Hydrochloric Acid → HCID 57518479、化合物

温度

-78 °C

3-Trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 27d (0.85 g, 2.54 mmol) was dissolved in a mixture of 25 mL of anhydrous toluene and 8 mL of anhydrous tetrahydrofuran. The reaction flask was placed in a dry ice-acetone bath and cooled to −78° C., and then tetramethyl-ethylenediamine (1.32 mL, 8087 mmol) was added to the flask. n-Butyllithium (5.55 mL, 8.87 mmol) was added dropwise in 5 minutes. After reacting at −78° C. for 15 minutes, iodomethane (0.4 mL, 6.34 mmol) was added dropwise. The reaction mixture was reacted at −78° C. for 10 minutes, then was allowed to warm up to room temperature and reacted for 2 hours until thin lay chromatography showed the starting material disappeared. 15 mL of saturated ammonium chloride and 20 mL of water were added to the reaction mixture successively. The mixture was adjusted to pH 3-4 with 2 N hydrochloric acid, and extracted with ethyl acetate (30 mL×3). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 8-methyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 39a (0.215 g, yield 24.3%) as a white solid.

1. customThe reaction flask was placed in a dry ice-acetone bath
2. customThe reaction mixture was reacted at −78° C. for 10 minutes
3. temperatureto warm up to room temperature
4. customreacted for 2 hours
5. extractionextracted with ethyl acetate (30 mL×3)
6. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography

ORDレコード

ord-8dcb8062099041baa5a45e330e162828

出典データセット

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08207161B2