title: Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists.
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.
authors.affiliation: Department of Process Research, Merck Research Laboratories, Rahway, NJ 07065, USA. fred_hartner@merck.com
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Hartner
authors.forename: Yi
authors.initials: Y
authors.lastname: Hsiao
authors.forename: Kan K
authors.initials: KK
authors.lastname: Eng
authors.forename: Nelo R
authors.initials: NR
authors.lastname: Rivera
authors.forename: Michael
authors.initials: M
authors.lastname: Palucki
authors.forename: Lushi
authors.initials: L
authors.lastname: Tan
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yasuda
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes
authors.forename: Steven
authors.initials: S
authors.lastname: Weissman
authors.forename: Daniel
authors.initials: D
authors.lastname: Zewge
authors.forename: Tony
authors.initials: T
authors.lastname: King
authors.forename: Dave
authors.initials: D
authors.lastname: Tschaen
authors.forename: R P
authors.initials: RP
authors.lastname: Volante
mesh_terms: D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis*; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
chemical_list: C496034:3-((7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine; C496033:3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine; D039302:Integrin alphaVbeta3; D009287:Naphthyridines; D011407:Propane