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【结 构 式】

【分子编号】17708

【品名】O-[(2R,3R,4S,5R)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4-fluoro-5-methoxytetrahydro-3-furanyl] S-methyl carbonodithioate

【CA登记号】

【 分 子 式 】C24H31FO4S2Si

【 分 子 量 】494.7236432

【元素组成】C 58.27% H 6.32% F 3.84% O 12.94% S 12.96% Si 5.68%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXV)

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
Extended Information