Diisopropylethylamine → tert-butyl (S)-1-((2S,4R)-4-(biphenyl-4-yl)-4-(butylthio)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-(2,2-difluoroethyl)cyclopropylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

Participants

Reaction Steps

To a solution of (2S,4R)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylic acid (15 mg, 0.026 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-(2,2-difluoroethyl)cyclopropanecarboxamide (8.84 mg, 0.029 mmol), and HATU (15.03 mg, 0.040 mmol) in DMF (1 mL) was added N,N-Diisopropylethylamine (0.014 mL, 0.079 mmol). The formed light yellow solution was stirred at room temperature for 5 h. Diluted with MeOH, purified by prep-HPLC to yield the desired product tert-butyl (S)-1-((2S,4R)-4-(biphenyl-4-yl)-4-(butylthio)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-(2,2-difluoroethyl)cyclopropylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (14 mg, 0.015 mmol, 58.3% yield) as a white solid. 1H NMR (500 MHz, MeOD) ppm 0.83 (t, J=7.17 Hz, 3H), 1.09-1.12 (m, 10H), 1.22-1.45 (m, 7H) 1.47-1.52 (m, 10H), 1.66 (s, 2H), 2.07-2.38 (m, 4H), 2.37-2.51 (m, 1H), 2.76-2.87 (m, 1H), 2.91-3.04 (m, 11H), 3.85-4.06 (m, 2H), 4.51 (d, J=9.77 Hz, 1H), 5.05 (d, J=11.29 Hz, 1H), 5.73-6.09 (m, 1H), 7.37 (t, J=7.02 Hz, 1H), 7.46 (t, J=7.48 Hz, 2H), 7.54-7.64 (m, 4H), 7.68 (d, J=8.24 Hz, 2H). LC-MS (retention time: 3.48 min, method B), MS m/z 819 (M+H).

Provenance & Evidence