Abstract: An efficient synthesis method of sulfonic acid pyrimidine derivatives is reported. In this paper, substituted 3-formylchromones, sulfonyl chlorides, and ethylamine are used as reaction substrates, and sulfonic acid intermediates are obtained by reaction under the catalysis of potassium tert-butoxide. Without purification, the intermediates continue to react with amidinium salts under the catalysis of cesium carbonate, and a series of sulfonic acid pyrimidine salt derivatives are synthesized through a one-pot tandem reaction. All the synthesized products are characterized by ¹H NMR, ¹³C NMR, HRMS, and IR. This synthesis method has the advantages of stable yield, mild reaction conditions, easily available reaction substrates, and simple separation and purification. This method provides another effective way to synthesize sulfonic acid pyrimidine derivatives with potential biological activity.