Abstract: Under the action of the thionyl chloride, different pyrazinamide derivatives were gotten from 2, 3 - pyrazinedicarboxylic acid and α-amino acids (glycine, valine, leucine) by fractional steps and one-step. Its structure was confirmed by 1H NMR, 13C NMR, IR and HR MS spectral analysis. The effect of different reaction conditions on the synthesis of pyrazinamide derivatives was discussed. The results showed that: In the presence of thionyl chloride, N-(2-carboxy-3-formyl-pyrazine)-α-amino acid methyl ester and N-(2, 3-acyl dimethyl pyrazine)-α-amino acid methyl esters were obtained by the sub-step or step, respectively.