[F:1][C:2]([F:28])([F:27])[C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C@@H:12]2[CH2:16][O:17][C:18]2[C:19]([C:24]([NH2:26])=[O:25])=[N:20][CH:21]=[CH:22][CH:23]=2)=[O:10])[CH2:5][CH2:4]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][N:79]=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[N:79]1[CH:80]=[CH:81][CH:82]=[CH:83][C:78]=1[NH:26][C:24](=[O:25])[C:19]1[C:18]([O:17][CH2:16][C@H:12]2[CH2:13][CH2:14][CH2:15][N:11]2[C:9]([C@H:6]2[CH2:7][CH2:8][C@H:3]([C:2]([F:1])([F:27])[F:28])[CH2:4][CH2:5]2)=[O:10])=[CH:23][CH:22]=[CH:21][N:20]=1To a stirred mixture of 3-(((R)-1-(trans-4-(trifluoromethyl)cyclohexanecarbonyl)pyrrolidin-2-yl)methoxy)picolinamide (30 mg, 0.08 mmol, EXAMPLE 75 Step 1), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (XANTPHOS) (3.47 mg, 6.00 micromol), cesium carbonate (0.10 g, 0.30 mmol), and tris(dibenzylideneacetone)dipalladium (Pd2(dba)3) (1.56 mg, 1.50 micromol) in 1,4-dioxane (2 mL) was added 2-bromopyridine (14 mg, 0.09 mmol) at room temperature. After being stirred at 120° C. for 12 h under microwave irradiation, water was added to the mixture. The mixture was extracted with ethyl acetate twice. The extracts were combined and dried over magnesium sulfate and concentrated in vacuo to afford an oil. The residual oil was purified by preparative HPLC.
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