p-Toluenesulfonic acid → tert-butyl (3S,13R,15S,E)-13-(biphenyl-4-yl)-15-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-en-3-ylcarbamate

Participants

Reaction Steps

To an iced slurry of (3S,13R,15S,Z)-13-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-ene-15-carboxylic acid (28 mg, 0.050 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, pTSA, 0.68H2O (25.7 mg, 0.062 mmol), and HATU (28.5 mg, 0.075 mmol) in DCM (1 mL) was added N,N-Diisopropylethylamine (0.043 mL, 0.248 mmol). The formed light brown solution was stirred at room temperature overnight. Diluted with EtOAc, washed it with 5% citric acid, and brine, dried over MgSO4, filtered, evaporated. The formed residue was purified by prep-HPLC to afford the desired product tert-butyl (3S,13R,15S,E)-13-(biphenyl-4-yl)-15-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-en-3-ylcarbamate (22 mg, 0.026 mmol, 52.5% yield) as a white solid.

Provenance & Evidence