反应详情

温度

135 °C

To a mixture of 6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 2, 500 mg, 1.49 mmol), CuI (85.2 mg, 0.45 mmol), Cs2CO3 (971.6 mg, 2.98 mmol) and 2-(dimethylamino)acetic acid (76.87 mg, 0.75 mmol) in dioxane (20 mL) was added 3-bromo-5-(trifluoromethyl)pyridine (842.9 mg, 3.73 mmol). The reaction was heated at 135° C. for 5 hours, followed by heating at 100° C. for 18 h, cooled to RT and diluted with EA (25 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (460 mg, 64.2% yield) as a yellow oil. LCMS MH+ 397 and TR=1.540 min.

1. temperatureby heating at 100° C. for 18 h
2. temperaturecooled to RT
3. washThe organic layer was washed with water (20 mL) and brine (20 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated to a residue which
6. customwas purified by chromatography
7. washeluted with PE/EA (10:1 to 1:1)