Sodium hydride → 5-(2-Aminopyridin-4-yloxy)-2,3-dihydro-1H-indole-1-carboxylic acid methylamide

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Reaction Conditions

Reaction Steps

Sodium hydride (202 mg, 3.89 mmol, 60% in oil) was suspended in dimethyl sulfoxide (5.0 ml), then 5-hydroxy-2,3-dihydro-1H-indole-1-carboxylic acid methylamide (971 mg, 5.06 mmol) and 2-amino-4-chloropyridine (500 mg, 3.89 mmol) were added at room temperature under nitrogen atmosphere, and the reaction mixture was heated and stirred at 160° C. for 12 hours under nitrogen atmosphere. After naturally cooled down to room temperature, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, was dried over anhydrous magnesium sulfate, and was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300; eluent:ethyl acetate, ethyl acetate:methanol=85:10 in this order). The fractions containing the desired compound were concentrated, and the residue was further purified by silica gel column chromatography (Fuji Silysia NH, eluent; from ethyl acetate to ethyl acetate:methanol=90:10). The obtained crystals were suspended in diethyl ether:acetone=3:1, filtered off, washed with diethyl ether, and dried under aeration to yield the title compound (51 mg, 0.18 mmol, 4.6%) as pale green crystals.

Provenance & Evidence