A Fit-for-Purpose Synthesis of (R)-2-Methylazepane

Abstract

The preparation of new RSV inhibitors required an efficient synthesis of (R)-2-methylazepane ((R)-1) amenable to large-scale production to support preclinical studies. After consideration of different options, an efficient five-step synthesis relying on the preparation of the racemic N-Boc precursor and its purification by chiral SFC was developed and successfully implemented on a 400 g scale.

Iron Catalyzed Dearomatization of Pyridines into Annelated Azepine Derivatives in a One-Step, Three-Component Reaction

“… These motifs possess a wide range of biological activities leading to various applications in medicine and pharmacology . As a result, many approaches have been developed to construct the 7-membered core, such as nucleophilic substitution, lactamization, ring reorganization, ring-closing metathesis, and cycloadditions, including the use of azomethine ylides …”