新产品编号:704499
Chemical Name: 3-[7-(3-Benzylureidomethyl)-4-oxo-4H-quinolizin-2-ylcarboxamido]-2(S)-(phenylsulfonamido)propionic acid
CAS No. 262278-00-2
项目整合开发状态: Biological Testing
项目研究机构: Shire BioChem (Originator)
合成路线:6-Methylnicotinonitrile (I) is oxidized by means of SeO2 in refluxing dioxane to furnish aldehyde (II).Subsequent condensation of (II) with dimethyl 2-(diethoxyphosphoryl)succinate (III) gives rise to the quinolizine derivative (IV).The cyano group of (IV) is then reduced to the primary amine (V) by catalytic hydrogenation over Pd/C.After protecting amine (V) as the corresponding N-Boc derivative (VI),alkaline hydrolysis of the methyl ester group provides acid (VII) (1).Coupling of acid (VII) with (S) t-butyl 3-amino-2-(benzenesulfonylamino)propionate (VIII) by means of HATU leads to amide (IX) (1,2).
合成路线:Selective deprotection of the N-Boc group of (IX) is accomplished by means of trifluoroacetic acid in CH2Cl2 at 0 C.The resultant primary amine (X) is then coupled to benzyl isocyanate (XI) to furnish urea (XII).Then,acidic cleavage of the tert-butyl ester group of (XII) leads to the title carboxylic acid (1,2).
📌 参考资料/链接：
参考文献标题:Quinolizinones as integrin inhibitors
文献作者:Attardo,G.; Lamothe,S.; Rej,R.; Zacharie,B.; Falardeau,G.; Labrecque,D.; Courchesne,M.; Abbott,S.(Shire BioChem Inc.)
参考来源:EP 1115724; US 6630488; WO 0017197
📄 详细内容
合成路线:6-Methylnicotinonitrile (I) is oxidized by means of SeO2 in refluxing dioxane to furnish aldehyde (II).Subsequent condensation of (II) with dimethyl 2-(diethoxyphosphoryl)succinate (III) gives rise to the quinolizine derivative (IV).The cyano group of (IV) is then reduced to the primary amine (V) by catalytic hydrogenation over Pd/C.After protecting amine (V) as the corresponding N-Boc derivative (VI),alkaline hydrolysis of the methyl ester group provides acid (VII) (1).Coupling of acid (VII) with (S) t-butyl 3-amino-2-(benzenesulfonylamino)propionate (VIII) by means of HATU leads to amide (IX) (1,2).
合成路线:Selective deprotection of the N-Boc group of (IX) is accomplished by means of trifluoroacetic acid in CH2Cl2 at 0 C.The resultant primary amine (X) is then coupled to benzyl isocyanate (XI) to furnish urea (XII).Then,acidic cleavage of the tert-butyl ester group of (XII) leads to the title carboxylic acid (1,2).
参考文献标题:Synthesis and in vitro potency of quinolizinone-based alphavbeta3 receptor antagonists
文献作者:Rej,R.; Lamothe,S.; Zacharie,B.; Labrecque,D.; Courchesne,M.; Falardeau,G.; Abbot,S.; Wang,W.; Chan,L.; Meerovitch,K.; Bergeron,F.; Attardo,G.
参考来源:Proc Am Assoc Cancer Res 2002,43