Synthesis and Microbiological Activities of 3-Nitropyrazolo-[1,5-d][1,2,4]triazin-7(6 H )-ones and Derivatives †

A new synthetic strategy for pyrazolo[1,5- d ][1,2,4]triazin-7(6 H )-ones 4 through intramolecular cyclization of alkyl 2-(4-nitro-1 H -pyrazol-3-yl)methylene)hydrazine-1-carboxylates 3 is described, allowing us to selectively modify the N -substituent in 3-position. The reduction in nitro compounds 4 with tin(II) chloride leads to amines 5 , and their acetylation leads to acetamides 6 . Via alkylation of 4 with bromoacetic acid alkyl esters and 2-chloro-5-(chloromethyl)pyridine, and the subsequent reduction in alkylated nitro compounds 7, the corresponding amines 8 and amides 9 were accessible in very good yields. The molecular structure of ethyl 2-(2-morpholino-3-nitro-7-oxopyrazolo[1,5- d ][1,2,4]triazin-6(7 H )-yl)acetate ( 7b ) was confirmed by single-crystal X-Ray diffraction analysis. Antibacterial and cytotoxic properties were evaluated for 61 synthesized compounds.