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【结 构 式】 
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【分子编号】28825 【品名】sodium 2-[(1-methyl-3-pyrrolidinyl)oxy]nicotinate 【CA登记号】 |
【 分 子 式 】C11H13N2NaO3 【 分 子 量 】244.225668 【元素组成】C 54.1% H 5.37% N 11.47% Na 9.41% O 19.65% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of 3-hydroxy-1-methylpyrrolidine (I) with 2-chloronicotinic acid (II) by means of NaH in DMSO gives sodium 2-(1-methylpyrrolidin-3-yloxy)pyridine-3-carboxylate (III), which is then cyclized by a treatment with dry HCl in chloroform followed by a reaction with triphenylphosphine and CCl4 yielding finally 2-(2-chloroethyl)-4-methyl-3,4-dihydropyrido[3,2-f]-1,4-oxazepin-5(2H)-one (IV). The reaction of (IV) with P2S5 and K2S in refluxing toluene affords the corresponding thione (V), which is finally treated with 40% aqueous dimethylamine in ethanol at 100 C in a pressure vessel, and with fumaric acid (VI) in methanol.
| 【1】 Cale, A.D. Jr.; Franko, B.V.; Leonard, C.A. (A.H. Robins Co. Inc.); Fused aromatic oxazepinones and sulphur analogues thereof and their preparation and use in counteracting histamine. EP 0107930; ES 8607956; ES 8802574; US 4592866; US 4604388 . |
| 【2】 Pento, J.T.; Castaner, R.M.; Serradell, M.N.; Castaner, J.; AHR-11325. Drugs Fut 1987, 12, 10, 924. |
| 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) | 28823 | 1-methyl-3-pyrrolidinol | 13220-33-2 | C5H11NO | 详情 | 详情 |
| (II) | 28824 | 2-Chloropyridine-3-carboxylic acid; 2-Chloronicotinic acid | 2942-59-8 | C6H4ClNO2 | 详情 | 详情 |
| (III) | 28825 | sodium 2-[(1-methyl-3-pyrrolidinyl)oxy]nicotinate | C11H13N2NaO3 | 详情 | 详情 | |
| (IV) | 28826 | 2-(2-chloroethyl)-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one | C11H13ClN2O2 | 详情 | 详情 | |
| (V) | 28827 | 2-(2-chloroethyl)-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepine-5(2H)-thione | C11H13ClN2OS | 详情 | 详情 | |
| (VI) | 23808 | Fumaric acid; (E)-2-butenedioic acid | 110-17-8 | C4H4O4 | 详情 | 详情 |