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【结 构 式】 
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【分子编号】48599 【品名】(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[3-(aminocarbonyl)-1H-1,2,4-triazol-1-yl]tetrahydro-3-furanyl acetate 【CA登记号】 |
【 分 子 式 】C14H18N4O8 【 分 子 量 】370.31908 【元素组成】C 45.41% H 4.9% N 15.13% O 34.56% |
合成路线1
该中间体在本合成路线中的序号：(II)This compound has been obtained by several related ways: The acylation of Ribavirin (1-(beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide) (I) with Ac2O gives the triacetate (II), which is anhydrized by means of POCl3 and TEA in chloroform to yield the carbonitrile (III). The reaction of (III) with NaOMe in methanol affords the methyl carboximidate (IV), which is finally treated with NH4Cl and NH3 in methanol to provide the target carboxamidine. Alternatively, the intermediate carbonitrile (III) can be treated with NH4Cl and NH3 in methanol at 85 C in a steel bomb to give the target carboxamidine. Finally, the condensation of 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose (V) with 1,2,4-triazole-3-carbonitrile (VI) by means of bis-(4-nitrophenyl)phosphate (BNPP) at 150 C also gives the intermediate triacetyl carbonitrile derivative (III).
| 【1】 Laguna, N; Robins, R.K.; Witkowski, J.T. (ICN Pharmaceuticals, Inc.); 1,2,4-Triazole nucleosides. DE 2220246; US 3798209 . |
| 【2】 Robins, R.K.; Kini, G.D.; Synthesis and anti-leukemic activity of alkyl-1-(beta-ribofuranosyl)[1,2,4]triazole-3-carboximidates. US 4925930 . |
| 【3】 Ramasamy, K.; Hong, Z.; Tam, R.; Lau, J. (ICN Pharmaceuticals, Inc.); Nucleoside analogs with carboxamidine modified monocyclic base. WO 0160379 . |
| 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) | 48598 | 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-1,2,4-triazole-3-carboxamide | C8H12N4O5 | 详情 | 详情 | |
| (II) | 48599 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[3-(aminocarbonyl)-1H-1,2,4-triazol-1-yl]tetrahydro-3-furanyl acetate | C14H18N4O8 | 详情 | 详情 | |
| (III) | 48600 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(3-cyano-1H-1,2,4-triazol-1-yl)tetrahydro-3-furanyl acetate | C14H16N4O7 | 详情 | 详情 | |
| (IV) | 48601 | methyl 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-1,2,4-triazole-3-carboximidoate | C9H14N4O5 | 详情 | 详情 | |
| (V) | 33835 | (2R,3R,4R,5S)-4,5-bis(acetoxy)-2-[(acetoxy)methyl]tetrahydro-3-furanyl acetate | 13035-61-5 | C13H18O9 | 详情 | 详情 |
| (VI) | 48602 | 1H-1,2,4-triazole-3-carbonitrile | C3H2N4 | 详情 | 详情 |