反应详情

To a solution of the product from Step 4, methyl (4R)-4-[(7-methoxy-2-oxo-6-vinyl-1,2-dihydroquinolin-4-yl)oxy]-L-prolinate hydrochloride (0.84 g, 2.206 mmol) and linker B20, (2S)-cyclohexyl({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetic acid (0.689 g, 2.316 mmol) in DMF (2 mL) was added DIPEA (1.156 mL, 6.62 mmol) and HATU (1.090 g, 2.87 mmol). After 15 min, the reaction was complete and 1 N HCl and EtOAc were added. The organic layer was washed with water and brine, dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified on silica (gradient elution, 0-5% MeOH/DCM) to yield 1.65 g of material which still contained HATU residue. This was removed by extracting the material with EtOAc and 1N HCl (4×), water (1×) and brine (1×). The organic layer was dried over MgSO4 and the solvent was removed in vacuo to yield 1.13 g (82%) of the title compound. LRMS ESI+(M+H)+ 624.6.

1. washThe organic layer was washed with water and brine
2. dry with materialdried over MgSO4
3. customthe solvent was removed in vacuo
4. customThe crude product was purified on silica (gradient elution, 0-5% MeOH/DCM)