Methanol → Imidazo[1,2-a]pyrazine-3-carboxylic acid, ethyl ester

Pyrazin-2-amine 4a (1 g, 10 mmol) was dissolved in 50 mL of ethylene glycol dimethyl ether, followed by addition of 50 mL of methanol and 3-bromo-2-oxo-propionate (2.30 g, 12 mmol). After stirring for 4 hours at room temperature, the reaction mixture was cooled to 0° C. and stirred for 30 minutes until a solid precipitated. The reaction mixture was filtered, and the filter cake was washed with ether (10 mL×3). The solid was dissolved in 50 mL of anhydrous ethanol and the solution was refluxed for 4 hours. The reaction mixture was concentrated under reduced pressure, added with 100 mL of dichloromethane, washed successively with saturated sodium carbonate solution (40 mL) and saturated sodium chloride solution (40 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain ethyl imidazo[1,2-a]pyrazine-3-carboxylate 14a (0.55 g, yield 28.9%) as a brown solid.

1. temperaturethe reaction mixture was cooled to 0° C.
2. stirringstirred for 30 minutes until a solid
3. customprecipitated
4. filtrationThe reaction mixture was filtered
5. washthe filter cake was washed with ether (10 mL×3)
6. dissolutionThe solid was dissolved in 50 mL of anhydrous ethanol
7. temperaturethe solution was refluxed for 4 hours
8. concentrationThe reaction mixture was concentrated under reduced pressure
9. additionadded with 100 mL of dichloromethane
10. washwashed successively with saturated sodium carbonate solution (40 mL) and saturated sodium chloride solution (40 mL)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-945c18af5f3f44ee80c995df1422b802

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273052B2