1-(Piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one is a widely prevalent substructure found in >1000 CGRP receptor antagonists.  Two complimentary and scalable syntheses of 1-(Piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one will be described.  One route involves a chemoselective reductive amination of 1,2-diaminopyridine. A strong acid effect is observed in controlling selectivity and output for this reaction. The second route exploits a Pd-catalyzed amination reaction. Overamination is addressed by exploring ammonia surrogates, weak bases and ligand to metal ratios. Both the routes developed will exhibit wide utility in CGRP receptor antagonists synthesis.

Development of two complementary syntheses for a privileged CGRP receptor antagonist substructure

243rd National Meeting (2012)

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