Toluene → (4-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-8-fluoro-3-methyl-1-oxo-1H-isoquinolin-2-yl)-(3-fluoro-propyl)-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To (4-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-8-fluoro-3-methyl-1-oxo-1H-isoquinolin-2-yl)-carbamic acid tert-butyl ester (0.5000 g, 1.005 mmol; prepared as described in example 8) and tetra-N-butylammonium bromide (0.340 g, 1.05 mmol) in toluene (10 mL, 90 mmol) was added potassium hydroxide (84.6 mg, 1.51 mmol) (powdered). The reaction was stirred at 50° C. for 10 minutes. 1-Iodo-3-fluoropropane (0.525 g, 2.79 mmol) was added and the reaction mixture was stirred for 1 hour at 50° C. The temperature was raised to 80° C. and the reaction mixture was stirred for another for 2 hours. The reaction mixture was cooled to room temperature and washed with 50 ml of water, dried over MgSO4 and was concentrated in vacuo to give 0.76 g (4-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-8-fluoro-3-methyl-1-oxo-1H-isoquinolin-2-yl)-(3-fluoro-propyl)-carbamic acid tert-butyl ester as an oil. The Boc-protection group was removed analogously to the method described in example 6 with trifluoroacetic acid in 1,2-dichloroethane to give the title compound.

Provenance & Evidence