14C‐radiolabeling of a new steroidal antiandrogen with a C‐18 angular methyl extension

Abstract

The synthesis of a 14C‐labeled C‐18 functionalized steroid (as referred as EM‐6798) that will serve as a probe for the research of novel antiandrogens has been accomplished. This radioactive steroid was obtained in nine steps by coupling racemic N‐cyclohexyl‐1‐(3′‐hydroxy[U‐14C]phenyl)propylamine with protected 18‐bromomethyl‐3,17‐androstenedione. Incorporation of the radiolabel on the C‐18 side chain was achieved using commercially available 3‐bromo[U‐14C]phenol. Alkylation of N‐cyclohexyl‐1‐(3′‐hydroxy[U‐14C]phenyl)propylamine with 3‐ethylenedioxy‐18‐bromomethyl‐3,17‐androstenedione furnished after reduction and deprotection, [phenyl‐U‐14C]EM‐6798 in a 20% overall yield from 3‐bromo[U‐14C]phenol at a specific activity of 156 μCi/mg with 97.9% radiochemical purity as determined by HPLC.