posted on 2019-12-09, 20:34authored byPatrick 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.