Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction

Org Lett. 2009 May 7;11(9):1999-2002. doi: 10.1021/ol900350k.

Abstract

An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.

MeSH terms

  • Benzoates / chemistry
  • Catalysis
  • Janus Kinases / antagonists & inhibitors*
  • Molecular Structure
  • Nitriles
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Pyrimidines
  • Stereoisomerism

Substances

  • Benzoates
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Janus Kinases