Polymorph of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt

Abstract

A polymorphic form of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt (the “Polymorph”) characterized in that it provides: (i) an infra red spectrum containing peaks at 1763, 912, 856 and 709 cm −1 ; and/or (ii) a Raman spectrum containing peaks at 1762, 1284, 912 and 888 cm −1 ; and/or (iii) a solid-state 13 C nuclear magnetic resonance spectrum containing peaks at 111.0, 113.6, 119.8, 129.1, 130.9, 131.8, 134.7, 138.7, 146.5, 152.7, 157.5, 169.5, 171.0, 178.7 ppm; and/or (iv) an X-ray powder diffraction (XRPD) pattern which gives calculated lattice spacings at 5.87, 5.30, 4.69, 4.09, 3.88, 3.61, 3.53, and 3.46 Angstroms; a process for preparing such a compound, a pharmaceutical composition containing such a compound and the use of such a compound in medicine.

1 - 14 . (canceled)  
     
     
         15 . A process for converting a compound, 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt, into a polymorph of said compound, wherein said process comprises the steps of: 
 (a) mixing said compound in acetone and heating the resulting mixture to reflux to form a solution;    (b) cooling;    (c) seeding the solution with the polymorph of said compound;    (d) recovering the polymorph of said compound, wherein said compound provides at least one of:    (i) an infra red spectrum containing peaks at 1763, 912, 856 and 709 cm −1 ;    (ii) a Raman spectrum containing peaks at 1762, 1284, 912 and 888 cm −1 ;    (iii) a solid-state  13 C nuclear magnetic resonance spectrum containing peaks at 111.0, 113.6, 119.8, 129.1, 130.9, 131.8, 134.7, 138.7, 146.5, 152.7, 157.5, 169.5. 171.0, 178.7 ppm; and    (iv) an X-ray powder diffraction pattern having calculated lattice spacings at 5.87, 5.30, 4.69, 4.09, 3.88, 3.61, 3.53 and 3.46 Angstroms.    
     
     
         16 . A process according to  claim 15 , further comprising filtering the solution formed in step (a).  
     
     
         17 . A process according to  claim 16 , further comprising heating or concentrating said filtered solution.  
     
     
         18 . A process according to  claim 15 , comprising cooling at a rate of 1° C./min.  
     
     
         19 . A process according to  claim 16 , comprising cooling at a rate of 1° C./min.  
     
     
         20 . A process according to  claim 17 , comprising cooling at a rate of 1° C./min.  
     
     
         21 . A process according to  claim 15 , comprising seeding at a temperature of 50° C.  
     
     
         22 . A process according to  claim 16 , comprising seeding at a temperature of 50° C.  
     
     
         23 . A process according to  claim 17 , comprising seeding at a temperature of 50° C.  
     
     
         24 . A process according to  claim 18 , comprising seeding at a temperature of 50° C.  
     
     
         25 . A process for converting a compound, 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt, into a polymorph of said compound, wherein said process comprises the steps of: 
 (a) forming a solution of said compound in ethanol and stirring said solution at a temperature of 62° C. for 30 minutes;    (b) adjusting the temperature of said solution to a temperature of 60° C.;    (c) cooling;    (d) seeding with the polymorph of said compound;    (e) recovering the polymorph of said compound, wherein said compound provides at least one of:    (i) an infra red spectrum containing peaks at 1763, 912, 856 and 709 cm −1 ;    (ii) a Raman spectrum containing peaks at 1762, 1284, 912 and 888 cm −1 ;    (iii) a solid-state  13 C nuclear magnetic resonance spectrum containing peaks at 111.0, 113.6, 119.8, 129.1, 130.9, 131.8, 134.7, 138.7, 146.5, 152.7, 157.5, 169.5. 171.0, 178.7 ppm; and    (iv) an X-ray powder diffraction pattern having calculated lattice spacings at 5.87, 5.30, 4.69, 4.09, 3.88, 3.61, 3.53 and 3.46 Angstroms.    
     
     
         26 . A process according to  claim 25  further comprising filtering the solution formed in step (a).  
     
     
         27 . A process according to  claim 26 , further comprising filtering said solution into a vessel preheated to 55° C.  
     
     
         28 . A process according to  claim 25 , comprising cooling at a rate of 1° C./min.  
     
     
         29 . A process according to  claim 26 , comprising cooling at a rate of 1° C./min.  
     
     
         30 . A process according to  claim 27 , comprising cooling at a rate of 1° C./min.  
     
     
         31 . A process according to  claim 25 , comprising seeding at a temperature of 52° C.  
     
     
         32 . A process according to  claim 26 , comprising seeding at a temperature of 52° C.  
     
     
         33 . A process according to  claim 27 , comprising seeding at a temperature of 52° C.  
     
     
         34 . A process according to  claim 28 , comprising seeding at a temperature of 52° C.