Trifluoroacetic acid → 2-(2-methyl-1-phenyl-1H-imidazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Participants

Reaction Steps

2-(2-Methyl-1-phenyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (68 mg, 0.111 mmol) was dissolved in 0.6 mL of dichloromethane and then stirred in an ice bath. Trifluoroacetic acid (0.4 mL) was added slowly and the ice bath was removed. The reaction was stirred for 3 h and then cooled in ice bath. Sodium bicarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was dissolved in 4 mL of absolute ethanol, sodium acetate (183 mg) was added and the mixture was stirred for 20 h at 60° C. The reaction was cooled, and water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 33 mg (62%) of 2-(2-methyl-1-phenyl-1H-imidazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide. MS: (M+H)+=481; mp=175-179° C.

Provenance & Evidence