Abstract:
Arylamino purine derivatives represented by formula I and their preparation method are disclosed, wherein each substituent is defined as in the description. The derivatives have an inhibitory effect on non-small cell lung cancer with deletion mutation of exon 19 or L858R point mutation of exon 21 in epidermal growth factor receptor (EGFR).

Description:
TECHNICAL FIELD 
     The present invention relates to the organically synthesized pharmaceutical field and in particular to arylamino purine derivatives, preparation method and pharmaceutical use thereof. 
     BACKGROUNDS 
     Malignant tumor is one of the most severe diseases threatening the human physical health, and has become the second leading cause of death, right behind the cardiovascular disease. 
     Moreover, the most recent statistical data indicate that the incidence rate and the death rate of malignant tumor are rising up year by year all over the world, especially in the developing countries. 
     The chemotherapy is the most important treatment means for malignant tumor besides operation and radiotherapy. The traditional chemotherapeutics mainly act on DNA, RNA, microtubule protein and the like, which are the common parts involving the life and death of all cells, and therefore have low selectivity and high toxicity. The targeted medicines act on the key molecules in the tumor cell, which regulate the cell growth and proliferation and are quite different from the normal cell, and their signal transduction pathways. They have the advantages such as a high selectivity on the tumor cells and low toxicity to normal tissues, and therefore become a hot point in the study of anti-tumor drug. 
     In many of molecules regulating signal transduction pathway of the cell, the family of protein kinases is the most important signal transduction molecule. It is found in the study that the occurrence and development of many tumors are relevant to the gene abnormality or excess activation of protein kinase. Therefore, protein kinases have become the most important anti-tumor treatment target. Tyrosine or serine/threonine protein kinase such as EGFR (Epidermal Growth Factor Receptor), VEGFR (Vascular Endothelial Growth Factor Receptor), PDGFR (Platelet Derived Growth Factor Receptor), c-Kit, c-SRC, MET, BTK, ALK, Abl, and FLT3 are most important among the members of the family of protein kinases, and have been listed as oncogene or oncoprotein. 
     Currently, more than 10 small molecule inhibitors targeting these tyrosine and serine/threonine protein kinases have been applied to clinical tumor treatment. The typical example includes: two EGFR inhibitors, i.e., Gefitinib and Erlotinib, mainly useful for the treatment of non-small cell lung carcinoma; two new-vessel inhibitors (their main targets are VEGFR, PDGFR and the like), i.e., Sunitinib and Sorafenib, useful for the anti-new-vessels treatment in the solid tumor; and Bcr-Abl kinase inhibitor Imatinib, mainly useful for the treatment of chronic myelocytic leukemia with positive Philadelphia chromosome. 
     However, these current antitumor drugs target a single or a very small number of kinase oncogenes or oncoproteins and therefore have the disadvantages such as low efficiency and being prone to develop the drug resistance. The typical example includes EGFR kinase inhibitors Gefitinib and Erlotinib. These two drugs have good effects on only 10-20% of patients with non-small cell lung carcinoma. It is found in the study on its mechanism of action that Gefitinib and Erlotinib belong to the selective EGFR kinase inhibitor, and are most sensitive to the patients having deletion mutation of exon 19 or L858R point mutation of exon 21 in EGFR (deletion mutation of exon 19 and L858R point mutation of exon 21 in EGFR are collectively referred to as EGFR sensitive mutation). Even if these patients with EGFR sensitive mutation are treated with Gefitinib and Erlotinib, most of them have developed the drug resistance after 6-9 months. It is found that there are many reasons for the development of the drug resistance, which mainly include (1) a second mutation occurs based on EGFR sensitive mutation, i.e., T790M mutation in EGFR; and (2) MET gene (MET is a tyrosine kinase) is subjected to amplification. 
     Solving the low efficiency and the drug resistance of small molecule kinase inhibitor antitumor drug is not only a hot point in the study but also a task of top priority. Currently, the researchers and scientists are exploring the effective solutions, in which the most promising solutions mainly include: (1) a multiple-kinase inhibitor that simultaneously targets multiple kinases relevant to the occurrence and development of tumor; (2) directly targeting the kinase that has developed the drug-resistant mutation. For example, EGFR is over expressed or abnormally and excessively activated in several tumor tissues of human. If a certain small molecule kinase inhibitor not only can inhibit the activity of EGFR, but also can inhibit the new-vessels or the activity of the oncogene or oncoprotein of the other key kinases regulating the cell growth and proliferation, e.g. kinases such as c-Kit, c-SRC, MET, BTK, ALK, Abl and FLT3, it can improve the efficiency of tumor treatment and reduce the occurrence rate of the drug resistance. For example, as stated hereinbefore, after EGFR inhibitors Gefitinib and Erlotinib are used, EGFR itself is prone to experience a second mutation based on the original mutation (i.e., EGFR sensitive mutation), i.e., T790M mutation in EGFR. The occurrence of this second mutation is one of the main reasons causing EGFR inhibitors Gefitinib and Erlotinib to be ineffective. Therefore, the research and development of an EGFR kinase inhibitor that directly targets the drug resistant mutation (i.e. T790M mutation) is a direct approach of overcoming the drug resistance of this tumor. 
     SUMMARY OF INVENTION 
     A technical solution to be solved in the present invention is to provide an arylamino purine derivative represented by formula (I). 
                                
R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) , heterocyclyl containing 3-8 carbon atoms, amino substituted by heterocyclyl containing 3-8 carbon atoms, aryl containing 6-8 carbon atoms, or heteroaryl containing 6-8 carbon atoms; said heterocyclyl contains 1-3 heteroatoms selected from N, O and S; said heteroaryl contains 1-3 heteroatoms selected from N, O and S;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 3  represents C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) , aryl containing 6-80 carbon atoms, or heteroaryl containing 6-80 carbon atoms; said heteroaryl contains 1-15 heteroatoms selected from N, O and S;
 
R 4 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
     
       
                 
         
             
             
         
      
     
     Said aryl containing 6-8 carbon atoms may be an aryl only containing C and H, or may be an aryl having a substituent, wherein said substituent can be —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C y H (2y+1) , —OC y H (2y+1)  and/or —NHC y H (2y+1) , where y=1-5. Said aryl having a substituent can contain 0-8 nitrogen or oxygen heteroatoms; and 
     Said heteroaryl may be a heteroaryl only containing C, H, N, O or S, or may be a heteroaryl having a substituent, wherein said heteroaryl can be —NH 2 , —OH, —F, —Cl, —Br and/or —CF 3 . 
     Preferably, the arylamino purine derivative is represented by formula (I), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 3  represents 
                                
pyrimidinyl, halopyrimidinyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ;
 
R 4 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (I), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 3  represents 
                                
halopyrimidin-3-yl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ;
 
R 4 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Most preferably, the arylamino purine derivative is represented by formula (I), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 2 cycloalkyl, or C 3 -C 2 cycloalkyl; 
     R 2  represents —H, —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) ; 
     R 3  represents 
                                
halopyrimidin-3-yl, or
 
                                
R 4  represents
 
                                
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, CF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
m=1-8.
 
     Further, the arylamino purine derivative is represented by formula (II), wherein 
                                
R 1  represents —H, —C m H (2m+1) , —C 6 H 5 , —C m H (2m+1)  substituted by C 3 -C 2 cycloalkyl, C 3 -C 2 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 3  represents C 3 -C 2 cycloalkyl, C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) , aryl containing 6-80 carbon atoms or heteroaryl containing 6-80 carbon atoms; said heteroaryl contains 1-15 heteroatoms selected from N, O and S;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 15  represents
 
                                
m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (II), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, NH 2 , OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 3  represents 
                                
pyrimidinyl, halopyrimidinyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —CN, —C m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S;
 
R 15  represents
 
                                
m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (II), wherein 
     R 1  represents —H, —C m H (2m+1) , or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 3  represents 
                                
halopyrimidin-3-yl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 15  represents
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (II), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H;
 
R 3  represents
 
                                
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, CF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 15  represents
 
                                
and
 
m=1-8.
 
     Most preferably, the arylamino purine derivative is represented by formula (II), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H:
 
R 3  represents
 
                                
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 8 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 15  represents
 
                                
and
 
m=1-8.
 
     Further, the arylamino purine derivative is represented by formula (III), wherein 
                                
R 1  represents —H, —C m H (2m+1) , —C 6 H 5 , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms.
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S;
 
m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (III), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ; 
     R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) , 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (Ill), wherein 
     R 1  represents —H, —C m H (2m+1) , or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ; 
     R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) , 
                                
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (III), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H, —C m H (2m+1) , —C m H (2m+1) , or —NHC m H (2m+1) ;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (III), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
m=1-8.
 
     Most preferably, the arylamino purine derivative is represented by formula (III), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  represent —H;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
m=1-8.
 
     Further, the arylamino purine derivative is represented by formula (IV), wherein 
                                
R 1  represents —H, —C 11 H (2m+1) , —C 6 H 5 , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (IV), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ; 
     R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) , 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (IV), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 2 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) , 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (IV), wherein 
     R 1  represents —H, —C m H (2m+1) , or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —OC m H (2m+1) ; 
     R 9 -R 13  respectively represent —H, —F, —Cl, —Br, CF 3 , —C m H (2m+1) , —OC m H (2m+1) , 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (IV), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H, —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) ;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —C m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (IV), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Most preferably, the arylamino purine derivative is represented by formula (IV), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H;
 
R 5 -R 8  represent H;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or
 
                                
m=1-8.
 
     Further, the arylamino purine derivative is represented by formula (V), wherein 
                                
R 1  represents —H, —C m H (2m+1) , —C 6 H 5 , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 3  represents C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) , aryl containing 6-80 carbon atoms or heteroaryl containing 6-80 carbon atoms; said heteroaryl contains 1-15 heteroatoms selected from N, O and S;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (V), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ; 
     R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 3  represents 
                                
pyrimidinyl, halopyrimidinyl, C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (V), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1 , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 3  represents 
                                
halopyrimidin-3-yl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (V), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 3  represents 
                                
halopyrimidin-3-yl, or
 
                                
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m F (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (V), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H, —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) ;
 
R 3  represents
 
                                
halopyrimidin-3-yl, or
 
                                
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m Fl (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (V), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents-H;
 
R 3  represents
 
                                
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Most preferably, R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H;
 
R 3  represents
 
                                
R 5 -R 8  represent —H;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Further, the arylamino purine derivative is represented by formula (VI), wherein 
                                
R 1  represents —H, —C m H (2m+1) , —C 6 H 5 , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (VI), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) ; 
     R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) , 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (VI), wherein 
     R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —C m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) , 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (VI), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —OC m H (2m+1) ; 
     R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) , 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (VI), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H, —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) ;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (VI), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Most preferably, the arylamino purine derivative is represented by formula (VI), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  represent —H;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OC m H (2m+1) ,
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (VII), wherein 
                                
R 1  represents —H, —C m H (2m+1) , —C 6 H 5 , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) ;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 10 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 16  represents
 
                                
R 14  represents —C m H (2m+1) , aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (VII), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 2 cycloalkyl, or C 3 -C 2 cycloalkyl; 
     R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1 , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) , 
                                
R 10 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S;
 
R 16  represents
 
                                
m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (VII), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 2 cycloalkyl, or C 3 -C 2 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1 , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OC m H (2m+1) , 
                                
R 10 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 16  represents and
 
                                
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (VII), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —OC m H (2m+1) ; 
     R 10 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) , 
                                
R 16  represents
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (VII), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , or —OC m H (2m+1) ;
 
R 10 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 16  represents
 
                                
and
 
m=1-8.
 
     Preferably, the arylamino purine derivative is represented by formula (VII), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , or —OC m H (2m+1) ;
 
R 10 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —C m H (2m+1) , or —OC m H (2m+1) ;
 
R 16  represents
 
                                
and
 
m=1-8.
 
     Most preferably, the arylamino purine derivative is represented by formula (VII), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents-H;
 
R 5 -R 8  represent —H;
 
R 10 -R 13  respectively represent —H, —F, —Cl, or —Br;
 
R 16  represents
 
                                
and
 
m=1-8.
 
     Further, the arylamino purine derivative is represented by formula (VIII), wherein 
                                
R 1  represents —H, —C m H (2m+1) , C 3 -C 7 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl substituted by —C m H (2m+1) , heterocyclyl containing 3-8 carbon atoms, amino substituted by heterocyclyl containing 3-8 carbon atoms, aryl containing 6-8 carbon atoms, or heteroaryl containing 6-8 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) ,
 
                                
R 21  represents
 
                                
R 14  represents aryl or heteroaryl containing 6-10 carbon atoms; said heteroaryl contains 1-3 heteroatoms selected from N, O and S; m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (VIII), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —OC m H (2m+1) ; 
     R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —CN, —C m H (2m+1) , —OC m H (2m+1) , or 
                                
R 21  represents
 
                                
m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (VIII), wherein 
     R 1  represents —H, —C m H (2m+1) , —C m H (2m+1)  substituted by C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl; 
     R 2  represents —H, —C m H (2m+1) , —OC m H (2m+1) , or —NHC m H (2m+1) ; 
     R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , or —OC m H (2m+1) ; 
     R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , or —OC m H (2m+1) ; 
     R 21  represents 
                                
m=1-8; and
 
n=0-4.
 
     Preferably, the arylamino purine derivative is represented by formula (VIII), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , or —OC m H (2m+1) ;
 
R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) ;
 
R 21  represents
 
                                
m=1-8; and
 
n=0-4.
 
     Most preferably, the arylamino purine derivative is represented by formula (VIII), wherein 
     R 1  represents —H, —C m H (2m+1) , 
                                
R 2  represents —H; R 5 -R 8  represent —H; R 9 -R 13  respectively represent —H, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , or —OC m H (2m+1) ;
 
R 21  represents
 
                                
m=1-8, n=0-2.
 
     Further, the arylamino purine derivative is represented by formula (IX), wherein 
                                
R 17  represents H, C 1-4 alkyl, isopropyl, cyclopropyl, or cyclopentyl;
 
When R 18  represents H, R 19  represents 4-methylpiperazinyl-1-carbamoyl, 1-methylpiperidinyl-4-carbamoyl, 4-methyl piperazin-1-yl, 4-morpholinyl, 4-methylpiperazin-1-ylmethyl, 4-morpholinylmethyl, 3-(4-methylpiperazin-1-yl)ureido, or 3-(1-methylpiperidin-4-yl)ureido;
 
When R 18  represents fluoro, chloro, bromo, or methoxy, R 19  represents 4-methylpiperazinyl-1-carbamoyl, or 1-methylpiperidinyl-4-carbamoyl;
 
R 20  represents hydrogen, halogen, C 1-4 alkyl, ethynyl, 3-chloro-4-(pyridin-2-yl)methoxy, or 3-chloro-4-(3-fluorophenyl)methoxy.
 
     Preferably, R 17  represents H, C 1-4 alkyl, isopropyl, cyclopropyl, or cyclopentyl; 
     When R 18  represents H, R 19  represents 4-methylpiperazinyl-1-carbamoyl, 1-methylpiperidinyl-4-carbamoyl, 4-methyl piperazin-1-yl, 4-morpholinyl, 4-methylpiperazin-1-ylmethyl, 4-morpholinylmethyl, 3-(4-methylpiperazin-1-yl)ureido, or 3-(1-methyl piperidin-4-yl)ureido;
 
When R 18  represents fluoro, chloro, bromo, or methoxy, R 19  represents 4-methylpiperazinyl-1-carbamoyl, or 1-methylpiperidinyl-4-carbamoyl;
 
R 20  represents hydrogen, halogen, C 1-4 alkyl or ethynyl.
 
     Further, the arylamino purine derivative is as below.
     4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide,   4-(8-(3-chloro-4-fluorophenylamino)-9-isopropyl-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide,   4-(8-(3-acetamidophenylamino)-9-isopropyl-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide,   3-fluoro-4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide,   3-fluoro-4-(9-isopropyl-8-(3-chloro-4-fluorophenylamino)-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide,   3-fluoro-4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide,   3-methoxy-4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide,   4-(8-(3-chloro-4-fluorophenylamino)-9-isopropyl-9H-purin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide,   4-(8-phenylamino-9-isopropyl-9H-purin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide,   9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenylamino-9H-purine,   8-(3-bromophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-ethynylphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-chloro-4-fluorophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-bromophenylamino)-9-cyclopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(4-bromophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-trifluoromethylphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-methoxyphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(4-methoxyphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-chloro-4-((pyridin-2-yl)methoxy)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-(3-(3-chloro-4-fluorophenyl)ureido)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(4-(3-fluorophenylcarbamoyl)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-cyclopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(4-trifluoromethylphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-acrylylaminophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-p urine,   9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-(pyridin-3-yl)-9H-purine,   9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-cyclohexyl-9H-purine,   9-cyclopentyl-6-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine,   9-isopropyl-6-methoxy-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine,   9-isopropyl-6-methylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine,   9-isopropyl-6-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine,   9-isopropyl-6-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine,   9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-(pyridin-3-yl)-9H-purine,   4-(9-cyclopentylamino-8-(pyridin-3-ylamino)-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide,   N-(3-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)phenyl)acrylamide,   8-(4-bromophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-nitrophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-benzylamino-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-ethynylphenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(2-fluoro-4-bromophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-cyclopentyl-2-(4-(4-morpholinylmethyl)phenylamino)-9H-purine,   8-(3-fluorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-cyclohexyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-hydroxyphenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-chlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-methylphenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3,5-dichlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(2,5-difluorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-cyclopentyl-2-(4-(2-methoxyethoxy)phenylamino)-9H-purine,   8-(2,4,5-trichlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-cyclopentyl-2-(4-((4-ethylpiperazin-1-yl)methyl)phenylamino)-9H-purine,   8-phenylamino-9-cyclopentyl-2-(4-((4-methylpiperazin-1-yl)methyl)phenylamino)-9H-purine,   8-(2,5-dichlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(2,6-dichlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-(3-bromophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   8-phenylamino-9-cyclohexylmethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine,   9-isopropylamino-2-(4-(2-morpholinoethoxy)phenylamino))-8-phenylamino-9H-purine,   9-isopropylamino-2-(4-(3-(4-methylpiperazin-1-yl)propylamino)phenylamino)-8-phenylamino-9H-purine,   8-(6-chloropyrimidin-3-yl)-9-isopropylamino-2-(4-(3-(4-methylpiperazin-1-yl)propylamino)phenylamino)-9H-purine, or   8-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-9-isopropyl-2-(4-morpholinophenylamino)-9H-purine.   

