3-BROMO-4-CHLOROTHIENO[3,2-C]PYRIDINE

Synthesis

General procedure for the synthesis of 3-bromo-4-chlorothieno[3,2-c]pyridine from 3-bromo-4-hydroxythienopyridine: A mixture of 3-bromo-5H-thieno[3,2-c]pyridin-4-one (1.16 g, 5.04 mmol) and phosphorus trichloride (20 mL) was heated and refluxed with stirring for 4 hours. Upon completion of the reaction, it was cooled to room temperature and excess phosphorus trichloride was removed under vacuum. The residue was dissolved in dichloromethane (25 mL) and washed sequentially with distilled water (2 × 25 mL) and saturated sodium bicarbonate solution (25 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuum. The crude product was purified by fast column chromatography (eluent was petroleum ether 40-60 °C: ethyl acetate, 5:1, Rf 0.5) to afford the target compound 3-bromo-4-chlorothieno[3,2-c]pyridine as a yellow solid (398 mg, 32% yield).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 1, p. 250 - 254
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 5, p. 1167 - 1171
[3] Patent: US2007/161672, 2007, A1. Location in patent: Page/Page column 8
[4] Patent: WO2004/100947, 2004, A2. Location in patent: Page 27; 17
[5] Patent: US2005/20619, 2005, A1. Location in patent: Page 17