Roxindole mesilate, EMD-62100(free base), EMD-38362(HCl), EMD-49980

合成路线:The reaction of nicotinic acid (I) with SOCl2 gives the corresponding acyl chloride (II),which is condensed with 2-methylpyrazolo[1,5-a]pyridine (III) by heating at 160-80 C or in refluxing dioxane,yielding 2-methyl-3-(3-pyridylcarbonyl)pyrazolo[1,5-a]pyridine (IV).Finally,this compound is hydrogenated with H2 over Pd/C in ethanol at 13 Atm.pressure and 55-8 C.

合成路线:By demethylation of 5-methoxy-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-1H-indole (I) with diisobutylaluminum hydride (DBH) in hot toluene.The methylated compound (I) can be obtained by two similar ways:a) By condensation of 3-(4-chlorobutyl)-5-methoxy-1H-indole (II),or 3-(4-bromobutyl)-5-methoxy-1H-indole (III) with 4-phenyl-1,2,3,6-tetrahydropyridine (IV) in acetonitrile at room temperature.b) By condensation of 4-(3-indolyl)butyric acid (V) with 4-phenyl-1,2,3,6-tetrahydropyridine (IV) by means of carbonyldiimdazole (CDI) in THF yielding 1-[4-(3-indolyl)butyryl]-4-phenyl-1,2,3,6-tetrahydropyridine (VI),followed by reduction of the carbonyl group of (VI) with LiAlH4 in THF.

参考文献标题:Indolalkylamines,pharmaceutical compsns.containing them and process for their preparation
文献作者:Hausberg,H.-H.; Koppe,V.; Poetsch,E.; Saiko,O.; Seyfried,C.(Merck Patent GmbH)
参考来源:EP 0007399


合成路线:By demethylation of 5-methoxy-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-1H-indole (I) with diisobutylaluminum hydride (DBH) in hot toluene.The methylated compound (I) can be obtained by two similar ways:a) By condensation of 3-(4-chlorobutyl)-5-methoxy-1H-indole (II),or 3-(4-bromobutyl)-5-methoxy-1H-indole (III) with 4-phenyl-1,2,3,6-tetrahydropyridine (IV) in acetonitrile at room temperature.b) By condensation of 4-(3-indolyl)butyric acid (V) with 4-phenyl-1,2,3,6-tetrahydropyridine (IV) by means of carbonyldiimdazole (CDI) in THF yielding 1-[4-(3-indolyl)butyryl]-4-phenyl-1,2,3,6-tetrahydropyridine (VI),followed by reduction of the carbonyl group of (VI) with LiAlH4 in THF.

参考文献标题:Roxindole Mesylate
文献作者:Robinson,C.; Castar,J.
参考来源:Drugs Fut 1995,20(12),1228


合成路线:A new synthesis of roxindole has been described: The condensation of 5-methoxyindole (I) with succinic anhydride (II) by means of methylmagnesium bromide in hot anisole gives the 4-oxobutyric acid derivative (III),which is condensed with the 4-phenyltetrahydropyridine (IV) by means of EDC and DIPEA in DMF yielding the butanedione (V).The reduction of (V) with LiAlH4 in refluxing THF affords intermediate (VI),which is finally demethylated with DIBAH in refluxing toluene.
参考文献标题:A straightforward synthetic approach for roxindole
文献作者:Lange,J.H.; de Jong,J.C.; Sanders,H.J.; Visser,G.M.; Kruse,C.G.
参考来源:Bioorg Med Chem Lett 1999,9(7),1055