Indole-2-carboxylic acid → 1H-Indole-2-carboxylic acid [1-(Isopropyl-phenyl-carbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-amide

Participants

Reaction Steps

To a vigorously stirred solution of 2-{3-Amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo [b] [1, 4] diazepine-1-yl)-N-isopropyl-N-phenyl acetamide (0.116 g) in N,N-dimethylformamide (5 ml) at ambient temperature was added indole-2-carboxylic acid (0.0423 g, 0.262 mmol), N-hydroxybenzotriazole (0.0354 g), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.0503 g) successively. Triethylamine (8 drops) was added dropwise to maintain the basicity (pH=9) of the solution was reached. The resultant mixture was stirred at ambient temperature for five hours. The solvent was evaporated in vacuo to give a yellow oil which was purified by flash chromatography on silica gel (9 g) with an eluant of a mixture of ethyl acetate and hexane (2:3, 200 ml). Fractions containing the desired product were combined and evaporated in vacuo to give the title compound (0.141 g) as a white foam. 1H NMR (300 MHz, CDCl3): d 1.06 (d, J=7.3 Hz, 3H), 1.09 (d, J=7.3 Hz, 3H), 4.22 (d, J=16.6 Hz, 1H), 4.40(d, J=16.4 Hz, 1H), 5.02(m, 1H), 5.50(d, J=7.1 Hz, 1H), 7.02(d, J=8.1 Hz, 1H), 7.10-7.47 (m, 16H), 7.57 (d, J=6.8 Hz, 1H), 7.67 (d, J=7.8 Hz, 1H), 9.29 (br s, 1H); MS (FAB): m/z=586.0 (MH+); TLC (EtOAc/Hexane (2:3)): Rf =0.16; RP-HPLC (Vydac C-18, 25 cm×4.6 mm; 51-60% CH3CN in H2O with 0.1% TFA buffer;, 30 minutes; 1 ml/min): tf =19.5 min (to =3 min).

Provenance & Evidence