合成路线1

Zolmitriptan can be obtained by several related ways: 1) The esterification of L-4-nitrophenylalanine (I) with SOCl2 and methanol gives the corresponding methyl ester (II), which is reduced with NaBH4 in ethanol/water yielding (S)-2-amino-3-(4-nitrophenyl)-1-propanol (III). The cyclization of (III) with phosgene and KOH affords (S)-4-(4-nitrobenzyl)oxazolidin-2-one (IV), which is reduced with H2 over Pd/C in ethanol/water to the corresponding amino derivative (V). The diazotation of (V) with NaNO2.HCl, followed by reduction with SnCl2 in water affords the expected hydrazino derivative (VI), which is cyclized with 4-chlorobutanal diethylacetal (VII) in refluxing ethanol/water to give (S)-4-[3-(2-aminoethyl)-1H-indol-5-ylmethyl]oxazolidin-2-one (VIII). Finally, this compound is methylated with formaldehyde/sodium cyanoborohydride in methanol. 2) The reduction of L-4-nitrophenylalanine (I) to the propanol (III) can also be performed directly by treatment of (I) first with BF3.(Et)2O, followed by reduction with BH3.(CH3)2S complex in hot dimethoxyethane. 3) The cyclization of propanol (III) to oxazolidinone (IV) can also be performed with trichloromethyl chloroformate and NaOH in dichloromethane. 4) The cyclization of hydrazino derivative (VI) with 4-(dimethylamino)butanal diethylacetal (IX) in refluxing acetic acid/water directly yields zolmitriptan. 5) The condensation of hydrazino derivative (VI) with 3-cyanopropanal diethylacetal (X) in aqueous HCl gives (S)-4-[4-(N2-(3-cyanopropylidene)hydrazino]benzyl]oxazolidin-2-one (XI), which is cyclized with polyphosphate ester (PPE) in refluxing chloroform to yield (S)-4-[3-(cyanomethyl)-1H-indol-5-ylmethyl]oxazolidin-2-one (XII). Finally, this compound is reduced with H2 over Pd/C in 30% w/w ethanolic dimethylamine to afford zolmitriptan.