反应详情

To a stirred solution of 1′-methyl-2′-oxo-1,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxylic acid (0.200 g, 0.566 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (0.114 g, 0.736 mmol) in N,N-dimethylformamide (20 mL) was added N,N-diisoproylethylamine (0.30 mL, 1.72 mmol) and hydroxybenzotriazole (0.092 g, 0.68 mmol). The reaction mixture was stirred at ambient temperature for 10 min and cyclohexylamine (0.10 mL, 0.87 mmol) was added. The reaction mixture was stirred at ambient temperature for 40 h and concentrated in vacuo to remove most of the N,N-dimethylformamide. The mixture was diluted with ethyl acetate (150 mL), washed with water (3×150 mL) and brine (3×100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate/hexanes (1/1) to afford N-cyclohexyl-1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide (0.127 g, 51%) as a colorless solid: mp 139-140° C.; 1H NMR (300 MHz, CDCl3) δ7.42-7.36 (m, 1H), 7.24-7.20 (m, 1H), 6.98-6.94 (m, 1H), 6.51 (s, 1H), 6.17 (s, 1H), 5.30-5.27 (m, 1H), 4.95 (ABq, 2H), 4.24-4.04 (m, 4H), 3.71-3.61 (m, 1H), 3.26 (s, 3H), 1.78-1.57 (m, 5H), 1.36-1.22 (m, 2H), 1.12-0.99 (m, 1H), 0.89-0.82 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.6, 166.3, 155.9, 145.0, 144.3, 137.9. 134.7, 129.5, 127.4, 122.8, 120.4, 110.7, 109.9, 100.1. 78.0, 64.5, 64.0, 58.2, 48.7, 32.4, 32.1, 26.7, 25.5, 24.9, 24.7; MS (ES+) m/z 435.0 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature for 40 h
2. concentrationconcentrated in vacuo
3. customto remove most of the N,N-dimethylformamide
4. additionThe mixture was diluted with ethyl acetate (150 mL)
5. washwashed with water (3×150 mL) and brine (3×100 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography
10. washeluted with ethyl acetate/hexanes (1/1)