5-Bromo-3-cyano-2-methoxypyridine

Uses

5-Bromo-2-methoxynicotinonitrile can be used as a pharmaceutical synthesis intermediate.

Synthesis

General procedure for the synthesis of 5-bromo-3-cyano-2-methoxypyridine from 3-cyano-2-methoxypyridine: 12.23 g (149 mmol) of sodium acetate and 7.66 mL (149 mmol) of bromine were added drop-wise to 29 mL of acetic acid solution containing 10 g (74.6 mmol) of 3-cyano-2-methoxypyridine at 0 °C. The reaction mixture was then heated at 70 °C for overnight reaction. Upon completion of the reaction, the reaction system was cooled to room temperature and poured into an ice bath. The precipitated solid product was collected by filtration, washed thoroughly with water and dried at 50 °C to afford 11.6 g (73% yield) of the target compound 5-bromo-3-cyano-2-methoxypyridine as a white solid. The product was analyzed by LC-MS (EI, m/z) to confirm: (M+1) 214.95. 1H NMR (400 MHz, DMSO-d6) δ: 8.61 (1H, d, J = 2.4 Hz, Ar-H), 8.60 (1H, d, J = 2.4 Hz, Ar-H), 3.98 (3H, s, OCH3).

References

[1] Patent: WO2012/101239, 2012, A1. Location in patent: Page/Page column 55
[2] Patent: US2013/85144, 2013, A1. Location in patent: Paragraph 0281; 0282; 0283
[3] Patent: EP2689778, 2014, A1. Location in patent: Paragraph 0185
[4] Patent: WO2014/16433, 2014, A1. Location in patent: Page/Page column 54
[5] Patent: WO2014/16434, 2014, A1. Location in patent: Page/Page column 53-54