In our present research, we have designed an approach for the ring-opening reactions of fused pyrimidines such as purines, deazapurines, and quinazolines using different nucleophiles and the presence of azide-tetrazole equilibrium in the structure (Scheme 1). In our case tetrazole ring is acting firstly as a protecting group, forcing the addition of nucleophiles at the less active C2 position of fused pyrimidine D, and secondly as a leaving group when under the second nucleophile attack, the pyrimidine ring opens, forming tetrazolyl derivatives F. The obtained structures are proved by X-ray analysis. Further opened products can be used as starting materials to synthesize diazepine-type structures. In addition, we have investigated a method for synthesizing C5-substituted tetrazolopyridopyrimidines from 2,4-diazidopyridopyrimidines in SNAr reactions with N, O, and S nucleophiles. The tetrazolopyrimidine derivatives can be considered as 2 azidopyrimidines due to the present tetrazole-azidoazomethine equilibrium and functionalized in copper(I)-catalyzed azide-alkyne dipolar cycloaddition (CuAAC) and Staudinger reactions. In our group azide-tetrazole equilibrium of pyridopyrimidines is intensively studied in various solvents by NMR, and obtained monocrystals are studied by X-ray analysis.