Synthesis of [14C]-labelled repinotan hydrochloride and its major metabolite M-6

For studies of pharmacokinetics and drug metabolism of the new 5‐HT1A agonist repinotan, the 14C‐labelled version was synthesized. Starting from [U‐14C]phenol, a 10‐step synthesis led to 457 mg (1.58 GBq) of [U‐14C]repinotan hydrochloride, labelled uniformly in the aromatic ring of the chromane moiety. For a study in man, a mono‐carbon‐14 labelled substance was required. Therefore a 7‐step synthesis was performed starting from [carbonyl‐14C]2‐hydroxy‐acetophenone. The yield was 106 mg (0.396 GBq) of [4‐chromane‐14C]repinotan hydrochloride. The carbon‐14 labelled major metabolite, hydroxylated in the 6‐position of the chromane moiety, was synthesised as reference compound. Copyright © 2002 John Wiley & Sons, Ltd.