General procedure for the synthesis of 3,4,5-trichloropyridazine from 4,5-dichloropyridazin-3(2H)-one: 4,5-dichloro-3-hydroxypyridazine (25 g, 151 mmol) was mixed with phosphorochloridic acid chloride (80 mL), and the reaction was stirred under refluxing conditions (120 °C) for 24 hours. Upon completion of the reaction, the excess phosphoryl chloride was removed by distillation under reduced pressure. The residue was cooled to -78 °C and held for 5-10 min before ice (300 mL) was slowly added. Subsequently, the reaction system was transferred from a -78 °C bath to a 0 °C bath and gradually warmed to room temperature. After the ice was completely melted, the precipitated white solid was pulverized and the mixture continued to be stirred overnight. The solid product was collected by filtration, washed with water and dried to give Intermediate I-09 (26.105 g, 94% yield) as a white solid.HPLC-MS (Method 4) analyzed the results: retention time (Rt) = 3.3 min, [M + H]+ m/z = 183.
