反应详情

A solution of 2-(1-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-2-oxo-propyl)-6-fluoro-benzoic acid (2.148 g, 5.351 mmol) and tert-butyl carbazate (1.628 g, 12.32 mmol) in benzene (100 mL) was stirred under reflux for 20 hours. LC-MS indicated the formation of (4-{[(S)-Cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-8-fluoro-3-methyl-1-oxo-1H-isoquinolin-2-yl)-carbamic acid tert-butyl ester (tR=1.54, UV 39%, ELSD 80%, m/z 398.4 (major), 442.5, 498.7 (MH+)). The reaction mixture was rotovaped. The residue was dissolved in 1,2-dichloroethane (15 ml) and TFA (15 ml) was added. After 60 min it was evaporated, partitioned between sat. aq. NaHCO3 and ethyl acetate, evaporated to give a crude residue of the title compound (1.7 g) that was used in the next step without purification. LC-MS (m/z) 398.0 (MH+), tR=1.24.

1. temperatureunder reflux for 20 hours
2. customAfter 60 min it was evaporated
3. custompartitioned between sat. aq. NaHCO3 and ethyl acetate
4. customevaporated