合成路线1

The condensation of 6-chloro-5-methoxy-1H-indole (I) with Meldrum's acid (II) and acetaldehyde (III) catalyzed by L-proline in acetonitrile gives the adduct (IV), which is treated with Cu and ethanol in refluxing pyridine to yield 3-(6-chloro-5-methoxy-1H-indol-3-yl)butyric acid ethyl ester (V). The reaction of (V) with hydrazine at 140 C affords the hydrazide (VI), which is treated with NaNO2 and Ac-OH to provide the corresponding azide that, without isolation, is thermolyzed and rearranged in toluene at 80?C to give 7-chloro-6-methoxy-4-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indol-1-one (VII). The cleavage of the lactam ring of (VII) with KOH in refluxing ethanol/water yields 3-(2-amino-1-methylethyl)-6-chloro-5-methoxy-1H-indole-2-carboxylic acid (VIII). The decarboxylation of (VIII) by means of refluxing aq. 3M HCl affords 3-(2-amino-1-methylethyl)-6-chloro-5-methoxy-1H-indole (IX), which is finally acylated with acetic anhydride and pyridine in toluene to provide the target 6-chloromelatonin as a racemic compound.