反应详情

温度

100 °C

In a round-bottomed, 100-mL, single-necked flask equipped with a reflux condenser were placed a mixture of (R)-4-((R)-1-((6-chloro-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: and (R)-4-((R)-1-((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: (85.0 mg, 0.23 mmol), 1-(oxetan-3-yl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (103.9 mg, 0.30 mmol), and tetrakis(triphenylphosphine)palladium (10.3 mg, 0.010 mmol) in DME (3 mL) and 2N Na2CO3 (2 mL). The reaction mixture was sonicated for 30 sec, degassed with nitrogen gas for 30 sec, and heated at 100° C. for 3 h. Then, it was cooled to room temperature, quenched with water, and the organic layers extracted with EtOAc (3×5 mL). The combined organic layers were washed with water (2×5 mL) and brine (1×5 mL), dried (Na2SO4), concentrated, and purified by flash chromatography (100% dichloromethane to 25% MeOH in dichloromethane) to afford 55.9 mg (48%) of (R)-4-((R)-1-((3-cyclopropyl-6-(4-(1-(oxetan-3-yl)piperidin-4-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, d6-DMSO) δ 8.28 (s, 1H), 8.00 (d, J=8.4 Hz, 2H), 7.74 (s, 1H), 7.57 (s, 1H), 7.34 (s, 1H), 5.57 (m, 1H), 4.50 (m, 4H), 3.71 (m, 1H), 3.42 (m, 2H), 3.21 (m, 1H), 2.82 (m, 3H), 2.51 (m, 1H), 2.32 (m, 2H), 1.79 (m, 6H), 1.41 (d, J=6.3 Hz, 3H), 1.18 (m, 4H). MS (ESI+) m/z 502.2 (M+H).

1. customIn a round-bottomed, 100-mL, single-necked flask equipped with a reflux condenser
2. customThe reaction mixture was sonicated for 30 sec
3. customdegassed with nitrogen gas for 30 sec
4. temperatureThen, it was cooled to room temperature
5. customquenched with water
6. extractionthe organic layers extracted with EtOAc (3×5 mL)
7. washThe combined organic layers were washed with water (2×5 mL) and brine (1×5 mL)
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. custompurified by flash chromatography (100% dichloromethane to 25% MeOH in dichloromethane)