Sodium Hydroxide → 7-methyl-6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline

Participants

Reaction Conditions

Reaction Steps

A solution of trifluoromethanesulfonic acid 7-methyl-quinolin-6-yl ester (1.38 g, 4.74 mmol), diisopropylethylamine (1.5 mL, 8.61 mmol) in DMF (8 mL) under nitrogen was degassed by bubbling in nitrogen for 20 min. Tris(dibenzylideneacetone)dipalladium (99 mg, 0.11 mmol, Strem catalyst) and Xantphos (125 mg, 0.215 mmol) were added together in one portion, followed by 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (1 g, 4.36 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 poured onto 2 M aqueous NaOH (100 mL). The resulting precipitate was filtered, washed with water, and air-dried for 30 min. The resulting cake was dissolved in MeOH (80 mL) and CHCl3 (80 mL), and 2 g of activated decolorizing charcoal were added. The suspension was stirred at 60° C. for 2.5 h. Celite (10 g) was then added and the warm mixture was filtered over a short silica gel plug. The filtrate was evaporated in vacuo to give a beige solid. Recrystallization from EtOH and chloroform afforded 1.0 g of 7-methyl-6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline as white crystals (62% yield).

Provenance & Evidence