Design and synthesis of some tricyclic pyrimidines and triazines via cycloaddition and intermolecular cyclization of cyclic amidine

Abstract

The cyclic amidine 3 was used as a precursor in this research, which was synthesized by chlorination of compound 1, followed by ring closure with hydrazine hydrate. Cyclization of amidine compound 3 with acetylacetone, ethyl cyanoacetate, chalcone analogue 6 and benzylidenemalononitrile (8) tolerated the expected tricyclic pyrimidines 4, 5, 7 and 9, respectively. Reaction of 3 with ammonium thiocyanate followed by cyclization of the product 10 with DMF, ethyl chloroformate and chloroacetyl chloride afforded triazine derivatives 11–13, respectively. Nucleophilic substitution of the later compound with EtONa gave ethyl methyl ether derivative 14. The benzamide derivative 15 was obtained by reaction of 3 with benzoylisothiocyanate or benzoylation of compound 10 with benzoyl chloride. Finely, heterocylization of 15 in the presence of Et3N gave the triazine derivative 16. 6-(4-Chlorophenyl)-4-(4-isopropylphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine (3) was used as the starting material for the synthesis of pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine and pyrido[2′,3′:3,4]pyrazolo[1,5-a][1,3,5]triazine derivatives via cycloaddition and intermolecular cyclization reactions.