

[1396] A mixture of (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]-N-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]acetamide (0.1 g, 0.188 mmol), Sodium acetate (0.154 g) and Methyl bromoacetate (0.076 mL) was taken up in Ethanol (20 mL) and stirred at 40 C. for 12 h. The mixture was cooled to ambient temperature and Water (50 mL) was added and extracted with Ethyl acetate (250 mL). The combined Ethyl acetate extracts were dried over anhydrous Sodium sulphate and evaporated invacuo and the resultant residue was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to afford the desired product (0.05 g, 46%). LC/MS: Rt: 2.149 min; MS: m/z=572.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 10.36 (s, 1H), 8.66 (s, 2H), 7.67 (s, 1H), 7.49 (d, J=9.0 Hz, 3H), 7.37 (d, J=8.4 Hz, 3H), 7.26 (dd, J=7.9, 1.4 Hz, 1H), 4.51-3.98 (m, 2H), 3.48 (s, 3H), 1.13 (dd, J=6.9, 4.4 Hz, 6H).

Example 12: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]prop-2-enylidene]hydrazono]thiazolidin-4-one (C-12)

Step 1: Synthesis of 5-bromo-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine

[1397] A mixture of 2-amino-5-bromo pyridine (4.4 g), Copper (II) acetate (10.85 g) and Potassium phosphate (6.128 g) in Dimethylsulfoxide (70 mL) was heated at 100 C. for 24 h. The mixture was subsequently cooled to ambient temperature, Ethyl acetate was added and the mixture filtered through Celite. The organic layer was separated, washed with saturated Sodium chloride solution, Water and subsequently dried over anhydrous Sodium sulphate. The organic layer was then evaporated invacuo and the residue subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and heptane to afford the desired product as a brown solid. (2.3 g, 27%). LC/MS: Rt: 2.139 min; MS: m/z=335.30 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.29 (d, J=2.5 Hz, 1H), 7.79 (d, J=9.1 Hz, 2H), 7.48-7.14 (m, 2H), 6.88 (dd, J=8.9, 1.4 Hz, 2H).

Step 2: Synthesis of 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine

[1398] To a 0 C. solution of 5-bromo-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine (2.3 g) in N, N-Dimethyl formamide (15 mL) was added Sodium hydride (0.2 g). Methyl iodide (1.47 g) was added drop-wise and the mixture stirred at ambient temperature for 12 h. Saturated Ammonium chloride solution was added and the mixture extracted with Ethyl acetate and the extract was dried over anhydrous Sodium sulphate and evaporated invacuo and the residue obtained was subjected to silica gel flash column chromatography eluting with a gradient of Ethyl acetate and heptane to get the desired product as a off-white solid (1.75 g, 73%). LC/MS: Rt: 2.209 min; MS: m/z=349.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.23 (d, J=2.5 Hz, 1H), 7.65 (dt, J=9.1, 2.0 Hz, 1H), 7.43 (s, 4H), 6.58 (d, J=9.1 Hz, 1H), 3.37 (s, 3H).

Step 3: Synthesis of (E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]prop-2-enal

[1399] A mixture of 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine (1.75 g, 5.05 mmol), 1,4 Dioxane (20 mL) and Water (5 mL) was degassed with nitrogen gas. [1,1-Bis(diphenyl phosphino)ferrocene]palladium(II) dichloride (0.370 g), Cesium carbonate (3.3 g) and 2-[(E)-3,3-diethoxy-2-methyl-prop-1-enyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.59 g) were added and the degassing continued for a further 10 min. The mixture was heated at 90 C. for 3 h and cooled to ambient temperature. 1N Hydrochloric acid solution was added and the mixture was neutralized with solid Sodium bicarbonate. The mixture was extracted with Ethyl acetate and the extracts were dried over anhydrous Sodium sulphate and evaporated invacuo and the resultant residue was subjected to Silica gel flash chromatography eluting with a Ethyl acetate/Heptane gradient to get the desired compound as a white solid solid (1.2 g, 71%). LC/MS: Rt: 2.170 min; MS: m/z=337.2 (M+.sup.1); .sup.1H NMR (300 MHz, DMSO-d6) 9.49 (s, 1H), 8.47 (d, J=2.4 Hz, 1H), 7.84 (dd, J=9.1, 2.5 Hz, 1H), 7.61-7.41 (m, 4H), 7.37 (s, 1H), 6.66 (d, J=9.0 Hz, 1H), 3.47 (s, 3H), 1.97 (d, J=1.1 Hz, 3H).

Step 4: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy) anilino]-3-pyridyl]prop-2-enylidene]amino]thiourea

[1400] To a stirred solution of (E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]prop-2-enal (0.350 g) in Ethanol (4 mL) was added 1-amino-3-(2-isopropylphenyl)thiourea (0.217 g) and the mixture heated at 85 C. for 3 h. Water was added and the mixture was extracted with ethyl acetate, the extracts dried over anhydrous Sodium sulphate, evaporated and the residue was flash chromatographed over Silica gel to get the desired product as a yellow solid (0.22 g, 40%). LC/MS: Rt: 2.423 min; MS: m/z=528.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.68 (s, 1H), 9.66 (s, 1H), 8.37-8.25 (m, 1H), 7.94 (s, 1H), 7.77-7.62 (m, 1H), 7.52-7.38 (m, 5H), 7.44-7.26 (m, 2H), 7.27 (s, 1H), 7.26-7.10 (m, 1H), 6.72-6.61 (m, 2H), 4.03 (q, J=7.1 Hz, 1H), 3.44 (s, 4H), 3.09 (p, J=6.8 Hz, 1H), 2.16 (s, 3H), 1.99 (s, 1H), 1.18 (d, J=6.9 Hz, 6H).

Step 5: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]prop-2-enylidene]hydrazono]thiazolidin-4-one

[1401] To a stirred solution of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy) anilino]-3-pyridyl]prop-2-enylidene]amino]thiourea (0.175 g) in Ethanol (4 mL) were added sodium acetate (0.082 g), and Methyl-2-bromo acetate (0.25 g) and the mixture stirred for 16 h. The mixture was subsequently diluted with Water and extracted with Ethyl acetate, the extracts were dried over anhydrous Sodium sulfate and concentrated under reduced pressure to get a residue which was flash chromatographed to get the desired product as yellow solid (0.08 g, 40%, yield). LC/MS: Rt: 2.465 min; MS: m/z=568.4 (M+1).sup.+; 1H NMR (300 MHz, DMSO-d6) 8.26 (d, J=2.3 Hz, 1H), 7.99 (s, 1H), 7.64 (dd, J=9.0, 2.4 Hz, 1H), 7.55-7.38 (m, 6H), 7.32 (ddd, J=8.6, 6.8, 2.0 Hz, 1H), 7.23 (dd, J=7.9, 1.4 Hz, 1H), 6.80 (s, 1H), 6.64 (d, J=8.9 Hz, 1H), 4.20 (d, J=17.4 Hz, 1H), 4.09 (d, J=17.4 Hz, 1H), 3.43 (s, 3H), 2.76 (p, J=6.6 Hz, 1H), 2.14-2.07 (m, 3H), 1.13 (t, J=6.4 Hz, 6H).

Example 13: Synthesis of (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]-N-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]acetamide (C-13)

Step 1: N2-methyl-N2-[4-(trifluoromethoxy)phenyl]pyrimidine-2,5-diamine

[1402] To a solution of 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (1g) in N-Methylpyrrolidone (10 mL) in a sealed tube was added Copper (I) oxide (0.041 g) and a 30% solution of Methyl amine in water (10 mL). The mixture was heated at 80 C. for 12 h. Water (20 mL) and Ethyl acetate (20 mL) were added and the mixture filtered through Celite. The organic layer was separated, washed with a saturated solution of Sodium chloride, dried over anhydrous Sodium sulphate and evaporated invacuo. The residue obtained was subjected to Silica gel flash column chromatography using a Ethyl acetate/Heptane gradient to obtain the desired product (0.7 g, 85%) as a beige solid. LC/MS: Rt: 1.715 min; MS: m/z=285.2 (M-1).

