4,6-DICHLORO-1H-PYRROLO-[3,2-C]-PYRIDINE

Uses

4,6-dichloro-1H-pyrrolo[3,2-c]pyridine is an organic intermediate that can be used to prepare anti-influenza virus replication inhibitors.

Synthesis

Step A: Synthesis of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine: 2,6-dichloro-4-nitropyridine (11 g, 57 mmol) was dissolved in anhydrous tetrahydrofuran (300 mL) and cooled to -78 °C. Magnesium vinyl bromide (1M THF solution, 200 mL, 200 mmol) was added dropwise with stirring. The reaction was kept at -78 °C for 1 h, followed by a slow warming to -20 °C. Upon completion of the reaction, the reaction was quenched with 200 mL of saturated aqueous ammonium chloride solution. The reaction mixture was transferred to a partition funnel and the aqueous layer was extracted with ethyl acetate (200 mL x 3). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by Combi fast chromatography, first using a 120 g silica gel column eluting with a gradient of cyclohexane/ethyl acetate (0-100%), followed by switching to a 40 g silica gel column eluting with a gradient of dichloromethane/ethyl acetate (0-10%) to afford 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine as a brown solid (0.150 g, 1.4% yield) .

References

[1] Patent: WO2013/156431, 2013, A1. Location in patent: Page/Page column 52