Synthesis
The general procedure for the synthesis of (4-methylamino-2-methanesulfonyl-pyrimidin-5-yl)-methanol from ethyl 4-methylamino-2-methylthio-5-pyrimidinecarboxylate was as follows: lithium aluminium hydride (11.48 g, 302 mmol) was suspended in 600 mL of anhydrous tetrahydrofuran (THF) in a 2 L three-necked flask fitted with an overhead stirrer, protected by argon gas. Another 250 mL round-bottomed flask was taken and ethyl 4-methylamino-2-methylthio-5-pyrimidine carboxylate (43.71 g, 0.192 mol) was dissolved in 200 mL of anhydrous THF and transferred through a cannula to a 250 mL addition funnel. The pyrimidine solution was slowly added dropwise to the lithium aluminum hydride suspension at room temperature for a controlled time of 30 minutes. After the dropwise addition was completed, the reaction was continued with stirring for 1 hour. Subsequently, 25 mL of water was carefully added dropwise over 30 minutes to quench the reaction. Next, 25 mL of 15% (w/v) aqueous sodium hydroxide solution and 75 mL of water were added sequentially, at which point the reaction mixture faded from a light green color and formed a light green slurry, and stirring was continued for 1 hour. Upon completion of the reaction, the precipitated aluminum salt was removed by vacuum filtration and the solid was washed well with ethyl acetate (EtOAc). The filtrate was concentrated to give a light yellow slurry. The slurry was suspended in 250 mL of a 25% EtOAc/hexane solvent mixture and the colorless solid was separated by vacuum filtration. After vacuum drying, 31.9 g (90% yield) of the target product (4-methylamino-2-methylthio-pyrimidin-5-yl)-methanol was obtained, and the spectral data were consistent with those reported in the literature.
References
[1] Patent: WO2004/63195, 2004, A1. Location in patent: Page 53-54
[2] Patent: WO2006/71940, 2006, A2. Location in patent: Page/Page column 355
[3] Patent: WO2008/33999, 2008, A2. Location in patent: Page/Page column 88
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 7, p. 2255 - 2265
[5] Patent: US2003/207900, 2003, A1. Location in patent: Page/Page column 15
