Synthesis of stable isotopically labelled versions of lamotrigine and its methylated metabolite

Lamotrigine is a sodium channel antagonist used for the treatment of epilepsy. Synthesis of stable isotopically labelled (SIL) [M + 7] versions of Lamotrigme (1) and its N-methylated metabolite (2) are described. The routes to prepare these compounds used [M + 5] labelled [C-13, N-15(4)]-aminoguanidine (obtained from labelled thiourea). The overall yield for the metabolite (2) was 34% from [M + 3] labelled [C-13, N-15(2)]-thiourea. Copyright (C) 2002 John Wiley Sons, Ltd.