|
【结 构 式】 
|
【分子编号】17710 【品名】[[(2S,4S)-5-bromo-4-fluorotetrahydro-2-furanyl]methoxy](tert-butyl)diphenylsilane; [(2S,4S)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl tert-butyl(diphenyl)silyl ether 【CA登记号】 |
【 分 子 式 】C21H26BrFO2Si 【 分 子 量 】437.4241432 【元素组成】C 57.66% H 5.99% Br 18.27% F 4.34% O 7.32% Si 6.42% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)The selective silylation of 2-deoxy-2-fluoro-1-O-methyl-beta-D-arabinofuranose (XIII) with tert-butyldiphenylsilyl chloride (TBDPS-Cl) and imidazole in DMF gives the 5-O-silylated sugar (XXIV), which is treated with CS2/NaH/methyl iodide in DMF to yield compound (XXV). The reduction of (XXV) with tributyltin hydride and AIBN in refluxing toluene affords 2,3-dideoxy-2-fluoro-5-O-(tert-butyldiphenylsilyl)-beta-D-arabinofuranose (XXVI), which is treated with HBr in acetic acid to yield the bromosugar (XXVII). The condensation of (XXVII) with 6-chloropurine (V) in hot acetonitrile gives 6-chloro-9-[2,3-dideoxy-2-fluoro-5-O-(tert-butyldiphenylsilyl)-beta-D-arabinofuranosyl]purine (XXVIII), which is desilylated with tetrabutylammonium fluoride in THF, yielding 6-chloro-9-[2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl]purine (XXIX). Finally, this compound is treated with methanolic ammonia at 105 C as before.
| 【1】 Castaner, J.; Graul, A.; Silvestre, J.S.; Lodenosine. Drugs Fut 1998, 23, 11, 1176-1189. |
| 【2】 Marquez, V.E.; Siddiqui, M.A.; Driscoll, J.S.; Wysocki, R.J. Jr. (US Department of Health & Human Services); 2'-Fluorofuranosyl derivs. and methods for preparing 2'-fluoropyrimidine and 2'-fluoropurine nucleosides. US 5817799 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 17707 | (2R,3R,4S,5R)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4-fluoro-5-methoxytetrahydro-3-furanol | C22H29FO4Si | 详情 | 详情 | |
| (XXV) | 17708 | O-[(2R,3R,4S,5R)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4-fluoro-5-methoxytetrahydro-3-furanyl] S-methyl carbonodithioate | C24H31FO4S2Si | 详情 | 详情 | |
| (XXVI) | 17709 | tert-butyl(diphenyl)silyl [(2S,4S,5R)-4-fluoro-5-methoxytetrahydro-2-furanyl]methyl ether; tert-butyl[[(2S,4S,5R)-4-fluoro-5-methoxytetrahydro-2-furanyl]methoxy]diphenylsilane | C22H29FO3Si | 详情 | 详情 | |
| (XXVII) | 17710 | [[(2S,4S)-5-bromo-4-fluorotetrahydro-2-furanyl]methoxy](tert-butyl)diphenylsilane; [(2S,4S)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl tert-butyl(diphenyl)silyl ether | C21H26BrFO2Si | 详情 | 详情 | |
| (XXVIII) | 17711 | tert-butyl(diphenyl)silyl [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl ether; 9-[(2R,3S,5S)-5-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-fluorotetrahydro-2-furanyl]-6-chloro-9H-purine | C26H28ClFN4O2Si | 详情 | 详情 | |
| (XXIX) | 17712 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methanol | C10H10ClFN4O2 | 详情 | 详情 |