반응 #74531

반응 방정식

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

용매

dichloromethane

methanol

methanol

Methanol

N,N-dimethylformamide

methanol

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   여과filtered
2. 2
   기타to give a solid
3. 3
   workup.STIRRINGThe resulting solution was stirred for 16 hours
4. 4
   여과filtered off polymeric solid
5. 5
   농축The filtrate was concentrated in vacuo
6. 6
   기타to give a residue
7. 7
   농축The filtrate was concentrated in vacuo
8. 8
   기타purified by HPLC

실험 절차

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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