ORGN 107

Nucleoside analogues that inhibit nucleotide biosynthesis have a profound effect on cancer cells and are therefore of interest in anti-cancer research. In order to create desired adenosine analogues, nucleophilic addition of either a nitrogen or a cyano group onto C-3 of 3-bromo-4-substituted-1,2,4-triazole (1) was necessary. Generation of a triazolium intermediate (via oxidation or alkylation of a nitrogen adjacent to the halide) gives easy displacement of the halide, but difficult conversion to the desired products. Direct nucleophilic aromatic substitution onto the triazole using KCN in DMF, gives 3-cyano-4-phenyl-1,2,4-triazole (2), but in very low yield. Use of CuCN, on the other hand gives a much more efficient displacement, most likely due to complexation of the copper to the adjacent nitrogen. Reduction can then be performed by catalytic hydrogenation. The synthesis of 2 as well as further reactions of this compound will be discussed.