反应详情

A mixture of 0.05 g (0.15 mmole) of 2-chloro-9-cyclopentyl-5-ethyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-138), 0.04 g (0.18 mmole) of 4-amino-N-(1-methyl-piperidin-4-yl)-benzamide, 0.04 g (0.23 mmole) of p-toluenesulfonic acid monohydrate and 4.0 mL of 2-propanol was heated at 160 degrees for 2 hours in a microwave reactor. The cooled reaction mixture was concentrated under reduced pressure. The residue was diluted with dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phases were 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 purified by silica gel chromatography eluting with methanol-dichloromethane (gradient, 0:100-25:75) to give 0.041 g of 4-(9-cyclopentyl-5-ethyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide (I-141).

1. temperaturewas heated at 160 degrees for 2 hours in a microwave reactor
2. customThe cooled reaction mixture
3. concentrationwas concentrated under reduced pressure
4. additionThe residue was diluted with dichloromethane
5. washwashed twice with saturated aqueous sodium bicarbonate solution
6. extractionThe aqueous phases were extracted with dichloromethane
7. washthe combined organic layers washed with brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel chromatography
12. washeluting with methanol-dichloromethane (gradient, 0:100-25:75)