Efficient synthesis of 5-heteroatom-containing-pyrazoles

Abstract

An efficient synthesis of sulfonyl pyrazoles of formula I: wherein the ring of the formula (R 5 )—A—(SO m R 4 ), m, R 1 through R 9 are as defined in the specification, comprising reacting a compound of formula II: wherein the ring of the formula (R 5 )—A—(SO m R 4 ), m R 1 through R 9 are as defined above and wherein R 10 is halo, (C 1 -C 6 )alkyl-SO 3 —, (C 6 -C 10 )aryl-SO 3 —, (C 1 -C 6 )alkyl-SO 2 —, or (C 6 -C 10 )aryl-SO 2 —; wherein each of said (C 1 -C 6 )alkyl component of said (C 1 -C 6 )alkyl-SO 3 — and (C 1 -C 6 )alkyl-SO 2 — radicals may optionally be substituted on any carbon atom by one to six fluoro substituents per (C 1 -C 6 )alkyl component; with a compound of formula R 3 —H, wherein R 3 is as defined above, in the presence of a fluoride containing salt and in the presence of a solvent.

We claim:  
     
         1 . A process for preparing a compound of formula I:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof;  
         wherein the ring of the formula (R 5 )—A—(SO m R 4 ) is selected from the group consisting of  
         
           
             
             
                 
                 
             
           
         
         R 1  is a radical selected from the group consisting of H, —NO 2 , —CN, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-SO 2 —, (C 6 -C 10 )aryl-SO 2 —, H—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkyl-O—(C═O)—, (C 1 -C 9 )heteroaryl-(C═O)—, (C 1 -C 9 )heterocyclyl-(C═O)—, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—, [(C 6 -C 10 )aryl]-NH—(C═O)—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—(C═O)—, HO—NH—(C═O)—, and (C 1 -C 6 )alkyl-O—NH—(C═O)—;  
         R 2  is a radical selected from the group consisting of H, —NO 2 , —CN, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 7 )cycloalkyl, (C 6 -C 10 )aryl, (C 1 -C 9 )heteroaryl, (C 1 -C 9 )heterocyclyl, (C 1 -C 6 )alkyl-O—, (C 3 -C 7 )cycloalkyl-O—, (C 6 -C 10 )aryl-O—, (C 1 -C 9 )heteroaryl-O—, (C 1 -C 9 )heterocyclyl-O—, H—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—, (C 3 -C 7 )cycloalkyl-(C═O)—, (C 6 -C 10 )aryl-(C═O)—, (C 1 -C 9 )heteroaryl-(C═O)—, (C 1 -C 9 )heterocyclyl-(C═O)—, (C 1 -C 6 )alkyl-O—(C═O)—, (C 3 -C 7 )cycloalkyl-O—(C═O)—, (C 6 -C 10 )aryl-O—(C═O)—, (C 1 -C 9 )heteroaryl-O—(C═O)—, (C 1 -C 9 )heterocyclyl-O—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 3 -C 7 )cycloalkyl-(C═O)—O—, (C 6 -C 10 )aryl-(C═O)—O—, (C 1 -C 9 )heteroaryl-(C═O)—O—, (C 1 -C 9 )heterocyclyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—NH—, (C 3 -C 7 )cycloalkyl-(C═O)—NH—, (C 6 -C 10 )aryl-(C═O)—NH—, (C 1 -C 9 )heteroaryl-(C═O)—NH—, (C 1 -C 9 )heterocyclyl-(C═O)—NH—, (C 1 -C 6 )alkyl-O—(C═O)—NH—, (C 1 -C 6 )alkyl-NH, [(C 1 -C 6 )alkyl] 2 -N—, (C 3 -C 7 )cycloalkyl-NH—, [(C 3 -C 7 )cycloalkyl] 2 -N—, [(C 6 -C 10 )aryl]-NH—, [(C 6 -C 10 )aryl] 2 -N—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—, [(C 1 -C 9 )heteroaryl]-NH—, [(C 1 -C 9 )heteroaryl] 2 -N—, [(C 1 -C 9 )heterocyclyl]-NH—, [(C 1 -C 9 )heterocyclyl] 2 -N—, H 2 N—(C═O)—, HO—NH—(C═O)—, (C 1 -C 6 )alkyl-O—NH—(C═O)—, [(C 1 -C 6 )alkyl]-NH—(C═O)—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—, [(C 3 -C 7 )cycloalkyl]-NH—(C═O)—, [(C 3 -C 7 )cycloalkyl] 2 -N—(C═O)—, [(C 6 -C 10 )aryl]-NH—(C═O)—, [(C 6 -C 10 )aryl] 2 -N—(C═O)—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—(C═O)—, [(C 1 -C 9 )heteroaryl]-NH—(C═O)—, [(C 1 -C 9 )heteroaryl] 2 -N—(C═O)—, [(C 1 -C 9 )heterocyclyl]-NH—(C═O)—, (C 1 -C 6 )alkyl-S— and (C 1 -C 6 )alkyl optionally substituted by one —OH group or by one to four fluoro substituents;  
         R 3  is a radical selected from the group consisting of  
         
