The reaction was carried out with 2-((2,5-dichloropyrimidin-4-yl)amino)-N-methylbenzamide (149 mg, 0.503 mmol) and 4-(piperazin-1-yl)aniline hydrochloride (134 mg, 0.627 mmol) as raw materials and stirred for 16 hr at 95 °C in the presence of 2,2,2-trifluoroethanol (5 mL) and concentrated aqueous hydrochloric acid solution (2 drops). Upon completion of the reaction, the mixture was cooled to room temperature, diluted with 5% aqueous sodium hydroxide solution (100 mL) and subsequently extracted with ethyl acetate (3 x 100 mL). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Purification by reversed-phase column chromatography (12 g C18 column, 0-40% acetonitrile/methanol gradient elution) afforded the crude product was washed with dichloromethane (2 × 2 mL) and dried to afford the target compound 2-((5-chloro-2-((4-(piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide (33.4 mg, 15% yield) as an off-white solid.1H NMR (400 MHz, d6-DMSO) δ 9.19 (s, 1H), 8.78-8.71 (m, 2H), 8.15 (s, 1H), 7.74 (dd, J = 7.8, 1.3 Hz, 1H), 7.49-7.42 (m, 3H), 7.12 (t, J = 7.2 Hz, 1H), 6.86 ( d, J = 9.0 Hz, 2H), 3.00-2.95 (m, 4H), 2.86-2.79 (m, 7H).LCMS: retention time 4.28 min; m/z 438.1 [M + H]+.
