[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.Br[C:10]1[N:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][CH:11]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1(C)C=CC=CC=1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][C:10]2[N:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][CH:11]=2)[CH2:4][CH2:3]11-Methylpiperidin-4-ol (1.89 g, 0.0164 mol), 6-bromo-2-pyridinecarbonitrile (3.00 g, 0.0164 mol), Pd(OAc)2 (0.184 g, 0.820 mmol), 2-(di-t-butylphosphino)biphenyl (0.303 g, 1.02 mmol) and Cs(CO3)2 were mixed in 100 mL of toluene. The reaction mixture was stirred under argon and heated to 130° C. in an oil bath for 4 days. The reaction mixture was diluted with EtOAc and washed with water, dried over Na2SO4 and evaporated. The crude product was flash chromatographed on silica gel DCM/MeOH/TEA 95/5/1 to give 1.62 g (45%) of the desired product. 1H NMR (500 MHz, CDCl3) δ 7.67 (m, 1H), 7.29 (d, 1H), 6.95 (d, 1H), 5.12 (m, 1H), 2.74 (m, 2H), 2.40-2.30 (m, 5H, thereof a singlet at 2.35), 2.09 (m, 2H), 1.86 (m, 2H).
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