[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:6](I)=[CH:5]2.[CH2:23]([CH:25]1[O:30][CH2:29][CH2:28][NH:27][CH2:26]1)[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+].C(C1CCCCC1=O)(=O)C(C)C>CN(C=O)C.[Cu]I>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:6]([N:27]1[CH2:28][CH2:29][O:30][CH:25]([CH2:23][CH3:24])[CH2:26]1)=[CH:5]2A mixture of 6-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amine (0.30 g, 0.640 mmol, prepared as in Example 1, Step 1-2), 2-ethylmorpholine (1.105 g, 9.59 mmol), copper(I) iodide (6.09 mg, 0.032 mmol), cesium carbonate (0.417 g, 1.279 mmol), and 2-isobutyrylcyclohexanone (0.021 mL, 0.128 mmol) in DMF (3 mL) was heated at 125° C. for 10 min. Some product was observed but mostly starting material. The mixture was heated again at 125° C. for 10 min more. This process was repeated 3× until the starting material was completely consumed. The reaction was brought to RT, poured into water (20 mL) and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated, and chromatographed on silica gel using gradient 2:1 hexanes/EtOAc to afford a brown oil as 6-bromo-3-(2-ethylmorpholino)-N-(4-methoxybenzyl)quinolin-2-amine.
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