Triphenylphosphine → 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

Dichloromethane (225.0 mL) and 4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenol (50.0 g, 138 m mol) were charged to a suitable round bottom flask at 22-25° C. Triphenylphosphine (72.2 g, 275 m mol) and 1-[4-(2-hydroxy-ethyl)piperazin-1-yl]ethanone [CAS: 83502-55-0] (47.4 g, 275 m mol) were added successively to the reaction mass and stirred for 10 min at 22-25° C. Di-isopropyl azodicarboxylate (55.65 g, 275 m mol) in dichloromethane (75.0 mL) was added to the reaction mass slowly drop wise at 25-30° C. over a period of 60-90 min. The resulting reaction mass was stirred for 1.0 h at 25-30° C. to complete the reaction. n-Heptane (600.0 mL) was introduced to the reaction mass by drop wise addition over a period of 15-30 min at 22-25° C. and stirred for 30 min at the same temperature. Thus precipitated solid was filtered and washed with n-heptane (150.0 mL). The material was then suck dried for 30 min under reduced pressure. The crude material was purified by slurry washing in methanol (325.0 mL) at 22-25° C. The solid was then collected by filtration and washed with methanol (50.0 mL). The material was dried under reduced pressure with nitrogen gas bleed at 50° C. to afford the desired product 6-[4-[4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (61.2 g, 84%) as a free flowing solid.

Provenance & Evidence