Use of cyclohexylisocyanide and methyl 2-isocyanoacetate as convertible isocyanides for microwave-assisted fluorous synthesis of 1,4-benzodiazepine-2,5-dione library

J Comb Chem. 2010 Jan-Feb;12(1):206-14. doi: 10.1021/cc900157w.

Abstract

A new protocol in which cyclohexylisocyanide and methyl 2-isocyanoacetate are used as convertible isocyanides for Ugi/de-Boc/cyclization/Suzuki synthesis of biaryl-substituted 1,4-benzodiazepine-2,5-diones has been developed. Ugi reactions of Boc-protected anthranilic acids, fluorous benzaldehydes, amines, and cyclohexylisocyanide or methyl 2-isocyanoacetate were carried out at room temperature. Microwave-promoted de-Boc/cyclization reactions afforded 1,4-benzodiazepine-2,5-diones (BZDs). Suzuki coupling reactions further derivatized the BZD ring by removing the fluorous tag and introducing the biaryl group. A thirty three-member biaryl-substituted BZD library containing four points of diversity was prepared by microwave-assisted solution-phase fluorous parallel synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzodiazepinones / chemical synthesis*
  • Cyanides / chemistry*
  • Cyclization
  • Fluorine / chemistry*
  • Gas Chromatography-Mass Spectrometry
  • Isocyanates / chemistry*
  • Microwaves*
  • Molecular Structure

Substances

  • Benzodiazepinones
  • Cyanides
  • Isocyanates
  • Fluorine