反应详情

EDC (1.53 g, 7.99 mmol) was added to a solution of methyl (±)-7-carboxy-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetate (2.13 g, 7.26 mmol), 2-aminomethylindole (1.06 g, 7.26 mmol), HOBT.H2O (1.08 g, 7.99 mmol) and diisopropylethylamine (1.53 mL, 8.71 mmol) in anhydrous DMF (10 mL) at RT. After 20 h the reaction was concentrated on the rotavap (high vacuum). The residue was taken up in EtOAc and washed sequentially with H2O and 10% Na2CO3 (2×30 mL). Drying (MgSO4), concentration, and silica gel chromatography (2% MeOH/CH2Cl2) gave the title compound (1.8 g, 60%): 1H NMR (400 MHz, DMSO-d6) δ 8.56 (t, 1H), 7.95 (s, 1H), 7.59 (s, 1H), 7.56 (d, 1H), 7.43 (d, 1H), 7.33 (d, 1H), 7.01 (t, 1H), 6.93 (t, 1H), 6.55 (d, 1H), 6.33 (br, 1H), 6.25 (s, 1H), 5.49 (d, 1H), 5.14 (t, 1H), 4.56 (d, 2H), 3.82 (d, 1H), 3.61 (s, 3H), 2.92 (s, 3H), 2.75 (dd, 1H), 2.53 (d, 1H); MS(ES) m/e 421.2 (M+H)+.

1. customat RT
2. concentrationAfter 20 h the reaction was concentrated on the rotavap (high vacuum)
3. washwashed sequentially with H2O and 10% Na2CO3 (2×30 mL)
4. customDrying
5. concentration(MgSO4), concentration, and silica gel chromatography (2% MeOH/CH2Cl2)