An Efficient Synthesis of an αvβ3 Antagonist

Abstract

A practical preparation of an α_vβ₃ antagonist is reported. The antagonist consists of three key components, a tetrahydronaphthyridine moiety, a β-alanine moiety, and a central imidazolidone moiety. The tetrahydronaphthyridine component was prepared using two different methods, both of which relied on variations of the Friedländer reaction to establish the desired regiochemistry. The β-alanine component was prepared using Davies' asymmetric 1,4-addition methodology as the key stereo-defining step. The central imidazolidone portion was created from these two components using an effective three-step cyclization protocol. Thus, a highly convergent process for the drug candidate was defined.