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【结 构 式】 
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【分子编号】14091 【品名】4-Oxo-1-phenoxy-4H-quinolizine-3-carboxylic acid 【CA登记号】 |
【 分 子 式 】C16H11NO4 【 分 子 量 】281.26768 【元素组成】C 68.32% H 3.94% N 4.98% O 22.75% |
合成路线1
该中间体在本合成路线中的序号：(V)Reaction of 2-phenoxymethylpyridine (I) with diethyl ethoxymethylenemalonate (II) and n-butyllithium in THF gives ethyl 3-ethoxy-2-(ethoxycarbonyl)-4-phenoxy-4-(2-pyridyl)butyrate (III), which is cyclized to ethyl 4-oxo-1-phenoxy-4H-quinolizine-3-carboxylate (IV) by heating at 250 C in a mixture of diphenyl and diphenyl ether. Ester hydrolysis of (IV) with sodium hydroxide in methanol yields 4-oxo-1-phenoxy-4H-quinolizine-3-carboxylic acid (V), which is converted to 4-oxo-1-phenoxy-N-(1H-tetrazol-5-yl)-4H-quinolizine-3-carboxamide (VII) on treatment with carbonyldiimidazole and 5-amino-1H-tetrazole (VI) in DMF. Finally, the sodium salt of (VII) is formed by means of sodium hydroxide.
| 【1】 Kitaura, Y.; Oku, T.; Hirai, H.; Yamamoto, T.; Hashimoto, M. (Fujisawa Pharmaceutical Co., Ltd.); Quinolizinone cpd., processes for preparation thereof and pharmaceutical compsns. comprising the same. AU 8547341; EP 0157346; ES 8609321; JP 1985222482; JP 1987077385; JP 1988284174; JP 1989193268; JP 1990015029; US 4650804; US 4698349 . |
| 【2】 Kitamura, S.; Okamoto, Y.; Tada, T.; Momonaga, M. (Fujisawa Pharmaceutical Co., Ltd.); Crystalline monohydrate of sodium N-(1H-tetrazol-5-yl)-1-phenoxy-4H-quinolizin-4-one-3-carboxamide. EP 0301465; JP 1989104073 . |
| 【3】 Castaner, J.; Prous, J.; Mealy, N.; Quinotolast Sodium. Drugs Fut 1994, 19, 2, 118. |
| 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) | 14087 | Phenyl 2-pyridinylmethyl ether; 2-(Phenoxymethyl)pyridine | C12H11NO | 详情 | 详情 | |
| (II) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (III) | 14089 | diethyl 2-[1-ethoxy-2-phenoxy-2-(2-pyridinyl)ethyl]malonate | C22H27NO6 | 详情 | 详情 | |
| (IV) | 14090 | ethyl 4-oxo-1-phenoxy-4H-quinolizine-3-carboxylate | C18H15NO4 | 详情 | 详情 | |
| (V) | 14091 | 4-Oxo-1-phenoxy-4H-quinolizine-3-carboxylic acid | C16H11NO4 | 详情 | 详情 | |
| (VI) | 14092 | 1H-1,2,3,4-Tetraazol-5-ylamine; 1H-Tetrazol-5-amine; 1H-1,2,3,4-Tetraazol-5-amine; 5-Amino-1H-1,2,3,4-tetrazole | 4418-61-5 | CH3N5 | 详情 | 详情 |
| (VII) | 14093 | 4-Oxo-1-phenoxy-N-(1H-1,2,3,4-tetraazol-5-yl)-4H-quinolizine-3-carboxamide | C17H12N6O3 | 详情 | 详情 |