Chemical Properties
Colorless to pale yellow liquid
Uses
2,4,5-Trichloropyrimidine is used in the synthesis of potent and selective anaplastic lymphoma kinase (ALK-5) inhibitors, used as an anti-tumor treatment. Also used in the synthesis of EGFR inhibitors.
Synthesis
General procedure for the synthesis of 2,4,5-trichloropyrimidine from 5-chlorouracil: 5-chlorouracil (4.5 g, 30.82 mmol) was dissolved in phosphorochloridic acid (100 mL), followed by phosphorus pentachloride (19.2 g, 92.46 mmol). The reaction mixture was heated to reflux overnight; after completion of the reaction, it was cooled to room temperature and the solvent was removed by evaporation under reduced pressure. The residue was cooled to 0 °C and crushed ice was added slowly. The mixture was stirred for 10 min and partitioned between water and dichloromethane (DCM). The organic phase was separated and washed three times with water. The aqueous layer was combined and extracted twice with DCM. The combined organic extracts were dried over anhydrous sodium sulfate (Na2SO4), filtered and the solvent was evaporated under reduced pressure to give 2,4,5-trichloropyrimidine as a yellow oil, which did not require further purification.
References
[1] Patent: WO2008/28860, 2008, A1. Location in patent: Page/Page column 45
[2] Patent: US2006/25433, 2006, A1. Location in patent: Page/Page column 108
[3] Patent: US4299961, 1981, A
[4] Patent: WO2008/79719, 2008, A1. Location in patent: Page/Page column 43-44; 47-48; 49; 51
[5] Patent: WO2007/120339, 2007, A1. Location in patent: Page/Page column 39-42
