Quinotolast sodium, FR-71021, FK-021
喹托司特钠 喹托司特Chemical Name: 5-[4-Oxo-1-phenoxy-4H-quinolizine-3-carboxamido)tetrazole sodium salt monohydrate; 4-Oxo-1-phenoxy-N-(1H-tetrazol-5-yl)-4H-quinolizine-3-carboxamide sodium salt monohydrate
CAS No. 121191-32-0, 101193-62-8 (anhydrous), 101193-40-2 (anhydrous free base)
项目整合开发状态: Phase III
项目研究机构: Fujisawa (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Quinolizinone cpd.,processes for preparation thereof and pharmaceutical compsns.comprising the same
文献作者:Kitaura,Y.; Oku,T.; Hirai,H.; Yamamoto,T.; Hashimoto,M.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:AU 8547341; EP 0157346; ES 8609321; JP 1985222482; JP 1987077385; JP 1988284174; JP 1989193268; JP 1990015029; US 4650804; US 4698349
📄 详细内容
合成路线: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.
参考文献标题:Crystalline monohydrate of sodium N-(1H-tetrazol-5-yl)-1-phenoxy-4H-quinolizin-4-one-3-carboxamide
文献作者:Kitamura,S.; Okamoto,Y.; Tada,T.; Momonaga,M.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0301465; JP 1989104073
合成路线: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.
参考文献标题:Quinotolast Sodium
文献作者:Castar,J.; Prous,J.; Mealy,N.
参考来源:Drugs Fut 1994,19(2),118
产品链接: CAS No.101193-62-8›› 产品链接: CAS No.101193-40-2››