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

HRID 1874725Notes

Reaction equation

HRID 1874725 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][C:26]([O:29][CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])=[CH:25][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:24]=[CH:25][C:26]([O:29][CH2:30][CH2:31][N:32]([CH3:33])[CH3:34])=[CH:27][CH:28]=3)[N:12]=2)(=[O:8])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 580545145-Chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(4-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide

Product 1

HCID 594560635-Chloro-N-[1-[(4-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamideYield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 5-chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(4-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 18) (91 mg, 0.13 mmol) in MeOH (5 mL) was treated with a 2M aq. NaOH solution (1 mL) and the mixture was heated to 70° C. for 2 h, and then allowed to stand at RT over the weekend. The solvents evaporated by this time and the white solid residue was diluted with water and 2M HCl solution (1 mL) and extracted with ethyl acetate. The organic solution was washed with brine, dried (MgSO4) and evaporated to dryness (72 mg). The residue was dissolved in 1:1 MeOH:DMSO (1 mL) and purified by MDAP on Xbridge column using acetonitrile-water with an ammonium carbonate modifier. The solvent was evaporated in vacuo to give the title compound (43 mg, 64%) as a colourless gum. LCMS (System C) RT=2.20 min, ES+ve m/z 521/523 (M+H)+.

Workup

  1. customto stand at RT over the weekend
  2. customThe solvents evaporated by this time
  3. additionthe white solid residue was diluted with water and 2M HCl solution (1 mL)
  4. extractionextracted with ethyl acetate
  5. washThe organic solution was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness (72 mg)
  8. dissolutionThe residue was dissolved in 1:1 MeOH
  9. customDMSO (1 mL) and purified by MDAP on Xbridge column
  10. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-67a4934480c24d179d7fa1dae67ffb10
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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