Uses
4-Chloro-2,6-dimethylpyrimidine is used as an organic synthesis intermediate. It can be converted into amino- and substituted amino-pyrimidines via amination or substituted amination; these amino-pyrimidines are important intermediates in the preparation of sulphonamide drugs and purines.
Synthesis
General procedure for the synthesis of 4-chloro-2,6-dimethylpyrimidines from 2,4-dimethyl-6-hydroxypyrimidines: phosphorous trichloride (POCl3, 0.460 g, 3.0 mmol) was added to a solution of 2,4-dimethyl-6-hydroxypyrimidines (1.0 mmol) in toluene (15 mL), and the mixture was stirred for 3 hours under reflux conditions. Upon completion of the reaction, excess phosphorous trichloride was removed by distillation under reduced pressure and the reaction was subsequently quenched by the addition of ice water (10 mL). The pH of the reaction mixture was adjusted to 9-10 with sodium carbonate solution and then extracted with methyl tert-butyl ether (MTBE). The organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to afford the target product 4-chloro-2,6-dimethylpyrimidine (yield: 82%). Mass spectrometry (ESI) showed a molecular ion peak (m/z) [M + H]+ of 143.1.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 10, p. 1769 - 1775
[2] Tetrahedron Letters, 1999, vol. 40, # 42, p. 7477 - 7478
[3] Patent: US5438058, 1995, A
[4] Patent: US6093718, 2000, A
