|
【结 构 式】 
|
【药物名称】 【化学名称】1-(2-Adamantyl)-1-(4-fluorophenyl)-1-(perhydropyrrolizin-7a-yl)methanol hydrochloride 【CA登记号】152530-37-5, 152530-36-4 (free base) 【 分 子 式 】C24H33ClFNO 【 分 子 量 】405.98811 |
【开发单位】Sanwa (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Anti-Influenza A Virus Drugs, Anti-Influenza Virus Drugs, Antiviral Drugs |
合成路线1
The bicyclic nitrile (III) was prepared by reaction of 1,7-dichloroheptan-4-one (I) with 2-aminoisobutyronitrile (II) in the presence of methanolic ammonia (1). Addition of 2-adamantyllithium (IV) to nitrile (III) in Et2O at -50 C furnished ketone (V). Subsequent addition of 4-fluorophenylmagnesium bromide (VI) to ketone (V) in cold THF provided the desired carbinol, which was isolated as the corresponding hydrochloride salt by lyophilization of its solution in aqueous HCl.
| 【1】 Oka, M.; et al.; Synthesis and anti-influenza virus activity of tricyclic compounds with a unique amine moiety. Chem Pharm Bull 2001, 49, 4, 379. |
| 【2】 Kurono, M.; Baba, Y.; Oka, M.; Honda, N.; Matsumoto, Y.; Kakigami, T.; Iwata, N.; Ishiwata, Y.; Ohtuka, T.; Mitani, T.; Sawai, K. (Sanwa Kagaku Kenkyusho Co., Ltd.); Antivirally active N-cycloalkyl alkanol cpds.. EP 0558321; JP 1994048997 . |
| 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) | 19913 | 1,7-dichloro-4-heptanone | 40624-07-5 | C7H12Cl2O | 详情 | 详情 |
| (II) | 18745 | 2-amino-2-methylpropanenitrile | 19355-69-2 | C4H8N2 | 详情 | 详情 |
| (III) | 51398 | tetrahydro-1H-pyrrolizine-7a(5H)-carbonitrile | C8H12N2 | 详情 | 详情 | |
| (IV) | 51399 | 2-adamantyllithium | C10H15Li | 详情 | 详情 | |
| (V) | 51400 | 2-adamantyl[tetrahydro-1H-pyrrolizin-7(5H)-yl]methanone | C18H27NO | 详情 | 详情 | |
| (VI) | 13643 | 4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide | 352-13-6 | C6H4BrFMg | 详情 | 详情 |