2,5-Dimethoxybenzylamine reacts with ethyl bromoacetate to yield N-(2,5-dimethoxy)benzylglycine ethyl ester.
2,5-Dimethoxybenzylamine is used in the preparation of pyrrolo[2,3-b]pyrazine-7-carboxamide derivatives as JAK and SYK inhibitors for the treatment of autoimmune and inflammatory diseases.
Hexamethylenetetramine (urotropine) (2.1 g, 15.0 mmol) was dissolved in 60 mL of chloroform and heated to reflux; 2,5-dimethoxybenzyl bromide (2.97 g, 12.9 mmol) was dissolved in 60 mL of chloroform, then dripped into urotropine within 30 min, refluxed for 3 h, stored at 4 overnight, and a white solid precipitated. After filtration, 2.33 g of white solid was obtained. The above solid was dissolved in the mixture [V (methanol): V (concentrated hydrochloric acid): V (water) = 42:12:10], heated to reflux for 3 d. Concentration was performed by adding 10 mL of water, adding 6 mol/L sodium hydroxide aqueous solution (about 40 mL) to adjust the pH to neutral, and then extracted with ether (50 mL3), washed with saturated brine, and then concentrated by drying with anhydrous potassium carbonate to obtain 0.96 g of crude amine. The product was 0.96 g of crude amine, yield 44.5%.
