2-Iminopyrrolidine derivatives

Abstract

A 2-iminopyrrolidine derivative represented by the formula: {wherein ring B represents a benzene ring, pyridine ring, etc.; R 101 -R 103 represent hydrogen, halogen, C 1-6 alkyl, etc.; R 5 represents hydrogen, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, etc.; R 6 represents hydrogen, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, etc.; Y 1 represents a single bond, —CH 2 —, etc.; Y 2 represents a single bond, —CO—, etc.; and Ar represents hydrogen, a group represented by the formula: [wherein R 10 -R 14 represent hydrogen, C 1-6 alkyl, hydroxyl, C 1-6 alkoxy, etc.; and R 11 and R 12 or R 12 and R 13 may bond together to form a 5- to 8-membered heterocyclic ring], etc.}, or a salt thereof.

1 - 32 . (canceled)  
   
   
       33 . A process for preparing a compound represented by the formula:  
     
       
         
         
             
             
         
       
     
     which comprises reacting a compound represented by the formula:  
     
       
         
         
             
             
         
       
     
     with a compound represented by the formula:  
     
       
         
         
             
             
         
       
     
     wherein: 
 X 1  represents nitrogen or CR 1 , X 2  represents nitrogen or CR 2 , X 3  represents nitrogen or CR 3 , X 4  represents nitrogen or CR 4 ;  
 R 1  and R 4  are the same or different and each represents hydrogen, halogen, optionally substituted alkyl or optionally substituted alkoxy, R 2  and R 3  are the same or different and each represents hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkoxy, optionally substituted amino, optionally substituted carboxyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted sulfonylamino or optionally substituted alkanoylamino;  
 R 5  represents hydrogen or optionally substituted alkyl;  
 X represents chlorine or bromine;  
 R 11  and R 13  are the same or different and each represents hydrogen, cyano, halogen, nitro or a group selected from Substituent Group B;  
 R 15  represents hydrogen or a group selected from Substituent Group H; R 11  and R 15  may bond together to form a 5- to 8-membered heterocycle optionally having 1 to 4 heteroatoms selected from N, S and O and also optionally substituted with at least one group selected from Substituent Group F;  
 Substituent Group B consists of C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, acyl, carboxyl, carbamoyl, C 1-6  alkoxycarbonyl, C 1-6  alkylaminocarbonyl, hydroxyl, C 1-6  alkoxy, C 3-8  cycloalkyloxy, amino, C 1-6  aminoalkyl, C 1-6  alkylamino, C 3-8  cycloalkylamino, acylamino, ureido, sulfonylamino, sulfonyl, sulfamoyl, C 3-8  cycloalkyl, a 5- to 14-membered non-aromatic heterocyclic group, a C 6-14  aromatic hydrocarbon ring group and a 5- to 14-membered aromatic heterocyclic group, each of the foregoing members being optionally substituted with at least one group selected from Substituent Group B′;  
 Substituent Group B′ consists of C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, oxo, cyano, C 1-6  cyanoacyl, C 2-7  acyl, C 1-6  alkanoyl, benzoyl, aralkanoyl, C 1-6  alkoxyalkylcarbonyl, C 1-6  hydroxyalkylcarbonyl, carboxyl, C 1-6  carboxyalkyl, C 1-6  carboxyalkyloxy, carbamoyl, carbamoylalkyloxy, C 1-6  alkoxycarbonyl, C 1-10  alkoxycarbonyl-C 1-6  alkyl, C 1-10  alkoxycarbonyl-C 1-6  alkyloxy, C 1-6  monoalkylaminocarbonyl, C 2-6  dialkylaminocarbonyl, hydroxyl, C 1-6  alkoxy, C 1-10  alkoxyalkyl, C 1-10  aralkyloxyalkyl, C 1-6  hydroxyalkyl, C 1-8  cycloalkyloxy, amino, C 1-6  alkylamino, C 3-8  cycloalkylamino, acylamino, ureido, ureylene, C 1-6  alkylsulfonylamino, phenylsulfonylamino, C 1-6  alkylsulfonyl, phenylsulfonyl, C 1-6  monoalkylaminosulfonyl, C 2-6  dialkylaminosulfonyl, sulfamoyl, halogen, C 3-8  cycloalkyl, a 5- to 14-membered non-aromatic heterocyclic group, a C 6-14  aromatic hydrocarbon ring group, a 5- to 14-membered aromatic heterocyclic group, a heterocyclic aminocarbonyl group, a heterocyclic aminosulfonyl group and isoxazolinyl, wherein the 5- to 14-membered non-aromatic heterocyclic group, the C 6-14  aromatic hydrocarbon ring group, the 5- to 14-membered aromatic heterocyclic group and isoxazolinyl may be independently substituted with at least one group selected from the group consisting of C 1-6  alkyl, oxo, cyano, acyl, carboxyl, carbamoyl, C 1-6  alkoxycarbonyl, C 1-6  alkylaminocarbonyl, hydroxyl, C 1-6  alkoxy, C 3-8  cycloalkyloxy, nitro, amino, C 1-6  aminoalkyl, C 1-6  alkylamino, C 1-6  dialkylamino, C 3-8  cycloalkylamino, acylamino, ureido, ureylene, alkylsulfonylamino, alkylsulfonyl, sulfamoyl, halogen and C 3-8  cycloalkyl;  
 Substituent Group F consists of hydrogen, cyano, halogen, oxo and C 1-6  alkyl, alkenyl, alkynyl, acyl, C 1-6  alkanoyl, carboxyl, carbamoyl, C 1-6  alkoxycarbonyl, C 1-6  alkylaminocarbonyl, hydroxyl, C 1-6  alkoxy, C 3-8  cycloalkyloxy, amino, imino, C 1-6  aminoalkyl, C 1-6  alkylamino, C 3-8  cycloalkylamino, acylamino, ureido, sulfonylamino, sulfonyl, sulfamoyl, C 3-8  cycloalkyl, a 5- to 14-membered non-aromatic heterocyclic group, a C 6-14  aromatic hydrocarbon ring group and a 5- to 14-membered aromatic heterocyclic group, each of the foregoing members being optionally substituted with at least one group selected from Substituent Group F′;  
 Substituent Group F′ consists of C 1-6  alkyl, oxo, cyano, acyl, carboxyl, carbamoyl, C 1-6  alkoxycarbonyl, benzyloxycarbonyl, C 1-6  alkylaminocarbonyl, hydroxyl, C 1-6  alkoxy, C 3-8  cycloalkyloxy, amino, C 1-6  alkylamino, C 3-8  cycloalkylamino, acylamino, ureido, ureylene, C 1-6  alkylsulfonylamino, C 1-6  alkylsulfonyl, sulfamoyl, halogen, C 3-8  cycloalkyl, a 5- to 14-membered non-aromatic heterocyclic group, a C 6-14  aromatic hydrocarbon ring group and a 5- to 14-membered aromatic heterocyclic group;  
 Substituent Group H consists of C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, acyl, C 1-6  alkoxycarbony aminocarbonyl, C 1-6  alkylaminocarbonyl, C 3-8  cycloalkyl, C 1-6  aminoalkyl, sulfonyl, C 3-8  cycloalkylamino, a 5- to 14-membered non-aromatic heterocyclic group, a C 6-14  aromatic hydrocarbon ring group and a 5- to 14-membered aromatic heterocyclic group, each of the foregoing members being optionally substituted with at least one group selected from Substituent Group H′;  
 Substituent Group H′ consists of C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, oxo, cyano, C 1-6  cyanoalkyl, C 2-7  acyl, C 1-6  alkanoyl, benzoyl, aralkanoyl, C 1-6  alkoxyalkylcarbonyl, C 1-6  hydroxyalkylcarbonyl, carboxyl, C 1-6  carboxyalkyl, C 1-6  carboxyalkyloxy, carbamoyl, carbamoylalkyloxy, C 1-6  alkoxycarbonyl, C 1-10  alkoxycarbonyl-C 1-6  alkyl, C 1-10  alkoxycarbonyl-C 1-6  alkyloxy, C 1-6  monoalkylaminocarbonyl, C 2-6  dialkylaminocarbonyl, hydroxyl, C 1-6  alkoxy, C 1-10  alkoxyalkyl, C 1-10  aralkyloxyalkyl, C 1-6  hydroxyalkyl, C 3-8  cycloalkyloxy, amino, C 1-6  alkylamino, C 3-8  cycloalkylamino, acylamino, ureido, ureylene, C 1-6  alkylsulfonylamino, phenylsulfonylamino, C 1-6  alkylsulfonyl, phenylsulfonyl, C 1-6  monoalkylaminosulfonyl, C 2-6  dialkylaminosulfonyl, sulfamoyl, halogen, C 3-8  cycloalkyl, a 5- to 14-membered non-aromatic heterocyclic group, a C 6-14  aromatic hydrocarbon ring group, a 5- to 14-membered aromatic heterocyclic group, a heterocyclic aminocarbonyl group, a heterocyclic aminosulfonyl group and isoxazolinyl, wherein the 5- to 14-membered non-aromatic heterocyclic group, the C 6-14  aromatic hydrocarbon ring group, the 5- to 14-membered aromatic heterocyclic group and isoxazolinyl may be independently substituted with at least one group selected from the group consisting of C 1-6  alkyl, oxo, cyano, acyl, carboxyl, carbamoyl, C 1-6  alkoxycarbonyl, C 1-6  alkylaminocarbonyl, hydroxyl, C 1-6  alkoxy, C 3-8  cycloalkyloxy, nitro, amino, C 1-6  aminoalkyl, C 1-6  alkylamino, C 1-6  dialkylamino, C 3-8  cycloalkylamino, acylamino, ureido, ureylene, alkylsulfonylamino, alkylsulfonyl, sulfamoyl, halogen and C 3-8  cycloalkyl.  
 
   
   
       34 . The process of  claim 33 , wherein: 
 X 1  represents CR 1 , X 2  represents CR 2 , X 3  represents CR 3  and X 4  represents CR 4 ;    R 1  and R 4  are the same or different and each represents hydrogen or halogen, R 2  and R 3  are the same or different and each represents C 1-6  alkoxy or C 1-6  alkylaminocarbonyl;    R 5  represents hydrogen;    R 13  represents C 1-6  alkyl;    R 1  represents C 1-6  alkoxy, mono(C 1-6  alkyl)amino, di(C 1-6  alkyl)amino, morpholin-4-yl optionally substituted with at least one group selected from Substituent Group B″, piperidin-1-yl optionally substituted with at least one group selected from Substituent Group B″, piperazin-1-yl optionally substituted with at least one group selected from Substituent Group B″ or pyrrolidin-1-yl optionally substituted with at least one group selected from Substituent Group B″;    Substituent Group B″ consists of C 1-6  alkyl, C 1-6  alkoxy, oxo, C 1-6  alkanoyl, C 1-6  alkyloxycarbonyl-C 1-6  alkyl, C 1-6  carboxyalkyl, C 1-6  alkoxyalkylcarbonyl, hydroxyalkylcarbonyl and hydroxyl; and    R 15  represents hydrogen, C 1-6  alkyl or C 1-6  alkylaminocarbonyl.    
   
   
       35 . The process of  claim 33 , wherein: 
 X 1  represents CF, X 2  and X 3  represent C—OCH 2 CH 3 , X 4  represents CH;    R 5  represents hydrogen;    R 11  represents morpholin-4-yl or piperazin-1-yl optionally substituted with at least one group selected from Substituent Group B″;    R 13  represents t-butyl; and    R 15  represents methyl.    
   
   
       36 . A process for preparing a compound represented by the formula:  
     
       
         
         
             
             
         
       
     
     which comprises reacting a compound represented by the formula:  
     
       
         
         
             
             
         
       
     
     with a compound represented by the formula:  
     
       
         
         
             
             
         
       
     
     wherein: 
 X 1  represents nitrogen or CR 1 , X 2  represents nitrogen or CR 2 , X 3  represents nitrogen or CR 3 , X 4  represents nitrogen or CR 4 ;  
 R 1  and R 4  are the same or different and each represents hydrogen, halogen, optionally substituted alkyl or optionally substituted alkoxy, R 2  and R 3  are the same or different and each represents hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkoxy, optionally substituted amino, optionally substituted carboxyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted sulfonylamino or optionally substituted alkanoylamino;  
 R 11  and R 13  are the same or different and each represents hydrogen, cyano, halogen, nitro or a group selected from Substituent Group B;  
 R 15  represents hydrogen or a group selected from Substituent Group H;  
 R 11  and R 15  may bond together to form a 5- to 8-membered heterocycle having 1 to 4 heteroatoms selected from N, S and O and also optionally substituted with at least one group selected from Substituent Group F;  
 wherein Substituent Group B, Substituent Group B′, Substituent Group F, Substituent Group F′, Substituent Group H, and Substituent Group H′ are the same as those recited in  claim 33 .  
 
   
   
       37 . The process of  claim 36 , wherein: 
 X 1  represents CR 1 , X 2  represents CR 2 , X 3  represents CR 3  and X 4  represents CR 4 ;    R 1  and R 4  are the same or different and each represents hydrogen or halogen, R 2  and R 3  are the same or different and each represents C 1-6  alkoxy or C 1-6  alkylaminocarbonyl; R 13  represents C 1-6  alkyl;    R 11  represents C 1-6  alkoxy, mono(C 1-6  alkyl)amino, di(C 1-6  alkyl)amino, morpholin-4-yl optionally substituted with at least one group selected from Substituent Group B″, piperidin-1-yl optionally substituted with at least one group selected from Substituent Group B″, piperazin-1-yl optionally substituted with at least one group selected from Substituent Group B″ or pyrrolidin-1-yl optionally substituted with at least one group selected from Substituent Group B″;    Substituent Group B″ consists of C 1-6  alkyl, C 1-6  alkoxy, oxo, C 1-6  alkanoyl, C 1-6  alkyloxycarbonyl-C 1-6  alkyl, C 1-6  carboxyalkyl, C 1-6  alkoxyalkylcarbonyl, hydroxyalkylcarbonyl and hydroxyl; and    R 15  represents hydrogen, C 1-6  alkyl or C 1-6  alkylaminocarbonyl.    
   
   
       38 . The process of  claim 36 , wherein: 
 X 1  represents CF, X 2  and X 3  represent C—OCH 2 CH 3 , X 4  represents CH;    R 11  represents morpholin-4-yl or piperazin-1-yl optionally substituted with at least one group selected from Substituent Group B″;    R 13  represents t-butyl; and    R 15  represents methyl.