Reaktion #74531

Reaktionsgleichung

trifluoroacetic acid

ammonia

N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

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

potassium carbonate

hydrochloric acid

→

2,5-difluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

Lösungsmittel

dichloromethane

methanol

methanol

Methanol

N,N-dimethylformamide

methanol

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationfiltered
2. 2
   Sonstigeto give a solid
3. 3
   workup.STIRRINGThe resulting solution was stirred for 16 hours
4. 4
   Filtrationfiltered off polymeric solid
5. 5
   EinengenThe filtrate was concentrated in vacuo
6. 6
   Sonstigeto give a residue
7. 7
   EinengenThe filtrate was concentrated in vacuo
8. 8
   Sonstigepurified by HPLC

Vorschrift

The mixture of N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Preparation 647, 44 mg, 0.10 mmol), 2-pyridazin-4-yl-4-(trifluoromethyl)phenol (Preparation 712, 34 mg, 0.10 mmol), and potassium carbonate (55 mg, 0.40 mmol) in N,N-dimethylformamide (1.0 ml) was stirred at room temperature for 24 hours. The reaction mixture was poured into aqueous 2 M hydrochloric acid solution (5.0 ml) and filtered to give a solid. The solid was dissolved in dichloromethane (1.0 ml) and trifluoroacetic acid (1.0 ml) was added to the solution. The resulting solution was stirred for 16 hours. Methanol (5.0 ml) was added to the reaction mixture and filtered off polymeric solid. The filtrate was concentrated in vacuo to give a residue. The residue was passed through a 5 g SCX™ column with 1:1 dichloromethane:methanol solution and then 1:0.75:0.25 dichloromethane:methanol:7N ammonia solution in methanol. The filtrate was concentrated in vacuo and purified by HPLC. Yield 7.3 mg, 14%.

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