     A second technical solution to be solved in the present invention is to provide a process for synthesizing an arylamino purine derivative represented by formula I, which process comprises: 
     using 2,4-dichloro-5-nitropyrimidine substituted at 6-position by a substituent group as starting material; introducing a R 1 -substituted amino at 4-position by a low temperature substituting process; then introducing 
                                
at 2-position by a high temperature substituting process; reducing the nitro at 5-position to amino; and finally forming a closed pyrazole ring with R 3 NCS (R 3 -substituted isothiocyanate), or
 
                                
(R 3 -substituted methyl phenylcarbamodithioate) to obtain the targeted product.
 
     The synthesis route is shown as below: 
                                
R 1  represents —H, —C 11 H (2m+1) , C 3 -C 2 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 2 cycloalkyl, C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) , heterocyclyl containing 3-8 carbon atoms, amino substituted by heterocyclyl containing 3-8 carbon atoms, aryl containing 6-8 carbon atoms, or heteroaryl containing 6-8 carbon atoms; said heterocyclyl contains 1-3 heteroatoms selected from N, O and S; said heteroaryl contains 1-3 heteroatoms selected from N, O and S;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 3  represents C 3 -C 2 cycloalkyl, C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) , aryl containing 6-80 carbon atoms, or heteroaryl containing 6-80 carbon atoms; said heteroaryl contains 1-15 heteroatoms selected from N, O and S;
 
R 4 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
m=1-8; and
 
n=0-4.
 
     The advantages of said process lie in the short reaction step and the cheap and easily obtainable starting materials and agents. 
     A third technical solution to be solved in the present invention is to provide a use of the above-mentioned arylamino purine derivative represented by formula I in the manufacture of a medicament for the treatment of tumors. 
     The present invention also provides a pharmaceutical composition containing an arylamino purine derivative represented by formula I or its pharmaceutical acceptable salt. Said pharmaceutical composition can be used to prepare antitumor drugs. 
     The advantages of the present inventions lie in that it is proved by experiment that the present arylamino purine derivative is a multiple-kinase inhibitor that targets the kinases such as EGFR, VEGFR and MET. The present arylamino purine derivative has not only a good inhibitory effect on the non-small cell lung carcinoma with deletion mutation of exon 19 and L858R point mutation of exon 21 in EGFR, but also a good inhibitory effect on the non-small cell lung carcinoma that is resistant to Gefitinib. The present arylamino purine derivative also has a good inhibitory effect on other types of tumors. Therefore, the present arylamino purine derivative can be useful to prepare a pharmaceutical composition against these tumors. The present invention provides a new option in the field of preparing antitumor drugs, and has a good market prospect. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  illustrates the in-vivo anti-tumor effect of Compound 8-10 and provides the tumor growth curves in a nude mouse subcutaneously transplanted human non-small cell lung carcinoma (HCC827 cell strain) model. 
         FIG. 2  illustrates the in-vivo anti-tumor effect of Compound 8-10 and provides a photograph of photograph of tumors obtained by dissection after the assay of the nude mouse subcutaneously transplanted human non-small cell lung carcinoma (HCC827 cell strain) model. 
         FIG. 3  illustrates the in-vivo anti-tumor effect of Compound 8-29 and provides the tumor growth curves in a nude mouse subcutaneously transplanted human acute myelogenous leukemia (MV4-11 cell strain) model. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Hereinafter, the present invention will be further illustrated with reference to the following examples. However, these examples are only provided for illustration purposes, and are not to limit the scope of the present invention. All of the modifications made based on the above disclosures will fall into the scope of the present invention. 
     The reaction formulae in the Example are summarized as follows: 
                                
R 1  represents —H, —C m H (2m+1) , C 3 -C 2 cycloalkyl, —C m H (2m+1)  substituted by C 3 -C 2 cycloalkyl, C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) , heterocyclyl containing 3-8 carbon atoms, amino substituted by heterocyclyl containing 3-8 carbon atoms, aryl containing 6-8 carbon atoms, or heteroaryl containing 6-8 carbon atoms; said heterocyclyl contains 1-3 heteroatoms selected from N, O and S; said heteroaryl contains 1-3 heteroatoms selected from N, O and S;
 
R 2  represents —H, —NH 2 , —OH, —F, —Cl, —Br, —CF 3 , —C m H (2m+1) , —OC m H (2m+1) , —NHC m H (2m+1) , aryloxy containing 6-12 carbon atoms, or arylamino containing 6-12 carbon atoms;
 
R 3  represents C 3 -C 2 cycloalkyl, C 3 -C 2 cycloalkyl substituted by —C m H (2m+1) , aryl containing 6-80 carbon atoms, or heteroaryl containing 6-80 carbon atoms; said heteroaryl contains 1-15 heteroatoms selected from N, O and S;
 
R 4 -R 8  respectively represent —H, —F, —Cl, —Br, —CF 3 , —OCF 3 , —OC m H (2m+1) ,
 
                                
m=1-8; and
 
n=0-4.
 
     Example 1 
     The Preparation of 2-chloro-4-amino-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     Aqueous ammonia (8.0 ml) and N,N-diisopropylethylamine (13.2 ml) were dissolved into 150 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (10.0 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 1 hour. The precipitate was filtered off. The filter cake was recrystallized to obtain a yellow solid (8.1 g) in a yield of 90.1%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.20 (s, 1H), 9.02 (s, 1H), 8.60 (s, 1H) ppm. 
     Example 2 
     The Preparation of 2-chloro-4-methylamino-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     A solution of methyl amine-ethanol (7.6 ml) and N,N-diisopropylethylamine (13.2 ml) were dissolved into 150 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (10.0 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for half an hour. Purification was conducted by a column chromatography to obtain a yellow solid (8.3 g) in a yield of 85.4%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.05 (s, 1H), 8.41 (s, 1H), 3.22 (s, 3H) ppm. 
     Example 3 
     The Preparation of 2-chloro-4-isopropylamino-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     Isopropylamine (4.5 ml) and N,N-diisopropylethylamine (13.2 ml) were dissolved into 150 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (10.0 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for half an hour. Purification was conducted by a column chromatography to obtain a bright-yellow solid (10.1 g) in a yield of 90.4%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.03 (s, 1H), 8.24 (s, 1H), 4.53 (m, 1H), 1.34 (d, J=6.8 Hz, 6H) ppm. 
     Example 4 
     The Preparation of 2-chloro-4-cyclopropylamino-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     Cyclopropylamine (1.8 ml) and N,N-diisopropylethylamine (6.6 ml) were dissolved into 75 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (5.0 g) in dichloromethane (15 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 40 min. Purification was conducted by a column chromatography to obtain a bright-yellow solid (2.6 g) in a yield of 47%.  1 H NMR (400 MHz, CDCl 3 ): δ 8.84 (s, 1H), 7.35 (s, 1H), 3.84 (m, 1H), 1.36 (m, 4H) ppm. 
     Example 5 
     The Preparation of 2-chloro-4-cyclopentylamino-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     Cyclopentylamine (5.17 ml) and N,N-diisopropylethylamine (12.4 ml) were dissolved into 125 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (9.7 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 80 min. Purification was conducted by a column chromatography to obtain a bright-yellow solid (7.9 g) in a yield of 65.13%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.03 (s, 1H), 8.38 (s, 1H), 4.59 (m, 1H), 2.13-2.21 (m, 2H), 1.72-1.85 (m, 4H), 1.53-1.71 (m, 2H) ppm. 
     Example 6 
     The Preparation of 2-chloro-4-cyclopentylamino-5-nitro-6-methylpyrimidine 
     
       
                 
         
             
             
         
      
     
     Cyclopentylamine (5.2 ml) and N,N-diisopropylethylamine (13.2 ml) were dissolved into 150 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitro-6-methylpyrimidine (10.7 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 1 hour. Purification was conducted by a column chromatography to obtain a bright-yellow solid (11.2 g) in a yield of 84.8%.  1 H NMR (400 MHz, CDCl 3 ): δ 8.44 (s, 2H), 4.41 (m, 1H), 2.64 (s, 3H), 2.01-2.15 (m, 2H), 1.61-1.76 (m, 4H), 1.45-1.63 (m, 2H) ppm. 
     Example 7 
     The Preparation of 2-chloro-4-isopropylamino-5-nitro-6-methoxypyrimidine 
     
       
                 
         
             
             
         
      
     
     Isopropylamine (4.5 ml) and N,N-diisopropylethylamine (13.2 ml) were dissolved into 150 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitro-6-methoxypyrimidine (11.5 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 45 min. Purification was conducted by a column chromatography to obtain a yellow solid (10.9 g) in a yield of 86.1%.  1 H NMR (400 MHz, CDCl 3 ): δ 8.25 (s, 1H), 4.42 (m, 1H), 4.01 (s, 3H), 1.23 (d, J=6.8 Hz, 6H) ppm. 
     Example 8 
     The Preparation of 2-chloro-4-isopropylamino-5-nitro-6-methylaminopyrimidine 
     
       
                 
         
             
             
         
      
     
     Isopropylamine (4.5 ml) and N,N-diisopropylethylamine (13.2 ml) were dissolved into 150 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitro-6-methylaminopyrimidine (11.5 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for half an hour. Purification was conducted by a column chromatography to obtain a yellow solid (10.4 g) in a yield of 82.1%.  1 H NMR (400 MHz, CDCl 3 ): δ8.17 (s, 1H), 4.48 (m, 1H), 2.78 (s, 3H), 1.31 (d, J=6.8 Hz, 6H) ppm. 
     Example 9 
     The Preparation of 2-chloro-4-isopropylamino-5-nitro-6-methylpyrimidine 
     
       
                 
         
             
             
         
      
     
     Isopropylamine (4.5 ml) and N,N-diisopropylethylamine (13.2 ml) were dissolved into 150 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitro-6-methylpyrimidine (10.7 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for half an hour. Purification was conducted by a column chromatography to obtain a bright-yellow solid (10.2 g) in a yield of 86.8%.  1 H NMR (400 MHz, CDCl 3 ): δ 8.01 (s, 1H), 4.48 (m, J=4.1, 1H), 2.72 (s, 3H), 1.32 (d, J=6.8 Hz, 6H) ppm. 
     Example 10 
     The Preparation of 2-chloro-4-cyclohexylamino-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     Cyclohexylamine (5.72 ml) and N,N-diisopropylethylamine (12.4 ml) were dissolved into 125 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (9.7 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 80 min. Purification was conducted by a column chromatography to obtain a bright-yellow solid (9.1 g) in a yield of 71.2%. ESI-MS (m/z, %) 258 (M−H) + ;  1 H NMR (400 MHz, CDCl 3 ): δ9.04 (s, 1H), 8.35 (s, 1H), 4.34 (m, 1H), 2.03 (m, 2H), 1.79 (m, 2H), 1.53-1.25 (m, 6H). 
     Example 11 
     The Preparation of 2-chloro-4-cyclohexylmethylamino-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     Cyclohexylmethylamine (3.11 g) and N,N-diisopropylethylamine (6.2 ml) were dissolved into 45 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (4.85 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 20 min. Purification was conducted by a column chromatography to obtain a bright-yellow sheet-like solid (1.73 g) in a yield of 26%. ESI-MS (m/z, %) 272 (M−H) + .  1 H NMR (400 MHz, CDCl 3 ): δ 9.03 (s, 1H), 8.48 (s, 1H), 3.52 (m, 2H), 1.78-1.64 (m, 7H), 1.33-1.14 (m, 4H), 1.08-1.00 (m, 2H). 
     Example 12 
     The Preparation of 4-(4-isopropylamino-5-nitropyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     4-amino-N-(4-methylpiperazin-1-yl)benzamide (4.7 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3.5 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow solid (5.9 g) in a yield of 71.2%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.01 (s, 1H), 9.32 (s, 1H), 8.78 (s, 1H), 8.21 (m, 2H), 7.84 (s, 1H), 7.63 (m, 2H), 4.31 (m, 1H), 2.75 (t, J=4.8 Hz, 4H), 2.38 (br, 4H), 2.13 (s, 3H), 1.19 (d, J=6.8 Hz, 6H) ppm. 
     Example 13 
     The Preparation of 3-fluoro-4-(4-isopropylamino-5-nitropyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     4-amino-3-fluoro-N-(4-methylpiperazin-1-yl)benzamide (5.0 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow solid (6.5 g) in a yield of 75.7%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.11 (s, 1H), 9.47 (s, 1H), 8.99 (s, 1H), 8.38 (d, J=7.6 Hz, 1H), 7.86 (m, 1H), 7.65 (m, 2H), 4.27 (m, 1H), 2.89 (t, J=4.8 Hz, 4H), 2.42 (br, 4H), 2.19 (s, 3H), 1.23 (d, J=6.4 Hz, 6H) ppm. 
     Example 14 
     The Preparation of 3-methoxy-4-(4-isopropylamino-5-nitropyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     4-amino-3-methoxy-N-(4-methylpiperazin-1-yl)benzamide (5.3 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4.5 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow solid (6.8 g) in a yield of 77.1%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.13 (s, 1H), 8.38 (d, J=6.8 Hz, 1H), 7.93 (m, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.46 (m, 1H), 7.08 (m, 1H), 7.01 (m, 1H), 4.31 (m, 1H), 3.86 (s, 3H), 3.55 (br, 4H), 2.52 (br, 4H), 2.32 (s, 3H), 1.24 (d, J=6.4 Hz, 6H) ppm. 
     Example 15 
     The Preparation of 4-(4-isopropylamino-5-nitropyrimidin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     4-amino-N-(4-methylpiperidin-1-yl)benzamide (4.6 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4.5 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow solid (5.7 g) in a yield of 70.0%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.58 (s, 1H), 9.02 (s, 1H), 8.48 (d, J=5.6 Hz, 1H), 8.20 (d, J=6.8 Hz, 1H), 7.86 (m, 4H), 4.45 (m, 1H), 3.80 (m, 1H), 2.94 (br, 4H), 2.32 (s, 3H), 1.62-1.83 (m, 4H), 1.33 (d, J=6.4 Hz, 6H) ppm. 
     Example 16 
     The Preparation of 4-amino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-1 (3.5 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4.5 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (5.2 g) in a yield of 79.5%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.07 (s, 1H), 8.52 (s, 2H), 8.40 (s, 1H), 7.57 (s, 1H), 7.51 (s, 1H), 7.10 (m, 2H), 3.31 (t, J=4.8 Hz, 4H), 2.81 (t, J=4.8 Hz, 4H), 2.30 (s, 3H) ppm. 
     Example 17 
     The Preparation of 4-methylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-2 (3.8 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3.5 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (5.1 g) in a yield of 74.8%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.11 (s, 1H), 8.34 (s, 1H), 7.59 (s, 1H), 7.51 (m, 2H), 7.23 (m, 2H), 4.21 (s, 3H), 3.15 (t, J=4.8 Hz, 4H), 2.87 (t, J=4.8 Hz, 4H), 2.48 (s, 3H) ppm. 
     Example 18 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.2 g) in a yield of 84.1%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.02 (s, 1H), 8.42 (s, 1H), 7.63 (s, 1H), 7.51 (s, 2H), 6.95 (m, 2H), 4.41 (m, 1H), 3.22 (t, J=4.8 Hz, 4H), 2.61 (t, J=4.8 Hz, 4H), 2.37 (s, 3H), 1.33 (d, J=6.4 Hz, 6H) ppm. 
     Example 19 
     The Preparation of 4-cyclopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-4 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3.5 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.4 g) in a yield of 87.2%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.08 (s, 1H), 8.39 (s, 1H), 7.90 (s, 1H), 7.58 (m, 2H), 6.94 (m, 2H), 4.32 (m, 1H), 3.05 (t, J=4.8 Hz, 4H), 2.90 (t, J=4.8 Hz, 4H), 2.67 (s, 3H), 1.39 (m, 4H) ppm. 
     Example 20 
     The Preparation of 4-cyclopentylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-5 (4.8 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.0 g) in a yield of 76.0%.  1 H NMR (400 MHz, CDCl 3 ): δ 9.03 (s, 1H), 8.47 (s, 1H), 7.69 (s, 1H), 7.51 (m, 2H), 7.11 (m, 2H), 4.43 (m, 1H), 3.28 (t, J=4.8 Hz, 4H), 2.67 (t, J=4.8 Hz, 4H), 2.45 (s, 3H), 2.15-2.23 (m, 2H), 1.74-1.86 (m, 4H), 1.50-1.72 (m, 2H) ppm. 
     Example 21 
     The Preparation of 4-cyclopentylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitro-6-methylpyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-6 (5.1 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 5 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.4 g) in a yield of 78.3%.  1 H NMR (400 MHz, CDCl 3 ): δ 8.42 (s, 1H), 7.62 (s, 1H), 7.41 (s, 2H), 6.98 (m, 2H), 4.21 (m, 1H), 3.14 (t, J=4.8 Hz, 4H), 2.56 (t, J=4.8 Hz, 4H), 2.51 (s, 3H), 2.34 (s, 3H), 1.47-1.85 (m, 8H) ppm. 
     Example 22 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitro-6-methoxypyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-7 (4.9 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 5.5 hours, cooled to room temperature, filtered, washed and dried to obtain a reddish-brown solid (6.5 g) in a yield of 81.5%.  1 H NMR (400 MHz, CDCl 3 ): δ 8.51 (s, 1H), 7.86 (s, 1H), 7.43 (s, 2H), 7.01 (m, 2H), 4.32 (m, 1H), 3.94 (s, 3H), 3.08 (t, J=4.8 Hz, 4H), 2.64 (t, J=4.8 Hz, 4H), 2.53 (s, 3H), 1.43 (d, J=6.4 Hz, 6H) ppm. 
     Example 23 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitro-6-methylaminopyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-8 (4.9 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 6 hours, cooled to room temperature, filtered, washed and dried to obtain a reddish-brown solid (6.0 g) in a yield of 75.4%.  1 H NMR (400 MHz, CDCl 3 ): δ 8.58 (s, 1H), 7.81 (s, 1H), 7.47 (s, 2H), 7.08 (m, 2H), 4.45 (m, 1H), 3.14 (t, J=4.8 Hz, 4H), 2.79 (s, 3H), 2.54 (t, J=4.8 Hz, 4H), 2.42 (s, 3H), 1.45 (d, J=6.4 Hz, 6H) ppm. 
     Example 24 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitro-6-methylpyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.8 g) was added to a solution of Compound 2-9 (4.6 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3.5 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.3 g) in a yield of 82.3%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 11.01 (s, 1H), 10.15 (s, 1H), 7.66 (d, J=8.4, 2H), 6.99 (d, J=9.2, 2H), 4.35 (s, 1H), 3.76 (d, J=11.2, 2H), 3.46 (d, J=10.8, 2H), 3.11 (m, J=13.6, 4H), 2.79 (s, 3H), 2.60 (s, 3H), 1.27 (d, J=6.4, 6H) ppm. 
     Example 25 
     The Preparation of 4-(4-cyclopentylamino-5-nitropyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     4-amino-N-(4-methylpiperazin-1-yl)benzamide (4.85 g) was added to a solution of Compound 2-5 (4.7 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4.5 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow solid (6.4 g) in a yield of 72.6%. MS m/z (ESI): 441 [M+H] + . 
     Example 26 
     The Preparation of 4-(4-isopropylamino-5-nitropyrimidin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     4-amino-3-fluoro-N-(4-methylpiperidin-1-yl)benzamide (5.0 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4.0 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow solid (6.3 g) in a yield of 72.8%. MS m/z (ESI): 432 [M+H] + . 
     Example 27 
     The Preparation of N-(3-(4-isopropylamino-5-nitropyrimidin-2-ylamino)phenyl)acrylamide 
     
       
                 
         
             
             
         
      
     
     N-(3-aminophenyl)acrylamide (3.2 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.0 g) in a yield of 88.3%. MS m/z (ESI): 344 [M+H] + . 
     Example 28 
     The Preparation of 4-isopropylamino-2-(4-(2-morpholinoethoxy)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(2-morpholinoethoxy)phenylamine (4.4 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3.5 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.4 g) in a yield of 80.0%. MS m/z (ESI): 403 [M+H] + . 
     Example 29 
     The Preparation of 4-isopropylamino-2-(4-(3-(4-methylpiperazin-1-yl)propylamino)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(3-(4-methylpiperazin-1-yl)propylamino)phenylamine (4.9 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.8 g) in a yield of 79.9%. MS m/z (ESI): 429 [M+H] + . 
     Example 30 
     The Preparation of 4-isopropylamino-2-(4-morpholinophenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-morpholinophenylamine (3.6 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (5.3 g) in a yield of 74.7%. MS m/z (ESI): 359 [M+H] + . 
     Example 31 
     The Preparation of 4-cyclopentylamino-2-(4-(4-morpholinylmethyl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-morpholinomethylphenylamine (3.8 g) was added to a solution of Compound 2-5 (4.8 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 4.0 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow solid (6.3 g) in a yield of 80.6%. MS m/z (ESI): 399 [M+H] + . 
     Example 32 
     The Preparation of 4-cyclohexylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (3.1 g) was added to a solution of Compound 2-10 (2.3 g) in n-butanol (40 ml). The mixture was reacted at 90° C. for 4.0 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (4.13 g) in a yield of 83.8%. MS m/z (ESI): 412 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.71 (s, 1H), 10.35 (s, 1H), 8.96 (s, 1H), 8.48 (d, J=6.8 Hz, 1H), 7.71 (d, J=8.8 Hz, 1H), 6.99 (d, J=9.2 Hz, 2H), 4.04 (m, 1H), 3.78 (m, 2H), 3.46 (m, 2H), 3.15 (m, 2H), 3.04 (m, 2H), 2.83 (s, 1H), 1.98 (m, 2H), 1.65 (m, 1H), 1.43 (m, 4H), 1.26 (m, 1H) ppm. 
     Example 33 
     The Preparation of 4-cyclopentylamino-2-(4-(2-methoxyethoxy)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(2-methoxyethoxy)phenylamine (2.7 g) was added to a solution of Compound 2-5 (3.7 g) in n-butanol (80 ml). The mixture was reacted at 90° C. for 4.0 hours, cooled to room temperature, filtered, washed and dried to obtain a yellow floc-like solid (4.53 g) in a yield of 80.9%. MS m/z (ESI): 374 [M+H] + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ10.34 (s, 1H), 8.95 (s, 1H), 8.50 (s, 1H), 7.70 (d, J=6.0 Hz, 2H), 6.93 (d, J=8.8 Hz, 2H), 4.43 (m, 1H), 4.07 (m, 2H), 3.64 (m, 2H), 3.30 (s, 3H), 2.03 (m, 2H), 1.72 (m, 2H), 1.61 (m, 4H) ppm. 
     Example 34 
     The Preparation of 4-cyclopentylamino-2-(4-((4-ethyl piperazin-1-yl)methyl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-((4-ethylpiperazin-1-yl)methyl)phenylamine (3.6 g) was added to a solution of Compound 2-5 (6.0 g) in n-butanol (130 ml). The mixture was reacted at 90° C. for 4.0 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid in a yield of 81.8%. MS m/z (ESI): 426 [M+H] + . 
     Example 35 
     The Preparation of 4-cyclopentylamino-2-(4-((4-methylpiperazin-1-yl)methyl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-((4-methylpiperazin-1-yl)methyl)phenylamine (4.7 g) was added to a solution of Compound 2-5 (5.28 g) in n-butanol (130 ml). The mixture was reacted at 90° C. for 4.0 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid in a yield of 85.7%. MS m/z (ESI): 412 [M+H] + . 
     Example 36 
     The Preparation of 4-cyclohexylmethylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-nitropyrimidine 
     
       
                 
         
             
             
         
      
     
     4-(4-methylpiperazinyl)phenylamine (1.13 g) was added to a solution of Compound 2-11 (1.6 g) in n-butanol (25 ml). The mixture was reacted at 90° C. for 4.0 hours, cooled to room temperature, filtered, washed and dried to obtain an orange-red solid (4.13 g) in a yield of 87.6%. MS m/z (ESI): 426 [M+H] + . 
     Example 37 
     The Preparation of 4-(4-isopropylamino-5-aminopyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     A solution of rongalite (sodium dithionite) (9.6 g) in water (30 ml) was added to a solution of 4-1 (2.1 g) in tetrahydrofuran (25 ml). The mixture was stirred at room temperature for 6-12 hours, adjusted to a pH of 7-8 by adding a saturated potassium carbonate solution, and then extracted with dichloromethane (5×20 ml). The organic phase was dried over anhydrous sodium sulfate, and rotary evaporated to dryness to obtain a jade-green solid (1.2 g) in a yield of 63.2%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.01 (s, 1H), 9.32 (s, 1H), 8.78 (s, 1H), 8.01 (m, 2H), 7.83 (s, 1H), 7.72 (m, 2H), 4.29 (m, 1H), 4.08 (s, 2H), 2.87 (t, J=4.8 Hz, 4H), 2.47 (br, 4H), 2.24 (s, 3H), 1.22 (d, J=6.8 Hz, 6H) ppm. 
     Example 38 
     The Preparation of 3-fluoro-4-(4-isopropylamino-5-aminopyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     A solution of rongalite (9.6 g) in water (30 ml) was added to a solution of 4-2 (2.2 g) in tetrahydrofuran (25 ml). The mixture was stirred at room temperature for 6-12 hours, adjusted to a pH of 7-8 by adding a saturated potassium carbonate solution, and then extracted with dichloromethane (5×20 ml). The organic phase was dried over anhydrous sodium sulfate, and rotary evaporated to dryness to obtain a jade-green solid (1.4 g) in a yield of 68.4%.  1 H NMR (400 MHz, DMSO-d 6 ): δ9.26 (s, 1H), 8.44 (m, 1H), 7.81 (s, 1H), 7.56 (d, J=10.8 Hz, 2H), 7.40 (s, 1H), 6.24 (d, J=7.2 Hz, 1H), 4.31 (s, 2H), 4.22 (m, 1H), 2.86 (t, J=4.8 Hz, 4H), 2.41 (br, 4H), 2.18 (s, 3H), 1.22 (d, J=6.4 Hz, 6H) ppm. 
     Example 39 
     The Preparation of 3-methoxy-4-(4-isopropylamino-5-aminopyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-3 (4.0 g) was dissolved into 150 ml ethanol, and then 40 ml water and 5.0 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.7 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (2.8 g) in a yield of 75.0%. MS m/z (ESI): 415 [M+H] + . 
     Example 40 
     The Preparation of 4-(4-isopropylamino-5-aminopyrimidin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-4 (4.0 g) was dissolved into 150 ml ethanol, and then 40 ml water and 5.0 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.7 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 4.2 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (2.6 g) in a yield of 70.8%. MS m/z (ESI): 384 [M+H] + . 
     Example 41 
     The Preparation of 4-amino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-5 (6.6 g) was dissolved into 160 ml ethanol, and then 40 ml water and 5.35 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 6.6 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 4.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and recrystallized to obtain a bluish-black solid in a yield of 71.0%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 8.18 (s, 1H), 7.56 (d, J=9.2 Hz, 2H), 6.79 (d, J=8.8 Hz, 2H), 6.00 (d, J=7.6 Hz, 1H), 4.24 (m, 1H), 4.01 (s, 2H), 2.99 (t, J=4.4 Hz, 4H), 2.43 (t, J=4.8 Hz, 4H), 2.21 (s, 3H), 1.21 (d, J=6.4 Hz, 6H) ppm. 
     Example 42 
     The Preparation of 4-methylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 100 ml round-bottom flask, Compound 4-6 (1.0 g) was dissolved into 60 ml ethanol, and then 15 ml water and 0.8 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 0.84 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 1.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (0.7 g) in a yield of 70.2%. MS m/z (ESI): 314 [M+H] + . 
     Example 43 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-7 (3.7 g) was dissolved into 200 ml ethanol, and then 50 ml water and 2.7 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.8 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (2.4 g) in a yield of 70.6%.  1 H NMR (400 MHz, DMSO-d 6 ): δ 8.18 (s, 1H), 7.56 (d, J=9.2 Hz, 2H), 6.79 (d, J=8.8 Hz, 2H), 6.00 (d, J=7.6 Hz, 1H), 4.24 (m, 1H), 4.01 (s, 2H), 2.99 (t, J=4.4 Hz, 4H), 2.43 (t, J=4.8 Hz, 4H), 2.21 (s, 3H), 1.21 (d, J=6.4 Hz, 6H) ppm. 
     Example 44 
     The Preparation of 4-cyclopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 100 ml round-bottom flask, Compound 4-8 (1.1 g) was dissolved into 60 ml ethanol, and then 15 ml water and 0.8 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 0.84 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 1.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a column chromatography to obtain bluish-black solid (0.8 g) in a yield of 79.2%. MS m/z (ESI): 340 [M+H] + . 
     Example 45 
     The Preparation of 4-cyclopentylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 250 ml round-bottom flask, Compound 4-9 (2.0 g) was dissolved into 100 ml ethanol, and then 25 ml water and 1.4 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 1.4 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 2.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and recrystallized to obtain a bluish-black solid (1.1 g) in a yield of 59.3%. MS m/z (ESI): 368 [M+H] + . 
     Example 46 
     The Preparation of 4-cyclopentylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-amino-6-methylpyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-10 (3.7 g) was dissolved into 200 ml ethanol, and then 50 ml water and 2.7 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.8 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (2.6 g) in a yield of 75.7%. MS m/z (ESI): 382 [M+H] + . 
     Example 47 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-amino-6-methoxypyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-11 (3.9 g) was dissolved into 200 ml ethanol, and then 50 ml water and 2.7 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.8 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (2.5 g) in a yield of 70.0%. MS m/z (ESI): 372 [M+H] + . 
     Example 48 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-amino-6-methylaminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-12 (3.8 g) was dissolved into 200 ml ethanol, and then 50 ml water and 2.7 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.8 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (2.4 g) in a yield of 67.3%. MS m/z (ESI): 371 [M+H] + . 
     Example 49 
     The Preparation of 4-isopropylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-amino-6-methylpyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-13 (3.7 g) was dissolved into 200 ml ethanol, and then 50 ml water and 2.7 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.8 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid (2.5 g) in a yield of 73.3%.  1 H NMR (400 MHz, CDCl 3 ): δ 7.51 (d, J=8.8, 2H), 6.89 (d, J=8.8, 2H), 6.59 (s, 1H), 5.17 (d, J=7.2, 1H), 4.63 (s, 2H), 4.22 (m, J=6.72, 1H), 3.14 (t, J=5.0, 4H), 2.59 (t, J=4.8, 4H), 2.35 (s, 3H), 2.25 (s, 3H), 1.26 (d, J=6.4, 6H) ppm. 
     Example 50 
     The Preparation of 4-(4-cyclopentylamino-5-aminopyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-14 (4.4 g) was dissolved into 150 ml ethanol, and then 40 ml water and 5.0 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.7 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and recrystallized to obtain a bluish-black solid (3.2 g) in a yield of 77.9%. MS m/z (ESI): 411 [M+H] + . 
     Example 51 
     The Preparation of 4-(4-isopropylamino-5-aminopyrimidin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     A solution of rongalite (9.6 g) in water (30 ml) was added to a solution of 4-15 (2.2 g) in tetrahydrofuran (25 ml). The mixture was stirred at room temperature for 6-12 hours, adjusted to a pH of 7-8 by adding a saturated potassium carbonate solution, and then extracted with dichloromethane (5×20 ml). The organic phase was dried over anhydrous sodium sulfate, and rotary evaporated to dryness to obtain a jade-green solid (1.5 g) in a yield of 69.6%. MS m/z (ESI): 402 [M+H] + . 
     Example 52 
     The Preparation of N-(3-(4-isopropylamino-5-nitropyrimidin-2-ylamino)phenyl)acrylamide 
     
       
                 
         
             
             
         
      
     
