American Chemical Society
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Efficient Multikilogram Synthesis of a VLA‑4 Antagonist via a Povarov Reaction

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journal contribution
posted on 2019-12-09, 20:34 authored by Patrick Cerfontaine, Frank Driessens, Marie-France Deltent, Sylvain Petit
Herein we describe the practical synthesis of a novel VLA-4 antagonist 1 as a potential treatment for multiple sclerosis. The key step is based on the Povarov reaction of an imine with an alkene to access a tetrahydroquinoline intermediate, leading to the corresponding quinoline core after an oxidative aromatization step. The development of the synthesis of 1 led to decreased complexity and the elimination of chromatographic purifications. These improvements were demonstrated at scale by the production of 32 kg of 1 in high yield with excellent purity.