Synthesis of compound J.1. To a 250 mL round bottom flask was added 3,6-dichloropyridazine (1.49 g, 10 mmol, 1.0 eq.), silver nitrate (0.17 g, 1 mmol, 0.1 eq.), deionized water (30 mL), pivalic acid (3.57 g, 35 mmol, 3.5 eq.), and concentrated sulfuric acid (1.6 mL, 30 mmol, 3.0 eq.). The reaction mixture was heated to 70 °C and kept at a constant temperature. An aqueous solution (10 mL) of ammonium persulfate (2.28 g, 10 mmol, 1.0 eq.) was added slowly and dropwise over 10 minutes. After the dropwise addition, the reaction was continued with stirring at 70 °C for 1 hour. After completion of the reaction, the mixture was cooled to room temperature. The reaction mixture was slowly poured into ice water (100 mL) and the pH was adjusted with aqueous ammonium hydroxide to 8. The aqueous phase was extracted with dichloromethane (3 × 250 mL). The organic phases were combined, filtered through a cotton plug, washed with 1N aqueous NaOH (70 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the crude product by fast column chromatography (20% ethyl acetate/hexane) afforded 4-tert-butyl-3,6-dichloropyridazine (1.32 g, 64% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ: 7.5 (s, 1H), 1.5 (s, 9H); Rf = 0.5 (80% ethyl acetate/hexane).
