Diversification of the three-component coupling of 2-aminoheterocycles, aldehydes, and isonitriles: efficient parallel synthesis of a diverse and druglike library of imidazo- and tetrahydroimidazo[1,2-a] heterocycles

J Comb Chem. 2007 Nov-Dec;9(6):1177-87. doi: 10.1021/cc0700290. Epub 2007 Sep 8.

Abstract

Due to their diverse range of biological activities, imidazoheterocycles are recognized as privileged structures making these structural motifs attractive targets for library preparation. We report herein the synthesis of a sizable collection of imidazo[1,2- a]heterocycle scaffolds well-suited for divergent library preparation by virtue of amine functional handles with diverse positioning and connectivities. Partial reduction of imidazo[1,2- a]pyrazines to the tetrahydroimidazo[1,2- a]pyrazines and regiospecific Mannich-type bond formation at the C-3 of imidazo[1,2- a]pyridine under mild conditions achieved additional topological and connective diversity within the scaffold collection. Subsequent parallel reaction of the functionalized imidazoheterocycles with polystyrene-tetrafluorophenol esters and sulfonates produced a 7500 compound library in high purity.

MeSH terms

  • Aldehydes / chemistry*
  • Amines / chemistry*
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Combinatorial Chemistry Techniques*
  • Esters / chemistry
  • Heterocyclic Compounds / chemical synthesis*
  • Imidazoles / chemical synthesis*
  • Models, Chemical
  • Nitriles / chemistry*
  • Phenols / chemistry
  • Polystyrenes / chemistry
  • Pyridines / chemistry
  • Sulfonic Acids / chemistry

Substances

  • Aldehydes
  • Amines
  • Esters
  • Heterocyclic Compounds
  • Imidazoles
  • Nitriles
  • Phenols
  • Polystyrenes
  • Pyridines
  • Sulfonic Acids
  • pyridine