反应详情

温度

150 °C

A stirred mixture of (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole (Example 14, 37.0 mg, 0.10 mmol), 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (31 mg, 0.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (7.0 mg, 0.01 mmol), (2-biphenyl)dicyclohexylphosphine (3.5 mg, 0.01 mmol) in 1:1 ethanol/dioxane (0.40 mL) was treated with 1 M aqueous sodium carbonate (0.150 mL, 0.15 mmol). The reaction tube was sealed and the stirred mixture was heated to 150° C. under microwave irradiation for 10 minutes. The reaction mixture was cooled to room temperature then diluted with dichloromethane (2 mL) and filtered through diatomaceous earth, followed by an acetonitrile/dichloromethane rinse (10 mL). The filtrate was dried (Na2SO4) and concentrated under reduced pressure and the residue was purified by silica gel chromatography (70:30:0 to 63:30:7 dichloromethane/acetonitrile/methanol). Fractions containing product were combined and concentrated under reduced pressure to give (R)-6-(2-methoxypyrimidin-5-yl)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD2Cl2) δ ppm 1.43-1.50 (m, 2H), 1.61 (pentet, J=5 Hz, 4H), 2.00 (pentet, J=10 Hz, 1H), 2.24-2.31 (m, 1H), 2.40-2.58 (m, 4H), 3.01 (pentet, J=8 Hz, 1H), 3.40 (t, J=9 Hz, 1H), 3.50-3.57 (m, 1H), 3.73 (t, J=9 Hz, 1H), 3.79-3.86 (m, 1H), 4.02 (s, 3H), 7.44 (dd, J=2, 8 Hz, 1H), 7.56 (d, J=8 Hz, 1H), 7.78 (d, J=2 Hz, 1H), 8.72 (s, 2H); MS (ESI) m/z 396 (M+H)+.

1. customThe reaction tube was sealed
2. temperatureThe reaction mixture was cooled to room temperature
3. filtrationfiltered through diatomaceous earth
4. washrinse (10 mL)
5. dry with materialThe filtrate was dried (Na2SO4)
6. concentrationconcentrated under reduced pressure
7. customthe residue was purified by silica gel chromatography (70:30:0 to 63:30:7 dichloromethane/acetonitrile/methanol)
8. additionFractions containing product
9. concentrationconcentrated under reduced pressure