Phosphorus oxide (P4O10) → 3-(Trifluoromethyl)imidazo[1,5-a]pyrazine

2,2,2-Trifluoro-N-pyrazin-2-ylmethyl-acetamide 1i (21.0 g, 100 mmol) was added into a reaction flask at room temperature, followed by addition of 100 mL of phosphorus oxychloride. After stirring at room temperature for 30 minutes, phosphorous pentoxide (17.8 g, 125 mmol) was added to the solution. The reaction mixture was heated to reflux for 5 hours and monitored by thin layer chromatography until the disappearance of the starting materials. Phosphorus oxychloride was removed, and the reaction system was quenched with deionized water. The mixture was adjusted to pH 5-6 with 20% sodium hydroxide solution in an ice-water bath. The mixture was extracted with ethyl acetate (250 mL×4), and the combined organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 3-trifluoromethyl-imidazo[1,5-a]pyrazine 1j (12.0 g, yield 65%) as a yellow solid.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 5 hours
3. customPhosphorus oxychloride was removed
4. customthe reaction system was quenched with deionized water
5. customThe mixture was adjusted to pH 5-6 with 20% sodium hydroxide solution in an ice-water bath
6. extractionThe mixture was extracted with ethyl acetate (250 mL×4)
7. dry with materialthe combined organic phase was dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by silica gel column chromatography

ORDレコード

ord-c837455c9d6646459360c1f594425fe9

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08513411B2