Uses
4,6-Dichloro-2-methylpyrimidine, is a versatile building block used for the synthesis of more complex pharmaceutical and biologically active compounds, such as Dasatinib (D290002), and its derivatives.
Application
The primary application of 4,6-dichloro-2-methylpyrimidine is as a key intermediate in the synthesis of the antihypertensive drug Moxonidine. Moxonidine is a centrally acting antihypertensive drug that exerts its antihypertensive effect by activating central α₂ receptors and imidazoline receptors. In its synthetic route, 4,6-dichloro-2-methylpyrimidine is used to construct the pyrimidine ring core structure, and key groups are introduced through substitution and other reactions to ultimately synthesize the target drug.
Synthesis
General procedure for the synthesis of 4,6-dichloro-2-methylpyrimidine from 6-hydroxy-2-methylpyrimidin-4-one: 4,6-dihydroxy-2-methylpyrimidine (5.0 g, 0.04 mol) was added to a mixed solution of thionyl chloride (18.9 g, 0.16 mol) with acetonitrile. The reaction mixture was stirred at 80 °C for 3 h and the completion of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, excess thionyl chloride was removed by distillation under reduced pressure and the residue was slowly poured into 50 g of ice water. The precipitated solid was filtered and purified by column chromatography to give 6.1 g (yield: 94%) of 4,6-dichloro-2-methylpyrimidine as a white solid.
References
[1] Tetrahedron Letters, 2009, vol. 50, # 41, p. 5729 - 5732
[2] Patent: CN106478519, 2017, A. Location in patent: Paragraph 0020-0023; 0030-0032; 0038-0040; 0049-0052
[3] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2969 - 2973
[4] Tetrahedron, 2006, vol. 62, # 10, p. 2304 - 2312
[5] Patent: WO2004/46133, 2004, A1. Location in patent: Page 40-41
