General procedure for the synthesis of 4,6-dihydroxy-2-methoxypyrimidines from O-methylisourea hydrochloride and dimethyl malonate:
Step 1: Synthesis of 2-methoxy-pyrimidine-4,6-diols
In a sealed tube, O-methylisourea hydrochloride (3.0 g, 27 mmol) and dimethyl malonate (3.1 mL, 27 mmol) were dissolved in a 30% w/v sodium methanol solution in methanol. The reaction mixture was heated to reflux for 4 h, followed by cooling to room temperature and allowed to stand overnight. The resulting white precipitate was collected by filtration and dried under vacuum to give 4.2 g (quantitative yield) of 4,6-dihydroxy-2-methoxypyrimidine.
1H NMR (DMSO-d6, 400 MHz) δ: 10.21 (br s, 1H), 4.09 (s, 1H), 3.65 (s, 3H).
