Cyanomethylenetributylphosphorane → cis-3-[(4-isopropoxy-1H-indazol-5-yl)oxy]cyclohexanamine

Participants

Reaction Conditions

Reaction Steps

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%).

Provenance & Evidence