Water → 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

Participants

Reaction Conditions

Reaction Steps

2-Bromo-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 (115 mg, 0.188 mmol) and 2-methyl-1-phenyl-4-tributylstannanyl-1H-imidazole (101 mg, 0.225 mmol) were dissolved in 1.9 mL of DMF and the mixture was purged with Ar gas. Tetrakis(triphenylphosphine)palladium (10.8 mg, 0.0094 mmol) and then copper (I) iodide (7.1 mg, 0.038 mmol) were added and the reaction was sealed and stirred in an 80° C. oil bath for 18 h. The reaction was cooled and water, dichloromethane, and sodium bicarbonate solution were added. The layers were separated, and the aqueous layer was extracted twice more with dichloromethane. The combined organic layers were washed with water and then brine, and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to provide 68 mg (59%) of 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. (M+H)+=611.

Provenance & Evidence