Hydrate of n-methyl-n-(3-phenyl)acetamide and processes and methods related thereto

Abstract

A novel hydrate form of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)acetamide (“Compound No. 1”) and processes related to the use thereof in the synthesis of a polymorphic form of Compound No. 1.

1 . A hydrate of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)-acetamide. 
     
     
         2 . The hydrate according to  claim 1  wherein said hydrate has a broad endotherm at about 40° C.-90° C. and an endotherm peak at about 193° C. as measured by Differential Scanning Calorimeter at a scan rate of 10° C. per minute. 
     
     
         3 . The hydrate of  claim 2  wherein the broad endotherm has a maximum peak at about 80° C. 
     
     
         4 . A hydrate of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)-acetamide having an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ×+/−0.2°θ at 6.1 and 17.2. 
     
     
         5 . The hydrate of  claim 4  further comprising an X-ray powder diffraction pattern peak at 26.3. 
     
     
         6 . The hydrate of  claim 5  further comprising X-ray powder diffraction pattern peaks at 20.7 and 25. 
     
     
         7 . The hydrate of  claim 4 , wherein said hydrate comprises X-ray diffraction peaks at diffraction angles (20), X-ray diffraction d-spacings and intensities of about: 
       
         
           
                 
                 
                 
               
                     
                 
                   2-θ° 
                   d value 
                   Intensity % 
                 
                     
                 
                     
                 
                 
                 
                 
               
                   6.099 
                   14.4802 
                   100.0 
                 
                   17.151 
                   5.1657 
                   66.1 
                 
                   20.749 
                   4.2773 
                   29.3 
                 
                   24.999 
                   3.5590 
                   23.4 
                 
                   26.253 
                   3.3918 
                   36.4 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         8 - 17 . (canceled) 
     
     
         18 . A hydrate of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)-acetamide prepared by combining an acetic acid solution comprising N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)-acetamide and acetic acid with an aqueous solution comprising water and one or more optional cosolvents. 
     
     
         19 . The hydrate of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)-acetamide prepared according to the process of  claim 18  wherein the acetic acid solution is heated to a maximum temperature of between 40° C. and reflux prior to combining the acetic acid solution with the aqueous solution. 
     
     
         20 . The hydrate of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)-acetamide prepared according to the process of  claim 18 , wherein said N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)-acetamide is synthesized in acetic acid to provide the acetic acid solution.