Imidazo[1,2-a]pyridin-5-ylamine

Synthesis

The general procedure for the synthesis of imidazo[1,2-a]pyridin-5-amine from chloroacetaldehyde and 2,6-diaminopyridine was as follows: 2,6-diaminopyridine (5.0 g, 46 mmol) and chloroacetaldehyde (50% wt. aqueous solution, 6.4 mL, 50 mmol) were dissolved in anhydrous ethanol (120 mL). The reaction mixture was heated to reflux at 75°C for 1 hour. Upon completion of the reaction, the mixture was cooled to room temperature and the solvent was removed by concentration with a rotary evaporator. The concentrated residue was dissolved in a solvent mixture of saturated sodium bicarbonate solution and ethyl acetate. The aqueous phase was extracted with ethyl acetate (3 times), the organic phases were combined and dried with anhydrous magnesium sulfate. The dried organic phase was concentrated to give a brown solid product. Final isolation afforded 4.85 g of imidazo[1,2-a]pyridin-5-amine in 80% yield. The structure of the product was confirmed by 1H NMR (CDCl3) and mass spectrometry (MS): 1H NMR (CDCl3) δ 4.48 (s, 2H), 6.10 (dd, J = 7.2, 1.2 Hz, 1H), 7.10-7.20 (m, 2H), 7.42 (d, J = 1.2 Hz, 1H), 7.65 (d, J = 1.2 Hz. 1H); MS calculated value: 133, measured value: 134 (M + H).

References

[1] Patent: WO2005/44793, 2005, A2. Location in patent: Page/Page column 153-154
[2] Patent: WO2010/68452, 2010, A1. Location in patent: Page/Page column 28
[3] Patent: WO2010/68453, 2010, A1. Location in patent: Page/Page column 32