[Br:1][C:2]1[C:3](=[O:20])[N:4]([C:10]2[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:13](O)=[O:14])[C:5]([CH3:9])=[CH:6][C:7]=1[OH:8].[C:21](N1C=CN=C1)([N:23]1C=CN=C1)=O.CN.O1CCCC1.Cl>CN(C)C=O>[Br:1][C:2]1[C:3](=[O:20])[N:4]([C:10]2[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:13]([NH:23][CH3:21])=[O:14])[C:5]([CH3:9])=[CH:6][C:7]=1[OH:8](−)3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid (10) (1.50 kg, 4.44 moles), 1,1′-carbonyldiimidazole (1.08 kg, 6.66 moles) and N,N-dimethylformamide (3 mL) were mixed together at ambient temperature. Once the activation reaction was deemed complete, 2 M methylamine solution in tetrahydrofuran (5.5 L, 11.1 moles) was added at a rate that maintained the temperature below 30° C. The mixture became homogeneous as the reaction reached completion. A solution of 1 N hydrochloric acid solution (15.4 kg) was added to reach pH 3 or less. The acidification precipitated the product. The product was filtered, washed with water and vacuum dried at 60° C. overnight to give (−)3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-N,4-dimethylbenzamide (9) (1.56 kg, 4.44 moles, 97% purity).
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