In this paper, we report an efficient and convenient approach for the synthesis of tailored‐design target sulfapyrimidine derivatives expected to show remarkable antimicrobial activities. The approach is based on reacting arylsulfonyl guanidine with α,β‐unsaturated carbonyl compounds to afford N‐(4,6‐diarylpyrimidin‐2‐yl)arylsulfonamide or with ylidene derivatives to afford N‐(6‐aryl‐5‐cyanopyrimidin‐2‐yl)arylsulfonamide, N‐(4‐amino‐5‐cyano‐6‐(methylthio)‐pyrimidin‐2‐yl)‐arylsulfonamide, and N‐(5‐cyanopyrimidin‐2‐yl)arylsulfonamide compounds through Michael addition reaction. The structure of the newly synthesized compounds was confirmed from spectral data and elemental analysis.