6-Bromo-1H-pyrrolo[3,2-b]pyridine

Uses

6-Bromo-1H-pyrrolo[3,2-b]pyridine is used in the preparation of benzofuran and pyridine compounds in the treatment of viral diseases, respiratory illnesses, inflammatory diseases.

Synthesis

GENERAL STEPS: Preparative Example 15 Step 1: Synthesis of 6-bromo-1H-pyrrolo[3,2-b]pyridine. To an N,N-dimethylformamide solution (10 mL) of 5-bromo-2-methyl-3-nitropyridine (1.58 g, 7.28 mmol) was added N,N-dimethylformamide dimethyl acetal (1.65 mL, 12.37 mmol). The reaction mixture was heated to 100 °C and kept for 1 h. It was subsequently concentrated to dryness under vacuum. The residue was dissolved in acetic acid (20 mL) and iron powder (1.22 g, 21.8 mmol) was added. The reaction mixture was purged with nitrogen for 2 minutes and then heated to 100 °C and kept for 20 hours. After completion of the reaction, the mixture was cooled, diluted with methanol and filtered. The precipitate was washed with methanol. The filtrate and washings were combined and concentrated to dryness under vacuum. The resulting viscous material was diluted with aqueous sodium carbonate and extracted with ethyl acetate (2 x 60 mL). The organic layers were combined and dried with sodium sulfate and subsequently concentrated to dryness under vacuum. The residue was purified by column chromatography (silica gel, 100-200 mesh, 25% hexane solution of ethyl acetate as eluent) to afford 6-bromo-1H-pyrrolo[3,2-b]pyridine (820 mg, 60% yield). The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 11.48-11.45 (m, 1H), 8.36 (d, J = 2Hz, 1H), 8.02-8.00 (m, 1H), 7.69-7.66 (m, 1H), 6.59-6.56 (m, 1H).

References

[1] Patent: WO2016/142310, 2016, A1. Location in patent: Page/Page column 77-78