|
【结 构 式】 
|
【药物名称】 【化学名称】8-Methyl-3exo-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2exo-carboxylic acid 3-fluoropropyl ester 【CA登记号】 【 分 子 式 】C19H26FNO2 【 分 子 量 】319.42297 |
【开发单位】McLean Hospital (Originator), Natural Pharmacia (Originator) 【药理作用】Diagnostic Agents, Dopamine Transporter (DAT) Inhibitors |
合成路线1
Conjugate addition of 4-tolylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Hydrolysis of the ester function of (III) in aqueous dioxan gave the corresponding acid (IV). Treatment of (IV) with POCl3 yielded the acid chloride (V), which was condensed with 1,3-propanediol monomesylate (VI), yielding ester (VII). Finally, nucleophilic displacement of the mesylate group of (VII) with tetrabutylammonium fluoride in refluxing THF afforded the title fluoropropyl ester.
| 【1】 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049. |
| 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) | 21118 | methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate | C10H15NO2 | 详情 | 详情 | |
| (II) | 35657 | bromo(4-methylphenyl)magnesium | 4294-57-9 | C7H7BrMg | 详情 | 详情 |
| (III) | 50267 | methyl (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C17H23NO2 | 详情 | 详情 | |
| (IV) | 50268 | (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylic acid | C16H21NO2 | 详情 | 详情 | |
| (V) | 50269 | (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carbonyl chloride | C16H20ClNO | 详情 | 详情 | |
| (VI) | 50262 | 3-hydroxypropyl methanesulfonate | C4H10O4S | 详情 | 详情 | |
| (VII) | 50270 | 3-[(methylsulfonyl)oxy]propyl (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C20H29NO5S | 详情 | 详情 |