反应详情

(S)-Dimethyl 2-((3,7-dibromo-4-(hydroxymethyl)-1H-indazol-5-yl)methyl)succinate (460 mg, 0.991 mmol) was dissolved in thionyl chloride (2.0 M. in dichloromethane) (496 μl, 0.992 mmol). Reaction stirred at room temperature for 4 hours. Mixture was concentrated by roto-vap. Residue was dissolved in ethyl acetate. Material was washed twice with aqueous sodium bicarbonate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Residue (415 mg, 0.860 mmol) was dissolved in acetonitrile (15 mL). Potassium carbonate (165 mg, 1.194 mmol) was added to the mixture followed by 2,2,2-trifluoroethylamine (350 μl, 4.40 mmol). Mixture was warmed to reflux and held with stirring for 30 minutes. Mixture was cooled to room temperature. Mixture was filtered over celite. Filtrate was concentrated by roto-vap. Residue was dissolved in toluene (17 mL). Acetic acid (200 μl, 3.49 mmol) was added to the mixture. Reaction was warmed to reflux and held with stirring for 16 hours. Mixture was cooled to room temperature and then diluted with ethyl acetate. Mixture was washed with aqueous sodium bicarbonate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Silica gel chromatography eluting ethyl acetate-hexanes afforded the title compound as white solid in 45% yield. MS (M−H)−=512.1, 510.1, 514.1.

1. customReaction
2. concentrationMixture was concentrated by roto-vap
3. dissolutionResidue was dissolved in ethyl acetate
4. washMaterial was washed twice with aqueous sodium bicarbonate
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. temperatureMixture was warmed
8. temperatureto reflux
9. stirringwith stirring for 30 minutes
10. temperatureMixture was cooled to room temperature
11. filtrationMixture was filtered over celite
12. concentrationFiltrate was concentrated by roto-vap
13. dissolutionResidue was dissolved in toluene (17 mL)
14. customReaction
15. temperaturewas warmed
16. temperatureto reflux
17. stirringwith stirring for 16 hours
18. temperatureMixture was cooled to room temperature
19. washMixture was washed with aqueous sodium bicarbonate
20. filtrationfiltered
21. concentrationconcentrated to dryness
22. washSilica gel chromatography eluting ethyl acetate-hexanes