Sodium Hydroxide → 2-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoic acid

HRID 2270808Notes

Reaction equation

HRID 2270808 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH:18]=[N:19][N:20]3[CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH:18]=[N:19][N:20]3[CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 865851462-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester

Product 1

HCID 226615142-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoic acidYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 2-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester (87.8 mg, 0.206 mmol) in methanol (1 mL) was cooled to ˜0° C. and 1 M sodium hydroxide (0.206 mL, 0.206 mmol) was added. The cooling bath was removed and the reaction mixture was allowed to stir overnight. A further portion of sodium hydroxide (1 M; 0.2 mL, 0.2 mmol) was added and the mixture was stirred at room temperature for 7 h. The solvent was evaporated and the residue was dissolved in water (25 mL) and washed with ethyl acetate (2×10 mL). The aqueous layer was made acidic with 1 M HCl and extracted with ethyl acetate (2×20 mL). These extracts were combined, washed with brine (10 mL), dried (MgSO4), filtered, and concentrated to give 2-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoic acid (77.3 mg, 91%) as a white solid.

Workup

  1. customThe cooling bath was removed
  2. stirringthe mixture was stirred at room temperature for 7 h
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in water (25 mL)
  5. washwashed with ethyl acetate (2×10 mL)
  6. extractionextracted with ethyl acetate (2×20 mL)
  7. washwashed with brine (10 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f06f95ab4d8c455da486bb3dcca5bce0
Source dataset
uspto-grants-2001_12
Patent number
US06331640B1

Reaction notes

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