A practically useful approach for the cross-dehydrogenative coupling of quinazolin-4-one with simple nonactivated alkanes is reported. The products were smoothly formed under mild reaction conditions, within short reaction time at ambient temperature. The formation of new Csp3-Csp2 bonds occurred at the electron-poor C-2 position of quinazolin-4-one. The approach has the potential to be an important tool for the late-stage functionalization of advanced synthetic intermediates and may find many applications in medicinal chemistry.