4-Chloro-6-methylthieno[2,3-d]pyrimidine

Synthesis

GENERAL METHOD: A mixture of 6-methyl-3H-thieno[2,3-d]pyrimidin-4-one (0.01 mol), phosphorus trichloride (11 mL), and phosphorus pentachloride (1.5 g) was rapidly heated to 105°C and the reaction was carried out at reflux for 5-6 hours. After completion of the reaction, excess solvent was removed by distillation under reduced pressure. The crude product was dissolved in dichloromethane (12 mL) and neutralized with cold sodium hydroxide solution (0.5 N). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized with isopropanol to afford the target product 4-chloro-6-methylthieno[2,3-d]pyrimidine in 80% yield.

References

[1] Pharmaceutical Chemistry Journal, 1987, vol. 21, # 2, p. 126 - 129
[2] Khimiko-Farmatsevticheskii Zhurnal, 1987, vol. 21, # 2, p. 197 - 200
[3] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 148 - 160
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 2, p. 305 - 308
[5] European Journal of Medicinal Chemistry, 2011, vol. 46, # 3, p. 870 - 876