반응 #1514231

반응 방정식

Oxalyl chloride

6-(1-(tert-butoxycarbonyl)piperidin-4-yl)nicotinic acid

5-((2-aminopyridin-4-yl)oxy)-6-(2-ethoxyethoxy)-N-methyl-1H-indole-1-carboxamide

triethylamine

methylamine

→

title compound

수율 56.0%

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

수율 56.0%

용매

dichloromethane

water

ethyl acetate

반응 조건

후처리

1. 1
   기타The reaction liquid
2. 2
   농축was concentrated under vacuum
3. 3
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (2 mL)
4. 4
   workup.ADDITIONwere added
5. 5
   workup.WAITthe mixture was stiffed for 5 hours
6. 6
   기타for partition
7. 7
   세척The organic layer was washed with a saturated saline solution
8. 8
   건조dried over anhydrous sodium sulfate
9. 9
   기타The drying agent was separated by filtration
10. 10
    농축the filtrate was concentrated under vacuum
11. 11
    기타The residue was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:1)

실험 절차

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%).

출처