反应详情

A mixture of 0.05 g (0.17 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-20), 0.04 g (0.20 mmole) of 4-amino-N-(tetrahydro-pyran-4-yl)-benzamide and 0.05 g (0.25 mmole) of p-toluenesulfonic acid monohydrate in 4.0 mL of 2-propanol was heated at 160 degrees for 2 hours in a microwave reactor. The cooled mixture was then concentrated under reduced pressure. The residue was diluted with dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane, and the combined organic layers washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was washed with water and dried to give 0.070 g of 4-(9-cyclopentyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(tetrahydro-pyran-4-yl)-benzamide (I-136).

1. temperaturewas heated at 160 degrees for 2 hours in a microwave reactor
2. concentrationThe cooled mixture was then concentrated under reduced pressure
3. additionThe residue was diluted with dichloromethane
4. washwashed twice with saturated aqueous sodium bicarbonate solution
5. extractionThe aqueous phase was extracted with dichloromethane
6. washthe combined organic layers washed with brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. washThe residue was washed with water
11. customdried