Potassium Carbonate → 5-Chloro-4-(6-chloro-3'-fluoro-4-(pyridazin-4-yl)biphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 1619698Notes

Reaction equation

HRID 1619698 reaction equation
[Cl:1][C:2]1[C:3](F)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1.[Cl:30][C:31]1[C:36]([C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=2)=[CH:35][C:34]([OH:44])=[C:33]([C:45]2[CH:50]=[CH:49][N:48]=[N:47][CH:46]=2)[CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[OH-].[Na+]>[Cl:1][C:2]1[C:3]([O:44][C:34]2[CH:35]=[C:36]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=3)[C:31]([Cl:30])=[CH:32][C:33]=2[C:45]2[CH:50]=[CH:49][N:48]=[N:47][CH:46]=2)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideHCID 1362008776-Chloro-3'-fluoro-4-(pyridazin-4-yl)biphenyl-3-ol

Product 1

HCID 580422475-Chloro-4-(6-chloro-3'-fluoro-4-(pyridazin-4-yl)biphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideYield 27.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 14798Sodium HydroxideSolvent

Procedure

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide (Preparation 16, 136 mg, 0.29 mmol) was added to a solution of 6-chloro-3′-fluoro-4-(pyridazin-4-yl)biphenyl-3-ol (Preparation 98, 133 mg, 0.29 mmol) and potassium carbonate (183 mg, 0.88 mmol) in dimethylsulfoxide (5 mL). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with sodium hydroxide (1M, 5 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The residue was dissolved in dimethylsulfoxide:acetonitrile (2.5 mL: 1.5 mL) and then purified on the reverse phase HPLC eluting with acetonitrile:water (from 5:95 to 95:5, 30 minutes gradient then 5 minutes isocratic) to give the title compound (60 mg, 18%) as a white solid.

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in dimethylsulfoxide
  6. customacetonitrile (2.5 mL: 1.5 mL) and then purified on the reverse phase HPLC
  7. washeluting with acetonitrile
  8. customto 95:5, 30 minutes

Sources & evidence

ORD record
ord-5058837b04cd43b5aec13e7a933ac95e
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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