新产品编号:750377
Chemical Name: 3-[N-[4-(4-Methylpyridin-2-ylamino)butyryl]glycylamino]-3-[4-(1-naphthyl)phenyl]propionic acid; N-[4-(4-Methylpyridin-2-ylamino)butyryl]glycyl-3-[4-(1-naphthyl)phenyl]-beta-alanine
CAS No. 287961-15-3, 287961-16-4 (Na salt), 287961-17-5 (trifluoroacetate)
项目整合开发状态: Biological Testing
项目研究机构: Merck KGaA (Originator)
合成路线:The 3-aryl-3-aminopropionic acid (II) was prepared by Knoevenagel condensation of 4-(1-naphthyl)benzaldehyde (I) with malonic acid in the presence of ammonium acetate.Subsequent esterification of (II) by means of thionyl chloride and methanol afforded the methyl ester (III).Coupling of amino ester (III) with N-Boc-glycine (IV) by means of TBTU and HOBt furnished amide (V).After acidic Boc group cleavage,the resultant dipeptide ester (VI) was acylated with 4-(4-methylpyridin-2-ylamino)butyric acid (VII),yielding tripeptide ester (VIII).The methyl ester group of (VIII) was finally hydrolyzed by NaOH in aqueous dioxan.
📌 参考资料/链接：
参考文献标题:beta-Alanine derivs.
文献作者:H鰈zemann,G.; Jonczyk,A.; Goodman,S.; St鋒le,W.(Merck Patent GmbH)
参考来源:WO 0048996
📄 详细内容
合成路线:The 3-aryl-3-aminopropionic acid (II) was prepared by Knoevenagel condensation of 4-(1-naphthyl)benzaldehyde (I) with malonic acid in the presence of ammonium acetate.Subsequent esterification of (II) by means of thionyl chloride and methanol afforded the methyl ester (III).Coupling of amino ester (III) with N-Boc-glycine (IV) by means of TBTU and HOBt furnished amide (V).After acidic Boc group cleavage,the resultant dipeptide ester (VI) was acylated with 4-(4-methylpyridin-2-ylamino)butyric acid (VII),yielding tripeptide ester (VIII).The methyl ester group of (VIII) was finally hydrolyzed by NaOH in aqueous dioxan.
参考文献标题:Nanomolar small molecule inhibitors for alphavbeta6,alphavbeta5,and +alphavbeta3 integrins
文献作者:Goodman,S.L.; H鰈zemann,G.; Sulyok,G.A.G.; Kessler,H.
参考来源:J Med Chem 2002,45(5),1045