Methane → 3-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

Participants

Reaction Conditions

Reaction Steps

A solution of trifluoromethanesulfonic acid 3-bromo-quinolin-6-yl ester (973 mg, 2.74 mmol), diisopropylethylamine (0.87 mL, 4.98 mmol) in DMF (9 mL) under nitrogen was degassed by bubbling in nitrogen for 20 min. Tris(dibenzylideneacetone)dipalladium (114 mg, 0.124 mmol, Strem catalyst) and Xantphos (144 mg, 0.249 mmol) were added together in one portion, followed by 6-methyl-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (450 mg, 2.49 mmol) under a stream of nitrogen. The reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature and 500 mg of activated decolorizing charcoal were added. The suspension was stirred for 2.5 h, and the mixture was directly filtered through a plug of silica gel, using DMF as eluent. The solvent was evaporated in vacuo, and the residue was partitioned between water and 10% methanol/dichloromethane. The organic layer was separated and adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-5% methanol/dichloromethane afforded 534 mg of 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline as a cream-colored solid (58% yield).

Provenance & Evidence