The general procedure for the synthesis of 3-methoxy-4-methyl-6-chloropyridazine from 6-methoxy-3-chloropyridazine and iodomethane was as follows: 2,2,6,6-tetramethylpiperidine (12.9 mL, 76.1 mmol) was dissolved in tetrahydrofuran (100 mL) under the protection of nitrogen and cooled down to -78°C. A hexane solution of 2.5 M n-butyllithium (30.4 mL, 76.1 mmol) was slowly added, followed by warming the reaction mixture to 0 °C and stirring for 1 hour. After cooling again to -78 °C, a tetrahydrofuran solution (75 mL, 34.6 mmol) of 0.46 M 3-chloro-6-methoxypyridazine was slowly added. After continued stirring at -78 °C for 1 h, iodomethane (4.74 mL, 76.1 mmol) was added and stirring was continued at the same temperature for 30 min. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution (50 mL), warmed to room temperature, diluted with water (50 mL) and extracted with ethyl acetate (2 x 250 mL). The organic phases were combined, washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the target product 3-methoxy-4-methyl-6-chloropyridazine (3.31 g, 60% yield). Mass spectrum (APCI) m/z = 159.0 (M + H).
