Dimethyl Sulfoxide → 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

HRID 46270Notes

Reaction equation

HRID 46270 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.[F:30][C:31]1[C:32]([C:44]([F:47])([F:46])[F:45])=[CH:33][C:34]([C:38]2[CH:43]=[CH:42][N:41]=[N:40][CH:39]=2)=[C:35]([OH:37])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O.[Cl-].[NH4+]>[Cl:1][C:2]1[C:3]([O:37][C:35]2[CH:36]=[C:31]([F:30])[C:32]([C:44]([F:47])([F:45])[F:46])=[CH:33][C:34]=2[C:38]2[CH:43]=[CH:42][N:41]=[N:40][CH:39]=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:9])=[O:10])[CH:7]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideHCID 1360636295-Fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol

Product 1

HCID 866438255-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideYield 23%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 25517Ammonium ChlorideSolvent

Procedure

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 247, 63 mg, 0.14 mmol) was added to a mixture of 5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol (Preparation 884, mg, 0.14 mmol) and potassium carbonate (22 mg, 0.16 mmol) in dimethyl sulfoxide (2 mL, 30 mmol). The reaction mixture was stirred at ambient temperature. After 3 hours the reaction mixture was diluted with water and saturated aqueous ammonium chloride and extracted with ethyl acetate (3×). The combined organic layers were washed with water then brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in methylene chloride, concentrated onto diatomaceous earth, and purified by automated flash chromatography (12 g SiO2, hexanes to ethyl acetate) to afford the intermediate 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide as a glass (22 mg, 23%).

Workup

  1. customPreparation 884
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with water
  4. dry with materialbrine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. concentrationconcentrated onto diatomaceous earth
  8. custompurified by automated flash chromatography (12 g SiO2, hexanes to ethyl acetate)

Sources & evidence

ORD record
ord-24719b386cdd4746b53de53bb7dd68ff
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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