Preparation of 8-substituted xanthine CVT-124 precursor by late stage pyrimidine ring closure

J Org Chem. 2002 Jan 11;67(1):188-93. doi: 10.1021/jo015925r.

Abstract

To develop a novel route for the scaleable synthesis of the chiral xanthine CVT-124 (1, aka. BG9719), a method for the late stage pyrimidine ring closure of the nitrogen-protected endo 2-norbornenyl imidazole 3 was developed. The three-component coupling of benzylamine, 2-cyanoglycine ethyl ester (4), and methyl 5-norbornene-2-carboximidate hydrochloride (5) was demonstrated to achieve 3 in 23-46% isolated yields. The imidazole 3 was then elaborated to construct the N-benzyl xanthine 2 as a 1:1 mixture of exo and endo isomers, which were separable at this stage by chromatography. The nitrogen-protected endo xanthine 2 is a key intermediate in the synthesis of CVT-124.

MeSH terms

  • Cyclization
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines / chemistry
  • Xanthines / chemical synthesis*

Substances

  • 1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines
  • Xanthines