合成路线1

Treatment of 2-chloro-3-(trifluoromethyl)pyridine (XVIII) with refluxing AcOH/H2O produces 3-(trifluoromethyl)-2-pyridinone (XIX), which is nitrated using HNO3 and H2SO4 at 90 °C to yield 5-nitro-3-(trifluoromethyl)-2-pyridinone (XX) . Halogenation of pyridone (XX) with POCl3 and PCl5 at 115 °C (1-4) or with Br2, POBr3 and PBr3 at 100 °C provides chloride (XXIa) (1-4) or bromide (XXIb) , respectively. Reduction of the nitro group in compound (XXIa) with H2 over Raney-Ni in THF affords the corresponding amine (XXII), which is protected with Boc2O in the presence of DMAP in pyridine to furnish the tert-butyl carbamate (XXIII). Displacement of chlorine in compound (XXIII) with KCN and CuCN in the presence of phenanthroline in DMAc at 110 °C produces nitrile (XXIV), which is finally N-deprotected by means of TFA in CH2Cl2 .
Alternatively, oxidation of 3-(trifluoromethyl)pyridine (XXV) with H2O2 in the presence of catalytic amounts of MeReO3, and MnO2 in CH2Cl2 gives the corresponding N-oxide (XXVI), which by treatment with TMSCN and Et3N in acetonitrile yields nitrile (XXVII). Nitration of compound (XXVII) with (Me4N)NO3 by means of TFAA in dichloroethane at 60 °C affords nitropyridine (XXVIII) . Also, nitrile (XXVIII) is obtained by displacement of pyridyl chloride (XXIa) with Zn(CN)2 in the presence of Pd2dba3 and dppf in DMF at 130 °C (4) or bromide (XXIb) using CuCN and phenanthroline in DMAc (1-3). Finally, the nitro group of compound (XXVIII) is reduced with Fe and AcOH in EtOAc .