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【结 构 式】 
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【分子编号】29867 【品名】tert-butyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate 【CA登记号】 |
【 分 子 式 】C11H17NO2 【 分 子 量 】195.26152 【元素组成】C 67.66% H 8.78% N 7.17% O 16.39% |
合成路线1
该中间体在本合成路线中的序号：(IV)21) A new synthesis of epibatidine has been reported: The reaction of 2-tosyl-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylic acid tert-butyl ester (I) with tributyltin hydride (II) by means of azobis(isobutyronitrile) (AIBN) in benzene gives the tin derivative (III), which by treatment with tetrabutylammonium fluoride in THF provides 7-azabicyclo[2.2.1]hept-2-ene-7-carboxylic acid tert-butyl ester (IV). The condensation of (IV) with 5-iodopyridine-2-amine (V) by means of palladium acetate/tetrabutylammonium chloride/potassium formate in hot DMF yields exo-2-(6-amino-3-pyridyl)-7-azabicyclo[2.2.1]heptane-7-carbo-xylic acid tert-butyl ester (VI), which is finally submitted to diazotization with NaNO2/HCl and treated with CuCl.
| 【1】 Abraham, P.; Brieaddy, L.E.; Carroll, F.I.; Lee, J.R.; Liang, F.; New synthesis of 7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]hept-2-ene. A key intermediate in the synthesis of epibatidine and analogs. Tetrahedron Lett 1998, 39, 30, 5321. |
| 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) | 29861 | tert-butyl (1S,4R)-2-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate | C18H23NO4S | 详情 | 详情 | |
| (II) | 29870 | butyl(dipentyl)stannane | C14H32Sn | 详情 | 详情 | |
| (III) | 29866 | tert-butyl (1R,4S)-2-[butyl(dipentyl)stannyl]-3-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]heptane-7-carboxylate | C32H55NO4SSn | 详情 | 详情 | |
| (IV) | 29867 | tert-butyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate | C11H17NO2 | 详情 | 详情 | |
| (V) | 29868 | 5-iodo-2-pyridinamine; 5-iodo-2-pyridinylamine | C5H5IN2 | 详情 | 详情 | |
| (VI) | 29869 | tert-butyl (1R,2R,4S)-2-(6-amino-3-pyridinyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate | C16H23N3O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Iodination of 2-amino-3-nitropyridine (I) using a combination of iodine and periodic acid yields 2-amino-5-iodo-3-nitropyridine (II). Sandmeyer reaction of aminopyridine (II) with sodium nitrite in concentrated HCl containing CuCl affords the chloro pyridine (III). The nitro group of (III) is then reduced to amine (IV) employing iron in ethanolic HCl. Palladium acetate-catalyzed addition of iodopyridine (IV) to N-Boc-7-azabicyclo[2.2.1]hept-2-ene (V) gives rise to the exo-adduct (VI). Finally, acidic cleavage of the Boc group of (VI) furnishes the title compound.
| 【1】 Carroll, F.I.; Lee, J.R.; Navarro, H.A.; Ma, W.; Brieaddy, L.E.; Abraham, P.; Damaj, M.I.; Martin, B.R.; Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2',3'-disubstituted 5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes: Epibatidine analogues. J Med Chem 2002, 45, 21, 4755. |
| 【2】 Carroll, F.I. (Research Triangle Institute); Cpds. and methods for promoting smoking cessation. US 6538010; WO 0237927 . |
| 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) | 62282 | 3-nitro-2-pyridinamine; 3-nitro-2-pyridinylamine | C5H5N3O2 | 详情 | 详情 | |
| (II) | 62283 | 5-iodo-3-nitro-2-pyridinamine; 5-iodo-3-nitro-2-pyridinylamine | C5H4IN3O2 | 详情 | 详情 | |
| (III) | 62284 | 2-chloro-5-iodo-3-nitropyridine | C5H2ClIN2O2 | 详情 | 详情 | |
| (IV) | 62285 | 2-chloro-5-iodo-3-pyridinylamine; 2-chloro-5-iodo-3-pyridinamine | C5H4ClIN2 | 详情 | 详情 | |
| (V) | 29867 | tert-butyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate | C11H17NO2 | 详情 | 详情 | |
| (VI) | 62286 | tert-butyl (1R,2R,4S)-2-(5-amino-6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate | C16H22ClN3O2 | 详情 | 详情 |