Under conventional and silica-supported Muffle furnace methods, water-soluble substituted trimeric triaryl pyridinium cations with various inorganic counter anions are synthesized. The solvent-free synthesis method is superior to the conventional method in terms of non-toxicity, quicker reaction times, ease of workup, and higher yields. Trimeric substituted pyridinium salts acted as excellent catalytic responses for the preparation of Gem-bisamide derivatives compared with available literature. To evaluate the molecular docking, benzyl/4-nitrobenzyl substituted triaryl pyridinium salt compounds with VEGFR-2 kinase were used with H-bonds, π-π stacking, salt bridges, and hydrophobic contacts. The results showed that the VEGFR-2 kinase protein had the most potent inhibitory activity. Intriguingly, the compound [NBTAPy]PF6- had a strongly binds to VEGFR-2 kinase and controlled its activity in cancer treatment and prevention.