Efficient process for the preparation of lamotrigine and related 3,5-diamino-6-substituted-1,2,4-triazines

A process for the manufacture of 3,5-diamino-6-substituted-1,2,4-triazines of formula (I):

• wherein R is optionally substituted C1-C4 alkyl or aryl group, the process comprising the steps of:
• (a) reacting a compound of formula (II):
• wherein R is optionally substituted C1-C4 alkyl or aryl group,
• with aminoguanidine in the presence of an organic sulphonic acid in an organic solvent under anhydrous conditions to form a cyanohydrin of formula III:
• wherein R is optionally substituted C1-C4 alkyl or aryl group,
• (b) dehydrating the cyanohydrin of formula III to form a compound of formula IV by using a dehydrating reagent,
• wherein R is optionally substituted C1-C4 alkyl or aryl group,
• and
• (c) cyclization of the compound of formula IV into a 3,5-diamino-6-substituted-1,2,4-triazine compound of formula I or into a hydrated form thereof.