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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 1892959
Notes
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Reaction equation

HRID 1892959 reaction equation
[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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887Methanol
Solvent

Conditions

Temperature
60 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-8c65c087a18f4fd2b624ab2b80518192
Source dataset
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08507543B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes