Potassium Carbonate → 7-chloro-5-methyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one

Temperature

60 °C

To a stirred solution of triphosgene (2.86 g, 9.66 mmol) in THF (10 mL) at room temperature under argon was added a suspension of 4-chloro-6-hydrazinyl-2-methylpyrimidine (10.0 mmol) in THF (15 mL). The reaction mixture was stirred overnight. Analysis by HPLC/MS indicated that no starting material remained. Solvent was removed under reduced pressure. DMF (5 mL) was added to the residue, followed by K2CO3 (2.76 g, 20.0 mmol) and 5-(chloromethyl)-2-(trifluoromethyl)pyridine (2.34 g, 12.0 mmol). The resulting mixture was heated at 60° C. for 2 h, after which time analysis by HPLC/MS indicated that the reaction was complete. After cooling the reaction mixture to room temperature, water (20 mL) was added. The resulting mixture was extracted with EtOAc (2×20 mL). The combined organic layers were washed with saturated aqueous NaCl (20 mL), then dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluted with ethyl acetate-dichloromethane to obtain 2.1 g of the title compound a solid. HPLC/MS: retention time=2.82 min, [M+H]30 =344.

1. customSolvent was removed under reduced pressure
2. additionDMF (5 mL) was added to the residue
3. temperatureAfter cooling the reaction mixture to room temperature
4. extractionThe resulting mixture was extracted with EtOAc (2×20 mL)
5. washThe combined organic layers were washed with saturated aqueous NaCl (20 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by column chromatography
10. washeluted with ethyl acetate-dichloromethane

ORD record

ord-75fdb4c1416b49c28ae3d7645843d849

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07452892B2