Triethylamine → tert-Butyl 4-{[4-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)phenyl]carbonyl}piperazine-1-carboxylate

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Reaction Steps

The compound (200 mg, 0.311 mmol) obtained in Example 15c was dissolved in 1,4-dioxane, a 4 N hydrochloric acid-dioxane solution (4.67 mL, 18.7 mmol) was added, and the mixture was stirred at room temperature for 12 hours. After the reaction was completed, toluene was added, and then the solvent was evaporated under reduced pressure to give crude 4-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)benzoic acid. The resulting crude carboxylic acid compound and tert-butyl piperazine-1-carboxylate (58 mg, 0.311 mmol) were dissolved in methylene chloride, triethylamine (0.259 mL, 1.87 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (90 mg, 0.467 mmol) were added, and the mixture was stirred at room temperature for 17 hours. The solvent was evaporated under reduced pressure, the resulting residue was dissolved in ethyl acetate, water and saturated aqueous sodium hydrogencarbonate were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=1:2→0:100, v/v) to give the title compound (98 mg; yield, 42%) as a white solid.

Provenance & Evidence