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

Chemical Properties

Off-white to brown solid

Synthesis

Step 1: Synthesis of ethyl imidazo[1,2-a]pyridine-2-carboxylate Under magnetic stirring, 3 g (31.9 mmol) of 2-aminopyridine was dissolved in 65 mL of tetrahydrofuran. 4.44 mL (31.9 mmol) of ethyl 3-bromopyruvate was added slowly and solid precipitate formation was observed. The resulting non-homogeneous mixture was heated to reflux and stirred continuously for 4 hours. Upon completion of the reaction, it was cooled to room temperature and the solid product was isolated by filtration. The solid was dissolved in 65 mL of ethanol and again heated to reflux and stirred for 16 hours. The reaction mixture was cooled to room temperature and the solids were separated by filtration. The filtrate was placed in an ice bath to promote crystallization of the product until the liquid phase remained clear. The crystallized product was collected by filtration and washed with 30 mL of diisopropyl ether. Finally, the product was dried in a vacuum desiccator to afford 5.14 g (84% yield) of ethyl imidazo[1,2-a]pyridine-2-carboxylate as a white powder. Product characterization: LC-MS showed m/z=191 (MH+); UV purity was 99% at 254 nm.1H NMR (300 MHz, DMSO) δ 8.95 (s, 1H), 8.84 (d, J=6.8 Hz, 1H), 7.98-7.80 (m, 2H), 7.46 (t, J=7.2 Hz, 1H), 4.43 ( q, J=7.1Hz, 2H), 1.35 (d, J=7.1Hz, 3H).

References

[1] ACS Combinatorial Science, 2018, vol. 20, # 3, p. 164 - 171
[2] Patent: US2015/182507, 2015, A1. Location in patent: Paragraph 0204; 0205
[3] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 3, p. 359 - 362
[4] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 216 - 231
[5] ChemMedChem, 2017, vol. 12, # 3, p. 257 - 270