反应详情

A mixture of 2.00 g (6.6 mmole) of 2-chloro-9-cyclobutyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-1), 1.655 g (12.08 mmole) of 4-amino-benzoic acid and 200 mL of ethanol-water-hydrochloric acid (20:80:1) was refluxed for 18 hours, then concentrated under reduced pressure. The solid was washed with water and then purified by silica gel chromatography, eluting with dichloromethane-methanol-ammonium hydroxide (92:8:0.3) to give 1.600 g of 4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid (I-11).

1. temperaturewas refluxed for 18 hours
2. concentrationconcentrated under reduced pressure
3. washThe solid was washed with water
4. custompurified by silica gel chromatography
5. washeluting with dichloromethane-methanol-ammonium hydroxide (92:8:0.3)