反应详情

温度

120 °C

A mixture of 2-tert-butoxycarbonyloxy-4-[3-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-oxo-prop-1-ynyl]-5-fluoro-indole-1-carboxylic acid tert-butyl ester (from Example 4 above) (230 mg, 0.40 mmol) and 3-hydroxy-piperidine (Aldrich, 1.23 g, 12.13 mmol) in DMF (15 ml) was heated to 120° C. for 1.5 hours. The mixture was cooled and NaH (Aldrich, 140 mg, 5.83 mmol) was added in small portions with stirring. After 30 minutes at room temperature and then 20 hours at 120° C. the mixture was cooled and poured into a mixture of ethyl acetate and water. The aqueous layer was extracted few more times with ethyl acetate and the combined organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 60% ethyl acetate in hexanes) and further purified by HPLC (silica gel, 35% ethyl acetate in hexanes) and a precipitation out of THF with excess of pentane to give 6-fluoro-5-(3-hydroxy-piperidin-1-yl)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 45 mg, 31%).

1. temperatureThe mixture was cooled
2. temperature20 hours at 120° C. the mixture was cooled
3. extractionThe aqueous layer was extracted few more times with ethyl acetate
4. dry with materialthe combined organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by flash chromatography (silica gel, 60% ethyl acetate in hexanes)
8. customfurther purified by HPLC (silica gel, 35% ethyl acetate in hexanes)
9. customa precipitation out of THF with excess of pentane