合成路线1

The starting compound is 3,6-dichloropyridazine (I), which is reacted with morpholine (II) in a suitable solvent to give 3-morpholino-6-chloropyridazine (III). This, upon reaction with hydrazine hydrate as solvent, gives the hydrazine derivative (IV), which by reaction with acetonylacetone (V) in acetic acid yields directly the title compound. [14C]-Labeled compound is synthesized by a microscale procedure with 45% chemical yield and 98% radiochemical purity.

合成路线2

The cyclization of 5-methoxy-1H-indole (I) with hexane-2,6-dione (II) by means of BF3 ethearate in refluxing dioxane gives 6-methoxy-1,4-dimethylcarbazole (III), which is formylated with N-methylformanilide (IV) and POCl3 in hot o-dichlorobenzene yielding the 3-formyl derivative (V). The condensation of (V) with 2-aminoacetaldehyde diethylacetal (VI) by heating at 100 C affords the expected imino derivative (VII), which is cyclized by acid (HCl) hydrolysis of the acetal group and cyclization of the resulting aldehyde by means of NaOH in water to the 9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (VIII). The oxidation of (VIII) with m-chloroperbenzoic acid (MCPBA) in acetone gives the correponding N-oxide (IX), which is treated with BBr3 in dichloromethane yielding 9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (X). Finally, this compound is treated with 1-bromo-3-methoxy-2-propanone in DMF to afford the desired quaternary salt.

合成路线3

2-Amino-6-bromopyridine (II) was prepared by reaction of 2,6-dibromopyridine (I) with ammonium hydroxide in a pressure bomb at 170 C. The amino group of (III) was subsequently blocked as the pyrrole derivative (IV) by condensation with 2,5-hexanedione (III). Diazotization of p-aminophenyl ethanol (V) followed by treatment with KI gave iodo derivative (VI). Subsequent reaction of (VI) with SOCl2 provided chloride (VII). Arylpyridine (VIII) was obtained by lithiation of bromopyridine (IV) with BuLi, followed by conversion to the corresponding organozinc compound with ZnCl2 and palladium-catalyzed coupling with iodide (VII). Pyrrole ring cleavage in (VIII) upon treatment with hydroxylamine furnished aminopyridine (IX). Subsequent condensation with N-Boc-piperazine (X) provided adduct (XI). After acid cleavage of the Boc group of (XI), alkylation of the resulting piperazine with phenacyl chloride (XII) yielded the title compound. Alternatively, the title compound was obtained by condensation of chloride (IX) with N-phenacylpiperazine (XIII).

合成路线4