General procedure for the synthesis of 2-bromo-5-amino-6-methylpyridine from 2-bromo-5-nitro-6-methylpyridine: 6-bromo-2-methyl-3-nitropyridine (XIV) (250 g, 1.15 mol, 1.00 equiv) and NH4Cl (300 g, 5.61 mol, 4.88 equiv) were suspended in a mixture of EtOH (3.50 L) and water ( 150 mL) in a solvent mixture. The suspension was heated to 65 °C under stirring. Subsequently, Fe (130 g, 2.33 mol, 2.02 eq.) and HCl (15.3 g, 419 mmol, 0.36 eq.) were added to the reaction system. The reaction mixture was heated to 80 °C and maintained at this temperature for 3 hours. After completion of the reaction, the mixture was cooled to 25 °C and filtered through a diatomaceous earth plug. The filtrate was concentrated under reduced pressure to give the crude product. The crude product was dissolved in EtOAc (1 L x 3) and washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 6-bromo-2-methylpyridin-3-amine (XV) as a brown solid (373 g, 1.99 mol, 86.7% yield), which could be used in the next reaction without further purification.1H NMR (DMSO-d6, 400 MHz) δ ppm: 6.01 (dd, J = 2.3, 7.9 Hz, 2H). 7.9 Hz, 2H), 7.03 (d, J = 8.2 Hz, 1H); ESIMS m/z: 186.8 ([M + H]+).
