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【结 构 式】 
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【分子编号】62928 【品名】{(2S,3R,5S)-3-(acetyloxy)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate 【CA登记号】 |
【 分 子 式 】C14H18N2O7 【 分 子 量 】326.3062 【元素组成】C 51.53% H 5.56% N 8.59% O 34.32% |
合成路线1
该中间体在本合成路线中的序号：(XLVI)Condensation of the bicyclic oxazoline (XV) with 2-(chloromethyl)acrylic acid ethyl ester (XLI) - obtained by treatment of the hydroxymethyl analogue (XLII) with SOCl2 - in dimethylacetamide gives the aduct (XLIII), which is treated first with hydroquinone and Na2CO3 in water and then with H2 over Pd/Al2O3 in the same solvent to provide 2,2'-anhydro-b-L-thymidine (XLIV). Reaction of compound (XLIV) with acetyl bromide in DMF/AcOEt yields 2'-bromo-3',5'-di-O-acetyl-b-L-thymidine (XLV), which is debrominated with H2 over Pd/Al2O3.to afford the 2'-deoxynucleoside (XLVI). Finally, this compound is deacetylated by means of NH3 in MeOH.
| 【1】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Bayes, M.; Telbivudine. Drugs Fut 2003, 28, 9, 870. |
| 【2】 Suzuki, T.; Iizuka, H.; Togashi, K. (Mitsui Chemicals, Inc.); L-Nucleic acid derivs. and processes for the synthesis thereof. EP 1348712; JP 2002241390; WO 0244194 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 56918 | (3aS,5S,6S,6aR)-5-(hydroxymethyl)-2-iminohexahydrofuro[2,3-d][1,3]oxazol-6-ol | C6H10N2O4 | 详情 | 详情 | |
| (XLI) | 62924 | ethyl 2-(chloromethyl)acrylate | C6H9ClO2 | 详情 | 详情 | |
| (XLII) | 11327 | ethyl 2-(hydroxymethyl)acrylate | 10029-04-6 | C6H10O3 | 详情 | 详情 |
| (XLIII) | 62923 | ethyl 2-{[(3aS,5S,6S,6aR)-6-hydroxy-5-(hydroxymethyl)-2-iminotetrahydrofuro[2,3-d][1,3]oxazol-3(2H)-yl]methyl}acrylate | C12H18N2O6 | 详情 | 详情 | |
| (XLIV) | 62927 | (2S,3S,3aR,9aS)-3-hydroxy-2-(hydroxymethyl)-7-methyl-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5][1,3]oxazolo[3,2-a]pyrimidin-6-one | C10H12N2O5 | 详情 | 详情 | |
| (XLV) | 12213 | [(2R,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl acetate | C14H17BrN2O7 | 详情 | 详情 | |
| (XLVI) | 62928 | {(2S,3R,5S)-3-(acetyloxy)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C14H18N2O7 | 详情 | 详情 |