合成路线1

The methylation of 1,6-naphthalenediol (I) with dimethyl sulfate gives 1,6-dimethoxynaphthalene (II), which by reaction with sodium-ethanol is converted to 5-methoxy-2-tetralone (III). The condensation of (III) with propylamine - p-toluenesulfonic acid and subsequent hydrogenation with H2 over Pt affords 5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine (IV). which is demethylated with HBr to 5-hydroxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine (V). Finally, this compound is reductively alkytated with 2-thienylacetic acid (VI) using boranetrimethylamine complex to yield N-0437.

合成路线2

The overall synthetic approach to N-0923 is described: Methylation of 1,6-dihydroxynaphthalene (I) with dimethyl sulfate provides 1,6-dimethoxynaphthalene (II), which is converted to 5-methoxy-2-tetralone (III) by reduction with sodium in ethanol. Reductive amination of (III) with propylamine results in the racemic 5-methoxy-2-N-propylaminotetralin (IV), from which the (-)-enantiomer (V) is obtained by fractional crystallization of the dibenzoyl-L-tartaric acid (L-DBTA) salt. Demethylation with aqueous hydrobromic acid affords (-)-(S)-5-hydroxy-2-N-propylaminotetralin (VI), which is reductively alkylated with thienylacetic acid in the presence of trimethylaminoborane to (-)-(S)-5-hydroxy-2-[N-propyl-N-[2-(2-thienyl)ethyl]amino]tetralin (VII). Treatment with anhydrous hydrogen chloride in ether provides N-0923.

合成路线3

Alkylation of aminotetralin (I) with bromoacetonitrile in boiling acetone gave cyanomethyl compound (II). This was subsequently reduced to diamine (III) using LiAlH4. Condensation of (III) with benzoyl chloride under Schotten-Baumann conditions then yielded the corresponding benzamide.

合成路线4