60% |
With 1,2-dichloro-ethane; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; |
d Methyl (+-)-7-[[[(2-indolyl)methyl]amino]carbonyl]-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetate 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), <strong>[21109-25-1]2-aminomethylindole</strong> (1.06 g, 7.26 mmol), HOBT.H2 O (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 H2 O and 10percent Na2 CO3 (2*30 mL). Drying (MgSO4), concentration, and silica gel chromatography (2percent MeOH/CH2 Cl2) gave the title compound (1.8 g, 60percent): 1 H NMR (400 MHz, DMSO-d6) delta 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)+. |