合成路线1

Amination of 2-phenylethyl bromide (XII) with methylamine in THF gives N-methylphenethylamine (XIII) , which upon N-acylation with chloroacetyl chloride (XIV) in the presence of NaHCO3 in CH2Cl2 or methyl t-butyl ether yields the chloroacetamide derivative (XV) . Cyclization of intermediate (XV) by Friedel-Crafts alkylation by means of AlCl3 in 1,2-dichlorobenzene at 165 °C gives 3-methyl-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one (XVI) . Alternatively, compound (XVI) can be obtained from 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one (XVII) by N-methylation with methyl iodide by means of NaH in DMF . Treatment of lactam (XVI) with isoamyl nitrite (i-AmONO) in the presence of NaHMDS or LiHMDS in THF yields the 1-hydroxyiminobenzazepinone (XVIII), which is finally hydrogenated with H2 over Pd/C in the presence of HCl in EtOH at 50 °C or with H2 over Raney-Ni in the presence of NH3 in EtOH at 100 °C .
Alternatively, phenylacetyl chloride (XIX) is condensed with N-(2,2-dimethoxyethyl)-N-methylamine (XX) by means of NaHCO3 in methyl t-butyl ether/H2O to furnish the phenylacetamide derivative (XXI), which upon cyclization in the presence of H2SO4 at 110 °C affords the benzazepin-2-one derivative (XXII). Treatment of intermediate (XXII) with i-AmONO in the presence of LiHMDS in THF gives the hydroxyimino derivative (XXIII), which is finally hydrogenated with H2 over Pd/C in the presence of HCl in EtOH at 50 °C .