Synthesis
General procedure for the synthesis of 4-sulfo-5-methoxy-6-chloropyrimidine from 4,6-dichloro-5-methoxypyrimidine: a mixture of 4,6-dichloro-5-methoxypyrimidine (5.0 g, 28.1 mmol), 30% ammonia (45 mL), and n-butanol (15 mL) was heated and reacted in a sealed tube for 8 hr at 85 °C. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure and the concentrate was subsequently suspended in brine (150 mL). A white precipitate was collected by filtration and the filter cake was recrystallized from ethanol to afford the target compound 4-sulfo-5-methoxy-6-chloropyrimidine as an off-white solid in a yield of 4.1 g in 90% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 7.97 (s, 1H), 7.29 (s, 2H), 3.71 (s, 3H). Mass spectrum (ESI, cation mode) showed m/z: 159.91 [M + H]+.
References
[1] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 1148 - 1164
[2] Patent: CN108164548, 2018, A. Location in patent: Paragraph 0209; 0210; 0211
[3] Organic Process Research and Development, 2015, vol. 19, # 6, p. 639 - 645
[4] Patent: WO2005/47279, 2005, A1. Location in patent: Page/Page column 33
