Reaktion #74548

Reaktionsgleichung

dimethyl sulfoxide

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol

potassium carbonate

→

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

Ausbeute 23.0%

Lösungsmittel

water

ammonium chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigePreparation 884
2. 2
   Extraktionextracted with ethyl acetate (3×)
3. 3
   WaschenThe combined organic layers were washed with water
4. 4
   Trocknenbrine, dried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated in vacuo
7. 7
   Einengenconcentrated onto diatomaceous earth
8. 8
   Sonstigepurified by automated flash chromatography (12 g SiO2, hexanes to ethyl acetate)

Vorschrift

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%).

Quelle