【结 构 式】 |
【药物名称】Luliconazole, PR-2699, NND-502 【化学名称】(-)-(R)-(E)-2-[4-(2,4-Dichlorophenyl)-1,3-dithiolan-2-ylidene]-2-(1-imidazolyl)acetonitrile 【CA登记号】187164-19-8 【 分 子 式 】C14H9Cl2N3S2 【 分 子 量 】354.28193 |
【开发单位】Nihon Nohyaku (Originator), Bayer (Licensee) 【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY |
合成路线1
This compound has been obtained by two similar ways: The enantiocontrolled reduction of 2,4-dichlorophenacyl bromide (I) with BH3/THF and a chiral oxazaborole catalyst gives 1(S)-(2,4-dichlorophenyl)-2-bromoethanol (II), which is treated with Ms-Cl and TEA in dichloromethane to yield the corresponding mesylate (III). Finally, this compound is cyclized with 2-(1-imidazolyl)-3,3-disulfanylacrylonitrile (VI) by means of KOH in DMSO. Alternatively, 1(S)-(2,4-dichlorophenyl)ethane-1,2-diol (VII) is treated with Ms-Cl and TEA in dichloromethane to give the corresponding dimesylate (VIII), which is condensed with the acrylonitrile (VI) with KOH as before. The intermediate acrylonitrile (VI) has been obtained by condensation of 2-(1-imidazolyl)acetonitrile (IV) with CS2 (V) by means of KOH in DMSO.
【1】 Kodama, H.; Niwano, Y.; Kanai, K.; Yoshida, M. (Nihon Nohyaku Co., Ltd.); Antifungal agent, cpd. therefor, process for producing the same. JP 1997100279; JP 1998158168; US 5900488; WO 9702821 . |
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) | 36408 | 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone | C8H5BrCl2O | 详情 | 详情 | |
(II) | 53962 | (1S)-2-bromo-1-(2,4-dichlorophenyl)-1-ethanol | n/a | C8H7BrCl2O | 详情 | 详情 |
(III) | 53963 | (1S)-2-bromo-1-(2,4-dichlorophenyl)ethyl methanesulfonate | n/a | C9H9BrCl2O3S | 详情 | 详情 |
(IV) | 13535 | 2-(1H-Imidazol-1-yl)acetonitrile | C5H5N3 | 详情 | 详情 | |
(V) | 53967 | Alcohol of sulfur; Carbon bisulfuret; Carbon disulfide; Carbon sulfide; Dithiocarbonic anhydride; Methyl disulfide; Sulfocarbonic anhydride | 75-15-0 | CS2 | 详情 | 详情 |
(VI) | 53964 | 2-(1H-imidazol-1-yl)-3,3-disulfanylacrylonitrile | n/a | C6H5N3S2 | 详情 | 详情 |
(VII) | 53965 | (1S)-1-(2,4-dichlorophenyl)-1,2-ethanediol | n/a | C8H8Cl2O2 | 详情 | 详情 |
(VIII) | 53966 | (1S)-1-(2,4-dichlorophenyl)-2-[(methylsulfonyl)oxy]ethyl methanesulfonate | n/a | C10H12Cl2O6S2 | 详情 | 详情 |