合成路线1

3) The condensation of 2-hydroxy-5-methylbenzaldehyde (XVII) with 2-nitrobenzyl alcohol (XVIII) by means of methanesulfonyl chloride and K2CO3 in dioxane/dimethylacetamide gives 5-methyl-2-(2-nitrobenzyloxy)benzaldehyde (XIX), which is cyclized by means of NaOMe in dimethylacetamide, yielding 5-methyl-2-(2-nitrophenyl)benzofuran (XX). The bromination of (XX) with Br2 and azobis(isobutyronitrile) (AIBN) in 1,1,1-trichloroethane affords 3-bromo-5-(bromomethyl)-2-(2-nitrophenyl)benzofuran (XXI), which is condensed with 4-cyclopropyl-2-ethylimidazole-5-carboxylic acid ethyl ester (IX) (already obtained in the preceding Scheme) by means of K2CO3 in dimethylacetamide to give 1-[3-bromo-2-(2-nitrophenyl)benzofuran-5-ylmethyl]-4-cyclopropyl-2-ethylimidazole-5-carboxylic acid ethyl ester (XXII). The reduction of (XXII) with Fe in ethanol/acetic acid yields the corresponding amino derivative (XI) already described, which is converted into the final product as described in Scheme 19090801a. 4) [13C]-Labeled saprisartan has been synthesized as follows: The decarboxylative iodination of 1-[3-bromo-2-(2-nitrophenyl)benzofuran-5-ylmethyl]-4-cyclopropyl-2-ethylimidazole-5-carboxylic acid ethyl ester (XXII) (already described in Scheme 2) by hydrolysis with NaOH in refluxing methanol, followed by reaction with iodine yields the corresponding 5-iodoimidazole derivative (XXIII), which is treated with [13C]-labeled potassium cyanide and copper iodide in DMF to afford the labeled imidazole-5-carbonitrile derivative (XXIV). The reduction of the nitro group of (XXIV) with iron filings in acetic acid/water yields the corresponding amino derivative (XXV), which is acylated with trifluoromethanesulfonic anhydride and triethylamine to give the sulfonamide (XXVI). Finally, the cyano group of (XXVI) is selectively hydrolyzed with aqueous ammonia and hydrogen peroxide to afford saprisartan labeled at the carboxamide group. 5) [14C]-Labeled saprisartan has been synthesized by the same synthetic sequence described previously for the [13C]-labeled compound.