Process for the preparation of 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine, commonly known as lamotrigine

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 27-35° C.;
• b) diazotisation of the resulting 2,3-dichloroaniline of the formula X:
• with sodium nitrite and a mineral acid at −5° to 5° C. followed by cyano-de-diazonation with a metal cyanide at 65-80° 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 55-130° 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 90-125° 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;
• and
• g) purification of the resulting crude lamotrigine of the formula I:
• by a known method such as recrystallisation from an aliphatic alkanol or chromatographic separation.