Potassium Carbonate → 5-chloro-6-(2,4-difluoro-3-methyl-benzyloxy)-3-{5-[2-(1-hydroxy-1-methyl-ethyl)-pyrimidin-4-yl]-2-methyl-phenyl}-2-methyl-3H-pyrimidin-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of Intermediate 1 (50 mg, 0.13 mmol) in N,N-dimethylformamide (1.5 mL) was added 1-chloromethyl-2,4-difluoro-3-methyl-benzene from Step C (23 mg, 0.13 mmol), potassium carbonate (36 mg, 0.26 mmol) and 18-crown-6 (3 mg). The slurry was heated at 60° C. for three hours. After cooling to room temperature, the reaction was partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The slurry was filtered and concentrated in vacuo. The crude material was purified using normal phase chromatography (ethyl acetate/heptane) to provide the title compound as a colorless oil (25 mg, 37% yield). MS (M+H): 527; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.18 (s, 3H), 2.19 (s, 3H), 2.21 (s, 3H), 5.45-5.59 (m, 2H), 6.88-6.92 (m, 1H), 7.34-7.40 (m, 1H), 7.55-7.58 (m, 2H), 7.93 (s, 1H), 8.14 (d, J=7.83 Hz, 1H), 8.78 (d, J=5.09, 1H).

Provenance & Evidence