Sodium Hydroxide → 6-[4-[4-[2-(4-Acetylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

Participants

Reaction Conditions

Reaction Steps

DIPEA (107 mL, 613.00 mmol) was added to 2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (99 g, 204.33 mmol) and N-acetylpiperazine (28.8 g, 224.77 mmol) in DMA (500 mL). The resulting solution was stirred at 110° C. for 1 hour. The reaction mixture was cooled to room temperature and the solvents were evaporated. The residue was dissolved in ethyl acetate (1 L) and the solution was washed with water (1 L). The aqueous was re-extracted with ethyl acetate (1 L) and the combined organics were washed with brine (1 L), dried over MgSO4, filtered and evaporated to give crude product. The aqueous layer was basified to pH 12 with 2M NaOH, then extracted with ethyl acetate (1 L), washed with brine (1 L), dried over MgSO4, filtered and evaporated to give further crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM then 5% MeOH in DCM. Pure fractions were evaporated to give 6-[4-[4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (81 g, 77%) as a solid.

Provenance & Evidence