Cis-diiodo-(trans-L-1,2-cyclohexanediamine) platinum (II) complex and processes for preparing high purity oxaliplatin

Abstract

The present invention is related to pure cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex, and a process of its preparation. The present invention is further related to the preparation of oxaliplatin using said cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex.

1 . Isolated cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex of formula (2).  
     
       
         
         
             
             
         
       
     
   
   
       2 . The cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex of  claim 1 , having a melting point ranging from about 275° C. to about 300° C.  
   
   
       3 . The cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex of  claim 1 , wherein the level of the cis-diiodo-(trans-D-1,2-cyclohexanediamine) Pt (II) complex isomer is less than about 3% area by HPLC.  
   
   
       4 . Cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex, wherein the level of the cis-diiodo-(trans-D-1,2-cyclohexanediamine) Pt (II) complex isomer is less than about 3% area by HPLC.  
   
   
       5 . The cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex of any one of claims  3  and  4 , wherein the level of the cis-diiodo-(trans-D-1,2-cyclohexanediamine) Pt (II) complex isomer is less than about 2% area by HPLC.  
   
   
       6 . The cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex of  claim 5 , wherein the level of the cis-diiodo-(trans-D-1,2-cyclohexanediamine) Pt (II) complex isomer is less than about 1% area by HPLC.  
   
   
       7 . The cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex of  claim 5 , wherein the level of the cis-diiodo-(trans-D-1,2-cyclohexanediamine) Pt (II) complex isomer is less than about 0.1% area by HPLC.  
   
   
       8 . A process for preparing cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex comprising: 
 a) combining trans-L-1,2-cyclohexanediamine of the formula (5)                          with M 2 PtX 4  and KI to obtain a mixture;    b) maintaining the mixture at room temperature; and    c) recovering cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex,    wherein M is Li, Na or K, and    wherein X is I, Cl or Br.    
   
   
       9 . The process of  claim 8 , wherein the trans-L-1,2-cyclohexanediamine in step a) has less than about 3% area by HPLC of the trans-D-1,2-cyclohexanediamine isomer.  
   
   
       10 . The process of  claim 9 , wherein the cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex has less than about 3% area by HPLC of the cis-diiodo-(trans-D-1,2-cyclohexanediamine) Pt (II) complex isomer.  
   
   
       11 . The process of  claim 8 , wherein M is K.  
   
   
       12 . The process of  claim 8 , wherein X is I.  
   
   
       13 . The process of  claim 8 , further comprising purifying the cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex of step c) by suspending it in a solvent selected from the group consisting of an amide, a C 1-4  alkyl ester, a ketone, a halogenated hydrocarbon, water and a mixture thereof.  
   
   
       14 . The process of  claim 13 , wherein the solvent is selected from the group consisting of methylformamide, dimethylformamide, ethyl acetate, methyl acetate, acetone, carbon tetrachloride, chloroform and dichloromethane.  
   
   
       15 . The process of  claim 14 , wherein the organic solvent is dimethylformamide.  
   
   
       16 . The process of  claim 13 , wherein the purifying step is repeated.