Features of the synthesis of 5,7-di(het)aryltriazolo[1,5-a]pyrimidine derivatives

Abstract

To date, the synthesis of 5,7-di(het)arylazolo[1,5-a]pyrimidines, including 6-nitro-substituted derivatives, is represented by a limited number of original studies. To expand the synthetic approaches in this field of azaheterocyclic chemistry, we have developed a universal method for the preparation of 5,7-di(het)aryl-6-nitro-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidines and the corresponding 6-unsubstituted 5,7-di(hetero)aryl[1,2,4]triazolo[1,5-a]pyrimidines using imines and nitrostyrenes as starting reagents. It was shown that the reaction of 3-substituted-(E)-1-(4-nitrophenyl)-N-(1H-1,2,4-triazol-5-yl)methanimines (1) with nitrostyrene derivatives (2) in acetonitrile and one equivalent of NEt₃ results in the products of denitration-aromatization – 7-(het)aryl-2-(methylthio)-5-(4-nitrophenyl)-[1,2,4]triazolo[1,5-a]pyrimidines (3). This process of nitro group elimination with concomitant aromatization is also observed for 5,7-di(het)aryl-6-nitro-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidines and depends on the electronegativity of the substituent at the C-5 atom, the nature of the basic or acidic activators used, and the solvent. A series of experiments were conducted to establish the mechanism of nitro group elimination using 4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine (6a) as the starting reagent. During the study, the nitro group reduction product – 7-(4-methoxyphenyl)-2-(methylthio)-5-(pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-6-amine (8) was obtained.