[H-].[Na+].[Br:3][C:4]1[C:5]([C:14]2[S:15][CH:16]=[CH:17][N:18]=2)=[N:6][NH:7][C:8]=1[CH:9]([O:12][CH3:13])[O:10][CH3:11].I[CH3:20].O>CN(C)C=O>[Br:3][C:4]1[C:5]([C:14]2[S:15][CH:16]=[CH:17][N:18]=2)=[N:6][N:7]([CH3:20])[C:8]=1[CH:9]([O:12][CH3:13])[O:10][CH3:11]Under a nitrogen atmosphere, sodium hydride 60% in oil (0.236 g, 5.92 mmol) was added portionwise to a solution of 2-[4-bromo-5-(dimethoxymethyl)-1H-pyrazol-3-yl]-1,3-thiazole (8c) (900 mg, 2.96 mmol) in dry dimethylformamide (5 mL). After 10 minutes stirring, iodomethane (0.28 mL, 4.44 mmol) was added and the reaction mixture was stirred at room temperature for 40 minutes. Water (15 mL) was added and the mixture was extracted with ethyl acetate (2×15 mL). The organic layer was washed with brine (2×10 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 100/0 to 95/5) to provide 2-[4-bromo-5-(dimethoxymethyl)-1-methyl-1H-pyrazol-3-yl]-1,3-thiazole (8d) (586 mg, 1.84 mmol, 62%) and the regioisomer 2-[4-bromo-3-(dimethoxymethyl)-1-methyl-1H-pyrazol-5-yl]-1,3-thiazole (199 mg, 0.62 mmol, 21%).
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