3-Carbethoxy-2-piperidone → ethyl 3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate

To a mixture of ethyl 2-oxopiperidine-3-carboxylate (3.5 g) in acetonitrile (100 mL) was added trimethyloxonium tetrafluoroborate (3.0 g) at room temperature, and the mixture was stirred at room temperature for 2 hr. 6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridine-2-carbohydrazide (5.0 g) was added to the reaction mixture at room temperature, and the solvent was evaporated under reduced pressure. Methanol (100 mL) was added to the residue at room temperature, and the mixture was stirred for 2 hr under reflux. The solvent in the reaction mixture was evaporated under reduced pressure, acetonitrile (100 mL) was added to the residue at room temperature, and the mixture was stirred at 80° C. overnight. The solvent in the reaction mixture was evaporated under reduced pressure, the residue was diluted with ethyl acetate and saturated aqueous sodium hydrogen carbonate solution, the mixture was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue of another lot synthesized similarly was combined, and the mixture was purified by silica gel column chromatography (methanol/ethyl acetate) to give the title compound (3.1 g).

1. customthe solvent was evaporated under reduced pressure
2. additionMethanol (100 mL) was added to the residue at room temperature
3. stirringthe mixture was stirred for 2 hr
4. temperatureunder reflux
5. customThe solvent in the reaction mixture was evaporated under reduced pressure, acetonitrile (100 mL)
6. additionwas added to the residue at room temperature
7. stirringthe mixture was stirred at 80° C. overnight
8. customThe solvent in the reaction mixture was evaporated under reduced pressure
9. additionthe residue was diluted with ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
10. washthe mixture was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customthe solvent was evaporated under reduced pressure
13. customThe residue of another lot synthesized similarly
14. customthe mixture was purified by silica gel column chromatography (methanol/ethyl acetate)

ORD 기록

ord-4cf9fdc16a2e4e439ba3b09fe645dcf0

출처 데이터셋

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08822699B2