Regorafenib salt and crystal form thereof, and preparation method

The present invention relates to two types of regorafenib organic acid salts as represented by formulas (I, II), that is, 2-hydroxyl esylate (isethionate salt) and ethyl sulphonate of regorafenib. The present invention also relates to two types of crystal forms of the regorafenib isethionate salt (formula I), named as crystal form A and crystal form B. The present invention also relates to two types of crystal forms of the regorafenib ethyl sulphonate (formula II), named as crystal form α and crystal form β. Also disclosed is a new crystal form of the regorafenib p-toluenesulphonic acid salt, named as crystal form N-1. Also disclosed is a preparation method of regorafenib isethionate salt crystal forms A, B, regorafenib ethyl sulphonate crystal forms α, β and regorafenib p-toluenesulphonic acid salt crystal form N-1. The disclosed regorafenib isethionate salt crystal forms A, B, regorafenib ethyl sulphonate crystal forms α, β and regorafenib p-toluenesulphonic acid salt crystal form N-1 have X-ray powder diffraction characteristic absorption peaks and differential scanning calorimetry (DSC) characteristic absorption peaks, and regorafenib isethionate salt crystal form A, regorafenib ethyl sulphonate crystal form β and regorafenib p-toluenesulphonic acid salt crystal form N-1 are stable, do not absorb moisture easily, and have good solubility.