Synthesis of alkyl- and aryl-amino-substituted anthraquinone derivatives by microwave-assisted copper(0)-catalyzed Ullmann coupling reactions

Nat Protoc. 2010 May;5(5):945-53. doi: 10.1038/nprot.2010.63. Epub 2010 Apr 29.

Abstract

This protocol describes the efficient, generally applicable Ullmann coupling reaction of bromaminic acid with alkyl- or aryl-amines in phosphate buffer under microwave irradiation using elemental copper as a catalyst. The reaction leads to a number of biologically active compounds. As a prototypical example, the synthesis of a new, potent antagonist of human platelet P2Y(12) receptors, which has potential as an antithrombotic drug, is described in detail. The optimized protocol includes a description of an appropriate reaction setup, thin layer chromatography for monitoring the reaction and a procedure for the isolation, purification and characterization of the anticipated product. The reaction is performed without the use of a glove box and there is no requirement for an inert atmosphere. The reaction typically proceeds within 2-30 min, the protocol, including workup, generally takes 1-3 h to complete.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / chemical synthesis*
  • Anthraquinones / chemistry
  • Catalysis
  • Copper / chemistry*
  • Drug Discovery
  • Enzyme Inhibitors
  • Microwaves*
  • Molecular Structure
  • Purinergic P2 Receptor Antagonists
  • Stereoisomerism

Substances

  • Anthraquinones
  • Enzyme Inhibitors
  • Purinergic P2 Receptor Antagonists
  • Copper