Br[C:2]1[CH:18]=[CH:17][C:5]([C:6]([NH:8][CH2:9][C:10]2[C:11]([CH3:16])=[N:12][O:13][C:14]=2[CH3:15])=[O:7])=[CH:4][C:3]=1[F:19].Br[C:21]1[CH:29]=[CH:28][C:24]([C:25](O)=O)=[CH:23][C:22]=1F.[C:31](Cl)([C:33](Cl)=O)=O.CC1[C:42]([CH2:43][NH2:44])=C(C)ON=1.[OH2:46]>ClCCCl.CN(C=O)C>[CH2:6]([N:8]([CH2:31][CH3:33])[C:9]([CH:25]([C:24]1[CH:28]=[CH:29][CH:21]=[CH:22][CH:23]=1)[N:44]1[CH2:43][CH2:42][N:12]([C:2]2[CH:18]=[CH:17][C:5]([C:6]([NH:8][CH2:9][C:10]3[C:11]([CH3:16])=[N:12][O:13][C:14]=3[CH3:15])=[O:7])=[CH:4][C:3]=2[F:19])[CH2:11][CH2:10]1)=[O:46])[CH3:5]4-Bromo-N-(3,5-dimethyl-isoxazol-4-ylmethyl)-3-fluoro-benzamide. To a mixture of 4-bromo-3-fluoro-benzoic acid (3.0 mmol) and DMF (0.10 mL) in DCE (10 mL) was added (COCl)2 (4.0 mL) dropwise. After 30 min, the mixture was concentrated and dried under vacuum. The residue was dissolved in DCE (20 mL), treated with C-(3,5-dimethyl-isoxazol-4-yl)-methylamine (3.0 mmol) and TEA (8.0 mmol), and stirred at rt for 16 h. The mixture was treated with H2O (10 mL). The resulting precipitate was collected by filtration to give the title compound (650 mg, 69%).
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