SnAr Reactions of 2,4-Diazidopyrido[3,2- d ]pyrimidine and Azide-Tetrazole Equilibrium Studies of the Obtained 5-Substituted Tetrazolo[1,5- a ]pyrido[2,3- e ]pyrimidines.

A straightforward method for the synthesis of 5-substituted tetrazolo[1,5- a ]pyrido[2,3- e ]pyrimidines from 2,4-diazidopyrido[3,2- d ]pyrimidine in SnAr reactions with N -, O -, and S - nucleophiles has been developed. The various N - and S -substituted products were obtained with yields from 47% to 98%, but the substitution with O -nucleophiles gave lower yields (20-32%). Furthermore, the fused tetrazolo[1,5- a ]pyrimidine derivatives can be regarded as 2-azidopyrimidines and functionalized in copper(I)-catalyzed azide-alkyne dipolar cycloaddition (CuAAC) and Staudinger reactions due to the presence of a sufficient concentration of the reactive azide tautomer in solution. In total, seven products were fully characterized by their single crystal X-ray studies, while five of them were representatives of the tetrazolo[1,5- a ]pyrido[2,3- e ]pyrimidine heterocyclic system. Equilibrium constants and thermodynamic values were determined using variable temperature 1 H NMR and are in agreement of favoring the tetrazole tautomeric form (ΔG 298 = -3.33 to -7.52 (kJ/mol), ΔH = -19.92 to -48.02 (kJ/mol) and ΔS = -43.74 to -143.27 (J/mol·K)). The key starting material 2,4-diazidopyrido[3,2- d ]pyrimidine presents a high degree of tautomerization in different solvents.