[F:1][C:2]([F:23])([F:22])[C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:16][C:15](N)=[N:14][N:13]=2)[CH2:8][CH2:7]1.[C:24]([Cu])#[N:25].O.C(Cl)Cl>CC#N>[F:23][C:2]([F:22])([F:1])[C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[O:5][CH:6]1[CH2:7][CH2:8][N:9]([C:12]2[S:16][C:15]([C:24]#[N:25])=[N:14][N:13]=2)[CH2:10][CH2:11]1
To a suspension of 5-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazol-2-amine (10.0 g, 29.0 mmol) in CH3CN (150 mL) was added CuCN (5.3 g, 59.2 mmol) and t-BuONO (90%) (8 mL, 60.0 mmol) at room temperature. The reaction mixture was heated at 50-60° C. for 2 h until TLC indicated disappearance of the starting material. The reaction mixture was poured into water and CH2Cl2 was added. The solid was removed by filtration and the filtrate was extracted with CH2Cl2, dried (Na2SO4) and filtered. Solvents were removed in vacuo to afford the crude product, which was purified by column chromatography on silica gel (eluting with 5:1 petroleum ether/EtOAc) to afford the title compound. 1H NMR (400 MHz, CDCl3): δ7.61 (d, 1H), 7.50 (t, 1H), 6.93-7.06 (m, 2H), 4.86 (br s, 1H), 3.77-3.83 (m, 4H), 2.01-2.20 (m, 4H). MS: m/z 355 (MH+).
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