Synthesis of 3H‐ and 14C‐labelled astemizole (R 43 512)

Astemizole, a new antihistamine drug, was specifically labelled with tritium and 14C at three distinct positions. Tritium was introduced either in the 4‐methoxyphenyl (II) or in the 4‐fluorophenylmethyl (IV) moiety by catalytic dehalogenation of the corresponding halogenated analogues with tritium gas, yielding 3H‐astemizole with specific activities of 28.7 and 5.0 Ci/mmol respectively. Starting from [14C]urea, [14C]astemizole was synthesized with the label being placed in the 2‐position of the benzimidazole moiety. The radioactive yield of the three‐step synthesis was 22.4 %, spread over three fractions with specific activities of 4.5 mCi/mmol, 1.7 mCi/mmol and 0.4 mCi/mmol. The labelled compounds were radiochemically pure according to thin‐layer (TLC) and high‐performance liquid chromatography (HPLC).