[Synthesis]
Step 5: Water (253 mL) and tetrahydrofuran (THF, 842 mL) were added to the reaction flask. The following reagents were added sequentially to the stirred reaction mixture: potassium phosphate monohydrate (86.2 g, 374 mmol), BTEAC (2.25 g, 9.88 mmol), 3-chloro-6-iodopyridazine (45 g, 187.2 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazole (46.73 g, 224.6 mmol), triphenylphosphine (96 g, 7.49 mmol) and palladium diacetate (420 mg, 1.87 mmol). The reaction mixture was heated at 65°C for 16 hours. After the reaction was complete, the mixture was cooled to 60°C, water (935 mL) and sodium chloride (301.5 g) were added, stirred for 15 min and cooled to 45°C. The phases were separated and the organic layer was washed with a solution of sodium chloride (45 g) in water (374 mL). The organic layer was separated again and magnesium sulfate (225 g) and activated carbon (4.5 g) were added and stirred. The mixture was filtered and concentrated. The concentrated residue was co-evaporated twice with toluene and further concentrated to a final volume of 200 mL. The residue was stirred at room temperature for 16 h. The resulting solid was collected by filtration. The solid was dried under reduced pressure to afford the title compound 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine (29.7 g, 152.6 mmol, 82% yield).1H NMR (600 MHz, chloroform-d) δ ppm: 4.00 (s, 3H), 7.46 (d, J = 8.69 Hz, 1H), 7.56 (d, J = 9.06 Hz, 1H), 7.98 (s, 1H), 8.11 (s, 1H). |