Sodium hydride → 6-fluoro-5-(4-hydroxy-piperidin-1-yl)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

Participants

Reaction Conditions

Reaction Steps

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) (392 mg, 0.69 mmol) and 4-hydroxy-piperidine (Aldrich, 2.12 g, 20.94 mmol) in DMF(6 mL) was treated with NaH. (Aldrich, 250 mg, 10.42 mmol). The mixture was stirred for 30 minutes at room temperature and overnight at 120° C. The reaction mixture was poured in a mixture of ethyl acetate and water. The aqueous layer was extracted a 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, with 0-50% ethyl acetate in hexanes gradient), and further purified by HPLC (silica gel, 50% ethyl acetate in hexanes) and precipitation out of THF with excess of pentane to give 6-fluoro-5-(4-hydroxy-piperidin-1-yl)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 85 mg, 38%).

Provenance & Evidence