Cesium carbonate → spiro[cyclopent-3-ene-1,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Temperature

45 °C

To a solution of cis-1,4-dichloro-2-butene (1.98 g, 15.8 mmol) and 1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (3.49 g, 13.2 mmol) in DMF (175 mL) was added cesium carbonate (10.7 g, 32.9 mmol). After 24 h the reaction mixture was partitioned between Et2O (200 mL) and H2O (200 mL). The aqueous layer was extracted further with Et2O (2×200 mL). The combined organic layers were washed with H2O (2×100 mL), then brine (100 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. To a solution of this material in dichloromethane (150 mL) was added trifluoroacetic acid (150 mL). After 1 h, the reaction was concentrated, dissolved in EtOH (150 mL) and 2N HCl (150 mL) was added. This mixture was heated at 45° C. for 48 h. The mixture was concentrated, diluted with saturated aqueous NaHCO3, and extracted with dichloromethane (2×). The combined organic layers were dried and concentrated. The crude product was purified by silica gel chromatography, eluting with a gradient of 0 to 5% methanol:dichloromethane to give the title compound (0.62 g). MS: m/z=187.1 (M+1).

1. customAfter 24 h the reaction mixture was partitioned between Et2O (200 mL) and H2O (200 mL)
2. extractionThe aqueous layer was extracted further with Et2O (2×200 mL)
3. washThe combined organic layers were washed with H2O (2×100 mL)
4. dry with materialbrine (100 mL), dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. additionTo a solution of this material in dichloromethane (150 mL) was added trifluoroacetic acid (150 mL)
8. concentrationthe reaction was concentrated
9. dissolutiondissolved in EtOH (150 mL)
10. addition2N HCl (150 mL) was added
11. concentrationThe mixture was concentrated
12. additiondiluted with saturated aqueous NaHCO3
13. extractionextracted with dichloromethane (2×)
14. customThe combined organic layers were dried
15. concentrationconcentrated
16. customThe crude product was purified by silica gel chromatography
17. washeluting with a gradient of 0 to 5% methanol

ORD record

ord-8d28a245e9cb4722bd6ab4fe0e025b93

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08039460B2