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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence