Phenyl Methylcarbamate → 5-((2-Aminopyridin-4-yl)oxy)-6-isopropoxy-N-methyl-1H-indole-1-carboxamide

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Reaction Steps

4-((6-Isopropoxy-1H-indol-5-yl)oxy)pyridin-2-amine described in Production Example 17-6 (65.6 mg, 0.232 mmol) was dissolved in N,N-dimethylformamide (1.5 mL), 50-72% oily sodium hydride (16.7 mg) was added under nitrogen atmosphere at 0° C., and the mixture was stirred at room temperature for 50 minutes. The mixture was cooled to 0° C. again, phenyl methylcarbamate described in Production Example 1-7 (69.2 mg, 0.458 mmol) was added, and the mixture was stirred at room temperature for 3 hours. A saturated aqueous ammonium chloride solution, water, and ethyl acetate were added to the reaction mixture for partition. The aqueous layer was extracted with ethyl acetate and the combined organic layer was washed with water and then with a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate and then filtered, then the filtrate was concentrated under vacuum. The residue was dissolved in dichloromethane and the resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=3:7-0:1-ethyl acetate:methanol=99:1-19:1), then the target fraction was concentrated under vacuum to obtain the title compound (77.0 mg, 98%).

Provenance & Evidence