新产品编号:1016153
Chemical Name: 9-Cyclopropyl-6,8-difluoro-7-piperazino-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione methanesulfonate
项目整合开发状态: Biological Testing
项目研究机构: Abbott (Originator)
合成路线:The condensation of 2-(2,4,5-trifluorobenzoyl)acetic acid ethyl ester (I) with cyclopropyl isothiocyanate (II) by means of NaH in DMF gives the sodium salt (IIIa-b),which is methylated with methyl iodide to afford the methylsulfanyl derivative (IVa-b).The cyclization of (IVa-b) by means of NaH in THF provides the methylsulfanyl quinolone (V),which is oxidized with MCPBA to the corresponding methylsulfinyl compound (VI).The reaction of (VI) with NaSH in THF furnishes 1-cyclopropyl-6,7-difluoro-4-oxo-2-sulfanyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (VII),which is cyclized with hydroxylamine-O-sulfonic acid and NaHCO3 through the intermediate (VIII),affording the isothiazoloquinoline (IX).Finally,this compound is condensed with piperazine (X) in pyridine to give the target compound.
合成路线:The cyclization of 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropionic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid ethyl ester (III),which is oxidized with MCPBA in dichloromethane,yielding the sulfinyl derivative (IV).The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazolonaphthyridine (V),which is finally condensed with piperazine in pyridine to furnish the target compound.
合成路线:The cyclization of 2-(2,4-dichloro-3,5-difluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III),which is oxidized with MCPBA in dichloromethane,yielding the sulfinyl derivative (IV).The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V),which is finally condensed with piperazine in pyridine to furnish the target compound.
📌 参考资料/链接：
参考文献标题:Sulfonylurea signal transduction
文献作者:Aquilar-Bryan,L.; Bryan,J.; Boyd,A.E.III; et al.
参考来源:Recent Prog Horm Res 1991,47299-317
📄 详细内容
合成路线:The cyclization of 2-(2,4-dichloro-5-fluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III),which is oxidized with MCPBA in dichloromethane,yielding the sulfinyl derivative (IV).The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V),which is finally condensed with piperazine in pyridine to furnish the target compound.
合成路线:The condensation of 2-(2,4,5-trifluorobenzoyl)acetic acid ethyl ester (I) with cyclopropyl isothiocyanate (II) by means of NaH in DMF gives the sodium salt (IIIa-b),which is methylated with methyl iodide to afford the methylsulfanyl derivative (IVa-b).The cyclization of (IVa-b) by means of NaH in THF provides the methylsulfanyl quinolone (V),which is oxidized with MCPBA to the corresponding methylsulfinyl compound (VI).The reaction of (VI) with NaSH in THF furnishes 1-cyclopropyl-6,7-difluoro-4-oxo-2-sulfanyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (VII),which is cyclized with hydroxylamine-O-sulfonic acid and NaHCO3 through the intermediate (VIII),affording the isothiazoloquinoline (IX).Finally,this compound is condensed with piperazine (X) in pyridine to give the target compound.
合成路线:The cyclization of 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropionic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid ethyl ester (III),which is oxidized with MCPBA in dichloromethane,yielding the sulfinyl derivative (IV).The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazolonaphthyridine (V),which is finally condensed with piperazine in pyridine to furnish the target compound.
合成路线:The cyclization of 2-(2,4-dichloro-3,5-difluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III),which is oxidized with MCPBA in dichloromethane,yielding the sulfinyl derivative (IV).The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V),which is finally condensed with piperazine in pyridine to furnish the target compound.
参考文献标题:Isothiazoloquinolones: Antibacterial and antineoplastic agents
文献作者:Chu,D.T.W.
参考来源:Drugs Fut 1992,17(12),1101