Direct B-alkyl Suzuki-Miyaura cross-coupling of 2-halopurines. Practical synthesis of ST1535, a potent adenosine A2A receptor antagonist

J Org Chem. 2010 Aug 6;75(15):5398-401. doi: 10.1021/jo101027h.

Abstract

The scope and limitations of using palladium-catalyzed cross-coupling reactions of diverse butyl metal species with two different 2-halopurines were evaluated. While tributylboranes reacted readily and regioselectively with both 2-chloro-6-dibenzylaminopurines and 2-iodo-6-chloropurines, all the other alkyl metal species were much less reactive and gave very poor yield and/or selectivity of the desired product. This protocol was applied to the synthesis of an important adenosine A(2A) receptor antagonist, ST1535.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis
  • Adenine / chemistry
  • Magnetic Resonance Spectroscopy
  • Purines / chemistry*
  • Receptor, Adenosine A2A / metabolism*
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry

Substances

  • 2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine
  • Purines
  • Receptor, Adenosine A2A
  • Triazoles
  • Adenine