反应详情

温度

100 °C

N-[5-bromo-4-(4-phenyl-1,3-thiazol-2-yl)pyridin-2-yl]-N′-ethylurea (Intermediate 69, 0.17 g, 0.42 mmol), ethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (0.14 g, 0.51 mmol), tetrakis triphenyl phosphine palladium (0.024 g, 0.02 mmol), and cesium carbonate (0.165 g, 0.51 mmol) were combined in a microwave vial and degassed with nitrogen. 1,4-dioxane:water (4:1, 2.5 mL) was added to the mixture and the reaction mixture was heated to 100° C. for 60 minutes. The reaction mixture was partitioned between water and ethyl acetate and the layers separated. The organic layer was washed with saturated NaHCO3, water, and brine, then dried over magnesium sulfate. The organic layer was concentrated to form a precipitate, and the resulting solids were filtered and then washed with acetonitrile followed by chloroform to yield 200 mg of the title compound as an off-white solid. LC/MS (ES+)[(M+H)+]: 474 for C25H23N5O3S. 1H NMR (300 MHz, CHCl3): 1.28 (t, 3H), 1.39 (t, 3H), 3.44-3.49 (m, 2H), 4.41 (q, 2H), 7.31-7.39 (m, 2H), 7.52 (s, 1H), 7.62 (d, 2H), 8.17 (s, 1H), 8.28 (t, 1H), 8.32 (t, 1H), 8.4 (s, 1H), 8.71 (d, 1H), 8.73 (d, 1H), 9.23 (d, 1H), 9.27 (s, 1H).

1. customdegassed with nitrogen
2. addition1,4-dioxane:water (4:1, 2.5 mL) was added to the mixture
3. customThe reaction mixture was partitioned between water and ethyl acetate
4. customthe layers separated
5. washThe organic layer was washed with saturated NaHCO3, water, and brine
6. dry with materialdried over magnesium sulfate
7. concentrationThe organic layer was concentrated
8. customto form a precipitate
9. filtrationthe resulting solids were filtered
10. washwashed with acetonitrile