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Sodium Hydroxide → 5-Chloro-N-[1-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide

HRID 1808618
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1808618
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10](S(C2SC(Cl)=CC=2)(=O)=O)[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])[CH:24]=3)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH2:30][CH2:31][N:32]([CH3:33])[CH3:34])[CH:24]=3)[N:12]=2)(=[O:8])=[O:9])=[CH:4][CH:3]=1
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Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 580544865-Chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide

Produkt 1

HCID 594560905-Chloro-N-[1-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamideAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887
Methanol
Lösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

5-Chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 18) (140 mg, 0.2 mmol) was suspended in methanol (25 mL) and treated with 2M NaOH aqueous solution (2 mL). The mixture was heated to 60° C. for 4 h and then concentrated under reduced pressure. The residue was partitioned between 2M HCl (2 mL) and ethyl acetate. The aq. layer was back-extracted and the organic solution was washed with brine, dried (MgSO4) and evaporated. The residue was dissolved in 1:1 MeOH:DMSO (1.5 mL) and purified by MDAP on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier. Appropriate fractions were evaporated in vacuo to give the title product (40 mg, 39%). LCMS (System C) RT=2.29 min, ES+ve m/z 521/523 (M+H)+.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between 2M HCl (2 mL) and ethyl acetate
  3. extractionThe aq. layer was back-extracted
  4. washthe organic solution was washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. dissolutionThe residue was dissolved in 1:1 MeOH
  8. customDMSO (1.5 mL) and purified by MDAP on Xbridge column
  9. customAppropriate fractions were evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-68045c5841c84cb4a8a7ceb6a68024a6
Quelldatensatz
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08357716B2

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