[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]3[O:20][C:19]([C:21]4[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=4)=[N:18][C:17]=13)=[O:11])[CH2:2]2.[NH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]3[O:20][C:19]([C:21]4[CH:26]=[CH:25][C:24]([NH:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)=[CH:23][CH:22]=4)=[N:18][C:17]=13)=[O:11])[CH2:2]2A mixture of N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-iodophenyl)benzoxazole-4-carboxamide (27 mg, 0.057 mmol), aniline (10.4 μL, 0.114 mmol), palladium acetate (1.3 mg, 0.0057 mmol), racemic BINAP (10.6 mg, 0.017 mmol) and toluene (2 mL) was stirred under nitrogen at room temperature for 30 min. Cesium carbonate (37 mg, 0.11 mmol) was added and the mixture was heated at 110° C. under nitrogen for 5 h. The mixture was cooled to room temperature, quenched with saturated aqueous sodium bicarbonate, extracted with methylene chloride. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude material was purified by semi-preparative HPLC to afford N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-phenylaminophenyl)benzoxazole-4-carboxamide (21 mg, 84%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.66 (d, J=7.5 Hz, 1H), 8.15 (dd, J=8.0, 1.0 Hz, 1H), 8.09 (dd, J=7.5, 2.0 Hz, 2H), 7.66 (dd, J=8.0, 1.0 Hz, 1H), 7.41-7.36 (m, 3H), 7.22 (d, J=7.5 Hz, 2H), 7.12-7.10 (m, 3H), 6.15 (s, 1H), 4.32-4.28 (m, 1H), 3.52 (ddd, J=14.0, 9.5, 2.0 Hz, 1H), 3.10-2.81 (m, 5H), 2.17-2.06 (m, 2H), 1.78-1.64 (m, 3H); MS (ESI+) m/z 439 (M+H); HPLC>99% (AUC), tR=14.32 min.
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