Potassium Carbonate → 4-(4-chloro-2-(2-oxoindolin-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 2203443Notes

Reaction equation

HRID 2203443 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:18])=[C:6]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12](=[O:17])[CH2:11]3)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:25][O:26][C:27]1[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:28]=1[CH2:29][N:30]([C:43]1[S:47][N:46]=[CH:45][N:44]=1)[S:31]([C:34]1[CH:39]=[C:38]([F:40])[C:37](F)=[CH:36][C:35]=1[F:42])(=[O:33])=[O:32]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][C:37]2[C:38]([F:40])=[CH:39][C:34]([S:31]([N:30]([CH2:29][C:28]3[CH:48]=[CH:49][C:50]([O:52][CH3:53])=[CH:51][C:27]=3[O:26][CH3:25])[C:43]3[S:47][N:46]=[CH:45][N:44]=3)(=[O:32])=[O:33])=[C:35]([F:42])[CH:36]=2)=[C:6]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12](=[O:17])[CH2:11]3)[CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 59436583N-(2,4-Dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 895442065-(5-Chloro-2-hydroxyphenyl)indolin-2-one

Product 1

HCID 903891774-(4-chloro-2-(2-oxoindolin-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of 5-(5-chloro-2-hydroxyphenyl)indolin-2-one (0.132 g, 0.51 mmol) and potassium carbonate (0.105 g, 0.76 mmol) in dimethylsulfoxide (3 mL) was added N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.239 g, 0.54 mmol). The reaction mixture was degassed with nitrogen for 10 minutes and stirred for 16 h at ambient temperature. The reaction mixture was partitioned between ethyl acetate (50 mL) and water (5 mL). The organic phase was washed with water (2 5 mL) and brine (2 5 mL), dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with a 10-50% gradient of ethyl acetate in hexanes to afford 4-(4-chloro-2-(2-oxoindolin-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a colorless foam that was carried forward without further purification.

Workup

  1. customThe reaction mixture was degassed with nitrogen for 10 minutes
  2. customThe reaction mixture was partitioned between ethyl acetate (50 mL) and water (5 mL)
  3. washThe organic phase was washed with water (2 5 mL) and brine (2 5 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluting with a 10-50% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-af1d994468b244b89ab707339024a77b
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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