6-CHLORO-2-PYRAZINECARBOXAMIDE

Synthesis

Intermediate 13-2: Synthesis of 6-chloropyrazine-2-carboxamide 6-Chloropyrazine-2-carboxylic acid (2.00 g, 12.62 mmol) was dissolved in DMF (7 mL) and the solution was cooled to -40 °C. Under stirring, N-methylpyrrolidone (NMP, 2.77 mL, 25.23 mmol) and isobutyl chloroformate (3.27 mL, 25.23 mmol) were added sequentially. After controlling the reaction temperature to slowly rise to -20 °C over 20 min, ammonia (NH4OH) was added. A precipitate rapidly formed in the reaction mixture and after continued stirring for 15 min, the precipitate was collected by filtration and washed with cold water. Purification by recrystallization from ethanol (EtOH) afforded the title compound 6-chloropyrazine-2-carboxamide (670 mg, 34% yield) as light brown needle-like crystals. The product was characterized by 1H NMR (500 MHz, DMSO-d6): δ 7.93 (br s, 1H), 8.24 (br s, 1H), 8.99 (s, 1H), 9.12 (s, 1H).

References

[1] Patent: WO2009/81195, 2009, A1. Location in patent: Page/Page column 77
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 2, p. 450 - 453