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【结 构 式】 
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【分子编号】40518 【品名】2-methyl 8-(2,2,2-trichloroethyl) (1R,2S,3S,5R)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate 【CA登记号】 |
【 分 子 式 】C19H22Cl3NO4 【 分 子 量 】434.74612 【元素组成】C 52.49% H 5.1% Cl 24.46% N 3.22% O 14.72% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of anhydroecgonine methyl ester (I) with 4-methylphenylmagnesium bromide (II) in ethyl ether gives 3beta-(4-methylphenyl)tropane-2beta-carboxylic acid methyl ester (III), which is demethylated by reaction with 2,2,2-trichloroethyl chloroformate (IV) yielding the carbamate (V), followed by reduction with Zn/AcOH to afford the nortropane derivative (VI). The alkylation of (VI) with the tributylstannane (VII), TEA and iodine in ethanol provides the adduct (VIII), which is finally brominated with NBS in THF.
| 【1】 Clarke, R.L.; et al.; Compounds affecting the central nervous system. 4. 3beta-Phenyltropane-2-carboxylic esters and analogs. J Med Chem 1973, 16, 1, 1260-67. |
| 【2】 Carroll, F.I.; Gao, Y.; Rahman, M.A.; Abraham, P.; Parham, K.; Lewin, A.H.; Boja, J.W.; Kuhar, M.J.; Synthesis, ligand binding, QSAR, and CoMFA study of 3beta-(p-substitutedphenyl)tropane-2beta-carboxylic acid methyl esters. J Med Chem 1991, 34, 9, 2719. |
| 【3】 Helfenbein, J.; et al.; Synthesis of (E)-N-(3-bromoprop-2-enyl)-2 beta-carbomethoxy-3 beta-(4 '-tolyl) nortropane (PE2Br) and radiolabelling of [Br-76]PE2Br: A potential ligand for exploration of the dopamine transporter by PET. J Label Compd Radiopharm 1999, 42, 6, 581. |
| 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) | 40516 | methyl (1R,5R)-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) | 40517 | methyl (1R,2S,3S,5R)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C17H23NO2 | 详情 | 详情 | |
| (IV) | 13664 | 1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate | 17341-93-4 | C3H2Cl4O2 | 详情 | 详情 |
| (V) | 40518 | 2-methyl 8-(2,2,2-trichloroethyl) (1R,2S,3S,5R)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate | C19H22Cl3NO4 | 详情 | 详情 | |
| (VI) | 40519 | methyl (1R,2S,3S,5R)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C16H21NO2 | 详情 | 详情 | |
| (VII) | 40520 | tributyl[(E)-3-chloro-2-propenyl]stannane | C15H31ClSn | 详情 | 详情 | |
| (VIII) | 40521 | methyl (1R,2S,3S,5R)-3-(4-methylphenyl)-8-[(E)-3-(tributylstannyl)-1-propenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate | C31H51NO2Sn | 详情 | 详情 |