Zaldaride maleate, KW-5617, Zy-17617B, CGS-9343B
扎达来特马来酸盐 1,3-二氢-1-[1-[(4-甲基-4H,6H-吡咯并[1,2-a][4,1]苯并氮杂-4-基)甲基]-4-哌啶]-2H-苯并咪唑-2-酮 Chemical Name: 1-[1-(4-Methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-ylmethyl)piperidin-4-yl]-2,3-dihydro-1H-benzimidazol-2-one maleate (1:1) salt
CAS No. 109826-27-9, 109826-26-8 (free base)
项目整合开发状态: Phase III
项目研究机构: Gebro Pharma (Originator), Novartis (Originator), Kyowa Hakko (Licensee)
合成路线:The cyclization of methyl 2-aminobenzoate (I) with 2,5-dimethoxytetrahydrofuran (II) in refluxing acetic acid gives methyl 2-(pyrrol-1-yl)benzoate (III),which by reduction with LiAlH4 in ether is converted into 2-(pyrrol-1-yl)benzyl alcohol (IV).The cyclization of (IV) with ethyl 2-oxopropionate (V) by means of butyllithium and tetramethylethylenediamine (TMEDA) in THF affords 4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine-4-carboxylic acid ethyl ester (VI),which is hydrolyzed with NaOH in refluxing ethanol to the corresponding free acid (VII).The condensation of (VII) with 1-(piperidin-4-yl)-2,3-dihydro-1H-benzimidazol-2-one (VIII) by means of carbonyldiimidazol (CDI) in THF gives 1-[1-(4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-ylcarbonyl) piperidin-4-yl]-2,3-dihydro-1H-benzimidazol-2-one (IX),which is finally reduced with LiAlH4 in THF,and treated with maleic acid in acetone.
📌 参考资料/链接：
参考文献标题:Pyrrolo[1,2-a][4,1]benzoxazepins,process for their preparation,pharmaceutical compsns.containing them as well as therapeutic use
文献作者:Wasley,J.W.F.; Norman,J.(Novartis AG)
参考来源:EP 0233483; JP 1987169791; JP 1995089966; US 4758559
📄 详细内容
合成路线:The cyclization of methyl 2-aminobenzoate (I) with 2,5-dimethoxytetrahydrofuran (II) in refluxing acetic acid gives methyl 2-(pyrrol-1-yl)benzoate (III),which by reduction with LiAlH4 in ether is converted into 2-(pyrrol-1-yl)benzyl alcohol (IV).The cyclization of (IV) with ethyl 2-oxopropionate (V) by means of butyllithium and tetramethylethylenediamine (TMEDA) in THF affords 4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine-4-carboxylic acid ethyl ester (VI),which is hydrolyzed with NaOH in refluxing ethanol to the corresponding free acid (VII).The condensation of (VII) with 1-(piperidin-4-yl)-2,3-dihydro-1H-benzimidazol-2-one (VIII) by means of carbonyldiimidazol (CDI) in THF gives 1-[1-(4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-ylcarbonyl) piperidin-4-yl]-2,3-dihydro-1H-benzimidazol-2-one (IX),which is finally reduced with LiAlH4 in THF,and treated with maleic acid in acetone.
参考文献标题:Zaldaride Maleate
文献作者:Robinson,C.; Robinson,K.; Castar,J.
参考来源:Drugs Fut 1996,21(7),719
产品链接: CAS No. 109826-27-9›› 产品链接: CAS No.109826-26-8››