反应详情

温度

70 °C

The above mentioned crude tert-butyl (S)-1-(5-(3-(methylamino)-4-aminophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate was dissolved in 150 mL THF in a round bottom flask. To this flask was added a 50 mL THF solution of 1,1′-carbonyldiimidazole (1.37 g, 8.45 mmol). The mixture was stirred at 70° C. for 10 hours. After removing the solvent under reduced pressure, the remaining residue was mixed with 200 mL EtOAc. The organic solution was washed with water, three times with saturated ammonium chloride, and dried over sodium sulfate. After removing the solvent, the remaining residue was subjected to silica gel column chromatograph separation using 40% EtOAc in hexane as the eluant. There were two very close major spots on TLC (Rf=0.16, 0.17). The pure fractions for the bottom spot were combined. After removing the solvent, tert-butyl (S)-1-(5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.36 g) was obtained as a tan solid. LCMS (API-ES) m/z (%): 649.3 (100%, M++H); 1H NMR (400 MHz, CDCl3) δ ppm 1.21 (s, 9H) 1.42 (s, 9H) 2.83 (m, 1H) 2.98 (m, 1H) 3.40 (s, 3H) 3.93-4.09 (m, 1H) 4.21-4.44 (m, 2H) 4.97-5.13 (m, 1H) 7.05 (d, J=8.02 Hz, 1H) 7.32 (d, J=7.82 Hz, 2H) 7.50 (m, 3H) 7.60 (s, 1H) 9.24 (s, 1H).

1. customAfter removing the solvent under reduced pressure
2. additionthe remaining residue was mixed with 200 mL EtOAc
3. washThe organic solution was washed with water, three times with saturated ammonium chloride
4. dry with materialdried over sodium sulfate
5. customAfter removing the solvent
6. customthe remaining residue was subjected to silica gel column chromatograph separation
7. customAfter removing the solvent