Trifluoroacetic acid → HCID 58438590, compound

Participants

Reaction Steps

[(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester (0.99 g, 3.54 mmol) was dissolved in 24 mL of dichloromethane and cooled in an ice bath. Trifluoroacetic acid (10.6 mL) was added slowly and the reaction was then stirred at room temperature. After 3 h., the reaction was judged complete by TLC and was then evaporated under high vacuum. The residue was dissolved in 34 mL of acetonitrile to which was then added 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1.28 g, 3.44 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.21 g, 3.78 mmol) and N,N-diisopropylethylamine (2.1 mL, 12 mmol). The reaction was stirred for 18 h and then water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane). The resultant viscous oil was triturated with hexanes to provide 0.93 g (50%) of 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 as a white solid.

Provenance & Evidence