1-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid → tert-butyl 4{[(1H-indazol-5-ylmethyl)amino]carbonyl}-1-piperidinecarboxylate

Participants

Reaction Steps

To a solution of 1-(1H-indazol-5-yl)methanamine (291 mg) in N,N-dimethylformamide (8 ml) were added 1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid (507 mg, 2.21 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide monohydrochloride (578 mg, 3.02 mmol) and hydroxybenzotriazole (229 mg, 2.21 mmol), and the resulting mixture was stirred at room temperature for 14 hours. Subsequently, a saturated aqueous sodium hydrogencarbonate solution and then water were added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=40/1). To a solution of the resulting solid in a mixture of methanol (1 ml) and tetrahydrofuran (1 ml) was added a 2N-aqueous lithium hydroxide solution (0.68 ml), and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=30/1) to obtain tert-butyl 4{[(1H-indazol-5-ylmethyl)amino]carbonyl}-1-piperidinecarboxylate (179 mg).

Provenance & Evidence