A series of 4H-pyrido[1,2-a]pyrimidin-4-one derivatives were obtained by lignosulfonic acid-catalyzed annulation of 2-aminopyridines with β-oxo esters under the condition of ethanol as solvent at 100 °C for 24 hours. The structures of products were elucidated by 1H NMR and 13C NMR, and the maximum yield can reach 84%. The lignosulfonic acid catalyst is obtained by acidification of lignosulfonate, a byproduct of the paper-making industry. After 4 repeated uses, the yield can reach 75%, and the catalytic activity does not significantly decrease. The reaction scale is expanded to the gram level, and the catalytic effect remains unchanged.