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【结 构 式】 
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【药物名称】Fadolmidine hydrochloride, Radolmidine hydrochloride, MPV-2426 【化学名称】3-(1H-Imidazol-4-ylmethyl)indan-5-ol hydrochloride 【CA登记号】189353-32-0, 189353-31-9 (free base) 【 分 子 式 】C13H15ClN2O 【 分 子 量 】250.7303 |
【开发单位】Orion Corp. (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, alpha2-Adrenoceptor Agonists |
合成路线1
Reductive coupling of 6-methoxy-1-indanone (I) with 1-benzylimidazole-5-carbaldehyde (II) using TiCl4 and Zn in boiling THF afforded the indanylidenemethyl imidazole (III). Hydrogenation of the double bond of (III) and simultaneous debenzylation in the presence of Pd/C provided the indanylmethyl derivative (IV). The methyl ether group of (IV) was finally cleaved by refluxing in concentrated HBr, and the title compound was isolated after conversion to the hydrochloride salt.
| 【1】 Karjalainen, A.; Huhtala, P.; Savola, J.-M.; Wurster, S.; Eloranta, M.; Savola, M.; Saxlund, R.; Cockcroft, V. (Orion Corporation); Imidazole derivs. having affinity for alpha2 receptors activity. EP 0888309; JP 2000507914; WO 9712874 . |
| 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) | 34514 | 6-methoxy-1-indanone | 13623-25-1 | C10H10O2 | 详情 | 详情 |
| (II) | 36347 | 1-benzyl-1H-imidazole-5-carbaldehyde | C11H10N2O | 详情 | 详情 | |
| (III) | 36348 | 1-benzyl-5-[(6-methoxy-2,3-dihydro-1H-inden-1-ylidene)methyl]-1H-imidazole; 1-[(E)-(1-benzyl-1H-imidazol-5-yl)methylidene]-2,3-dihydro-1H-inden-6-yl methyl ether | C21H20N2O | 详情 | 详情 | |
| (IV) | 36349 | 4-[(6-methoxy-2,3-dihydro-1H-inden-1-yl)methyl]-1H-imidazole; 3-(1H-imidazol-4-ylmethyl)-2,3-dihydro-1H-inden-5-yl methyl ether | C14H16N2O | 详情 | 详情 |