Utilizing Native Directing Groups: Synthesis of a Selective IKur Inhibitor, BMS-919373, via a Regioselective C-H
Steven R Wisniewski1, Jason M Stevens1, Miao Yu1
1Chemical and Synthetic Development , Bristol-Myers Squibb Company , One Squibb Drive , New Brunswick , New Jersey 08903 , United States.
Abstract:
BMS-919373 is a highly functionalized quinazoline under investigation as a selective, potent IKur current blocker. By utilizing the aminomethylpyridine side chain at C-4, a selective C-H functionalization at C-5 was invented, enabling the efficient synthesis of this molecule. The strategy of leveraging this inherent directing group allowed the synthesis of this complex heterocycle in only six steps from commodity chemicals. The scope of the C-H activation was further investigated, and the generality of the transformation across a series of bicyclic aromatic heterocycles was explored.
Related Concept Videos
Antihypertensive Drugs: Direct Renin Inhibitors
Nomenclature of Aryl and Heterocyclic Amines
Regioselectivity of Electrophilic Additions-Peroxide Effect
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Regioselective Formation of Enolates


