Reaktion #41295

Reaktionsgleichung

(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

Lösungsmittel

MeOH

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

(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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