Ethanone, 1-[2-(methylthio)-4-pyrimidinyl]- (9CI)

Synthesis

75-97-8

4637-24-5

17356-08-0

74-88-4

496863-48-0

1) Synthesis of 4-acetyl-2-methylthiopyrimidine: 3,3-dimethylbutan-2-one (25.15 g) was mixed with N,N-dimethylformamide dimethyl acetal (126 mL) and stirred in an oil bath at 100 °C for 48 hours. Upon completion of the reaction, the reaction was air cooled and the low-boiling component was removed by distillation under reduced pressure. Methanol (400 mL), thiourea (28.92 g) and sodium methanol (15.39 g) were added to the residue and heated to reflux for 118 hours. After air cooling again, sodium methanol (10.26 g) was added and under ice bath cooling, iodomethane (17.8 mL) was added dropwise over 5 minutes and stirring was continued for 5 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure and the residue was partitioned with water and ethyl acetate. The organic layer was washed sequentially with water and saturated saline and dried over anhydrous sodium sulfate. After filtration, it was concentrated under reduced pressure and the residue was dissolved in 3N aqueous hydrochloric acid (400 mL) and stirred at room temperature for 15 hours. The reaction solution was extracted with ethyl acetate, the organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate-hexane) to afford 4-acetyl-2-methylthiopyrimidine (26.34 g, 82% yield) as a solid.1H-NMR (400 MHz, CDCl3) δ: 2.63 (3H, s), 2.70 (3H, s), 7.51 (1H, d, J = 4.9 Hz), 8.74 (1H , d, J = 4.9 Hz).ESI-MS m/z: 169 ([M + H]+).

References