反应详情

(S)-2-(4-Fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (58 mg, 0.30 mmol) was dissolved in 10 ml of THF and cooled to −40° C. n-BuLi (1.1 eq, 0.16 ml of a 2.5M soln) was added dropwise, forming a purple suspension. This mixture was allowed to stir for 30 minutes until the purple color changed to white. 5-Bromo-6-isocyanato-3-methyl-1-(toluene-4-sulfonyl)-1H-indazole (1 eq, 146 mg) was added and the mixture was allowed to stir for 1 hour at −40° C., then warmed to warm to room temperature and stirred for 2 hours. The reaction was then quenched with saturated aqueous ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate) to give (S)-2-(4-fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid [5-bromo-3-methyl-1-(toluene-4-sulfonyl)-1H-indazol-6-yl]-amide (140 mg, 65.1%) as a yellow foam.

1. additionwas added dropwise
2. customforming a purple suspension
3. stirringto stir for 1 hour at −40° C.
4. temperaturewarmed
5. stirringstirred for 2 hours
6. customThe reaction was then quenched with saturated aqueous ammonium chloride solution
7. additionThe mixture was diluted with water
8. extractionextracted with ethyl acetate
9. washThe combined organic extracts were washed with brine
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate)