合成路线1

This compound has been obtained by two different ways: 1) The condensation of 2-bromobenzyl alcohol (I) with cyclohexane-1,4-dione monoethyleneketal (II) by means of BuLi in THF gives the expected adduct (III), which is cyclized and deprotected with TFA yielding the spirocyclohexanone (IV). The reduction of (IV) with NaBH4 in ethanol affords the cis-spirocyclohexanol (V), which by reaction with MsCl and TEA in dichloromethane is converted into the mesylate (VI). The condensation of (VI) with piperazine (VII) in refluxing isopropanol provides the trans-intermediate (VIII), which is finally condensed with 2,4-difluorobenzonitrile (IX) by means of K2CO3 in refluxing acetonitrile. 2) The condensation of piperazine (VII) with 2,4-difluorobenzonitrile (IX) by means of K2CO3 in acetonitrile gives 2-fluoro-4-(1-piperazinyl)benzonitrile (X), which is then reductocondensed with spirocyclohexanone (IV) by means of NaBH4 and 2-ethylhexanoic acid in CH2Cl2 to afford the target compound.