Oxalyl chloride → (6-cyano-1-methyl-1H-indol-3-yl)glyoxylyl chloride

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Reaction Steps

1-methyl-1H-indole-6-carbonitrile (1.0 g, 6.4 mmole), a known compound, was dissolved in ethyl ether (Et2O) (25 mL), chilled in an ice bath and treated with oxalyl chloride (0.95 mL, 10.9 mmole, 1.7 equiv.). After removal of the ice bath, yellow solids soon precipitated. This mixture was stirred at room temperature overnight, the solids were then collected and washed with ethyl ether and dried under vacuum for 30 minutes to provide 1.53 g (96%) of (6-cyano-1-methyl-1H-indol-3-yl)oxo-acetyl chloride. This material (1.53 g, 6.2 mmole) along with 2-(1-methyl-1H-indol-3yl)-acetimidic acid isopropyl ester hydrochloride (1.66 g, 6.2 mmole, 1 equiv.) was suspended in CH2Cl2 (100 mL) and cooled in an ice bath. The mixture was treated with Et3N (3.5 mL, 24.8 mmole, 4 equiv.), stirred at 0° for 30 minutes, then at room temperature for an additional 3 hours. The reaction mixture was then diluted with CH2Cl2 (150 mL), washed with H2O (50 mL), and then 0.5N HCl (50 mL). The organic fractions were dried over MgSO4, filtered and evaporated to give a dark oil. The residue was taken up in toluene (30 mL), chilled in an ice bath, then treated with pTsOH(1.3 g, 6.8 mmole, 1.1 equiv.), then stirred at room temperature for 2 hours. The red solids which precipitated were collected, washed with a small volume of toluene, hexane, the H2O, then partitioned between 500 mL CH2Cl2 and 75 mL saturated NaHCO3. The organic layer was dried over MgSO4, filtered and evaporated to provide 2 g of a red solid. The solid was washed with cold CH2Cl2, then recrystallized from acetone/hexane to give 938 mg of 1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indole-6-carbonitrile.

Provenance & Evidence