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), 0.05 g (0.18 mmole) of 4-amino-3-methoxy-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. The combined organic layers were washed with brine, dried, 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 0.040 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)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-159).

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 were washed with brine
8. customdried
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by silica gel chromatography
13. washeluting with methanol-dichloromethane (gradient, 0:100-25:75)