7-Bromopyrido[2,3-b]pyrazine-2,3(1H,4H)-dione

Synthesis

General procedure for the synthesis of 7-bromopyrido[2,3-b]pyrazine-2,3(1H,4H)-dione from 2,3-diamino-5-bromopyridine and diethyl oxalate: a mixture of 2,3-diamino-5-bromopyridine (1 mmol) and diethyl oxalate (10 mL) was heated and refluxed for 4 hours. After completion of the reaction, it was cooled to room temperature. The resulting solid was collected by filtration and washed sequentially with ethyl acetate and 95% ethanol. Subsequently, the solid was decolorized using activated charcoal and recrystallized in a solvent mixture of water and DMF or DMSO to afford 7-bromopyrido[2,3-b]pyrazine-2,3(1H,4H)-dione as a white solid (620 mg, 25.6% yield). The product was characterized by IR (KBr) ν 31199, 3138, 3045, 2751, 1715, 1603, 1446, 1389 cm-1; 1H NMR (400 MHz, DMSO-d6) δ 7.55 (1H, d, J = 1.6 Hz, H-6), 8.15 (1H, d, J = 1.6 Hz, H-8); 13C NMR (100 MHz, DMSO-d6) δ 112.36, 123.20, 123.80, 138.46, 141.83, 154.55, 155.58; HRMS-EI C7H4BrN3O2 calculated value [M + H]+ 241.9565, measured value 241.9567.

References

[1] European Journal of Medicinal Chemistry, 2016, vol. 117, p. 19 - 32
[2] European Journal of Medicinal Chemistry, 2016, vol. 121, p. 308 - 317
[3] Journal of Medicinal Chemistry, 2018, vol. 61, # 7, p. 2949 - 2961