A new and suitable multicomponent one-pot reaction was developed for the synthesis of 2-amino-3-cyanopyridine derivatives. Background: This synthesis was demonstrated by the efficient and easy access to a variety of substituted 2-aminopyridines using enaminones as key precursors under solvent-free conditions. Methods: A range of spectroscopic techniques was used to determine and confirm the chemical structures (FTIR, ¹H NMR, ¹³C NMR). The antimicrobial potency of synthesized compounds (2a–d) was tested using disk diffusion assays, and the Minimum Inhibitory Concentration (MIC) for the active compounds was determined against a panel of microorganisms, including Gram-positive and Gram-negative bacteria and yeasts. Moreover, a docking analysis was conducted by Molecular Operating Environment (MOE) software to provide supplementary information about the potential, as well as an ADME-T prediction to describe the pharmacokinetic properties of the best compound and its toxicity. Results: The results of the antimicrobial activity indicated that compound 2c showed the highest activity against Gram-positive bacteria, particularly S. aureus and B. subtilis whose MIC values were 0.039 ± 0.000 µg·mL⁻¹. The results of the theoretical study of compound 2c were in line with the experimental data and exhibited excellent antibacterial potential. Conclusions: On the basis of the obtained results, compound 2c can be used as an antibacterial agent model with high antibacterial potency.

Nitrogen heterocycles represent one of the most important units in modern organic chemistry besides their wide existence broadly in natural products, pharmaceuticals, and functional materials. Among these heterocycles, pyrazole, the molecule of the present work, received much attention in organic synthesis because it delivers significant therapeutic and biological values as it was found to be the core unit of many drugs, agrochemicals, and related candidates. Due to this fact, the development of practical methodologies for the preparation of pyrazoles has attracted the long-standing interest of synthetic chemists. Synthetic heterocyclic chemistry using green methods has captivated many researchers in the recent past due to its easy operation and environmentally friendliness. In this review, we summarized systematic approaches for the synthesis of pyrazole derivatives via heterogeneous catalysis, ionic liquid catalysis, and multicomponent reactions.