Cesium fluoride → HCID 58438550, compound

Participants

Reaction Steps

A solution of 2-[1-(2,5-difluoro-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 (0.037 g, 0.058 mmol), 18-crown-6 (0.016 g, 0.058 mmol) and cesium fluoride (0.093 g, 0.58 mmol) in 1 mL of acetonitrile was stirred at 75° C. for 5 d, then concentrated. The resulting residue was partitioned between 5 mL of a 1 M citric acid solution and 5 mL of dichloromethane. The aqueous layer was extracted with two 5 mL portions of dichloromethane. The combined organic layers were dried over Na2SO4, filtered and concentrated. Dichloromethane (1 mL) and 1 mL of trifluoroacetic acid were added, and the yellow solution was stirred 2 h, then concentrated. Dichloromethane (0.5 mL) and 0.5 mL of ethylene diamine were added, and the yellow-orange solution was stirred 1 h. The solution was partitioned between 10 mL of ethyl acetate and 5 mL of water, and the aqueous layer was extracted with 10 mL of ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated. Column chromatography (0->10% MeOH/EtOAc) afforded 0.0055 g (19%) of 2-[1-(2,5-difluoro-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 as a pale yellow solid. MS: (M−H)−=501.

Provenance & Evidence