Water → ((4-(1-methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acid

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Reaction Steps

Methyl aminoacetate hydrochloride (300 mg, 2.3 mmol) was dissolved in N,N-dimethylformamide (4 ml), and then triethylamine (1 ml) was added. Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate (250 mg, 0.48 mmol) synthesized in Production example 5-2 was added thereto. The reaction mixture was stirred at room temperature for 22 hours. After water was added to the reaction mixture, extraction was performed with a solvent mixture of ethyl acetate-tetrahydrofuran. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300, ethyl acetate). The obtained pale yellow oil was dissolved in a solvent mixture of tetrahydrofuran (2 ml)-methanol (1 ml), then 4N aqueous solution of lithium hydroxide (0.48 ml) was added, and the reaction mixture was stirred at room temperature for 1 hour. After that, 1N hydrochloric acid (2 ml) was added, and this was subjected to extraction with ethyl acetate-tetrahydrofuran. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield the title compound (145 mg, 0.38 mmol, 79%) as colorless crystals.

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