Synthesis
General procedure for the synthesis of 2-(methylthio)-4-aminopyrimidine-5-carboxylic acid from ethyl 2-(methylthio)-4-aminopyrimidine-5-carboxylate: ethyl 4-amino-2-(methylthio)pyrimidine-5-carboxylate (72.3 g, 339 mmol) was dissolved in tetrahydrofuran (THF, 900 mL) and the solution was cooled to 0 °C. A solution of LiAlH4 (2 M in THF, 195 mL, 390 mmol) was added slowly and dropwise over 1 hour. The reaction mixture was kept stirred at 0 °C for 2 h, then allowed to warm slowly to room temperature and continued stirring overnight. Upon completion of the reaction, the mixture was again cooled to 0 °C and water (15 mL), 20% aqueous potassium hydroxide solution (15 mL) and water (30 mL) were carefully added in turn to quench the reaction. The resulting mixture was stirred for 1 hour. Subsequently, it was dried with anhydrous magnesium sulfate (MgSO4), filtered, and the filtrate was concentrated under reduced pressure and finally dried under vacuum to afford the target product 2-methylthio-4-aminopyrimidine-5-methanol (55.85 g, 96% yield). Mass spectrometry (MS) analysis showed m/z: 172.1 ([M + H]+).
References
[1] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2371 - 2387
[2] Patent: WO2013/134243, 2013, A1. Location in patent: Page/Page column 16
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[4] Patent: WO2014/151682, 2014, A1. Location in patent: Page/Page column 57; 58
[5] Journal of Medicinal Chemistry, 2014, vol. 57, # 3, p. 578 - 599
