Synthesis of flutamide-d(7) and its main metabolite-d(6)

With the main objective of examining the pharmacokinetics of flutamide, flutamide-d(7) and its main metabolite-d(6) have been prepared. By carboxylation of Grignard-derivative (IV), deuterocarboxylic acid (V) was prepared from which acyl chloride (VI) was obtained by reaction with (COCl)(2). Subsequent reaction of (VI) with 4-nitro-3-trifluoromethylaniline afforded (I). Compound (X) was obtained starting from hydroxyacid (IX), through reaction with TMSCI, (COCl)(2) and subsequent condensation with 4-nitro-3-trifluoromethylaniline. Desilylation of(X) by tetrabutylammonium fluoride, gave (II).