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

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