Benzyl Alcohol → tert-Butyl [3-(6-amino-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)propyl]methylcarbamate

Participants

Reaction Conditions

Reaction Steps

The compound (535 mg, 1.41 mmol) obtained in Example 61c was dissolved in a mixed solvent (6 mL) of tetrahydrofuran and methanol (1:1), a 1 N aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at 60° C. for 5 hours. After the reaction was completed, a 1 N aqueous hydrochloric acid solution (10 mL) was added to the reaction mixture under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in 1,4-dioxane (6 mL), diphenyl phosphate azide (0.238 mL, 1.10 mmol), triethylamine (0.154 mL, 1.10 mmol) and benzyl alcohol (0.228 mL, 2.21 mmol) were added under ice cooling, and the mixture was stirred at 100° C. under a nitrogen atmosphere for 16 hours. After the reaction was completed, the solvent was evaporated under reduced pressure. The resulting residue was dissolved in a mixed solvent (12 mL) of ethyl acetate and methanol (1:2), 10% palladium-carbon (53 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 1 hour. After the reaction was completed, the reaction mixture was filtered through celite, the filtrate was washed with ethanol, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol, 10:1, v/v) to give the title compound (149 mg; yield, 81%) as a colorless oily substance.

Provenance & Evidence