Design, synthesis, and in vitro antimicrobial activity of novel isoxazolo[2,3-a]pyrimido[4,5-d]pyrimidin-4-yl-1H-pyrazolo-[3,4-b]pyridines

Abstract

A new series of hybrid compounds, viz., isoxazolo[2,3-a]pyrimido[4,5-d]pyrimidin-4-yl-1H-pyrazolo[3,4-b]pyridines 5 were efficiently synthesized by reaction of 5-amino-2-methyl-7aryl-7H-isoxazolo[2,3-a]pyrimidin-6-carbonitriles 1 with triethyl ortho formate followed by treatment with excess of hydrazine hydrate, which underwent Dimroth rearrangement to afford the key intermediate 4-hydrazinyl-8-methyl-5-aryl-5H-isoxazolo[2,3-a]pyrimidin[4,5-d]pyrimidines 3. The reaction of 3 with benzoylacetonitrile afforded the compounds 4, which upon treatment with aromatic aldehydes and benzoyl acetonitrile in presence of FeCl₃ and basic Al₂O₃ produced the title compounds 5 by a three-component one-pot reaction. The structures of newly synthesized compounds 2-5 have been established on the basis of spectral and analytical data, and the title compounds were evaluated for their in vitro antimicrobial activity.