反应详情

(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. Yield 59 mg (79%).

1. customthe solvents was removed by evaporation
2. additionthe residual material was treated with water and a few drops of dilute HCl(aq) until slightly acidic
3. extractionThe formed slurry was extracted with DCM and EtOAc
4. concentrationthe combined organic phases was concentrated
5. custompurified by semi-preparative HPLC
6. customFlow 10 mL/min, 15 min gradient of 50%-90% MeCN in water
7. concentrationconcentration until product
8. washhad eluted