Quinazoline ditosylate salt compounds

Abstract

Ditosylate salts of 4-quinazolineamines are described as well as methods of using the same in the treatment of disorders characterized by aberrant erbB family PTK activity.

1 . (canceled)  
     
     
         2 . A process for preparing a compound of formula (C),  
       
         
           
           
               
               
           
         
         comprising the steps of:  
         reacting a compound of formula (A)  
         
           
             
             
                 
                 
             
           
         
         with a compound of formula (B)  
         
           
             
             
                 
                 
             
           
         
         to form the compound of formula (C),  
         wherein U is an organic group;  
         and the compound of formula (A) is generated in situ; and  
         L is iodine or bromine;  
         R is —C(Q)(T)W where Q and T are independently selected from —OCH 3  or —OCH 2 CH 3  and W is hydrogen; and  
         Z is B(OH) 2 ;  
         or the compound of formula (A) is generated in situ; and  
         L is iodine or bromine;  
         R is —C(O)H; and  
         Z is B(OH) 2 ;  
         or the compound of formula (B) is generated in situ, and  
         L is B(OH) 2 ;  
         R is —C(O)H; and  
         Z is bromine.  
       
     
     
         3 . A process as claimed in  claim 2  wherein U represents a phenyl or 1H-indazolyl group substituted by an R 2  group and optionally substituted by at least one independently selected R 4  group; wherein R 2  is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl; and each R 4  is selected from the group hydroxy, halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C,-4 alkoxy, amino, C 1-4  alkylamino, di[C 1-4  alkyl]amino, C 1-4  alkylthio, C 1-4  alkylsulphinyl, C 1-4  alkylsulphonyl, C 1-4  alkylcarbonyl, carboxy, carbamoyl, C 1-4  alkoxycarbonyl, C 1-4  alkanoylamino, N-(C 1-4  alkyl)carbamoyl, N,N-di(C 1-4  alkyl)carbamoyl, cyano, nitro and trifluoromethyl.  
     
     
         4 . A process as claimed in  claim 3  wherein R 2  represents 3-fluorobenzyloxy.  
     
     
         5 . A process as claimed in  claim 3  wherein the phenyl or 1H-indazolyl group of U is substituted by an R 4  group, wherein R 4  represents halo.  
     
     
         6 . A process as claimed in  claim 1  wherein U is selected from the group consisting of 3-fluorobenzyloxy-3-chlorophenyl, benzyloxy-3-chlorophenyl, benzyloxy-3-trifluoromethylphenyl, (benzyloxy)-3-fluorophenyl, (3-fluorobenzyloxy)-3-fluorophenyl or (3-fluorobenzyl)indazolyl.  
     
     
         7 . A process as claimed in any  claim 1  wherein the compound of formula (A) is generated in situ; L is iodine or bromine; and Z is B(OH) 2 .  
     
     
         8 . A process as claimed in any  claim 1  wherein the compound of formula (A) is generated in situ; L is iodine; and Z is B(OH) 2 .  
     
     
         9 . A process as claimed in  claim 1  wherein the compound of formula (C) is 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde.