Methylamine → tert-Butyl 4-(4-((4-((6-(2-ethoxyethoxy)-1-(methylcarbamoyl)-1H-indol-5-yl)oxy)pyridin-2-yl)carbamoyl)phenyl)piperidine-1-carboxylate

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Reaction Steps

Thionyl chloride (370 μL, 5.06 mmol) was added to a solution of benzotriazole (603 mg, 5.06 mmol) in dichloromethane (20 mL) under nitrogen atmosphere at room temperature. The mixture was stirred at room temperature for 5 minutes, then 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid described in Production Example 1-12 (1.03 g, 3.38 mmol) was added, and the mixture was stirred for 1 hour. The reaction liquid was filtered through anhydrous sodium sulfate on the glass filter, and the resultant was washed with dichloromethane. Triethylamine (1.87 mL, 13.5 mmol), 4-dimethylaminopyridine (16.5 mg, 0.135 mmol), and a solution of 5-((2-aminopyridin-4-yl)oxy)-6-(2-ethoxyethoxy)-N-methyl-1H-indole-1-carboxamide described in Production Example 24-8 (500 mg, 1.35 mmol) in tetrahydrofuran (5 mL) were serially added to the resultant filtrate under nitrogen atmosphere at 0° C., and the mixture was stirred at room temperature for 4 hours. An excessive quantity of methylamine was added to the reaction liquid and then the resultant was diluted with ethyl acetate and water for partition. The organic layer was washed with a saturated saline solution and then dried over anhydrous sodium sulfate, and the drying agent was separated by filtration. The filtrate was concentrated under vacuum. The resultant residue was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=2:3-0:1) to obtain the title compound (383 mg, 43%).

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