Triphenylphosphine → 5-(azepin-4-yloxy)-4-chloro-1H-indazole

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Reaction Steps

Under a nitrogen atmosphere, triphenylphosphine (280 mg, 1.07 mmol), the tert-butyl 4-hydroxyazepane-1-carboxylate (192 mg, 0.890 mmol) obtained in Example 322, (c) and diisopropyl azodicarboxylate (193 μl, 0.979 mmol) were added at 0° C. to a solution of the 4-chloro-1H-indazol-5-ol (150 mg, 0.890 mmol) obtained in Example 468 in tetrahydrofuran (6 ml). After 30 minutes, the mixture thus obtained was warmed up to room temperature and stirred overnight. The reaction solution was concentrated under reduced pressure, and the resulting residue was diluted with chloroform (20 ml) and washed with a 1M-aqueous sodium hydroxide solution (10 ml). After the aqueous layer was re-extracted with chloroform (10 ml), 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). The oil thus obtained was dissolved in methanol (3 ml) at room temperature and 4N-hydrochloric acid-dioxane (3 ml) was added thereto. After 1 hour, the mixture thus obtained was concentrated under reduced pressure, and the resulting residue was dissolved in methanol (5 ml) and the resulting solution was adjusted to pH 10 by dropwise addition of a 2M-aqueous sodium hydroxide solution. The solution adjusted was concentrated under reduced pressure and the resulting residue was re-dissolved in methanol (5 ml). Silica gel (1 g) was added thereto and the resulting mixture was concentrated under reduced pressure and then dried. The resulting solid was purified by a silica gel column chromatography (eluent: chloroform/methanol→chloroform/methanol (1%-aqueous ammonia)) to obtain 5-(azepin-4-yloxy)-4-chloro-1H-indazole (128.1 mg, 54%).

Provenance & Evidence