US2017305905A1PendingUtilityA1

Crystalline form of an anxiolytic compound

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Assignee: BIONOMICS LTDPriority: Mar 15, 2013Filed: Jun 29, 2017Published: Oct 26, 2017
Est. expiryMar 15, 2033(~6.7 yrs left)· nominal 20-yr term from priority
A61P 9/10A61P 9/00A61P 25/20A61P 25/24A61P 25/18A61P 25/16A61P 25/22A61P 29/00A61P 25/28A61P 25/14A61P 25/04A61P 1/04A61P 25/00A61P 21/02A61P 21/00C07D 471/04C07B 2200/13
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Claims

Abstract

The present invention provides a crystalline Form B of compound 1, and pharmaceutically compositions thereof. The present invention also provides methods of treating a disease (e.g., a disease of the central nervous system) using the pharmaceutical compositions.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of preparing a crystalline Form B of compound I of formula: 
       
         
           
           
               
               
           
         
         the method comprising mixing a solution of compound 1 in methanol with an aqueous solution of a base to provide a mixture. 
       
     
     
         2 . The method of  claim 1 , further comprising lowering the temperature of the mixture to provide a solid. 
     
     
         3 . The method of  claim 2 , further comprising isolating the solid from the mixture. 
     
     
         4 . The method of  claim 1  wherein the base is selected from the group consisting of Na 2 CO 3  and NaHCO 3 . 
     
     
         5 . The method of  claim 4  wherein the base is Na 2 CO 3 . 
     
     
         6 . The method of  claim 1  wherein Form B is prepared in greater than 99% purity. 
     
     
         7 . The method of  claim 1  wherein the crystalline Form B is a hydrate. 
     
     
         8 . The method of  claim 1  wherein the crystalline Form B is a hemihydrate. 
     
     
         9 . The method of  claim 1  wherein the crystalline Form B is a non-stoichiometric hydrate. 
     
     
         10 . The method of  claim 1  wherein the crystalline Form B is substantially free of amorphous compound 1. 
     
     
         11 . The method of  claim 1  wherein the crystalline Form B is characterized by having four or more peaks in its XRPD pattern selected from those in the following table: 
       
         
           
                 
               
                     
                 
                   Angle 
                 
                   2-Theta ° 
                 
                     
                 
                   13.94 
                 
                   14.52 
                 
                   16.27 
                 
                   16.60 
                 
                   17.62 
                 
                   18.76 
                 
                   19.02 
                 
                   19.29 
                 
                   19.64 
                 
                   22.32 
                 
                   22.77 
                 
                   23.02 
                 
                    23.16. 
                 
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The method of  claim 1  wherein the crystalline Form B is characterized by a Raman spectrum with characteristic peaks selected from those in the following table: 
       
         
           
                 
               
                     
                 
                   Wavenumber 
                 
                   (cm −1 ) 
                 
                     
                 
                     
                 
                 
               
                   3322 
                 
                   3070 
                 
                   3007 
                 
                   2993 
                 
                   2963 
                 
                   2931 
                 
                   2910 
                 
                   2871 
                 
                   2842 
                 
                   1636 
                 
                   1611 
                 
                   1604 
                 
                   1508 
                 
                   1497 
                 
                   1478 
                 
                   1459 
                 
                   1446 
                 
                   1425 
                 
                   1393 
                 
                   1355 
                 
                   1344 
                 
                   1319 
                 
                   1304 
                 
                   1285 
                 
                   1271 
                 
                   1243 
                 
                   1225 
                 
                   1208 
                 
                   1150 
                 
                   1136 
                 
                   1112 
                 
                   1095 
                 
                   1064 
                 
                   1039 
                 
                   1025 
                 
                   1010 
                 
                   996 
                 
                   957 
                 
                   943 
                 
                   849 
                 
                   819 
                 
                   810 
                 
                   789 
                 
                   741 
                 
                   713 
                 
                   681 
                 
                   603 
                 
                   585 
                 
                   555 
                 
                   501 
                 
                   484 
                 
                   446 
                 
                   419 
                 
                   372 
                 
                   349 
                 
                   316 
                 
                   261 
                 
                   234 
                 
                   185 
                 
                   141. 
                 
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The method of  claim 1  wherein the crystalline Form B is characterized by a DSC thermogram with an endotherm having a peak temperature (T max ) of about 176° C. 
     
     
         14 . The method of  claim 1  wherein the crystalline Form B is characterized by a DSC thermogram with a ΔH of about 105 J/g. 
     
     
         15 . The method of  claim 1  wherein the crystalline Form B is characterized by a glass transition (T g ) of about 71° C. after quench cooling. 
     
     
         16 . The method of  claim 1  wherein the crystalline Form B is characterized by a ΔC p  of about 0.48 J/(g° C.) after quench cooling.

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