反应详情

To a slurry of (2S,4R)-4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid (16 mg, 0.029 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, pTSA, 0.68H2O (15.01 mg, 0.036 mmol), and HATU (16.51 mg, 0.043 mmol) in DCM (1 mL) was added N,N-diisopropylethylamine (0.025 mL, 0.145 mmol). The formed solution was stirred at room temperature overnight. Diluted with DCM, washed with 1M HCl and brine, dried over MgSO4, filtered, evaporated. The residue was purified by BIOTAGE® column, eluted with gradient 5%˜50% acetone-hexane to afford the desired product tert-butyl (S)-1-((2S,4R)-4-(allylthio)-4-(biphenyl-4-yl)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (13 mg, 0.016 mmol, 55.2% yield) as a white foam. 1H NMR (500 MHz, MeOD) ppm 0.99-1.15 (m, 10H) 1.24 (d, J=4.52 Hz, 2H) 1.42 (dd, J=9.41, 5.40 Hz, 1H) 1.49 (s, 9H) 1.86 (dd, J=8.03, 5.52 Hz, 1H) 2.19 (q, J=8.78 Hz, 1H) 2.34 (t, J=41.54 Hz, 1H) 2.81 (dd, J=12.17, 6.40 Hz, 1H) 2.87-3.07 (m, 3H) 3.89 (dd, J=10.54, 6.27 Hz, 1H) 3.97 (d, J=11.04 Hz, 1H) 4.48 (d, J=9.79 Hz, 1H) 4.97-5.15 (m, 4H) 5.27 (d, J=17.07 Hz, 1H) 5.64-5.88 (m, 2H) 6.75 (d, J=9.79 Hz, 1H) 7.30-7.40 (m, 1H) 7.45 (t, J=7.53 Hz, 2H) 7.54-7.63 (m, 4H) 7.64-7.74 (m, 2H). LC-MS (retention time: 3.00 mm, method B), MS m/z 765 (M+H).

1. washwashed with 1M HCl and brine
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. customevaporated
5. customThe residue was purified by BIOTAGE® column
6. washeluted with gradient 5%˜50% acetone-hexane