反应详情

(±)-[1-(2,4-Dichloro-pyrimidin-5-yl)-ethyl]-(2-fluoro-4-methoxy-phenyl)-amine (1.15 g; 3.63 mmol) (from Example 8b supra) was combined with 3-cyanophenyl isocyanate (0.55 g; 3.81 mmol) (Aldrich) in toluene (10 mL) and heated in an oil bath at 110–115° C. for 2 hours and then up to 128° C. over the next 3 hours. Upon cooling to room temperature, the reaction was concentrated and triturated with hexanes. The crude material was purified by flash chromatography (Biotage, 40M; 50:50 ethyl acetate-hexanes) to give the intermediate (±)-1-[1-(2-chloro-pyrimidin-5-yl)-ethyl]-3-(3-cyano-pheny)-1-(2-fluoro-4-methoxy-phenyl)-urea. (Yield 1.20 g; 71.8%).

1. temperatureheated in an oil bath at 110–115° C. for 2 hours
2. customup to 128° C.
3. customover the next 3 hours
4. concentrationthe reaction was concentrated
5. customtriturated with hexanes
6. customThe crude material was purified by flash chromatography (Biotage, 40M; 50:50 ethyl acetate-hexanes)