Tetrahydrofuran → 1-(6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanone

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Reaction Steps

A 100 mL round bottom flask was charged with ethyl 6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate (3.04 g, 7.41 mmol). THF (37.0 mL) was added and the mixture was stirred at ambient temperature for about 15 min. The slurry was cooled to about −40° C. and a solution of methylmagnesium chloride (3 M in THF, 9.88 mL, 29.6 mmol) was added slowly while keeping the internal temperature between about −30° C. and −40° C. After about 15 min the mixture was cooled to about −55° C. followed by the slow addition of saturated ammonium chloride solution (about 10 mL). The mixture was then warmed to ambient temperature and diluted with water (50 mL), DCM (75 mL), and saturated aqueous ammonium chloride solution (50 mL). The layers were separated and the aqueous solution was extracted with DCM (2×100 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated under reduced pressure to give the title compound (2.74 g, 97%): LC/MS (Table 1, Method h) Rt=1.22 min; MS m/z: 381.1 (M+H)+.

Provenance & Evidence