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【结 构 式】 
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【药物名称】Broxaterol, Z-1170, Summair 【化学名称】(±)-3-Bromo-alpha-[(tert-butylamino)methyl]-5-isoxazolemethanol 【CA登记号】76596-57-1 【 分 子 式 】C9H15BrN2O2 【 分 子 量 】263.1361 |
【开发单位】Zambon (Originator) 【药理作用】Asthma Therapy, Bronchodilators, RESPIRATORY DRUGS, beta2-Adrenoceptor Agonists |
合成路线1
The condensation of 3-bromo-5-isoxazolylcarbonyl chloride (I) with diethyl malonate (II) gives the corresponding malonyl derivative (III), which is submitted to a decarboxylative hydrolysis yielding 5-acetyl-3-bromoisoxazole (IV). Bromination of (IV) affords 5-(bromoacetyl)-3-bromoisoxazole (V), which is reduced to 2-bromo-1-(3-bromo-5-isoxazolyl)ethanol (VI). Title compound is obtained by reaction of (VI) with tert-butylamine directly or via oxirane (VII), which is obtained by reaction of (VI) with sodium hydride, and finally by reaction of (VII) with tert-butylamine.
| 【1】 Fantucci, M.; Sala, R.; Chiarino, D.; Frigeni, V.; Della Bella, D.; Carenzi, A.; New isoxazole derivatives with a potent and select. Farm Sci Ed 1986, 41, 6, 440. |
| 【2】 Chiarino, D.; Della Bella, D. (Zambon Group SpA); 1-(3-Bromo-isoxazol-5-yl)-2-tert-butylaminoethanol. JP 1980108862; US 4276299 . |
| 【3】 Castaner, J.; Prous, J.; Broxaterol. Drugs Fut 1987, 12, 2, 107. |
| 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) | 22864 | 3-bromo-5-isoxazolecarbonyl chloride | C4HBrClNO2 | 详情 | 详情 | |
| (II) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (III) | 22866 | diethyl 2-[(3-bromo-5-isoxazolyl)carbonyl]malonate | C11H12BrNO6 | 详情 | 详情 | |
| (IV) | 22867 | 1-(3-bromo-5-isoxazolyl)-1-ethanone | C5H4BrNO2 | 详情 | 详情 | |
| (V) | 22868 | 2-bromo-1-(3-bromo-5-isoxazolyl)-1-ethanone | C5H3Br2NO2 | 详情 | 详情 | |
| (VI) | 22869 | 2-bromo-1-(3-bromo-5-isoxazolyl)-1-ethanol | C5H5Br2NO2 | 详情 | 详情 | |
| (VII) | 22870 | 3-bromo-5-(2-oxiranyl)isoxazole | C5H4BrNO2 | 详情 | 详情 |