Synthesis of Alalevonadifloxacin mesylate 

Alalevonadifloxacin mesylate is synthesized using 2-Bromo-4,5-difluoroacetylaniline as raw material through a series of chemical reactions. The specific synthesis method is as follows:

2-Bromo-4,5-difluoroacetylaniline was treated with crotonaldehyde under Skraup-Doeber-Von Miller conditions to generate quinoline 2 in 67% yield. Catalytic hydrogenation using palladium on carbon reduced the carbon? bromine bond within 2. Filtration of the reaction mixture to remove the catalyst followed by the addition of platinum on carbon and resubjection to hydrogenation conditions gave tetrahydroquinoline 3 in 97% yield.

Compound 3 was treated with 2,3-di-O-benzoyl-L-tartaric acid (L-DBTA) followed by recrystallization from 60% aqueous methanol to give S-isomer 4 in 35% yield and 100% ee. Although not shown, the recovered Risomer from the resolution could be racemized by treatment with methanesulfonic acid (MsOH). Compound 4 was treated with diethylethoxymethylenemalonate (EMME) in polyphosphoric acid (PPA) and treated with HCl to give tricyclic acid 5 in 88% yield. Chelation of 5 with boron triacetate (generated in situ) gave the cyclic borate complex 6, which was further reacted with 4-hydroxypiperidine to give levonadifloxacin 8 in good yield for the 2 steps. Coupling 8 with Boc-alanine followed by removal of the Boc group and salt formation with methanesulfonic acid gave alalevonadifloxacin mesylate in 95% yield.