           
             
             
                 
                 
             
           
         
         R 7  is a radical independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, H—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkyl-O—(C═O)—, H 2 N—(C═O)—, [(C 1 -C 6 )alkyl]-NH—(C═O)—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—, [(C 6 -C 10 )aryl]-NH—(C═O)—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—(C═O)—, (C 1 -C 6 )alkyl-O—NH—(C═O)—, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl; or  
         R 8  is a radical selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, H—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkyl-O—(C═O)—, H 2 N—(C═O)—, [(C 1 -C 6 )alkyl]-NH—(C═O)—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—, [(C 6 -C 10 )aryl]-NH—(C═O)—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—(C═O)—, (C 1 -C 6 )alkyl-O—NH—(C═O)—, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl; or  
         R 7  and R 8  may optionally be taken together with the nitrogen to which they are attached to form a 3- to 8-membered heterocyclic ring radical; wherein said 3- to 8-membered heterocyclic ring radical may optionally contain at least one nitrogen or one oxygen heteroatom in addition to said nitrogen to which R 7  and R 8  are attached;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 7  and R 8  may optionally be substituted on any ring carbon atom by one to three substituents per ring independently selected from the group consisting of halo, —OH, (C 1 -C 6 )alkyl-O— and (C 1 -C 6 )alkyl optionally substituted by one to four fluoro moieties;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 7  and R 8  may optionally be substituted on any ring carbon atom by at least one oxo or one (C 1 -C 6 )alkylidene substituent per ring;  
         wherein each of R 7 , or R 8  (C 1 -C 6 )alkyl radicals may optionally be substituted on any carbon atom by one to three substituents per (C 1 -C 6 )alkyl components independently selected from the group consisting of halo, —OH, (C 1 -C 6 )alkyl-O—, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 7 )cycloalkyl, (C 6 -C 10 )aryl, (C 1 -C 9 )heteroaryl, (C 1 -C 10 )heterocyclyl, —CN, H—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, HO—(C═O)—, (C 1 -C 6 )alkyl-O—(C═O)—, (C 1 -C 6 )alkyl-NH—, [(C 1 -C 6 )alkyl] 2 -N—, (C 3 -C 7 )cycloalkyl-NH—, (C 6 -C 10 )aryl-NH—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—, (C 1 -C 9 )heteroaryl-NH—, (C 1 -C 10 )heterocyclyl-NH—, H 2 N—(C═O)—, [(C 1 -C 6 )alkyl]-NH—(C═O)—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—, [(C 6 -C 10 )aryl]-NH—(C═O)—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—(C═O)—, (C 1 -C 6 )alkyl-O—NH—(C═O)—, and (C 1 -C 6 )alkyl-S—;  
