Synthetic Research On Febrifugine And Halofuginone

This thesis is focusing on the synthesis of anti-coccidiosis drug Febrifugine and Halofuginone.3-Bromoaniline was the raw material. After Sandmyer reaction and condensation, 6-bromo-isatin was formed. Then in the presence of sulfuryl dichloride,6-bromo isatin was changed into 6-bromo-5-chloro-isatin which was used to synthesize 2-amino-5-bromo-4-chlorobenzoic acid by strong base solution and 3% hydrogen peroxide. At last, condensing 2-amino-5-bromo-4-chlorobenzoic acid and formamide got Halofuginone intermediate A (7-bromo-6-chloroquinazolin-4(3H)-one). The overall yield is 11.2%. In addition,another synthesis route including bromination, oxidation, amination and condensation was tried and Halofuginone intermediate A was also obtained in 25.5% overall yield. Compared with the former route, this one has some advantages including less reaction steps, higher yield and lower cost. Meanwhile, Febrifugine intermediate A quinazolin-4(3H)-one was prepared by condensing 2-aminobenzoic acid and formamide in 73.0% yield.3-Hydroxy pyridine was employed as the starting material to synthesize Febrifugine and Halofuginone intermediate B, benzyl 2-(bromomethyl)-hexahydrofuro[3,2-b]pyridine-4(2H)-carboxylate, by steps of amino-protection, allylation, reduction, protecting group interchange, Claisen rearrangement, reduction and NBS bromination in 22.5% overall yield.Efforts on condensing intermediate A and B according to the literatures to get Febrifugine and Halofuginone failed. The research was under investigation.