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【结 构 式】 
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【药物名称】Cinoxacin, Cinobac 【化学名称】1-Ethyl-4-oxo-1,4-dihydro[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid 【CA登记号】28657-80-9 【 分 子 式 】C12H10N2O5 【 分 子 量 】262.2239 |
【开发单位】Lilly (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY |
合成路线1
The reduction of 2-nitro-4,5-methylenedioxyacetophenone (I) with H2 over PtO2 in ethanol gives 2-amino-4,5-methylenedioxyacetophenone (II), which is cyclized by treatment with NaNO2 and HCl in water yielding 6,7-methylenedioxycinnolin-4-ol (III). The bromination of (III) with Br2 and potassium acetate in refluxing acetic acid affords 3-bromo-6,7-methylenedioxycinnolin-4-ol (IV), which is treated with Cu2(CN)2 in refluxing DMF giving 4-hydroxy-6,7-methylenedioxycinnolin-3-carbonitrile (V). Alkylation of (V) with ethyl iodide (A) by means of NaH in DMF affords 1-ethyl-6,7-methylenedioxy-4(1H)-oxocinnolin-3-carbonitrile (VI), which is finally hydrolyzed with HCl in refluxing acetic acid.
| 【1】 Roberts, P.J.; Castañer, J.; Cinoxacin. Drugs Fut 1978, 3, 1, 22. |
| 【2】 Un metodo para la preparacion de acidos 6,7-metilendioxi-4(1H)-oxocinnolin-3-carboxilicos. ES 376173; ES 402312 . |
| 【3】 Maas, I.M. Pfeiffer, W.G.; Voithenleitner, F.; 1-niederalkyl- oder -alkylensubstituierte 6,7-Methylendioxyd-4(1H)-oxocinnolin-3-carbosauren und Zwiswhenprodukte dafur. DE 2005104; FR 2034519; GB 1296753; GB 1296754 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 |
| (I) | 39691 | 1-(6-nitro-1,3-benzodioxol-5-yl)-1-ethanone | 56136-84-6 | C9H7NO5 | 详情 | 详情 |
| (II) | 18886 | 1-(6-amino-1,3-benzodioxol-5-yl)-1-ethanone | 28657-75-2 | C9H9NO3 | 详情 | 详情 |
| (III) | 39692 | [1,3]dioxolo[4,5-g]cinnolin-4-ol | C9H6N2O3 | 详情 | 详情 | |
| (IV) | 39693 | 3-bromo[1,3]dioxolo[4,5-g]cinnolin-4-ol | C9H5BrN2O3 | 详情 | 详情 | |
| (V) | 39694 | 4-hydroxy[1,3]dioxolo[4,5-g]cinnoline-3-carbonitrile | C10H5N3O3 | 详情 | 详情 | |
| (VI) | 39695 | 1-ethyl-4-oxo-1,4-dihydro[1,3]dioxolo[4,5-g]cinnoline-3-carbonitrile | C12H9N3O3 | 详情 | 详情 |