反应详情

To a mixture of 6-(4-chlorophenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4400 mg, 1 mmol), CuI (24.7 mg, 0.13 mmol), Cs2CO3 (650 mg, 2 mmol), 2-(dimethylamino)acetic acid (51.5 mg, 0.5 mmol) in dioxane (6 mL) was added 4-chlorophenol (192 mg, 1.5 mmol). The reaction was heated at 140° C. (MW) for 1.5 h, cooled to RT and filtered. The filtrate was diluted with EA (5 mL) and water (5 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (5:1) to give 6-(4-chlorophenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (250 mg, 56.2% yield) as an oil. LCMS: MH+ 446 and TR=3.000 min.

1. temperatureThe reaction was heated at 140° C. (MW) for 1.5 h
2. filtrationfiltered
3. additionThe filtrate was diluted with EA (5 mL) and water (5 mL)
4. dry with materialThe organic layer was dried over Na2SO4
5. concentrationconcentrated to a residue which
6. customwas purified by chromatography
7. washeluted with PE/EA (5:1)