Processes For Preparing A Polymeric Compound

Abstract

The present invention provides methods for preparing a polymeric compound of Formula I: or pharmaceutically acceptable salt thereof. The present invention also provides useful intermediates for preparing the compound of Formula I or pharmaceutically acceptable salt thereof.

What is claimed is: 
     
         1 . A method for preparing a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, comprising:
 a) removing the Cbz groups from a compound of Formula II: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, under a hydrogenation/hydrogenolysis condition to form the compound of Formula I, or pharmaceutically acceptable salt thereof; and
 b) optionally isolating the compound of Formula I, or pharmaceutically acceptable salt thereof. 
 
     
     
         2 . The method of  claim 1  further comprising:
 c) removing the Boc group from a compound of Formula III: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula II, or pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 2  further comprising:
 d) reacting a compound of Formula IV: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula V: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula III, or pharmaceutically acceptable salt thereof. 
     
     
         4 . The method of  claim 3  further comprising:
 e) reacting a compound of Formula IV: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with ammonia or an ammonia producing reagent, in the presence of an activating reagent and an organic base to form a compound of Formula VI: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof; and
 f) removing the Boc group from the compound of Formula VI, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula V, or pharmaceutically acceptable salt thereof. 
 
     
     
         5 . The method of  claim 4  further comprising:
 g) hydrolyzing a compound of Formula VII: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a base to form the compound of Formula IV. 
     
     
         6 . The method of  claim 5  further comprising:
 h) reacting a compound of Formula VIII: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula IX: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula VII, or pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 6  further comprising:
 i) hydrolyzing a compound of Formula X: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a base to form the compound of Formula IX; and
 j) removing the Boc group from a compound of Formula X, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula VIII, or pharmaceutically acceptable salt thereof. 
 
     
     
         8 . The method of  claim 7  further comprising:
 k) reacting a compound of Formula XI: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula XII: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula X, or pharmaceutically acceptable salt thereof. 
     
     
         9 . A method for preparing a compound of formula I: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, comprising:
 a1) removing the Cbz groups from a compound of Formula II-1: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, under a hydrogenation/hydrogenolysis condition to form the compound of Formula I, or pharmaceutically acceptable salt thereof; and
 b1) optionally isolating the compound of Formula I, or pharmaceutically acceptable salt thereof. 
 
     
     
         10 . The method of  claim 9  further comprising:
 c1) reacting a compound of Formula III-1: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula IV-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula II-1, or pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 10  further comprising:
 d1) reacting a compound of Formula VI-1: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula VII-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form a compound of Formula V-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof; and
 e1) removing the Boc group from the compound of Formula V-1, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula III-1, or pharmaceutically acceptable salt thereof. 
 
     
     
         12 . The method of  claim 10  further comprising:
 f1) reacting a compound of Formula VIII-1: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula VII-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form a compound of Formula IX-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof; and
 g1) removing the Boc group from the compound of Formula IX-1, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula VI-1, or pharmaceutically acceptable salt thereof. 
 
     
     
         13 . The method of  claim 12  further comprising:
 h1) reacting a compound of Formula XI-1: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula XII-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, optionally in the presence of an organic base to form a compound of Formula X-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof; and
 i1) removing the Boc group from the compound of Formula X-1 or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula VIII-1, or pharmaceutically acceptable salt thereof. 
 
     
     
         14 . The method of  claim 12  further comprising:
 j1) reacting a compound of Formula XI-1: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula XIII-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, to form the compound of Formula VII-1, or pharmaceutically acceptable salt thereof. 
     
     
         15 . The method of  claim 14  further comprising:
 k1) reacting a compound of Formula XIV-1: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula XIII-1: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, to form the compound of Formula IV-1, or pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 9  further comprising:
 c2) reacting a compound of Formula III-2: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula IV-2: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula II-1, or pharmaceutically acceptable salt thereof. 
     
     
         17 . The method of  claim 16  further comprising:
 d2) removing the Boc group from a compound of Formula V-2: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, under an acidic condition to form the compound of Formula III-2, or pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 17 , further comprising:
 e2) reacting a compound of Formula VI-2:   
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula VII-2: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula V-2, or pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 18  further comprising:
 f2) removing the Boc group from a compound of Formula VIII-2: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, under an acidic condition to form the compound of Formula VI-2, or pharmaceutically acceptable salt thereof. 
     
     
         20 . The method of  claim 19  further comprising:
 g2) reacting a compound of Formula IX-2: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula VII-2: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula VIII-2, or pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 20  further comprising:
 h2) removing the Boc group from a compound of Formula X-2: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, under an acidic condition to form the compound of Formula IX-2, or pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 21  further comprising:
 i2) reacting a compound of Formula VII-2: 
 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, with a compound of Formula XI-2: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula X-2, or pharmaceutically acceptable salt thereof. 
     
     
         23 . A compound chosen from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof.