反应详情

To a stirred solution of 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.164 mmol) in DMF (1 mL) was added a 1M solution of sodium hexamethyldisilazide in THF (0.164 mmol). The reaction was stirred at RT for 10 minutes before adding 4-fluorobenzonitrile (0.164 mmol) The reaction was stirred overnight at RT, then heated to 60° C. and stirred for a further 4 hours. The reaction was allowed to cool to RT, and treated with a further 0.2 equivalents of 4-fluorobenzonitrile and sodium hexamethyldisilazide, heated to 70° C. and stirred at this temperature for 3 hours. The reaction was cooled to RT, and treated with a further 0.2 equivalents of sodium hexamethyldisilazide, warmed to 70° C., and stirred at this temperature overnight. The solvent was removed in vacuo and the residual oil partitioned between ethyl acetate and water. The water layer was separated and re-extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated to a residue which was chromatographed on silica, using 0-1% methanol in DCM as the eluent, to give the desired product (60% yield).

1. stirringwas stirred overnight at RT
2. temperatureheated to 60° C.
3. stirringstirred for a further 4 hours
4. temperatureto cool to RT
5. temperatureheated to 70° C.
6. stirringstirred at this temperature for 3 hours
7. temperatureThe reaction was cooled to RT
8. temperaturewarmed to 70° C.
9. stirringstirred at this temperature overnight
10. customThe solvent was removed in vacuo
11. customthe residual oil partitioned between ethyl acetate and water
12. customThe water layer was separated
13. extractionre-extracted with ethyl acetate
14. washThe combined organic layers were washed with brine
15. dry with materialdried (MgSO4)
16. filtrationfiltered
17. customevaporated to a residue which
18. customwas chromatographed on silica