反应详情

温度

100 °C

Under a nitrogen atmosphere, the 4-isopropoxy-1H-indazol-5-ol (118 mg, 0.614 mmol) obtained in Example 638 and the trans-2-(3-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (100 mg, 0.408 mmol) obtained in Example 385, (b) were added to a solution of 90%-cyanomethylenetri-n-butylphosphorane (155 mg, 0.614 mmol) in toluene (4 ml) at room temperature, and the resulting mixture was heated to 100° C. After 4.5 hours, the reaction solution was concentrated under reduced pressure and the resulting residue was diluted with chloroform and washed with a 1M-aqueous sodium hydroxide solution. The aqueous layer was re-extracted with chloroform and then the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate). To the resulting oil was added a 30%-methylamine-ethanol solution at room temperature, and the resulting mixture was refluxed. After 4 hours, the mixture was concentrated under reduced pressure at room temperature, and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol→chloroform/methanol (1%-aqueous ammonia)) to obtain cis-3-[(4-isopropoxy-1H-indazol-5-yl)oxy]cyclohexanamine (71.0 mg, 60%).

1. concentrationthe reaction solution was concentrated under reduced pressure
2. additionthe resulting residue was diluted with chloroform
3. washwashed with a 1M-aqueous sodium hydroxide solution
4. extractionThe aqueous layer was re-extracted with chloroform
5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
6. customThe organic layer dried
7. concentrationwas concentrated under reduced pressure
8. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
9. additionTo the resulting oil was added a 30%-methylamine-ethanol solution at room temperature
10. temperaturethe resulting mixture was refluxed
11. waitAfter 4 hours
12. concentrationthe mixture was concentrated under reduced pressure at room temperature
13. customthe resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol→chloroform/methanol (1%-aqueous ammonia))