Potassium Hydroxide → N-[2,4-Difluoro-3-(7-pyridin-4-yl-2,3-dihydro-pyrazolo[5,1-b]thiazol-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide

HRID 38109Notes

Reaction equation

HRID 38109 reaction equation
[F:1][C:2]1[C:7]([C:8]2[C:15]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)=[C:11]3[S:12][CH2:13][CH2:14][N:10]3[N:9]=2)=[C:6]([F:22])[CH:5]=[CH:4][C:3]=1[NH2:23].[F:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[S:32](Cl)(=[O:34])=[O:33].[OH-].[K+]>N1C=CC=CC=1.C(OCC)(=O)C.C1COCC1>[F:1][C:2]1[C:7]([C:8]2[C:15]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)=[C:11]3[S:12][CH2:13][CH2:14][N:10]3[N:9]=2)=[C:6]([F:22])[CH:5]=[CH:4][C:3]=1[NH:23][S:32]([C:26]1[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:25]=1[F:24])(=[O:34])=[O:33]

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 27369112,5-Difluorobenzenesulfonyl chlorideHCID 584771122,4-Difluoro-3-(7-pyridin-4-yl-2,3-dihydro-pyrazolo[5,1-b]thiazol-6-yl)phenylamine

Product 1

HCID 46220513N-[2,4-Difluoro-3-(7-pyridin-4-yl-2,3-dihydro-pyrazolo[5,1-b]thiazol-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamideYield 37%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2,4-difluoro-3-(7-pyridin-4-yl-2,3-dihydro-pyrazolo[5,1-b]thiazol-6-yl)phenylamine (115 mg, 0.54 mmol) in pyridine (3 mL) was added 2,5-difluoro-benzenesulfonyl chloride (88 μL, 0.81 mmol) and the mixture was stirred under nitrogen atmosphere for one hour. The mixture was diluted with ethyl acetate and washed with NaHCO3 saturated solution and with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and dried. The solvent was removed under reduce pressure to give a mixture of mono and bis-sulfonamide. The crude was dissolved in THF (4 mL). A 1 M KOH solution (4 mL) was added and the mixture was stirred at 70° C. overnight. The solvent was removed under reduced pressure and the crude was dissolved in ethyl acetate and washed with NaHCO3 saturated solution twice. The organic layer was dried over sodium sulphate, filtered and the solvent was removed under reduced pressure. N-[2,4-Difluoro-3-(7-pyridin-4-yl-2,3-dihydro-pyrazolo[5,1-b]thiazol-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide (64 mg, 37%) was isolated by silica gel chromatography column eluting with ethyl acetate 5% in hexane.

Workup

  1. washwashed with NaHCO3 saturated solution and with brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customdried
  5. customThe solvent was removed
  6. customto give
  7. stirringthe mixture was stirred at 70° C. overnight
  8. customThe solvent was removed under reduced pressure
  9. dissolutionthe crude was dissolved in ethyl acetate
  10. washwashed with NaHCO3 saturated solution twice
  11. dry with materialThe organic layer was dried over sodium sulphate
  12. filtrationfiltered
  13. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-6f1311de290e44579a8b525122484279
Source dataset
uspto-grants-2013_09
Patent number
US08524707B2

Reaction notes

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