反应详情

To a solution of 2.2 g (0.0056 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-2,2-dichloro-propanoic acid methyl ester (IV-298) in 40 mL of acetic acid was added 2.2 g (0.039 g-atom) of iron powder. The mixture was heated to 80 degrees for 2 hours and then filtered while hot. Water and ethyl acetate were added to the filtrate and the mixture was stirred for 10 minutes and then filtered. The layers were separated. The organic layer was washed successively with ammonium hydroxide and water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The combined organic layers were washed three times with sodium carbonate, three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with hexane-ethyl acetate (gradient, 95:5-50:50) gave 0.66 g of 2-chloro-9-cyclopentyl-7,7-dichloro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-298).

1. temperatureThe mixture was heated to 80 degrees for 2 hours
2. filtrationfiltered while hot
3. additionWater and ethyl acetate were added to the filtrate
4. filtrationfiltered
5. customThe layers were separated
6. washThe organic layer was washed successively with ammonium hydroxide and water
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. washThe combined organic layers were washed three times with sodium carbonate, three times with brine
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customPurification by silica gel chromatography
15. washeluting with hexane-ethyl acetate (gradient, 95:5-50:50)