[NH2:1][CH2:2][C:3]([OH:21])([CH2:8][C:9]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH3:20])([CH3:11])[CH3:10])[C:4]([F:7])([F:6])[F:5].Br[C:23]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]2[C:24]=1[CH:25]=[N:26][N:27]2[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=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.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:5][C:4]([F:7])([F:6])[C:3]([CH2:2][NH:1][C:23]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]2[C:24]=1[CH:25]=[N:26][N:27]2[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)([OH:21])[CH2:8][C:9]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH3:20])([CH3:11])[CH3:10]To a mixture of 2-(aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol (Intermediate 18, 200 mg, 0.65 mmol) and 4-bromo-6-methyl-1-[4-(methyloxy)phenyl]-1H-indazole (Intermediate 15, 190 mg, 0.6 mmol) in toluene (3 mL) were added tris(dibenzylideneacetone)dipalladium(0) (28 mg, 0.03 mmol), racemic-BINAP (37 mg, 0.06 mmol) and sodium tert-butoxide (85 mg, 0.84 mmol). The mixture was heated in a microwave at 120° C. for 30 min and then cooled and partitioned between ethyl acetate (60 mL) and 1M hydrochloric acid (60 mL). The organic layer was separated, washed sequentially with aqueous sodium bicarbonate (30 mL) and brine (30 mL), passed through a hydrophobic frit and evaporated under reduced pressure. The residue was dissolved in dichloromethane (1.5 mL) and loaded onto a silica SPE cartridge and eluted with a gradient of ethyl acetate:petroleum ether (1:9 to 1:4) to give the title compound (194 mg).
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