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【结 构 式】 
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【分子编号】17693 【品名】[(2R,3R,4S,5R)-3-(acetoxy)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl benzoate 【CA登记号】 |
【 分 子 式 】C19H16ClFN4O5 【 分 子 量 】434.8111032 【元素组成】C 52.48% H 3.71% Cl 8.15% F 4.37% N 12.89% O 18.4% |
合成路线1
该中间体在本合成路线中的序号：(VI)The TLC monitored reaction of 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose (III) with 30% HBr in acetic acid gives the bromosugar (IV), which is condensed with 6-chloropurine (V) in refluxing dichloromethane, yielding the chloropurine derivative (VI). The reaction of (VI) with methanolic NH3 at 100 C in a steel bomb affords 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (VII), which is selectively silylated with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole in DMF, giving the 5'-O-silyl derivative (VIII). The reaction of (VIII) with phenyl chlorothioformate by means of dimethylaminopyridine in DMF yields the thiocarbonate (IX), which is reduced with tributyltin hydride and AIBN in hot toluene, affording 9-[2,3-dideoxy-2-fluoro-5-O-(tert-butyldimethylsilyl)-beta-D-arabinofuranosyl]adenine (X). Finally, this compound is desilylated with tetrabutylammonium fluoride in THF.
| 【1】 Castaner, J.; Graul, A.; Silvestre, J.S.; Lodenosine. Drugs Fut 1998, 23, 11, 1176-1189. |
| 【2】 Ford, H. Jr.; Driscoll, J.S.; Aoki, S.; Kelley, J.A.; Johns, D.G.; Roth, J.S.; Tseng, C.K.-H.; Broder, S.; Marquez, V.E.; Mitsuya, H.; Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV. J Med Chem 1990, 33, 3, 978-85. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 17690 | [(2R,3R,4S)-5-(acetoxy)-4-fluoro-3-[(1-hydroxyvinyl)oxy]tetrahydro-2-furanyl]methyl benzoate | C16H17FO7 | 详情 | 详情 | |
| (IV) | 17691 | [(2R,3R,4S)-3-(acetoxy)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl benzoate | C14H14BrFO5 | 详情 | 详情 | |
| (V) | 17692 | 6-Chloropurine; 6-chloro-9H-purine | 87-42-3 | C5H3ClN4 | 详情 | 详情 |
| (VI) | 17693 | [(2R,3R,4S,5R)-3-(acetoxy)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl benzoate | C19H16ClFN4O5 | 详情 | 详情 | |
| (VII) | 17694 | (2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydro-3-furanol | C10H12FN5O3 | 详情 | 详情 | |
| (VIII) | 17695 | (2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-fluorotetrahydro-3-furanol | C16H26FN5O3Si | 详情 | 详情 | |
| (IX) | 17696 | O-[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-fluorotetrahydro-3-furanyl] O-phenyl carbonothioate | C23H30FN5O4SSi | 详情 | 详情 | |
| (X) | 17697 | 9-[(2R,3S,5S)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluorotetrahydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,3S,5S)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluorotetrahydro-2-furanyl]-9H-purin-6-amine | C16H26FN5O2Si | 详情 | 详情 |