[CH3:1][C:2]1[S:6][C:5]([C:7]([O:9]C)=[O:8])=[CH:4][C:3]=1[C:11]1[N:15]([CH3:16])[N:14]=[CH:13][CH:12]=1.[Br:17]N1C(=O)CCC1=O.[OH-].[Na+]>O1CCCC1>[Br:17][C:12]1[CH:13]=[N:14][N:15]([CH3:16])[C:11]=1[C:3]1[CH:4]=[C:5]([C:7]([OH:9])=[O:8])[S:6][C:2]=1[CH3:1]A solution of methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (250 mg, 1.058 mmol) [prepared in Example 99] and N-bromosuccinimide (188 mg, 1.06 mmol) in tetrahydrofuran (5.29 ml) was stirred in a sealed tube for 1 h at 70° C. Sodium hydroxide (3.53 ml, 21.16 mmol) was added in one portion and the solution stirred an additional 1 h. The reaction mixture was then partitioned between H2O-DCM and the pH of the aqueous phase was adjusted to ˜4 and washed several times with DCM. The combined organic fractions were dried over Na2SO4 and concentrated yielding 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylic acid (289 mg, 0.96 mmol, 91% yield) as a yellow oil: LCMS (ES) m/e 301, 303 (M, M+2)+.
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