6-Nitroimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester

Synthesis

The reaction was carried out at reflux for 16 hours with 2-amino-5-nitropyridine (1.5 g, 10.80 mmol) and ethyl 3-bromopyruvate (1.6 mL, 13.00 mmol) dissolved in ethanol (15.0 mL). After completion of the reaction, the reaction mixture was filtered and a light yellow solid was collected. The filtrate was extracted with ethyl acetate and washed sequentially with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by fast column chromatography (silica gel, n-hexane: ethyl acetate = 2:1) to afford ethyl 6-nitroimidazo[1,2-A]pyridine-2-carboxylate (2.3 g, 90% yield) as a yellow solid.LC/MS ESI(+): m/z 236 [M + H]+. 1H NMR (300 MHz, CDCl3) δ: 9.30 (s, 1H), 8.38 (s, 1H), 8.06 (d, 1H, J = 10.0 Hz), 7.84 (d, 1H, J = 10.4 Hz), 4.50 (q, 2H, J = 7.2 Hz), 1.46 (t, 3H, J = 7.2 Hz).

References

[1] Patent: WO2014/196793, 2014, A1. Location in patent: Page/Page column 64; 65
[2] Molecular Pharmaceutics, 2015, vol. 12, # 6, p. 1813 - 1835
[3] Patent: WO2015/185142, 2015, A1. Location in patent: Page/Page column 20
[4] Patent: WO2008/100423, 2008, A1. Location in patent: Page/Page column 111
[5] Patent: EP1657242, 2006, A1. Location in patent: Page/Page column 27