An Efficient Synthesis of an αvβ3 Antagonist

TLDR: A practical preparation of an alpha(v)beta(3) antagonist is reported, which consists of three key components, a tetrahydronaphthyridine moiety, a beta-alanine moieties, and a central imidazolidone moiety.

Abstract: A practical preparation of an αvβ3 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 Friedlander 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.