Hydrochloric Acid → (E)-N-(cyclopropylmethoxy)-1-[3-[1-(5,7-difluoroquinolin-6-yl)ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethanimine

Participants

Reaction Steps

2-(cyclopropylmethoxy)isoindoline-1,3-dione (300 mg, 1.42 mmol), and hydrazine monohydrate (35 μL, 0.71 mmol) in methanol (5 mL) was heated at 75° C. for 3 hr. The reaction mixture was cooled, and the precipitate was filtered off, and washed twice with minimum methanol. To the combined methanol solution was added 1-(3-(1-(5,7-difluoroquinolin-6-yl)ethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (53.6, 100 mg, 0.28 mmol), followed by hydrochloride (1N in dioxane) dropwise to give a clear solution. The reaction mixture was stirred at rt overnight, LCMS showed the reaction was complete. 1N NaOH aqueous solution was added until pH 8-9. The mixture was concentrated, and purified by column chromatography to afford 109 mg (91% yield) of the title compound as a white solid. 1H-NMR (400 MHz, CDCl3) δ ppm 8.93 (dd, 1H), 8.33 (d, 1H), 7.96 (d, 1H), 7.75 (d, 1H), 7.59 (d, 1H), 7.41 (dd, 1H), 5.28 (q, 1H), 4.03 (d, 2H), 2.19 (d, 3H), 2.02 (s, 3H), 1.13-1.22 (m, 1H), 0.52-0.62 (m, 2H), 0.22-0.31 (m, 2H). LCMS (method A): [MH]+=423, tR=5.49 min.

Provenance & Evidence