反应详情

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).

1. extractionfollowed by extraction with ethyl acetate
2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
3. distillationdistilled under reduced pressure
4. customto remove the solvent
5. customThe resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=40/1)
6. additionTo a solution of the resulting solid in a mixture of methanol (1 ml) and tetrahydrofuran (1 ml)
7. additionwas added a 2N-aqueous lithium hydroxide solution (0.68 ml)
8. stirringthe resulting mixture was stirred at room temperature for 30 minutes
9. additionThen, the reaction solution was poured into water
10. extractionextracted with ethyl acetate
11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
12. distillationdistilled under reduced pressure
13. customto remove the solvent
14. customThe resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=30/1)