反应详情

To a mixture of 0.67 g (0.0021 mole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20), 0.63 g (0.00317 mole) of 4-amino-2-fluoro-5-methoxy-benzoic acid methyl ester and 30 mL of dioxane was added 0.05 g (0.00021 mole) of palladium (II) acetate and 1.91 g (0.00588 mole) of cesium carbonate. The mixture was stirred at room temperature for 5 minutes and then heated to 100 degrees for 18 hours. The solid was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with water then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with hexanes-ethyl acetate (60:40) to give 0.81 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxy-benzoic acid methyl ester (I-168).

1. temperatureheated to 100 degrees for 18 hours
2. customThe solid was removed by filtration
3. concentrationthe filtrate was concentrated under reduced pressure
4. additionThe residue was diluted with ethyl acetate
5. washwashed with water
6. dry with materialbrine, dried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel chromatography
10. washeluting with hexanes-ethyl acetate (60:40)