Multicomponent synthesis of diverse 1,4-benzodiazepine scaffolds

Abstract

The 1,4-benzodiazepine (BDZ) scaffold is of particular interest in drug design due to a balanced ensemble of beneficial physicochemical properties including a semirigid and compact diazepine ring with spatial placements of several substituents, combined with low number of rotatable bonds, hydrogen bond donors and acceptors, and intermediate lipophilicity. As an alternative to traditional multistep sequential syntheses, we designed routes employing one-pot MCRs to accelerate access diverse BDZ scaffolds in two or three steps.

Scheme 1

A general strategy for the design of novel BDZ scaffolds by employing bifunctional orthogonal starting materials in the Ugi-4CR and subsequent intramolecular cyclization.