1-Bromo-2-chlorobenzene → 4-(2-Chlorophenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol

Participants

Reaction Conditions

Reaction Steps

Isopropylmagnesium chloride-lithium chloride complex (1.0M in THF, 10 mL, 10.00 mmol) was added dropwise to 1-bromo-2-chlorobenzene (1.91 g, 9.98 mmol) in THF (2.0 mL) cooled to 0° C. over a period of 10 minutes. The resulting solution was stirred at 0° C. for 1 hour then a 2.0 mL aliquot was added dropwise to 1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-one (400 mg, 1.40 mmol) in THF (10 mL) cooled to 0° C. over a period of 10 minutes. The resulting solution was stirred at 0° C. for 10 minutes then allowed to warm slowly to room temperature and stirred for a further hour. The reaction mixture was then quenched with saturated ammonium chloride (30 mL) and extracted with EtOAc. The extract was washed with saturated brine, dried over MgSO4 and concentrated by evaporation, then purified by flash silica chromatography, eluting with EtOAc. Pure fractions were evaporated to dryness to afford 4-(2-chlorophenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (230 mg, 41%) as a colourless solid.

Provenance & Evidence