Nitrogen → 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-6-methyl-9-[2-(methylamino)pyrimidin-5-yl]-7-(propan-2-yloxy)-3,4-dihydro-1,4-benzoxazepin-5(2H)-one

Participants

Reaction Conditions

Reaction Steps

A solution of 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-9-bromo-6-methyl-7-(propan-2-yloxy)-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (116 g, 121 mg, 0.224 mmol), N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (52.7 mg, 0.224 mmol) and sodium carbonate (2.0 M, 71.2 mg, 0.672 mmol) in 1,4-dioxane (2.0 mL) was degassed (N2) for 5 min, then PdCl2(dppf)-DCM (50.0 mg, 0.0610 mmol) was added. The reaction was heated at 100° C. for 1 hour. The reaction was diluted with water (25 mL) and EtOAc (25 mL). The layers were separated and the organic phase was dried with magnesium sulfate and concentrated under vacuum. The residue was purified by column chromatography (silica gel, heptanes/EtOAc) to give 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-6-methyl-9-[2-(methylamino)pyrimidin-5-yl]-7-(propan-2-yloxy)-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (128a, 94 mg, 74% yield) as a white solid.

Provenance & Evidence