Solution phase synthesis of a library of tetrasubstituted pyrrole amides

J Comb Chem. 2006 Jul-Aug;8(4):491-9. doi: 10.1021/cc060008q.

Abstract

An efficient strategy for the solution-phase parallel synthesis of a library of pyrrole-amides is described. Key reactions include functional homologation of beta-ketoesters with a set of aldehydes followed by oxidation to produce a series of differently substituted 1,4-dicarbonyl compounds. Rapid cyclization using a microwave-assisted Paal-Knorr reaction provided a set of 24 pyrrole esters that were further functionalized through a trimethylaluminum-mediated aminolysis to obtain a larger library of 288 diverse pyrrole-3-amides. The tetrasubstitution allows a good exploration of the chemical space around the central pyrrole core. The last step was entirely automated with a Bohdan Myriad personal synthesizer.

MeSH terms

  • Amides / chemical synthesis*
  • Automation
  • Combinatorial Chemistry Techniques*
  • Cyclization
  • Microwaves
  • Models, Chemical
  • Molecular Structure
  • Pharmaceutical Preparations / chemical synthesis*
  • Pyrroles / chemical synthesis*

Substances

  • Amides
  • Pharmaceutical Preparations
  • Pyrroles