Cu-free Sonogashira Type Cross-Coupling of 6-Halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl) Quinazolin-4(3H)-ones as Potential Antimicrobial Agents

C(sp)-C(sp2) bond formation via Sonogashira cross-coupling reactions on 6-halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-ones with appropriate alkynes was explored. Optimization of reaction conditions with various catalysts, ligands, bases, and solvents was conducted. The combination of PdCl2(MeCN)(2) with X-Phos proved to be the best metal-ligand system for this conversion in the presence of triethylamine (Et3N) in tetrahydrofuran at room temperature for iodosubstrates, at 80 degrees C for the bromosubstrates in 8h, and also for the chlorosubstrates in 16h. We also demonstrated synthesis of a successful diversity-oriented synthesis library of highly functionalized quinazolinones via Cu-free Sonogashira coupling of diverse aryl halides and azido-alkyne (click) ligation reactions with substituted azides. The library exhibited significant antimicrobial activity when screened against several microorganisms.