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【结 构 式】 
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【分子编号】16178 【品名】3-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1-methylpyridinium iodide 【CA登记号】 |
【 分 子 式 】C14H20IN3OS 【 分 子 量 】405.30289 【元素组成】C 41.49% H 4.97% I 31.31% N 10.37% O 3.95% S 7.91% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of pyridine-3-carbaldehyde (I) with KCN in acetic acid, followed by a treatment with NH4Cl in aqueous NH4OH yields 2-amino-2-(3-pyridyl)acetonitrile (II), which is cyclized to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (III) by a treatment with S2Cl2 in DMF. The reaction of (III) with sodium hexyloxide in hexanol yields 3-(hexyloxy)-4-(3-pyridyl)-1,2,5-thiadiazole (IV), which is treated with methyl iodide in acetone to afford the corresponding N-methylpyridinium salt (V). Finally, this compound is hydrogenated with NaBH4 in ethanol and salified with oxalic or L-tartaric acid in acetone or isopropanol.
| 【1】 Graul, A.; Castaner, J.; Xanomeline. Drugs Fut 1996, 21, 9, 911. |
| 【2】 Sauerberg, P.; Olesen, P.H. (Ferrosan A/S); Piperidine cpds. and their preparation and use. EP 0384288; US 5260311; US 5264444; US 5328925 . |
| 【3】 Sauerberg, P.; Olesen, P.H.; Mitch, c.H. (Novo Nordisk A/S); Heterocyclic cpds. and their preparation and use. EP 0687265; JP 1996507298; WO 9420495 . |
| 【4】 Osborne, L.M.; Shipley, L.A.; Treppendahl, S.; Petersen, T.G. (Novo Nordisk A/S); Heterocyclic chemistry. US 5834495; WO 9429303 . |
| 【5】 Sauerberg, P.; Olesen, P.H.; Nielsen, S.; et al.; Novel functional M1selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines. J Med Chem 1992, 35, 12, 2274-83. |
| 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) | 12849 | Nicotinaldehyde; 3-Pyridinecarboxaldehyde | 500-22-1 | C6H5NO | 详情 | 详情 |
| (II) | 16175 | 2-amino-2-(3-pyridinyl)acetonitrile | C7H7N3 | 详情 | 详情 | |
| (III) | 16176 | 3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine | C7H4ClN3S | 详情 | 详情 | |
| (IV) | 16177 | 3-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]pyridine; hexyl 4-(3-pyridinyl)-1,2,5-thiadiazol-3-yl ether | C13H17N3OS | 详情 | 详情 | |
| (V) | 16178 | 3-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1-methylpyridinium iodide | C14H20IN3OS | 详情 | 详情 |