反应详情

温度

40 °C

To a solution of 0.5 g (1.78 mmol) 2,6-bis-acetylamino-N-methoxy-N-methyl-isonicotinamide in 8 ml THF was added at room temperature 7.14 ml (7.14 mmol) of a 1M solution of 4-fluorophenylmagnesium bromide in THF and stirred for 80 min at room temperature and subsequently for 2 h at 40° C. After cooling to room temperature 0.8 ml 37% HCl was added and the mixture was evaporated to dryness. The residue was taken up in ethyl acetate and 2M Na2CO3. The aqueous phase was extracted with ethyl acetate and the combined organic fraction were dried with MgSO4 and evaporated to dryness. The residue was taken up in 3 ml MeOH and 1 ml 37% HCl and heated to reflux for 4 h. After evaporation to dryness the residue was taken up in ethyl acetate and 2M Na2CO3. The aqueous phase was extracted with ethyl acetate and the combined organic fraction were dried with MgSO4 and evaporated to dryness. The title compound was further purified by reversed phase HPLC eluting with an acetonitrile/water gradient and yielded 131 mg (32%) yellow crystals.

1. additionwas added
2. customthe mixture was evaporated to dryness
3. extractionThe aqueous phase was extracted with ethyl acetate
4. dry with materialthe combined organic fraction were dried with MgSO4
5. customevaporated to dryness
6. temperature1 ml 37% HCl and heated
7. temperatureto reflux for 4 h
8. customAfter evaporation to dryness the residue
9. extractionThe aqueous phase was extracted with ethyl acetate
10. dry with materialthe combined organic fraction were dried with MgSO4
11. customevaporated to dryness
12. customThe title compound was further purified by reversed phase HPLC
13. washeluting with an acetonitrile/water gradient