ETHYL 7-AMINOTHIENO[2,3-B]PYRAZINE-6-CARBOXYLATE

Synthesis

Step 7: Synthesis of ethyl 7-aminothieno[2,3-b]pyrazine-6-carboxylate (7) 3-Chloropyrazine-2-carbonitrile (17.9 g, 128 mmol), sodium carbonate (17.7 g, 167 mmol), and ethyl ethyl-2-mercaptoacetate (18.4 mL, 167 mmol) were dissolved in ethanol (120 mL) and heated and refluxed for 4.5 hours. After completion of the reaction, the reaction was quenched with deionized water (1.5 L) and stirring was continued for 30 minutes. The precipitate was collected by filtration and washed with deionized water. The solid residue was dissolved in ether and filtered to remove the black precipitate. The ether was evaporated under reduced pressure to give pure ethyl 7-aminothieno[2,3-b]pyrazine-6-carboxylate (7) (19.6 g, 68.5% yield). 1H-NMR (400 MHz, CDCl3) δ: 1.42 (t, J=7.2 Hz, 3H), 4.40 (q, J=7.2 Hz, 2H), 6.19 (br s, 1H), 8.58 (d, J=2.2 Hz, 1H), 8.63 (d, J=2.2 Hz, 1H).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 11, p. 3643 - 3647
[2] Tetrahedron, 2008, vol. 64, # 7, p. 1333 - 1344
[3] Patent: WO2011/147764, 2011, A1. Location in patent: Page/Page column 27
[4] Patent: US2013/79341, 2013, A1. Location in patent: Paragraph 0110
[5] Journal of Heterocyclic Chemistry, 1975, vol. 12, p. 513 - 516