The general procedure for the synthesis of 2-pyrazinamidine hydrochloride from 2-cyanopyrazine was as follows: 2-cyanopyrazine (1.00 kg, 9.53 mol) was slowly added to a solution of sodium methanol (NaOCH3, 51.4 g, 0.952 mol) in methanol (3800 mL) at room temperature. The reaction mixture was heated to 30 °C and stirred for 6 hours. Upon completion of the reaction, the mixture was cooled to 25 °C, followed by the addition of ammonium chloride (NH4Cl, 572 g, 10.5 mol). Stirring of the reaction mixture was continued for 22 hours. At the end of the reaction, methyl tert-butyl ether (4000 mL) was added and stirred for 15 minutes to promote solid formation. The solid product was collected by filtration and washed with methyl tert-butyl ether (2 x 1000 mL). Finally, the product was dried at 40 °C, 0-10 mmHg for 17 h to give the white solid product 2-pyrazinamidine hydrochloride (1435 g) in 95% yield and 95% purity by HPLC.1H NMR (DMSO-D6) data were as follows: δ 9.7 (broad single peak, 3H), 9.49 (double peak, 1H, J=1.5Hz), 9.04 (multiple peaks, 1H), 8.93 (multiple peaks, 1H), 9.04 (multiple peaks, 1H), 8.93 (multiple peaks 1H), 8.93 (triple peak, 1H, J=1.5Hz).
