反应详情

To a solution of 2-(3-carboxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 1.682 mmol), EDC (346 mg, 1.766 mmol), and HOBt (240 mg, 1.682 mmol) in DMF (5 mL) add Et3N (0.355 mL, 2.523 mmol) and stir the solution at room temperature for 15 min. To this add a solution of the 7-amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (500 mg, 1.682 mmol) as a solution in DMF (5 mL) and stir the solution at 65° C. for 24 h. Dilute the reaction with EtOAc (250 mL) and wash with sat. NH4Cl (250 mL), sat. NaHCO3 (250 mL), then water (250 mL). Extract the aqueous layers with more EtOAc (250 mL) and dry the combined organics (Na2SO4), and concentrate in vacuo to give 902 mg of 7-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-benzoylamino]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester as a solid.

1. stirringstir the solution at 65° C. for 24 h
2. additionDilute
3. washwash with sat. NH4Cl (250 mL), sat. NaHCO3 (250 mL)
4. extractionExtract the aqueous layers with more EtOAc (250 mL)
5. dry with materialdry the combined organics (Na2SO4)
6. concentrationconcentrate in vacuo