Reacción #41296

Ecuación de reacción

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

1,1,3,3-tetramethylguanidine

ethyl trifluoroacetate

→

title compound

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

Disolventes

MeOH

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe solvents was removed by evaporation
2. 2
   workup.ADDITIONthe residual material was treated with water and a few drops of dilute HCl(aq) until slightly acidic
3. 3
   ExtracciónThe formed slurry was extracted with DCM and EtOAc
4. 4
   Concentraciónthe combined organic phases was concentrated
5. 5
   Otropurified by semi-preparative HPLC
6. 6
   OtroFlow 10 mL/min, 15 min gradient of 50%-90% MeCN in water
7. 7
   Concentraciónconcentration until product
8. 8
   Lavadohad eluted

Procedimiento

(1R,2S)-1-{[1-(4-Fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(cyclopropylthio)phenyl]propan-2-amine (62 mg, 0.14 mmol) was dissolved in MeOH (2 mL), 1,1,3,3-tetramethylguanidine (100 μL, 0.8 mmol) and ethyl trifluoroacetate (83 μL, 0.7 mmol) was added. The mixture was stirred at r.t. for 2 h, the solvents was removed by evaporation and the residual material was treated with water and a few drops of dilute HCl(aq) until slightly acidic. The formed slurry was extracted with DCM and EtOAc, the combined organic phases was concentrated and purified by semi-preparative HPLC using a Kromasil® C18 250×20 mm, 5 μm column. Flow 10 mL/min, 15 min gradient of 50%-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.

Fuente