反应详情

A mixture of 3-amino-2-ethoxycarbonyl-pyrrole (0.276 g 1.79 mmol), 5-(6-chloro-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (0.5 g, 1.79 mmol) and 1,3-cyclohexanedione (0.201 g, 1.79 mmol) in 5 ml of ethanol is heated at reflux temperature for 2 hours. The reaction mixture is then concentrated under reduced pressure and purified on a silica gel column (120 g) eluted with a mixture of dichloromethane and methanol (99/1, v/v). The fractions containing the expected products are concentrated under reduced pressure and then purified using preparative LC/MS method B on a Xbridge C18 column (Waters, 30*100 mm) eluted with a 0 to 50% gradient of acetonitrile in aqueous 10 mM ammonium formate pH=9.0 at a 30 ml/min. flow rate in 12 min. The fraction containing the expected product are concentrated under reduced pressure. The residue is resuspended in 2 ml of acetonitrile, heated at reflux temperature and cold to room temperature. The insoluble material is collected by filtration, washed with diisopropyl ether (2×2 ml) and dried under vacuum to yield 115 mg of 9-[5-(5-chloro-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester as a white powder. Yield=12%. Analytical LC/MS (method B): m/z=509 (positive ion mode, [M+H]+, 1 Cl present), m/z=507 (negative ion mode, [M−H]−, 1 Cl present)

1. temperatureis heated
2. temperatureat reflux temperature for 2 hours
3. concentrationThe reaction mixture is then concentrated under reduced pressure
4. custompurified on a silica gel column (120 g)
5. washeluted with a mixture of dichloromethane and methanol (99/1
6. additionThe fractions containing the expected products
7. concentrationare concentrated under reduced pressure
8. custompurified
9. washeluted with a 0 to 50% gradient of acetonitrile in aqueous 10 mM ammonium formate pH=9.0 at a 30 ml/min. flow rate in 12 min
10. additionThe fraction containing the expected product
11. concentrationare concentrated under reduced pressure
12. temperatureheated
13. temperatureat reflux temperature
14. customcold to room temperature
15. filtrationThe insoluble material is collected by filtration
16. washwashed with diisopropyl ether (2×2 ml)
17. customdried under vacuum