tert-Butyl 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylate

Weigh 2, 4-dichloropyrimidine (2.0 g, 13.43 mmol), Dissolved in DMF (15 mL), followed by triethylamine (TEA) (2.72 g, 26.85 mmol).1-Boc piperazine (2.75 g, 14.77 mmol), stirred at room temperature overnight.A white solid precipitated in the reaction solution, and the reaction was completed by TLC.The reaction solution was poured into 200 mL of ice water, and a large amount of white solid precipitated.Filter and dry to give a white solid C-2 (3.8 g, 13.43 mmol)(1) A mixture of 2, 4-dichloropyrimidine (1.00g, 6.71mmol), N-Boc-piperazine (1.37g, 7.38mmol), triethylamine (1.40mL, 10.1mmol), and DMF (10mL) was stirred at room temperature for 4.0h. The mixture was diluted with water, and extracted with EtOAc. The organic layer was washed with water, dried over anhydrous MgSOA solution of 2, 4-dichloropyrimidine (500 mg, 3.35 mmol) and tert-butyl piperazine-1-carboxylate (685 mg, 3.67 mmol) in DMF (5 mL) was charged with triethylamine (0.7 mL, 5.02 mmol). The reaction mixture was stirred at ambient temperature for 16 h. The reaction suspended in water, the solids formed were collected by filtration, washed with water, dried under reduced pressure. The crude material was purified by combi-flash companion (silica gel, CHMethod B: t-butyl 4-(2-chloropyhmidin-4-yl)piperazine-1 -carboxylate. To a mixture of 2, 4-dichloropyrimidine (2Og, 0.135mol, 1 eq.) and DIPEA (26g, 0.203mol, 1.5eq) in /-PrOH (40OmL) was added tert-butyl piperazine-1- carboxylate (27g, 0.148mol, 1.1 eq) by portions at 0 (1)