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

Participants

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) (230 mg, 0.40 mmol) and 3-hydroxymethyl-piperidine (Aldrich, 1.20 g, 12.10 mmol) in DMF (6 ml) was treated with NaH (Aldrich, 146 mg, 6.08 mmol). After stirring for 30 minutes at room temperature and then 30 hours at 120° C. the mixture was cooled and 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 resulting residue was purified by flash chromatography (silica gel,0-50% ethyl acetate in hexanes gradient) and then further purified by HPLC (silica gel, 30% ethyl acetate in hexanes) and precipitation out of THF with excess of pentane to give 6-fluoro-5-(3-hydroxymethyl-piperidin-1-yl)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 12 mg, 8%).

Provenance & Evidence