[Br:1][C:2]1[C:7](=[O:8])[N:6]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:5]2=[N:4][C:3]=1[CH:14]([NH:16][CH2:17][CH2:18][S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])[CH3:15].[F:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][C:32](O)=[O:33])=[CH:27][C:26]=1[C:35]([F:38])([F:37])[F:36].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>C(OCC)(=O)C.ClCCl.O.C(OCC)(=O)C.CN(C=O)C>[Br:1][C:2]1[C:7](=[O:8])[N:6]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:5]2=[N:4][C:3]=1[CH:14]([N:16]([CH2:17][CH2:18][S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])[C:32](=[O:33])[CH2:31][C:28]1[CH:29]=[CH:30][C:25]([F:24])=[C:26]([C:35]([F:36])([F:38])[F:37])[CH:27]=1)[CH3:15]To a flask with E4 (310 mg, 0.77 mmol) was added 2-(4-fluoro-3-(trifluoromethyl)phenyl)acetic acid (187 mg, 0.84 mmol), EDC (440 g, 2.3 mmol), HOBt (52 mg, 0.38 mmol), followed by 14 mL of anhydrous DMF and N-methyl morpholine (0.25 mL, 2.3 mmol). The reaction was stirred at room temperature overnight and worked up with ethyl acetate and water. Column chromatography with gradient ethyl acetate/dichloromethane (3:1 to 2:1 to 1:1) gave 460 mg E5 as an yellow foamy solid.
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