C-5 Substituted pyrido[3,2-e]tetrazolo[1,5-a]pyrimidines were obtained by simple azidation of 2,4-dichloropyrido[2,3-d]pyrimidine followed by SNAr reactions with S-, N- and O-nucleophiles. Their NMR and IR studies revealed that the mono-azido products undergo azide-tetrazole equilibrium, whereas 2,4-diazidopyrido[2,3-d]pyrimidine exists in four tautomeric forms in various solutions, and its solid phase tautomer was established by the X-ray analysis. In total, nine of the obtained products are fully characterized by their single crystal X-ray structures and seven of them revealed a novel annulated pyrido[3,2-e]tetrazolo[1,5-a]pyrimidine skeleton. Among the studied products the amino derivatives - 5-aminopyrido[3,2-e]tetrazolo[1,5-a]pyrimidines - exist mainly in their tetrazole form both in the solid phase and in the solutions. However, also the latter enter the tautomeric equilibrium and the liberated azido group is able to undergo copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and form the corresponding 1,2,3-triazole derivatives. Free Gibbs energies of the tautomerization of C-5 substituted cyclohexylmercapto-, isopropyloxy- and phenoxy-pyrido[3,2-e]tetrazolo[1,5-a]pyrimidines were found to be -21.30, -23.19 and -17.02 kJ/mol, respectively.