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【结 构 式】 
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【分子编号】13906 【品名】5-Chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonitrile 【CA登记号】 |
【 分 子 式 】C11H10ClNO 【 分 子 量 】207.65924 【元素组成】C 63.62% H 4.85% Cl 17.07% N 6.75% O 7.7% |
合成路线1
该中间体在本合成路线中的序号：(XII)2) The title compound, with or without [14C]-radiolabeling at the carboxamide group, is synthesized as follows: The alkylation of 2-bromo-4-chlorophenol (VIII) with 2-methylallyl chloride (III) by means of cesium carbonate in acetone gives the corresponding allyl ether (IX), which is submitted to an allylic transposition to the ortho allyl phenol (X); the latter, without isolation, is thermically cyclized to 7-bromo-5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran (XI). The reaction of (XI) with KCN (with or without [14C]-radiolabel) by means of CuCN yields 5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carbonitrile (XII), which is hydrolyzed with methanolic KOH to the corresponding acid (XIII). The reaction of (XIII) with oxalyl chloride in toluene affords the corresponding acyl chloride (XIV), which is finally condensed with endo-3-amino-8-methyl-8-azabicyclo[3.2.1]octane (3alpha-aminotropane) (VII) in toluene as solvent.
| 【1】 O'Bannon, D.D.; Wheeler, W.J.; The synthesis of the carbonyl-14C analog of zatosetron maleate, a potent, long-acting, orally effective 5-HT3 receptor antagonist. J Label Compd Radiopharm 1991, 29, 6, 625-32. |
| 【2】 Graul, A.; Castaner, J.; Prous, J.; Zatosetron Maleate. Drugs Fut 1994, 19, 9, 850. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 12127 | 3-Chloro-2-methyl-1-propene; Isobutenyl chloride | 563-47-3 | C4H7Cl | 详情 | 详情 |
| (VII) | 12412 | (1R,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-amine; (1R,5S)-8-Methyl-8-azabicyclo[3.2.1]oct-3-ylamine | C8H16N2 | 详情 | 详情 | |
| (VIII) | 13902 | 2-Bromo-4-chlorophenol | 695-96-5 | C6H4BrClO | 详情 | 详情 |
| (IX) | 13903 | 2-Bromo-4-chlorophenyl 2-methyl-2-propenyl ether; 2-Bromo-4-chloro-1-[(2-methyl-2-propenyl)oxy]benzene | C10H10BrClO | 详情 | 详情 | |
| (X) | 13904 | 2-Bromo-4-chloro-6-(2-methyl-2-propenyl)phenol | C10H10BrClO | 详情 | 详情 | |
| (XI) | 13905 | 7-Bromo-5-chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran | C10H10BrClO | 详情 | 详情 | |
| (XII) | 13906 | 5-Chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonitrile | C11H10ClNO | 详情 | 详情 | |
| (XII) | 45187 | 5-chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carboxylic acid | C11H11ClO3 | 详情 | 详情 | |
| (XIII) | 13900 | 5-Chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carboxylic acid | C11H11ClO3 | 详情 | 详情 | |
| (XIII) | 45188 | 5-chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonitrile | C11H10ClNO | 详情 | 详情 | |
| (XIV) | 13908 | 5-Chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride | C11H10Cl2O2 | 详情 | 详情 | |
| (XIV) | 45189 | 5-chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride | C11H10Cl2O2 | 详情 | 详情 |