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【结 构 式】 
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【分子编号】16428 【品名】methyl 5-[(1R,4S)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-en-2-yl]-2-pyridinyl ether; (1R,4S)-2-(6-methoxy-3-pyridinyl)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-ene 【CA登记号】 |
【 分 子 式 】C19H20N2O3S 【 分 子 量 】356.44548 【元素组成】C 64.02% H 5.66% N 7.86% O 13.47% S 9% |
合成路线1
该中间体在本合成路线中的序号：rac-(LXII)15) Natsume's approach to epibatidine was to construct the basic skeleton of (I) by condensation of N-protected 7-azabicyclo[2.2.1]heptan-2-one with 5-lithio-2-chloropyridine, which was similar to Fletcher's synthesis. However, the azabicycloheptanone (LX) was derived from the Diels-Alder adduct (LIX) of 1-(p-toluenesulfonyl)pyrrole and dimethyl acetylenedicarboxylate through a standard sequence of reactions. Reaction of (LX) with 5-lithio-2-methoxypyridine gave (LXI), which was dehydrated to (LXII) with Burgess reagent. Catalytic hydrogenation of (LXII) over palladium-on-charcoal in 2-propanol/water (12:1) containing 1% HCl afforded (LXIII) and (LXIV) in 22% and 72% yields, respectively. Treatment of (LXIV) with POCl3/DMF obtained (LXV) in 70% yield.
| 【1】 Bai, D.; Xu, R.; Zhu, X.; Epibatidine. Drugs Fut 1997, 22, 11, 1210. |
| 【2】 Okabe, K.; Natsume, M.; Total synthesis of a frog poison, (±)-epibatidine, a potent non-opioid analgesic. Chem Pharm Bull 1994, 42, 7, 1432-6. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| rac(LXIV) | 16395 | (1R,2R,4S)-2-(6-methoxy-3-pyridinyl)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]heptane; methyl 5-[(1R,2R,4S)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-yl]-2-pyridinyl ether | C19H22N2O3S | 详情 | 详情 | |
| rac-(LIX) | 16425 | dimethyl (1R,4S)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-ene-2,3-dicarboxylate | C17H19NO6S | 详情 | 详情 | |
| rac-(LX) | 16426 | (1R,4S)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]heptan-2-one | C13H15NO3S | 详情 | 详情 | |
| rac-(LXI) | 16427 | (1R,2S,4S)-2-(6-methoxy-3-pyridinyl)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]heptan-2-ol | C19H22N2O4S | 详情 | 详情 | |
| rac-(LXII) | 16428 | methyl 5-[(1R,4S)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-en-2-yl]-2-pyridinyl ether; (1R,4S)-2-(6-methoxy-3-pyridinyl)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-ene | C19H20N2O3S | 详情 | 详情 | |
| rac-(LXIII) | 16429 | (1R,2S,4S)-2-(6-methoxy-3-pyridinyl)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]heptane; methyl 5-[(1R,2S,4S)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-yl]-2-pyridinyl ether | C19H22N2O3S | 详情 | 详情 | |
| rac-(LXV) | 16431 | (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]heptane | C18H19ClN2O2S | 详情 | 详情 |