反应详情

温度

0 °C

To a solution of (R)-2-((tert-butoxycarbonyl)amino)-3-((2-methoxy-2-oxoethyl)thio)-3-methylbutanoic acid (0.19 g, 0.58 mmol) in DMF (4 mL) was added HATU (0.24 g, 0.62 mmol) at ice bath temperature. The reaction mixture was stirred at 0° C. for 10 min, followed by addition of a solution of benzyl ((S)-3,3-dimethyl-1-oxo-1-((2S,4R)-2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-4-((S)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidin-1-yl)butan-2-yl)carbamate (Compound A, 0.35 g, 0.44 mmol) in DMF (2 mL) and NMM (0.08 mL, 0.71 mmol). The resulting mixture was stirred at rt for 4 h. The reaction mixture was poured into a separatory funnel containing EtOAc and brine. The organic layer was separated and washed with sat. aq. NaHCO3 solution and brine successively. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by flash chromatography (gradient elution from 0 to 60% EtOAc/DCM) to afford the title compound (0.40 g, 82%) as a white foam. MS (ESI+) m/z 1099.6 (M+H)+.

1. stirringThe resulting mixture was stirred at rt for 4 h
2. additionThe reaction mixture was poured into a separatory funnel
3. customThe organic layer was separated
4. washwashed with sat. aq. NaHCO3 solution and brine successively
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo
8. customThe residue was purified by flash chromatography (gradient elution from 0 to 60% EtOAc/DCM)