Purines, pyrimidines and imidazoles. Part 66. New syntheses of some uridine and N-alkoxycarbonyl 5-carboxamides, N-carbamoyl 5-carboxamides and 5-carboxamides

Abstract

Ethoxymethylene-N,N′-(methoxy-, ethoxy- and benzyloxy-carbonyl)malonamides have been prepared from the corresponding N,N′-alkoxycarbonylmalonamides with triethyl orthoformate and acetic anhydride. The three ethoxymethylene derivatives with primary alkyl- or aryl-amines including 2,3-O-isopropylidene-D-ribofuranosylamine gave 1 -substituted -N-alkoxycarbonyluracil - 5-carboxamides. The three isopropylidene nucleosides were isolated as β-anomers but in one example (benzyloxy) the α-anomer was also produced in small yield. The four isopropylidene nucleosides were deblocked with 50% aqueous trifluoroacetic acid to afford N-methoxy-, ethoxy- and benzyloxy-carbonyluridine-5-carboxamides and N-benzyloxycarbonyl-1-α-D-ribofuranosyluracil-5-carboxamide. Hydrolysis of each of the three β-anomeric isopropylidene nucleosides with sodium hydroxide produced 1-(2,3-O-isopropylidene)uridine-5-carboxamide which with aqueous trifluoroacetic acid gave uridine-5-carboxamide. Benzyloxycarbonyluridine-5-carboxamide however with aqueous ammonia (d 0.88) at room temperature soon gave N-carbamoyluridine-5-carboxamide in good yield. N-Carbamoyluridine-5-carboxamide was obtained directly from N,N′-ethoxycarbonylethoxymethylenemalonamide and aqueous ammonia. N-Benzyloxycarbonyluridine-5-carboxamide was converted into N-benzyloxycarbonyl-2′-deoxyuridine-5-carboxamide by successive reaction with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, p-tolyl chlorothioformate and tributyltin hydride followed by deblocking with tetrabutylammonium fluoride. The deoxyuridine with aqueous ammonia (d 0.88) at room temperature gave N-carbamoyl-2′-deoxyuridine 5-carboxamide in high yield. Structures were confirmed by elemental analysis, and FAB mass and ¹H NMR spectroscopy.