Step-2: (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]-N-[2-[N-methyl-4-(trifluoromethoxy) anilino]pyrimidin-5-yl]acetamide

[1403] To a solution of N2-methyl-N2-[4-(trifluoromethoxy)phenyl]pyrimidine-2,5-diamine (0.1 g) and (2E)-2-[(2-isopropylphenyl)carbamothioylhydrazono]acetic acid (0.10 g) in Dichloromethane (10 mL) was added Diisopropylethylamine (0.125 mL) and a 50% solution of Propylphosphonic anhydride solution (0.45 g). The mixture was stirred at ambient temperature for 12 h. Water (30 mL) was added and the mixture extracted with Ethyl acetate (220 mL). The organic extracts were dried over anhydrous Sodium sulphate and evaporated under reduced pressure and the resultant residue was subjected to Silica gel flash column chromatography to get the desired product (0.32g, 87%) as a yellow solid. LC/MS: Rt: 2.134 min; MS: m/z=532 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 12.29 (s, 1H), 10.36 (s, 1H), 10.13 (s, 1H), 8.55 (s, 2H), 7.56-7.45 (m, 3H), 7.45-7.34 (m, 4H), 7.26 (dtd, J=22.5, 8.5, 7.8, 1.7 Hz, 2H), 3.48 (s, 3H), 3.07 (p, J=6.8 Hz, 1H), 1.19 (d, J=6.9 Hz, 6H).

Example 14: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-3-[2-[N-methyl-4-(trifluoromethoxy) anilino]pyrimidin-5-yl]prop-2-enylidene]amino]imidazolidine-2,4-dione (C-14)

[1404] A mixture of (E)-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.135 g), 3-amino-1-(2-isopropylphenyl)imidazolidine-2,4-dione (0.097g) and Concentrated Hydrochloric acid (2 drops) in Ethanol was heated at 80 C. for 3 h. The mixture was cooled to ambient temperature and the precipitated solids were filtered and washed with cold ethanol and dried under vacuum to afford the desired product as a beige colored solid. (0.064 g, 28%). LC/MS: Rt: 2.180 min; MS: m/z=539 (M+1).sup.+.

Example 15: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]prop-2-enylidene]amino]thiourea (C-15)

[1405] A mixture of (E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]prop-2-enal (0.32 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.217 g) in Ethanol (5 mL) was heated at 85 C. for 3 h. The mixture was cooled to ambient temperature, diluted with water, extracted with Ethyl acetate and the extracts were dried over anhydrous Sodium sulphate and evaporated invacuo. The residue obtained was subjected to flash column chromatography using a gradient of Ethyl acetate and heptane as eluent to afford the desired product as a yellow solid (0.26 g, 46%). LC/MS: Rt: 2.39 min; MS: m/z=528.7 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.70 (s, 1H), 9.68 (s, 1H), 8.31 (d, J=2.3 Hz, 2H), 7.94 (s, 1H), 7.81 (dd, J=9.2, 2.4 Hz, 2H), 7.59-7.14 (m, 12H), 6.72 (d, J=8.5 Hz, 3H), 3.09 (p, J=6.8 Hz, 1H), 2.16 (s, 3H), 1.18 (d, J=6.8 Hz, 7H).

Example 16: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (C-16)

Step 1: 5-bromo-2-chloro-4-methyl-pyrimidine

[1406] A mixture of 5-Bromo 2,4-dichloropyrimidine (0.4 g) and Iron(III)acetylacetonate (0.062 g) in Tetrahydrofuran (10 mL) was cooled to 0 C. Methyl magnesium bromide (3 M solution in Diethyl ether) (0.76 mL) was added dropwise and the mixture stirred for 2 h. Saturated Ammonium Chloride solution was added and the mixture extracted with Ethyl acetate (220 mL). The organic extracts were dried over anhydrous Sodium sulphate and evaporated under reduced pressure to get a residue which was purified by Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and n-heptane to afford the desired product (0.220 g, 60%) as a white solid. 1H NMR (300 MHz, CDCl3) 8.52 (s, 1H), 2.57 (s, 3H).

Step 2: 5-bromo-4-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1407] A mixture of 5-bromo-2-chloro-4-methyl-pyrimidine (2 g), 4-Trifluoromethoxyaniline (2.04 g), concentrated Hydrochloric acid solution (0.2 mL) in in 2-propanol (20 mL) was heated at 100 C. for 4 h. The mixture was subsequently cooled to room temperature, poured into ice and basified with a saturated solution Sodium bicarbonate solution and precipitated solids were filtered. The filtered solid was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and n-Heptane to afford the desired product (1.75 g, 52%) as an off-white solid. LC/MS: Rt: 2.20 min; MS: m/z=346.1 (M-1); 1H NMR (300 MHz, CDCl3) 8.32 (s, 1H), 7.88 (s, 1H), 7.63-7.51 (m, 2H), 7.19-7.07 (m, 2H), 2.50 (s, 3H).

Step 3: 5-bromo-N,4-dimethyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1408] To the solution of 5-bromo-4-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (1.5 g) in N, N-Dimethylformamide (30 mL) at 0 C. was added Sodium hydride (60% dispersion in mineral oil) (0.207g) portion wise. Methyl iodide (0.35 mL) was added and the mixture stirred at 0 C. for 1 h. The reaction mixture was poured into ice and extracted with Ethyl acetate (220 mL). The combined organic layer was dried over anhydrous Sodium sulphate and evaporated under reduced pressure and the residue subjected to Silica gel flash column chromatography using a gradient of Ethyl acetate and n-heptane as eluent to get the desired product to get the desired product (1.4 g, 89% yield) as a beige solid. LC/MS: Rt: 2.388 min; MS: m/z=364.3 (M+1).sup.+; .sup.1H NMR (300 MHz, CDCl3) 8.20 (s, 1H), 7.27 (d, J=9.0 Hz, 2H), 7.17 (d, J=8.1 Hz, 2H), 3.47 (d, J=1.3 Hz, 3H), 2.40 (d, J=7.0 Hz, 3H).

Step 4: (E)-2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal

[1409] A mixture of 5-bromo-N,4-dimethyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (0.25 g), Cesium carbonate (0.45 g) and 2-[(Z)-3,3-diethoxy-1-methyl-prop-1-enyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.28 g) in 1,4-Dioxane (12 mL) and water (3 mL) was degassed for 10 min, followed by the addition of [1,1-Bis(diphenylphosphino)ferrocene] palladium(II) dichloride (0.05 g) and the mixture heated at 90 C. for 2 h. The mixture was subsequently cooled to ambient temperature and water (10 mL) was added and the mixture extracted with Ethyl acetate (20 mL). The Ethyl acetate extracts were dried over anhydrous Sodium sulphate and evaporated under reduced pressure and the residue obtained was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate/n-Heptane to afford the desired product (0.2 4g, 99%) as an off white solid. Rt: 2.173 min; MS: m/z=352.4 (M+1).sup.+; .sup.1H NMR (300 MHz, CDCl.sub.3) 9.52 (s, 1H), 8.33 (s, 1H), 7.29 (d, 2H), 7.17 (d, 2H), 3.52 (s, 3H), 2.39 (s, 3H).

Step 5: 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy) anilino] pyrimidin-5-yl]prop-2-enylidene]amino]thiourea

[1410] A mixture of (E)-2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.2 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.12 g) in Ethanol (10 mL) was heated at 80 C. for 2 h. The mixture was cooled to ambient temperature and the precipitated solids were collected by filtration, washed with cold Ethanol and dried under vacuum to afford the title compound 0.2 g (65%) as a yellow solid. LC/MS: Rt: 2.411 min; MS: m/z=541.7 (M).sup.; .sup.1H NMR (DMSO-d6): 11.71 (s, 1H), 9.67 (s, 1H), 8.32 (s, 1H), 7.98 (s, 1H), 7.56-7.46 (m, 2H), 7.43-7.30 (m, 3H), 7.30-7.14 (m, 3H), 6.74 (s, 1H), 3.51 (s, 3H), 3.08 (p, J=6.9 Hz, 2H), 2.34 (s, 3H), 2.06-1.98 (m, 3H), 1.18 (d, J=6.9 Hz, 6H).

