General procedure for the synthesis of 6-chloro-4-iodo-3-methoxypyridazine from 6-methoxy-3-chloropyridazine: n-butyllithium (16 mL, 2.5 M hexane solution, 40 mmol) was slowly added to a stirred solution of 2,2,6,6-tetramethylpiperidine (6.9 mL, 41 mmol) in tetrahydrofuran (200 mL, 2.5 mol) at -70°C . Subsequently, 3-chloro-6-methoxypyridazine (2.90 g, 20.1 mmol) dissolved in tetrahydrofuran (150 mL) was added dropwise and the reaction mixture was stirred at -78°C for 30 min. Next, iodine (5.30 g, 20.9 mmol) dissolved in tetrahydrofuran (50 mL) was added and stirring was continued at -78°C for 2 hours. Upon completion of the reaction, the reaction was quenched by the addition of 1 M aqueous sodium thiosulfate (150 mL) and the mixture was extracted with ether. The organic phase was dried with magnesium sulfate, filtered and the solvent was removed in vacuum. Purification by silica gel column chromatography afforded 925 mg of 6-chloro-4-iodo-3-methoxypyridazine.LC-MS (Method 5): retention time R = 2.94 min; MS (ESIpos): m/z = 271 [M + H]+. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.495 (0.64). 2.500 (0.88), 2.505 (0.64), 3.316 (11.53), 3.992 (0.76), 4.049 (16.00), 8.416 (5.48).
