Synthesis
General procedure for the synthesis of 5-chloropyrazine-2-carboxylic acid hydrazide from methyl 5-chloropyrazine-2-carboxylate:
1. Preparation of 5-chloropyrazine-2-carboxylic acid hydrazide: 5-chloropyrazine-2-carboxylic acid methyl ester (10.02 g, 58.25 mmol) and hydrazine monohydrate (12.5 mL, 250 mmol) were dissolved in methanol (400 mL). The reaction mixture was heated to reflux for 48 hours. Upon completion of the reaction, the mixture was filtered, the precipitate was collected and dried under vacuum to afford the target product 5-chloropyrazine-2-carboxylic acid hydrazine in a yield of 5.01 g (50% yield).
Product characterization data:
1H NMR (CDCl3, 400 MHz) δ: 4.09 (d, 2H), 8.52 (s, 1H), 8.66 (bs, 1H), 9.14 (s, 1H).
Elemental analysis: C5H5ClN4O Theoretical values: C 34.80; H 2.92; N 32.47; Measured values: C 34.89; H 2.91; N 32.32.
Mass spectral data: MS APCI+ m/z 173 [MH]+.
References
[1] Journal of Medicinal Chemistry, 2015, vol. 58, # 13, p. 5344 - 5354
[2] Patent: WO2007/17752, 2007, A1. Location in patent: Page/Page column 33
[3] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 10, p. 2634 - 2636
[4] Patent: WO2006/100557, 2006, A1. Location in patent: Page/Page column 24