Example 17: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[(E)-2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enylidene]hydrazono]thiazolidin-4-one (C-17)

[1411] A mixture of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy) anilino] pyrimidin-5-yl]prop-2-enylidene]amino]thiourea (0.1g), Sodium acetate (0.091 g), Methyl bromoacetate (0.075 mL) was taken up in Ethanol (20 mL) and the mixture stirred at 40 C. for 12 h. The mixture was diluted with water (50 mL) at ambient temperature and extracted with Ethyl acetate (250 mL). The combined organic layers were dried over anhydrous Sodium sulphate and evaporated invacuo and the residue obtained was subjected to Silica gel Flash column chromatography using a gradient of Ethylacetate/Heptane to afford the title compound (0.08 g, 75%) as a yellow solid. LC/MS: Rt: 2.498 min; MS: m/z=583.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.33 (s, 1H), 8.10 (s, 1H), 7.55-7.46 (m, 4H), 7.41 (dd, J=19.5, 8.0 Hz, 3H), 7.36-7.19 (m, 2H), 6.91 (s, 1H), 4.28-4.03 (m, 2H), 3.50 (s, 3H), 2.28 (s, 3H), 1.98 (d, J=1.2 Hz, 3H), 1.19-1.08 (m, 6H).

Example 18: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxyethylideneamino]thiourea (C-18)

Step 1: 2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-ol

[1412] A mixture of 5-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (1.8 g) and Triisopropylborate (1.82 mL) was taken up in Tetrahydrofuran (30 mL) and cooled to 78 C. A solution of n-BuLi (1.6 M in n-hexane, 4.827 mL) was added and the mixture allowed to warm upto 20 C. for 20 min. Acetic acid (1.5 mL) followed by Methanol (8 mL) was added and the mixture evaporated under reduced pressure. To the resultant residue, Methanol (2 mL), Water (12 mL) and a solution of Hydrogen Peroxide (20% in water, 1.5 mL, 10.34 mmol) was added and the mixture stirred at ambient temperature for 12 h. The mixture was subsequently diluted with water (50 mL) and extracted with Ethyl acetate (250 mL). The combined organic layer was dried over anhydrous Sodium sulphate and evaporated invacuo and the resultant solid was purified by Silica gel flash column chromatography with a gradient of Ethyl acetate/Heptane as eluent to afford the desired product (1 g, 68% yield) as a white solid. LC/MS: Rt: 1.788 min; MS: m/z=286.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 9.47 (s, 1H), 8.05 (s, 2H), 7.48-7.37 (m, 2H), 7.32 (d, J=8.6 Hz, 2H), 3.43 (s, 3H).

Step 2: 5-(2,2-diethoxyethoxy)-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1413] To a solution of 2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-ol (0.25 g) in N,N-Dimethylacetamide (2 mL), was added KOH (0.098 g) followed by Bromoacetaldehyde diethylacetal (0.2 mL). The mixture was heated to 100 C. for 2 h and subsequently cooled to room temperature. The mixture was diluted with water (20 mL) and extracted with Ethyl acetate EtOAc (220 mL). The combined organic extracts were washed with a saturated solution of Sodium chloride, dried over anhydrous Sodium sulphate and evaporated under reduced pressure to afford the title compound as a pale yellow oil (0.25g, 71%). LC/MS: Rt: 2.23 min; MS: m/z=402.9 (M+1).sup.+; .sup.1H NMR (300 MHz, CDCl3) 8.10 (s, 1H), 7.32-7.21 (m, 1H), 7.16 (d, J=8.5 Hz, 3H), 4.72 (t, J=5.1 Hz, 1H), 3.91 (d, J=5.1 Hz, 1H), 3.77-3.63 (m, 2H), 3.63-3.48 (m, 3H), 3.46 (s, 2H), 3.30 (d, J=5.5 Hz, 1H), 1.17 (td, J=7.1, 1.8 Hz, 6H).

Step 3: 2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxyacetaldehyde

[1414] To a solution of 5-(2,2-diethoxyethoxy)-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (0.2 g) in Acetone (4 mL) was added a solution of Hydrochloric acid (1 N, 1 ml) and the mixture heated at 70 C. for 5 h. The reaction was diluted with water (4 mL) and extracted with Ethyl acetate (210 mL). The combined organic layer was dried over anhydrous Sodium sulphate and evaporated under reduced pressure and the resultant residue was subjected to flash column chromatography using a gradient of Ethyl acetate/Heptane to afford the title compound as a colorless oil (0.14 g, 86%). LC/MS: Rt: 1.612 min; MS: m/z=327 (M+1).sup.+; .sup.1H NMR (300 MHz, CDCl3) 9.85 (s, 1H), 8.17 (s, 2H), 7.36 (d, J=9.0 Hz, 2H), 7.25 (d, J=8.4 Hz, 2H), 4.61 (s, 2H), 3.54 (s, 3H).

Step 4: 1-(2-isopropylphenyl)-3-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxyethylideneamino]thiourea

[1415] A mixture of 2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxyacetaldehyde (0.15 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.10 g) in Ethanol (5 mL) was heated at 80 C. for 1 h. Subsequently, the mixture was evaporated under reduced pressure to get the title compound as a white solid (0.16 g, 67%). LC/MS: Rt: 2.187 min; MS: m/z=519.65 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.73 (s, 1H), 9.82 (s, 1H), 8.34 (s, 2H), 7.57 (t, J=5.2 Hz, 1H), 7.51-7.39 (m, 2H), 7.36 (s, 2H), 7.30 (dd, J=11.3, 5.3 Hz, 2H), 7.27-7.11 (m, 3H), 4.77 (d, J=5.2 Hz, 2H), 3.45 (s, 3H), 3.02 (p, J=6.9 Hz, 2H), 1.12 (d, J=6.9 Hz, 6H).

Example 19: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxyethylidenehydrazono]thiazolidin-4-one (C-19)

[1416] A mixture of 1-(2-isopropylphenyl)-3-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxyethylideneamino]thiourea (0.1 g), Sodium acetate (0.095 g), Methyl bromoacetate (0.078 mL) in Ethanol (20 mL) was stirred at 40 C. for 12 h. The mixture was subsequently diluted with Water (50 mL) and extracted with Ethyl acetate (220 mL). The combined extracts were dried over anhydrous Sodium sulphate and evaporated invacuo and the residue obtained was purified by Silica gel flash column chromatography using a gradient of Ethyl acetate and heptane as eluent to afford the title compound (0.06 g, 56%) as a white solid. LC/MS: Rt: 2.25 min; MS: m/z=559.3 (M+1)+. .sup.1H NMR (300 MHz, DMSO-d6) 8.256 (s, 2H), 7.672 (m, 1H), 7.431-7.462 (m, 4H), 7.327-7.356 (m, 3H), 7.195-7.251 (m, 1H), 4.79 (d, J=4.5 Hz, 2H), 4.112 (m, 2H), 3.443 (s, 3H), 2.702-2.790 (m, 1H), 1.096-1.127 (m, 6H).

Example 20: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxypropylideneamino]thiourea (C-20)

Step 1: 5-(2,2-dimethoxy-1-methyl-ethoxy)-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine

[1417] A mixture of 2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-ol (0.4 g), Potassium hydroxide (0.158 g) and 2-bromo-1,1-dimethoxy-propane (0.4 mL) in N,N-Dimethylacetamide (4 mL) was heated at 100 C. for 24 h. The mixture was cooled to ambient temperature and water (50 mL) was added and the mixture extracted with Ethyl acetate (230 mL). The combined organic layer was washed with a saturated solution of Sodium chloride and dried over anhydrous Sodium sulphate and evaporated under reduced pressure and the crude obtained was purified by Silica gel flash column chromatography using a gradient of Ethyl acetate/Hepatane to obtain the title compound (0.1 g, 18%). LC/MS: Rt: 2.144 min; MS: m/z=388.4 (M+1).sup.+; .sup.1H NMR (300 MHz, Chloroform-d) 8.14 (s, 2H), 7.36 (s, 3H), 7.25 (s, 2H), 7.16 (s, 1H), 3.51 (s, 2H), 3.43 (d, J=5.7 Hz, 4H), 3.39 (t, J=2.8 Hz, 5H).

