Trifluoroacetic acid → N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-phenyl-propan-2-yl]cyclopropanesulfonamide

Participants

Reaction Conditions

Reaction Steps

(1R,2S)-1-[1-(4-Fluorophenyl)indazol-5-yl]oxy-1-phenyl-propan-2-amine (1a, 16 mg, 0.044 mmole) was dissolved in dry pyridine (2 mL) and cooled to 0° C. Cyclopropanesulfonyl chloride (16 μl, 0.056 mmole) was added and the mixture was stirred at room temperature for 45 mm. The progression of the reaction was followed by HPLC (R.P C-18, 20-90% gradient of CH3CN in water, 0.1% TFA). After 45 and 75 mm additional portions of cyclopropanesulfonyl chloride (5 and 6 μl respectively) were added. As the reaction proceeded very slowly, triethylamine (27 μl, 0.2 mmol) was added after a total of 2.5 h of stirring. The stirring was continued at ambient temperature for additional 18.5h and the reaction mixture was then partitioned between ethyl acetate and aqueous hydrochloric acid (1.7M). The organic phase was washed twice with aqueous hydrochloric acid (1.7M), then with water and finally with brine. Evaporation and flash chromatography (SiO2, gradient of 0-50% EtOAc in heptane) and finally lyophilization from dioxane gave the title compound (7 mg, 33%) containing 15 mol % of dioxane.

Provenance & Evidence