Design, Synthesis, Fungicidal Activity and Molecular Docking Study of Novel 2-(1-Methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamides

In order to develop novel pyrimidine fungicides, thirteen 2-(1-methyl-1H-pyrazol-4-yl) pyrimidine-4-carboxami-des were synthesized from 2-chloropyrimidine-4-carboxylic acid, 1-methyl-4-pyrazole borate pinacol ester, substituted anilines or substituted benzylamines as starting materials. The structures of target compounds were characterized by 1H NMR, 13C NMR, IR, HRMS, and the crystal structure of N-benzyl-2-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamide (4h) was also determined by X-ray diffraction method. The preliminary fungicidal activities against three plant fungi were evaluated, and the results showed that at a dosage of 100 mg/L, N-(4-methyl)phenyl-2-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamide (4f) and N-(4-chlorobenzyl)-2-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamide (4j) possessed relatively high activities against Rhizoctonia solani with inhibitory rates of 85.3% and 79.1%, respectively. Molecular docking study showed that 4f can form two hydrogen bonds and one cation-p interaction with succinate dehydrogenase.

Automated summary

Thirteen 2-(1-methyl-1H-pyrazol-4-yl) pyrimidine-4-carboxami-des were synthesized to develop new pyrimidine fungicides. The structures of the compounds were characterized and a crystal structure was determined. Two compounds, 4f and 4j, showed high fungicidal activity against Rhizoctonia solani, with inhibitory rates of 85.3% and 79.1%, respectively. Molecular docking study revealed the interaction between 4f and succinate dehydrogenase.