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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information