To 3,6-dichloropyridazine (57.3 g, 385 mmol) and N-BOC-piperazine (71.6 g, 358 mmol) in 1,4-dioxane (250 mL) was added N,N-diisopropylethylamine (66.9 mL, 385 mmol). The reaction mixture was stirred at 80 °C overnight. Upon completion of the reaction, the mixture was concentrated under reduced pressure. The concentrated residue was dissolved in ethyl acetate (3 L) and washed sequentially with 10% citric acid solution, water and saturated saline. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by recrystallization from ethyl acetate to give tert-butyl 4-(6-chloropyridazin-3-yl)piperazine-1-carboxylate as an off-white solid (101 g, 88% yield). The product was confirmed by 1H NMR (400 MHz, CDCl3) and mass spectrometry (ESI): 1H NMR δ 1.25 (9H, s), 3.26-3.47 (8H, m), 6.67 (1H, d, J = 9.6 Hz), 7.00 (1H, d, J = 9.6 Hz); MS (ESI) m/z: 299.0 [M + H]+.
