Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:29])=[C:6]([CH:28]=1)[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:18]=[C:17]([C:19]3[N:20]=[N:21][N:22]([CH2:24][C:25]([OH:27])=[O:26])[N:23]=3)[O:16][N:15]=2)[CH2:10][CH2:9]1.[F:30][C:31]([F:43])([F:42])[O:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:29][C:5]1[CH:4]=[CH:3][C:2]([C:36]2[CH:35]=[CH:34][C:33]([O:32][C:31]([F:30])([F:42])[F:43])=[CH:38][CH:37]=2)=[CH:28][C:6]=1[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:18]=[C:17]([C:19]3[N:20]=[N:21][N:22]([CH2:24][C:25]([OH:27])=[O:26])[N:23]=3)[O:16][N:15]=2)[CH2:10][CH2:9]1To a suspension of (5-{3-[4-(5-bromo-2-chlorophenoxy)piperidin-1-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetic acid (130 mg, 0.269 mmol), [4-(trifluoromethoxy)phenyl]boronic acid (98 mg, 0.476 mmol) and Pd(Ph3P)4 (25 mg, 0.022 mmol) in toluene (4 mL) was added aqueous 2 M Na2CO3 (1.5 mL, 3.00 mmol). After the resulting heterogeneous mixture was purged with nitrogen, it was gently heated to 80° C. for 6 h with stirring under a nitrogen atmosphere. After cooling to room temperature, the reaction was poured into aqueous 1 N HCl and extracted with EtOAc. The organic layer was washed with brine and dried (Na2SO4). Solvents were removed under reduced pressure and the crude material was purified by column chromatography on silica gel (gradient from 0% to 3% HOAc/EtOAc). After concentration, the white solid was co-evaporated twice and triturated with Et2O/heptane to give the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6): δ13.92 (br s, 1H), 7.88-7.83 (m, 2H), 7.57-7.54 (m, 2H), 7.49 (d, 2H), 7.30 (dd, 1H), 7.27 (s, 1H), 5.83 (s, 2H), 5.00-4.93 (m, 1H), 3.68-3.60 (m, 2H), 3.41-3.35 (m, 2H), 2.12-2.02 (s, 2H), 1.87-1.78 (m, 2H). MS: m/z 565 (MH+).
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