反应详情

To a mixture of 3-(6-bromo-1-methyl-2,4-dioxo-5-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (40 mg, 0.08 mmol) and 3-chlorophenol (26 mg, 0.2 mmol) in dioxane (2 mL) was added Cs2CO3 (78 mg, 0.24 mmol), 2-(dimethylamino)acetic acid (4.1 mg, 0.04 mmol) and CuI (1.9 mg, 0.01 mmol). The reaction was degassed with nitrogen (3×), heated at 130° C. (MW) for 1.5 h, cooled to RT, diluted with water (10 mL) then extracted with EA (2×10 mL). The combined organic layers were dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-1-methyl-5-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (5.2 mg, 12.5% yield) as a white solid. 1H NMR (CDCl3) δ: 8.66 (s, 1H), 8.39 (s, 1H), 7.79 (d, J=7.2 Hz, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.30-7.25 (overlap with CDCl3, 1H), 7.12 (dd, J=8.0, 0.8 Hz, 1H), 6.87-6.79 (m, 2H), 4.81 (s, 2H), 4.23 (t, J=6.4 Hz, 2H), 3.72 (s, 3H), 3.55-3.58 (m, 2H), 2.95 (brd s, 1H), 1.95-1.90 (m, 2H). LCMS: MH+ 521 and TR=3.068 min.

1. customThe reaction was degassed with nitrogen (3×)
2. temperatureheated at 130° C. (MW) for 1.5 h
3. additiondiluted with water (10 mL)
4. extractionthen extracted with EA (2×10 mL)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. concentrationconcentrated to a residue which
7. customwas purified by Prep HPLC