Bromine → 3-Bromo-6-[6-(1-methyl-1h-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline

Participants

Reaction Steps

To a solution of 6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline (1 g, 2.785 mmol) in glacial acetic acid (20 mL) was added bromine (0.716 mL, 13.93 mmol) dropwise. The reaction mixture was stirred at room temperature for 5 min then at 100° C. for 3 h. The reaction was cooled to room temperature, and the mixture was concentrated in vacuo. The residue was partitioned between 10% aqueous NaOH and 10% methanol/di-chloromethane. The organic layer was separated, washed with 1 M aqueous Na2S2O3, dried over sodium sulfate, filtered, and adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-7% methanol/dichloromethane afforded 381 mg of 3-bromo-6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline as a beige solid (31% yield): 1H NMR (DMSO-d6): δ 3.89 (s, 3H), 7.77 (dd, 1H), 7.80 (d, 1H), 7.99 (d, 1H), 8.00 (s, 1H), 8.43 (s, 1H), 8.48 (d, 1H), 8.68 (d, 1H), 8.92 (d, 1H); MS (m/z) 438, 440 [M+H+]+.

Provenance & Evidence