[Cl:1][C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16](S(C)(=O)=O)=[CH:15][CH:14]=2)=[C:10]([Cl:23])[C:9]2[C:4](=[C:5]([CH3:32])[CH:6]=[C:7]([C:24]([C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)=[O:25])[CH:8]=2)[N:3]=1.[F:33][C:34]([F:50])([F:49])C1C=C(C=CC=1)CC(C(O)=O)C(O)=O>O=P(Cl)(Cl)Cl>[Cl:1][C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:34]([F:50])([F:49])[F:33])[CH:14]=2)=[C:10]([Cl:23])[C:9]2[C:4](=[C:5]([CH3:32])[CH:6]=[C:7]([C:24]([C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)=[O:25])[CH:8]=2)[N:3]=1A heterogeneous mixture of (4-amino-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone (1.3 g, 6.04 mmol, Intermediate 13: step c), 2-(3-(trifluoromethyl)benzyl)malonic acid (2.06 g, 7.85 mmol, Intermediate 15: step b) and POCl3 (10 mL) was heated at 105° C. for 4 hours. The mixture was cooled to room temperature and concentrated to remove excess POCl3. Ice water was then added and the mixture treated with aqueous NH4OH (kept adding ice during addition) to a basic pH 8-9. The aqueous mixture was extracted with EtOAc (2×). The EtOAc extracts were dried over Na2SO4, evaporated in vacuo and chromatographed (DCM/EtOAc, gradient) to provide the title compound as an off-white solid.
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