|
【结 构 式】 
|
【药物名称】Galocitabine, Ro-09-1390 【化学名称】5'-Deoxy-5-fluoro-N4-(3,4,5-trimethoxybenzoyl)cytidine 【CA登记号】124012-42-6 【 分 子 式 】C19H22FN3O8 【 分 子 量 】439.40089 |
【开发单位】Roche (Originator) 【药理作用】Oncolytic Drugs, Antimetabolites, Thymidylate Synthase Inhibitors |
合成路线1
The silylation of 5'-deoxy-5-fluorocytidine (I) with tert-butyldimethylsilyl chloride and imidazole in DMF gives 2'-O,3'-O-bis(tert-butyldimethylsilyl)-5'-deoxy-5-fluorocytidine (II), which is acylated with 3,4,5-trimethoxybenzoyl chloride (III) and dimethylaminopyridine in dichloromethane to afford 2'-O,3'-O-bis(tert-butyldimethylsilyl)-5'-deoxy-5-fluoro-N4-(3,4,5-trimethoxybenzoyl)cytidine (IV). Finally, this compound is deprotected with tetrabutylammonium fluoride in THF.
| 【1】 Fujiu, M.; Ishitsuka, H.; Miwa, M.; Umeda, I.; Yokose, K. (F. Hoffmann-La Roche AG); Fluorocytidine derivs., their preparation and medical preparations containing them. AU 8825168; EP 0316704; JP 1989153696; US 4966891 . |
| 【2】 Hoshi, A.; Castaner, J.; Galocitabine. Drugs Fut 1993, 18, 4, 316. |
| 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) | 13569 | 4-Amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydro-2-furanyl]-5-fluoro-2(1H)-pyrimidinone | C9H12FN3O4 | 详情 | 详情 | |
| (II) | 13570 | 4-Amino-1-((2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyltetrahydro-2-furanyl)-5-fluoro-2(1H)-pyrimidinone | C21H40FN3O4Si2 | 详情 | 详情 | |
| (III) | 13571 | 3,4,5Ttrimethoxybenzoyl chloride | 4521-61-3 | C10H11ClO4 | 详情 | 详情 |
| (IV) | 13572 | N-[1-((2R,3R,4R,5R)-3,4-Bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyltetrahydro-2-furanyl)-5-fluoro-2-oxo-1,2-dihydro-4-pyrimidinyl]-3,4,5-trimethoxybenzamide | C31H50FN3O8Si2 | 详情 | 详情 |