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

Participants

Reaction Steps

Oxalyl chloride (74 μL, 0.864 mmol) and one drop of N,N-dimethylformamide were added to a solution of 6-(1-(tert-butoxycarbonyl)piperidin-4-yl)nicotinic acid described in Production Example 28-3 (80 mg, 0.216 mmol) in dichloromethane (2 mL) at 0° C., and the mixture was stirred for 30 minutes. The reaction liquid was concentrated under vacuum. The residue was dissolved in tetrahydrofuran (2 mL), then triethylamine (301 μL, 2.16 mmol) and 5-((2-aminopyridin-4-yl)oxy)-6-(2-ethoxyethoxy)-N-methyl-1H-indole-1-carboxamide described in Production Example 24-8 (80 mg, 0.216 mmol) were added, and the mixture was stiffed for 5 hours. An excessive quantity of methylamine was added to the reaction liquid, and then the mixture was diluted with water and ethyl acetate for partition. The organic layer was washed with a saturated saline solution and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration and then the filtrate was concentrated under vacuum. The residue was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:1) to obtain the title compound (80 mg, 56%).

Provenance & Evidence