AD-5467
4H-1,4-苯并嗪-4-醋酸,2,3-二氢-2,8-双(1-甲基乙基)-3-噻氧基-Chemical Name: (?-2,8-Diisopropyl-3-thioxo-3,4-dihydro-2H-1,4-benzoxazine-4-acetic acid; (?-2,8-Bis(1-methylethyl)-3-thioxo-2,3-dihydro-4H-1,4-benzoxazine-4-acetic acid
CAS No. 112808-22-7, 112808-42-1 (R-isomer), 112808-43-2 (S-isomer)
项目整合开发状态: Phase II
项目研究机构: Takeda (Originator), Senju (Licensee)
合成路线:The cyclization of 2-amino-6-isoproylphenol (I) with 2-bromo-3-methylbutyryl chloride (II) by means of NaHCO3 in ethyl acetate - water gives 2,8-diisopropyl-2H-1,4-benzoxazin-3(4H)-one (III),which is condensed with methyl bromoacetate (IV) by means of NaH in DMF yielding 2,8-diisopropyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-acetic acid methyl ester (V).The reaction of (V) with P2S5 in refluxing toluene affords the corresponding thioxo derivative (VI),which is finally hydrolyzed with NaOH in dioxane - methanol.
📌 参考资料/链接：
参考文献标题:Thiolactam-N-acetic acid derivs.,their production and use
文献作者:Meguro,K.; Ikeda,H.; Yamamoto,Y.(Senju Pharmaceuticals Co.,Ltd.; Takeda Chemical Industries,Ltd.)
参考来源:EP 0243018; JP 1988107970; US 4771050
📄 详细内容
合成路线:The cyclization of 2-amino-6-isoproylphenol (I) with 2-bromo-3-methylbutyryl chloride (II) by means of NaHCO3 in ethyl acetate - water gives 2,8-diisopropyl-2H-1,4-benzoxazin-3(4H)-one (III),which is condensed with methyl bromoacetate (IV) by means of NaH in DMF yielding 2,8-diisopropyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-acetic acid methyl ester (V).The reaction of (V) with P2S5 in refluxing toluene affords the corresponding thioxo derivative (VI),which is finally hydrolyzed with NaOH in dioxane - methanol.
参考文献标题:Studies on antidiabetic agents.IX.A new aldose reductase inhibitor,AD-5467,and related 1,4-benzoxazine and 1,4-benzothiazine derivatives: Synthesis and biological activity
文献作者:Ikeda,H.; Meguro,K.; Yamamoto,Y.; Tawada,Sugiyama,Y.
参考来源:Chem Pharm Bull 1990,38(5),1238-45
合成路线:The cyclization of 2-amino-6-isoproylphenol (I) with 2-bromo-3-methylbutyryl chloride (II) by means of NaHCO3 in ethyl acetate - water gives 2,8-diisopropyl-2H-1,4-benzoxazin-3(4H)-one (III),which is condensed with methyl bromoacetate (IV) by means of NaH in DMF yielding 2,8-diisopropyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-acetic acid methyl ester (V).The reaction of (V) with P2S5 in refluxing toluene affords the corresponding thioxo derivative (VI),which is finally hydrolyzed with NaOH in dioxane - methanol.
参考文献标题:AD-5467
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1991,16(1),13
产品链接: CAS No. 112808-22-7››