Step 2: 2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxypropanal

[1418] A solution of 5-(2,2-dimethoxy-1-methyl-ethoxy)-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (0.1 g) and a solution of Hydrochloric acid (1 N, 1 mL) was taken up in in Acetone (4 mL) and heated at 70 C. for 12 h. The reaction was diluted with water (20 mL) and extracted with Ethyl acetate (220 mL). The combined organic layer was dried over anhydrous Sodium sulphate and evaporated under reduced pressure to get the title compound. (0.07 g, 79.4%) LC/MS: Rt: 1.685 min; MS: m/z=342.2 (M+1).sup.+; .sup.1H NMR (300 MHz, CDCl3) 9.67 (s, 1H), 8.08 (s, 2H), 7.26 (dd, J=7.5, 5.1 Hz, 2H), 7.16 (d, J=7.9 Hz, 2H), 4.417-4.444 (m, 1H), 3.43 (s, 3H), 1.59 (d, J=7.5 Hz, 3H).

Step 3: 1-(2-isopropylphenyl)-3-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxypropylideneamino]thiourea

[1419] The mixture of 2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxypropanal (0.15 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.09 g) in Ethanol (2 mL) was heated at 80 C. for 1 h. The mixture was evaporated under reduced pressure and the residue subjected to Silica gel column chromatography to get the title compound (0.16 g, 68%). LC/MS: Rt: 2.275 min; MS: m/z=533.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.63 (s, 1H), 9.81 (s, 1H), 8.34 (s, 2H), 7.51-7.40 (m, 2H), 7.38 (d, J=6.3 Hz, 1H), 7.35-7.22 (m, 4H), 7.22-7.11 (m, 2H), 4.97 (p, J=6.4 Hz, 2H), 3.44 (s, 3H), 3.01 (p, J=6.9 Hz, 2H), 1.49 (d, J=6.3 Hz, 3H), 1.11 (dd, J=6.9, 2.4 Hz, 7H).

Example 21: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy) anilino] pyrimidin-5-yl]oxypropylidenehydrazono]thiazolidin-4-one (C-21)

[1420] A mixture of 1-(2-isopropylphenyl)-3-[(E)-2-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]oxypropylideneamino]thiourea (0.1 g), Sodium acetate (0.092 g) and Methyl bromoacetate (0.076 mL) in Ethanol (20 mL) was heated at 40 C. for 12 h. The mixture was cooled to ambient temperature diluted with Water (50 mL) and extracted with Ethyl acetate (215 mL). The combined Ethyl acetate extracts were dried over anhydrous Sodium sulphate and the were evaporated invacuo and the resultant residue was subjected to flash column chromatography with Silica gel, eluting with a Ethyl acetate/Heptane gradient wo get the title compound as a yellow solid 0.108 g (70%). LC/MS: Rt: 2.309 min; MS: m/z=573.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.23 (d, J=2.0 Hz, 2H), 7.57 (t, J=5.4 Hz, 1H), 7.52-7.39 (m, 4H), 7.39-7.28 (m, 3H), 7.20 (d, J=7.9 Hz, 1H), 5.03 (q, J=6.1 Hz, 1H), 4.40-3.93 (m, 2H), 3.44 (s, 3H), 1.42 (dd, J=6.4, 1.7 Hz, 3H), 1.16-1.02 (m, 6H).

Example 22: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]propylidene]amino]thiourea (C-22)

Step 1

[1421] To the solution of (E)-2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.2 g) in Ethyl acetate (5 mL) was added 10% Palladium on charcoal (0.02 g) and the mixture stirred under a Hydrogen atmosphere via a gas bladder for 12 h. The mixture was filtered through a Celite bed and evaporated under reduced pressure, the residue obtained subjected to flash column chromatography to afford the desired product (0.11 g). LC/MS Rt: 2.166 min; MS: m/z=354.4 (M+1)+.

Step 2: 1-(2-isopropylphenyl)-3-[(E)-[2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy) anilino] pyrimidin-5-yl]propylidene]amino]thiourea

[1422] A mixture of 2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]propanal (0.1 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.06 g) in Ethanol (2 mL) was heated at 80 C. for 2 h. The mixture was evaporated invacuo and the residue obtained was subjected to flash column chromatography to afford the desired product (0.13 g, 84%) as a yellow solid. LC/MS Rt: 2.374 min; MS: m/z=545.6 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.42 (s, 1H), 9.49 (s, 1H), 8.13 (s, 1H), 7.48-7.42 (m, 3H), 7.38-7.14 (m, 6H), 3.46 (s, 3H), 2.91 (ddd, J=47.9, 13.5, 7.0 Hz, 2H), 2.33 (s, 3H).

Example 23: Synthesis of N-methyl-5-[(E,3E)-2-methyl-3-[(3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl]oxyimino-prop-1-enyl]-N-[4-(trifluoromethoxy)phenyl]pyrimidin-2-amine (C-23)

[1423] (E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.17 g), O[(3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl]hydroxylamine (0.123 g) and Concentrated hydrochloric acid solution (1.5 mL) was taken in Ethanol (15 mL) and the mixture heated to 80 C. for 48 h. The mixture was diluted with Ethyl acetate (20 mL) and the organic layer separated, dried over anhydrous Sodium sulphate, evaporated invacuo and the residue subjected to flash column chromatography on Silica gel eluting with a gradient of Ethyl acetate and n-heptane to afford the title compound (0.055 g, 18%). LC/MS: Rt: 2.278 min; MS: m/z=541 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.51 (s, 1H), 8.09 (s, OH), 7.68-7.21 (m, 2H), 6.71 (s, 1H), 5.37 (dd, J=27.0, 2.0 Hz, 1H), 3.52 (s, 2H), 3.44-3.36 (m, 6H), 2.03 (d, J=1.2 Hz, 2H), 1.83 (d, J=1.4 Hz, 1H), 1.16 (d, J=5.9 Hz, 2H).

Example 24: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]propylidene]hydrazono]thiazolidin-4-one (C-24)

[1424] A mixture of 1-(2-isopropylphenyl)-3-[(E)-[2-methyl-3-[4-methyl-2-[N-methyl-4-(trifluoromethoxy) anilino] pyrimidin-5-yl]propylidene]amino]thiourea (0.07 g), Sodium acetate (0.063 g), Methyl bromoacetate (0.04 mL) in Ethanol (10 mL) was stirred at 40 C. for 12 h. The reaction mixture was cooled to ambient temperature, diluted with Water (50 mL), Sodium hydroxide solution (1 N, 2 mL) and extracted with Ethyl acetate (250 mL). The combined organic extracts were dried over anhydrous Sodium sulphate, evaporated invacuo and the residue subjected to flash column chromatography on Silic gel, eluting with a gradient of Ethyl acetate and Heptane to obtain the title compound as a white solid 0.05 g (67%). LC/MS: Rt: 2.409 min; MS: m/z=585.4 (M+1)+. 1H NMR (300 MHz, DMSO-d6) 8.05 (d, J=8.2 Hz, 1H), 7.54 (dd, J=7.6, 5.3 Hz, 1H), 7.46 (dt, J=7.7, 3.0 Hz, 4H), 7.40-7.23 (m, 3H), 7.27-7.11 (m, 1H), 4.28-3.86 (m, 2H), 3.45 (s, 3H), 2.77-2.61 (m, 1H), 2.27 (d, J=2.5 Hz, 3H), 1.16-0.92 (m, 10H).

Example 25: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enylidene]amino]imidazolidine-2,4-dione (C-25)

[1425] (E)-2-methyl-3-[2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-yl]prop-2-enal (0.227 g) and 3-amino-1-(2-isopropylphenyl)imidazolidine-2,4-dione (0.157 g) were taken up in Ethanol (10 mL. 2 drops of conc. Hydrochloric acid solution was added and the mixture heated to 80 C. for 3 h. The mixture was evaporated invacuo and the residue taken up in Ethyl acetate and washed with a saturated solution of Sodium bicarbonate solution. The organic layer was separated, dried and evaporated to obtain a residue which was subjected to preparative HPLC to get the title compound (0.058 g, 13%), LC/MS: Rt: 2.26 min; MS: m/z=553.8 (M)+.

