Compound of eoc315 mod.i crystal form and preparation method thereof

Abstract

The present application relates to a crystalline form of 4-(4-chloroanilino)-7-(2-methylaminocarbonyl-4-oxymethyl)pyridylfuro[2,3-d]pyridazine mesylate (EOC315) that contains crystalline form Mod. I. The present application also relates to a process for the preparation of the crystalline form and the pharmaceutical use of the crystalline form.

1 . The crystalline form Mod.I of Formula I: 
       
         
           
           
               
               
           
         
         which has an X-ray powder diffraction diagram with peaks at diffraction angles 2θ of 7.85°±0.1°, 9.94°±0.1°, 13.04°±0.1°, 19.08°±0.1°, 21.82°±0.1°, 22.49°±0.1°, and 28.52°±0.1°, when analyzed with X-ray powder diffraction using CuKα radiation. 
       
     
     
         2 . The crystalline form of  claim 1 , wherein said crystalline form Mod. I has an X-ray powder diffraction diagram with peaks at diffraction angles 2θ of 4.01°±0.1°, 7.85°±0.1°, 9.94°±0.1° 13.04°±0.1° 19.08°±0.1° 19.46°±0.1° 20.10°±0.1° 21.82°±0.1°, 22.49°±0.1°, 23.76°±0.1°, 24.26°±0.1°, 27.17°±0.1°, 28.52°±0.1°, and 30.48°±0.1°, when analyzed with X-ray powder diffraction using CuKα radiation. 
     
     
         3 . The crystalline form of  claim 1 , wherein said crystalline form Mod. I has an X-ray powder diffraction diagram substantially the same as the X-ray powder diffraction diagram shown in  FIG. 1  when analyzed with the X-ray powder diffraction using CuKα radiation. 
     
     
         4 . The crystalline form of  claim 1 , wherein said crystalline form Mod. I has absorption peaks at 3415 cm −1 ±2 cm −1 , 3058 cm −1 ±2 cm −1 , 2805 cm −1 ±2 cm −1 , 1668 cm −1 ±2 cm −1 , 1652 cm −1 ±2 cm −1 , and 1227 cm −1 ±2 cm −1 , when analyzed with an infrared spectroscopy using KBr pellet. 
     
     
         5 . The crystalline form of  claim 1 , wherein said crystalline form Mod. I has an infrared spectrum substantially the same as the infrared spectrum shown in  FIG. 7 . 
     
     
         6 . The crystalline form of  claim 1 , wherein said crystalline form Mod. I has a melting point of about 200.6° C. 
     
     
         7 . The crystalline form of  claim 1 , wherein said crystalline form Mod. I has a differential scanning calorimetry thermogram that is substantially the same as that shown in  FIG. 3 . 
     
     
         8 . The crystalline form of  claim 1 , wherein said crystalline form Mod. I has a TGA graph substantially the same as the TGA graph shown in  FIG. 8 . 
     
     
         9 . A micropowder of the crystalline form of  claim 1 , wherein said micropowder has a particle size D90≤15 μm. 
     
     
         10 . The micropowder of  claim 9 , wherein said micropowder has an X-ray powder diffraction diagram with peaks at diffraction angles 2θ of 7.77°±0.1°, 9.86°±0.1°, 12.95°±0.1°, 19.00°±0.1°, 22.40°±0.1°, 26.10°±0.1°, and 28.61°±0.1°, when analyzed with X-ray powder diffraction using CuKα radiation. 
     
     
         11 . The micropowder of  claim 9 , wherein said micropowder has an X-ray powder diffraction diagram substantially the same as the X-ray powder diffraction diagram shown in  FIG. 2  when analyzed with the X-ray powder diffraction using CuKα radiation. 
     
     
         12 . The micropowder of  claim 9 , wherein said micropowder has a transition temperature of about 196.39° C. 
     
     
         13 . The micropowder of  claim 9 , wherein said micropowder has a differential scanning calorimetry thermogram that is substantially the same as that shown in  FIG. 4 . 
     
     
         14 . A process for preparing the crystalline form of  claim 1 , the process comprising:
 a) dissolving the compound 4-(4-chloroanilino)-7-(2-methylaminocarbonyl-4-oxymethyl) pyridylfuro[2,3-d]pyridazine mesylate in methanol to obtain a solution of the compound, and dissolving methanesulfonic acid in said methanol to obtain a methanesulfonic acid solution;   b) adding methanesulfonic acid solution to the solution of the compound;   c) adding isopropanol and vacuum distilling, and collecting a filter cake after filtration; and   d) drying the filter cake.