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【结 构 式】 
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【分子编号】33826 【品名】1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1H-1,2,4-triazole-3-carboxamide 【CA登记号】 |
【 分 子 式 】C11H16N4O5 【 分 子 量 】284.272 【元素组成】C 46.48% H 5.67% N 19.71% O 28.14% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 2,3-O-isopropylidene-D-ribofuranose (I) with cyanoformidic acid hydrazone (II) and formic acid gives N1-(2,3-O-isopropyliene-D-ribofuranosyl)formamidrazone (III), which is cyclized with triethyl orthoformate (IV) by means of bis(p-nitrophenyl)phosphate (PNPP) yielding 1-(2,3-O-isopropylidene-D-ribofuranosyl)-1,2,4-triazole-3-carbonitrile (V). The amonolysis of the nitrile group of (V) with NH4OH in refluxing ethanol affords the corresponding carboxamide as a mixture of the alpha and beta isomers that are separated by column chromatography. The desired beta isomer (VI) is finally deprotected with 80% aqueous trifluoroacetic acid. The reaction of 1,2,4-triazole-3-carboxylic acid methyl ester (VII) with aqueous NH4OH gives the corresponding amide (VIII), which is condensed with D-ribofuranose-1-phosphate (IX) by digestion with the enzyme Nucleoside Phosphorylase (purified calf spleen).
| 【1】 Christensen, L.F.; Witkowski, J.T. (ICN Pharmaceuticals, Inc.); Process for preparing 1,2,4-triazole nucleosides. US 4138547 . |
| 【2】 Witkowski, J.T.; Robins, R.K. (ICN Pharmaceuticals, Inc.); 1,2,4-Triazole-3-carboxamides as antiviral agents. US 3976545 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 17718 | (3aR,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol | C8H14O5 | 详情 | 详情 | |
| (II) | 33823 | 2-nitriloethanehydrazonamide | C2H4N4 | 详情 | 详情 | |
| (III) | 33824 | N'-[(3aR,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-nitriloethanehydrazonamide | C10H16N4O4 | 详情 | 详情 | |
| (IV) | 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 |
| (V) | 33825 | 1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1H-1,2,4-triazole-3-carbonitrile | C11H14N4O4 | 详情 | 详情 | |
| (VI) | 33826 | 1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1H-1,2,4-triazole-3-carboxamide | C11H16N4O5 | 详情 | 详情 | |
| (VII) | 33827 | methyl 1H-1,2,4-triazole-3-carboxylate | 4928-88-5 | C4H5N3O2 | 详情 | 详情 |
| (VIII) | 33828 | 1H-1,2,4-triazole-3-carboxamide | C3H4N4O | 详情 | 详情 | |
| (IX) | 33829 | (3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl dihydrogen phosphate | 58459-37-3 | C5H11O8P | 详情 | 详情 |