In this work, the synthetic approaches for a series of aminopyrimiclinylmethanone derivatives 1a-i, which versatile biological activities such as antibacterial and anticancer activities are expected from a structural point of view, were described. Nicotinic acid was converted to (2-methylsulfonylpyrimidin-4-yl) (pyridin-3-yl)methanone, a key intermediate, which was reacted with nucleophiles to yield the desired aminopyrimidinylmethanone derivatives 1a-i bearing various substituents.