Mild and efficient DBU-catalyzed amidation of cyanoacetates

Org Lett. 2009 May 7;11(9):2003-6. doi: 10.1021/ol900435t.

Abstract

A mild, high-yielding, and practical protocol for the direct amidation of alkyl cyanoacetates using DBU is presented. This method eliminates the need for activation of cyanoacetic acid and/or high temperatures. It has been applied to the large-scale synthesis of CP-690,550-10 (1), a compound under development for the treatment of autoimmune diseases.

MeSH terms

  • Acetates / chemistry*
  • Amides / chemistry*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry*
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology
  • Molecular Structure
  • Piperazines / chemistry
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology

Substances

  • Acetates
  • Amides
  • Bridged Bicyclo Compounds, Heterocyclic
  • CP-690,550-10
  • Immunosuppressive Agents
  • Piperazines
  • Pyrimidines
  • Pyrroles
  • 1,8-diazabicyclo(5.4.0)undec-7-ene
  • cyanoacetic acid
  • triethylenediamine