Example 26: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]prop-2-enylidene]amino]thiourea (C-26)

Step 1: Synthesis of 6-chloro-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine

[1426] A mixture of 3,6 Dichloro pyridazine (0.2 g) and 4-(trifluoromethoxy) aniline (0.180 g) was taken up in in Acetic acid (3 mL) and heated at 90 C. for 4 h. The mixture was cooled to ambient temperature, neutralized with Sodium bicarbonate solution and extracted with Ethyl acetate. The organic layer was dried over anhydrous Sodium sulfate and concentrated under reduced pressure and the residue obtained, was purified by column chromatography using Ethyl acetate and heptane as eluent to offer the desired compound as off-white solid (0.150 g, 51%). LC/MS: Rt: 1.841 min; MS: m/z=290.25 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 9.69 (s, 1H), 7.89-7.74 (m, 2H), 7.62 (d, J=9.3 Hz, 1H), 7.35 (d, J=8.6 Hz, 2H), 7.22 (d, J=9.3 Hz, 1H).

Step 2: Synthesis of 6-chloro-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine

[1427] To a stirred solution of 6-chloro-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine (2.6 g) in dry DMF (35 mL) was added Sodium hydride (0.323 g) at 0 C. and stirred for 10 min. Methyl iodide (2.55 g) was added and the mixture stirred at ambient temperature for 12 h. Saturated ammonium chloride solution was added and the mixture extracted with Ethyl acetate. The Ethyl acetate extracts were dried over anhydrous Sodium sulfate and concentrated under reduced pressure and the residue obtained was subjected to flash column chromatography to get the title compound as a light brown solid. (1.9 g, 70%). LC/MS: Rt: 1.996 min; MS: m/z=304.1 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 7.55-7.41 (m, 5H), 6.98 (d, J=9.5 Hz, 1H), 3.47 (s, 3H).

Step 3: Synthesis of (E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]prop-2-enal

[1428] A mixture of 6-bromo-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine (1.8 g), [1,1-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.434 g), Cesium carbonate (3.9 g), and 2-[(E)-3,3-diethoxy-2-methyl-prop-1-enyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3 g) was taken up in a mixture of Dioxan (4 mL) and water (16 mL) and degassed with Nitrogen gas for 10 min and subsequently heated at 95 C. for 2 h. The mixture was diluted with 1N HCl solution, neutralized with Sodium bicarbonate solution and filtered through Celite. The filtrate was extracted with Ethyl acetate and the extracts dried over anhydrous Sodium sulfate and evaporated invacuo to obtain a residue which was subjected to Silica gel flash column chromatography to obtain the desired compound as an off-white solid (1 g, 57%). LC/MS: Rt: 2.00 min; MS: m/z=338.5 (M+1).sup.+; 1H NMR (300 MHz, DMSO-d6) 9.63 (s, 1H), 7.63 (d, J=9.5 Hz, 1H), 7.65-7.23 (m, 5H), 6.97 (d, J=9.5 Hz, 1H), 3.57 (s, 3H), 2.13 (d, J=1.2 Hz, 3H).

Step 4: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy) anilino]pyridazin-3-yl]prop-2-enylidene]amino]thiourea

[1429] A mixture of (E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]prop-2-enal (0.25 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.150 g) in Methanol (4 mL) was heated at 80 C. for 3 h. The mixture was evaporated, Water and Ethyl acetate added and the ethyl acetate layer separated, dried evaporated invacuo to obtain a residue which was subjected to flash column chromatography to obtain the title compound as a brown solid (0.190 g, 47%). LC/MS: Rt: 2.256 min; MS: m/z=529.3 (M+1,)+; 1H NMR (300 MHz, DMSO-d6) 11.77 (s, 1H), 9.74 (s, 1H), 7.99 (s, 1H), 7.79-7.44 (m, 5H), 7.37-7.12 (m, 2H), 6.94 (d, J=9.5 Hz, 1H), 6.79 (s, 1H), 3.54 (s, 3H), 3.19-3.02 (m, 1H), 2.44-2.23 (m, 3H), 1.19 (d, J=6.9 Hz, 6H).

Example 27: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]prop-2-enylidene]hydrazono]thiazolidin-4-one (C-27)

[1430] A mixture of 1-(2-isopropylphenyl)-3-[(E)-[(E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy) anilino]pyridazin-3-yl]prop-2-enylidene]amino]thiourea (0.158 g), Sodium acetate (0.049 g), and Methylbromo acetate (0.137 g) in Methanol (4 mL) was stirred for 12 h. The mixture was evaporated invacuo and the residue was subjected to Silica gel column chromatography eluting with a gradient of Dichloromethane and methanol to obtain the title compound as a brown solid (0.09 g, 50%). LC/MS: Rt: 2.261 min; MS: m/z=569.90 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.08 (s, 1H), 7.55-7.38 (m, 7H), 7.38-7.20 (m, 2H), 6.97-6.87 (m, 2H), 4.29-4.04 (m, 2H), 3.54 (s, 3H), 2.90-2.67 (m, 1H), 2.30 (d, J=1.2 Hz, 3H), 1.14 (t, J=6.7 Hz, 6H).

Example 28: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxypropylidenehydrazono]thiazolidin-4-one (C-28)

Step 1: Synthesis of N-methyl-6-(1-methylallyloxy)-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine

[1431] To a stirred solution of 6-chloro-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine (1 g) and allyl alcohol (0.475 g) in N, N-Dimethylformamide (15 mL) at 0 C. was added Sodium hydride (0.160 g) and the mixture stirred at ambient temperature for 12 h. Saturated Ammonium chloride solution was subsequently added and the mixture extracted with Ethy acetate. The Ethyl acetate extracts were separated, dried over anhydrous Sodium sulphate and evaporated invacuo, and the residue obtained was subjected to flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to get the desired product as a brown solid (0.56 g, 50%). LC/MS: Rt: 2.193 min; MS: m/z=340.5 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 7.38 (s, 4H), 7.06 (d, J=9.6 Hz, 1H), 6.96 (d, J=9.6 Hz, 1H), 6.00 (ddd, J=17.3, 10.6, 5.5 Hz, 1H), 5.69 (dtd, J=7.8, 6.4, 5.1 Hz, 1H), 5.29 (dt, J=17.3, 1.5 Hz, 1H), 5.15 (dt, J=10.6, 1.4 Hz, 1H), 3.42 (s, 3H), 1.40 (d, J=6.5 Hz, 3H).

Step 2: 2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxypropanal

[1432] A mixture of N-methyl-6-(1-methylallyloxy)-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine (0.580 g), Osmium tetroxide (0.022 g) in Water (2 mL) and Sodium periodate (1 g) was taken up in a mixture of 1,4 Dioxane (16 mL) and water (2 mL) and the mixture stirred at ambient temperature for 4 h. 2% Sodium sulfite solution was added and the mixture extracted with Ethyl acetate. The Ethyl acetate extracts were dried over anhydrous Sodium sulfate and concentrated under reduced pressure to get a solid residue which was purified by Silica gel flash column chromatography using Ethyl acetate/heptane mixture as eluent to afford the title compound. (0.32 g, 55%). LC/MS: Rt: 1.420 min; MS: m/z=342.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 9.65 (d, J=1.3 Hz, 1H), 7.39 (d, J=6.7 Hz, 5H), 7.11 (d, J=1.7 Hz, 1H), 3.42 (s, 3H), 3.28 (d, J=2.8 Hz, 1H), 1.44 (d, J=7.1 Hz, 3H).

Step 3:1-(2-isopropylphenyl)-3-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxypropylideneamino]thiourea

[1433] A mixture of (E)-2-methyl-3-[6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]prop-2-enal (0.220 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.150 g) was taken up in Tetrahydrofuran (5 mL) and heated at 50 C. for 4 h. The mixture was diluted with Water and extracted with Ethyl acetate, the Ethyl acetate extracts dried over anhydrous Sodium sulphate and evaporated invacuo and the residue obtained was subjected to Silica gel flash column chromatography to obtain the title compound as a viscous liquid. (0.130 g, 38%). LC/MS: Rt: 2.233 min; MS: m/z=533.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.62 (s, 1H), 9.62 (s, 1H), 7.66 (d, J=4.4 Hz, 1H), 7.47-6.86 (m, 11H), 5.76 (dd, J=6.6, 4.5 Hz, 1H), 3.43 (s, 3H), 3.07-2.93 (m, 1H), 1.56 (d, J=6.5 Hz, 3H), 1.15 (d, J=6.9 Hz, 7H).

