title: An efficient synthesis of an alphavbeta3 antagonist.
abstract: A practical preparation of an alpha(v)beta(3) antagonist is reported. The antagonist consists of three key components, a tetrahydronaphthyridine moiety, a beta-alanine moiety, and a central imidazolidone moiety. The tetrahydronaphthyridine component was prepared using two different methods, both of which relied on variations of the Friedländer reaction to establish the desired regiochemistry. The beta-alanine component was prepared using Davies' asymmetric 1,4-addition methodology as the key stereo-defining step. The central imidazolidone portion was created from these two components using an effective three-step cyclization protocol. Thus, a highly convergent process for the drug candidate was defined.
authors.affiliation: Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. nobuyoshi_yasuda@merck.com
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yasuda
authors.forename: Yi
authors.initials: Y
authors.lastname: Hsiao
authors.forename: Mark S
authors.initials: MS
authors.lastname: Jensen
authors.forename: Nelo R
authors.initials: NR
authors.lastname: Rivera
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yang
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Wells
authors.forename: James
authors.initials: J
authors.lastname: Yau
authors.forename: Michael
authors.initials: M
authors.lastname: Palucki
authors.forename: Lushi
authors.initials: L
authors.lastname: Tan
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dormer
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Volante
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Reider
mesh_terms: D002384:Catalysis; D003500:Cyclization; D007093:Imidazoles / Q000138:chemical synthesis*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis*; D013237:Stereoisomerism; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D007093:Imidazoles; D039302:Integrin alphaVbeta3; D009287:Naphthyridines; D015091:beta-Alanine