General procedure: 2-methylthiopyrimidine-4-carbaldehyde dimethyl acetal (19.2 mL, 159.1 mmol) was mixed with N,N-dimethylformamide dimethyl acetal (21.12 mL, 159.1 mmol) in a 500 mL flask and the reaction was heated at 100 °C for 4.5 hours. After the reaction was completed, thiourea (11.0 g, 144.5 mmol), NaOMe (25 wt% MeOH solution, 39.7 mL, 173 mmol) and 30 mL of MeOH were added to the flask, and the reaction continued to be heated at 65°C for 18 hours. At the end of the reaction, the reaction solution was cooled to 25 °C and MeI (10.8 mL, 173 mmol) was added slowly over 5 min (note exothermic). After continuing the reaction for 3 h, the reaction solution was diluted with 250 mL of H2O and extracted with EtOAc (3 × 100 mL). The organic phases were combined, dried over Na2SO4 and concentrated to give 4-(dimethoxymethyl)-2-methylthiopyrimidine (26.8 g, 93% yield) as a brown oil.
