Synthesis Of 4-alkyl/Arylamino-6-alkylthiopyrimidine Derivatives

Pyrimidine derivatives are widely found in many plants and animals,such as thymine,uracil,etc.Besides they can maintain the life activities of plants and animals,they also perform well in the fields of anti-platelet aggregation,anti-cancer,and anti-virus,biologists,etc.In this paper,we mainly study new methods for the synthesis of pyrimidine derivatives with antiplatelet agglutinating activity,and specifically modify the 4 and 6 positions on the pyrimidine ring.Firstly,2-substituted-4,6-dihydroxypyrimidine is used as raw.material to obtain 2-substituted-4,6-dichloropyrimidine by chlorination of phosphorus oxychloride.Then the substitution of C-4 and C-6 of pyrimidine is explored.The order of introduction and reaction conditions were explored.Experiments showed that the preferred reaction sequence was to perform 4-position alkyl/aryl amino modification to obtain 2-substituted-4-alkylamino/aryl-6-chloropyrimidine compounds,and then used alkane Substitution of the thio group at the 6-position chlorine atom led to the successful synthesis of 4-alkyl/arylamino-6-alkylthiopyrimidine derivatives.Compared to traditional methods,this method requires no catalyst,and avoids the use of nitrogen protection and the use of strong bases.In addition,this method can avoid the production of dialkylated products,and the arylamino group can also be effectively introduced into the pyrimidine ring,providing a more direct and simple synthesis route for pyrimidine derivatives having anti-platelet aggregation.The twenty two intermediates synthesized and the twenty four 4-alkane/arylamino-6-alkylthiopyrimidine derivatives have been comfirmed by 1H-NMR,13C-NMR,IR and HRMS.All the fourty six compounds are new.