反应详情

温度

100 °C

A 20-mL vial was charged with (3S)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-methylmorpholine (0.797 g, 2.04 mmol, step 4), (2-chloro-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.859 g, 3.06 mmol, Intermediate D), DIPEA (1.10 mL, 6.30 mmol) and 1,4-dioxane (10 mL). The vial was sealed and heated at 100° C. for 12 h. The reaction mixture was allowed to cool to room temperature and then partitioned between water (30 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (40 mL). The combined organic phases were washed with saturated aqueous NaCl (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes) to afford 2-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.936 g) as a tan solid.

1. customThe vial was sealed
2. temperatureto cool to room temperature
3. custompartitioned between water (30 mL) and EtOAc (20 mL)
4. extractionThe aqueous phase was extracted with EtOAc (40 mL)
5. washThe combined organic phases were washed with saturated aqueous NaCl (50 mL)
6. dry with materialThe organic phase was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes)