反应详情

To an iced slurry of (3S,14R,16S,E)-14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-ene-16-carboxylic acid, (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, pTSA, 0.68H2O (29.6 mg, 0.071 mmol), and HATU (32.5 mg, 0.0855 mmol) in DCM (2 mL) was added N,N-Diisopropylethylamine (0.050 mL, 0.285 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 Biotage column, eluted with gradient 5%˜40% Acetone-Hexane to afford the desired product tert-butyl (3S,14R,16S,E)-14-(biphenyl-4-yl)-16-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-en-3-ylcarbamate (31 mg, 0.038 mmol, 66.0% yield) as a white foam. 1H NMR (500 MHz, MeOD) δ ppm 1.09 (s, 1 H) 1.16-1.32 (m, 3 H) 1.33-1.40 (m, 2 H) 1.41-1.63 (m, 16 H) 1.64-1.83 (m, 4 H) 1.87-1.99 (m, 2 H) 2.00-2.11 (m, 1 H) 2.13-2.24 (m, 1 H) 2.24-2.34 (m, 1 H) 2.40 (t, J=11.29 Hz, 1 H) 2.62-2.75 (m, 2 H) 2.87-3.01 (m, 1 H) 3.08 (d, J=14.95 Hz, 1 H) 3.87 (dd, J=10.38, 6.41 Hz, 1 H) 4.01 (d, J=10.68 Hz, 1 H) 4.59-4.80 (m, 2 H) 5.12 (d, J=10.07 Hz, 1 H) 5.29 (d, J=17.09 Hz, 1 H) 5.53-5.63 (m, 2 H) 5.64-5.80 (m, 1 H) 7.37 (t, J=7.48 Hz, 1 H) 7.47 (t, J=7.48 Hz, 2 H) 7.57-7.64 (m, 2 H), 7.68-7.82 (m, 4 H). LC-MS (retention time: 3.48 min, method C), MS ink 792 (M+H), 735 (M-t-Bu), 691 (M-BOC).

1. washwashed it with 5% citric acid, and brine
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. customevaporated
5. customThe formed residue was purified by Biotage column
6. washeluted with gradient 5%˜40% Acetone-Hexane