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【结 构 式】

【药物名称】

【化学名称】(2R*,3R*,3aS*,5aR*,10R*,10aR*)-N-(3,4-Dichlorophenyl)-10-hydroxy-4-oxo-2-phenyl-2,3,3a,4,5a,10-hexahydrofuro[2,3-c]indeno[1,2-b]furan-3-carboxamide

【CA登记号】261157-64-6 (undefined stereochem.)

【 分 子 式 】C26H19Cl2NO5

【 分 子 量 】496.35103

【开发单位】Cubist (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Aminoacyl-tRNA Synthetase Inhibitors

合成路线1

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.

1 Hill, J.M.; Oliver, N.; Yu, X.; Wang, Z.; Finn, J.; Silverman, J.; Gallant, P.; Wendler, P.; Keith, D.; Synthesis and activity of spirocyclic tetrahydrofurans as inhibitors of phenylalanine tRNA synthetase. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1707.
2 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Condensed imidazolidinones as tRNA synthetase inhibitors. WO 0018772 .
3 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Tetracyclic heterocycles as antimicrobial agents. US 6153645; WO 0017206 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 53530 1,3-Diketohydrindene; 1,3-Indandione; 1,3-Indanedione 606-23-5 C9H6O2 详情 详情
(II) 23540 Phenol 108-95-2 C6H6O 详情 详情
(III) 53531 2-Benzylidene-1,3-indandione n/a C16H10O2 详情 详情
(IV) 53532   n/a C16H10O3 详情 详情
(V) 53533 1-(3,4-dichlorophenyl)-1H-pyrrole-2,5-dione 19844-27-0 C10H5Cl2NO2 详情 详情
(VI) 23629 3,4-dichloroaniline 95-76-1 C6H5Cl2N 详情 详情
(VII) 11182 2,5-Furandione; Maleic anhydride 108-31-6 C4H2O3 详情 详情
(VIII) 53598   n/a C26H15Cl2NO5 详情 详情
Extended Information