反应详情

温度

45 °C

A solution of 4-(trifluoromethoxy)benzoic acid (85 mg, 0.41 mmol) and CDI (66 mg, 0.41 mmol) in DCM (2 mL) was stirred at RT for 4 h before being added to a solution of N-hydroxy-5-methyl-1-(3-(4-methylpiperazin-1-yl)benzyl)-1H-1,2,4-triazole-3-carboximidamide (66 mg, 0.2 mmol) in DCM (1 mL). The reaction was then stirred at 45° C. for 6 h. The solvent was removed under reduced pressure, DMF (2 mL) was added and the reaction was stirred at 135° C. for 2 h. The reaction was then diluted with H2O (10 mL), extracted with 4:1 CHCl3:iPrOH (3×10 mL), dried with MgSO4 and concentrated under reduced pressure. The crude product was purified by pre-HPLC (Mobile phase: A=0.1% CF3CO2H/H2O, B=MeCN; Gradient: B=10%-40% in 30 min; Column: Waters C18) to afford 3-(5-methyl-1-(3-(4-methylpiperazin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-5-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole (18 mg, 18%) as a yellow oil. MS (ES+) C24H24F3N7O2 requires: 499. found: 500 [M+H]+; 1H-NMR (600 MHz, CDCl3) δ ppm 8.34 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 7.23 (t, J=7.6 Hz, 1H), 6.86 (d, J=8.1 Hz, 1H), 6.77 (s, 1H), 6.67 (d, J=7.5 Hz, 1H), 5.40 (s, 2H), 3.18 (m, 4H), 2.54 (m, 4H), 2.49 (s, 3H), 2.33 (s, 3H).

1. customThe solvent was removed under reduced pressure, DMF (2 mL)
2. additionwas added
3. stirringthe reaction was stirred at 135° C. for 2 h
4. additionThe reaction was then diluted with H2O (10 mL)
5. extractionextracted with 4:1 CHCl3
6. dry with materialiPrOH (3×10 mL), dried with MgSO4
7. concentrationconcentrated under reduced pressure
8. customThe crude product was purified by pre-HPLC (Mobile phase
9. waitGradient: B=10%-40% in 30 min