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

HRID 46273Notes

Reaction equation

HRID 46273 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:12]=[C:11]([O:13][C:14]([F:17])([F:16])[F:15])[CH:10]=[CH:9][C:8]=2[OH:18])=[CH:3][N:2]=1.CS(C)=O.C(=O)([O-])[O-].[K+].[K+].COC1C=C(OC)C=CC=1C[N:34]([C:47]1[S:48][CH:49]=[N:50][N:51]=1)[S:35]([C:38]1[CH:43]=[C:42]([CH3:44])[C:41](F)=[CH:40][C:39]=1[F:46])(=[O:37])=[O:36].C(Cl)Cl.FC(F)(F)C(O)=O>Cl>[F:46][C:39]1[CH:40]=[C:41]([O:18][C:8]2[CH:9]=[CH:10][C:11]([O:13][C:14]([F:16])([F:17])[F:15])=[CH:12][C:7]=2[C:4]2[CH:5]=[CH:6][N:1]=[N:2][CH:3]=2)[C:42]([CH3:44])=[CH:43][C:38]=1[S:35]([NH:34][C:47]1[S:48][CH:49]=[N:50][N:51]=1)(=[O:36])=[O:37]

Participants

8

Reactant 6

HCID 679Dimethyl SulfoxideHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 59436572N-(2,4-dimethoxybenzyl)-2,4-difluoro-5-methyl-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideHCID 1360636182-Pyridazin-4-yl-4-(trifluoromethoxy)phenol

Product 1

HCID 468420882-fluoro-5-methyl-4-[2-pyridazin-4-yl-4-(trifluoromethoxy)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideYield 18.1%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
60 °C

Procedure

2-pyridazin-4-yl-4-(trifluoromethoxy)phenol (Preparation 888, 30 mg, 0.12 mmol) was taken up in dimethyl sulfoxide (1 mL, 20 mmol) and potassium carbonate (30 mg, 0.22 mmol) added, followed by N-(2,4-dimethoxybenzyl)-2,4-difluoro-5-methyl-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 889, 51.7 mg, 0.117 mmol). The reaction was heated at 60° C. for 72 hours. The reaction was cooled and diluted with 1N HCl. The resulting precipitate was collected by filtration. The solid was dissolved in methylene chloride (1.0 mL, 16 mmol) and dried over magneisum sulfate. The solution was then treated with trifluoroacetic acid (45 uL, 0.58 mmol) and stirred for 2 hours. The reaction mixture was concentrated in vacuo. The residue was purified by reverse phase HPLC. Product fractions were combined and the solvent removed in vacuo to give a residue. The product was purified a second time by column chromatography (4 g silica gel column, 0 to 10% methanol in methylene chloride gradient elution). Product fractions were combined and concentrated in vacuo to give 11.2 mg of colorless glass.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationThe resulting precipitate was collected by filtration
  3. dry with materialdried over magneisum sulfate
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customThe residue was purified by reverse phase HPLC
  6. customthe solvent removed in vacuo
  7. customto give a residue
  8. customThe product was purified a second time
  9. washby column chromatography (4 g silica gel column, 0 to 10% methanol in methylene chloride gradient elution)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8132842d62164cbd9cd2a1f11a791d1f
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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