     N-(3-aminophenyl)acrylamide (3.2 g) was added to a solution of Compound 2-3 (4.3 g) in n-butanol (150 ml). The mixture was reacted at 90° C. for 3 hours, cooled to room temperature, filtered, washed and dried to obtain a red solid (6.0 g) in a yield of 88.3%. MS m/z (ESI): 344 [M+H] + . 
     Example 53 
     The Preparation of 4-isopropylamino-2-(4-(2-morpholinoethoxy)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 100 ml round-bottom flask, Compound 4-17 (1.21 g) was dissolved into 60 ml ethanol, and then 15 ml water and 0.8 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 0.84 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 1.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid in a yield of 75.2%. MS m/z (ESI): 373 [M+H] + . 
     Example 54 
     The Preparation of 4-isopropylamino-2-(4-(3-(4-methylpiperazin-1-yl)propylamino)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 100 ml round-bottom flask, Compound 4-18 (1.3 g) was dissolved into 60 ml ethanol, and then 15 ml water and 0.8 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 0.84 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 1.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid in a yield of 78.9%. MS m/z (ESI): 399 [M+H] + . 
     Example 55 
     The Preparation of 4-isopropylamino-2-(4-morpholinophenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 100 ml round-bottom flask, Compound 4-19 (1.1 g) was dissolved into 60 ml ethanol, and then 15 ml water and 0.8 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 0.84 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 2.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid in a yield of 74.1%. MS m/z (ESI): 329 [M+H] + . 
     Example 56 
     The Preparation of 4-cyclopentylamino-2-(4-(4-morpholinylmethyl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-20 (3.85 g) was dissolved into 150 ml ethanol, and then 40 ml water and 5.0 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.7 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3.5 hours. The mixture was filtered while hot, rotary evaporated to dryness, and subjected to a column chromatography to obtain a bluish-black solid in a yield of 74.5%. MS m/z (ESI): 369 [M+H] + . 
     Example 57 
     The Preparation of 4-cyclohexylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 100 ml round-bottom flask, Compound 4-21 (1.03 g) was dissolved into 40 ml ethanol, and then 10 ml water and 0.67 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 0.7 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 3.7 hours. The mixture was filtered while hot, and rotary-evaporated to dryness to obtain a crude product in a yield of 78.9%. MS m/z (ESI): 382 [M+H] + . 
     Example 58 
     The Preparation of 4-cyclopentylamino-2-(4-(2-methoxyethoxy)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 250 ml round-bottom flask, Compound 4-22 (3.73 g) was dissolved into 120 ml ethanol, and then 30 ml water and 2.67 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 2.8 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 4 hours. The mixture was filtered while hot, and rotary-evaporated to dryness to obtain a crude product in a yield of 84.6%. MS m/z (ESI): 344 [M+H] + . 
     Example 59 
     The Preparation of 4-cyclopentylamino-2-(4-((4-ethyl piperazin-1-yl)methyl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-23 (10 g) was dissolved into 240 ml ethanol, and then 60 ml water and 2.67 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 6.6 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 4 hours. The mixture was filtered while hot, and rotary-evaporated to dryness to obtain a crude product in a yield of 82.7%. MS m/z (ESI): 396 [M+H] + . 
     Example 60 
     The Preparation of 4-cyclopentylamino-2-(4-((4-methyl piperazin-1-yl)methyl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 500 ml round-bottom flask, Compound 4-24 (9.42 g) was dissolved into 240 ml ethanol, and then 60 ml water and 1.92 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 6.85 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The reaction time was 4 hours. The mixture was filtered while hot, and rotary-evaporated to dryness to obtain a crude product in a yield of 80.6%. MS m/z (ESI): 382 [M+H] + . 
     Example 61 
     The Preparation of 4-cyclohexylmethylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
     
       
                 
         
             
             
         
      
     
     In a 100 ml round-bottom flask, Compound 4-23 (2.0 g) was dissolved into 30 ml ethanol, and then 10 ml water and 0.62 g NH 4 Cl were added thereto. The mixture was stirred at room temperature for 10 minutes, and warmed to 90° C. 1.29 g Fe powder was added to the mixture in three portions. TLC detection indicated the completion of the reaction of the starting material. The mixture was filtered while hot, and rotary-evaporated to dryness to obtain a crude product in a yield of 81.4%. MS m/z (ESI): 396 [M+H] + . 
     Example 62 
     The Preparation of 4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-1 (2.3 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-1. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 64.3%. ESI-MS (m/z, %) 484.29 (M−H) − ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.63 (s, 1H), 9.21 (s, 1H), 9.11 (s, 1H), 7.85 (m, 4H), 7.73 (d, J=8.4 Hz, 2H), 7.34 (m, 2H), 7.00 (m, 1H), 4.94 (m, 1H), 2.88 (t, J=4.4 Hz, 4H), 2.42 (br, 4H), 2.19 (s, 3H), 1.70 (d, J=6.8 Hz, 6H) ppm. 
     Example 63 
     The Preparation of 4-(8-(3-chloro-4-fluorophenylamino)-9-isopropyl-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-1 (2.3 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-chloro-4-fluorophenyl isothiocyanate (1.35 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-1. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 62.9%. ESI-MS (m/z, %) 536.27 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.65 (s, 1H), 9.31 (s, 1H), 9.20 (s, 1H), 8.51 (s, 1H), 8.23 (m, 1H), 7.86 (d, J=8.8 Hz, 2H), 7.78 (m, 1H), 7.75 (t, J=6.6 Hz, 2H), 7.41 (t, J=9.2 Hz, 1H), 4.90 (s, 1H), 2.88 (d, J=4 Hz, 4H), 2.43 (m, 4H), 2.20 (s, 3H), 1.70 (d, J=6.8 Hz, 6H) ppm. 
     Example 64 
     The Preparation of 4-(8-(3-acetamidophenylamino)-9-isopropyl-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-2 (2.4 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and meta-acetamidophenyl isothiocyanate (1.4 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-2. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69.1%. ESI-MS (m/z, %) 561.18 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.00 (s, 1H), 9.52 (s, 1H), 9.20 (s, 1H), 8.88 (s, 1H), 8.42 (s, 1H), 8.26 (m, 1H), 8.08 (s, 1H), 7.66 (d, J=10.0 Hz, 2H), 7.57 (d, J=7.2 Hz, 1H), 7.21 (m, 2H), 4.94 (m, 1H), 2.90 (s, 4H), 2.68 (br, 4H), 2.06 (s, 3H), 1.64 (d, J=6.0 Hz, 6H) ppm. 
     Example 65 
     The Preparation of 3-fluoro-4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-2 (2.4 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-2. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 64.8%. ESI-MS (m/z, %) 502.17 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.37 (s, 1H), 9.10 (s, 1H), 8.88 (s, 1H), 8.43 (s, 1H), 8.25 (m, 1H), 7.84 (d, J=8.4 Hz, 2H), 7.64 (d, J=10.4 Hz, 2H), 7.00 (m, 2H), 4.90 (m, 1H), 2.89 (s, 4H), 2.42 (br, 4H), 2.19 (s, 3H), 1.65 (d, J=6.4 Hz, 6H) ppm. 
     Example 66 
     The Preparation of 3-fluoro-4-(9-isopropyl-8-(3-chloro-4-fluorophenylamino)-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-2 (2.4 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-chloro-4-fluorophenyl isothiocyanate (1.35 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-2. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 68.8%. ESI-MS (m/z, %) 554.30 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ9.21 (s, 1H), 9.04 (s, 1H), 8.41 (s, 1H), 8.22 (d, J=5.2 Hz, 1H), 7.74 (m, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.39 (m, 1H), 6.87 (d, J=8.4 Hz, 2H), 4.84 (m, 1H), 3.05 (s, 4H), 2.45 (br, 4H), 2.22 (s, 3H), 1.66 (d, J=6.4 Hz, 6H) ppm. 
     Example 67 
     The Preparation of 3-fluoro-4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-15 (2.4 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-15. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67.6%. ESI-MS (m/z, %) 502.22 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.22 (s, 1H), 8.87 (s, 1H), 8.49 (s, 1H), 8.44 (s, 1H), 8.29 (t, J=8.4, 1H), 7.86 (d, J=8.0, 2H), 7.78 (d, J=8.8, 2H), 7.34 (t, J=7.6, 2H), 7.01 (t, J=7.2, 1H), 4.97 (m, 1H), 4.04 (m, 1H), 3.38 (m, 2H), 3.09 (m, 2H), 2.72 (s, 3H), 1.99 (m, 4H), 1.65 (d, J=6.8, 6H) ppm. 
     Example 68 
     The Preparation of 3-methoxy-4-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-3 (2.5 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-3. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66.5%. ESI-MS (m/z, %) 514.21 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.98 (s, 1H), 9.65 (s, 1H), 8.90 (s, 1H), 8.50 (s, 1H), 8.27 (d, J=7.6 Hz, 1H), 7.83 (d, J=7.6 Hz, 2H), 7.39 (t, J=8 Hz, 2H), 7.18-7.08 (m, 3H), 5.026 (m, 1H), 3.94 (s, 4H), 3.42 (d, J=7.6 Hz, 2H), 3.09 (d, J=12 Hz, 2H), 2.79 (d, J=7.2 Hz, 3H), 1.66 (d, J=6.4 Hz, 6H) ppm. 
     Example 69 
     The Preparation of 4-(8-(3-chloro-4-fluorophenylamino)-9-isopropyl-9H-purin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     To a solution of Compound 5-4 (2.0 g) and methyl 3-ethynylphenylcarbamodithioate (1.3 g) in N,N-dimethylformamide (30 ml) were added copper oxide (0.08 g) and potassium carbonate (1.4 g). The mixture was heated to 60° C. and reacted for 2-6 hours. The reaction solution was cooled to room temperature and filtered. The filtrate was washed with ethyl acetate, a saturated saline solution and water. The organic layer was dried over anhydrous sodium sulfate and concentrated. Purification was conducted by a column chromatography to obtain an off-white solid in a yield of 64.1%. ESI-MS (m/z, %) 507.22 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ 9.51 (s, 1H), 9.04 (s, 1H), 8.91 (s, 1H), 7.88 (m, 4H), 7.65 (d, 2H), 7.41 (m, 2H), 7.12 (m, 1H), 4.80 (m, 1H), 4.14 (s, 1H), 3.71 (m, 1H), 2.80 (m, 4H), 2.39 (br, 4H), 2.21 (s, 3H), 1.62 (d, 6H) ppm. 
     Example 70 
     The Preparation of 4-(8-phenylamino-9-isopropyl-9H-purin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-4 (2.3 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-4. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67.9%. ESI-MS (m/z, %) 483.25 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.72 (s, 1H), 9.63 (s, 1H), 9.11 (s, 1H), 8.45 (s, 1H), 8.28 (s, 1H), 7.89-7.81 (m, 5H), 7.34 (t, J=7.8 Hz, 2H), 7.00 (t, J=7.2 Hz, 1H), 4.95 (m, 1H), 4.02 (s, 1H), 3.44 (d, J=10.8 Hz, 2H), 3.08 (s, 2H), 2.75 (s, 3H), 1.99 (s, 2H), 1.82 (d, J=11.2 Hz, 2H), 1.70 (d, J=6.8 Hz, 6H) ppm. 
     Example 71 
     The Preparation of 9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenylamino-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67.5%. ESI-MS (m/z, %) 441.29 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ 9.09 (d, J=6.8 Hz, 2H), 8.36 (s, 1H), 7.83 (d, J=8.0 Hz, 2H), 7.69 (d, J=9.2 Hz, 2H), 7.33 (m, 2H), 6.97 (m, 3H), 4.92 (m, 1H), 3.44 (br, 4H), 3.17 (br, 4H), 2.81 (s, 3H), 1.67 (d, J=6.8 Hz, 6H) ppm. 
     Example 72 
     The Preparation of 8-(3-bromophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and meta-bromophenyl isothiocyanate (1.5 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 57.4%. ESI-MS (m/z, %) 519.19 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.47 (s, 1H), 9.09 (s, 1H), 8.42 (s, 1H), 8.25 (s, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.67 (d, J=8.8 Hz, 2H), 7.28 (t, J=8.4 Hz, 1H), 7.14 (d, J=8.0 Hz, 1H), 6.93 (d, J=8.8 Hz, 2H), 4.99 (m, 1H), 3.51-3.40 (m, 2H), 3.25 (s, 2H), 3.07 (s, 4H), 2.64 (s, 3H), 1.66 (d, J=6.8; H, 6H) ppm. 
     Example 73 
     The Preparation of 8-(3-ethynylphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and meta-ethynylphenyl isothiocyanate (1.1 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 53.9%. ESI-MS (m/z, %) 465.23 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.10 (s, 1H), 9.02 (s, 1H), 8.41 (s, 1H), 8.07 (s, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.64 (d, J=9.2 Hz, 2H), 7.34 (t, J=8.0, 1H), 7.08 (d, J=7.2 Hz, 1H), 6.88 (d, J=9.2 Hz, 2H), 4.85 (m, 1H), 4.18 (s, 1H), 3.05 (s, 4H), 2.47 (t, J=9.0, 4H), 2.22 (s, 3H), 1.67 (d, J=6.8 Hz, 6H) ppm. 
     Example 74 
     The Preparation of 8-(3-chloro-4-fluorophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-chloro-4-fluorophenyl isothiocyanate (1.35 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 60.8%. ESI-MS (m/z, %) 493.16 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ 9.21 (s, 1H), 9.04 (s, 1H), 8.41 (s, 1H), 8.22 (d, J=5.2 Hz, 1H), 7.74 (m, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.39 (m, 1H), 6.87 (d, J=8.4 Hz, 2H), 4.84 (m, 1H), 3.05 (br, 4H), 2.45 (br, 4H), 2.22 (s, 3H), 1.66 (d, J=6.4 Hz, 6H) ppm. 
     Example 75 
     The Preparation of 8-(3-bromophenylamino)-9-cyclopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-8 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and meta-bromophenyl isothiocyanate (1.5 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-8. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58.2%. ESI-MS (m/z, %) 517.21 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ 9.78 (s, 1H), 9.32 (s, 1H), 8.45 (s, 1H), 7.79 (m, 2H), 7.61 (m, 2H), 7.49 (m, 2H), 7.36 (m, 1H), 4.15 (m, 1H), 2.94 (tr, 4H), 2.63 (br, 4H), 2.19 (s, 3H), 1.26 (m, 4H) ppm. 
