Hydrochloric Acid → 2-Chloro-5-[(1-methyl-1H-imidazol-5-yl)carbonyl]pyridine

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Reaction Steps

Into a 250-mL 3-necked round-bottom flask, was placed a solution of 1-methyl-1H-imidazole (5 g, 60.90 mmol) in tetrahydrofuran (40 mL). This was followed by the addition of n-BuLi (29.3 mL, 2.5 M in hexanes) at −78° C., then stirred for 45 minutes. To this was added Et3SiCl (9.15 g, 61.00 mmol, 100%), the solution was stirred for 1 hour at −78° C. To the mixture was added n-BuLi (26 mL, 2.5M in hexanes), and stirred for another 45 minutes. To the mixture was added a solution of 6-chloro-N-methoxy-N-methylpyridine-3-carboxamide (8.13 g, 40.52 mmol, 37: step b) in tetrahydrofuran (20 mL) at −78° C. The resulting solution was stirred overnight at room temperature. The pH value of the solution was adjusted to 3-4 with aqueous hydrogen chloride (1 mol/L), then stirred for 2 hours at room temperature. Aqueous sodium hydroxide (1.5 mol/L) was employed to adjust the pH to 9-10. The resulting solution was diluted with 100 mL of H2O. The resulting solution was extracted with 3×100 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (100:0˜15:1) to give the title compound as a yellow solid.

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