Process for the preparation of aniline-derived thyroid receptor ligands

Abstract

Provided are processes for the synthesis of aniline derivatives, specifically certain aniline derivatives which have activity as thyroid receptor ligands.

1 - 27 . (cancel)  
     
     
         28 . A compound of formula IIA  
       
         
           
           
               
               
           
         
       
       wherein 
 R 2  and R 3  independently represent bromo, chloro, or methyl;  
 R 4  represents hydrogen or methyl; and  
 L represents mesyl, tosyl, p-nitrobenzenesulfonyl, trihaloacetate, or triflate.  
 
     
     
         29 . The compound according to  claim 28 , selected from the group consisting of trifluoro-methanesulfonic acid 2,6-dibromo-4-nitrophenyl ester, trifluoro-methanesulfonic acid 2,6-dibromo-3-methyl-4-nitrophenyl ester, trifluoro-methanesulfonic acid 2,6-dichloro-4-nitrophenyl ester, and trifluoro-methanesulfonic acid 2,6-dichloro-3-methyl-4-nitrophenyl ester.  
     
     
         30 . The compound according to  claim 28 , trifluoro-methanesulfonic acid 2,6-dibromo-4-nitrophenyl ester.  
     
     
         31 . A compound of formula IIIA  
       
         
           
           
               
               
           
         
       
       wherein 
 R 2  and R 3  independently represent bromo, chloro, or methyl; and  
 R 4  represents hydrogen or methyl.  
 
     
     
         32 . The compound according to  claim 31 , selected from the group consisting of l,3-dibromo-2-iodo-5-nitrobenzene, 1,3-dibromo-2-iodo-4-methyl-5-nitrobenzene, 1,3-dichloro-2-iodo-5-nitrobenzene, and 1,3-dichloro-2-iodo-4-methyl-5-nitrobenzene.  
     
     
         33 . The compound according to  claim 31 , 1,3-dibromo-2-iodo-5-nitrobenzene.  
     
     
         34 . A process for the synthesis of a phenol of formula A  
       
         
           
           
               
               
           
         
       
       wherein 
 G is a protecting group; and  
 R 1  represents halogen, trifluoromethyl, an alkyl group of 1 to 6 carbons, or a cycloalkyl group of 3 to 7 carbons;  
 comprising the steps of:  
 a) reacting an aldehyde of formula A-I with MHSO 3  to form a sulfonate of formula A-II  
                     
 wherein M is a metal; and  
 b) reacting the sulfonate-of formula A-II with an oxidant, in the presence of a proton source, to form the phenol of formula A[, above].  
 
     
     
         35 . A compound selected from the group consisting of compounds of formula A-I and formula A-II,  
       
         
           
           
               
               
           
         
       
       wherein 
 G represents a protecting group;  
 M represents a metal; and  
 R 1  represents halogen, trifluoromethyl, an alkyl group of 1 to 6 carbons, or a cycloalkyl group of 3 to 7 carbons.  
 
     
     
         36 . The compound according to  claim 35 , 3-isopropyl-4-methoxybenzaldehyde.  
     
     
         37 . The compound according to  claim 35 , hydroxy-(3-isopropyl-4-methoxyphenyl)methanesulfonic acid, sodium salt.  
     
     
         38 . A compound of formula A  
       
         
           
           
               
               
           
         
       
       wherein 
 G represents a protecting group; and  
 R 1  represents halogen, trifluoromethyl, an alkyl group of 1 to 6 carbons, or a cycloalkyl group of 3 to 7 carbons;  
 with the proviso that, when G is a methyl group, R 1  is not a member of the group consisting of bromo, chloro, iodo, t-butyl, cyclohexyl, cyclopentyl, and isopropyl.