Synthesis
The general procedure for the synthesis of 5-amino-2-chloro-4-methylpyrimidine from 2,4-dichloro-5-nitro-6-methylpyrimidine was as follows: to a stirred methanol (100 mL) solution of 2,4-dichloro-6-methyl-5-nitropyrimidine (10 g, 48.1 mmol) and ammonium chloride (25.7 g, 481 mmol) under nitrogen protection was added in batches zinc powder ( 31.4 g, 481 mmol). The reaction mixture was stirred at 70 °C for 50 hours. After completion of the reaction, the mixture was filtered and the filtrate was concentrated under vacuum. The residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol, 30:1). All fractions containing the target product were collected and detected by thin layer chromatography (unfolding agent: ethyl acetate/petroleum ether, 1:1, Rf=0.6), combined and concentrated to give 2-chloro-4-methylpyrimidin-5-amine (2 g, 13.93 mmol, 29.0% yield) as a light yellow solid. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 3.66 (s, 2H), 2.88 (s, 3H); ESI-MS m/z: 144.2 ([M+H]+).
References
[1] Patent: WO2016/37578, 2016, A1. Location in patent: Page/Page column 138
[2] Chemische Berichte, 1901, vol. 34, p. 1242
[3] Yakugaku Zasshi, 1942, vol. 62, p. 315,333; dtsch. Ref. S. 95, 106
[4] Chem.Abstr., 1951, p. 5150
[5] Patent: EP2100894, 2009, A1. Location in patent: Page/Page column 20
