反应详情

温度

90 °C

To a solution of (1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (1.4 g, 5.1 mmol) in DMF (20 ml) was added 2-bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (1.6 g, 4.6 mmol) and triethyl amine (2.0 ml, 14 mmol). The mixture was heated at 90° C. overnight. The solvent was removed in vacuo. The resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with water (30 ml×2), brine (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo and the resulted oil was purified by silica gel column to give (1S)-cyclopropanecarboxylic acid {7-chloro-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (650 mg, 30%): mp, 197-199° C.; 1H NMR (CDCl3) δ 0.89-0.93 (m, 2H, c-CH2), 1.08-1.12 (m, 2H, c-CH2), 1.44 (t, J=7.0 Hz, 3H, OCH2CH3), 1.65-1.69 (m, 1H, c-CH), 2.97 (s, 3H, CH3SO2), 3.70 (dd, J=5, 15 Hz, 1H, CHH), 3.87(s, 3H, OCH3), 4.05-4.23 (m, 4H, NCH+CH+OCH2CH3), 4.41 (d, J=17 Hz, 1H, CHH), 5.75-5.81 (m, 1H, CHN), 6.86-6.96 (m, 3H, Ar), 7.39 (d, J=9.0 Hz, 1H, Ar), 8.45(d, J=9.0 Hz, 1H, Ar), 10.36 (s, 1H, NHCO). 13CNMR (CDCl3): δ 8.5, 14.7, 16.2, 41.6, 46.9, 51.3, 55.5, 56.0, 64.7, 111.7, 112.3, 118.6, 119.3, 119.7, 121.8, 129.1, 133.2, 136.8, 139.0, 149.0, 149.9, 169.2, 172.6; Anal Calcd for C24H27ClN2O6S: C, 56.86; H, 5.37; N, 5.53; Found: C, 56.81; H, 5.26; N, 5.56.

1. customThe solvent was removed in vacuo
2. extractionThe resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml)
3. washThe organic layer was washed with water (30 ml×2), brine (30 ml)
4. dry with materialdried over magnesium sulfate
5. customThe solvent was removed in vacuo
6. customthe resulted oil was purified by silica gel column