Synthesis
The general procedure for the synthesis of 3-aminopyrazine-2-carboxylic acid methyl ester from 3-aminopyrazine-2-carboxylic acid was as follows: hydrazine monohydrate (34 mL, 1094.95 mmol) was added batchwise to a stirred ethanol (65 mL) suspension of 3-aminopyrazine-2-carboxylic acid methyl ester (21.3 g, 139.09 mmol) at room temperature. The resulting mixture was stirred continuously at 60 °C for 2 h, followed by cooling to room temperature and filtration. The solid product was washed with cold ethanol (2 x 25 mL) and after drying to constant weight, 3-aminopyrazine-2-carbohydrazide (20.75 g, 97% yield) was obtained as a beige solid. The product was characterized by 1H NMR (DMSO-d6): δ 4.49 (2H, d), 7.46 (2H, br s), 7.78 (1H, d), 8.17 (1H, d), 9.79 (1H, t); mass spectrometry analysis showed [M + H]+ m/z = 154.
References
[1] Patent: US2014/206700, 2014, A1. Location in patent: Paragraph 0542; 0550
[2] Patent: WO2014/114928, 2014, A1. Location in patent: Page/Page column 103; 106
[3] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 22, p. 5155 - 5162
[4] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 4, p. 845 - 850
[5] Journal of the Chemical Society, 1951, p. 474,478
