Synthesis
Step 1: 5-bromo-2-cyano-3-nitropyridine (K1, 5 g, 21.9 mmol) was dissolved in cooled concentrated hydrochloric acid (30 mL), and tin chloride dihydrate (SnCl2-2H2O, 24.7 g, 109.5 mmol) was added in batches. After the addition was completed, the reaction mixture was stirred at room temperature overnight. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent ratio PE:EA = 3:1) to confirm the completion of the reaction. Subsequently, the mixture was alkalized with aqueous sodium carbonate and extracted with ethyl acetate. The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and the resulting residue was purified by column chromatography (eluent ratio PE:EA = 20:1 to 5:1) to afford 3-amino-5-bromopyridine-2-carbonitrile (K2, 1.9 g). Mass spectrometry (MS) analysis showed molecular ion peaks m/e = 198 and 200 (M + 1) for K2.
References
[1] Patent: WO2005/42498, 2005, A2. Location in patent: Page/Page column 44
[2] Patent: WO2011/51540, 2011, A1. Location in patent: Page/Page column 74
[3] Patent: WO2016/118404, 2016, A1. Location in patent: Page/Page column 46; 47
