Step A: Preparation of methyl pyrimidine-2-carboxylate: a saturated HCl methanol solution was prepared by passing dry HCl gas into methanol (700 mL) for 30 min at 0 °C. To this solution was added pyrimidine-2-carbonitrile (21.585 g, 205.38 mmol) and the reaction was stirred at room temperature for 16 h. The reaction was then warmed up to 40-50 °C and continued to be stirred for 3 h. The reaction was then carried out under reduced pressure and concentrated. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and the residue was dissolved in water. The pH of the aqueous phase was adjusted with solid sodium bicarbonate to 7.0. The aqueous phase was extracted with a 20% isopropanol/dichloromethane solvent mixture (3 times). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the white solid product methyl pyrimidine-2-carboxylate (23.0 g, 81% yield). The product was characterized by 1H NMR (400 MHz, CDCl3): δ 8.97-8.96 (d, J = 4.7 Hz, 2H), 7.53-7.50 (t, J = 4.7 Hz, 1H), 4.09 (s, 3H).
