Design, synthesis, and characterization of novel pyrazolopyridine and pyridopyrazolopyrimidine derivatives

Abstract

Novel derivatives of pyrazolopyridine and pyridopyrazolopyrimidine were synthesized as these nitrogen heterocyclic compounds have biological and pharmaceutical application. Reaction of 4,6‐dimethyl‐1H‐pyrazolo[3,4‐b]pyridin‐3‐amine 1 with ethyl acetoacetate afforded 3‐(4,6‐dimethyl‐2H‐pyrazolo[3,4‐b]pyridin‐3‐ylamino)‐but‐2‐enoic acid ethyl ester 2 and 2,8,10‐Trimethylpyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidin‐4‐ol 3. The reaction product depends on the reaction time and catalyst applied. The reaction of ester 2 with POCl3 afforded pyridopyrazolopyrimidine 3 which reacted with ethyl bromoacetate to afford (2,8,10‐trimethylpyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidin‐4‐yloxy)acetic acid ethyl ester 4, while the reaction of compound 3 with POCl3 afforded 4‐chloro‐derivative 5, which reacted with hydrazine and a series of amines (primary and secondary) to yield 6 and 7a–n, respectively. 4‐Hydrazino pyridopyrazolopyrimidine 6 reacted with aromatic aldehydes, aromatic ketones, acetylacetone, and ethyl acetoacetate to afford condensation products 8–11. The reaction of ester 2 with ethyl chloroacetate afforded diester 12, which reacted with ethanolamine and hydrazine to afford 13, 14. Pyrazolopyridine 14 reacted with excess acetylacetone to yield pentenone derivative 15. The newly synthesized compound structure was confirmed by elemental analysis and spectral data (IR, NMR and mass spectra).