     Example 76 
     The Preparation of 8-(4-bromophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and para-bromophenyl isothiocyanate (1.5 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 53.4%. ESI-MS (m/z, %) 519.22 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.25 (s, 1H), 9.11 (s, 1H), 8.39 (s, 1H), 7.85 (d, J=8.8 Hz, 2H), 7.69 (d, J=9.2 Hz, 2H), 7.50 (d, J=8.8 Hz, 2H), 6.95 (d, J=9.2 Hz, 2H), 4.91 (m, 1H), 3.69 (s, 1H), 3.45 (s, 1H), 3.17 (s, 1H), 3.00 (s, 1H), 2.82 (s, 3H), 1.66 (d, J=6.8 Hz, 6H) ppm. 
     Example 77 
     The Preparation of 8-(3-trifluoromethylphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and meta-trifluoromethylphenyl isothiocyanate (1.4 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 55.8%. ESI-MS (m/z, %) 509.24 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.80 (s, 1H), 10.03 (s, 1H), 8.50 (s, 1H), 8.32 (s, 1H), 8.19 (d, J=8.0, 1H), 7.62 (t, J=7.8, 1H), 7.55 (d, J=8.8, 2H), 7.40 (d, J=7.6, 1H), 7.04 (d, J=9.2, 2H), 5.05 (m, 1H), 3.78 (d, J=12.4, 4H), 3.04-3.20 (m, 4H), 2.82 (d, J=4.0, 3H), 1.64 (d, J=6.4, 6H) ppm. 
     Example 78 
     The Preparation of 8-(3-methoxyphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and meta-methoxyphenyl isothiocyanate (1.2 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58.8%. ESI-MS (m/z, %) 471.28 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.06 (d, J=16.8, 2H), 8.37 (s, 1H), 7.69 (d, J=8.8, 2H), 7.52 (s, 1H), 7.42 (d, J=4.0, 1H), 7.22 (t, J=8.2, 1H), 6.95 (d, J=9.2, 2H), 6.56 (m, 1H), 4.91 (m, 1H), 3.76 (s, 1H), 2.81 (s, 1H), 1.66 (d, J=6.8, 6H) ppm. 
     Example 79 
     The Preparation of 8-(4-methoxyphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and para-methoxyphenyl isothiocyanate (1.2 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 59.8%. ESI-MS (m/z, %) 471.28 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.04 (s, 1H), 8.93 (s, 1H), 8.30 (s, 1H), 7.71 (m, J=8.9, 4H), 6.94 (t, J=9.4, 4H), 4.90 (m, 1H), 3.75 (s, 3H), 3.46-3.43 (m, 4H), 3.17-3.06 (m, 4H), 2.81 (s, 3H), 1.67 (d, J=6.8, 6H) ppm. 
     Example 80 
     The Preparation of 8-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-chloro-4-(3-fluorobenzyloxy)phenyl isothiocyanate (2.1 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65.7%. ESI-MS (m/z, %) 599.22 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.02 (d, J=4.8 Hz, 2H), 8.36 (s, 1H), 8.08 (d, J=2.4 Hz, 1H), 7.67 (m, 3H), 7.46 (m, 1H), 7.31 (t, J=7.6 Hz, 2H), 7.20 (m, 2H), 6.91 (d, J=8.8 Hz, 2H), 5.21 (s, 2H), 4.83 (m, 1H), 3.15 (s, 4H), 2.81 (s, 3H), 2.48 (s, 2H), 2.30 (s, 2H), 1.66 (d, J=6.8 Hz, 6H) ppm. 
     Example 81 
     The Preparation of 8-(3-chloro-4-((pyridin-2-yl)methoxy)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and (3-chloro-4-(pyridin-2-yl)methoxy)phenyl isothiocyanate (2.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65.9%. ESI-MS (m/z, %) 582.31 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ 9.13 (s, 1H), 8.60 (d, 1H), 8.30 (s, 1H), 7.85 (m, 3H), 7.69 (m, 1H), 7.60 (d, 2H), 7.30-7.15 (m, 4H), 7.05 (d, 1H), 4.88 (m, 1H), 3.48 (br, 4H), 2.97 (br, 4H), 2.78 (s, 3H), 1.59 (d, J=6.8 Hz, 6H) ppm. 
     Example 82 
     The Preparation of 8-(3-(3-(3-chloro-4-fluorophenyl)ureido)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-(3-(3-chloro-4-fluorophenyl)ureido)phenyl isothiocyanate (2.3 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 62.5%. ESI-MS (m/z, %) 627.21 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 8.99 (d, J=9.6 Hz, 2H), 8.88 (s, 1H), 8.80 (s, 1H), 8.34 (s, 1H), 7.94 (s, 1H), 7.84 (m, 1H), 7.63 (d, J=9.2 Hz, 2H), 7.47 (d, J=8 Hz, 1H), 7.37-7.28 (m, 2H), 7.22 (t, J=8 Hz, 1H), 7.11 (d, J=8 Hz, 1H), 6.88 (d, J=9.2 Hz, 2H), 4.90 (m, 1H), 3.06 (t, J=4.8 Hz, 3H), 2.51 (m, 4H), 2.48 (d, J=4.4 Hz, 2H), 2.26 (d, J=19.6 Hz, 2H), 1.67 (d, J=6.8 Hz, 6H) ppm. 
     Example 83 
     The Preparation of 8-(4-(3-fluorophenylcarbamoyl)phenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 4-(3-fluorophenylcarbamoyl)phenyl isothiocyanate (2.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 54.6%. ESI-MS (m/z, %) 578.22 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.30 (s, 1H), 9.44 (s, 1H), 9.12 (s, 1H), 8.44 (s, 1H), 7.98 (s, 3H), 7.78 (d, J=11.6 Hz, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.59 (d, J=7.2 Hz, 2H), 7.38 (m, 1H), 6.91 (m, 3H), 4.94 (m, 1H), 3.27 (s, 4H), 2.96 (d, J=8 Hz, 2H), 2.73 (s, 3H), 2.55 (s, 2H), 1.69 (d, J=6.4 Hz, 6H) ppm; 
     Example 84 
     The Preparation of 8-phenylamino-9-cyclopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-8 (2.0 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.86 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-8. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58.3%. ESI-MS (m/z, %) 439.23 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.14 (s, 1H), 9.64 (s, 1H), 8.39 (s, 1H), 7.851 (d, J=8 Hz, 2H), 7.60 (d, J=8.8 Hz, 2H), 7.41 (t, J=8 Hz, 2H), 7.13 (t, J=7.2 Hz, 1H), 7.05 (d, J=9.2 Hz, 2H), 3.43-3.50 (m, 4H), 3.20-3.24 (m, 4H), 2.82 (d, J=3.2 Hz, 3H), 1.19-1.30 (m, 4H) ppm. 
     Example 85 
     The Preparation of 8-phenylamino-9-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-6 (1.9 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.86 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-6. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 51.1%. ESI-MS (m/z, %) 413.24 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.57 (s, 1H), 9.52 (s, 1H), 8.37 (s, 1H), 7.88 (d, J=7.6 Hz, 2H), 7.656 (d, J=8.4 Hz, 2H), 7.37 (t, J=8 Hz, 2H), 7.05 (t, J=7.2 Hz, 1H), 6.99 (d, J=8.8 Hz, 2H), 3.69 (s, 3H), 3.381 (s, 4H), 3.16 (d, J=8.8 Hz, 2H), 3.03 (d, J=12 Hz, 2H), 2.82 (s, 3H) ppm. 
     Example 86 
     The Preparation of 8-phenylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-5 (2.4 g) was dissolved into dichloromethane (120 ml). To the mixture were successively added EDCI (3.1 g), N,N-diisopropylethylamine (6.6 ml), and para-trifluoromethylphenyl isothiocyanate (1.1 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-5. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 57.3%. ESI-MS (m/z, %) 399.27 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.89 (s, 1H), 9.93 (s, 1H), 8.77 (s, 1H), 8.20 (s, 1H), 7.30 (d, J=7.2 Hz, 2H), 7.63 (d, J=8.4 Hz, 2H), 7.34 (t, J=6.8 Hz, 2H), 7.00 (s, 1H), 6.87 (d, J=8.8 Hz, 2H), 3.04 (t, J=4.4 Hz, 4H), 2.46 (t, J=4.4 Hz, 4H), 2.23 (s, 3H) ppm. 
     Example 87 
     The Preparation of 8-phenylamino-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (1.6 g) was dissolved into dichloromethane (65 ml). To the mixture were successively added EDCI (1.7 g), N,N-diisopropylethylamine (3.7 ml), and phenyl isothiocyanate (0.6 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 52.1%. ESI-MS (m/z, %) 467.26 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.18 (s, 1H), 9.08 (s, 1H), 8.36 (s, 1H), 7.85 (d, J=7.6 Hz, 2H), 7.67 (d, J=8.4 Hz, 2H), 7.32 (t, J=3.6 Hz, 2H), 6.93-7.00 (m, 3H), 5.04 (t, J=8 Hz, 1H), 3.36 (s, 8H), 2.79 (s, 3H), 2.46 (s, 2H), 2.05 (s, 4H), 1.70 (s, 2H) ppm. 
     Example 88 
     The Preparation of 8-(4-trifluoromethylphenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and para-trifluoromethylphenyl isothiocyanate (1.4 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 55.4%. ESI-MS (m/z, %) 509.25 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.46 (s, 1H), 9.09 (s, 1H), 8.44 (s, 1H), 8.03 (d, J=8.4 Hz, 2H), 7.67 (m, J=8.8 Hz, 4H), 6.90 (d, J=8.8 Hz, 2H), 4.90 (m, 1H), 3.10 (s, 4H), 2.59 (s, 4H), 2.32 (s, 3H), 1.68 (d, J=6.4 Hz, 6H) ppm. 
     Example 89 
     The Preparation of 8-(3-acrylylaminophenylamino)-9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-acrylylaminophenyl isothiocyanate (1.5 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58.9%. ESI-MS (m/z, %) 510.25 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.51 (s, 1H), 9.07 (s, 1H), 8.52 (s, 1H), 8.09 (d, J=8.4 Hz, 2H), 7.61 (m, 4H), 6.92 (d, J=8.8 Hz, 2H), 6.54 (s, 1H), 6.05 (s, 1H), 5.59 (s, 1H), 4.79 (m, 1H), 2.93 (s, 4H), 2.62 (br, 4H), 2.38 (s, 3H), 1.61 (d, J=6.4 Hz, 6H) ppm. 
     Example 90 
     The Preparation of 9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-(pyridin-3-yl)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-pyridinyl isothiocyanate (1.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65.7%. ESI-MS (m/z, %) 442.26 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.38 (s, 1H), 9.13 (s, 1H), 8.99 (s, 1H), 8.40 (s, 1H), 8.36 (d, J=8.4 Hz, 1H), 8.20 (d, J=4.4 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 7.37 (m, 1H), 6.96 (d, J=8.8 Hz, 2H), 4.97-4.92 (m, 1H), 3.35 (s, 6H), 2.80 (s, 3H), 2.53 (s, 2H), 1.69 (s, 6H) ppm. 
     Example 91 
     The Preparation of 9-isopropyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-cyclohexyl-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and cyclohexyl isothiocyanate (1.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67.8%. ESI-MS (m/z, %) 447.28 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.89 (s, 1H), 9.26 (s, 1H), 8.23 (s, 1H), 7.62 (d, J=9.2, 2H), 6.95 (d, J=8.8, 2H), 4.72 (m, 1H), 4.03 (m, J=7.1, 1H), 3.69 (s, 4H), 3.13-3.09 (m, 4H), 2.80 (s, 3H), 1.98 (d, J=5.6, 2H), 1.76 (d, J=9.6, 2H), 1.57 (d, J=6.8, 6H), 1.37-1.26 (m, 6H) ppm. 
     Example 92 
     The Preparation of 9-cyclopentyl-6-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-10 (2.3 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 mlg). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-10. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 61.1%. ESI-MS (m/z, %) 481.27 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.12 (s, 1H), 8.39 (s, 1H), 7.75 (m, 2H), 7.59 (m, 2H), 7.46 (m, 2H), 7.10 m, 3H), 4.62 (m, 1H), 3.38 (s, 6H), 2.75 (s, 3H), 2.68 (s, 3H), 2.42 (br, 2H), 2.15 (s, 4H), 1.76 (m, 4H) ppm. 
     Example 93 
     The Preparation of 9-isopropyl-6-methoxy-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-11 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 mlg). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-11. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 63.5%. ESI-MS (m/z, %) 471.28 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ 8.56 (s, 1H), 7.82 (d, J=8.0 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 7.39 (m, 2H), 7.26 (m, 2H), 7.02 (m, 2H), 4.92 (m, 1H), 4.06 (s, 3H), 3.49 (br, 4H), 3.27 (br, 4H), 2.83 (s, 3H), 1.61 (d, J=6.8 Hz, 6H) ppm. 
     Example 94 
     The Preparation of 9-isopropyl-6-methylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-12 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 mlg). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-12. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65.4%. ESI-MS (m/z, %) 470.25 (M−H) − .  1 H NMR (400 MHz, DMSO-d6): δ 8.61 (s, 1H), 7.83 (d, J=8.0 Hz, 2H), 7.69 (m, 2H), 7.37 (m, 2H), 7.25 (m, 1H), 7.04 (m, 3H), 4.71 (m, 1H), 3.49 (br, 4H), 3.27 (br, 4H), 2.86 (s, 3H), 1.65 (d, J=6.8 Hz, 6H) ppm. 
     Example 95 
     The Preparation of 9-isopropyl-6-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-phenyl-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-13 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-13. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66.7%. ESI-MS (m/z, %) 455.28 (M−H) − ;  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.08 (s, 1H), 9.01 (s, 1H), 7.84 (d, J=8.0, 2H), 7.71 (d, J=8.8, 2H), 7.32 (t, J=7.8, 2H), 6.96 (t, J=8.4, 3H), 4.91 (m, J=6.6, 1H), 3.67 (s, 4H), 3.27 (s, 4H), 2.80 (s, 3H), 2.49 (s, 3H), 1.66 (d, J=6.8, 6H) ppm. 
     Example 96 
     The Preparation of 8-(3-chloro-4-fluorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-chloro-4-fluorophenyl isothiocyanate (1.35 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67.6%. ESI-MS (m/z, %) 519.20 (M−H) − ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.41 (s, 1H), 9.10 (s, 1H), 8.42 (s, 1H), 8.23 (m, J=3.07, 1H), 7.80 (m, 1H), 7.66 (d, J=8.8, 2H), 7.39 (t, J=9.2, 1H), 6.94 (d, J=9.2, 2H), 5.01 (m, 1H), 3.41 (s, 4H), 2.81 (s, 3H), 2.54 (s, 4H), 2.46 (s, 2H), 2.05 (s, 4H), 1.70 (d, J=4.4, 2H) ppm. 
     Example 97 
     The Preparation of 9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-8-(pyridin-3-yl)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-pyridinyl isothiocyanate (1.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 64.3%. ESI-MS (m/z,%) 468.23 (M−H) − ;  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.40 (s, 1H), 9.11 (s, 1H), 8.97 (d, J=2.0, 1H), 8.40 (s, 1H), 8.35 (d, J=8.4, 1H), 8.20 (d, J=4.4, 1H), 7.66 (d, J=8.8, 2H), 7.36 (m, J=6.6, 1H), 6.93 (d, J=8.8, 2H), 5.02 (m, 1H), 3.20 (s, 4H), 2.73 (s, 3H), 2.47 (s, 4H), 2.06 (s, 4H), 1.71 (s, 2H), 1.23 (s, 2H) ppm. 
     Example 98 
     The Preparation of 4-(9-cyclopentylamino-8-(pyridin-3-ylamino)-9H-purin-2-ylamino)-N-(4-methylpiperidin-1-yl)benzamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-14 (2.46 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-pyridinyl isothiocyanate (1.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-14. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70.3%. ESI-MS (m/z, %) 511.23 (M−H) − ;  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.66 (d, J=11.2, 2H), 9.48 (s, 1H), 8.99 (d, J=2.0, 1H), 8.49 (s, 1H), 8.36 (d, J=7.6, 1H), 8.22 (d, J=4.0, 1H), 7.86 (d, J=8.8, 2H), 7.75 (d, J=8.4, 2H), 7.39 (m, J=4.3, 1H), 5.06 (m, 1H), 3.21 (s, 4H), 2.78 (s, 3H), 2.51 (s, 4H), 2.10 (s, 4H), 1.76 (s, 2H), 1.24 (s, 2H) ppm. 
     Example 99 
     The Preparation of N-(3-(9-isopropyl-8-phenylamino-9H-purin-2-ylamino)phenyl)acrylamide 
     
