A higher yielding synthesis of the clinical prodrug ZD2767P using di-protected 4-[N,N-bis(2-hydroxyethyl)amino]phenyl chloroformate

A novel synthesis is described of the prodrug ZD2767P (in Phase I/II clinical trials) that improves the overall yield from 13% to 45%. The method involves the synthesis of 4-[N,N-bis(2-hydroxyethyl)amino]phenyl chloroformate protected as the bis-silyl ether, coupled with di-tert-butyl glutamate. There are clear advantages of this method compared to the literature procedure.