General procedure for the synthesis of (4,6-dimethylpyrimidin-2-yl)methanol from methyl 4,6-dimethylpyrimidine-2-carboxylate: 4,6-dimethylpyrimidine-2-carboxylic acid methyl ester (400 mg, 2.40 mmol) was dissolved in ethanol (10 mL) under argon protection and cooled to 0 °C. Sodium borohydride (137 mg, 3.60 mmol) was then added and the reaction was slowly warmed to room temperature and stirred for 2 hours. The reaction progress was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction was quenched with deionized water (15 mL) and extracted with dichloromethane (2 x 30 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product (4,6-dimethylpyrimidin-2-yl)methanol (285 mg, 86% yield) as a thick slurry. The crude product was used directly in the next reaction without further purification. The product was confirmed by 1H-NMR (CDCl3, 400 MHz): δ 6.91 (s, 1H), 4.71 (s, 2H), 2.50 (s, 6H). Liquid chromatography-mass spectrometry (LC-MS) analysis showed a purity of 96.66%, m/z 139.3 (M++1); chromatographic conditions: Eclipse XDB C-18 column (150×4.6 mm, 5 μm), mobile phase 0.05% trifluoroacetic acid/acetonitrile at a flow rate of 1.0 mL/min, and retention time of 4.03 min. TLC unfolding agent was 40% ethyl acetate/hexane (Rf=0.5).
