2,5-Dibromo-4-methylpyridine

Uses

2,5-Dibromo-4-methylpyridine is mainly used in organic synthesis, and in the pharmaceutical industry, it is used to synthesize heart disease drugs such as disopyramide (disopyramide phosphate). Disopyramide is used to maintain sinus rhythm in atrial fibrillation and atrial flutter, or to prevent the recurrence of ventricular tachycardia and ventricular fibrillation. It can also be used for premature atrial contractions, paroxysmal atrial tachycardia, premature ventricular contractions, etc.

Chemical Properties

Light yellow to orange low melting solid

Synthesis

General procedure for the synthesis of 2,5-dibromo-4-methylpyridine from 2-amino-5-bromo-4-methylpyridine: 2-amino-5-bromo-4-methylpyridine (2.0 g, 10.7 mmol) was dissolved in 48% aqueous hydrobromic acid (14 mL, 123 mmol) and cooled to 2 °C in a salt/ice bath. Bromine (1.65 mL, 32.1 mmol) was added dropwise while keeping the internal temperature below 2 °C. Subsequently, a solution of sodium nitrite (3.69 g, 53.5 mmol) in water (5 mL) was added, keeping the internal temperature below 5 °C and the reaction mixture was stirred between 0 °C and 5 °C for 1 hour. The pH of the reaction mixture was adjusted to about 13 by slowly adding and cooling a 50% aqueous sodium hydroxide solution. after warming the reaction mixture to room temperature, it was extracted with ether. The organic phases were combined, dried with anhydrous magnesium sulfate and concentrated to give a brown oil. Purification by fast column chromatography on silica gel, using 5% ether/hexane as eluent, afforded the target product 2,5-dibromo-4-methylpyridine as a white solid (1.83 g, 7.29 mmol, 68% yield). Mass spectrometry analysis showed the [M + H]+ peak to be 251.9; the retention time (tR) was 2.3 min (Method 1).

References

[1] Patent: WO2008/124610, 2008, A1. Location in patent: Page/Page column 46
[2] Patent: WO2008/124614, 2008, A1. Location in patent: Page/Page column 38-39