合成路线1

Treatment of piperidine (I) with 9-BBN in refluxing THF followed by reaction with bromo derivative (II) by means of K2CO3, PdCl2(dppf) and Ph3As in DMF/H2O provides chlorophenylsulfonyl derivative (III), whose Boc group is removed by means of TFA in CH2Cl2/H2O to afford secondary amine (IV). Reductive amination between amine (IV) and piperidone (V) by means of NaB(OAc)3H in CH2Cl2 in the presence of HOAc furnishes compound (VI), which is then deprotected by means of TFA in CH2Cl2/H2O to yield bipiperidinyl derivative (VII). Finally, coupling of (VII) with 2-amino-3-methyl benzoic acid (VIII) by means of HOBt, DIEA and EDCI in DMF provides the target product. Alternatively, the synthesis of intermediate (VII) can be performed as follows: Protection of the piperidine moiety of (IX) by means of trifluoroacetic anhydride in CH2Cl2 followed by treatment with methanesulfonic acid and dibromodimethylhydantoin (DBDMH) affords bromo derivative (X), whose trifluoroacetate moiety is then removed by reaction with K2CO3 in MeOH/H2O to give piperidine derivative (XI). Reductive amination between (XI) and piperidone (V) by means of NaB(OAc)3H in CH2Cl2 in the presence of HOAc furnishes compound (XII), which is condensed with 3-chlorbenzenesulfonyl fluoride (XIII) by means of BuLi in THF and finally treated with TFA in CH2Cl2/H2O for Boc removal to provide the intermediate chlorophenylsulfonyl derivative (VII).