18-Crown-6 → tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoate

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Reaction Steps

In a two-necked flask the inner atmosphere of which had been replaced with nitrogen were placed tert-butyl 4-bromobenzoate (2.57 mg, 1.00 mmol), toluene (2 ml), 18-crown-6 (380 mg, 1.40 mmol), the 1-(2-tetrahydropyranyl)-1H-indazol-5-amine (261 mg, 1.23 mmol) obtained in Example 317, (e) and sodium tert-butoxide (135 mg, 1.40 mmol) in that order. After the inner atmosphere of the flask was replaced with nitrogen again, tris(dibenzylideneacetone)(chloroform) dipalladium(0) (52 mg, 0.050 mmol) and (S)-2,2′-bis(diphenylphophino)-1,1′-binaphthyl (94 mg, 0.151 mmol) were added. After the third replacement of the inner atmosphere of the flask with nitrogen, stirring was conducted at 80° C. for 8 hours. The resulting mixture was diluted with diethyl ether and the solid was removed by filtration using Celite. Then, the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1) to obtain tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoate (218 mg, 56%).

Provenance & Evidence