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【结 构 式】 
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【分子编号】34162 【品名】1-(1,1,4,5-tetrachloro-1,1a,3,7b-tetrahydro-2H-cyclopropa[c]isoquinolin-2-yl)-1-ethanone 【CA登记号】 |
【 分 子 式 】C12H9Cl4NO 【 分 子 量 】325.0204 【元素组成】C 44.35% H 2.79% Cl 43.63% N 4.31% O 4.92% |
合成路线1
该中间体在本合成路线中的序号：(VI)The condensation of 2,3-dichlorobenzaldehyde (I) with 2,2-dimethoxyethylamine (II) in refluxing toluene gives the corresponding Schiff base (III), which is reduced with H2 over PtO2 in ethyl acetate and acetylated with acetic anhydride yielding N-(2,3-dichlororobenzyl)-N-(2,2-dimethoxyethyl)acetamide (IV). The cyclization of (IV) with AlCl3 in dichloroethane affords 7,8-dichloro-2-acetyl-1,2-dihydroisoquinoline (V), which is submitted to cyclopropanation with CHCl3, NaOH and benzyltriethylammonium chloride giving 1,1,4,5-tetrachloro-2-acetyl-1a,2,3,7b-tetrahydro-1H-cycloprop[c]isoquinoline (VI). Ring opening of (VI) by refluxing with tert-butyl alcohol yields 2-acetyl-3-(tert-butoxy)-4,8,9-trichloro-2,3-dihydro-1H-2-benzazepine (VII), which is reduced with H2 over PtO2 in methanol affording 2-acetyl-8,9-dichloro 2,3,4,5-tetrahydro-1H-2-benzazepine (VIII). Finally, this compound is desacetylated by means of refluxing aqueous HCl.
| 【1】 Perchonock, C.D.; Lantos, I.; Holden, K.G.; Finkelstei, J.A.; Facile synthesis of halo-substituted tetrahydroisoquinolines and tetrahydro-2-benzazepines via N-acetyl-1,2-dihydroisoquinolines. J Org Chem 1980, 45, 10, 1950-53. |
| 【2】 Serradell, M.N.; Castaner, J.; LY-134046. Drugs Fut 1984, 9, 4, 268. |
| 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) | 14742 | 2,3-dichlorobenzaldehyde | 6334-18-5 | C7H4Cl2O | 详情 | 详情 |
| (II) | 34158 | aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine | 22483-09-6 | C4H11NO2 | 详情 | 详情 |
| (III) | 34159 | N-[(Z)-(2,3-dichlorophenyl)methylidene]-2,2-dimethoxy-1-ethanamine; N-[(Z)-(2,3-dichlorophenyl)methylidene]-N-(2,2-dimethoxyethyl)amine | C11H13Cl2NO2 | 详情 | 详情 | |
| (IV) | 34160 | N-(2,3-dichlorobenzyl)-N-(2,2-dimethoxyethyl)acetamide | C13H17Cl2NO3 | 详情 | 详情 | |
| (V) | 34161 | 1-[7,8-dichloro-2(1H)-isoquinolinyl]-1-ethanone | C11H9Cl2NO | 详情 | 详情 | |
| (VI) | 34162 | 1-(1,1,4,5-tetrachloro-1,1a,3,7b-tetrahydro-2H-cyclopropa[c]isoquinolin-2-yl)-1-ethanone | C12H9Cl4NO | 详情 | 详情 | |
| (VII) | 34163 | 1-[3-(tert-butoxy)-4,8,9-trichloro-1,3-dihydro-2H-2-benzazepin-2-yl]-1-ethanone | C16H18Cl3NO2 | 详情 | 详情 | |
| (VIII) | 34164 | 1-(8,9-dichloro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-1-ethanone | C12H13Cl2NO | 详情 | 详情 |