       
                 
         
             
             
         
      
     
     Compound 5-16 (1.87 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-16. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65.5%. ESI-MS (m/z, %) 414.23 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ 10.05 (s, 1H), 9.29 (s, 1H), 9.02 (s, 1H), 8.40 (s, 1H), 8.02 (s, 1H), 7.84 (d, J=8.0, 2H), 7.57 (d, J=6.8, 1H), 7.34 (t, J=7.2, 2H), 7.20 (t, J=7.4, 2H), 7.00 (t, J=7.2, 1H), 6.49 (m, J=9.1, 1H), 6.26 (d, J=16.8, 1H), 5.74 (d, J=10.0, 1H), 4.90 (m, 1H), 1.68 (d, J=6.8, 6H) ppm. 
     Example 100 
     The Preparation of 9-isopropylamino-2-(4-(2-morpholinoethoxy)phenylamino))-8-phenylamino-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-17 (2.23 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-17. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70.5%. ESI-MS (m/z, %) 474.26 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.08 (s, 1H), 8.30 (s, 1H), 8.01 (s, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.71 (d, J=9.2 Hz, 2H), 7.30 (m, 2H), 7.17 (m, 3H), 4.84 (m, 1H), 4.04 (m, 2H), 3.84 (m, 4H), 3.24 (br, 4H), 2.81 (m, 2H), 1.63 (d, J=6.8 Hz, 6H) ppm. 
     Example 101 
     The Preparation of 9-isopropylamino-2-(4-(3-(4-methylpiperazin-1-yl)propylamino)phenylamino)-8-phenylamino-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-18 (2.39 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-18. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69.1%. ESI-MS (m/z, %) 500.29 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.09 (s, 1H), 8.56 (s, 1H), 7.83 (s, 1H), 7.69 (s, 1H), 7.53 (m, 2H), 7.36 (m, 4H), 6.96 (m, 3H), 4.95 (m, 1H), 3.44 (m, 2H), 3.11 (m, 2H), 2.95 (m, 8H), 2.41 (s, 3H), 1.68 (m, 2H), 1.62 (d, J=6.8 Hz, 6H) ppm. 
     Example 102 
     The Preparation of 8-(6-chloropyrimidin-3-yl)-9-isopropylamino-2-(4-(3-(4-methylpiperazin-1-yl)propylamino)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-7 (2.05 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 2-chloro-5-pyridinyl isothiocyanate (1.3 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-7. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69.8%. ESI-MS (m/z, %) 476.29 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.65 (s, 1H), 9.21 (s, 1H), 8.85 (s, 1H), 8.44 (d, J=6.8 Hz, 2H), 7.68 (d, J=8.0 Hz, 2H), 7.49 (d, J=8.8 Hz, 1H), 6.96 (d, J=8.0 Hz, 2H), 4.96 (m, 1H), 3.71 (m, 2H), 3.47 (m, 2H), 3.15 (br, 2H), 3.03 (m, 2H), 2.82 (s, 2H), 1.67 (d, J=6.4 Hz, 6H) ppm. 
     Example 103 
     The Preparation of 8-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-9-isopropyl-2-(4-morpholinophenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-19 (1.97 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (0.9 ml). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-19. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 70.6%. ESI-MS (m/z, %) 586.27 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ 9.01 (d, J=7.2 Hz, 2H), 8.37 (s, 1H), 8.08 (d, J=2.4 Hz, 1H), 7.67 (m, 3H), 7.46 (m, 1H), 7.31 (m, 2H), 7.20 (m, 2H), 6.91 (d, J=9.2 Hz, 2H), 5.21 (s, 2H), 4.83 (m, 1H), 3.74 (m, 4H), 3.03 (m, 4H), 1.67 (d, J=6.4 Hz, 6H) ppm. 
     Example 104 
     The Preparation of 8-(4-bromophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 4-bromophenyl isothiocyanate (1.65 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66.7%. ESI-MS (m/z, %) 548.18 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.22 (s, 1H), 9.09 (s, 1H), 8.39 (s, 1H), 7.83 (d, J=9.2 Hz, 2H), 7.65 (d, J=7.0 Hz, 2H), 7.50 (d, J=9.2 Hz, 2H), 6.93 (d, J=8.8 Hz, 2H), 4.95 (m, 1H), 3.27-3.02 (m, 4H), 2.75 (m, 4H), 2.45 (s, 3H), 2.05 (m, 4H), 1.68 (m, 2H), 1.23 (m, 2H). 
     Example 105 
     The Preparation of 8-(3-nitrophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-nitrophenyl isothiocyanate (1.50 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65.4%. ESI-MS (m/z, %) 514.23 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.75 (s, 1H), 9.23 (s, 1H), 8.87 (s, 1H), 8.45 (s, 1H), 8.32 (d, J=7.6 Hz, 1H), 7.84 (d, J=7.2 Hz, 1H), 7.65 (m, 3H), 6.95 (d, J=8.8 Hz, 2H), 5.04 (m, 1H), 3.72 (m, 2H), 3.49 (m, 2H), 3.16 (m, 2H), 2.99 (m, 2H), 2.83 (s, 3H), 2.45 (m, 2H), 2.06 (m, 4H), 1.71 (m, 2H). 
     Example 106 
     The Preparation of 8-benzylamino-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and benzyl isothiocyanate (1.45 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 63.9%. ESI-MS (m/z, %) 483.26 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ8.97 (s, 1H), 8.15 (s, 1H), 7.63 (m, 3H), 7.35 (m, 4H), 7.25 (m, 1H), 6.91 (d, J=9.2 Hz, 2H), 4.75 (m, 1H), 4.56 (d, J=8.0 Hz, 2H), 3.67 (m, 2H), 3.44 (m, 2H), 3.16 (m, 2H), 2.97 (m, 2H), 2.82 (s, 3H), 2.38 (m, 2H), 1.99 (m, 4H), 1.65 (m, 2H). 
     Example 107 
     The Preparation of 8-(3-ethynylphenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-ethynylphenyl isothiocyanate (1.34 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69.5%. ESI-MS (m/z, %) 493.28 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.26 (s, 1H), 9.13 (s, 1H), 8.43 (s, 1H), 8.09 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.67 (d, J=8.4 Hz, 2H), 7.34 (m, 1H), 7.09 (d, J=7.2 Hz, 1H), 6.94 (d, J=10.8 Hz, 2H), 5.00 (m, 1H), 4.20 (s, 1H), 3.67 (m, 2H), 3.47 (m, 2H), 3.17 (m, 2H), 3.00 (m, 2H), 2.78 (s, 3H), 2.46 (m, 2H), 2.05 (m, 4H), 1.71 (m, 2H). 
     Example 108 
     The Preparation of 8-(2-fluoro-4-bromophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 2-fluoro-4-bromophenyl isothiocyanate (1.60 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69.7%. ESI-MS (m/z, %) 565.20 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.06 (s, 1H), 8.93 (s, 1H), 8.35 (s, 1H), 7.85 (m, 1H), 7.61 (m, 3H), 7.40 (d, J=8.4 Hz, 1H), 8.67 (d, J=9.2 Hz, 2H), 4.88 (m, 1H), 3.10 (m, 4H), 2.62 (m, 4H), 2.43 (m, 2H), 2.34 (s, 3H), 2.03 (m, 4H), 1.68 (m, 2H). 
     Example 109 
     The Preparation of 8-phenylamino-9-cyclopentyl-2-(4-(4-morpholinylmethyl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-20 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and phenyl isothiocyanate (1.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69.9%. ESI-MS (m/z, %) 470.27 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.57 (s, 1H), 9.16 (s, 1H), 8.45 (s, 1H), 7.91 (s, 1H), 7.86 (d, J=8.0 Hz, 2H), 7.76 (s, 1H), 7.47 (s, 1H), 7.38 (m, 2H), 7.22 (s, 1H), 7.03 (m, 1H), 5.04 (m, 1H), 4.10 (m, 2H), 3.70 (m, 4H), 3.15 (m, 2H), 2.37 (m, 2H), 2.05 (m, 4H), 1.75 (m, 2H), 1.29 (m, 2H). 
     Example 110 
     The Preparation of 8-(3-fluorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (4.9 ml), and 3-fluorophenyl isothiocyanate (1.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67.4%. ESI-MS (m/z, %) 487.25 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.42 (s, 1H), 9.13 (s, 1H), 8.42 (s, 1H), 7.92 (d, J=12.0 Hz, 1H), 7.67 (d, J=9.2 Hz, 2H), 7.59 (d, J=8.0 Hz, 1H), 7.35 (m, 1H), 6.94 (d, J=8.8 Hz, 2H), 6.79 (m, 1H), 5.02 (m, 1H), 3.68 (m, 2H), 3.44 (m, 2H), 3.18 (m, 2H), 3.01 (m, 2H), 2.81 (s, 3H), 2.44 (m, 2H), 2.05 (m, 4H), 1.70 (m, 2H). 
     Example 111 
     The Preparation of 8-phenylamino-9-cyclohexyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-21 (1.53 g) was dissolved into dichloromethane (35 ml). To the mixture were successively added EDCI (1.54 g), N,N-diisopropylethylamine (3.31 ml), and phenyl isothiocyanate (0.56 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-21. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69.4%. ESI-MS (m/z, %) 483.25 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.04 (s, 1H), 8.99 (s, 1H), 8.34 (s, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.67 (d, J=8.8 Hz, 2H), 7.33 (m, 2H), 6.98 (m, 1H), 6.87 (d, J=8.4 Hz, 2H), 4.74 (m, 1H), 3.05 (m, 4H), 2.61 (m, 2H), 5.47 (m, 4H), 2.23 (s, 3H), 1.91 (m, 2H), 1.81 (m, 3H), 1.44 (m, 2H), 1.34 (m, 1H). 
     Example 112 
     The Preparation of 8-(3-hydroxyphenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.1 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine-2.1 ml), and 3-hydroxyphenyl isothiocyanate (1.05 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70.4%. ESI-MS (m/z, %) 485.25 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.36 (s, 1H), 9.07 (s, 1H), 8.93 (s, 1H), 8.35 (s, 1H), 7.67 (d, J=9.2 Hz, 2H), 7.38 (s, 1H), 7.16 (d, J=9.2 Hz, 1H), 7.08 (m, 1H), 6.93 (d, J=9.2 Hz, 2H), 6.39 (s, 1H), 4.96 (m, 1H), 3.43 (m, 2H), 3.34 (m, 2H), 3.16 (m, 4H), 2.75 (s, 1H), 2.46 (m, 2H), 2.04 (m, 4H), 1.69 (m, 2H). 
     Example 113 
     The Preparation of 8-(3-chlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (70 ml). To the mixture were successively added EDCI (2.7 g), N,N-diisopropylethylamine (2.5 ml), and 3-chlorophenyl isothiocyanate (1.42 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 71.7%. ESI-MS (m/z, %) 503.25 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.38 (s, 1H), 9.13 (s, 1H), 8.44 (s, 1H), 8.11 (s, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.35 (m, 1H), 7.02 (m, 1H), 6.94 (d, J=8.8 Hz, 2H), 5.01 (m, 1H), 3.43 (m, 4H), 3.10 (m, 4H), 2.82 (s, 3H), 2.45 (m, 2H), 2.05 (m, 4H), 1.70 (m, 2H) ppm. 
     Example 114 
     The Preparation of 8-(3-methylphenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.1 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine 2.1 ml), and 3-methylphenyl isothiocyanate (1.0 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 72.7%. ESI-MS (m/z, %) 483.25 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.08 (s, 1H), 9.02 (s, 1H), 8.37 (s, 1H), 7.68-7.62 (m, 4H), 7.22 (m, 1H), 6.93 (d, J=8.8 Hz, 2H), 6.80 (d, J=7.6 Hz, 1H), 4.99 (m, 1H), 3.67 (m, 2H), 3.44 (m, 2H), 3.03 (m, 4H), 2.81 (s, 3H), 2.45 (m, 2H), 2.31 (s, 3H), 2.04 (m, 4H), 1.69 (m, 2H) ppm. 
     Example 115 
     The Preparation of 8-(3,5-dichlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.55 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (2.67 g), N,N-diisopropylethylamine 2.7 ml), and 3,5-dichlorophenyl isothiocyanate (1.7 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 73.7%. ESI-MS (m/z, %) 537.25 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.40 (s, 1H), 9.08 (s, 1H), 8.48 (s, 1H), 7.97 (s, 1H), 7.60 (d, J=8.8 Hz, 2H), 7.21 (m, 2H), 6.99 (m, 2H), 4.90 (m, 1H), 3.12 (m, 2H), 3.04 (m, 2H), 2.54 (m, 4H), 2.21 (m, 4H), 2.04 (s, 3H), 1.67 (m, 2H), 1.19 (m, 2H) ppm. 
     Example 116 
     The Preparation of 8-(2,5-difluorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.7 g) was dissolved into dichloromethane (100 ml). To the mixture were successively added EDCI (2.8 g), N,N-diisopropylethylamine (3 ml), and 2,5-difluorophenyl isothiocyanate (1.5 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70.6%. ESI-MS (m/z, %) 505.25 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.16 (s, 1H), 9.06 (s, 1H), 8.43 (s, 1H), 7.91 (m, 1H), 7.56 (m, 2H), 7.32 (m, 1H), 6.91 (m, 3H), 4.92 (m, 1H), 3.45 (m, 4H), 3.23-3.03 (m, 4H), 2.80 (s, 3H), 2.42 (m, 2H), 2.03 (m, 4H), 1.68 (m, 2H) ppm. 
     Example 117 
     The Preparation of 8-phenylamino-9-cyclopentyl-2-(4-(2-methoxyethoxy)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-22 (3.2 g) was dissolved into dichloromethane (90 ml). To the mixture were successively added EDCI (3.6 g), N,N-diisopropylethylamine 3.3 ml), and phenyl isothiocyanate (1.52 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 75.3%. ESI-MS (m/z, %) 443.25 (M−H) − .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.20 (s, 1H), 9.06 (s, 1H), 8.36 (s, 1H), 7.86 (d, J=9.6 Hz, 2H), 7.65 (d, J=8.0 Hz, 2H), 7.34 (m, 2H), 6.97 (m, 1H), 6.85 (d, J=8.0 Hz, 2H), 5.05 (m, 1H), 4.04 (m, 2H), 3.64 (m, 2H), 3.31 (s, 3H), 2.43 (m, 2H), 2.03 (m, 4H), 1.68 (m, 2H) ppm. 
     Example 118 
     The Preparation of 8-(2,4,5-trichlorophenylamino)-9-cyclopentyl-2-(4-(4-methyl piperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.1 g) was dissolved into dichloromethane (60 ml). To the mixture were successively added EDCI (2.15 g), N,N-diisopropylethylamine (2 ml), and 2,4,5-trichlorophenyl isothiocyanate (1.6 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. After cooling the mixture, a solid was separated out and purified by recrystallization to obtain a pale yellow solid in a yield of 74.3%. ESI-MS (m/z, %) 571.25 (M−H) + ;  1 H NMR (400 MHz, DMSO-d 6 ): δ9.09 (s, 1H), 9.01 (s, 1H), 8.27 (s, 1H), 7.64 (m, 2H), 7.12 (m, 1H), 6.89 (d, J=8.4 Hz, 2H), 6.78 (d, J=7.2 Hz, 1H), 4.93 (m, 1H), 3.64 (m, 2H), 3.41 (m, 2H), 3.13 (m, 4H), 2.75 (s, 3H), 2.43 (m, 2H), 2.14 (m, 4H), 1.65 (m, 2H) ppm. 
     Example 119 
     The Preparation of 8-phenylamino-9-cyclopentyl-2-(4-((4-ethylpiperazin-1-yl)methyl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-23 (4.6 g) was dissolved into dichloromethane (100 ml). To the mixture were successively added EDCI (1.67 g), N,N-diisopropylethylamine 1.2 ml), and phenyl isothiocyanate (0.79 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-25. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65.1%. ESI-MS (m/z, %) 497.25 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.25 (s, 1H), 9.06 (s, 1H), 8.40 (s, 1H), 7.82 (d, J=8.0 Hz, 2H), 7.71 (d, J=8.4 Hz, 2H), 7.34 (m, 2H), 7.15 (d, J=8.4 Hz, 2H), 6.99 (m, 1H), 4.97 (m, 1H), 3.38 (s, 2H), 2.47-2.29 (m, 12H), 2.05 (m, 2H), 1.71 (m, 2H), 0.97 (m, 3H) ppm. 
     Example 120 
     The Preparation of 8-phenylamino-9-cyclopentyl-2-(4-((4-methylpiperazin-1-yl)methyl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-25 (4.6 g) was dissolved into dichloromethane (100 ml). To the mixture were successively added EDCI (1.74 g), N,N-diisopropylethylamine 1.2 ml), and phenyl isothiocyanate (0.82 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-25. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 71.8%. ESI-MS (m/z, %) 483.25 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.25 (s, 1H), 9.05 (s, 1H), 8.39 (s, 1H), 7.82 (d, J=8.0 Hz, 2H), 7.70 (d, J=8.0 Hz, 2H), 7.33 (m, 2H), 7.15 (d, J=8.0 Hz, 2H), 6.99 (m, 1H), 4.97 (m, 2H), 3.38 (m, 4H), 2.50 (m, 4H), 2.33 (m, 4H), 2.14 (s, 3H), 2.05 (m, 4H), 1.71 (m, 2H) ppm. 
     Example 121 
     The Preparation of 8-(2,5-dichlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (1.3 g) was dissolved into dichloromethane (60 ml). To the mixture were successively added EDCI (0.8 g), N,N-diisopropylethylamine (2 ml), and 2,5-dichlorophenyl isothiocyanate (0.72 g). The mixture was stirred at room temperature for half an hour, and refluxed for 16 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. Purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 64.3%. ESI-MS (m/z, %) 537.23 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.02 (s, 1H), 8.62 (s, 1H), 8.37 (s, 1H), 7.91 (s, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.49 (d, J=7.6 Hz, 1H), 7.10 (m, 1H), 6.86 (d, J=9.2 Hz, 2H), 4.91 (m, 1H), 3.04 (m, 4H), 2.45 (m, 4H), 2.22 (s, 3H), 2.00 (m, 4H), 1.67 (m, 2H) ppm. 
     Example 122 
     The Preparation of 8-(2,6-dichlorophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (40 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (5 ml), and 2,4-dichlorophenyl isothiocyanate (1.5 g). The mixture was stirred at room temperature for half an hour, and refluxed for 12 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. Purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 67.4%. ESI-MS (m/z, %) 537.22 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.01 (s, 1H), 8.70 (s, 1H), 8.26 (s, 1H), 7.59 (d, J=8.4 Hz, 4H), 7.39 (s, 1H), 6.86 (d, J=8.8 Hz, 2H), 4.90 (m, 1H), 3.04 (m, 4H), 2.45 (m, 6H), 2.22 (s, 3H), 2.00 (m, 4H), 1.67 (m, 2H) ppm. 
     Example 123 
     The Preparation of 8-(3-bromophenylamino)-9-cyclopentyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-9 (2.2 g) was dissolved into dichloromethane (40 ml). To the mixture were successively added EDCI (2.3 g), N,N-diisopropylethylamine (5 ml), and 3-bromophenyl isothiocyanate (1.54 g). The mixture was stirred at room temperature for half an hour, and refluxed for 12 hours. TLC detection indicated the completion of the reaction of the starting material 5-9. Purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 69.5%. ESI-MS (m/z, %) 547.12 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.34 (s, 1H), 9.13 (s, 1H), 8.44 (s, 1H), 8.22 (s, 1H), 7.83 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.8 Hz, 2H), 7.29 (m, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.94 (d, J=9.2 Hz, 2H), 5.01 (m, 1H), 3.65 (m, 4H), 3.28 (m, 4H), 2.81 (s, 3H), 2.45 (m, 2H), 2.05 (m, 4H), 1.70 (m, 2H) ppm. 
     Example 124 
     The Preparation of 8-phenylamino-9-cyclohexylmethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-9H-purine 
     
       
                 
         
             
             
         
      
     
     Compound 5-23 (2.0 g) was dissolved into dichloromethane (25 ml). To the mixture were successively added EDCI (1.92 g), N,N-diisopropylethylamine (2.25 ml), and phenyl isothiocyanate (0.82 g). The mixture was stirred at room temperature for half an hour, and refluxed for 10 hours. TLC detection indicated the completion of the reaction of the starting material 5-23. After cooling the mixture, purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66.2%. ESI-MS (m/z, %) 497.26 (M−H) + .  1 H NMR (400 MHz, DMSO-d 6 ): δ9.04 (s, 1H), 8.59 (s, 1H), 8.30 (s, 1H), 7.81 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.8 Hz, 2H), 7.31 (m, 2H), 6.88 (m, 1H), 6.75 (d, J=8.4 Hz, 2H), 3.78 (m, 2H), 3.05 (m, 4H), 1.82-1.54 (m, 7H), 1.36-1.18 (m, 4H), 1.12-1.00 (m, 2H). 
     Assay 
     Biological Assessment 
     Assay 1: The Test of the Arylamino Purine Derivatives for the Kinase Inhibitory Activity 
     The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the γ phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRα and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC 50  value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 μM. The IC 50  value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 
     1. Materials 
     20 mM 3-(N-morpholinyl)propylsulfonic acid (MOPS); 
     1 mM Ethylenediaminetetraacetic acid (EDTA); 
     0.01% Polyethylene glycol lauryl ether (Brij-35); 
     5% Glycerol; 
     0.1% Mercaptoethanol; 
     1 mg/ml Bovine serum albumin (BSA); 
     10 mM Manganous dichloride solution (MnCl2); 
     0.1 mg/ml Glutamic acid/tyrosine (4:1) polymerized polypeptide (poly(Glu,Tyr)4:1) (the substrate for wild type and L858R mono mutant type EGFRs, c-KIT and PDGFRα); 
     250 μM polypeptide GGMEDIYFEFMGGKKK (the substrate for L858R/T790M double mutant type EGFR); 
     250 μM polypeptide KKKSPGEYVNIEFG (the substrate for ALK and MET); 
     250 μM polypeptide KVEKIGEGTY GVVYK (the substrate for BTK and c-SRC); 
     0.33 mg/ml myelin basic protein (the substrate for VEGFR2); 
     50 μM EAIYAAPFAKKK (the substrate for FLT3); 
     10 mM a solution of magnesium acetate and γ- 33  P-ATP; 
     Terminating buffer solution (3% buffer solution of phosphate salt); 
     Washing buffer solution (75 mM phosphate solution); 
     Methanol; 
     Filtermat A membrane; 
     EGFRs (including wild type, L858R mono mutant type and L858R/T790M double mutant type EGFRs), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRα, FLT3 kinase, and the tested compounds. 
     2. Procedure 
     To a reaction tube were successively added the buffer solution (8 mM MOPS, pH 7.0, 0.2 mM EDTA, 10 mM MnCl 2 ), the kinase to be tested (5-10 mU) (EGFR/ALK/BTK/c-KIT/c-SRC/MET/PDGFRα/VEGFR2), the substrate for the kinase to be tested (a reference material), 10 mM of the solution of magnesium acetate and γ- 33  P-ATP, and different concentrations of the tested compounds. The reaction was started by adding MgATP (the final concentration of ATP is the Km value of the corresponding kinase, i.e., 10 μM for EGFRWild Type, 200 μM for EGFR L858R, 45 μM for EGFR L858R/T790M, 200 μM for ALK, 200 μM for BTK, 200 μM for c-KIT, 90 μM for VEGFR2, 200 μM for c-SRC, 45 μM for MET, 120 μM for PDGFRα, and 200 μM for FLT3), and incubated at room temperature for 40 minutes. The reaction was terminated with 54 of the 3% phosphate buffer solution. 10 μL of the reaction liquid was titrated on the Filtermat A membrane. The membrane was washed with 75 mM of the phosphate solution thrice (5 minutes each time), and then with methanol once, and finally dried. The membrane was subjected to a scintillation counting. The value of the scintillation counting reflected the phosphorylation level of the substrate and therefore could characterize the inhibition of the kinase activity. 
     3. Results 
     Through the above procedures, the inhibitory activities of the present compounds were tested for the kinases EGFRs (comprising wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRα, and FLT3. The kinase inhibitory activities (IC 50  values) of the tested compounds for EGFRs (comprising wild type, L858R mutant type and L858R/T790M double mutant type) and VEGFR2 are shown in Table 1. The activity inhibition ratio (%) of the tested compounds at 10 μM for the kinases ALK, BTK, c-KIT, c-SRC, MET, PDGFRα, and FLT3 are shown in Table 2. 
     The results indicated that the tested compounds had strong inhibitory activities on the wild type, L858R mutant type and L858R/T790M double mutant type EGFRs, and some of the tested compounds also had good inhibitory activities on VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRα, FLT3 kinases. 
     
