Synthesis
The general procedure for the synthesis of pyrazine-2-carboxylic acid methyl ester as a raw material for the synthesis of pyrazine-2-carbohydrazide was as follows: to a stirred solution of methyl pyrazine-2-carboxylic acid methyl ester (11.1 g, 80 mmol) dissolved in 140 mL of ethanol (EtOH) was slowly added hydrazine hydrate (15.6 mL, 320 mmol). The reaction mixture was heated to reflux and kept for 2 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure and the resulting residue was dried under high vacuum to afford the title compound pyrazine-2-carbohydrazide (11.1 g, 100% yield) as a white solid. The product can be used directly in the subsequent reaction steps without further purification.
References
[1] Patent: WO2005/16909, 2005, A1. Location in patent: Page/Page column 73
[2] Patent: WO2005/66163, 2005, A2. Location in patent: Page/Page column 128
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 14, p. 5007 - 5015
[4] European Journal of Inorganic Chemistry, 2011, # 32, p. 5036 - 5042
[5] European Journal of Medicinal Chemistry, 2009, vol. 44, # 12, p. 4954 - 4959
