反应详情

Sodium bis(trimethylsilyl)amide (22 ml of 1M solution in THF) was added to a stirred solution of imidazo(4,5-c]pyridine (2.60 g, 0.02 mol) in dry TEF (200 ml) under-argon. A fine white precipitate formed. After 90 m the mixture was treated with purified N-cyclohexyl-N-methyl 4-bromomethylbenzamide (6.20 g, 0.02 mol) dissolved in dry THF (50 ml). The mixture was allowed to warm to ambient temperature and stirred overnight. Methanol (1 ml) was added, followed by water and the product extracted using ethyl acetate (3×150 ml). The combined organic layers were washed with water (2×100 ml), dried over K2CO3 and the solvent removed to give the crude product. Flash chromatography (flash silica, 10% methanol in ethyl acetate) followed by repeated fractional crystallisation (6 times from ethyl acetate/DIPE) gave the desired regioisomer N-cyclohexyl-N-methyl 4-(1H-imidazo(4,5-c]pyridin-1-ylmethyl)benzamide (0.39 g, 5%) as an off white crystalline solid.

1. customA fine white precipitate formed
2. extractionthe product extracted
3. washThe combined organic layers were washed with water (2×100 ml)
4. dry with materialdried over K2CO3
5. customthe solvent removed
6. customto give the crude product
7. customcrystallisation (6 times from ethyl acetate/DIPE)