|
【结 构 式】 
|
【分子编号】65581 【品名】3-Bromo-5-isopropoxypyridine; 3-Bromo-5-[(1-methylethyl)oxy]pyridine; 3-Bromo-5-(1-methylethoxy)pyridine; 5-Bromo-3-isopropoxypyridine; 5-Isopropoxy-3-bromopyridine 【CA登记号】212332-40-6 |
【 分 子 式 】C8H10BrNO 【 分 子 量 】216.07754 【元素组成】C 44.47% H 4.66% Br 36.98% N 6.48% O 7.4% |
合成路线1
该中间体在本合成路线中的序号：(III)Ispronicline can be synthesized as follows. The reaction of 3,5-dibromopyridine (I) with potassium isopropoxide (II) and powdered Cu in isopropanol at 140 °C gives 3-bromo-5-isopropoxypyridine (III), which is condensed with 4-penten-2(R)-ol (IV) by means of Pd(OAc)2, TOTP and TEA in acetonitrile at 140 °C to yield [2(R),4(E)]-5-(5-isopropoxypyridin-3-yl)-4-penten-2-ol (V). The treatment of (V) with Ts-Cl in pyridine affords the corresponding tosylate (VI), which is finally treated with methylamine in ethanol/water to obtain the target secondary amine (1-4). Scheme 1.
| 【1】 Caldwell, W.S., Dull, G.M., Bhatti, B.S. et al. (R.J. Reynolds Tobacco Co.). Aryl substituted olefinic amines and their use as cholinergic receptor agonists. EP 1086082, JP 2002518373, WO 9965876. |
| 【2】 Dull, M.D., Miller, C.H., Caldwell, W.S. et al. (Targacept, Inc.). Pharmaceutical compositions and methods for use. EP 1185514, JP 2003501416, US 6492399, WO 0075110. |
| 【3】 Bencherif, M. (R.J. Reynolds Tobacco Co.). Pharmaceutical compositions for the prevention and treatment of central nervous system disorders. CA 2335012, EP 1102588, US 6218383, WO 0007600. |
| 【4】 Caldwell, W.S., Dull, G.M., Bhatti, B.S. et al. (Targacept, Inc.). Compounds capable of activating cholinergic receptors. EP 1556352, JP 2006511482, US 2003125345, US 6979695, WO 2004031151. |
| 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) | 65580 | 2-Propanol Potassium salt | 6831-82-9 | C3H7KO | 详情 | 详情 |
| (III) | 65581 | 3-Bromo-5-isopropoxypyridine; 3-Bromo-5-[(1-methylethyl)oxy]pyridine; 3-Bromo-5-(1-methylethoxy)pyridine; 5-Bromo-3-isopropoxypyridine; 5-Isopropoxy-3-bromopyridine | 212332-40-6 | C8H10BrNO | 详情 | 详情 |
| (IV) | 65582 | (R )-(-)-4-Penten-2-ol | 64584-92-5 | C5H10O | 详情 | 详情 |
| (V) | 65583 | [(2R),(4E)]-5-(5-isopropoxypyridin-3-yl)-4-penten-2-ol | C13H19NO2 | 详情 | 详情 | |
| (VI) | 65584 | C20H25NO4S | 详情 | 详情 |