反应详情

To a chilled (−78° C.) solution of 490 mg (1.68 mmol) of 5-bromo-1-(4-fluorophenyl)-1H-indazole in 5 mL of anhydrous THF was added 0.69 mL (1.73 mmol) of a 2.5 M solution of n-BuLi in hexanes. The mixture stirred for 5 minutes, and was then added to a chilled (dry ice-acetone) solution of the sodium salt of 1-(7-chloro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2,2,2-trifluoroethanone prepared by adding at room temperature 83 mg (2.08 mmol) of 60% sodium hydride in mineral oil to 374 mg (1.50 mmol) of 1-(7-chloro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2,2,2-trifluoroethanone (prepared as described in J. Org. Chem. 2002, 76, 6226) in 5 mL of THF. The mixture stirred for 30 minutes with the cold bath removed and was then diluted with 30 mL of saturated aqueous ammonium chloride and extracted with three 25 mL portions of ethyl acetate. The combined organic layers were washed with three 25 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel using dichloromethane to load the sample and then eluting with dichloromethane-hexanes (50-100% gradient) and then ethyl acetate-dichloromethane (0-25%) to afford partially purified product. A second column eluting with ether-hexanes (5-50% gradient) followed by solidifying the material from the column from ether-hexanes gave 344 mg (49%) of the title compound. MS m/z 461.25 (MH+).

1. additionwas then added to
2. customprepared
3. stirringThe mixture stirred for 30 minutes with the cold bath
4. customremoved
5. additionwas then diluted with 30 mL of saturated aqueous ammonium chloride
6. extractionextracted with three 25 mL portions of ethyl acetate
7. washThe combined organic layers were washed with three 25 mL portions of brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude residue was chromatographed on silica gel
12. washeluting with dichloromethane-hexanes (50-100% gradient)
13. customethyl acetate-dichloromethane (0-25%) to afford partially purified product
14. washA second column eluting with ether-hexanes (5-50% gradient)