反应详情

温度

130 °C

To a solution of (S)-3-amino-1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)pyrrolidin-2-one (Example 150, Step C, 0.30 g, 0.83 mmol) in DMSO (3 mL) was added 3,4-difluorobenzonitrile (0.35 g, 2.5 mmol) and potassium carbonate (0.34 g, 2.5 mmol) and the reaction was heated to 130° C. for 6 hours. The reaction was diluted with EtOAc (20 mL) and washed with water (20 mL), and brine (20 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum. The crude material was purified on silica using a gradient of 1:9 to 1:4 EtOAc:DCM as eluent to give a solid, which was further triturated with DCM to give (S)-4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylamino)-3-fluorobenzonitrile (0.006 g, 0.012 mmol, 2% yield). Mass spectrum (apci) m/z=482.0, 483.9 (M+H).

1. washwashed with water (20 mL), and brine (20 mL)
2. dry with materialthe combined organic phases were dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated under vacuum
5. customThe crude material was purified on silica using a gradient of 1:9 to 1:4 EtOAc
6. customDCM as eluent to give a solid, which
7. customwas further triturated with DCM