Development and Large-Scale Preparation of an Oral TACE Inhibitor

An efficient, expedient synthesis of BMS-561392, 1, which enabled rapid delivery of drug substance for clinical development is described. The key features of the synthesis include an efficient synthesis of a phenolic α,α-disubstituted amino ester via carbon alkylation without protection of the phenol, an effective enzymatic resolution of this racemic amino ester, and a process for the preparation of a hydroxamic acid drug substance with undetectable levels of hydroxylamine.