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【结 构 式】 
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【分子编号】37845 【品名】(1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol 【CA登记号】 |
【 分 子 式 】C11H15NO2 【 分 子 量 】193.24564 【元素组成】C 68.37% H 7.82% N 7.25% O 16.56% |
合成路线1
该中间体在本合成路线中的序号：(VII)The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).
| 【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| 40727 | 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine | 585-32-0 | C9H13N | 详情 | 详情 | |
| (I) | 37841 | methyl 3,5-dimethoxybenzoate | 2150-37-0 | C10H12O4 | 详情 | 详情 |
| (II) | 35424 | (3,5-dimethoxyphenyl)methanol | 705-76-0 | C9H12O3 | 详情 | 详情 |
| (III) | 21720 | 3,5-dimethoxybenzaldehyde | 7311-34-4 | C9H10O3 | 详情 | 详情 |
| (IV) | 37842 | (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine | C20H27NO2 | 详情 | 详情 | |
| (V) | 37843 | (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline | C13H17NO2 | 详情 | 详情 | |
| (VI) | 37844 | (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C13H19NO2 | 详情 | 详情 | |
| (VII) | 37845 | (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol | C11H15NO2 | 详情 | 详情 | |
| (VIII) | 37846 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H33NO2 | 详情 | 详情 | |
| (IX) | 37847 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H32INO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).
| 【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 | |
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| 40727 | 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine | 585-32-0 | C9H13N | 详情 | 详情 | |
| (I) | 37841 | methyl 3,5-dimethoxybenzoate | 2150-37-0 | C10H12O4 | 详情 | 详情 |
| (II) | 35424 | (3,5-dimethoxyphenyl)methanol | 705-76-0 | C9H12O3 | 详情 | 详情 |
| (III) | 21720 | 3,5-dimethoxybenzaldehyde | 7311-34-4 | C9H10O3 | 详情 | 详情 |
| (IV) | 37842 | (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine | C20H27NO2 | 详情 | 详情 | |
| (V) | 37843 | (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline | C13H17NO2 | 详情 | 详情 | |
| (VI) | 37844 | (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C13H19NO2 | 详情 | 详情 | |
| (VII) | 37845 | (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol | C11H15NO2 | 详情 | 详情 | |
| (VIII) | 37846 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H33NO2 | 详情 | 详情 | |
| (IX) | 37847 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H32INO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VII)The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).
| 【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| 40727 | 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine | 585-32-0 | C9H13N | 详情 | 详情 | |
| (I) | 37841 | methyl 3,5-dimethoxybenzoate | 2150-37-0 | C10H12O4 | 详情 | 详情 |
| (II) | 35424 | (3,5-dimethoxyphenyl)methanol | 705-76-0 | C9H12O3 | 详情 | 详情 |
| (III) | 21720 | 3,5-dimethoxybenzaldehyde | 7311-34-4 | C9H10O3 | 详情 | 详情 |
| (IV) | 37842 | (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine | C20H27NO2 | 详情 | 详情 | |
| (V) | 37843 | (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline | C13H17NO2 | 详情 | 详情 | |
| (VI) | 37844 | (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C13H19NO2 | 详情 | 详情 | |
| (VII) | 37845 | (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol | C11H15NO2 | 详情 | 详情 | |
| (VIII) | 37846 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H33NO2 | 详情 | 详情 | |
| (IX) | 37847 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H32INO2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(VII)The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).
| 【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| 40727 | 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine | 585-32-0 | C9H13N | 详情 | 详情 | |
| (I) | 37841 | methyl 3,5-dimethoxybenzoate | 2150-37-0 | C10H12O4 | 详情 | 详情 |
| (II) | 35424 | (3,5-dimethoxyphenyl)methanol | 705-76-0 | C9H12O3 | 详情 | 详情 |
| (III) | 21720 | 3,5-dimethoxybenzaldehyde | 7311-34-4 | C9H10O3 | 详情 | 详情 |
| (IV) | 37842 | (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine | C20H27NO2 | 详情 | 详情 | |
| (V) | 37843 | (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline | C13H17NO2 | 详情 | 详情 | |
| (VI) | 37844 | (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C13H19NO2 | 详情 | 详情 | |
| (VII) | 37845 | (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol | C11H15NO2 | 详情 | 详情 | |
| (VIII) | 37846 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H33NO2 | 详情 | 详情 | |
| (IX) | 37847 | benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C32H32INO2 | 详情 | 详情 |