反应详情

To a chilled (−78° C.) solution of 7-bromo-4-chloro-5H-pyrrolo[3,2-d]pyrimidine (80 mg, 0.34 mmol, 1 equiv.) in 5 mL of THF was added tert-BuLi (1.7 M in pentane, 0.43 mL, 0.73 mmol, 2.1 equiv.) dropwise. After 5 minutes, a chilled (−78° C.) solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (106 mg, 0.34 mmol, 1 equiv.) in 1 mL of THF was added in one portion. After 15 minutes, the reaction was quenched with 15 mL of water, warmed to room temperature, diluted with 100 mL of saturated aqueous ammonium chloride, and then extracted with EtOAc. The combined organic layers were dried, filtered, and concentrated in vacuo. The residue was dissolved in DMF and purified by reverse phase HPLC (5-95% CH3CN/water+0.1% TFA). The major fractions collected were made basic with saturated NaHCO3 and the CH3CN was concentrated in vacuo. The aqueous was extracted with EtOAc and washed with brine. The organic layers were dried, filtered, and concentrated in vacuo to provide 52 mg (32%) of the title compound as a white solid. MS m/z 462.56 (MH+).

1. additionwas added in one portion
2. waitAfter 15 minutes
3. customthe reaction was quenched with 15 mL of water
4. additiondiluted with 100 mL of saturated aqueous ammonium chloride
5. extractionextracted with EtOAc
6. customThe combined organic layers were dried
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in DMF
10. custompurified by reverse phase HPLC (5-95% CH3CN/water+0.1% TFA)
11. customThe major fractions collected
12. concentrationthe CH3CN was concentrated in vacuo
13. extractionThe aqueous was extracted with EtOAc
14. washwashed with brine
15. customThe organic layers were dried
16. filtrationfiltered
17. concentrationconcentrated in vacuo