4,6-Dichloro-2-(methylthio)pyrimidine-5-carboxylic acid

Synthesis

1. 4,6-dichloro-2-methylthioalkylpyrimidine (1.00 g, 5.13 mmol) was dissolved in tetrahydrofuran (THF, 10 mL). 2. 2.0 M lithium diisopropylammonium (LDA) solution in THF (5.9 mL, 11.8 mmol) was added to the solution at -78 °C and stirred for 1 hour. 3. carbon dioxide gas (dry ice) was passed into the reaction mixture at -78 °C. 4. the reaction mixture was warmed to room temperature and stirring was continued for 1.5 hours. 5. Upon completion of the reaction, the organic layer was separated by adding 10% aqueous hydrochloric acid and ethyl acetate for extraction. 6. The organic layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure to remove the solvent. 7. The residue was re-slurried with hexane and the solid was collected by filtration to afford 2-(methylthio)-4,6-dichloropyrimidine-5-carboxylic acid (964 mg, 79% yield). 8. The product was passed through ESI-MSR. 8. The product was characterized by ESI-MS and 1H-NMR: ESI-MS m/z 237 [M-H]-; 1H-NMR (CDCl3) δ 2.60 (s, 3H), 9.68 (brs, 1H).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4642 - 4646
[2] Patent: EP2163554, 2010, A1. Location in patent: Page/Page column 49
[3] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 5, p. 1485 - 1488
[4] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 20, p. 5717 - 5732
[5] Patent: EP1496059, 2005, A1. Location in patent: Page 19-20