<p>A new furan-based 1<i>H</i>-pyrazole-3,5-amine was utilized as a useful precursor for the preparation of numerous pyrazolo[1,5-<i>a</i>]pyrimidine hybrids and their related bis-analogues by its reaction with the appropriate 1,3-bielectrophiles. It was reacted with mono- or bis(enaminones) in refluxing acetic acid for 5–8&#xa0;h to produce the desired products in 83–92% yields. Moreover, a binary mixture of 1<i>H</i>-pyrazole-3,5-amine and the suitable mono- or bis-cinnamonitriles was reacted in refluxing dioxane in the presence of triethylamine for 5–8&#xa0;h to give the desired pyrimidine-6-carbonitriles in 70–91% yields. Moreover, 1<i>H</i>-pyrazole-3,5-amine was reacted with several β-dicarbonyl-containing reagents in refluxing acetic acid for 4–6&#xa0;h to give 5,7-disubstituted pyrazolo[1,5-<i>a</i>]pyrimidines and 5-substituted pyrazolo[1,5-<i>a</i>]pyrimidin-7(4<i>H</i>)-ones in 84–90% yields. The structure of the newly prepared pyrimidines was elucidated by considering their experimental NMR data as well as their theoretical data derived from DFT computations. The chemical shifts of ¹H- and ¹³C-NMR in DMSO were determined using the DFT-GIAO approach under the B3LYP and mPW1PW91 functions and a range of basis sets, including 6-31G(d, p), 6–31 + G(d), 6-311G(d), 6-311 + G(d, p), 6-311 + + G-(d, p), and 6-311 + G(2d, p). The new products showed broad antibacterial activity, particularly against <i>S. aureus</i> and <i>E. coli</i>. Overall, we found that the bis(pyrazolopyrimidines) were more potent than their monopodial counterparts. The propane-linked bis(3-(furan-2-ylmethyl)pyrazolo[1,5-<i>a</i>]pyrimidin-2-amine) displayed a comparable potency to ciprofloxacin with an MIC of 3.0 µM. Moreover, the thieno[2,3-<i>b</i>]thiophene-linked bis(2,7-diamino-3-(furan-2-ylmethyl)pyrazolo[1,5-<i>a</i>]pyrimidine-6-carbonitrile) displayed the best potency that exceeds ciprofloxacin with an MIC of 2.7 µM.</p> Graphical abstract <p></p>