To a 500 mL four-necked round-bottomed flask equipped with a thermometer and condenser tube were added 100 g of 1,2-dichloroethane, 12.5 g (0.1 mol) of 5-(aminomethyl)pyridin-2-amine (IV) and 30.0 g of potassium carbonate. A solution consisting of 25.0 g (0.15 mol) N,N-diethylethylamine and 20 g of 1,2-dichloroethane was added slowly and dropwise over a period of about 2 hours at 30 to 35 °C. The reaction temperature was maintained at 30~35°C and stirring was continued for 6 hours. After completion of the reaction, it was cooled to 20~25°C and layered. The aqueous layer was extracted twice with 1,2-dichloroethane at 20 g. The organic phases were combined and the 1,2-dichloroethane was removed by distillation. To the residue was added 75 g of methyl tert-butyl ether and 0.5 g of activated charcoal and stirred at 80~82°C for 1 hr. After hot filtration, the filtrate was cooled to 0~5°C for crystallization, filtered and dried to afford 18.2 g of 5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-amine as a white solid in 82.7% yield and 99.3% purity of the liquid phase.
