1. 4-(4-(4-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazol-2-yl)piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine (the target compound) was dissolved in 360 mL of acetone to form a homogeneous solution.
2. p-Toluenesulfonic acid monohydrate (10.25 g, 53.9 mmol, 1.2 eq.) dissolved in a 20:1 solution of water:acetone mixture (40 mL) was slowly added to the above solution at 20 °C. The addition process was controlled to be completed within 20 minutes.
3. The reaction mixture was heated to 55 °C and maintained at this temperature for 1 hour.
4. Upon completion of the reaction, the mixture was slowly cooled to 25°C over a period of 1 hour.
5. The precipitated solid product was collected by filtration and the filter cake was washed with 40 mL of water to remove impurities.
6. The resulting solid was dried under vacuum at 50 °C to afford 4-(4-(4-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazol-2-yl)piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine p-toluenesulfonate (23.9 g, 86% yield) as a white solid.
