Ni-Catalyzed C-H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor BMS-911543

J Org Chem. 2015 Jun 19;80(12):6001-11. doi: 10.1021/acs.joc.5b00572. Epub 2015 May 1.

Abstract

BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.

MeSH terms

  • Catalysis
  • Heterocyclic Compounds, 3-Ring / chemical synthesis*
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Hydrogen Bonding
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / chemistry
  • Molecular Structure
  • Nickel / chemistry*

Substances

  • Heterocyclic Compounds, 3-Ring
  • N,N-dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo(4,5-d)pyrrolo(2,3b)pyridine-7-carboxamide
  • Nickel
  • Janus Kinase 2