8-Benzyloxy-2-methyl-imidazo[1,2-a]pyridine-3-carboxylic acid ethyl ester

Synthesis

Example 1A Synthesis of ethyl 8-(benzyloxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylate: 25 g (124.8 mmol) of 2-amino-3-benzyloxypyridine was dissolved in 781 ml of anhydrous ethanol, followed by the addition of 102.7 g (624.2 mmol) of ethyl 2-chloroacetoacetate and 2 tablespoons of 4A molecular sieves. The reaction mixture was heated to reflux (oil bath temperature 100 °C) for 2 days. Upon completion of the reaction, the mixture was concentrated and excess ethyl 2-chloroacetoacetate was removed by rotary evaporator under dry ice cooling conditions. The residue was purified by silica gel column chromatography with a mobile phase of cyclohexane: ethyl acetate (gradient elution from 9:1 to 4:1). Finally, 20.81 g of the target compound ethyl 2-methyl-8-(benzyloxy)imidazo[1,2-a]pyridine-3-carboxylate was obtained in 54% yield and 99% purity. The product was analyzed by LC-MS (Method 2): retention time Rt = 1.12 min, mass spectrum (ESpos): m/z = 311 (M + H)+. 1H NMR (400 MHz, DMSO-d6) data were as follows: δ= 1.35 (t, 3H), 2.59 (s, 3H), 4.34 (q, 2H), 5.32 (s, 2H). 7.01-7.09 (m, 2H), 7.33-7.48 (m, 3H), 7.52 (d, 2H), 8.81-8.86 (m, 1H).

References

[1] Patent: US2014/128386, 2014, A1. Location in patent: Paragraph 0984; 0985; 0986; 0987; 0988
[2] Patent: US2014/128372, 2014, A1. Location in patent: Paragraph 0489; 0490; 0491; 0492; 0493
[3] Patent: US2017/57954, 2017, A1. Location in patent: Paragraph 0620; 0621; 0622; 0623; 0624
[4] Patent: US2016/347770, 2016, A1. Location in patent: Paragraph 0691; 0692; 0693; 0694; 0695
[5] Journal of Medicinal Chemistry, 1985, vol. 28, # 7, p. 876 - 892