O-[(2R,3R,4S,5R)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4-fluoro-5-methoxytetrahydro-3-furanyl] S-methyl carbonodithioate -Drug Synthesis Database

【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.

参考文献中间体

合成目标

【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	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