Synthesis of 14C‐labeled and stable isotope‐labeled CGS 16617

Abstract

AbstractThe synthesis of a 14C‐labeled and two stable isotope‐labeled analogs of CGS 16617 is described. The synthetic method involved the preparation of tetrahydro‐3‐bromo‐1‐benzazepin‐2‐one, labeled with a 14C or four deuterium atoms, followed by introduction of two side chains at 1‐ and 3‐positions. The labeled bromobenzazepinones were prepared by Beckmann rearrangement of bromooximes of α‐tetralones, obtained by cyclization of labeled benzenebutanoic acids. The 14C‐labeled acid was prepared by hydrolysis of the nitrile, prepared by reaction of 3‐bromopropylbenzene and K14CN. The tetradeutero acid was prepared from ethyl phenylpropynoate by catalytic reduction of the triple bond with deuterium gas, followed by reduction of the deuterated ester with lithium aluminum hydride and conversion of the resulting alcohol into the carboxylic acid. The acetic acid side chain was introduced by N‐alkylation with ethyl bromoacetate or ethyl bromoacetate‐1,2‐13C2 followed by hydrolysis, and the L‐lysine side chain, by reaction with L‐(−)‐3‐amino‐caprolactam followed by hydrolysis of the caprolactam ring.