CB-126229
Chemical Name: (3'R*,3'aR*,6'aS*)-5'-(3,4-Dichlorophenyl)-3'-phenylspiro[indane-2,1'-perhydrofuro[3,4-c]pyrrole]-1,3,4',6'-tetraone
CAS No. 262847-89-2, 262847-99-4 (undefined stereochem.)
项目整合开发状态: Biological Testing
项目研究机构: Cubist (Originator)
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords the title product as a mixture of two diastereomeric racemates that are separated by column chromatography.
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords the title product as a mixture of two diastereomeric racemates that are separated by column chromatography.
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords a mixture of two diastereomeric racemates from which the desired isomer (VIII) is separated by column chromatography (1-3).Finally,(VIII) is reduced with NaBH4 in methanol to provide a diastereomeric mixture from which the title product is separated by chromatography.
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (III),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords a mixture of two diastereomeric racemates from which the desired isomer (VIII) is separated by column chromatography (1-3).Finally,(VIII) is reduced with NaBH4 in methanol to provide a diastereomeric mixture from which the title product is separated by chromatography.
📌 参考资料/链接：
参考文献标题:Condensed imidazolidinones as tRNA synthetase inhibitors
文献作者:Wang,Z.; Hill,J.; Finn,J.; Yu,X.Y.; Keith,D.; Gallant,P.; Wendler,P.(Cubist Pharmaceuticals,Inc.)
参考来源:WO 0018772
📄 详细内容
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords the title product as a mixture of two diastereomeric racemates that are separated by column chromatography.
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords the title product as a mixture of two diastereomeric racemates that are separated by column chromatography.
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords a mixture of two diastereomeric racemates from which the desired isomer (VIII) is separated by column chromatography (1-3).Finally,(VIII) is reduced with NaBH4 in methanol to provide a diastereomeric mixture from which the title product is separated by chromatography.
合成路线:The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (III),which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV).The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords a mixture of two diastereomeric racemates from which the desired isomer (VIII) is separated by column chromatography (1-3).Finally,(VIII) is reduced with NaBH4 in methanol to provide a diastereomeric mixture from which the title product is separated by chromatography.
参考文献标题:Synthesis and activity of spirocyclic tetrahydrofurans as inhibitors of phenylalanine tRNA synthetase
文献作者:Hill,J.M.; Oliver,N.; Yu,X.; Wang,Z.; Finn,J.; Silverman,J.; Gallant,P.; Wendler,P.; Keith,D.
参考来源:41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001,Chicago) 2001,Abst F-1707