反应详情

温度

140 °C

To a 20 mL vial was added 1-((6-chloro-3-pyridinyl)sulfonyl)-3-(1-propyn-1-yl)piperazine (1.70 g, 7.47 mmol, Example 240, Step 4), diisopropylethylamine (4.20 mL, 24.2 mmol), and NMP (8.0 mL), and 2-(2-chloro-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (1.4 g, 6.37 mmol, Intermediate E). The vial was sealed and heated at 140° C. for 9 h. The reaction mixture was cooled to rt and partitioned between EtOAc (200 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (2×75 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography (120 g of silica, 10 to 50% EtOAc in hexanes) to afford 2-(2-(4-((6-chloro-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (1.5 g) as a light yellow solid.

1. customThe vial was sealed
2. temperatureThe reaction mixture was cooled to rt
3. custompartitioned between EtOAc (200 mL) and water (100 mL)
4. extractionThe aqueous layer was extracted with EtOAc (2×75 mL)
5. dry with materialThe combined organic extracts were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by column chromatography (120 g of silica, 10 to 50% EtOAc in hexanes)