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【结 构 式】 
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【药物名称】NPS-846.HCl 【化学名称】3,3-Bis(3-fluorophenyl)propylamine hydrochloride 【CA登记号】 【 分 子 式 】C15H16ClF2N 【 分 子 量 】283.75127 |
【开发单位】NPS Pharmaceuticals (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Calcium Channel Blockers |
合成路线1
This compound has been obtained by two related ways: 1) The condensation of 3,3'-difluorobenzophenone (I) with diethyl cyanomethylphosphonate (II) by means of NaH in dimethoxyethane gives 3,3-bis(3-fluorophenyl)-2-propenenitrile (III), which is reduced with H2 over Pd(OH)2 in ethanol yielding 3,3-bis(3-fluorophenyl)propionitrile (IV). Finally, this compound is reduced with B2H6 in THF. 2) The condensation of 3,3'-difluorobenzophenone (I) with acetonitrile (V) by means of BuLi in THF gives 3,3-bis(3-fluorophenyl)-3-hydroxypropionitrile (VI), which is reduced with H2 over Ni/Al in ethanol yielding 3,3-bis(3-fluorophenyl)-3-hydroxypropylamine (VII). The dehydration of (VII) by means of HCl in refluxing ethanol affords 3,3-bis(3-fluorophenyl)-2-propenamine (VIII), which is finally reduced with H2 over Pd/C in ethanol.
| 【1】 Barmore, R.M.; DelMar, E.G.; Balandrin, M.F.; VanWagenen, B.C.; Artman, L.D.; Mueller, A.L.; Moe, S.T. (NPS Pharmaceuticals, Inc.); Cpds. active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases. US 6071970 . |
| 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) | 35077 | bis(3-fluorophenyl)methanone | 345-70-0 | C13H8F2O | 详情 | 详情 |
| (II) | 10045 | Diethyl cyanomethylphosphonate | 2537-48-6 | C6H12NO3P | 详情 | 详情 |
| (III) | 35078 | 3,3-bis(3-fluorophenyl)acrylonitrile | C15H9F2N | 详情 | 详情 | |
| (IV) | 35079 | 3,3-bis(3-fluorophenyl)propanenitrile | C15H11F2N | 详情 | 详情 | |
| (V) | 37210 | acetonitrile | 75-05-8 | C2H3N | 详情 | 详情 |
| (VI) | 37211 | 3,3-bis(3-fluorophenyl)-3-hydroxypropanenitrile | C15H11F2NO | 详情 | 详情 | |
| (VII) | 37212 | 3-amino-1,1-bis(3-fluorophenyl)-1-propanol | C15H15F2NO | 详情 | 详情 | |
| (VIII) | 37213 | 3,3-bis(3-fluorophenyl)-2-propen-1-amine; 3,3-bis(3-fluorophenyl)-2-propenylamine | C15H13F2N | 详情 | 详情 |