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

For studies of pharmacokinetics and drug metabolism of the new 5-HT<INF>1A</INF> 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.