反应详情

Into tetrahydrofuran (5 ml), 2-(trimethylsilyl)ethyl [4-(2-2-(tetrahydro-2H-pyran-4-yloxy)ethoxy)phenyl]isoquinoline-6-carboxylate (305 mg, 0.62 mmol) synthesized in Example 4 (4a) was dissolved, to which a solution of 1 M tetrabutylammonium fluoride in tetrahydrofuran (1.2 ml, 1.2 mmol) was added. The resulting mixture was stirred at room temperature for two hours and then concentrated under reduced pressure. The residue thus obtained was dissolved in dimethylformamide (10 ml), to which ammonium chloride (660 mg, 12.3 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (590 mg, 3.1 mmol), 1-hydroxy-1H-benzotriazole monohydrate (470 mg, 3.1 mmol), and triethylamine (2.1 ml, 15.1 mmol) were added. The resulting mixture was stirred overnight at room temperature, to which water was added, followed by extraction with dichloromethane three times. The resulting organic layer was collected and washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (ethyl acetate:methanol, 100:0-95:5, V/V) and recrystallized from methanol-ethyl acetate-hexane to give the desired title compound (108 mg, yield 45%).

1. additionwas added
2. concentrationconcentrated under reduced pressure
3. customThe residue thus obtained
4. additionwere added
5. additionwas added
6. extractionfollowed by extraction with dichloromethane three times
7. customThe resulting organic layer was collected
8. washwashed with saturated brine
9. dry with materialdried over anhydrous sodium sulfate
10. distillationThe solvent was distilled off under reduced pressure
11. customThe residue thus obtained
12. customwas purified by silica gel column chromatography (ethyl acetate:methanol, 100:0-95:5, V/V)
13. customrecrystallized from methanol-ethyl acetate-hexane