反应详情

温度

106 °C

To a solution of 5-(1-(3-bromobenzyl)-5-methyl-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-isoxazole (48 mg, 0.1 mmol) in toluene (5 ml) were added 4-(methylsulfonyl)-piperidine (33 mg, 0.2 mmol), Ruphos (4.8 mg, 0.01 mmol), Pd2(dba)3 (9.2 mg, 0.01 mmol) and t-BuONa (19.2 mg, 0.2 mmol). The mixture was stirred under Ar atmosphere at 106° C. for 16 h, then cooled to RT, diluted with H2O (20 mL), and extracted with EtOAc (3×10 mL). The combined organic layers were washed with H2O (10 mL) and brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure; the residue was purified by silica gel chromatography (Petroleum ether:EtOAc=1:1) to give the title compound as a white solid; MS (ES+) C26H26F3N5O4S requires: 561. found: 562[M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.91 (d, J=6.8 Hz, 2H), 7.33 (d, J=6.4 Hz, 2H), 7.25 (m, 1H), 7.10 (s, 1H), 6.89 (d, J=6.4 Hz, 1H), 6.80 (s, 1H), 6.72 (d, J=6.0 Hz, 1H), 5.34 (s, 2H), 3.82 (bd, J=10.0 Hz, 2H), 2.96 (m, 1H), 2.86 (s, 3H), 2.77 (m, 2H), 2.50 (s, 3H), 2.24 (bd, J=10.0 Hz, 2H), 1.95 (m, 2H).

1. temperaturecooled to RT
2. extractionextracted with EtOAc (3×10 mL)
3. washThe combined organic layers were washed with H2O (10 mL) and brine (10 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customthe residue was purified by silica gel chromatography (Petroleum ether:EtOAc=1:1)