Synthesis of Chloro-pyrimidine Intermediate

To a solution N-(4-((2-chloropyrimidin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (16, 2.01 g, 6.37 mmol) and 2,4-dichloropyrimidine (1.04 g, 7.01 mmol) in DMF (15 mL), K₂CO₃ (0.97 g, 7.01 mmol) was added under N₂ atmosphere. The reaction solution was stirred at 80 °C for 6 h and monitored by TLC. The reaction mixture was poured into ice water (100 mL), and the precipitate was filtered off, washed, and dried in a vacuum to obtain the crude product, which was purified by silica gel chromatography using a mixture of DCM/MeOH (100:1~40:1) to afford the intermediate 17 as a white solid (2.34 g, 75.7%).