Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]C(=O)C)=[CH:5][C:4]=1[C:13]1[N:17]([CH3:18])[N:16]=[CH:15][C:14]=1[Br:19].BrN1C(=O)CCC1=O.COC1C=CC(NC(=O)C)=CC=1C1N(C)N=CC=1.[OH-].[Na+]>CO.BrN1C(=O)CCC1=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][C:4]=1[C:13]1[N:17]([CH3:18])[N:16]=[CH:15][C:14]=1[Br:19]
Reactant: COc1ccc(NC(C)=O)cc1-c1c(Br)cnn1C
Agent: COc1ccc(NC(C)=O)cc1-c1ccnn1C
Agent: O=C1CCC(=O)N1Br
Agent: [Na+]
Solvent: CO
Product: COc1ccc(N)cc1-c1c(Br)cnn1C
Temperature: 22 °C
Reaction time: 0.25 h
Yield: 81.2 %

Procedure:
The 5-(2′-methoxy-5′-acetamidophenyl)-4-bromo-1-methyl-1H-pyrazole (6, 1385.7 g) from the previous example, which was contaminated with ca. 3.2 mole % 5, was slurried in methanol (13.3 L) at 22° C. under nitrogen. To the resulting suspension stirred at 22° C. under nitrogen was added solid N-bromosuccinimide (136.7 g total) in three portions. The first portion of N-bromosuccinimide (68.3 g) left ca. 2.8 mole % unreacted 5 after 80 minutes. Then the second portion of N-bromosuccinimide (34.2 g) left ca. 1.8 mole % unreacted 5 after an additional 60 minutes. Then, after the third portion of N-bromosuccinimide (34.2 g) was added, conversion of 5 to 6 was complete within 15 minutes. There was no detectable starting material 5. Aqueous sodium hydroxide (50 wt %; 2606.8 g) was then added to the stirred suspension of 6 over 35 minutes at a rate sufficiently slow to enable the reaction mixture to be maintained at 10.4-24° C. with reactor jacket cooling. After the addition of aqueous sodium hydroxide, a reaction mixture sample was found to contain debrominated 5 in about 2.5 mole % of the amount of 6. Methanol (about 12 L) was then distilled off the stirred reaction mixture over eight hours at 10 mm HgA and internal temperatures rising to 84° C. LC/MS analysis of the reaction mixture, now about 5.5 L of a thick but stirrable suspension, showed complete hydrolysis of 6 to 7 plus about 2 mole % of the desbromo analog of 7. Removal of substantially all remaining methanol (about 1.6 L) by continued distillation over four hours at 10 mm HgA and internal temperatures rising to 55° C. left an unstirrable residue. Upon addition of diisopropyl ether (12 L) and water (1000 mL) and heating to 65° C., the mixture became stirrable, and the solids dissolved completely to provide two liquid phases. The lower (aqueous) phase was drained from the upper (organic) phase, which was then extracted with additional water (1000 mL). The aqueous phases were combined and extracted with more diisopropyl ether (4 L). After extraction with water (1000 mL), the second upper (organic) phase was combined with the first, and the resulting mixture was reheated to 50° C. to completely dissolve all solids. The resulting diisopropyl ether solution was then cooled to −5° C. with stirring over seven hours, during which time 7 crystallized. After being stirred at −5° C. for five more hours, the resulting suspension was filtered by suction. The filtered solid was washed with 0° C. diisopropyl ether (1.0 L) and dried at 40° C. and <1 mm HgA to provide 7 (979.6 g, 81.2 % yield) of 99.2% purity by HPLC with ca. 0.3 wt % desbromo 7 as the largest impurity. The crystallization and wash liquors were combined and evaporated first at 69° C. and atmospheric pressure to 1 L volume and then at <40° C. and 10 mm HgA on a rotary evaporator to provide a residue of pale yellow solid 7 (151.49 g, 12.6% yield) of 94.3% purity by HPLC with ca. 3.5 wt % desbromo 7 as the largest impurity.