Utilizing Native Directing Groups: Synthesis of a Selective IKur Inhibitor, BMS-919373, via a Regioselective C-H Arylation

  • J Org Chem. 2019 Apr 19;84(8):4704-4714. doi: 10.1021/acs.joc.8b02254.
Steven R Wisniewski  1 ,  Jason M Stevens  1 ,  Miao Yu  1 ,  Kenneth J Fraunhoffer  1 ,  Evan O Romero  1 ,  Scott A Savage  1
Affiliations
  • 1. Chemical and Synthetic Development , Bristol-Myers Squibb Company , One Squibb Drive , New Brunswick , New Jersey 08903 , United States.
PMID: 30395712 DOI: 10.1021/acs.joc.8b02254
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.

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