Aminopyrazine → 2-(Trifluoromethyl)imidazo[1,2-a]pyrazine

Pyrazin-2-amine 4a (5.25 g, 55.20 mmol) was dissolved in 120 mL of ethanol, followed by addition of 3-bromo-1,1,1-trifluoro-propan-2-one 12a (5.7 mL, 55.20 mmol). The reaction mixture was heated to reflux for 16 hours. The reaction mixture was concentrated under reduced pressure, added with 100 mL of ethyl acetate and 100 mL of saturated sodium bicarbonate solution and separated. The aqueous phase was extracted with ethyl acetate (50 mL×3). The organic phase was combined, washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography with elution system B to obtain 2-(trifluoromethyl)imidazo[1,2-a]pyrazine 12b (2.40 g, yield 22.8%) as a yellow solid.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 16 hours
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. additionadded with 100 mL of ethyl acetate and 100 mL of saturated sodium bicarbonate solution
5. customseparated
6. extractionThe aqueous phase was extracted with ethyl acetate (50 mL×3)
7. washwashed with saturated sodium chloride solution (50 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customthe resulting residue was purified by silica gel column chromatography with elution system B

ORD record

ord-c036952bf35f4481860051a468596f63

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273052B2