Synthesis of Fluorinated Triazole Compound

Example 119

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The mixture of compound 127-1 (100 mg, 0.25 mmol, 1 eq), BrCN (82.2 mg, 0.77 mmol, 57.1 uL, 3 eq) and TEA (104.7 mg, 1.04 mmol, 0.14 mL, 4 eq) in DCM (2 mL) was stirred at 0° C. for 1 hr. LC-MS and HPLC showed the desired compound was detected. The reaction mixture was diluted with H₂O (10 mL) and the mixture was extracted with EA (10 mL*3). The combined organic phase was washed with brine (10 mL*2), dried with anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by prep-HPLC. The title compound (18 mg, 43.3 umol, 16.7% yield) was obtained as brown solid. LCMS (ESI): RT=0.960 min, mass calcd for C₂₃H₂₀F₃N₃O 411.42 m/z, found 412.0 [M+H]⁺; ¹H NMR (400 MHz, CD₃OD) δ 8.47 (d, J=1.5 Hz, 1H), 8.07-8.03 (m, 1H), 7.88-7.80 (m, 5H), 7.67-7.61 (m, 3H), 7.55-7.51 (m, 1H), 3.54 (t, J=6.9 Hz, 2H), 3.37-3.31 (m, 1H), 3.16 (t, J=7.0 Hz, 2H), 2.91 (s, 3H), 2.01 (quin, J=7.0 Hz, 2H).