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 1 
               
             
             
               
                   
                   
               
               
                   
                 EGFR(IC 50 , μM) 
                   
               
             
          
           
               
                 Tested 
                 Wild 
                   
                 L858R/ 
                   
               
               
                 Compounds 
                 Type 
                 L858R 
                 T790M 
                 VEGFR2(IC 50 , μM) 
               
               
                   
               
             
          
           
               
                 8-1 
                 0.003 
                 0.008 
                 0.090 
                 &gt;1.000 
               
               
                 8-2 
                 0.002 
                 0.001 
                 &lt;0.001 
                 &gt;1.000 
               
               
                 8-3 
                 0.025 
                 0.060 
                 0.245 
                 &gt;1.000 
               
               
                 8-4 
                 0.030 
                 0.018 
                 0.046 
                 &gt;1.000 
               
               
                 8-5 
                 0.004 
                 0.005 
                 0.006 
                 &gt;1.000 
               
               
                 8-6 
                 0.001 
                 0.0004 
                 0.018 
                 &gt;1.000 
               
               
                 8-7 
                 0.007 
                 0.001 
                 0.128 
                 &gt;1.000 
               
               
                 8-9 
                 &lt;0.001 
                 0.0004 
                 0.006 
                 &gt;1.000 
               
               
                 8-10 
                 0.005 
                 0.005 
                 0.046 
                 &gt;1.000 
               
               
                 8-11 
                 0.007 
                 0.004 
                 0.005 
                 0.140 
               
               
                 8-12 
                 0.004 
                 0.003 
                 0.003 
                 0.050 
               
               
                 8-13 
                 0.004 
                 0.003 
                 0.009 
                 &gt;1.000 
               
               
                 8-15 
                 0.003 
                 0.001 
                 0.015 
                 0.004 
               
               
                 8-16 
                 0.003 
                 0.001 
                 0.012 
                 &gt;1.000 
               
               
                 8-17 
                 0.004 
                 0.001 
                 0.004 
                 &gt;1.000 
               
               
                 8-18 
                 0.030 
                 0.005 
                 0.057 
                 0.021 
               
               
                 8-19 
                 0.005 
                 0.004 
                 0.004 
                 &gt;1.000 
               
               
                 8-21 
                 0.011 
                 0.005 
                 0.005 
                 &gt;1.000 
               
               
                 8-22 
                 0.117 
                 0.010 
                 0.087 
                 &gt;1.000 
               
               
                 8-23 
                 0.007 
                 0.002 
                 0.041 
                 &gt;1.000 
               
               
                 8-24 
                 0.012 
                 0.003 
                 0.522 
                 &gt;1.000 
               
               
                 8-25 
                 0.029 
                 0.005 
                 0.458 
                 &gt;1.000 
               
               
                 8-26 
                 &lt;0.001 
                 0.0004 
                 &lt;0.001 
                 0.007 
               
               
                 8-27 
                 0.034 
                 0.005 
                 0.054 
                 0.009 
               
               
                 8-29 
                 0.031 
                 0.004 
                 0.064 
                 &gt;1.000 
               
               
                 8-30 
                 0.015 
                 0.005 
                 0.228 
                 &gt;1.000 
               
               
                 8-38 
                 0.002 
                 0.0006 
                 0.037 
                 &gt;1.000 
               
               
                   
               
             
          
         
       
     
                                                                                             TABLE 2                   Tested   The kinase activity inhibitory rate (%) by the tested       Com-   compounds at 10 μM            pounds   ALK   BTK   c-KIT   c-SRC   MET   PDGFRα   FLT3                    8-1    23   46   26   11   83   43   85       8-2    63   98   90   99   100   84   78       8-3    16   11   54   67   2   20   0       8-4    64   45   23   12   67   16   43       8-5    54   78   54   32   64   19   35       8-6    15   46   21   82   14   39   56       8-7    61   12   8   28   0   9   0       8-9    36   88   96   98   67   88   76       8-10   45   32   3   23   64   87   87       8-11   33   77   67   98   93   58   67       8-12   80   78   82   98   93   55   56       8-13   78   45   87   31   100   90   89       8-15   40   95   94   97   45   94   90       8-16   17   57   62   90   93   39   45       8-17   35   100   89   99   52   72   86       8-18   13   56   76   93   7   60   75       8-19   90   71   12   97   97   34   43       8-21   97   92   101   98   99   100   78       8-22   70   63   10   98   69   43   87       8-23   3   30   26   83   1   28   68       8-24   8   14   48   75   0   29   75       8-25   13   45   8   78   0   21   32       8-26   71   99   94   99   86   95   86       8-27   30   74   93   98   36   68   83       8-29   15   60   36   97   50   42   99       8-30   8   25   0   67   0   21   43       8-38   22   93   63   93   74   55   86                    
Assay 2: The Test of the Arylamino Purine Derivatives for the In-Vitro Tumor Cell Proliferation Inhibition
 
     The object of this assay was to test the inventive compounds for the inhibitory activity of in-vitro tumor cell proliferation. The MTT (tetreamethyl-azo-zole-salt) colorimetric method was used in this assay. 
     1. Materials 
     1.1 Main Agents 
     RPMI-1640, fetal bovine serum, pancreatin and the like were purchased from Gibco BRL Company (Invitrogen Corporation, USA). The IMDM culture medium was purchased from ATCC (American Type Culture Collection). Tetreamethyl-azo-zole-salt (MTT) and dimethylsulfoxide (DMSO) were the products available from Sigma Company (USA). The arylamino purine derivatives were synthesized by the present inventors. In this in-vitro assay, 100% DMSO was formulated into a 10 mM stocking solution and preserved in a freezer at −20° C. and in dark place for use. The stocking solution was diluted with a complete culture solution to a desired concentration immediately before use. 
     1.2 Cell Lines and their Culturing 
     Human non-small cell lung carcinoma cell strains HCC827, PC-9, H1975 (EGFR L858R/T790M mutation) and H292 (EGFR WT), and other tumor type cell strains, including human acute myelogenous leukemia cell strain MV4-11, human chronic granulocytic leukemia cell strain K562, human squamous cell carcinoma cell strain A431, human breast carcinoma cell strains MDA-MB-468 and BT 474, human colon cancer cell strains SW480, HCT116 and SW620, human liver cancer cell strain Hep G2, human gastric cancer cell strain MK-45, and human malignant melanoma cell strain A375 used in this assay were all purchased from ATCC company, USA and kept in the laboratory. All of the above-mentioned non-small cell lung carcinoma cell strains and the breast carcinoma cell strain BT 474 were cultured with a RPMI-1640 complete culture medium containing 10% fetal bovine serum, 100 U/ml penicillin and 100 μg/ml streptomycin under 5% CO2 and at 37° C. The other cell strains were cultured with a DMEM complete culture medium containing 10% fetal bovine serum (having a MV4-11 cell content of 20%), 100 U/ml penicillin and 100 μg/ml streptomycin under 5% CO2 and 37° C. 
     2. Procedure 
     A cell suspension having a cell concentration of 1-2×10 4  cells/ml was treated with a complete cell culture solution to adjust the cell concentration, wherein the cell concentrations for HCC827 and MV4-11 were adjusted to 6×10 4  cells/ml and 1×10 5  cells/ml respectively. The cell suspension was inoculated in a 96-well plate with 200 μl cell suspension/well and cultured overnight. Next day, the supernatant was drawn off and discarded. Then, the cells were treated with the tested compounds in a gradient concentration respectively. In the meanwhile, a negative control group free of the drug substance and an isovolumetric solvent control group (having a DMSO concentration of 1%) were used. The triplicate wells were used for each of dose groups. The culturing was conducted at 37° C. under 5% CO2. After 72 hours, 200 MTT agent having a concentration of 5 mg/ml was added to each of wells. The culturing was further conducted for 2-4 hours. The supernatant was discarded. Then 1504 DMSO was added to each of wells. The contents in the well were mixed homogenously by oscillation for 15 minutes. The absorbance (A) value was measured with a microplate reader at λ=570 nm (the A value is in the direct proportion to the number of living cells) and averaged. The relative cell proliferation inhibitory rate is (A 570 control-group −A 570 dose-group )/A 570 control-group ×100%. The assay was repeated for at least three times. The data was expressed as number average. The statistical data were analyzed using t-test. P&lt;0.05 was considered significant. The cell proliferation inhibition of the following compounds was expressed as IC50 or inhibitory rate. 
     3. Results 
     According to the above-mentioned procedure, human non-small cell lung carcinoma cell strains HCC827, PC-9 (EGFR delE746-A750 deletion mutation), H1975 (EGFR L858R/T790M mutation) and H292 (EGFR WT), and other tumor type cell strains, including human acute myelogenous leukemia cell strain MV4-11, human chronic granulocytic leukemia cell strain K562, human squamous cell carcinoma cell strain A431, human breast carcinoma cell strains MDA-MB-468 and BT 474, human colon cancer cell strains SW480, HCT116 and SW620, human liver cancer cell strain Hep G2, human gastric cancer cell strain MK-45, and human malignant melanoma cell strain A375 were subjected to the proliferation inhibition activity test. 
     The proliferation inhibitory activities (IC 50 ) of the tested compounds for human non-small cell lung carcinoma cell strains HCC827, PC-9 and H1975 are shown in the table 3. The proliferation inhibitory activities (IC 50 ) of the tested compounds for human tumor cell strains MV4-11, K562, A431, MDA-MB-468, BT474, SW480, HCT116, HepG2, SW620, MK-45, H292 and A375 are shown in the tables 4 and 5. The results indicated that the tested compounds had strong inhibitory activities on the cell strains HCC827 and PC-9 which were sensitive to Gefitinib; some of the tested compounds also had a good inhibitory activity on the cell strain H1975 which was resistant to Gefitinib; and in addition, some of the tested compounds also had good inhibitory activities on the other tumor cell strains including human MV4-11, K562, A431, MDA-MB-468, BT474, SW480, HCT116, HepG2, SW620, MK-45, H292, A375 and the like. 
     
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 3 
               
               
                   
                   
               
               
                   
                 Tested 
                 HCC827 
                 PC-9 
                 H1975 
               
               
                   
                 Compounds 
                 (IC 50 , μM) 
                 (IC 50 , μM) 
                 (IC 50 , μM) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 8-1  
                 0.0020 
                 0.1047 
                 7.6 
               
               
                   
                 8-2  
                 0.0013 
                 0.5580 
                 &gt;10 
               
               
                   
                 8-3  
                 &gt;1 
                 &gt;1 
                 &gt;10 
               
               
                   
                 8-4  
                 0.0030 
                 0.0680 
                 0.86 
               
               
                   
                 8-5  
                 0.0013 
                 0.5580 
                 &gt;10 
               
               
                   
                 8-6  
                 0.0002 
                 0.0137 
                 &gt;10 
               
               
                   
                 8-7  
                 0.0075 
                 0.0121 
                 &gt;10 
               
               
                   
                 8-9  
                 0.0042 
                 0.0723 
                 &gt;10 
               
               
                   
                 8-10 
                 0.0001 
                 0.0009 
                 2 
               
               
                   
                 8-11 
                 0.0002 
                 0.0002 
                 1.726 
               
               
                   
                 8-12 
                 0.0002 
                 0.0002 
                 1.929 
               
               
                   
                 8-13 
                 0.0002 
                 0.0003 
                 2 
               
               
                   
                 8-15 
                 0.0002 
                 0.0064 
                 &gt;10 
               
               
                   
                 8-16 
                 0.0002 
                 0.0168 
                 1.822 
               
               
                   
                 8-17 
                 0.0002 
                 0.0025 
                 1.904 
               
               
                   
                 8-18 
                 0.1172 
                 0.0349 
                 &gt;10 
               
               
                   
                 8-19 
                 0.9116 
                 0.4591 
                 7.32 
               
               
                   
                 8-21 
                 0.0516 
                 0.0859 
                 7.312 
               
               
                   
                 8-22 
                 &gt;1 
                 2.7947 
                 &gt;10 
               
               
                   
                 8-23 
                 0.0002 
                 0.0359 
                 &gt;10 
               
               
                   
                 8-24 
                 0.0002 
                 0.0060 
                 &gt;10 
               
               
                   
                 8-25 
                 0.0528 
                 0.2582 
                 &gt;10 
               
               
                   
                 8-26 
                 0.0011 
                 0.0002 
                 0.369 
               
               
                   
                 8-27 
                 0.0823 
                 0.1149 
                 &gt;10 
               
               
                   
                 8-29 
                 0.0072 
                 0.0100 
                 &gt;10 
               
               
                   
                 8-30 
                 0.4828 
                 0.0551 
                 &gt;10 
               
               
                   
                 8-34 
                 0.0631 
                 0.4199 
                 6.3076 
               
               
                   
                 8-35 
                 0.0002 
                 0.0015 
                 1.5162 
               
               
                   
                 8-36 
                 0.0002 
                 0.0209 
                 0.8518 
               
               
                   
                 8-37 
                 0.1297 
                 0.3476 
                 &gt;10 
               
               
                   
                 8-38 
                 0.0005 
                 0.0007 
                 0.6445 
               
               
                   
                 8-41 
                 0.0165 
                 0.2092 
                 0.5013 
               
               
                   
                 8-42 
                 4.2614 
                 3.3210 
                 &gt;10 
               
               
                   
                 8-43 
                 0.0003 
                 0.0519 
                 0.2309 
               
               
                   
                 8-44 
                 0.0003 
                 0.0015 
                 0.6947 
               
               
                   
                 8-45 
                 0.0002 
                 0.0097 
                 1.1359 
               
               
                   
                 8-46 
                 0.0003 
                 0.0035 
                 0.7702 
               
               
                   
                 8-47 
                 0.0003 
                 0.0163 
                 0.8844 
               
               
                   
                 8-48 
                 0.0002 
                 0.0262 
                 4.5828 
               
               
                   
                 8-49 
                 0.0003 
                 0.0002 
                 0.3103 
               
               
                   
                 8-50 
                 0.0003 
                 0.0035 
                 0.1822 
               
               
                   
                 8-51 
                 0.0002 
                 0.0095 
                 0.6302 
               
               
                   
                 8-52 
                 0.0003 
                 0.0006 
                 0.2714 
               
               
                   
                 8-53 
                 0.0002 
                 0.0002 
                 0.5516 
               
               
                   
                 8-54 
                 0.0063 
                 0.2045 
                 1.7011 
               
               
                   
                 8-55 
                 0.0002 
                 0.0010 
                 0.3228 
               
               
                   
                 8-56 
                 0.0006 
                 0.0070 
                 &gt;10 
               
               
                   
                 8-57 
                 0.0280 
                 0.1773 
                 &gt;10 
               
               
                   
                 8-58 
                 0.0002 
                 0.0181 
                 0.2521 
               
               
                   
                 8-59 
                 0.0002 
                 0.0021 
                 0.2482 
               
               
                   
                 8-60 
                 0.0002 
                 0.0117 
                 0.4731 
               
               
                   
                 8-61 
                 0.0143 
                 0.1165 
                 4.2103 
               
               
                   
                 8-62 
                 0.0002 
                 0.0091 
                 0.3920 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
               
                   
               
               
                 Tested 
                 MV4-11 
                 K562 
                 A431 
                 MDA-MB-468 
                 BT474 
                 SW480 
               
