5-broMo-1,4-diMethyl-3-nitropyridin-2(1H)-one

Synthesis

Step 1. Synthesis of 5-bromo-1,4-dimethyl-3-nitropyridin-2(1H)-one 5-Bromo-4-methyl-3-nitropyridin-2-ol (15.00 g, 64.37 mmol) was dissolved in N,N-dimethylformamide (250 mL). Sodium hydride (3.09 g, 77.3 mmol, 60% dispersed in mineral oil) was added slowly and in batches at room temperature and the reaction mixture was stirred for 30 minutes. Subsequently, iodomethane (4.81 mL, 77.2 mmol) was added dropwise and stirring was continued for 3 h at room temperature. The generation of methylation products was confirmed by LCMS. The reaction mixture was slowly poured into a water/ice mixture (~400 mL) and stirred until the ice completely melted. The aqueous phase mixture was extracted with ethyl acetate. The organic layers were combined, washed sequentially with water (3 times) and brine, dried over magnesium sulfate, filtered and concentrated to afford the crude product 5-bromo-1,4-dimethyl-3-nitropyridin-2(1H)-one (14.9 g, 93% yield), which could be used in the subsequent reaction without further purification.Calculated LCMS values for C7H8BrN2O3 (M+H)+: m/z = 247.0, 249.0; measured values: 247.0, 248.9.

References

[1] Patent: US2015/148375, 2015, A1. Location in patent: Paragraph 0309; 0310
[2] Patent: US2015/148342, 2015, A1. Location in patent: Paragraph 0336; 0337
[3] Patent: WO2014/125408, 2014, A2. Location in patent: Page/Page column 38; 39