Acetic Acid → 2,5-Dimethoxy-4-cyanoaminopyrimidine

To a 100 milliliter (mL) three-neck round bottom flask were added sequentially 7.8 grams (g) (121.53 millimole (mmol)) of sodium hydrogen cyanamide and 34.2 g of N-methyl-2-pyrrolidinone (NMP) in one portion, and the slurry mixture was cooled in an ambient temperature water bath. To this mixture was added 10.0 g (54.99 mmol) of 96% 4-chloro-2,5-dimethoxypyrimidine (1; CDMP) in one portion. The mixture was allowed to stir at ambient temperature (<20° C.). After 65 hours (h), 3.55 g (59.11 mmol) of glacial acetic acid was added in one portion and the internal pot temperature rose from 18° C. to 23° C. This reaction slurry was pipetted over 87.1 g of crushed ice and the ice was allowed to melt. To this mixture was added 10.3 g of sodium chloride. The mixture was allowed to stand until the crushed ice was fully melted. Once melted, the cold slurry was suction filtered and the filter cake was washed with one 10 mL portion of water and then two 20-mL portions of water. The wet cake was isolated to afford 9.39 g (80.2% pure by NMR assay using benzyl acetate) of 2,5-dimethoxy-4-cyanoaminopyrimidine (2) as a light yellow solid mp 164-171° C. in 76% yield; 1H NMR (DMSO-d6, 400 MHz) δ 3.72 (s, 3H), 3.94 (s, 3H), 7.46 (s, 1H), 12.48 (br s, ˜1H); 13C NMR (DMSO, 100 MHz) δ 55.21, 56.60, 116.20, 121.8 (br s), 138.9, 153.9, 162.6 (br s).