To a stirred, ice-cooled solution of 2,2,2-trifluoro-N-((1R,2S)-1-(1-(3-(hydroxymethyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)acetamide (144, 119 mg, 0.35 mmol) and triethylamine (0.35 mL, 2.5 mmol) was added methanesulfonyl chloride (140 μL, 1.8 mmol). The mixture was stirred for 55 min at 0° C. and brine was then added followed by dichloromethane (10 mL) and aqueous KHSO4 (1M). The phases were separated and the organic phase washed with sat aqueous NaHCO3. To the organic phase was the added morpholine (1 mL, 11.5 mmol). The mixture was stirred at ambient temperature for 16 h and was then evaporated. The residue was subjected to preparative HPLC (Kromasil C-18, 2.5×20 cm) using a gradient (holding 0.1% TfA) of 30-90% acetonitrile in water/60 min. Fractions containing the title compound were combined and evaporated. The residue, comprising the TfA-salt of the title compound was dissolved in MeOH and absorbed on a plug of acidic ion exchange resin (SCX, 5 g, pre-washed with MeOH). Eluting with MeOH and methanolic ammonia (2M) subsequently afforded after evaporation, re-dissolving in water and lyophilization 2,2,2-trifluoro-N-((1R,2S)-1-(1-(3-(morpholinomethyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)acetamide (105 mg, 77%).
