반응 #41295

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(1R,2S)-1-{[1-(4-Fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride

(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride

1,1,3,3-tetramethylguanidine

ethyl trifluoroacetate

→

title compound

2,2,2-trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-yl]acetamide

용매

MeOH

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction mixture was stirred at r.t. for 2.5 h
2. 2
   기타The reaction mixture was evaporated
3. 3
   기타the residual material was purified by semi-preparative HPLC
4. 4
   기타Flow 10 mL/min, 20 min gradient of 20%-90% MeCN in water
5. 5
   농축concentration until product
6. 6
   세척had eluted

실험 절차

(1R,2S)-1-{[1-(4-Fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride (9a) (150 mg, 0.34 mmol) was dissolved in MeOH (2 mL). 1,1,3,3-tetramethylguanidine (128 μL, 1.02 mmol) was added and the mixture was stirred for 5 min, ethyl trifluoroacetate (83 μL, 0.7 mmol) was added and the reaction mixture was stirred at r.t. for 2.5 h. The reaction mixture was evaporated and the residual material was purified by semi-preparative HPLC using a Kromasil® C18 250×20 mm, 5 μm column. Flow 10 mL/min, 20 min gradient of 20%-90% MeCN in water followed by isocratic final concentration until product had eluted. UV=254 nm was used for detection. Fractions with product was combined and lyophilized to afford the title compound as a colourless solid. Yield 128 mg (74%)

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