Difloxacin hydrochloride, A-56619, ABBOTT-56619
盐酸二氟沙星 双氟沙星 Chemical Name: 1-(4-Fluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(4-methyl-1-piperazinyl)quinoline-3-carboxylic acid hydrochloride
CAS No. 91296-86-5, 98106-17-3 (free base)
项目整合开发状态: Phase II
项目研究机构: Abbott (Originator), Solvay (Licensee)
合成路线:Condensation of 2,4-dichoro-5-fluoroacetophenone (I) with diethyicarbonate (II) in the presence of sodium hydride gives ethyl 2,4-dichloro-5-fluorobenzoylacetate (III).The condensation of (III) with triethylorthoformate in reftuxing acetic anhydride yields ethyl 2-(2,4-dichloro-5-fluornbenzoyl)-3-ethoxyacrylate (IV),which is treated with p-fluoroaniline in methylene chloride to yield ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(p-fluoroanilino)acrylate (V).Cyclization of (V) with sodium hydride in tetrahydrofuran followed by hydrolysis yields 7-chloro-1-(p-fluorophenyl)-8 fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (VI).Condensation of (VI) with N-methylpiperazine in 1-methyl-2-pyrrolidinone followed by treatment with hydrochloric acid yields A-56619.
📌 参考资料/链接：
参考文献标题:Abbott-56619
文献作者:Granneman,G.R.; Chu,D.T.W.; Fernandes,P.B.
参考来源:Drugs Fut 1985,10(7),543
📄 详细内容
合成路线:Condensation of 2,4-dichoro-5-fluoroacetophenone (I) with diethyicarbonate (II) in the presence of sodium hydride gives ethyl 2,4-dichloro-5-fluorobenzoylacetate (III).The condensation of (III) with triethylorthoformate in reftuxing acetic anhydride yields ethyl 2-(2,4-dichloro-5-fluornbenzoyl)-3-ethoxyacrylate (IV),which is treated with p-fluoroaniline in methylene chloride to yield ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(p-fluoroanilino)acrylate (V).Cyclization of (V) with sodium hydride in tetrahydrofuran followed by hydrolysis yields 7-chloro-1-(p-fluorophenyl)-8 fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (VI).Condensation of (VI) with N-methylpiperazine in 1-methyl-2-pyrrolidinone followed by treatment with hydrochloric acid yields A-56619.
合成路线:Condensation of 7-chloro-1-(p-fluorophenyl)-6-fluoro-1,4-dihydro-4-oxoquinoline-3 carboxylic acid (I) with N-carboethoxypiperazine (II) in hot 1-methyl-2-pyrrolidinone yields 7-(4-carboethoxypiperazinyl)-1-(p-fluorophenyl)-6-fluoro-1,4-dihydro-4 oxoquinoline-3-carboxylic acid (III).Hydrolysis of (III) with aqueous sodium hydroxide in ethanol followed by treatment with dilute hydrochloric acid gives A-56620.
参考文献标题:A-56619 and A-56620: Synthesis and antibacterial activities of the novel aryl-fluoro-quinolones and their analogs
文献作者:Clairbone,A.K.; Pihuleac,E.; Nordeen,C.; Fernandes,P.B.; Pernet,A.; Chu,D.T.W.; O'Donell,T.J.
参考来源:24th Intersci Conf Antimicrob Agents Chemother (Oct 8-10,Washington,D.C) 1984,Abs 72
产品链接: CAS No. 91296-86-5›› 产品链接: CAS No.98106-17-3››