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【结 构 式】 
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【药物名称】RTI-362 【化学名称】3alpha-(4-Methylphenyl)nortropane-2beta-carboxylic acid methyl ester 【CA登记号】 【 分 子 式 】C16H21NO2 【 分 子 量 】259.35127 |
【开发单位】National Institute on Drug Abuse (Originator), Research Triangle Institute (Originator) 【药理作用】Treatment of Cocaine Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, Norepinephrine Transporter (NET) Inhibitors |
合成路线1
Treatment of azabicyclo[3.2.1]octene derivative (I) with lithiated compound (II) in THF followed by quenching with trifluoroacetic acid yields tropane (III), whose oxadiazole group is converted into a methyl ester by treatment with nickel boride (Ni2B) and HCl in refluxing methanol to provide the 2-beta,3-alpha stereoisomer (IV). Finally, the desired nortropane compound is obtained by refluxing tropane (IV) with alpha-chloroethyl chloroformate (ACE-Cl) in dichloromethane followed by solvolysis with methanol.
| 【1】 Kuhar, M.J.; Blough, B.E.; Holmquist, C.R.; Carroll, F.I.; Abraham, P.; 3alpha-(4-Substituted phenyl) mortropane-2beta-carboxylic acid methyl esters show selective binding at the norepinephrine transporter. Bioorg Med Chem Lett 2000, 10, 21, 2445. |
| 【2】 Holmquist, C.R.; et al.; 3alpha-(4'-Substituted phenyl)tropane-2beta-carboxylic acid methyl esters: Novel ligands with high affinity and selectivity at the dopamine transporter. J Med Chem 1996, 39, 21, 4139. |
| 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) | 47190 | (1R,5S)-8-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-8-azabicyclo[3.2.1]oct-2-ene | C11H15N3O | 详情 | 详情 | |
| (II) | 29629 | (4-methylphenyl)lithium | C7H7Li | 详情 | 详情 | |
| (III) | 47191 | (1R,2R,3R,5S)-8-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane | C18H23N3O | 详情 | 详情 | |
| (IV) | 47192 | methyl (1R,2S,3R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C17H23NO2 | 详情 | 详情 |