Triethylamine → 3-[6-(2-imidazol-1-yl-ethoxy)-1-methyl-1H-indol-3-yl]-4-(1-methyl-6-nitro-1H-indol-3-yl)-pyrrole-2,5-dione

Participants

Reaction Conditions

Reaction Steps

6-(2-Imidazol-1-yl-ethoxy)-1-methyl-1H-indole (185 mg, 0.77 mmol) was dissolved in CH2Cl2 (2 mL) under argon at 0° C. To this was added oxalyl chloride (0.19 mL, 2.18 mmol) in CH2Cl2 (2 mL). After stirring at 0° C. for 4 h, the mixture was evaporated and dried under vacuum for 2 h. 2-(1-Methyl-6-nitro-1H-indol-3-yl)acetimidic acid isopropyl ester hydrochloride (239 mg, 0.77 mmol) and CH2Cl2 (3mL) were added to the above green solid. Triethylamine (0.81 mL, 5.82 mmol) was added slowly at 0° C. and the mixture was stirred at room temperature for 16 h. The mixture was evaporated to dryness and methanol (5 mL) and 12 N hydrochloric acid (1 mL) were added. The mixture was heated to 85° C. for 1 h. After the solvents were evaporated, ethyl acetate (50 mL) was added and the mixture was carefully washed with 5% sodium bicarbonate (3×50 mL). The aqueous layer was back-extracted with ethyl acetate (2×50 mL), then the combined organic extracts were dried (MgSO4), filtered though a pad of silica gel and the pad was washed with 10% methanol/CH2C2 (400 mL). The filtrates were concentrated and the crude product was chromatographed on silica gel with 1% to 5% methanol/ethyl acetate gave an orange solid. Further purification by dissolving the solid in hot CH2C2 (3 mL) and precipitating with ether (20 mL) yielded 3-[6-(2-imidazol-1-yl-ethoxy)-1-methyl-1H-indol-3-yl]-4-(1-methyl-6-nitro-1H-indol-3-yl)-pyrrole-2,5-dione as an orange solid (0.103 g, 26%).

Provenance & Evidence