反应详情

温度

-40 °C

To a solution of THF (500 mL) was added 1-{4-[4-amino-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea (2.29 g, 4.65 mmol). The solution was cooled to −40° C. and then 1,3-dibromo-5,5-dimethylhydantoin (665 mg, 2.33 mmol) was added in two batches 20 min apart. The reaction was stirred at −40° C. for 1 h and then allowed to warm to rt over the following 2 h. Aq saturated Na2SO3 was added to the reaction followed by EtOAc. The layers were separated and the aqueous layer was back extracted with EtOAc. The organic layer was washed with 1 N NaOH and water, dried (Na2SO4), filtered and evaporated to yield 2.83 g crude (107%) of the desired product. MS [M+H]+=571; LCMS RT=3.54.

1. temperatureto warm to rt over the following 2 h
2. customThe layers were separated
3. extractionthe aqueous layer was back extracted with EtOAc
4. washThe organic layer was washed with 1 N NaOH and water
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customevaporated