Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for αvβ3 integrin antagonists

Article abstract of DOI:10.1021/jo0486950

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 α_vβ 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.