A new strategy for the construction of the imidazo[1,5-a]quinoxalin-4-one ring system and its application to the efficient synthesis of BMS-238497, a novel and potent Lck inhibitor

J Org Chem. 2004 Feb 6;69(3):977-9. doi: 10.1021/jo0355348.

Abstract

A new efficient strategy was developed for the construction of the imidazo[1,5-a]quinoxalin-4-one ring system. The new method involves condensation of o-nitroaniline with glyoxylate in methanol followed by treatment of the resulting alpha-(o-nitroanilino)-alpha-methoxy acetate with tosylmethyl isocyanide (TosMIC) reagent to give 1-(o-nitrophenyl)imidazole-5-carboxylate. Reductive cyclization of the nitro imidazole carboxylate afforded imidazo[1,5-a]quinoxalin-4-one in three steps and 60% overall yield. The new method was successfully applied to the synthesis of BMS-238497, a novel and potent Lck inhibitor.

MeSH terms

  • Aniline Compounds / chemistry
  • Cyclization
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Glyoxylates / chemistry
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry

Substances

  • 4-(2-chloro-6-methylphenylamino)-7,8-dimethoxyimidazo(1,5-a)quinoxalin-4-one
  • Aniline Compounds
  • Enzyme Inhibitors
  • Glyoxylates
  • Imidazoles
  • Quinoxalines
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)