反应详情

A mixture of acetoxyhydroamic acid (27 mg, 2.5eq) and K2CO3 (98 mg, 5eq) in DMF/H2O (3:1, 4 ml) was stirred at room temperature for 20min. To this mixture was added 2-fluoro-5-[1-(3-fluoro-2′-methanesulfonyl-biphenyl-4-yl)-2-oxo-piperidin-3-ylamino]-benzonitrile (68 mg, 0.141 mmol) prepared as described under Ex. 58a above. The whole was stirred and heated at 110° C. for 18 h. The mixture was diluted with water and extracted 3× with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered and evaporated. Purification by reverse phase HPLC yielded the title compound (50 mg, 72%) 1H NMR (DMSO-d6) δ 8.11 (1H, d, J=8 Hz), 7.79 (1H, t, J=7,3 Hz), 7.71 (1H, t, J=7,73 Hz), 7.46 (2H, m), 7.37 (1H, d, J=11 Hz), 7.28 (1H, d, J=8 Hz), 7.18 (1H, t, J=9.5 Hz), 6.98 (1H, m), 6,85 (1H, m), 4.29 (1H, m), 3.72 (2H, t, J=6.2 Hz), 2.91 (3H, s), 2.28 (1H, m), 2.08 (2H, m), 1,84 (1H, m). MS 515.3 (M+H)+.

1. customprepared
2. stirringThe whole was stirred
3. temperatureheated at 110° C. for 18 h
4. extractionextracted 3× with EtOAc
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customPurification by reverse phase HPLC