• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】43974

【品名】methyl 7-(benzyloxy)-2-[4-[(tert-butoxycarbonyl)amino]phenyl]-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate

【CA登记号】

【 分 子 式 】C38H38N2O9

【 分 子 量 】666.7278

【元素组成】C 68.46% H 5.74% N 4.2% O 21.6%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XI)

Lithiation of 5-benzyloxy-2-bromobenzaldehyde dimethyl acetal (I), followed by addition to N,N-dimethyl-3,4,5-trimethoxybenzamide (II), gave rise to benzophenone (III). After acetal hydrolysis using an acidic ion exchange resin, the resulting aldehyde (IV) was oxidized to carboxylic acid (V) by means of sodium chlorite. Condensation of this keto acid (V) with diethyl bromomalonate (VI), followed by acidic treatment, furnished the isocoumarin derivative (VII). Subsequent addition of water to the double bond upon treatment with NaOH in aqueous methanol produced (VIII). This compound was condensed with N-Boc-p-phenylenediamine (IX) in the presence of N-methylmorpholine in hot 1,3-dimethyl-2-imidazolinone to afford the isoquinolinone (X). The methyl ester (XI) was prepared by reaction of carboxylic acid (X) with iodomethane and K2CO3.

1 Ikeo, T.; Ukita, T.; Omori, K. (Tanabe Seiyaku Co., Ltd.); Isoquinolinone derivs., process for preparing the same, and their use as phosphodiesterase inhibitors. JP 1998298164; WO 9838168 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 43965 4-(benzyloxy)-1-bromo-2-(dimethoxymethyl)benzene; benzyl 4-bromo-3-(dimethoxymethyl)phenyl ether C16H17BrO3 详情 详情
(II) 43966 3,4,5-trimethoxy-N,N-dimethylbenzamide C12H17NO4 详情 详情
(III) 43967 [4-(benzyloxy)-2-(dimethoxymethyl)phenyl](3,4,5-trimethoxyphenyl)methanone C26H28O7 详情 详情
(IV) 43968 5-(benzyloxy)-2-(3,4,5-trimethoxybenzoyl)benzaldehyde C24H22O6 详情 详情
(V) 43969 5-(benzyloxy)-2-(3,4,5-trimethoxybenzoyl)benzoic acid C24H22O7 详情 详情
(VI) 35647 diethyl 2-bromomalonate 685-87-0 C7H11BrO4 详情 详情
(VII) 43970 7-(benzyloxy)-1-oxo-4-(3,4,5-trimethoxyphenyl)-1H-isochromene-3-carboxylic acid C26H22O8 详情 详情
(VIII) 43971 7-(benzyloxy)-3-hydroxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-3,4-dihydro-1H-isochromene-3-carboxylic acid C26H24O9 详情 详情
(IX) 43972 4-(N-Boc-aminomethyl)aniline;tert-butyl (4-aminophenyl)carbamate;tert-butyl 4-aminophenylcarbamate C11H16N2O2 详情 详情
(X) 43973 7-(benzyloxy)-2-[4-[(tert-butoxycarbonyl)amino]phenyl]-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylic acid C37H36N2O9 详情 详情
(XI) 43974 methyl 7-(benzyloxy)-2-[4-[(tert-butoxycarbonyl)amino]phenyl]-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate C38H38N2O9 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XI)

Hydrogenolytic removal of the O-benzyl group provided phenol (XII), which was subsequently alkylated with 2-picolyl chloride (XIII) to produce ether (XIV). The Boc protecting group of (XIV) was finally cleaved by treatment with HCl in EtOAc.

1 Ikeo, T.; Ukita, T.; Omori, K. (Tanabe Seiyaku Co., Ltd.); Isoquinolinone derivs., process for preparing the same, and their use as phosphodiesterase inhibitors. JP 1998298164; WO 9838168 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XI) 43974 methyl 7-(benzyloxy)-2-[4-[(tert-butoxycarbonyl)amino]phenyl]-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate C38H38N2O9 详情 详情
(XII) 43975 methyl 2-[4-[(tert-butoxycarbonyl)amino]phenyl]-7-hydroxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate C31H32N2O9 详情 详情
(XIII) 26187 2-(Chloromethyl)pyridine 4377-33-7 C6H6ClN 详情 详情
(XIV) 43976 methyl 2-[4-[(tert-butoxycarbonyl)amino]phenyl]-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate C37H37N3O9 详情 详情
Extended Information