The synthesis of bicyclic N-4-amino-2 '-deoxycytidine derivatives

Nucleosides which have ambivalent tautomeric properties have value in a var iety of nucleic acid hybridization applications, and as mutagenic agents. W e describe here synthetic studies directed to stable derivatives of this ki nd of nucleoside based on N-4-aminocytosine. Treatment of the 4-(1H-1,2,4-t riazol-1-yl)-5-(chloroethyl)pyrimidinone nucleoside derivative 5 with hydra zine leads to formation of the 6,6-bicyclic pyrimido-pyridazin-7-one 3, and with methylhydrazine to the corresponding fixed tautomeric I-methyl deriva tive 7 (Scheme 1). If these cyclization reactions are carried out in the pr esence of a base, the 6-ring bicyclic derivatives undergo rearrangement to their corresponding 5-ring pyrrolo-pyrimidin-2-one analogues 8 (Scheme 2). In the reaction of the triazolyl derivative 5 with 1-[(benzyloxy)carbonyl]- 2-methylhydrazine, spontaneous cyclization gives the 5-ring derivative 13 r elated to 8 rather than the open-chain product 12 (Scheme 4). Reaction of a n acetylated analogue of triazolyl derivative 5 with 1,1-dimethylhydrazine gives rise to some of the open-chain product 9, but it too cyclizes to a pr oduct that we have assigned the structure of the 6,6-ring quaternary ammoni um salt 11 (Scheme 3).