Formulations of (s)-3-(1-(9h-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2h)-one

Abstract

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

1 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         Formula (I), wherein the compound is polymorph Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, or an amorphous form of a compound of Formula (I), or a salt, solvate, or hydrate thereof; or a mixture of two or more thereof. 
       
     
     
         2 . A mixture of two or more compounds of Formula (I): 
       
         
           
           
               
               
           
         
         wherein the compounds of Formula (I) are selected from: 
         i) polymorph Form C, or a salt, solvate, or hydrate thereof; and 
         ii) at least one non-Form C polymorph selected from Form A, Form B, Form D, Form E, Form F, Form G, Form H, Form I, Form J, or an amorphous form of a compound of Formula (I), or a salt, solvate, or hydrate thereof. 
       
     
     
         3 . A mixture of two or more compounds of Formula (I): 
       
         
           
           
               
               
           
         
         wherein the compounds of Formula (I) are selected from: 
         i) polymorph Form A, or a salt, solvate, or hydrate thereof; and 
         ii) at least one non-Form A polymorph selected from Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, or an amorphous form of a compound of Formula (I), or a salt, solvate, or hydrate thereof. 
       
     
     
         4 . A mixture according to  claim 2 , wherein the mixture is at least 50% by weight polymorph Form C, or a salt, solvate, or hydrate thereof. 
     
     
         5 . The compound of  claim 1 , which is Polymorph Form C of a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
     
     
         6 . The polymorph according to  claim 5 , wherein the polymorph has the following characteristic X-ray Powder Diffraction (XRPD) peaks: 20=10.4° (±0.2°), 13.3° (±0.2°), and 24.3° (±0.2°). 
     
     
         7 . The polymorph according to  claim 6 , further comprising at least one characteristic XRPD peak selected from 20=6.6° (±0.2°) and 12.5° (±0.2°). 
     
     
         8 . The polymorph according to  claim 5 , wherein the polymorph has the following characteristic XRPD peaks: 20=6.6° (±0.2°), 10.4° (±0.2°), 12.5° (±0.2°), 13.3° (±0.2°), and 24.3° (±0.2°), in combination with at least one XRPD peak selected from 20=8.8° (±0.2°), 9.9° (±0.2°), 13.4° (±0.2°), 15.50 (±0.2°), 16.9° (±0.2°), 19.8° (±0.2°), 21.3° (±0.2°), 23.6° (±0.2°), 25.3° (±0.2°), and 27.9° (±0.2°). 
     
     
         9 . The polymorph according to  claim 5 , wherein the polymorph has substantially all peaks in its XRPD pattern as shown in  FIG.  3   . 
     
     
         10 . The compound of  claim 1 , which is Polymorph Form B of a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
     
     
         11 . The polymorph according to  claim 10 , wherein the polymorph has the following characteristic XRPD peaks: 20=7.9° (±0.2°), 13.4° (±0.2°), and 23.4° (±0.2°). 
     
     
         12 . The polymorph according to  claim 11 , further comprising at least one characteristic XRPD peak selected from 20=14.0° (±0.2°) and 15.0° (±0.2°). 
     
     
         13 . The polymorph according to  claim 10 , wherein the polymorph has the following characteristic XRPD peaks: 20=7.9° (±0.2°), 13.4° (±0.2°), 14.0° (±0.2°), 15.0° (±0.2°), and 23.4° (±0.2°), in combination with at least one XRPD peak selected from 20=9.5° (±0.2°), 12.7° (±0.2°), 13.6° (±0.2°), 14.2° (±0.2°), 15.7° (±0.2°), 19.0° (±0.2°), 22.3° (±0.2°), 24.2° (±0.2°), 24.8° (±0.2°), and 26.9° (±0.2°). 
     
     
         14 . The polymorph according to  claim 10 , wherein the polymorph has substantially all peaks in its XRPD pattern as shown in  FIG.  2   . 
     
     
         15 . The compound of  claim 1 , which is Polymorph Form D of a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
     
     
         16 . The polymorph according to  claim 15 , wherein the polymorph has the following characteristic XRPD peaks: 20=11.4° (±0.2°), 17.4° (±0.2°), and 22.9° (±0.2°). 
     
     
         17 . The polymorph according to  claim 16 , further comprising at least one characteristic XRPD peak selected from 20=9.2° (±0.2°) and 18.3° (±0.2°). 
     
     
         18 . The polymorph according to  claim 15 , wherein the polymorph has the following characteristic XRPD peaks: 20=9.2° (±0.2°), 11.4° (±0.2°), 17.4° (±0.2°), 18.3° (±0.2°), and 22.9° (±0.2°), in combination with at least one XRPD peak selected from 20=9.8° (±0.20), 12.2° (±0.2°), 15.8° (±0.2°), 16.2° (±0.2°), 16.8° (±0.2°), 18.9° (±0.2°), 19.9° (±0.2°), 20.0° (±0.2°), 24.9° (±0.2°), and 29.3° (±0.2°). 
     
     
         19 . The polymorph according to  claim 15 , wherein the polymorph has substantially all peaks in its XRPD pattern as shown in  FIG.  4   . 
     
     
         20 . The compound of  claim 1 , which is Polymorph Form E of a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
     
     
         21 - 68 . (canceled)