反应详情

(S)-Dimethyl 2-((7-bromo-3-chloro-4-(hydroxymethyl)-1H-indazol-5-yl)methyl)succinate (450 mg, 1.072 mmol) was dissolved in thionyl chloride (2.0 M in dichloromethane) (5.0 mL, 10.00 mmol). Reaction stirred at room temperature for 2.5 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 (430 mg, 0.982 mmol) was dissolved in acetonitrile (15 mL). 2,2,2-Trifluoroethylamine (400 μl, 5.03 mmol) was added to the mixture followed by potassium carbonate (195 mg, 1.411 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 (15 mL). Acetic acid (500 μl, 8.73 mmol) was added to the mixture. Reaction was warmed to reflux and held with stirring for 14 hours. Mixture was cooled to room temperature. Mixture was diluted with 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. Silica gel chromatography eluting ethyl acetate-hexanes afforded the title compound as white solid in 46% yield. MS (M−H)−=467.9.

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 (15 mL)
14. customReaction
15. temperaturewas warmed
16. temperatureto reflux
17. stirringwith stirring for 14 hours
18. temperatureMixture was cooled to room temperature
19. washMaterial was washed twice with aqueous sodium bicarbonate
20. filtrationfiltered
21. concentrationconcentrated to dryness
22. washSilica gel chromatography eluting ethyl acetate-hexanes