反应详情

Sodium hydride (142 mg, 3.55 mmol) was added to 4-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 400 mg, 1.182 mmol) in DMF (7 mL) at room temperature and the mixture stirred for 30 min, 1,1-dimethoxy-4,4-bis(methylthio)but-3-en-2-one (394 mg, 1.773 mmol) was added and stirring continued overnight. The reaction mixture was diluted with ethyl acetate and washed with water, 10% lithium chloride and water. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (80 g column, eluting with 2-5% methanol/dichloromethane). (Z)-N,N-Dicyclopropyl-4-(4,4-dimethoxy-1-(methylthio)-3-oxobut-1-enylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (484 mg, 0.944 mmol, 80% yield) was obtained as a yellow solid.

1. stirringstirring continued overnight
2. washwashed with water, 10% lithium chloride and water
3. dry with materialThe organic layer was dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by flash chromatography on silica gel using
7. washan automated ISCO system (80 g column, eluting with 2-5% methanol/dichloromethane)