A-70826
Chemical Name: (?-1-(2,4-Difluorophenyl)-6-fluoro-7-[3-(L-norvalyl-L-norvalylamino)pyrrolidin-1-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid hydrochloride
CAS No. 129670-72-0 (free base, non-specified stereoch.), 129671-30-3 (undefined stereoch.)
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:Treatment of ethyl 2,6-dichloro-5-fluoronicotinylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with 2,4-difluoroaniline in methylene chloride at room temperature gives the enaminoketo ester derivative (II).Cyclization of (II) with sodium hydride in THF gives ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (III).Hydrolysis of (III) with hydrochloric acid yields 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (IV).Condensation of (IV) with 3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidine (V) in pyridine yields 7-(3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidin-1-yl)- 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (VI).Hydrolysis of (VI) in trifluoroacetic acid gives A-70826.
📌 参考资料/链接：
参考文献标题:Synthesis and biological properties of A-70826: A prodrug of tosufloxacin
文献作者:Chu,D.T.W.; Pernet,A.G.; Plattner,J.J.; Hallas,R.; Shipkowitz,N.; Marsh,K.C.
参考来源:31st Intersci Conf Antimicrob Agents Chemother (Sept 29-Oct 2,Chicago) 1991,Abst 1440
📄 详细内容
合成路线:Treatment of ethyl 2,6-dichloro-5-fluoronicotinylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with 2,4-difluoroaniline in methylene chloride at room temperature gives the enaminoketo ester derivative (II).Cyclization of (II) with sodium hydride in THF gives ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (III).Hydrolysis of (III) with hydrochloric acid yields 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (IV).Condensation of (IV) with 3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidine (V) in pyridine yields 7-(3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidin-1-yl)- 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (VI).Hydrolysis of (VI) in trifluoroacetic acid gives A-70826.
参考文献标题:A-70826
文献作者:Chu,D.T.W.
参考来源:Drugs Fut 1992,17(3),179