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【结 构 式】 
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【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 |