Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists

J Org Chem. 2004 Dec 10;69(25):8723-30. doi: 10.1021/jo0486950.

Abstract

The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.

MeSH terms

  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Molecular Structure
  • Naphthyridines / chemical synthesis*
  • Propane / analogs & derivatives*
  • Propane / chemical synthesis*

Substances

  • 3-((7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine
  • 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine
  • Integrin alphaVbeta3
  • Naphthyridines
  • Propane