We describe a general strategy for
the aza-Michael addition of
nucleophilic heterocycles into β-substituted acrylates using
potassium tert-butoxide as catalyst. Demonstrating
that the reaction is under thermodynamic control underpins optimization
efforts and enables rapid exploration of the substrate scope, with
yields ranging from 55% to 94%. We further leverage these lessons
in a significantly shortened synthesis of MK-0429, a potent pan-integrin
inhibitor previously taken into human clinical trials for the treatment
of prostate cancer and osteoporosis.
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