[Br:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1.[C:17](Cl)(=[O:21])[C:18](Cl)=O.C([N:25]([CH2:28][CH3:29])CC)C>ClCCl.CN(C)C=O.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:6]=[C:5]([C:7]([NH:25][C:28]2[C:29]([C:17](=[O:21])[CH2:18][CH:5]([CH3:7])[CH3:6])=[CH:12][CH:13]=[CH:14][C:15]=2[CH3:10])=[O:9])[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1
To a solution of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the pyrazole product of Step D) (500 mg, 1.65 mmol) in dichloromethane (10 mL) was added 1 drop of N,N-dimethylformamide. Oxalyl Chloride (0.43 mL, 5 mmol) was added and the mixture was stirred at 23° C. for 1 hour. The solvent was removed under reduced pressure and the residue was diluted with acetonitrile (20 mL) and the solvent was again removed under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL) and treated with 1-(2-amino-3-methylphenyl)-3-methyl-1-butanone, prepared according to Chem. Pharm. Bull., 2000, 48, 1-15, (330 mg, 1.6 mmol) and finally triethylamine (0.45 mL, 3.2 mmol). The mixture was heated at 60° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and water (50 mL). The organic layer was washed with water (2×30 mL) and 1N hydrochloric acid (2×30 mL). The separated organic layer was dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was subjected to silica gel chromatography using ethyl acetate/hexanes (3:7) as eluent. Appropriate fractions were pooled to afford, after removal of the solvents, the title compound, a compound of the invention (210 mg), as a yellow solid melting at 119-120° C.
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