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【结 构 式】 
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【分子编号】32332 【品名】(3S,4R)-1-azabicyclo[2.2.1]hept-3-yl benzoate 【CA登记号】 |
【 分 子 式 】C13H15NO2 【 分 子 量 】217.26764 【元素组成】C 71.87% H 6.96% N 6.45% O 14.73% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 2,3-dichloropyrazine (I) with hexanethiol (II) by means of NaH in DMF/THF gives 2-chloro-3-(hexylsulfanyl)pyrazine (III), which is condensed with rac-exo-1-azabicyclo[2.2.1]heptan-3-ol (IV) by means of NaH in THF afforing the target compound as a racemic mixture that is submitted to optical resolution with tartaric acid. The intermediate -exo-1-azabicyclo[2.2.1]heptan-3-ol (IV) has been obtained as follows: The reduction of 1-azabicyclo[2.2.1]heptan-3-one (V) with H2 over PtO2in ethanol gives the corresponding endo-alcohol (VI), which is esterified under Mitsunobu conditions (PPh3, diisopropyl azodicarboxylate (DIAD) and benzoyl chloride) yielding the exo-benzoate (VII). The hydrolysis of (VII) with sodium methoxide in methanol affords the target exo-alcohol (IV).
| 【1】 Abou-Gharbia, M.; Tokolics, J.; Stein, P.; Moyer, J.A.; Husbands, G.M.; Tasse, R.P.; Sabb, A.L.; Boast, C.A.; Discovery of a highly potent, functionally-selective muscarinic M1 agonist, WAY-132983 using rational drug design and receptor modelling. Bioorg Med Chem Lett 1999, 9, 14, 1895. |
| 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) | 32326 | 2,3-dichloropyrazine | 4858-85-9 | C4H2Cl2N2 | 详情 | 详情 |
| (II) | 32327 | hexylhydrosulfide; 1-hexanethiol | 111-31-9 | C6H14S | 详情 | 详情 |
| (III) | 32328 | 2-chloro-3-(hexylsulfanyl)pyrazine; 3-chloro-2-pyrazinyl hexyl sulfide | C10H15ClN2S | 详情 | 详情 | |
| (IV) | 32329 | (3S,4R)-1-azabicyclo[2.2.1]heptan-3-ol | C6H11NO | 详情 | 详情 | |
| (V) | 32330 | (4R)-1-azabicyclo[2.2.1]heptan-3-one | C6H9NO | 详情 | 详情 | |
| (VI) | 32331 | (3R,4R)-1-azabicyclo[2.2.1]heptan-3-ol | C6H11NO | 详情 | 详情 | |
| (VII) | 32332 | (3S,4R)-1-azabicyclo[2.2.1]hept-3-yl benzoate | C13H15NO2 | 详情 | 详情 |