合成路线1

c) Synthesis of metabolite M-V: The reduction of 6-methylpyridine-3-carboxylic acid methyl ester (XII) with LiAlH4 in THF gives the corresponding hydroxymethyl derivative (XIII), which is protected with chloromethyl methyl ether as before yielding the methoxymethoxymethyl compound (XIV). Hydroxymethylation of (XIV) with formaldehyde as described affords the ethanol derivative (XV), which is condensed with 4-fluoronitrobenzene (V) as before giving 5-(hydroxymethyl)-2-[2-(4-nitrophenoxy)ethyl]pyridine (XVI). The deprotection of (XVI) with HCl in refluxing methanol yields the hydroxymethyl compound (XVII), which is treated with SOCl2 in refluxing chloroform to afford the chloromethyl compound (XVIII). The reaction of (XVIII) with KCN in hot DMF gives the corresponding cyanomethyl derivative (XIX), which by reduction of the NO2 group with H2 over Pd/C in ethyl acetate yields the amino derivative (XX). The diazotation of (XX) with NaNO2 in aqueous HBr followed by condensation with methyl acrylate as before affords the 2-bromopropionate (XXI), which is cyclized with thiourea (X) as reported to give iminothiazolidinone derivative (XXII). Finally, the hydrolysis of the cyano gives Metabolite M-V.