         wherein each of R 7 , or R 8  (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl ring radicals may optionally be substituted on any ring carbon atom by one to three substituents per ring independently selected from the group consisting of halo, —OH, (C 1 -C 6 )alkyl-O—, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 7 )cycloalkyl, —CN, H—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, HO—(C═O)—, (C 1 -C 6 )alkyl-O—(C═O)—, (C 1 -C 6 )alkyl-NH—, [(C 1 -C 6 )alkyl] 2 -N—, (C 3 -C 7 )cycloalkyl-NH—, (C 6 -C 10 )aryl-NH—, [(C 1 -C 6 )alkyl]-[(C 6 -C 10 )aryl]-N—, (C 1 -C 9 )heteroaryl-NH—, H 2 N—(C═O)—, [(C 1 -C 6 )alkyl]-NH—(C═O)—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—, [(C 6 -C 10 )aryl]-NH—(C═O)—, [(C 1 -C 6 )alkyl]-[(C 6 -C 10 )aryl]-N—(C═O)—, (C 1 -C 6 )alkyl-O—NH—(C═O)—, (C 1 -C 6 )alkyl-S—, and (C 1 -C 6 )alkyl optionally substituted by one to four fluoro moieties;  
         wherein each of R 7 , or R 8  (C 3 -C 8 )cycloalkyl and (C 1 -C 10 )heterocyclyl radicals or substituents, respectively, may also optionally be substituted on any ring carbon atom by at least one oxo or one (C 1 -C 6 )alkylidene substituent or moiety, respectively, per ring;  
         R 4  is a radical selected from the group consisting of —NH 2 , (C 1 -C 6 )alkyl-NH—, [(C 1 -C 6 )alkyl] 2 -N—, (C 1 -C 6 )alkyl-(C═O)—NH—, (C 6 -C 10 )aryl-(C═O)—NH—, [(C 6 -C 10 )aryl(C 1 -C 6 )alkyl]-(C═O)—NH—, (C 1 -C 6 )alkyl-O—(C═O)—NH—, (C 6 -C 10 )aryl-O—(C═O)—NH—, [(C 1 -C 6 )alkyl]-NH—(C═O)—NH—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—NH—, [(C 6 -C 10 )aryl]-NH—(C═O)—NH—, [(C 1 -C 6 )alkyl]-NH—HC═N—, [C 1 -C 6 )alkyl] 2 N—HC═N—, or [(C 6 -C 10 )aryl]-NH—HC═N—, and and (C 1 -C 6 )alkyl optionally substituted by one to four —OH substituents; and  
         R 5  is a radical selected from the group consisting of H, halo, —OH, (C 1 -C 6 )alkyl-O—, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 7 )cycloalkyl, —CN, H—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, HO—(C═O)—, (C 1 -C 6 )alkyl-O—(C═O)—, (C 1 -C 6 )alkyl-NH—, [(C 1 -C 6 )alkyl] 2 -N—, (C 3 -C 7 )cycloalkyl-NH—, (C 6 -C 10 )aryl-NH—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—, (C 1 -C 9 )heteroaryl-NH—, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, [(C 1 -C 6 )alkyl] 2 -N—(C═O)—, (C 6 -C 10 )aryl-(C═O)—, [(C 1 -C 6 )alkyl]-[((C 6 -C 10 )aryl)-N]—(C═O)—, (C 1 -C 6 )alkyl-O—NH—(C═O)—, (C 1 -C 6 )alkyl-S—, and (C 1 -C 6 )alkyl optionally substituted by one to four fluoro substituents;  
         comprising reacting a compound of the formula II:  
         
