合成路线1

The reaction of 3,5-difluorophenylacetic acid with SOCl2 gives the corresponding acyl chloride (II), which is cyclized with ethylene (III) by means of AlCl3 in dichloromethane yielding the tetralone (IV). The stereoselective reduction of (IV) with LiAlH4 catalyzed by (1R,2S)-N-methylephedrine affords 5,7-difluoro-1,2,3,4-tetrahydro-2(R)-naphthol (V). The reaction of (V) with methanesulfonyl chloride and triethylamine gives the expected mesylate (VI), which is treated with LiN3 in DMF yielding the 2(S)-azide (VII). The reduction of (VII) with H2 over Pd/C in ethyl acetate affords the corresponding amine (VIII), which is treated with formaldehyde and KCN to give the 2-aminoacetonitrile (IX). The acylation of (IX) with butyl formate in refluxing acetonitrile yields the formamide (X), with is treated with ethyl formate and potassium tert-butoxide in THF to afford the hydroxyvinyl derivative (XI). The cyclization of (XI) with potassium thiocyanate in hot ethanol gives 1-(5,7-difluoro-1,2,3,4-tetrahydro naphthalen-2(S)-yl)-2-thioxo-2,3-dihydro-1H-imidazole-5-carbonitrile (XII), which is finally reduced with LiAlH4 in THF.