Example 4
First setup of salt screening was carried out with Sulfuric Acid, Phosphoric Acid, Toluene Sulfonic Acid and Succinic Acid.
Cooling crystallisations with stoichiometric 1:1 (base:acid) combinations in 2-Propanol, Toluene and THF/Water (0.5:1; v:v) were started. Approx. 20 mg API was dissolved at high temperature and the acid was dosed in the respective amount to the solution. Solid acids were weighed and added as solid into the API solution and liquid acids were dissolved in the respective solvent and given by a pipette to the API solution. In no case a spontaneous salt precipitation after dosage of acid could be observed. Then the solution was cooled down to 5° C. with a slow cooling rate, e.g. 1 K/min (in experiments with 2-PrOH 3-fold cycles heating→cooling were run). In cases where no crystallisation occurred, the vials were placed for further days in the fridge. From Acetone evaporation crystallisations were carried out at RT.
From cooling crystallisations either no solid residues, amorphous solid residues or parent form A1 were obtained. From evaporation crystallisations in Acetone only amorphous residues were obtained. These residues were further treated by dissolving in Ethanol and carrying out of vapour diffusion experiments with Diethyl ether. In no case a crystalline residue was obtained.
