合成路线1

6) Mass labeled saprisartan has been obtained as follows: The Wittig condensation of cyclopropylcarbonyl chloride (XXVII) with ethoxycarbonylmethylene triphenylphosphorane (XXVIII) by means of bis(trimethylsilyl)acetamide in dichloromethane gives 3-cyclopropyl-3-oxo-2-(triphenylphosphoranylidene)propionic acid ethyl ester (XXIX), which is oxidized with potassium peroxymonosulfate to the dicarbonyl compound (XXX). The cyclization of (XXX) with [all-13C]-propionaldehyde (XXXI) (obtained by hydrogenation of the corresponding acyl chloride (XXXII) with H2 over Pd/C in THF containing 2,6-lutidine) and [15N]-ammonium acetate by means of triethylamine in THF yields 4-cyclopropyl-2-[1,2-13C]-ethyl-[1,3-15N,2-13C]imidazole-5-carboxylic acid ethyl ester (XXXIII). The condensation of (XXXIII) with the benzofuran (XXI) (already described in Scheme 2) by means of K2CO3 in dimethylacetamide affords 1-[3-bromo-2-(2-nitrophenyl)benzofuran-5-ylmethyl]-4-cyclopropyl-2-[1,2-13C]-ethyl-[1,3-15N,2-13C]imidazole-5-carboxylic acid ethyl ester (XXXIV), which is finally treated sequentially with Fe and acetic acid to reduce the nitro group, with trifluoromethanesulfonic anhydride to acylate the amino group, with NaOH to hydrolyze the ester group, and with carbonyldiimidazole and ammonia to generate the amide group, thus obtaining mass labeled saprisartan. This sequence has already been described in Scheme 19090802a for the unlabeled compound.