反应详情

A mixture of (S)-3-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-ylcarbamoyl)benzoic acid (0.923 g, 1.77 mmol, 1.0 equiv), obtained as described above, N,O-dimethylhydroxylamine hydrochloride (0.378 g, 2.2 equiv), EDC (0.600 g, 1.8 equiv), HOBt (0.384 g, 1.6 equiv), and DIEA (3 mL, 9.7 equiv) in CH2Cl2 (20 mL) was stirred at rt for 3 d. The reaction mixture was diluted with brine and extracted with CH2Cl2 (3×). The combined organic extracts were dried over Na2SO4. After the solvent was removed, the crude product was purified by chromatography on a 40-g silica gel cartridge eluted with a gradient from 0% to 40% EtOAc in hexanes to give (S)—N1-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)-N3-methoxy-N3-methylisophthalamide (0.7388 g, 83%). TLC rf=0.38 (50% EtOAc in hexanes); LC-MS (3 min) tR=2.12 min, m/z 528 (MNa+), 506 (M+H+), 478; 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.84 (dt, J=7.9, 1.5 Hz, 1H), 7.75 (d, J=7.6 Hz, 1H), 7.42 (t, J=7.8 Hz, 1H), 677 (d, J=8.2 Hz, 1H), 4.48-4.39 (m, 1H), 4.11-3.97 (m, 2H), 3.72 (dd, J=14.3, 10.5 Hz, 1H), 3.54 (s, 3H), 3.33 (s, 3H), 3.01 (dd, J=14.3, 4.1 Hz, 1H), 2.90 (s, 3H), 1.85-0.80 (m, 15H), −0.06 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 169.03, 166.25, 158.12, 134.41, 130.84, 128.80, 128.12, 126.89, 63.75, 61.06, 52.51, 46.78, 40.64, 34.60, 34.35, 33.53, 33.15, 26.36, 26.13, 26.06, 17.56, −1.61.

1. customobtained
2. extractionextracted with CH2Cl2 (3×)
3. dry with materialThe combined organic extracts were dried over Na2SO4
4. customAfter the solvent was removed
5. customthe crude product was purified by chromatography on a 40-g silica gel cartridge
6. washeluted with a gradient from 0% to 40% EtOAc in hexanes