Acetic Acid → HCID 178500647, 화합물

HRID 132459노트

반응식

HRID 132459 반응식
[Br:1][C:2]1[CH:3]=[C:4]([CH2:14][C@@H:15]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[C:16]([O:18]C)=O)[C:5]([CH2:12]O)=[C:6]2[C:10]=1[NH:9][N:8]=[C:7]2[Cl:11].S(Cl)(Cl)=O.[F:29][C:30]([F:34])([F:33])[CH2:31][NH2:32].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>C(#N)C.C(OCC)(=O)C>[Br:1][C:2]1[C:10]2[NH:9][N:8]=[C:7]([Cl:11])[C:6]=2[C:5]2[CH2:12][N:32]([CH2:31][C:30]([F:34])([F:33])[F:29])[C:16](=[O:18])[C@H:15]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:14][C:4]=2[CH:3]=1

참가 물질

8

반응물 5

HCID 176Acetic AcidHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 178500725HCID 178500725, 화합물

생성물 1

HCID 178500647HCID 178500647, 화합물수율 46%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-70b6a2027b114e78b0cece73bacfe367
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384931B2

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