Design And Synthesis Of A Novel Anti - Tumor Drug EGFR - TKI Target For Molecular Targets

Objective:By a variety of chemical synthesis to complete target compounds 4-substituted anilino-6-methoxy-7-(2-hydroxypropyl-oxy)-q-uinazoline synthesis and structural modification of the target compounds, with a view to high activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).Methods:this article describes the design of a series of 4-substituted anilino-6-methoxy-7-(2-hydroxypropyl-oxy)-quinazoline derivatives,whi-ch consist of a quinazoline (the purine analog) nucleus with various substituted anilino groups and flexible side-chains on its 4-and 7-position. Synthesis of target compounds namely to vanillic acid as the starting material with methanol under reflux conditions for 4-hydroxy-3-methyl, then ether, and nitration, reduction, cyclization reaction 6-metho-xy-7-benzyloxy-quinazoline-4-one,and then by the chloride in place of aniline,benzyoxy-off,such as etherification reaction of the target compou-nds; target compounds with the second and third occurrence of substitute-ion reactions of amines by the TM1, that is 4-amino-benzene-6-methoxy-7-[2-hydroxy-3-(N,N-diethyl amino)-oxy]quinazoline; with ether occured Ornidazole reaction of TM2, namely,4-amino-benzene-6-methoxy-7-[2-hydroxy-3-(2-methyl-5-nitroimidazole)-oxy] quinazoline.Results:the molecular weight often intermediates were identified succe-ssfully by MS spectroscopic and TM2 were identified successfully by structure analysis of UV、IR、1H NMR、MS spectroscopic, it may be inferred that the structure of the nine intermediates is correct.Conclusion:The goal of the successful synthesis of compounds for the subsequent synthesis of a series of 4-substituted anilino-6-methoxy-7-(2-hydroxypropyl-oxy)-quinazoline compounds laid a good foundation.