64-17-5

51149-08-7

34127-22-5

To a suspension of 3,6-dichloropyridazine-4-carboxylic acid (15.0 g, 78 mmol) in tetrahydrofuran (THF, 150 mL) was sequentially added ethanol (18.15 mL, 311 mmol) and 4-dimethylaminopyridine (DMAP, 0.950 g, 7.77 mmol). 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC, 16.39 g, 85 mmol) was added in batches over 1 min, and mild exothermic phenomena were observed during the reaction. The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the mixture was transferred to a dispensing funnel and neutralized by adding saturated aqueous sodium bicarbonate (NaHCO3) solution (150 mL). The aqueous phase was extracted with ether (3×250 mL), and the combined organic phases were washed with saturated saline (100 mL), dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: 20%→40% ethyl acetate/hexane solution; amount of silica gel: 300 g) to afford ethyl 3,6-dichloro-4-pyridazine-carboxylate (13.2 g, 59.7 mmol, 77% yield) as a colorless oil. The product was characterized as follows: 1H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 4.50 (q, J = 7.0 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H); LCMS (ESI) m/e 221.1 [(M + H)+, theoretical value 221.0 (C7H7Cl2N2O2)].