3,4-dihydro-2H-pyran → HCID 69436428, compound

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Reaction Steps

Under nitrogen, the cis-3-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanamine (500 mg, 2.04 mmol) obtained in Example 411 was suspended in dichloromethane (10 ml), and 3,4-dihydro-2H-pyran (205 μl, 2.24 mmol) and pyridinium p-toluenesulfonate (51 mg, 0.204 mmol) were added thereto, followed by adding thereto p-toluenesulfonic acid monohydrate (387 mg, 2.04 mmol). N-methyl-2-pyrrolidinone (10 ml) was added thereto to effect dissolution, and the resulting solution was stirred as follows: at room temperature for 17 hours; at 60° C. for 3.5 hours; and then at 80° C. for 10 hours. The reaction solution was cooled to room temperature and a 1N-aqueous sodium hydroxide solution was added thereto, followed by extraction with chloroform (twice). The combined chloroform layer was washed with a saturated aqueous sodium chloride solution, dried by the addition of anhydrous magnesium sulfate, and then filtered. The solvent was distilled off under reduced pressure and the resulting concentration residue was purified by a silica gel column chromatography (eluents: chloroform/methanol=20/1 and chloroform/methanol/aqueous ammonia=10/0.8/0.1) to obtain cis-3-[(4-methyl-1-tetrahydro-2H-pyran-2-yl-1H-indazol-5-yl)oxy]cyclohexanamine (602 mg, yield 89.6%) as colorless tar.

Provenance & Evidence