           
             
             
                 
                 
             
           
         
         wherein the ring of the formula (R 5 )—A—(SO m R 4 ), m, and R 1  through R 5  are as defined above, and wherein R 10  is a radical selected from the group consisting of halo, (C 1 -C 6 )alkyl-SO 3 —, (C 6 -C 10 )aryl-SO 3 —, (C 1 -C 6 )alkyl-SO 2 —, and (C 6 -C 10 )aryl-SO 2 —, wherein each of said (C 1 -C 6 )alkyl component of said (C 1 -C 6 )alkyl-SO 3 — and (C 1 -C 6 )alkyl-SO 2 — radicals is optionally substituted by one to six fluoro substituents;  
         with a compound of formula R 3 —H, wherein R 3  is as defined above, in the presence of a fluoride containing salt; in the presence of a solvent.  
       
     
     
         2 . The process according to  claim 1  wherein said fluoride containing salt contains a cationic metal selected from the group consisting of lithium, sodium, potassium, cesium, magnesium, calcium, strontium, and barium.  
     
     
         3 . The process according to  claim 2  wherein about 0.05 to about 10 equivalents of said fluoride containing salt relative to the compound of formula I is used.  
     
     
         4 . The process according to  claim 2  wherein said process is performed at a temperature of about 10° C. to about 30° C.  
     
     
         5 . The process according to  claim 2  wherein said solvent is dimethylsulfoxide, dimethylformamide, dimethylacetamide, acetone, or acetonitrile.  
     
     
         6 . The process according to  claim 1  wherein said fluoride containing salt is tetra(C 1 -C 8 )alkylammonium fluoride or (C 1 -C 16 )alkyltri(C 1 -C 2 )alkylammonium fluoride.  
     
     
         7 . The process according to  claim 6  wherein 0.1 to 2 equivalents of said fluoride containing salt relative to the compound of formula I is used.  
     
     
         8 . The process according to  claim 6  wherein said process is performed at a temperature of about 20° C. to about 80° C.  
     
     
         9 . The process according to  claim 6  wherein said solvent is acetonitrile, dichloromethane, chloroform, tetrahydrofuran, or dichloroethane.  
     
     
         10 . The process according to  claim 1  wherein R 10  is chloro.  
     
     
         11 . The process according to  claim 1  wherein R 10  is CF 3 —SO 3 — or CF 3 CF 2 —SO 3 —.  
     
     
         12 . (Cancel) The process according to  claim 1  wherein in said compound of the formula R 3 —H, R 3  is a radical selected from the group consisting of  
       
         
           
           
               
               
           
         
         wherein R 7  is a radical selected from the group consisting of (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 ) heteroaryl and (C 1 -C 10 )heterocyclyl;  
         wherein each R 7  (C 1 -C 6 )alkyl radical may optionally be substituted on any carbon atom by one to three substituents per (C 1 -C 6 )alkyl radical independently selected from the group consisting of (C 3 -C 7 )cycloalkyl, (C 6 -C 10 )aryl, (C 1 -C 9 )heteroaryl, and (C 1 -C 10 )heterocyclyl;  
         wherein each R 7  (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl ring radicals may optionally be substituted on any ring carbon atom by one to three substituents per ring independently selected from the group consisting of halo and (C 1 -C 6 )alkyl optionally substituted by one to four fluoro moieties;  
         wherein each of R 7  (C 3 -C 8 )cycloalkyl and (C 1 -C 10 )heterocyclyl radicals may also optionally be substituted on any ring carbon atom by at least one (C 1 -C 6 )alkylidene substituent per ring.  
       
     
     
         13 . The process according to  claim 1  wherein in said compound of formula R 3 —H, R 3  is  
       
         
           
           
               
               
           
         
         wherein R 7  is a radical selected from the group consisting of (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl; and  
         R 8  is a radical selected from the group consisting of H and (C 1 -C 6 )alkyl;  
         wherein each of R 7  or R 8  (C 1 -C 6 )alkyl radicals may optionally be substituted on any carbon atom by one to three substituents per (C 1 -C 6 )alkyl radicals independently selected from the group consisting of halo and —OH;  
         wherein each of R 7  (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl ring radicals may optionally be substituted on any ring carbon atom by one to three (C 1 -C 6 )alkyl substituents per ring wherein each of said (C 1 -C 6 )alkyl substituents are optionally substituted by one to four fluoro moieties;  
         wherein each of R 7  (C 3 -C 8 )cycloalkyl and (C 1 -C 10 )heterocyclyl radicals may also optionally be substituted on any ring carbon atom by at least one oxo or one (C 1 -C 6 )alkylidene substituent per ring.  
       
     
     
         14 . The process according to  claim 1  wherein in said compound of formula R 3 —H, R 3  is  
       
         
           
           
               
               
           
         
         wherein R 7  and R 8  are taken together with the nitrogen to which they are attached to form a 3- to 8-membered heterocyclic ring radical;  
         wherein said 3- to 8-membered heterocyclic ring radical may optionally contain at least one nitrogen or one oxygen heteroatom in addition to said nitrogen to which R 7  and R 8  are attached;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 7  and R 8  may optionally be substituted on any ring carbon atom by one to three (C 1 -C 6 )alkyl substituents per ring;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 7  and R 8  may optionally be substituted on any ring carbon atom by at least one (C 1 -C 6 )alkylidene substituent per ring.  
       
