Zatebradine hydrochloride, UL-FS-49
3-[3-[[2-(3,4-二甲氧基苯基)乙基]甲基氨基]丙基]-1,3,4,5-四氢-7,8-二甲氧基-2H-3-苯并氮杂-2-酮盐酸盐扎替雷定Chemical Name: 1,3,4,5-Tetrahydro-7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylimino]propyl]-2H-3-benzazepin-2-one hydrochloride; 1-(7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl)-3-[N-methyl-N-[2-(3,4-dimethyoxyphenyl)ethyl]amino]propane hydrochloride
CAS No. 91940-87-3, 85175-64-0 (diHCl), 85175-67-3 (free base), 125846-52-8 (HCl.4H2O salt)
项目整合开发状态: Phase III
项目研究机构: Boehringer Ingelheim (Originator)
合成路线:The reaction of 3,4-dimethoxyphenylacetic acid (I) with SOCl2 in methylene chloride gives the corresponding acyl chloride (II),which is treated with aminoacetaldehyde dimethylacetal (III) and triethylamine in methylene chloride yielding N-(2,2-diethoxyethyl)-3,4-dimethoxyphenylacetamide (IV).The cyclization of (IV) by means of HCl in acetic acid atfords 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (V),which is alkylated with 1-bromo-3-chloro propane (VI) by means of potassium tert-butoxide in DMSO to give 3-(3-chloropropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (VII).The reaction of (VII) with N-methyl-2-(3,4-dimethoxyphenyl)ethylamine (VIII) at 100 C affords 7,8-dimethoxy-3-[3-[N-methyl-N-[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-1,3-dihydro-2H-3-benzazepin-2-one (IX),which is finally hydrogenated with H2 over Pd/C in acetic acid.
📌 参考资料/链接：
参考文献标题:Benzazepines,process for their preparation and their application as pharmaceutical preparations
文献作者:Reiffen,M.; et al.(Dr.Karl Thomae GmbH)
参考来源:DE 3119874; EP 0065229; GB 2099425; JP 57193462
📄 详细内容
合成路线:The reaction of 3,4-dimethoxyphenylacetic acid (I) with SOCl2 in methylene chloride gives the corresponding acyl chloride (II),which is treated with aminoacetaldehyde dimethylacetal (III) and triethylamine in methylene chloride yielding N-(2,2-diethoxyethyl)-3,4-dimethoxyphenylacetamide (IV).The cyclization of (IV) by means of HCl in acetic acid atfords 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (V),which is alkylated with 1-bromo-3-chloro propane (VI) by means of potassium tert-butoxide in DMSO to give 3-(3-chloropropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (VII).The reaction of (VII) with N-methyl-2-(3,4-dimethoxyphenyl)ethylamine (VIII) at 100 C affords 7,8-dimethoxy-3-[3-[N-methyl-N-[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-1,3-dihydro-2H-3-benzazepin-2-one (IX),which is finally hydrogenated with H2 over Pd/C in acetic acid.
参考文献标题:Process for the prepaation of benzazepine derivatives
文献作者:Reiffen,M.(Dr.Karl Thomae GmbH)
参考来源:CA 1207764; DD 215541; DE 3242345
合成路线:The reaction of 3,4-dimethoxyphenylacetic acid (I) with SOCl2 in methylene chloride gives the corresponding acyl chloride (II),which is treated with aminoacetaldehyde dimethylacetal (III) and triethylamine in methylene chloride yielding N-(2,2-diethoxyethyl)-3,4-dimethoxyphenylacetamide (IV).The cyclization of (IV) by means of HCl in acetic acid atfords 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (V),which is alkylated with 1-bromo-3-chloro propane (VI) by means of potassium tert-butoxide in DMSO to give 3-(3-chloropropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (VII).The reaction of (VII) with N-methyl-2-(3,4-dimethoxyphenyl)ethylamine (VIII) at 100 C affords 7,8-dimethoxy-3-[3-[N-methyl-N-[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-1,3-dihydro-2H-3-benzazepin-2-one (IX),which is finally hydrogenated with H2 over Pd/C in acetic acid.
参考文献标题:Ul-FS-49
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1985,10(8),639
产品链接: CAS No. 91940-87-3›› 产品链接: CAS No.85175-67-3››