Crystalline solvates of 6-(piperidin-4-yloxy)-2h-isoquinolin-1-one hydrochloride

Abstract

The present invention relates to crystalline solvates of 6-(Piperidin-4-yloxy)-2H-isoquinolin-1-one hydrochloride, processes for their preparation and the use thereof.

1 . A crystalline hydrate of 6-(Piperidin-4-yloxy)-2H-isoquinolin-1-one hydrochloride having the formula 
       
         
           
           
               
               
           
         
       
     
     
         2 .- 22 . (canceled) 
     
     
         23 . A process for preparing a crystalline hydrate of 6-(Piperidin-4-yloxy)-2H-isoquinolin-1-one hydrochloride having the formula 
       
         
           
           
               
               
           
         
       
       comprising the steps of:
 (a) dissolving 6-(Piperidin-4-yloxy)-2H-isoquinolin-1-one hydrochloride in a suitable solvent containing water or in water alone at a temperature suitable to obtain a solution, 
 (b) concentrating the solution by evaporating the solvent partially sufficient to allow formation of hydrate crystals or cooling down the solution and maintaining it for a time period sufficient to allow formation of hydrate crystals and 
 (c) isolating the hydrate. 
 
     
     
         24 . The process according to  claim 23  wherein the crystalline hydrate contains 1.85 to 2.2 molecules water per molecule (I). 
     
     
         25 . The process according to  claim 23  wherein the crystalline hydrate contains 2.0 molecules water per molecule (I). 
     
     
         26 . The process according to  claim 23 , wherein the crystalline hydrate contains 10.5-12.5% (w/w) water. 
     
     
         27 . The process according to  claim 23  wherein the suitable solvent containing water for dissolving and crystallizing 6-(Piperidin-4-yloxy)-2H-isoquinolin-1-one is selected from the group consisting of acetone, methyl ethyl ketone, methanol, ethanol, isopropanol, tetrahydrofuran and acetonitrile. 
     
     
         28 . The process according to  claim 23  wherein the suitable solvent is water. 
     
     
         29 . The process according to  claim 27  wherein said suitable solvent containing water is acetone. 
     
     
         30 . The process according to  claim 1  wherein the suitable solvent containing water is in a ratio of about 1-4 parts solvent to about 1-4 parts water by volume. 
     
     
         31 . The process according to  claim 30  wherein the suitable solvent containing water is in a ratio of 4 parts solvent to 1 part water by volume. 
     
     
         32 . The process according to  claim 29  wherein the acetone/water ratio is 3:1 by volume. 
     
     
         33 . The process according to  claim 29  wherein the acetone/water ratio is 3:2 by volume. 
     
     
         34 . The process according to  claim 23  wherein the temperature suitable to obtain a solution is about 55° C. to about 70° C. 
     
     
         35 . The process according to  claim 34  wherein the temperature suitable to obtain a solution is about 65° C. 
     
     
         36 . The process according to  claim 23  wherein step b further comprises the step of seeding the solution with dihydrate crystals.