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【结 构 式】 
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【分子编号】48049 【品名】N-[(E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl]-N-methylamine; (E)-4-(5-ethoxy-3-pyridinyl)-N-methyl-3-buten-1-amine 【CA登记号】 |
【 分 子 式 】C12H18N2O 【 分 子 量 】206.2878 【元素组成】C 69.87% H 8.79% N 13.58% O 7.76% |
合成路线1
该中间体在本合成路线中的序号：(VI)Reaction of 3,5-dibromopyridine (I) with sodium ethoxide gave 3-bromo-5-ethoxypyridine (II). Palladium-catalyzed coupling of bromopyridine (II) with 3-buten-1-ol (III) yielded the pyridinylbutenol (IV), which was further converted to tosylate (V). Displacement of the tosylate group of (V) with methylamine then gave amine (VI).
| 【1】 Caldwell, W.S.; Dull, G.M.; Miller, C.H.; [3-(5-Ethoxypyridin)yl]-alkenyl 1 amine cpds.. US 5616716 . |
| 【2】 Dull, G.M.; Dobson, G.P.; Caldwell, W.S. (R.J. Reynolds Tobacco Co.); Pharmaceutical compsns. for prevention and treatment of central nervous system disorders. WO 9740011 . |
| 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) | 48045 | 3,5-dibromopyridine | 625-92-3 | C5H3Br2N | 详情 | 详情 |
| (II) | 48046 | 3-bromo-5-ethoxypyridine; 5-bromo-3-pyridinyl ethyl ether | C7H8BrNO | 详情 | 详情 | |
| (III) | 19743 | 3-buten-1-ol | 627-27-0 | C4H8O | 详情 | 详情 |
| (IV) | 48047 | (E)-4-(5-ethoxy-3-pyridinyl)-3-buten-1-ol | C11H15NO2 | 详情 | 详情 | |
| (V) | 48048 | (E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl 4-methylbenzenesulfonate | C18H21NO4S | 详情 | 详情 | |
| (VI) | 48049 | N-[(E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl]-N-methylamine; (E)-4-(5-ethoxy-3-pyridinyl)-N-methyl-3-buten-1-amine | C12H18N2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)In a related method, 4-bromo-1-butene (VII) was reacted with methylamine to produce the secondary amine (VIII). After protection of (VIII) as the tert-butyl carbamate (IX), palladium-catalyzed coupling with 3-bromo-5-ethoxypyridine (II) furnished adduct (X). The N-Boc protecting group of (X) was then cleaved under acidic conditions to afford amine precursor (VI). The title hemigalactarate salt was finally prepared by treatment of amine (VI) with D-galactaric acid in aqueous ethanol.
| 【1】 Bane, A.J.; Dull, G.M.; Bencherif, M.; Miller, C.H.; Gatto, G.J.; TC-2559: A novel orally active ligand selective at neuronal acetylcholine receptors. Eur J Pharmacol 2000, 409, 1, 45. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 48046 | 3-bromo-5-ethoxypyridine; 5-bromo-3-pyridinyl ethyl ether | C7H8BrNO | 详情 | 详情 | |
| (VI) | 48049 | N-[(E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl]-N-methylamine; (E)-4-(5-ethoxy-3-pyridinyl)-N-methyl-3-buten-1-amine | C12H18N2O | 详情 | 详情 | |
| (VII) | 11720 | 4-Bromo-1-butene | 5162-44-7 | C4H7Br | 详情 | 详情 |
| (VIII) | 48050 | N-(3-butenyl)-N-methylamine; N-methyl-3-buten-1-amine | C5H11N | 详情 | 详情 | |
| (IX) | 48051 | tert-butyl 3-butenyl(methyl)carbamate | C10H19NO2 | 详情 | 详情 | |
| (X) | 48052 | tert-butyl (E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl(methyl)carbamate | C17H26N2O3 | 详情 | 详情 |