反应详情

温度

120 °C

To a stirred solution of 5-((2R,4S)-4-fluoro-2-(5-fluoro-2-(((S)-tetrahydrofuran-3-yl)oxy)phenyl)pyrrolidin-1-yl)pyridin-2-amine (4.2 g, 11.63 mmol) in dry toluene (11 ml) was added DMF-DMA (2.9 g, 24.43 mmol) under N2 atm and stirred for 2 h at 120° C. during which complete consumption of starting material was observed by TLC, cooled it to 10° C. then added Ethylbromoacetate (4.27 g, 25.59 mmol) drop wise and methanol (4 ml) was added under N2 atm then stirred for 16 h at 120° C. Reaction mixture was cooled to room temperature and solvent was removed in vacuo and residue was dissolved in DCM (200 ml), washed with water and brine, dried over anhydrous Na2SO4 and concentrated under vacuum to get crude product. Crude was purified by column chromatography (eluted with 30-40% ethyl acetate/Hexane) to afford pale green solid (1.3 g, yield: 30%), MS (ESI): 458.2 (M+H)

1. temperaturecooled it to 10° C.
2. stirringatm then stirred for 16 h at 120° C
3. customReaction mixture
4. temperaturewas cooled to room temperature
5. customsolvent was removed in vacuo and residue
6. dissolutionwas dissolved in DCM (200 ml)
7. washwashed with water and brine
8. dry with materialdried over anhydrous Na2SO4
9. concentrationconcentrated under vacuum
10. customto get crude product
11. customCrude was purified by column chromatography (eluted with 30-40% ethyl acetate/Hexane)