               
                 Compounds 
                 (IC 50 , μM) 
                 (IC 50 , μM) 
                 (IC 50 , μM) 
                 (IC 50 , μM) 
                 (IC 50 , μM) 
                 (IC 50 , μM) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 8-1  
                 0.089 
                 1.078 
                 2.059 
                 2.059 
                 2.132 
                 5.725 
               
               
                 8-2  
                 1.768 
                 3.734 
                 9.293 
                 6.134 
                 1.859 
                 &gt;10 
               
               
                 8-3  
                 &gt;10 
                 &gt;10 
                 12.9 
                 &gt;10 
                 &gt;10 
                 &gt;10 
               
               
                 8-4  
                 9.772 
                 1.391 
                 1.986 
                 4.766 
                 0.635 
                 &gt;10 
               
               
                 8-5  
                 1.768 
                 3.734 
                 9.293 
                 6.134 
                 1.859 
                 &gt;10 
               
               
                 8-6  
                 2.845 
                 7.354 
                 2.388 
                 2.985 
                 0.597 
                 &gt;10 
               
               
                 8-7  
                 &gt;10 
                 &gt;10 
                 &gt;10 
                 &gt;10 
                 5.818 
                 &gt;10 
               
               
                 8-9  
                 0.235 
                 0.143 
                 1.527 
                 1.321 
                 1.032 
                 &gt;10 
               
               
                 8-10 
                 0.102 
                 0.106 
                 1.582 
                 0.7 
                 0.226 
                 &gt;10 
               
               
                 8-11 
                 3.755 
                 0.366 
                 7.671 
                 1.189 
                 0.575 
                 &gt;10 
               
               
                 8-12 
                 1.711 
                 0.221 
                 2.572 
                 3.215 
                 2.143 
                 &gt;10 
               
               
                 8-13 
                 0.512 
                 0.086 
                 1.293 
                 2.101 
                 0.202 
                 &gt;10 
               
               
                 8-15 
                 0.197 
                 0.303 
                 9.397 
                 2.301 
                 1.918 
                 &gt;10 
               
               
                 8-16 
                 4.799 
                 2.523 
                 5.876 
                 1.959 
                 1.371 
                 6.481 
               
               
                 8-17 
                 0.684 
                 0.003 
                 8.464 
                 0.783 
                 0.635 
                 &gt;10 
               
               
                 8-18 
                 0.183 
                 1.221 
                 6.348 
                 3.174 
                 2.116 
                 &gt;10 
               
               
                 8-19 
                 4.778 
                 2.791 
                 9.316 
                 9.981 
                 4.991 
                 &gt;10 
               
               
                 8-21 
                 0.279 
                 1.335 
                 5.722 
                 0.89 
                 1.589 
                 &gt;10 
               
               
                 8-22 
                 0.283 
                 0.921 
                 5.52 
                 1.725 
                 1.725 
                 &gt;10 
               
               
                 8-23 
                 0.241 
                 5.198 
                 7.037 
                 5.221 
                 6.81 
                 &gt;10 
               
               
                 8-24 
                 0.288 
                 1.422 
                 9.65 
                 9.65 
                 2.412 
                 &gt;10 
               
               
                 8-25 
                 7.896 
                 &gt;10 
                 &gt;10 
                 &gt;10 
                 9.988 
                 &gt;10 
               
               
                 8-26 
                 0.093 
                 0.12 
                 1.046 
                 0.299 
                 0.107 
                 3.438 
               
               
                 8-27 
                 0.088 
                 0.777 
                 2.35 
                 1.959 
                 1.175 
                 2.597 
               
               
                 8-29 
                 0.004 
                 0.24 
                 9.018 
                 8.116 
                 2.255 
                 &gt;10 
               
               
                 8-30 
                 7.962 
                 5.756 
                 &gt;10 
                 &gt;10 
                 4.458 
                 &gt;10 
               
               
                 8-34 
                 0.1248 
                 1.5971 
                 2.5734 
                 3.2589 
                 2.6282 
                 9.9542 
               
               
                 8-35 
                 0.1353 
                 0.2322 
                 0.6351 
                 1.9193 
                 0.1919 
                 5.9306 
               
               
                 8-36 
                 0.0010 
                 0.0760 
                 0.4630 
                 &gt;10 
                 0.6389 
                 8.6758 
               
               
                 8-37 
                 0.1016 
                 0.8882 
                 &gt;10 
                 &gt;10 
                 4.5220 
                 &gt;10 
               
               
                 8-38 
                 0.7297 
                 0.2685 
                 0.1790 
                 0.2805 
                 1.6809 
                 &gt;10 
               
               
                 8-41 
                 1.9710 
                 0.1460 
                 2.7386 
                 4.4875 
                 2.0921 
                 5.3955 
               
               
                 8-42 
                 6.6387 
                 0.9223 
                 2.2395 
                 1.7005 
                 5.1014 
                 &gt;10 
               
               
                 8-43 
                 0.0212 
                 0.1225 
                 0.4844 
                 1.0296 
                 1.8265 
                 5.7535 
               
               
                 8-44 
                 1.1377 
                 0.0965 
                 0.4089 
                 2.6656 
                 0.6815 
                 6.1586 
               
               
                 8-45 
                 0.0594 
                 0.2184 
                 1.8855 
                 2.8739 
                 0.8702 
                 7.7514 
               
               
                 8-46 
                 4.6852 
                 0.2505 
                 0.4263 
                 0.7511 
                 0.7917 
                 4.0051 
               
               
                 8-47 
                 0.2242 
                 0.0972 
                 0.2989 
                 3.1902 
                 0.5542 
                 5.5316 
               
               
                 8-48 
                 0.5831 
                 0.2300 
                 0.7879 
                 2.1296 
                 0.5254 
                 9.8918 
               
               
                 8-49 
                 0.1930 
                 0.1207 
                 0.5865 
                 0.9871 
                 2.6675 
                 5.0433 
               
               
                 8-50 
                 0.0644 
                 0.0305 
                 0.0829 
                 0.2072 
                 2.1632 
                 2.7164 
               
               
                 8-51 
                 0.0036 
                 0.0113 
                 0.2476 
                 0.3508 
                 0.7635 
                 6.7231 
               
               
                 8-52 
                 0.6419 
                 0.1478 
                 0.0796 
                 0.7367 
                 0.1653 
                 4.6233 
               
               
                 8-53 
                 0.8986 
                 0.0953 
                 0.2486 
                 0.6216 
                 1.5126 
                 4.2104 
               
               
                 8-54 
                 1.0737 
                 0.8627 
                 2.0614 
                 3.3489 
                 3.9647 
                 6.7257 
               
               
                 8-55 
                 0.6823 
                 0.0880 
                 0.1982 
                 2.1800 
                 0.4558 
                 5.3193 
               
               
                 8-56 
                 4.4271 
                 &gt;10 
                 &gt;10 
                 &gt;10 
                 &gt;10 
                 &gt;10 
               
               
                 8-57 
                 6.1616 
                 0.3521 
                 5.7699 
                 &gt;10 
                 &gt;10 
                 9.7634 
               
               
                 8-58 
                 0.1806 
                 0.0671 
                 0.2416 
                 0.7450 
                 0.0805 
                 5.5452 
               
               
                 8-59 
                 0.0998 
                 0.1113 
                 0.4973 
                 6.8377 
                 1.1017 
                 4.7470 
               
               
                 8-60 
                 0.1459 
                 0.4510 
                 2.0465 
                 7.1257 
                 1.0240 
                 4.2550 
               
               
                 8-61 
                 1.6785 
                 1.0075 
                 5.2634 
                 6.1396 
                 1.8568 
                 8.1211 
               
               
                 8-62 
                 0.5772 
                 0.1391 
                 0.4932 
                 0.5553 
                 0.1867 
                 3.4996 
               
               
                   
               
             
          
         
       
     
                                                                           TABLE 5               Tested   HCT116   HEPG2   SW620   MK45   H292   A375       Compounds   (IC 50 , μM)   (IC 50 , μM)   (IC 50 , μM)   (IC 50 , μM)   (IC 50 , μM)   (IC 50 , μM)                                8-1    &gt;10   &gt;10   &gt;10   6.7960   1.3880   3.0211       8-2    7.812   &gt;10   5.567   &gt;1   0.8829   1.5864       8-3    &gt;10   &gt;10   &gt;10   &gt;10   1.3039   &gt;10       8-4    &gt;1   &gt;10   &gt;1   2.1844   0.1489   &gt;10       8-5    7.812   &gt;10   5.567   &gt;1   &gt;1   &gt;1       8-6    3.295   2.571   2.135   0.5398   0.1273   6.9321       8-7    &gt;10   &gt;10   &gt;10   3.7625   0.1377   1.3124       8-9    0.518   &gt;10   0.524   0.7635   0.1596   0.5861       8-10   1.091   4.797   6.056   &gt;1   0.0105   1.4891       8-11   1.682   11.215   1.96   &gt;1   0.0088   1.3865       8-12   4.008   6.606   1.292   &gt;1   0.0107   3.0927       8-13   2.543   5.962   3.675   &gt;1   0.0061   0.8384       8-15   2.2   7.794   2.992   0.7095   0.2205   0.7747       8-16   0.766   10.445   0.864   &gt;1   0.1293   3.1005       8-17   0.813   &gt;10   &gt;1   0.6642   0.0296   0.1896       8-18   6.289   &gt;10   4.003   1.5206   0.5311   6.4623       8-19   &gt;1   5.42   1.993   1.0055   0.3161   1.6636       8-21   0.772   8.933   2.225   1.3279   1.1603   0.7248       8-22   1.829   &gt;10   1.922   0.5108   1.7251   1.2973       8-23   &gt;10   &gt;10   &gt;10   2.7898   0.1544   3.1756       8-24   1.382   &gt;10   &gt;10   8.0818   0.1713   2.4004       8-25   &gt;10   &gt;10   &gt;10   5.3511   1.6455   &gt;10       8-26   0.239   6.255   0.282   &gt;1   0.0107   0.3777       8-27   &gt;1   &gt;1   &gt;1   6.1109   4.1856   9.7932       8-29   2.48   &gt;10   5.796   8.1682   0.1804   1.8758       8-30   &gt;10   &gt;10   4.217   5.4680   0.2006   &gt;10       8-34   10.4821   8.4627   &gt;10   1.6645   1.2331   6.5704       8-35   0.6756   4.3356   2.3031   1.1145   0.0203   3.2455       8-36   1.1223   3.5159   3.6139   1.5518   0.0341   1.4481       8-37   &gt;10   &gt;10   &gt;10   &gt;10   5.8524   &gt;10       8-38   0.4426   2.9046   0.3700   1.7897   0.0073   &gt;10       8-41   5.4311   2.1988   2.1402   3.3432   0.2678   &gt;10       8-42   &gt;10   &gt;10   &gt;10   5.1020   0.6734   0.4982       8-43   2.5663   5.9270   5.7535   0.2338   0.1017   1.9069       8-44   &gt;10   &gt;10   2.5098   1.3528   0.0029   1.7417       8-45   7.0842   &gt;10   4.9666   3.7400   0.0139   9.2557       8-46   9.0658   &gt;10   3.6194   0.4170   &gt;10   0.3999       8-47   6.0851   8.4636   4.9480   1.1820   0.0442   1.5739       8-48   &gt;10   &gt;10   2.9367   0.2969   0.0185   2.0848       8-49   1.4365   9.2439   1.4365   0.5426   0.0045   1.9811       8-50   2.4678   8.2487   0.9635   0.2176   &gt;10   1.5602       8-51   4.1374   8.2150   0.7326   0.2476   0.0223   0.5386       8-52   5.9255   7.2296   1.5690   0.4566   0.0040   0.9736       8-53   &gt;10   &gt;10   2.1135   0.5594   0.0041   8.0705       8-54   6.9601   5.9796   6.6383   0.6884   0.2791   5.5815       8-55   6.5500   4.6772   2.9748   1.7216   &gt;10   2.7686       8-56   &gt;10   &gt;10   &gt;10   &gt;10   0.0810   &gt;10       8-57   7.8646   &gt;10   8.3682   4.5862   0.7518   &gt;10       8-58   7.4640   &gt;10   1.2504   0.5638   0.0040   0.6604       8-59   5.7188   &gt;10   1.3344   0.8081   0.0033   1.1976       8-60   6.4206   &gt;10   1.2521   1.8443   0.0545   9.3025       8-61   &gt;10   &gt;10   5.9796   2.4503   0.1879   &gt;10       8-62   3.5197   6.8330   1.3023   0.4371   0.0055   1.0210                    
Assay 3: The In-Vivo Anti-Tumor Test for Compound 8-10
 
     The object of this assay was to determine the in-vivo anti-tumor effect of the present compound. In this assay, a nude mouse subcutaneously transplanted non-small cell lung carcinoma model was used to test the present compound 8-10 for the in-vivo anti-tumor activity. The used cell strain was human non-small cell lung carcinoma cell strain HCC827. 
     1. Materials 
     RPMI-1640, fetal bovine serum, pancreatin and the like were purchased from Gibco BRL company (Invitrogen Corporation, USA); RPMI 1640 culture medium was purchased from ATCC (American Type Culture Collection); human non-small cell lung carcinoma cell strain HCC827 was purchased from ATCC company, USA; and BALB/C nude mice were purchased from Institute of Zoology, Chinese Academy of Sciences. 
     2. Procedure 
     BALB/C nude mice, aged 6-8 weeks, were inoculated with HCC827 cell subcutaneously at the posterior segment of rib in a concentration of about 5×10 6  cells/0.1 ml per mouse. Upon the growth of the tumor up to 200-300 mm 3  (about 20 days), mice were grouped (n=6) and administrated intragastrically. 
     Groups: 
     Solvent control group: (5% DMSO+1% TWEEN80+94% water); 
     Gefitinib group: 100 mg/kg q.d.; 
     Compound 8-10 group: 2 mg/kg q.d.; 
     Compound 8-10 group: 5 mg/kg q.d.; 
     Compound 8-10 group: 10 mg/kg q.d.; 
     Compound 8-10 group: 20 mg/kg q.d. 
     (Each of drug groups was dissolved in 5% DMSO+1% TWEEN80+94% water). 
     Observation Indices: the mice were measured every three days for the weight, and the length and width of tumor, and the tumor volume was calculated as length×width 2 ×0.52. The mice were observed for the reactions such as diarrhea, convulsion, exanthema, and substantial weight reduction.
 
3. Results
 
     The measured tumor growth curves for each of the groups are shown in  FIG. 1 . The photograph of tumors obtained by dissection after the assay is shown in  FIG. 2 . The results indicated that the tested compound 8-10 had a substantial in-vivo growth inhibition for the EGFR delE746-A750  mutated human non-small cell lung carcinoma cell strain HCC827. Upon administrating in 2 mg/kg q.d. or higher, the tumor growth could be substantially inhibited, or even the tumor could be eliminated. In the course of administration, the nude mice did not show the untoward reactions such as weight reduction, exanthema, and diarrhea, which indicated that under the test doses, the tested compound 8-10 had a low toxicity in the dose range of administration. 
     Assay 4: The In-Vivo Anti-Tumor Test for Compound 8-29 
     The object of this assay was to determine the in-vivo anti-tumor effect of the present compound. In this assay, a NOD-SCID mouse subcutaneously transplanted human leukemic solid tumor model was used to test the present compound 8-29 for the in-vivo anti-tumor activity. The used cell strain was human acute myelogenous leukemia cell strain MV4-11. 
     1. Materials 
     IMDM, fetal bovine serum, pancreatin and the like were purchased from Gibco BRL company (Invitrogen Corporation, USA); IMDM culture medium was purchased from ATCC (American Type Culture Collection), human leukemia cell strain MV4-11 was purchased from ATCC company, USA; and the NOD-SCID mice were purchased from Laboratory Animal Center, Peking Union Medical College, China. 
     2. Procedure 
     NOD-SCID mice, aged 6-8 weeks, were inoculated with MV4-11 cell subcutaneously at the posterior segment of rib in a concentration of about 1×10 7  cells/0.1 ml per mouse. Upon the growth of the tumor up to 400-500 mm 3  (about 20 days), mice were grouped (n=6) and administrated intragastrically. 
     Groups: 
     Solvent control group: (5% DMSO+25% PEG400+70% water); 
     Compound 8-29 group: 5 mg/kg q.d.; 
     Compound 8-29 group: 10 mg/kg q.d.; 
     Compound 8-29 group: 20 mg/kg q.d. 
     (Each of drug groups was dissolved in 5% DMSO+25% PEG400+70% water) 
     Observation Indices: the mice were measured every three days for the weight, and the length and width of tumor, and the tumor volume was calculated as length×width 2 ×0.52. The mice were observed for the reactions such as diarrhea, convulsion, exanthema, and substantial weight reduction.
 
3. Results
 
     The measured tumor growth curves for each of the groups are shown in  FIG. 3 . The results indicated that the tested compound 8-29 had a substantial in-vivo growth inhibition for the FLT3-ITD mutated human acute myelogenous leukemia cell strain MV4-11. Upon administrating in 5 mg/kg q.d. or higher, the tumor growth could be substantially inhibited, or even the tumor could be eliminated. In the course of administration, the mice did not show the untoward reactions such as weight reduction, exanthema, and diarrhea, which indicated that under the test doses, the tested compound 8-29 had a low toxicity in the dose range of administration.