反应详情

To a solution of N-Boc-L-proline (2.5 g, 11.6 mmol) in N,N-dimethylformamide (18 mL), O-(Benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (TBTU, 3.73 g, 11.6 mmol), HOBt.H2O (0.36 g, 2.32 mmol) and DIPEA (10.2 ml, 58.1 mmol) were added. After the reaction mixture was stirred at room temperature for 5 minutes, 4-Bromo-N′-hydroxybenzimidamide 15 (2.5 g, 11.6 mmol) was added. The mixture was then stirred at 110° C. for 2.5 hours. After cooled to room temperature, the resulting mixture was extracted with ethyl acetate, dried over magnesium sulfate, filtered and concentrated to yield a crude yellow liquid, which was purified with chromatography (ethyl acetate: n-hexane=1:10) to give the desired product 16a (2.5 g).

1. stirringThe mixture was then stirred at 110° C. for 2.5 hours
2. temperatureAfter cooled to room temperature
3. extractionthe resulting mixture was extracted with ethyl acetate
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto yield a crude yellow liquid, which
8. customwas purified with chromatography (ethyl acetate: n-hexane=1:10)