5-Bromo-2-methyl-3-nitropyridine

Uses

5-Bromo-2-methyl-3-nitropyridine is used as a reactant in the synthesis of MLN0905, a potent and orally bioavailable inhibitor of Polo-like kinase 1 (PLK1).

Synthesis

Step 2 - Synthesis of 5-bromo-2-methyl-3-nitropyridine Diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate (1.2 g, 3.3 mmol) was dissolved in 7.0 N HCl (10 mL). The mixture was heated to reflux for 5 hours. After completion of the reaction, it was cooled to room temperature and extracted with dichloromethane: methanol (10:1, v/v). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using petroleum ether: ethyl acetate (4:1, v/v) as eluent to afford 5-bromo-2-methyl-3-nitropyridine (0.7 g, yield: 89.7%). 1H-NMR (CDCl3, 400 MHz) δ 8.76 (s, 1H), 8.40 (s, 1H), 2.80 (s, 3H).

References

[1] Patent: US2008/194552, 2008, A1. Location in patent: Page/Page column 40
[2] Patent: WO2010/68292, 2010, A1. Location in patent: Page/Page column 78
[3] Patent: WO2013/33899, 2013, A1. Location in patent: Page/Page column 39
[4] Patent: WO2013/34048, 2013, A1. Location in patent: Page/Page column 46; 47
[5] Patent: WO2012/88411, 2012, A1. Location in patent: Page/Page column 64