反应详情

EDC (112.7 mg, 0.59 mmole) was added all at once to a solution of ethyl (±)-10,11-dihydro-3-carboxy-5H-dibenzo[a,d]cycloheptene-10-acetate (157.8 mg, 0.49 mmole), 2-[(2-aminoethyl)amino]pyridine dihydrochloride (123.5 mg, 0.59 mmole), HOBt.H2O (79.5 mg, 0.59 mmole), and diisopropylethylamine (0.43 mL, 2.45 mmole) in anhydrous DMF (2.5 mL) at RT. The reaction was stirred at RT for 18 hr, then was concentrated. The residue was reconcentrated from xylenes, then was diluted with H2O (5 mL) and extracted sequentially with EtOAc (2×5 mL) and CHCl3 (2×5 mL). The organic layers were combined and treated with a little MeOH to dissolve a small amount of insoluble material. Drying (MgSO4), concentration, and silica gel chromatography (5% MeOH/CHCl3) gave the title compound (199.1 mg, 92%) as a yellow oil: TLC (5% MeOH/CHCl3) Rf 0.42; 1H NMR (400, CDCl3) δ 8.10 (d, J=3.5 Hz, 1 H), 8.02 (br s, 1 H), 7.60 (app. narrow d, 1 H), 7.53 (app. dd, 1 H), 7.33-7.42 (m, 1 H), 7.08-7.22 (m, 5 H), 6.57-6.65 (m, 1 H), 6.45 (d, J=8.3 Hz, 1 H), 4.79-4.90 (m, 1 H), 4.36 (d,J=15.1 Hz, 1 H), 4.11-4.26 (m, 2 H), 3.92 (d, J=15.1 Hz, 1 H), 3.80-3.95 (m, 1 H), 3.55-3.72 (m, 4 H), 3.38 (dd, J=15.2, 4.1 Hz, 1 H), 3.03 (dd, J=15.2, 9.5 Hz, 1 H), 2.66 (dd, J=15.8,4.8 Hz, 1 H), 2.50 (dd, J=15.8, 9.6 Hz, 1 H), 1.27 (t, J=7.2 Hz, 3 H); MS (ES) m/e 444 (M+H)+.

1. customat RT
2. concentrationwas concentrated
3. additionwas diluted with H2O (5 mL)
4. extractionextracted sequentially with EtOAc (2×5 mL) and CHCl3 (2×5 mL)
5. additiontreated with a little MeOH
6. dissolutionto dissolve a small amount of insoluble material
7. customDrying
8. concentration(MgSO4), concentration, and silica gel chromatography (5% MeOH/CHCl3)