Synthesis of New Polyheterocyclic Ring Systems Derived from 3-Amino-5-bromo-4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine

Abstract

3-Amino-5-bromo-4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine (2) was utilized as a precursor for the construction of new polyheterocyclic ring systems. It reacted with 4-substituted arylidene malononitriles and/or ethyl acetoacetate to furnish the corresponding pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine derivatives 4a–c and 6, respectively. Diazotization of the precursor 2 followed by coupling with ethyl cyanoacetate was the route for the formation of pyrido[2',3':3,4]pyrazolo[5,1-c]triazine derivative 8. The synthesized N-(5-bromo-4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-cyanoacetamide (10) was utilized for the synthesis of 6-amino-4-aryl-1-(pyrazolo[3,4-b]-pyridin-3-yl)-1,2-dihydropyridines derivatives 12a–c via its treatment with three types of arylidene malononitrile. N-(5-Bromopyrazolo[3,4-b]pyridinyl)-2-(4-oxothiazolidin-2-ylidene)acetamide 13 and N-(5-bromopyrazolo[3,4-b]pyridinyl)-2-cyano-2-(4-oxo-3-phenylthiazolidin-2-ylidene)acetamide 15 were picked up through the reactions of 10 with 2-mercaptoacetic acid and/or Ph-N = C = S with BrCH2COOEt. The tricyclic ring system, 9-bromo-3-cyano-2-oxo-pyrido[2',3':3,4]pyrazolo[1,5-a]-pyrimidine derivative 18, was used as building block for the construction of new tetra- and penta-heterocyclic compounds 19, 20, and 21 through its reaction with some bis-nucleophilic reagents; hydrazine hydrate, malononitrile and 4-(4-anisylazo)-1H-pyrazole-3,5-diamine. The newly synthesized pyrazolo[3,4-b]pyridine-based heterocycles were characterized by the IR and 1H NMR spectral techniques and their in vitro antibacterial properties were evaluated.