合成路线:Viramidine can be synthesized by several related ways: 1) Reaction of triethyl orthoformate (I) with 1-cyanoformimidic acid hydrazide (II) by means of anhydrous HCl in dioxane gives 1,2,4-triazole-3-carbonitrile (III),which is condensed with tetra-O-acetyl-?D-ribofuranose (IV) by means of di-p-nitrophenyl phosphate (BNPP) at 150 oC to yield a mixture of the regioisomeric ribonucleosides (V) and (VI),easily separated by chromatography.Finally,the suitable regiosomer 3-cyano-1-(2,3,5-tri-O-acetyl-?D-ribofuranosyl)-1,2,4-triazole (V) is treated with anhydrous NH3 and NH4Cl at 85 oC in a pressure bomb (1,2).2) Alternatively,condensation of 2,3,5-tri-O-acetyl-?D-ribofuranosyl bromide (VII) with 1-(trimethylsilyl)-1,2,4-triazole-3-carbonitrile (VIII) - prepared by treatment of triazole (III) with hexamethyldisilazane in dry acetonitrile - in acetonitrile also gives the regioisomeric mixture of nucleosides (V) and (VI) (1).3) Acylation of ribavirin (1-?D-ribofuranosyl-1,2,4-triazole-3-carboxamide) (IX) with Ac2O and pyridine gives the triacetate (X),which is dehydrated by means of POCl3 and triethylamine in chloroform to yield 3-cyano-1-(2,3,5-tri-O-acetyl-?D-ribofuranosyl)-1,2,4-triazole (V).Treatment of nucleoside (V) with NaOMe in methanol affords the methyl carboximidate (XI),which is finally treated with NH4Cl and dry NH3 gas in methanol (3).
参考文献标题:Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides
文献作者:Witkowski,J.T.; Robins,R.K.; Khare,G.P.; Sidwell,R.W.
参考来源:J Med Chem 1973,16(8),935
合成路线:Viramidine can be synthesized by several related ways: 1) Reaction of triethyl orthoformate (I) with 1-cyanoformimidic acid hydrazide (II) by means of anhydrous HCl in dioxane gives 1,2,4-triazole-3-carbonitrile (III),which is condensed with tetra-O-acetyl-?D-ribofuranose (IV) by means of di-p-nitrophenyl phosphate (BNPP) at 150 oC to yield a mixture of the regioisomeric ribonucleosides (V) and (VI),easily separated by chromatography.Finally,the suitable regiosomer 3-cyano-1-(2,3,5-tri-O-acetyl-?D-ribofuranosyl)-1,2,4-triazole (V) is treated with anhydrous NH3 and NH4Cl at 85 oC in a pressure bomb (1,2).2) Alternatively,condensation of 2,3,5-tri-O-acetyl-?D-ribofuranosyl bromide (VII) with 1-(trimethylsilyl)-1,2,4-triazole-3-carbonitrile (VIII) - prepared by treatment of triazole (III) with hexamethyldisilazane in dry acetonitrile - in acetonitrile also gives the regioisomeric mixture of nucleosides (V) and (VI) (1).3) Acylation of ribavirin (1-?D-ribofuranosyl-1,2,4-triazole-3-carboxamide) (IX) with Ac2O and pyridine gives the triacetate (X),which is dehydrated by means of POCl3 and triethylamine in chloroform to yield 3-cyano-1-(2,3,5-tri-O-acetyl-?D-ribofuranosyl)-1,2,4-triazole (V).Treatment of nucleoside (V) with NaOMe in methanol affords the methyl carboximidate (XI),which is finally treated with NH4Cl and dry NH3 gas in methanol (3).
参考文献标题:Synthesis and antitumor activity of ribavirin imidates.A new facile synthesis of ribavirin amidine (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride)
文献作者:Kini,G.D.; Robins,R.K.; Avery,T.L.
参考来源:J Med Chem 1989,32(7),1447
合成路线:Viramidine can be synthesized by several related ways: 1) Reaction of triethyl orthoformate (I) with 1-cyanoformimidic acid hydrazide (II) by means of anhydrous HCl in dioxane gives 1,2,4-triazole-3-carbonitrile (III),which is condensed with tetra-O-acetyl-?D-ribofuranose (IV) by means of di-p-nitrophenyl phosphate (BNPP) at 150 oC to yield a mixture of the regioisomeric ribonucleosides (V) and (VI),easily separated by chromatography.Finally,the suitable regiosomer 3-cyano-1-(2,3,5-tri-O-acetyl-?D-ribofuranosyl)-1,2,4-triazole (V) is treated with anhydrous NH3 and NH4Cl at 85 oC in a pressure bomb (1,2).2) Alternatively,condensation of 2,3,5-tri-O-acetyl-?D-ribofuranosyl bromide (VII) with 1-(trimethylsilyl)-1,2,4-triazole-3-carbonitrile (VIII) - prepared by treatment of triazole (III) with hexamethyldisilazane in dry acetonitrile - in acetonitrile also gives the regioisomeric mixture of nucleosides (V) and (VI) (1).3) Acylation of ribavirin (1-?D-ribofuranosyl-1,2,4-triazole-3-carboxamide) (IX) with Ac2O and pyridine gives the triacetate (X),which is dehydrated by means of POCl3 and triethylamine in chloroform to yield 3-cyano-1-(2,3,5-tri-O-acetyl-?D-ribofuranosyl)-1,2,4-triazole (V).Treatment of nucleoside (V) with NaOMe in methanol affords the methyl carboximidate (XI),which is finally treated with NH4Cl and dry NH3 gas in methanol (3).
参考文献标题:Viramidine hydrochloride
文献作者:Cox,S.; Castar,J.
参考来源:Drugs Fut 2004,29(7),687
产品链接: CAS No. 40372-00-7›› 产品链接: CAS No.119567-79-2››