Step 4: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxypropylidenehydrazono]thiazolidin-4-one

[1434] A mixture of 1-(2-isopropylphenyl)-3-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy)anilino]Pyridazine-3-yl]oxypropylideneamino]thiourea (0.160 g), Sodium acetate (0.050 g), and Methyl bromo acetate (0.138 g) in Methanol (4 mL) was stirred at ambient temperature for 12 h. The reaction mixture was subsequently diluted with Water and extracted with Ethyl acetate, the Ethyl acetate extracts dried over anhydrous Sodium sulphte and evaporated invacuo and the residue subjected to Silica gel flash column chromatography to afford the title compound (0.06 g, 37%). LC/MS: Rt: 2.264 min; MS: m/z=573.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 7.55 (dd, J=12.8, 4.1 Hz, 1H), 7.47-7.13 (m, 9H), 7.08 (dd, J=7.8, 1.4 Hz, 1H), 7.02-6.77 (m, 2H), 5.62 (ddd, J=6.4, 4.3, 2.0 Hz, 1H), 4.36-3.82 (m, 2H), 3.29 (s, 3H), 2.72-2.55 (m, 1H), 1.36 (d, J=6.6 Hz, 3H), 0.99 (dd, J=6.9, 1.9 Hz, 8H).

Example 29: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy) anilino]pyridazin-3-yl]oxyethylidenehydrazono]thiazolidin-4-one (C-29)

Step 1: Synthesis of 6-allyloxy-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine

[1435] To a stirred solution of Allyl alcohol (1 g) in N, N-Dimethylformamide (15 mL) at 0 C. was added Sodium hydride (0.320 g) and the mixture stirred for 20 min. A solution of 6-chloro-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine (2.7 g) in N,N-Dimethylformamide (5 mL) was added drop-wise and the mixture stirred for a further 3 h. Saturated Ammonium chloride solution was subsequently added, the mixture extracted with Ethyl acetate, the Ethyl acetate extracts dried over anhydrous Sodium sulphate and evaporated invacuo. The residue obtained was subjected to Silica gel flash column chromatography to obtain the title compound as a white solid (2.5 g, 86%). LC/MS: Rt: 2.086 min; MS: m/z=326.25 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 7.38 (d, J=1.5 Hz, 4H), 7.13-6.96 (m, 2H), 6.10 (ddt, J=17.3, 10.7, 5.5 Hz, 1H), 5.40 (dq, J=17.3, 1.7 Hz, 1H), 5.26 (dq, J=10.5, 1.5 Hz, 1H), 4.87 (dt, J=5.5, 1.5 Hz, 2H), 3.43 (s, 3H).

Step 2: 2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxyacetaldehyde

[1436] A mixture of 6-allyloxy-N-methyl-N-[4-(trifluoromethoxy)phenyl]pyridazin-3-amine (0.22 g), Sodium periodate (0.434 g) and Osmium tetraoxide (catalytic) was taken up in 1,4-Dioxane (6 mL) and Water (1 mL) and the mixture stirred at ambient temperature for 12 h. The mixture was subsequently quenched with Sodium sulfite solution and extracted with Ethyl acetate. The Ethyl acetate extracts were dried over anhydrous Sodium sulphate and evaporated invacuo and the residue obtained was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and n-Heptane to afford the desired compound as an off-white solid. (0.150 g, 68%). LC/MS: Rt: 1.382 min; MS: m/z=328.15 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 7.45-7.31 (m, 4H), 7.03 (q, J=9.6 Hz, 2H), 6.40 (d, J=7.8 Hz, 1H), 4.82 (dt, J=7.8, 5.1 Hz, 1H), 4.21 (h, J=5.7 Hz, 2H), 3.43 (s, 3H), 3.34 (s, 4H), 1.39-1.25 (m, 1H), 1.24 (s, 3H).

Step 3: Synthesis of 1-(2-isopropylphenyl)-3-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy) anilino]pyridazin-3-yl]oxyethylideneamino]thiourea

[1437] A mixture of 2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxyacetaldehyde (0.530 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.338 g) in Tetrahydrofuran (5 mL) was heated at 50 C. for 3 h. The mixture was diluted with Water and extracted with Ethyl acetate, the Ethyl acetate extracts dried over anhydrous Sodium sulphate and evaporated under reduced pressure. The residue obtained was subjected to Silica gel flash column chromatography using a gradient of Ethyl acetate and Heptane to obtain the title compound as a white solid (0.2 g, 24%). LC/MS: Rt: 2.175 min; MS: m/z=519.3 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 11.71 (s, 1H), 9.73 (s, 1H), 7.72 (t, J=5.0 Hz, 1H), 7.39 (s, 4H), 7.37-7.21 (m, 3H), 7.18 (dd, J=3.7, 2.3 Hz, 2H), 7.14-7.03 (m, 2H), 5.04 (d, J=4.9 Hz, 2H), 3.44 (s, 3H), 3.04 (p, J=6.9 Hz, 1H), 1.15 (d, J=6.8 Hz, 6H).

Step 4: Synthesis of (2Z)-3-(2-isopropylphenyl)-2-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxyethylidenehydrazono]thiazolidin-4-one

[1438] A mixture of 1-(2-isopropylphenyl)-3-[(E)-2-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyridazin-3-yl]oxyethylideneamino]thiourea (0.090 g), Sodium acetate (0.029 g) and Methyl bromoacetate (0.080 g) in Tetrahydrofuran (2 mL) was stirred at ambient temperature for 12 h. The mixture was subsequently diluted with Water, extracted with Ethyl acetate, the Ethyl acetate extracts dried over anhydrous Sodium sulphate and evaporated invacuo. The resultant solid was subjected to Silica gel flash column chromatography using Ethyl acetate/Heptane gradient to obtain the title compound as a white solid (0.070 g, 57%). LC/MS Rt: 2.189 min; MS: m/z=559.55 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6); 1H NMR (300 MHz, DMSO-d6) 7.47 (td, J=7.9, 1.7 Hz, 3H), 7.43-7.24 (m, 7H), 7.21 (d, J=7.5 Hz, 1H), 7.05 (q, J=9.3 Hz, 3H), 5.05 (d, J=4.4 Hz, 2H), 4.31-4.02 (m, 3H), 3.41 (d, J=5.3 Hz, 12H), 2.75 (h, J=6.8 Hz, 2H), 1.27-1.07 (m, 9H).

Example 30: Synthesis of 1-[(E)-2-[[2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]oxy]ethylideneamino]-3-(2-isopropylphenyl)thiourea (C-30)

Step 1: 5-Brom-4,6-dimethyl-pyridin-2-amine

[1439] A mixture of 4,6-dimethylpyridin-2-amine (3 g) and Bromine (1.39 mL) taken up in Acetonitrile (30 mL) was stirred at ambient temperature for 1 h. The mixture was diluted with Water (100 mL) and the precipitate was collected by filteration and dried to afford the title product as a off white solid (3.8 g, 77%). LC/MS: Rt: 1.2 min; MS: m/z=203 (M+1).sup.+; .sup.1H NMR (300 MHz, Chloroform-d) 7.28 (s, 1H), 6.37 (s, 2H), 2.43-2.12 (m, 6H).

Step 2: 5-bromo-4,6-dimethyl-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine

[1440] A mixture of 5-Bromo-4,6-dimethyl-pyridin-2-amine (2 g), Cesium carbonate (6.46 g), 4-Trifluoromethoxy iodobenzene (4.29 g), Palladium (II) acetate (0.22 g, 0.99 mmol) and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (0.57 g) was taken up in Toleune (40 mL) and degassed with nitrogen gas and heated at 120 C. for 5 h. The reaction was diluted with Water (50 mL) and extracted with Ethyl acetate (230 mL) and the combined organic extracts were dried over anhydrous Sodium sulphate and evaporated under reduced pressure. The residue was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to obtain the title compound as an off white solid (2.7 g, 75%). LC/MS: Rt: 2.44 min; MS: m/z=363.2 (M+2)+; .sup.1H NMR (300 MHz, CDCl3) 7.36 (d, J=9.0 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 2.66 (s, 3H), 2.39 (s, 3H).

