合成路线1

Claisen condensation of 4-chloropropiophenone (I) with diethyl oxalate in the presence of lithium hexamethyldisilazide afforded the corresponding diketo ester lithium salt (II). This was condensed with 2,4-dichlorophenylhydrazine (III) to afford hydrazone (IV), which was further cyclized to pyrazole (V) in refluxing HOAc. In an improved procedure, 4-chloropropiophenone (I) was initially converted to the silyl enol ether (VI) using chlorotrimethylsilane and triethylamine. Acylation of (VI) with ethyl chloroglyoxylate in the presence of ZnCl2 produced diketo ester (VII). Condensation of (VII) with hydrazine (III), followed by acid cyclization of the intermediate hydrazone (IV), also produced pyrazole (V). Hydrolysis of ethyl ester (V) gave carboxylic acid (VIII), which was then activated as the acid chloride (IX). Finally, coupling of acid chloride (IX) with N-aminopiperidine (X) furnished the title hydrazide.