Acetic Acid → HCID 178500649, 화합물

HRID 132464노트

반응식

HRID 132464 반응식
[Cl:1][C:2]1[C:10]2[C:5](=[C:6]([Cl:24])[CH:7]=[C:8]([CH2:13][C@@H:14]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:15]([O:17]C)=O)[C:9]=2[CH2:11]O)[NH:4][N:3]=1.S(Cl)(Cl)=O.[NH2:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>C(#N)C>[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:29]([CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)[C:15](=[O:17])[C@H:14]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:13][C:8]=3[CH:7]=[C:6]([Cl:24])[C:5]=2[NH:4][N:3]=1

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 33944N-(2-Aminoethyl)piperidineHCID 178500726(S)-dimethyl 2-((3,7-dichloro-4-(hydroxymethyl)-1H-indazol-5-yl)methyl)succinate

생성물 1

HCID 178500649HCID 178500649, 화합물수율 51%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

(S)-Dimethyl 2-((3,7-dichloro-4-(hydroxymethyl)-1H-indazol-5-yl)methyl)succinate (990 mg, 2.64 mmol) was dissolved in thionyl chloride (2.0 M in dichloromethane) (20 mL, 40.0 mmol). Mixture stirred at room temperature for 3 hours. Mixture was concentrated by roto-vap. Residue was dissolved in ethyl acetate. Mixture was washed twice with aqueous sodium bicarbonate. Organics were dried MgSO4, filtered and then concentrated to dryness. A portion of the residue (460 mg, 1.169 mmol) was dissolved in acetonitrile (15 mL). 1-(2-Aminoethyl)-piperidine (600 μl, 4.21 mmol) was added to the mixture followed by potassium carbonate (200 mg, 1.447 mmol). Mixture was warmed to reflux and held with stirring for 1 hour. Mixture was cooled to room temperature and then filtered over celite. Filtrate was concentrated by roto-vap. Residue was dissolved in toluene (15 mL). Acetic acid (1.0 mL, 17.47 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 concentrated by roto-vap. Residue was suspended in ethyl acetate. Mixture 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 2M ammonia in methanol-dichloromethane afforded the title compound as amber oil in 51% yield. (M+H)+=453.0, 455.0.

후처리

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

출처 및 근거

ORD 기록
ord-f9ca7eb236f24b81bf23114414505fdd
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384931B2

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