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【结 构 式】 
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【分子编号】17726 【品名】[(2S,4S,5S)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl 4-methylbenzoate 【CA登记号】 |
【 分 子 式 】C13H14BrFO3 【 分 子 量 】317.1547632 【元素组成】C 49.23% H 4.45% Br 25.19% F 5.99% O 15.13% |
合成路线1
该中间体在本合成路线中的序号：(XLIII)The reaction of 2,3-O-isopropylidene-D-ribofuranose (XXXV) with 4-methylbenzoyl chloride (XXXVI) by means of pyridine in butyl acetate gives 2,3-O-isopropylidene-5-O-(4-methylbenzoyl)-D-ribofuranose (XXXVII), which is methylated by means of NaH and dimethylsulfate in THF to yield the expected methyl ribofuranoside (XXXVIII). The hydrolysis of the acetonide group of (XXXVIII) with trifluoromethanesulfonic acid in acetonitrile affords 1-O-methyl-5-O-(4-methylbenzoyl)-alpha-D-ribofuranose (XXXIX), which is treated with SO2Cl2/triethylamine in butyl acetate to give the cyclic sulfate (XL). The reduction of (XL) with NaBH4 in THF yields 3-deoxy-1-O-methyl-5-O-(4-methylbenzoyl)-alpha-D-ribofuranose (XLI), which is treated with trifluoromethanesulfonic anhydride and tetrabutylammonium fluoride in dichloromethane/pyridine to afford 2,3-dideoxy-2-fluoro-1-O-methyl-alpha-D-arabinofuranose (XLII). The reaction of (XLII) with HBr in acetic acid as before gives the bromosugar (XLIII), which is condensed with 6-chloro-9-(trimethylsilyl)purine (XLIV) in dichloromethane to yield 6-chloro-9-[2,3-dideoxy-2-fluoro-5-O-(4-methylbenzoyl)-beta-D-arabinofuranosyl]purine (XLV). Finally, this compound is treated with ammonia in methanol at 90 C.
| 【1】 Castaner, J.; Graul, A.; Silvestre, J.S.; Lodenosine. Drugs Fut 1998, 23, 11, 1176-1189. |
| 【2】 Saischek, E.; Dax, K.; Braun, W.; Fuchs, F.; Saischek, G. (Chevron Research Co.); D-Xylofuranose derivs., method of preparing them, their use, and novel intermediate compounds for the method. WO 9606851 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IXL) | 17722 | [(2R,3S,4R,5S)-3,4-dihydroxy-5-methoxytetrahydro-2-furanyl]methyl 4-methylbenzoate | C14H18O6 | 详情 | 详情 | |
| (XXXV) | 17718 | (3aR,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol | C8H14O5 | 详情 | 详情 | |
| (XXXVI) | 17719 | p-Toluoyl chloride; 4-methylbenzoyl chloride | 874-60-2 | C8H7ClO | 详情 | 详情 |
| (XXXVII) | 17720 | [(3aR,4R,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl 4-methylbenzoate | C16H20O6 | 详情 | 详情 | |
| (XXXVIII) | 17721 | [(3aR,4R,6S,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl 4-methylbenzoate | C17H22O6 | 详情 | 详情 | |
| (XL) | 17723 | [(3aR,4R,6S,6aR)-6-methoxy-2,2-dioxotetrahydro-2lambda(6)-furo[3,4-d][1,3,2]dioxathiol-4-yl]methyl 4-methylbenzoate | C14H16O8S | 详情 | 详情 | |
| (XLI) | 17724 | [(2S,4R,5S)-4-hydroxy-5-methoxytetrahydro-2-furanyl]methyl 4-methylbenzoate | C14H18O5 | 详情 | 详情 | |
| (XLII) | 17725 | [(2S,4S,5S)-4-fluoro-5-methoxytetrahydro-2-furanyl]methyl 4-methylbenzoate | C14H17FO4 | 详情 | 详情 | |
| (XLIII) | 17726 | [(2S,4S,5S)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl 4-methylbenzoate | C13H14BrFO3 | 详情 | 详情 | |
| (XLIV) | 17727 | 6-chloro-9-(trimethylsilyl)-9H-purine | C8H11ClN4Si | 详情 | 详情 | |
| (XLV) | 17728 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl 4-methylbenzoate | C18H16ClFN4O3 | 详情 | 详情 |