Potassium Carbonate → 5-Chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

HRID 46406Notes

Reaction equation

HRID 46406 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.C(=O)([O-])[O-].[K+].[K+].[N:36]1[CH:41]=[CH:40][C:39]([C:42]2[CH:47]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:45]=[CH:44][C:43]=2[OH:52])=[CH:38][N:37]=1>CS(C)=O>[Cl:1][C:2]1[C:3]([O:52][C:43]2[CH:44]=[CH:45][C:46]([C:48]([F:49])([F:50])[F:51])=[CH:47][C:42]=2[C:39]2[CH:40]=[CH:41][N:36]=[N:37][CH:38]=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

5

Reactant 3

HCID 11430Potassium CarbonateHCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideHCID 1357416972-(Pyridazin-4-yl)-4-(trifluoromethyl)phenol

Product 1

HCID 594365325-Chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideYield 84.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 247, 378.0 g, 0.761 moles) was dissolved in dimethylsulphoxide (1.9 L). Potassium carbonate (117.8 g, 0.8524 moles) was added and stirred to give a suspension to which was added 2-pyridazin-4-yl-4-(trifluoromethyl)phenol (Preparation 712, 182.8 g, 0.761 moles) in one portion. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate (2.7 L) and aqueous sodium hydroxide solution (2.5 L of 1 molar). The organic phase was washed with water (2×2 L) and then saturated aqueous sodium chloride solution (250 mL). The solution was concentrated in vacuo to give the crude title product. The crude product was purified by column chromatography on silica gel (2 Kg) eluting with ethyl acetate/heptane (3:1). The cleanest fractions were combined and the solvents removed in vacuo to give the title compound as a dark red foam, (440 g). This material was dried in vacuo at 45° C. for 48 hours to give the title compound as a red solid (400 g).

Workup

  1. customto give a suspension to which
  2. stirringThe reaction mixture was stirred at room temperature for 18 hours
  3. customThe reaction mixture was partitioned between ethyl acetate (2.7 L) and aqueous sodium hydroxide solution (2.5 L of 1 molar)
  4. washThe organic phase was washed with water (2×2 L)
  5. concentrationThe solution was concentrated in vacuo
  6. customto give the crude title product
  7. customThe crude product was purified by column chromatography on silica gel (2 Kg)
  8. washeluting with ethyl acetate/heptane (3:1)
  9. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-604eda064bcf44b7ba3e1a91b63e4254
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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