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

온도

50 °C

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.

1. stirringthe reaction mixture was stirred for 1 hour at 50° C
2. temperatureThe temperature was raised to 80° C.
3. stirringthe reaction mixture was stirred for another for 2 hours
4. temperatureThe reaction mixture was cooled to room temperature
5. washwashed with 50 ml of water
6. dry with materialdried over MgSO4
7. concentrationwas concentrated in vacuo

ORD 기록

ord-f9b3ddf09a4c4a07afe58c114804b27d

출처 데이터셋

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08242134B2