Pyridine → HCID 22921552, compound

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, a stirred solution of 0.4 gram (0.0009 mole) of 2-[2-trifluoromethyl-5-fluoro-6-(1-methyl-6-trifluoromethyluracil-3-yl)benzimidazol-1-yl]propan-1-ol (Compound 7--prepared as in Step A of Example 8) in 10 mL of diethyl ether was cooled in an ice-water bath, and 0.07 mL (0.0009 mole) of pyridine was added at a rate to maintain the reaction mixture temperature below 5° C. Upon completion of the addition, 0.1 mL (0.0013 mole) of thionyl chloride was added dropwise from a syringe. Upon completion of the addition, the reaction mixture stirred at about 0° C. for 30 minutes. After this time, the reaction mixture was allowed to warm to ambient temperature, where it stirred for about 18 hours. Analysis of the reaction mixture by thin layer chromatography (TLC) indicated the reaction was not complete. The reaction mixture was concentrated under reduced pressure to a residue. The residue was dissolved in methylene chloride, and 0.1 mL of thionyl chloride and 0.07 mL of pyridine were added. The mixture was warmed to reflux, where it stirred for about 24 hours. Analysis of the reaction mixture using TLC indicated the reaction was still not complete. Additional equivalents of thionyl chloride and pyridine were were added to the reaction mixture each day for a period of five days, as the reaction mixture stirred at reflux. At the end of five days the reaction mixture was allowed to cool to ambient temperature, where it stirred for two days. The reaction mixture was then poured into water and extracted with ethyl acetate. The extract was washed with an aqueous solution saturated with sodium chloride and dried with sodium sulfate. The mixture was filtered, and the filtrate concentrated under reduced pressure, yielding about 0.3 gram of 1-methyl-3-[1-(1-methyl-2-chloroethyl)-2-trifluoromethyl-5-fluorobenzimidazol-6-yl]-6-trifluoromethyluracil, mp 93°-95° C. The NMR spectrum was consistent with the proposed structure.

Provenance & Evidence