反应详情

Thionyl chloride (11.42 g) is added slowly at room temperature to a suspension of 5-(5-carboxypentyl)imidazo[1,5-a]pyridine (21.0 g) and sulfamide (10.5 g) in 90 ml of sulfolane. The mixture is heated at 120° until gas evolution ceases and solid p-toluenesulfonic acid monohydrate (1.71 g) is added carefully. After heating an additional 3 hours at 120°, the reaction mixture is cooled, poured onto 200 g of ice and acidified with 130 ml of 1N hydrochloric acid. The aqueous phase is sequentially extracted with ethyl acetate (3×100 ml), made basic with solid sodium bicarbonate and reextracted with ethyl acetate (3×125 ml). The organic extracts are washed with 0.5N sodium hydroxide (5×50 ml), dried over sodium sulfate and evaporated to yield an oil which is chromatographed on 60 g of silica gel with ethyl acetate to yield 5-(5-cyanopentyl)-imidazo[1,5-a]pyridine as an oil.

1. additionis added carefully
2. temperatureAfter heating an additional 3 hours at 120°
3. temperaturethe reaction mixture is cooled
4. extractionThe aqueous phase is sequentially extracted with ethyl acetate (3×100 ml)
5. washThe organic extracts are washed with 0.5N sodium hydroxide (5×50 ml)
6. dry with materialdried over sodium sulfate
7. customevaporated
8. customto yield an oil which
9. customis chromatographed on 60 g of silica gel with ethyl acetate