反应详情

Under an argon atmosphere, to a solution of N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methylamine obtained in Example 4, Step 1 (40 mg, 0.14 mmol) and (3-oxomorpholin-4-yl)acetic acid obtained in Reference Example 4 (76 mg, 0.48 mmol) in pyridine (1.3 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (91 mg, 0.48 mmol) at room temperature, and the mixture was stirred at room temperature for 12 hr. Then, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in methanol (1.2 ml), 2 N aqueous sodium hydroxide solution (1.0 ml) was added, and the mixture was stirred at room temperature for 45 min. Then, to the reaction mixture were added water and ethyl acetate, and the organic layer was separated. The aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were washed successively with water and saturated brine, and dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (40 mg, yield 67%).

1. concentrationThen, the reaction mixture was concentrated under reduced pressure
2. dissolutionThe residue was dissolved in methanol (1.2 ml)
3. addition2 N aqueous sodium hydroxide solution (1.0 ml) was added
4. stirringthe mixture was stirred at room temperature for 45 min
5. additionThen, to the reaction mixture were added water and ethyl acetate
6. customthe organic layer was separated
7. extractionThe aqueous layer was extracted twice with ethyl acetate
8. washthe combined organic layers were washed successively with water and saturated brine
9. dry with materialdried over sodium sulfate
10. customSodium sulfate was removed by filtration
11. concentrationthe filtrate was concentrated under reduced pressure
12. customThe residue was purified by silica gel chromatography