Glipizide, an antidiabetic agent, was synthesized from 4-(2-aminoethyl)benzenesulfonamide by condensation with 5-methylpyrazine-2-carboxylic acid to give 5-methyl-N-(4-sulfamoylphenethyl)pyrazine-2-carboxamide, which was subjected to esterification with isocyanatocyclohexane with an overall yield about 84%. This synthetic method did not require the protection and deprotection of the amino group, which simplified the reaction steps, improved the yield and saved raw materials. Its work-up was also simple. This method has brought enormous economic benefits for the industrial production