合成路线1

1) The cyclization of 4-hydrazinobenzonitrile (I) with 4-(benzoyloxy)cyclohexanone (II) in refluxing acetic acid gives 3-(benzoyloxy)-1,2,3,4-tetrahydro-9H-carbazole-6-carbonitrile (III), which is hydrolyzed with aqueous KOH to the corresponding alcohol (IV). The tosylation of (IV) with tosyl chloride in pyridine yields the tosylate (V), which by treatment with methylamine in hot ethanol is converted into 3-(methylamino)-1,2,3,4-tetrahydro-9H-carbazole-6-carbonitrile (VI). The partial hydrolysis of the nitrile group with NaOH/H2O2, with previous protection of the amino group with di-tert-butyl dicarbonate, affords 3-(methylamino)-1,2,3,4-tetrahydro-9H-carbazole-6-carboxamide (VII) as a racemic mixture. The reaction of (VII) with di-tert-butyl dicarbonate gives the carbamate (VIII), which is submitted to chiral HPLC in hexane/ethanol giving the (R)-isomer (IX). Finally, this carbamate is hydrolyzed with aqueous HCl/methanol. 2) The optical resolution can also be performed with the benzoyloxycarbonyl derivative of (VII) in a similar way. 3) The optical resolution of (VII) can also be performed directly with (1S)-(+)-camphorsulfonic acid in methanol. 4) The reaction of cyclohexane-1,4-dione mono 2,2-dimethyltrimethylene ketal (X) with methylamine in toluene gives the corresponding methylimine (XI), which is reduced with H2 over Pd/C in ethanol to the expected methylamine (XII). Finally, this compound is cyclized with 4-aminobenzamide (XIII) by treatment first with NaNO2/HCl and then with sodium dithionite affording the racemic mixture (VII) already described.