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【结 构 式】 
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【药物名称】RTI-7527-33 【化学名称】exo-5-(7-Azabicyclo[2.2.1]hept-2-yl)-2-chloropyridin-3-amine hydrochloride 【CA登记号】426460-45-9 (free base) 【 分 子 式 】C11H15Cl2N3 【 分 子 量 】260.1683 |
【开发单位】Research Triangle Institute (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Nicotinic Receptor Agonists, Nicotinic Receptor Antagonists |
合成路线1
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 |