     
     
         15 . (Cancel) The process according to  claim 1  wherein in said compound of formula R 3 —H, R 3  is  
       
         
           
           
               
               
           
         
         R 6  is H or (C 1 -C 6 )alkyl;  
         R 7  is a radical independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl;  
         R 8  is a radical independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl;  
         wherein each of R 6 , R 7 , or R 8  (C 1 -C 6 )alkyl radicals may optionally be substituted on any carbon atom by one to three substituents per (C 1 -C 6 )alkyl radicals independently selected from the group consisting of halo, —OH, and (C 1 -C 6 )alkyl-O—;  
         wherein each of R 7  or R 8  (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 1 -C 10 )heteroaryl and (C 1 -C 10 )heterocyclyl ring radicals may optionally be substituted on any ring carbon atom by one to three substituents per ring independently selected from the group consisting of halo, —OH and (C 1 -C 6 )alkyl optionally substituted by one to four fluoro moieties;  
         wherein each of R 7  or R 8  (C 3 -C 8 )cycloalkyl and (C 1 -C 10 )heterocyclyl radicals may also optionally be substituted on any ring carbon atom by at least one methylidene substituent per ring.  
       
     
     
         16 . (Cancel) The process according to  claim 1  wherein in said compound of formula R 3 —H, R 3  is  
       
         
           
           
               
               
           
         
         wherein R 6  and R 7  are taken together with the nitrogen or the oxygen to which they are attached to form a 3- to 8-membered heterocyclic ring radical;  
         wherein said 3- to 8-membered heterocyclic ring radical may optionally contain at least one nitrogen or one oxygen heteroatorn in addition to said nitrogen or said oxygen to which R 6  and R 7  are attached;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 6  and R 7  may optionally be substituted on any ring carbon atom by one to three substituents per ring independently selected from the group consisting of halo, —OH, (C 1 -C 6 )alkyl-O—, and (C 1 -C 6 )alkyl optionally substituted by one to four fluoro moieties;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 6  and R 7  may optionally be substituted on any ring carbon atom by at least one oxo or one (C 1 -C 6 )alkylidene substituent per ring.  
       
     
     
         17 . (Cancel) The process according to  claim 1  wherein in said compound of formula R 3 —H, R 3  is  
       
         
           
           
               
               
           
         
         wherein R 7  and R 8  are taken together with the nitrogen to which they are attached to form a 3- to 8-membered heterocyclic ring radical;  
         wherein said 3- to 8-membered heterocyclic ring radical may optionally contain at least one nitrogen or one oxygen heteroatom in addition to said nitrogen to which R 7  and R 8  are attached;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 7  and R 8  may optionally be substituted on any ring carbon atom by one to three (C 1 -C 6 )alkyl substituents per ring;  
         wherein said 3- to 8-membered heterocyclic ring radical made up of R 7  and R 8  may also optionally be substituted on any ring carbon atom by at least one oxo substituent per ring.  
       
     
     
         18 . The compound according to  claim 1  wherein R 2  is a radical selected from the group consisting of H, —NO 2 , —CN, and (C 1 -C 6 )alkyl optionally substituted by one —OH or by one to three fluoro substituents.  
     
     
         19 . The process according to  claim 1  wherein R 2  is —CF 3  or —CHF 2 .  
     
     
         20 . The process according to  claim 1  wherein the ring of the formula (R 5 )—A—(SO m R 4 ) is of the formula  
       
         
           
           
               
               
           
         
       
       wherein X is >CH and m is 2.  
     
     
         21 . The process according to  claim 1  wherein the ring of the formula (R 5 )—A—(SO m R 4 ) is of the formula  
       
         
           
           
               
               
           
         
       
     
     
         22 . The compound according to  claim 1  wherein R 1  is —CN.  
     
     
         23 . The compound according to  claim 1  wherein R 4  is a radical selected from the group consisting of —NH 2  and (C 1 -C 6 )alkyl optionally substituted by one to four —OH substituents.  
     
     
         24 . The compound according to  claim 1  wherein R 5  is a radical selected from the group consisting of H, halo, —OH, and (C 1 -C 6 )alkyl optionally substituted by one to four fluoro substituents.