【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% |
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 |