2-(1H-Imidazol-2-yl)-pyrazine

Synthesis

Step 1: Synthesis of 2-(1H-imidazol-2-yl)pyrazine 2,2-Diethoxyethylamine (3 g, 2.25 mmol) was dissolved in anhydrous methanol (20 mL). To this solution was added sodium methanol (1.22 g, 22.5 mmol, as a 25% methanol solution). After stirring for 25 minutes at room temperature, pyrazine-2-carbonitrile (2.37 g, 22.5 mmol) and acetic acid (1.35 g, 22.5 mmol) were added sequentially, followed by stirring of the reaction mixture at 50 °C for 1 hour. Upon completion of the reaction, methanol (40 mL) and 6N hydrochloric acid (12 mL) were added and the reaction mixture was stirred overnight under reflux conditions. After cooling the reaction mixture to room temperature, the layers were separated by partitioning with 1:1 ether and water (60 mL). The aqueous layer was alkalized to pH 9-10 and extracted with a dichloromethane solution of 10% methanol. The organic extracts were combined, dried with magnesium sulfate, filtered and concentrated to afford the target compound 2-(1H-imidazol-2-yl)pyrazine (1.49 g, yellow solid). 1H NMR (400 MHz, MeOH-d4) δ ppm: 7.67 (s, 1H), 7.09 (d, J = 1.8 Hz, 1H), 6.99 (d, J = 2.5 Hz, 1H), 5.72 (s, 2H).

References

[1] Patent: WO2012/93148, 2012, A1. Location in patent: Page/Page column 36-37
[2] Patent: US2014/11802, 2014, A1. Location in patent: Paragraph 0196; 0197