4-{3-[4-(TRIFLUOROMETHYL)PHENYL]-1H-PYRAZOL-4-YL}PYRIDINE synthesis

Yield:400801-23-2 33%

Reaction Conditions:

with caesium carbonate in N,N-dimethyl-formamide;

Steps:

28.A 5-Chloro-3-(1-{2-hydroxy-3-[4-pyridin-4-yl-3-(4-trifluoromethyl-phenyl)-pyrazol-1-yl]-propyl}-piperidin-4-yl)-1-methyl-1,3-dihydro-benzoimidazol-2-one

A. 4-[1-Oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1 H-pyrazol-4-yl]-pyridine. To a solution of 4-[3-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyridine (0.5 g, 1.73 mmol) and epichlorohydrin (1.35 mL, 17.3 mmol) in DMF (2 mL) was added cesium carbonate (0.676 g, 2.07 mmol). The reaction mixture was allowed to stir for 24 h, diluted with EtOAc and washed successively with saturated NaHCO₃, water, and brine. The organic layer was dried over Na₂SO₄, concentrated and partially purified by running through a plug of silica gel (5% acetone/CH₂Cl₂) to afford 4-[1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyridine (0.198 g, 33%) as an unstable oil. TLC (silica, 20% acetone/CH₂Cl₂): R_f=0.39. MS (electrospray): exact mass calculated for C₁₈H₁₄F₃N₃O, 346.1 [M+H]⁺, m/z found, 346.1.

References:

US2005/101587,2005,A9