Synthesis
General procedure for the synthesis of 2-hydroxy-3-cyano-4,6-dimethyl-5-bromopyridine from 2-oxo-4,6-dimethyl-1,2-dihydropyridine-3-carbonitrile: To a solution of 4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (35 g, 236 mmol) in acetic acid (200 ml) is added slowly and dropwise bromine (41.5 g, 260 mmol). 260 mmol). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the mixture was concentrated to dryness under reduced pressure. The crude product was purified by recrystallization from ethanol-water mixed solvent to afford 5-bromo-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (70 g, 95% yield). The product was analyzed by LCMS (Table 1, method c) showing retention time RT = 1.63 min; mass spectrum m/z = 226,228 (M + H).
References
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[2] Patent: WO2016/198908, 2016, A1. Location in patent: Page/Page column 76
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[4] Khimiko-Farmatsevticheskii Zhurnal, 1989, vol. 23, # 12, p. 1459 - 1463
[5] Journal of Heterocyclic Chemistry, 2011, vol. 48, # 2, p. 272 - 278
