Selective Access to Heterocyclic Sulfonamides and Sulfonyl Fluorides via a Parallel Medicinal Chemistry Enabled Method

ACS Comb Sci. 2015 Nov 9;17(11):653-7. doi: 10.1021/acscombsci.5b00120. Epub 2015 Oct 14.

Abstract

A sulfur-functionalized aminoacrolein derivative is used for the efficient and selective synthesis of heterocyclic sulfonyl chlorides, sulfonyl fluorides, and sulfonamides. The development of a 3-step parallel medicinal chemistry (PMC) protocol for the synthesis of pyrazole-4-sulfonamides effectively demonstrates the utility of this reagent. This reactivity was expanded to provide rapid access to other heterocyclic sulfonyl fluorides, including pyrimidines and pyridines, whose corresponding sulfonyl chlorides lack suitable chemical stability.

Keywords: 3-step PMC protocol; heterocyclic sulfonamides; rapid access; sulfonyl fluorides.

MeSH terms

  • Chemistry, Pharmaceutical
  • Combinatorial Chemistry Techniques
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Molecular Structure
  • Sulfinic Acids / chemical synthesis*
  • Sulfinic Acids / chemistry
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry

Substances

  • Heterocyclic Compounds
  • Sulfinic Acids
  • Sulfonamides
  • sulfuryl fluoride