反应详情

温度

0 °C

To a solution of 2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine (28.8 mg, 0.15 mmol, from Step D) and (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3, 50.0 mg, 0.15 mmol) in DMF (3 mL) was added hydroxybenzotriazole (HOBT, 26.1 mg, 0.19 mmol) at 0° C. The reaction was stirred at 0° C. for 5 min, then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 37.0 mg, 0.19 mmol) was added. After removal of the ice-bath, the reaction was allowed to stir at ambient temperature for 16 h. After removal of the DMF by evaporation, the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. Concentration followed by preparative TLC (10% methanol/dichloromethane) gave the title compound as a foamy solid.

1. customAfter removal of the ice-bath
2. stirringto stir at ambient temperature for 16 h
3. customAfter removal of the DMF
4. customby evaporation
5. customthe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
6. extractionThe aqueous layer was extracted three times with ethyl acetate
7. washThe combined organic layers were washed with brine
8. dry with materialdried over magnesium sulfate
9. concentrationConcentration