Pyridine → HCID 46912083, compound

Participants

Reaction Steps

An ice-acetone cooled solution of anhydrous dimethylformamide (0.71 mL, 9.17 mmol) and anhydrous dichloromethane (1 mL) under a N2 atmosphere is treated drop-wise with phosphorus oxychloride (0.69 mL, 7.42 mmol). The resulting yellowish mixture is continued to stir for 30 mins to give an opaque gel. Crude 1-phenyl-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one is added portion wise as a solid over 10 minutes to form a red mixture. Further dichloromethane (1 mL) is added followed by pyridine (0.45 mL, 5.56 mmol) to give a dark red mixture. The reaction is allowed to warm slowly to room temperature over 1 hour, and stirred at room temperature for 38 hours. The red reaction mixture is concentrated, and the residue is treated with phosphorus oxychloride (8 mL) and the mixture heated in an oil bath at 110° C. for 3 hours. After concentration of the red mixture, the residue is treated with ice water, and treated with saturated aqueous sodium hydrogen carbonate solution until the effervescence ceases. The mixture is extracted with 5 portions of dichloromethane, the combined extracts are dried over magnesium sulfate, filtered and evaporated to leave an orange solid. The residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined and the solvent evaporated, and after trituration with heptane gives 220 mg of 2-chloro-1-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde as a fluffy pink solid (53% yield from 3,3-dibromo-1-phenyl-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one). MS: m/e 257/259 (M+H). 1H NMR (300 MHz, CDCl3): 10.24 (1H, s), 8.62 (1H, dd), 8.39 (1H, dd), 7.68-7.56 (3H, m), 7.49 (2H, d), 7.31 (1H, dd).

Provenance & Evidence