Efficient synthesis of [6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]-acetic acid, a novel COX-2 inhibitor

J Org Chem. 2003 May 16;68(10):4104-7. doi: 10.1021/jo034274r.

Abstract

The synthesis of 6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-ylacetic acid (1), a selective cyclooxygenase 2 (COX-2) inhibitor, is described. The synthesis relied on a novel indole formation that involved an alkylation/1,4-addition/elimination/isomerization cascade. It was demonstrated that the entire sequence from sulfonamide 13 and bromoketone 14 to the desired indole (1) could be executed in a single pot.

MeSH terms

  • Alkylation
  • Catalysis
  • Chlorobenzoates / chemical synthesis*
  • Chlorobenzoates / pharmacology
  • Combinatorial Chemistry Techniques*
  • Cyclooxygenase 2
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Indicators and Reagents
  • Indoleacetic Acids / chemical synthesis*
  • Indoleacetic Acids / pharmacology
  • Isoenzymes / antagonists & inhibitors*
  • Molecular Structure
  • Prostaglandin-Endoperoxide Synthases

Substances

  • (6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl)acetic acid
  • Chlorobenzoates
  • Enzyme Inhibitors
  • Indicators and Reagents
  • Indoleacetic Acids
  • Isoenzymes
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases