N-phenyl-2-pyrimidine-amine derivatives

Abstract

The present invention relates to novel amides and a process for preparing these amides.

1 . A process for the preparation of a compound of formula IV 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 4  and R 5  are independently
 a) a radical selected from the group consisting of lower alkyl, amino; mono- or di-lower alkylamino; lower alkanoylamino; lower alkoxy-carbonyl; and lower alkyl which is substituted by amino, mono- or di-lower alkylamino or lower alkanoylamino, or 
 b) an unsubstituted or substituted radical selected from the group consisting of benzylamino; benzoylamino; pyrrolidinyl; piperidyl, piperazinyl; piperazinyl-carbonyl; morpholinyl, thiomorpholinyl; and lower alkyl substituted by benzylamino, benzoylamino, halogene, pyrrolidinyl, piperidyl, piperazinyl, e.g. 4-methyl-piperazinyl-, thiomorpholinyl, or morpholinyl, the substituents of said substituted radical being selected from the group consisting of cyano; lower alkyl; hydroxy- or amino-substituted lower alkyl; trifluoromethyl; free, etherified or esterified hydroxy; lower alkoxy; lower alkanoyloxy; free, alkylated or acylated amino; mono- or di-lower alkylamino; lower alkanoylamino; benzoylamino; free or esterified carboxy; lower alkoxycarbonyl and halogen, and 
 and the other four radicals are independently hydrogen, cyano; lower alkyl; hydroxy- or amino-substituted lower alkyl; trifluoromethyl; free, etherified or esterified hydroxy; lower alkoxy; lower alkanoyloxy; free, alkylated or acylated amino; mono- or di-lower alkylamino; lower alkanoylamino; benzoylamino; free or esterified carboxy; lower alkoxycarbonyl and halogen; or 
 R 1  and R 2  or R 4  and R 5  together are a substituted or unsubstituted alkylene radical having 4 carbon atoms, the substituents preferably being selected from cyano, unsubstituted or hydroxy-, amino- or 4-methyl-piperazinyl-substituted lower alkyl, such as especially methyl, trifluoromethyl, free, etherified or esterified hydroxy, free, alkylated or acylated amino and free or esterified carboxy; 
 and the other three radicals are independently hydrogen, cyano; lower alkyl; hydroxy- or amino-substituted lower alkyl; trifluoromethyl; free, etherified or esterified hydroxy; lower alkoxy; lower alkanoyloxy; free, alkylated or acylated amino; mono- or di-lower alkylamino; lower afkanoylamino; benzoylamino; free or esterified carboxy; lower alkoxycarbonyl and halogen; 
 R 3  is (4-methyl-piperazinyl)-methyl, 
 R 6 ′ is 4-(3-pyridyl)-2-pyrimidinamino, 
 R 7 ′ is methyl and R 8 ′ is hydrogen, 
 or a pharmaceutically acceptable salt or crystal form thereof, by reacting a compound of formula I 
 
     
       
         
         
             
             
         
       
     
     wherein R 1  to R 5  are as defined above, R 6  is —NHC(NH)NH 2 , R 7  is methyl and R 8  is hydrogen;
 with a compound of formula VI 
 
     
       
         
         
             
             
         
       
     
     wherein R 10  is 3-pyridyl and R 11  is hydrogen or lower alkyl. 
   
   
       2 . The process according to  claim 1 , wherein R 11  is methyl. 
   
   
       3 . The process according to  claims 1  or  2 , wherein R 1 , R 2 , R 4  and R 5  are all hydrogen.