Water → (S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylic acid

HRID 1028023Notes

Reaction equation

HRID 1028023 reaction equation
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][C:11]([F:16])=[C:12]([CH3:15])[CH:13]=3)[C:8]([C:17]([O:19]C)=[O:18])=[C:7]2[C:21]2[CH:26]=[CH:25][C:24]([S:27](=[O:36])(=[O:35])[NH:28][C@@H:29]([CH3:34])[C:30]([F:33])([F:32])[F:31])=[CH:23][N:22]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].O>C(O)C>[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][C:11]([F:16])=[C:12]([CH3:15])[CH:13]=3)[C:8]([C:17]([OH:19])=[O:18])=[C:7]2[C:21]2[CH:26]=[CH:25][C:24]([S:27](=[O:36])(=[O:35])[NH:28][C@@H:29]([CH3:34])[C:30]([F:32])([F:33])[F:31])=[CH:23][N:22]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 66730643(S)-methyl 1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylate

Product 1

HCID 66730826(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-methyl 1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylate (0.45 g, 0.85 mmol), 25% aq. NaOH (2.0 mL) in ethanol (4.0 mL) was stirred at 80° C. overnight. The mixture was then treated with water and extracted with ether. The aqueous layer was acidified with 1N HCl to pH 4 and extracted with ethyl acetate. The organic layers were washed with brine, dried over Na2SO4 and evaporated to give(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylic acid (0.36 g, 82%). MS m/z 514.2 M+H+; 1H NMR (500 MHz, acetone-d6): δ 10.55 (1H, br s), 9.17 (1H, d, J=2.2 Hz), 8.38 (1H, dd, J=8.2 Hz, J=2.2 Hz), 7.96 (1H, dd, J=8.2, 0.8 Hz), 7.89 (1H, d, J=10.7 Hz), 7.70 (br s, 1H), 7.57 (1H, d, J=6.4 Hz), 4.63-4.56 (1H, m), 4.34-4.29 (1H, m), 2.44 (3H, d, J=1.8 Hz), 2.29-2.25 (2H, m), 2.10-1.90 (4H, m), 1.67-1.56 (2H, m), 1.25 (3H, d, J=7.0 Hz).

Workup

  1. extractionextracted with ether
  2. extractionextracted with ethyl acetate
  3. washThe organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated to give(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylic acid (0.36 g, 82%)

Sources & evidence

ORD record
ord-58925060ee12437db0572c8bc2673b7e
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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