Scalable, One-Pot, Microwave-Accelerated Tandem Synthesis of Unsymmetrical Urea Derivatives

J Org Chem. 2017 Jan 20;82(2):992-999. doi: 10.1021/acs.joc.6b02521. Epub 2016 Dec 30.

Abstract

We report a facile, microwave-accelerated, one-pot tandem synthesis of unsymmetrical ureas via a Curtius rearrangement. In this method, one-pot microwave irradiation of commercially available (hetero)aromatic acids and amines in the presence of diphenylphosphoryl azide enabled extremely rapid (1-5 min) construction of an array of unsymmetrical ureas in good to excellent yields. We demonstrate the utility of our method in the efficient, gram-scale synthesis of key biologically active compounds targeting the cannabinoid 1 and α7 nicotinic acetylcholine receptors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Azides / chemistry
  • Chemistry, Organic / methods*
  • Microwaves*
  • Molecular Structure
  • Urea* / analogs & derivatives
  • Urea* / chemical synthesis
  • Urea* / chemistry

Substances

  • Azides
  • Urea
  • diphenylphosphorazidate