The synthesis of N-[4-dimethylamino-1-butyl(1-13C)-N-nitrosobenzamide, an inhibitor of trypsin; cyanide does not exchange with acetonitrile

The synthesis of N-[4-dimethylamino-1-butyl(1-13C)-N-nitrobenzamide, a powerful active-site-directed inhibitor of trypsin, is reported. An efficient use of 13C-cyanide ion was achieved in the reaction with 1-chloro-3-dimethylaminopropane, the first step of the synthesis. Acetonitrile was used as a co-solvent with water in that step; no evidence was found for cyanide ion exchange with acetonitrile. The earlier report of such an exchange appears to be in error; the formation of hydrocyanic acid under the reaction conditions can account for the observations. (Author)