反应详情

温度

90 °C

To a solution of 1-(3-cyclopropylmethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (1.0 g, 3.3 mmol) in DMF (18 mL), were added 2-bromomethyl-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (1.0 g, 3.3 mmol) and triethylamine (1.3 mL, 9.8 mmol). The mixture was heated at 90° C. overnight. The solvent was removed in vacuo. The resulting oil was extracted with ethyl acetate (50 mL) and water (30 mL). The organic layer was washed with water (30 mL×4) and brine (30 mL), and dried over magnesium sulfate. The solvent was removed in vacuo and the resulting oil was purified by silica gel column to give cyclopropanecarboxylic acid {2-[1-(3-cyclopropylmethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (50 mg, 5%): mp 224-226° C.; 1H NMR (CDCl3) δ 0.35-0.39 (m, 2H, c-CH2), 0.60-0.63 (m, 2H, c-CH2), (0.88-0.93 (m, 2H, c-CH2), 1.08-1.12 (m, 2H, c-CH2), 1.25-132 (m, 1H c-CH), 1.63-1.69 (m, 1H, c-CH), 2.95 (s, 3H, CH3), 3.69 (dd, J=5, 15 Hz, 1H, CHH), 3.82 (d, J=4 Hz, 2H, c-CH), 3.86 (s, 3H, CH3), 4.19 (dd, J=10, 17 Hz, 1H, CHH), 4.20 (d, J=17 Hz, 1H, CHHN), 4.43 (d, J=17 Hz, 1H, CHHN), 5.72 (dd, J=5, 10 Hz, 1H, NCH), 6.84-7.02 (m, 4H, Ar), 7.45 (t, J=8 Hz, 1H, Ar), 8.43 (d, J=8 Hz, 1H, Ar), 10.46 (s, 1H, NHCO); 13C NMR (CDCl3) δ 3.3, 3.4, 8.3, 10.2, 16.2, 41.5, 47.9, 51.7, 55.9, 56.0, 74.3, 77.2, 111.8, 113.0, 116.7, 117.1, 117.9, 119.6, 129.4, 133.6, 138.2, 141.3, 149.1, 150.0, 170.1, 172.6. Analy. Calculated for C26H3oN2O6S: C, 62.63; H, 6.06; N, 5.62. Found: C, 62.41; H, 5.95; N, 5.43.

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