Acetic Acid → tert-butyl (1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutyl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask was added tert-butyl {1-[4-(5-{2-[(1-methyl-1H-imidazol-4-yl)carbonyl]hydrazino}-3-phenyl-1,6-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate (1-7) (2.73 g, 4.63 mmol), acetic acid (5.30 mL, 93 mmol), and 1,4-dioxane (20 mL). The reaction mixture was heated to 80° C. while stirring open to the atmosphere (capped) in a hot oil bath. After 3 hours the reaction mixture was permitted to cool to room temperature, suspended in ethyl acetate, washed with a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography 1-15% IPA/DCM. The appropriate fractions were combined and the solvent was removed in vacuo. The resulting residue was repurified by reverse phase column chromatography (Sunfire C18) eluting with 5 to 95% acetonitrile/(0.1% TFA/water) gradient. The appropriate fractions were free based by suspending in ethyl acetate, washed with a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give tert-butyl (1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutyl)carbamate (1-8) as an off-white solid. MS (M+H)+: observed=572.3, calculated=572.7.

Provenance & Evidence