BAY-069 is the most potent branched-chain amino acid transaminase 1(BCAT1)inhibitor;however,its reported synthetic route suffered from many shortcomings,such as expensive starting ma-terial,extremely low overall yield and insufficient structural characterizations of intermediates.The present study performed systematic optimization of the key synthetic processes based on the reported synthetic route,such as Ullmann coupling.Thus,starting from 1-nitronaphthalene(1),BAY-069 was prepared in 7 steps followed by chiral resolution on chiral column,and all the intermediates and BAY-069 were fully characterized by 1H NMR,13C NMR and HR-MS.The overall yield for the opti-mized synthetic route with the key step being Ullmann coupling is 11.0％(3b →(±)-BAY-069),which is 6.7-fold higher than the original overall yield of 1.6％(3a →(±)-BAY-069).
维普
万方数据