p-Toluenesulfonic acid → tert-butyl (3S,14R,16S)-14-(biphenyl-4-yl)-16-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadecan-3-ylcarbamate

Participants

Reaction Steps

To an iced slurry of (3S,14R,16S)-14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadecane-16-carboxylic acid (20 mg, 0.034 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, pTSA, 0.68H2O (17.85 mg, 0.043 mmol), and HATU (32.5 mg, 0.0855 mmol) in DCM (1 mL) was added N,N-Diisopropylethylamine (0.030 mL, 0.172 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,14R,16S)-14-(biphenyl-4-yl)-16-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadecan-3-ylcarbamate (7 mg, 8.65 mmol, 25.1% A yield) as a white foam. 1H NMR (400 MHz, MeOD) δ ppm 0.94-1.37 (m, 13 H) 1.35-1.63 (m, 12 H) 1.84 (dd, J=8.16, 5.40 Hz, 1 H) 1.91-2.08 (m, 4 H) 2.08-2.19 (m, 1 H) 2.19-2.45 (m, 4 H) 2.59 (dd, J=12.30, 6.53 Hz, 1 H) 2.82-2.99 (m, 1 H) 3.87 (dd, J=10.29, 6.53 Hz, 1 H) 4.00-4.22 (m, 2 H) 4.64 (t, J=8.53 Hz, 1 H) 5.07 (dd, J=10.29, 1.51 Hz, 1 H) 5.24 (dd, J=17.19, 1.38 Hz, 1 H) 5.60-5.78 (m, 1 H) 6.36 (d, J=8.53 Hz, 1 H) 7.32 (t, J=7.28 Hz, 1 H) 7.42 (t, J=7.53 Hz, 2 H) 7.53-7.74 (m, 6 H); LC-MS (retention time: 3.50 min, method C), MS m/z 793.5 (M+H), 737 (M-t-Bu), 693 (M-BOC).

Provenance & Evidence