Potassium bis(trimethylsilyl)amide → 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5-bromo-8-chloro-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one

Participants

Reaction Steps

To a solution of 5-bromo-8-chloro-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (77d, 188 mg, 0.590 mmol) in anhydrous 1,4-dioxane (10 mL) was added KHMDS (2.00 mL, 2.00 mmol). Upon addition, a dark red paste was formed. After stirring at room temperature for 30 minutes, 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 170 mg, 0.649 mmol) was added. The resulting reaction mixture was stirred at 100° C. for 5 hours. After cooling to room temperature, the reaction mixture was quenched with water, and extracted with ethyl acetate (2×50 mL). The combined organic phases were dried over sodium sulfate, concentrated under vacuum, and purified by column chromatography (0-40% EtOAc/heptanes) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5-bromo-8-chloro-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (77e, 140 mg, 44%).

Provenance & Evidence