|
【结 构 式】 
|
【药物名称】Butoconazole nitrate, RS-35887-00-10-3, RS-35887, Gynomyk, Gynazole-1, Femstat 【化学名称】(±)-1-[4-(p-Chlorophenyl)-2-[(2,6-dichlorophenyl)thio]butyl]imidazole mononitrate 【CA登记号】64872-77-1, 64872-76-0 (free base) 【 分 子 式 】C19H18Cl3N3O3S 【 分 子 量 】474.79661 |
【开发单位】Roche Bioscience (Originator), Bayer (Not Determined), Cassenne (Not Determined), KV Pharmaceutical (Not Determined), Arrow Pharmaceuticals (Marketer) 【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY |
合成路线1
The chlorohydrin (II) is obtained by the reaction of p-chlorobenzylmagnesium chloride (I) with epichlorohydrin (A) in ether. This is then converted to the crystalline alcohol (III) by reaction with sodium imidazole (B) in DMF. On treatment with thionyl chloride is converted to the corresponding chloro compound (IV). When (IV) is reacted with 2,6-dichloro thiophenol (C) in the presence of anhydrous potassium carbonate in acetone, the free base of butoconazole is formed. Neutralization of the free base (V) with nitric acid gives butoconazole.
| 【1】 Walker, K.A.M.; et al.; 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)n-butil]-1H-imidazole nitrate, a new patent antifungal agent. J Med Chem 1978, 21, 8, 840. |
| 【2】 Arya, V.P.; Butoconazole nitrate. Drugs Fut 1979, 4, 2, 89. |
| 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) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (B) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (I) | 33290 | Bromo(4-chlorobenzyl)magnesium; p-Chlorobenzylmagnesium chloride | C7H6BrClMg | 详情 | 详情 | |
| (II) | 33291 | 1-chloro-4-(4-chlorophenyl)-2-butanol | C10H12Cl2O | 详情 | 详情 | |
| (III) | 16486 | 4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol | C13H15ClN2O | 详情 | 详情 | |
| (IV) | 33292 | 1-[2-chloro-4-(4-chlorophenyl)butyl]-1H-imidazole | C13H14Cl2N2 | 详情 | 详情 | |
| (V) | 33294 | 1-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)sulfanyl]butyl]-1H-imidazole; 3-(4-chlorophenyl)-1-(1H-imidazol-1-ylmethyl)propyl 2,6-dichlorophenyl sulfide | C19H17Cl3N2S | 详情 | 详情 | |
| (C) | 33293 | 2,6-Dichloro thiophenol; 2,6-Dichlorobenzenethiol; 2,6-Dichlorophenylhydrosulfide | 24966-39-0 | C6H4Cl2S | 详情 | 详情 |