Hydrochloric Acid → 4-[4-Chloro-2-(1H-pyrazol-4-yl)phenoxy]-3-cyano-N-1,3-thiazol-2-ylbenzenesulfonamide

HRID 1692196Notes

Reaction equation

HRID 1692196 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:20])=[C:6]([C:8]2[CH:9]=[N:10][N:11](C(OC(C)(C)C)=O)[CH:12]=2)[CH:7]=1.[C:21]([C:23]1[CH:24]=[C:25]([S:30]([NH:33][C:34]2[S:35][CH:36]=[CH:37][N:38]=2)(=[O:32])=[O:31])[CH:26]=[CH:27][C:28]=1F)#[N:22].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:20][C:28]2[CH:27]=[CH:26][C:25]([S:30]([NH:33][C:34]3[S:35][CH:36]=[CH:37][N:38]=3)(=[O:31])=[O:32])=[CH:24][C:23]=2[C:21]#[N:22])=[C:6]([C:8]2[CH:12]=[N:11][NH:10][CH:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 580422683-Cyano-4-fluoro-N-(thiazol-2-yl)benzenesulfonamideHCID 59436518tert-butyl 4-(5-chloro-2-hydroxyphenyl)-1H-pyrazole-1-carboxylate

Product 1

HCID 468408134-[4-Chloro-2-(1H-pyrazol-4-yl)phenoxy]-3-cyano-N-1,3-thiazol-2-ylbenzenesulfonamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

tert-Butyl 4-(5-chloro-2-hydroxyphenyl)-1H-pyrazole-1-carboxylate (Preparation 205, 624 mg, 2.12 mmol), 3-cyano-4-fluoro-N-1,3-thiazol-2-ylbenzenesulfonamide (Preparation 46, 500 mg, 1.76 mmol) and potassium carbonate (732 mg, 5.30 mmol) were stirred in dimethyl sulphoxide (10 ml) at 50° C. for 2 hours. The reaction was cooled to room temperature and the mixture poured dropwise into hydrochloric acid (2M aqueous, 100 ml). The mixture was stirred at room temperature for 18 hours. The precipitate was filtered and suspended in methanol (10 ml). The mixture was treated with hydrogen chloride (4M in dioxane, 2 ml). The mixture was then stirred at room temperature over for 60 hours. The mixture was evaporated in vacuo. The residue was dissolved in methanol (5 ml). The black solution was passed through an ISOLUTE™ SCX cartridge. The cartridge was eluted with methanol (100 ml) followed by ammonia (2M in methanol). The dark ammonia solution was evaporated in vacuo. The residue was dissolved in dichloromethane/methanol (95/5, 5 ml) and passed through a pad of silica. The solution was evaporated in vacuo. The residue was purified using a silica gel column chromatography eluting with dichloromethane:ethyl acetate (gradient 1:0 to 1:9, by volume). Concentration in vacuo afforded the title compound as a white solid. Yield 427 mg, 53%

Workup

  1. filtrationThe precipitate was filtered
  2. additionThe mixture was treated with hydrogen chloride (4M in dioxane, 2 ml)
  3. stirringThe mixture was then stirred at room temperature over for 60 hours
  4. customThe mixture was evaporated in vacuo
  5. dissolutionThe residue was dissolved in methanol (5 ml)
  6. washThe cartridge was eluted with methanol (100 ml)
  7. customThe dark ammonia solution was evaporated in vacuo
  8. dissolutionThe residue was dissolved in dichloromethane/methanol (95/5, 5 ml)
  9. customThe solution was evaporated in vacuo
  10. customThe residue was purified
  11. washeluting with dichloromethane
  12. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-f444b67cd0b74c2582ab301a6593f933
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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