Step 3: 5-bromo-N,4,6-trimethyl-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine

[1441] To the solution of 5-bromo-4,6-dimethyl-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine (2.5 g) in N, N-Dimethylformamide (30 mL) at 0 C. was added Sodium hydride (60% dispersion in mineral oil, 0.415 g) portion wise. Methyl iodide (0.7 mL) was added and the mixture stirred at 0 C. for 1 h. The mixture was poured into ice water and extracted with Ethyl acetate (230 mL) and the extracts dried over anhydrous Sodium sulphate. The extracts were evaporated invacuo and the residue subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to afford the title compound as an off white solid (2.5 g, 96%). LC/MS: Rt: 2.628 min; MS: m/z=375.2 (M+2)+; .sup.1H NMR (300 MHz, CDCl3) 7.18 (d, J=5.3 Hz, 5H), 6.20 (s, 1H), 3.41 (s, 3H), 2.55 (d, J=2.6 Hz, 3H), 2.16 (s, 3H).

Step 4: 2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]pyridin-3-ol

[1442] A mixture of 5-bromo-N,4,6-trimethyl-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine (0.5 g), Tris(dibenzylideneacetone)dipalladium(0) (0.12 g), 2-Di-tert-butylphosphino-2,4,6-triisopropylbiphenyl (0.057 g) and Potassium hydroxide (0.15 g) was taken up in 1,4-Dioxan (4 mL) and Water (4 mL) and heated at 90 C. for 2 h. The mixture was cooled to ambient temperature and diluted with Water (50 mL) and extracted with Ethyl acetate (230 mL).The combined organic layer was dried over anhydrous Sodium sulphate evaporated invacuo and the residue was subjected to Silica gel flash column chromatography to get the title compound as an off white solid (0.4 g, 96%). LC/MS: Rt: 1.614 min; MS: m/z=313.25 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 8.25 (s, 1H), 7.22 (s, 1H), 7.10 (d, J=9.1 Hz, 1H), 6.59 (s, 1H), 3.28 (s, 3H), 2.29 (s, 3H), 2.11 (s, 3H).

Step 5: 5-(2, 2-diethoxyethoxy)-N,4,6-trimethyl-N-[4-(trifluoromethoxy)phenyl]pyridin-2-amine

[1443] A mixture of 2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]pyridin-3-ol (0.3 g), Potassium hydroxide (0.27 g) and Bromoacetaldehyde diethylacetal (0.217 mL) was taken up in N,N-Dimethylacetamide (4 mL) and heated at 100 C. for 1 h. The mixture was subsequently cooled to ambient temperature and Water (50 mL) was added and extracted with Ethyl acetate (220 mL). The combined Ethyl acetate extracts were washed with brine, dried over anhydrous Sodium sulphate and evaporated invacuo to get the title compound as a pale yellow oil (0.27 g, 66%). LC/MS: Rt: 2.45 min; MS: m/z=429.3 (M)+; .sup.1H NMR (DMSO-d6): 1H NMR (300 MHz, DMSO-d6) 7.32 (d, J=2.0 Hz, 4H), 6.42 (s, 1H), 4.78 (t, J=5.1 Hz, 1H), 3.79-3.46 (m, 5H), 2.32 (s, 4H), 2.13 (s, 3H), 1.15 (t, J=7.0 Hz, 6H).

Step 6: 2-[[2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]oxy]acetaldehyde

[1444] To the solution of 5-(2,2-diethoxyethoxy)-N,4,6-trimethyl-N-[4-(trifluoromethoxy)phenyl] pyridin-2-amine (0.25 g) in Acetone (5 mL) was added a solution of Hydrochloric acid (1 mL). The mixture was heated at 70 C. for 2 h. The mixture was subsequently basified with sat. Sodium bicarbonate solution and extracted with Ethyl acetate (220 mL). The combined Ethyl acetate extracts were dried over anhydrous Sodium sulphate and evaporated invacuo to get the title compound as a pale yellow oil (0.2 g, 96%). LC/MS: Rt: 1.56 min; MS: m/z=355 (M)+; 1H NMR (DMSO-d6): .sup.1H NMR (300 MHz, DMSO-d6) 9.70 (s, OH), 7.32 (d, J=5.0 Hz, 8H), 6.43 (d, J=5.5 Hz, 1H), 5.18 (s, OH), 4.55 (s, 1H), 2.30 (d, J=6.2 Hz, 3H), 2.17-1.91 (m, 3H).

Step 7: 1-[(E)-2-[[2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]oxy]ethylideneamino]-3-(2-isopropylphenyl)thiourea

[1445] A mixture of 2-[[2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]oxy]acetaldehyde (0.15 g) and 1-amino-3-(2-isopropylphenyl)thiourea (0.09 g) in Ethanol (4 mL) was heated at 80 C. for 2 h. The mixture was evaporated under reduced pressure and the residue obtained was subjected to Silica gel flash column chromatography eluting with a gradient of Ethyl acetate and Heptane to obtain the title compound as a white solid. (0.16 g, 69%). LC/MS: Rt: 2.37 min; MS: m/z=546.3 (M)+; .sup.1H NMR (DMSO-d6) 11.69 (s, 1H), 9.75 (s, 1H), 7.70 (t, J=5.4 Hz, 1H), 7.39-7.07 (m, 7H), 6.44 (s, 1H), 4.48 (d, J=5.4 Hz, 2H), 2.34 (s, 3H), 2.15 (s, 3H), 1.14 (d, J=6.8 Hz, 6H).

Example 31: Synthesis of (2Z)-2-[(E)-2-[[2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]oxy]ethylidenehydrazono]-3-(2-isopropylphenyl)thiazolidin-4-one (C-31)

[1446] A mixture of 1-[(E)-2-[[2,4-dimethyl-6-[N-methyl-4-(trifluoromethoxy)anilino]-3-pyridyl]oxy]ethylideneamino]-3-(2-isopropylphenyl)thiourea (0.1 g), Sodium acetate (0.09 g) and Methyl bromoacetate (0.056 mL) in Ethanol (4 mL) was stirred at 40 C. for 12 h. The mixture was cooled to ambient temperature and diluted with Water (50 mL) and a solution of Sodium hydroxide (1 N, 1 mL) and extracted with Ethyl acetate (250 mL). The combined Ethyl acetate extracts were dried over anhydrous Sodium sulphate, evaporated invacuo and the residue subjected to Silica gel flash column chromatography to get the title compound as a yellow solid (0.042 g, 39%). LC/MS: Rt: 2.41 min; MS: m/z=586.4 (M+1).sup.+; .sup.1H NMR (300 MHz, DMSO-d6) 7.75 (s, 1H), 7.48 (s, 1H), 7.32 (s, 7H), 7.24 (s, 1H), 6.42 (s, 2H), 4.67-4.37 (m, 4H), 4.16 (d, J=20.4 Hz, 3H), 2.28 (s, 8H), 2.10 (s, 6H), 1.12 (dd, J=6.9, 5.0 Hz, 12H).

