Patent ID: 6639072
Filing Date: 2003-10-28
Classification: C07D

Abstract:
A process for the preparation of 6-(2,3-dichlorophenyl)-1,2,4-triazine -3,5-diamine of the formula I: commonly known as lamotrigine which comprises:a) reduction of 2,3-dichloronitrobenzene of the formula IX: in C1-C6 aliphatic alkanol with hydrogen gas at a pressure of 55-90 psi in the presence of a metal catalyst at 27-35Â° C.;b) diazotisation of the resulting 2,3-dichloroaniline of the formula X: with sodium nitrite and a mineral acid at âˆ’5Â° to 5Â° C. followed by cyano-de-diazonation with a metal cyanide at 65-80Â° C.;c) hydrolysis of the resulting 2,3-dichlorobenzonitrile of the formula XI: under acidic or alkaline conditions;d) chlorination of the resulting 2,3-dichlorobenzoic acid of the formula VI: with a chlorinating agent at 55-130Â° C.;e) cyano-de-halogenation of the resulting 2,3-dichloro-benzoyl chloride of the formula VII: with a metal cyanide in the presence of an alkali metal iodide by refluxing in an aprotic solvent under an inert atmosphere;f) condensation of the resulting 2,3-dichlorobenzoyl cyanide of the formula VIII: with aminoguanidine bicarbonate in an organic solvent in acidic conditions in the presence of a catalyst at 90-125Â° C. followed by insitu cyclisation of the resulting Schiff's base of the formula IV: by refluxing in an aliphatic alkanol in the presence of a base; andg) purification of the resulting crude lamotrigine of the formula I: by a known method such as recrystallisation from an aliphatic alkanol or chromatographic separation.