Triethylamine → 4-{4-[2-(Tetrahydro-2H-pyran-4-yloxy)ethoxy]phenyl}isoquinoline-6-carboxamide

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Reaction Steps

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%).

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