##STR00076##

TABLE-US-00004 TABLE C No. Ar Q A G R R.sup.1 M/z Rt [min C-1 [00077] NH N CH H [00078] 515 1.95 C-2 [00079] NH N CH H [00080] 501 1.89 C-3 [00081] NH N CH H [00082] 555 1.99 C-4 [00083] NH N CH H [00084] 541 1.95 C-5 [00085] NCH.sub.3 N CH H [00086] 555 1.97 C-6 [00087] NCH.sub.3 N CH H [00088] 529.3 2.37 C-7 [00089] NCH.sub.3 N CH H [00090] 569.4 2.49 C-8 [00091] NCH.sub.3 CN(CH.sub.3).sub.2 CH H [00092] 571.4 2.498 C-9 [00093] NCH.sub.3 CN(CH.sub.3).sub.2 CH H [00094] 611.9 2.576 C-10 [00095] NCH.sub.3 N CH H [00096] 586.3 2.102 C-11 [00097] NCH.sub.3 N CH H [00098] 572.3 2.149 C-12 [00099] NCH.sub.3 CH CH H [00100] 568.4 2.465 C-13 [00101] NCH.sub.3 N CH H [00102] 532.3 2.134 C-14 [00103] NCH.sub.3 N CH H [00104] 539 2.18 C-15 [00105] NCH.sub.3 CH CH H [00106] 528.75 2.396 C-16 [00107] NCH.sub.3 N CH CH.sub.3 [00108] 543.7 2.411 C-17 [00109] NCH.sub.3 N CH CH.sub.3 [00110] 583.4 2.498 C-18 [00111] NCH.sub.3 N CH H [00112] 519.65 2.187 C-19 [00113] NCH.sub.3 N CH H [00114] 559.3 2.25 C-20 [00115] NCH.sub.3 N CH H [00116] 533.3 2.275 C-21 [00117] NCH.sub.3 N CH H [00118] 573.3 2.309 C-22 [00119] NCH.sub.3 N CH CH.sub.3 [00120] 545.65 2.374 C-23 [00121] NCH.sub.3 N CH H [00122] 541 2.3 C-24 [00123] NCH.sub.3 N CH CH.sub.3 [00124] 585.4 2.409 C-25 [00125] NCH.sub.3 N CH H [00126] 553.8 2.26 C-26 [00127] NCH.sub.3 CH N H [00128] 529.3 2.256 C-27 [00129] NCH.sub.3 CH N H [00130] 569.9 2.261 C-28 [00131] NCH.sub.3 CH N H [00132] 573.4 2.264 C-29 [00133] NCH.sub.3 CH N H [00134] 559.55 2.189 C-30 [00135] NCH.sub.3 CH CCH.sub.3 CH.sub.3 [00136] 546.3 2.37 C-31 [00137] NCH.sub.3 CH CCH.sub.3 CH.sub.3 [00138] 586.4 2.419

BIOLOGICAL EXAMPLES

Example B1: Action on Yellow Fever Mosquito (Aedes aegypti)

[1447] For evaluating control of yellow fever mosquito (Aedes aegypti) the test unit consisted of 96-well-microtiter plates containing 200 l of tap water per well and 5-15 freshly hatched A. aegypti larvae.

[1448] The active compounds were formulated using a solution containing 75% (v/v) water and 25% (v/v) DMSO. Different concentrations of formulated compounds or mixtures were sprayed onto the insect diet at 2.5 l, using a custom built micro atomizer, at two replications.

[1449] After application, microtiter plates were incubated at 281 C., 805% RH for 2 days. Larval mortality was then visually assessed.

[1450] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-9, C-12, C-16, C-17, C-23, C-27, and C-31 at 800 ppm showed at least 75% mortality in comparison with untreated controls.

Example B2: Action on Orchid thrips (Dichromothrips corbetti)

[1451] Dichromothrips corbetti adults used for bioassay were obtained from a colony maintained continuously under laboratory conditions. For testing purposes, the test compound is diluted in a 1:1 mixture of acetone:water (vol:vol), plus Kinetic HV at a rate of 0.01% v/v.

[1452] Thrips potency of each compound was evaluated by using a floral-immersion technique. All petals of individual, intact orchid flowers were dipped into treatment solution and allowed to dry in Petri dishes. Treated petals were placed into individual re-sealable plastic along with about 20 adult thrips. All test arenas were held under continuous light and a temperature of about 28 C. for duration of the assay. After 3 days, the numbers of live thrips were counted on each petal. The percent mortality was recorded 72 hours after treatment.

[1453] In this test, compounds C-1, C-3, C-5, C-6, C-7, C-9, C-12, C-14, C-15, C-16, C-17, C-23, C-26, C-27, and at 500 ppm showed at least 75% mortality in comparison with untreated controls.

Example B3: Action on Boll Weevil (Anthonomus grandis)

[1454] For evaluating control of boll weevil (Anthonomus grandis) the test unit consisted of 96-well-microtiter plates containing an insect diet and 5-10 A. grandis eggs.

[1455] The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 5 l, using a custom built micro atomizer, at two replications.

[1456] After application, microtiter plates were incubated at about 251 C. and about 755% relative humidity for 5 days. Egg and larval mortality was then visually assessed.

[1457] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-12, C-14, C-15, C-16, C-17, C-22, C-23, C-26, C-27, and C-31 at 800 ppm showed at least 75% mortality in comparison with untreated controls.

Example B4: Action on Silverleaf Whitefly (Bemisia argentifoli) (Adults)

[1458] The active compounds were formulated by a Tecan liquid handler in 100% cyclohexanone as a 10,000 ppm solution supplied in tubes. The 10,000 ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solutions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 5 or 10 ml glass vials. A nonionic surfactant (Kinetic) was included in the solution at a volume of 0.01% (v/v). The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.

[1459] Cotton plants at the cotyledon stage (one plant per pot) were sprayed by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was placed into a plastic cup and about 10 to 12 whitefly adults (approximately 3-5 days old) were introduced. The insects were collected using an aspirator and a nontoxic Tygon tubing connected to a barrier pipette tip. The tip, containing the collected insects, was then gently inserted into the soil containing the treated plant, allowing insects to crawl out of the tip to reach the foliage for feeding. Cups were covered with a reusable screened lid. Test plants were maintained in a growth room at about 250C and about 20-40% relative humidity for 3 days, avoiding direct exposure to fluorescent light (24 hour photoperiod) to prevent trapping of heat inside the cup. Mortality was assessed 3 days after treatment, compared to untreated control plants.

[1460] In this test, compounds C-3, C-5, C-6, C-7, C-8, C-12, C-15, C-16, C-17, C-22, C-23, and C-26 at 300 ppm showed at least 75% mortality in comparison with untreated controls.

Example B5: Action on Tobacco Budworm (Heliothis virescens)

[1461] For evaluating control of tobacco budworm (Helliothis virescens) the test unit consisted of 96-well-microtiter plates containing an insect diet and 15-25 H. virescens eggs.

[1462] The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 10 l, using a custom built micro atomizer, at two replications.

[1463] After application, microtiter plates were incubated at about 281 C. and about 805% relative humidity for 5 days. Egg and larval mortality was then visually assessed.

[1464] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-22, C-23, C-24, C-26, C-27, C-30, and C-31 at 800 ppm showed at least 75% mortality in comparison with untreated controls.

Example B6: Action on Diamond Back Moth (Plutella xylostella)

[1465] The active compound is dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water:acetone. Surfactant (Kinetic HV) is added at a rate of 0.01% (vol/vol).The test solution is prepared at the day of use.

[1466] Leaves of cabbage were dipped in test solution and air-dried. Treated leaves were placed in petri dishes lined with moist filter paper and inoculated with ten 3.sup.rd instar larvae. Mortality was recorded 72 hours after treatment. Feeding damages were also recorded using a scale of 0-100%.

[1467] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-23, C-24, C-26, C-27, C-28, C-29, C-30, and C31 at 500 ppm showed at least 75% mortality in comparison with untreated controls.

Example B7: Action on Southern Armyworm (Spodoptera eridania), 2nd Instar Larvae

[1468] The active compounds were formulated by a Tecan liquid handler in 100% cyclohexanone as a 10,000 ppm solution supplied in tubes. The 10,000 ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solutions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 10 or 20 ml glass vials. A nonionic surfactant (Kinetic) was included in the solution at a volume of 0.01% (v/v). The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.

[1469] Lima bean plants (variety Sieva) were grown 2 plants to a pot and selected for treatment at the 1.sup.st true leaf stage. Test solutions were sprayed onto the foliage by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was placed into perforated plastic bags with a zip closure. About 10 to 11 armyworm larvae were placed into the bag and the bags zipped closed. Test plants were maintained in a growth room at about 250C and about 20-40% relative humidity for 4 days, avoiding direct exposure to fluorescent light (24 hour photoperiod) to prevent trapping of heat inside the bags. Mortality and reduced feeding were assessed 4 days after treatment, compared to untreated control plants.

[1470] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-15, C-16, C-17, C-18, C-19, C-23, C-26, C-27, and C-31 at 300 ppm showed at least 75% mortality in comparison with untreated controls.