Chemical Properties
White to Off White Low Melting Solid
Uses
2,4-Dichloro-5-methylpyrimidine, is used in the synthesis of (2-chloro-6-methyl-pyrimidin-4-yl)-(2,3-dihydro-benzothiazol-6-yl)-amine. It can react with piperidineto produce 2-chloro-5-methyl-4-piperidin-1-yl-pyrimidine. This reaction will need solvent dioxane.
Synthesis
General procedure for the synthesis of 2,4-dichloro-5-methylpyrimidine from 5-methyluracil: 5-methyluracil (1 g, 7.93 mmol) was added to phosphorochloridic acid (7 eq., 5 ml), and the mixture was heated and refluxed for 3 hours. After completion of the reaction, the mixture was slowly poured into ice water to quench the reaction. The organic layer was extracted with chloroform (3 x 20 ml), the organic phases were combined and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give 2,4-dichloro-5-methylpyrimidine as yellow crystals (0.62 g, 48% yield). The structure of the product was confirmed by nuclear magnetic resonance hydrogen (1H NMR, 400 MHz, CDCl3) and carbon (13C NMR, 100 MHz, CDCl3) spectra: 1H NMR δ 8.35 (s, 1H), 2.39 (s, 3H); 13C NMR δ 162.5, 160.0, 158.2, 129.1, 15.8. The data obtained were in agreement with those of literature reports (Wang et al., Molecules, 2012, 17(4), 4533-4544).
References
[1] Journal of Fluorine Chemistry, 1996, vol. 77, # 1, p. 93 - 95
[2] Patent: WO2018/151681, 2018, A1. Location in patent: Paragraph 0099
[3] Synthetic Communications, 1992, vol. 22, # 20, p. 2927 - 2934
[4] Tetrahedron Letters, 1997, vol. 38, # 7, p. 1111 - 1114
[5] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 18, p. 2961 - 2966
