Propylamine → 2-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-ethynyl-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a suspension of 2-{2-[7-chloro-3-(3,5-dimethylphenyl)-6-iodo-2-oxo- 1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (EXAMPLE 4.2 Step B, 200 mg in 3 mL N,N-dimethylformamide) was added tetrakis(triphenylphosphine)palladium (18 mg) followed by copper(I) iodide (30 mg), n-propylamine (0.26 mL) and trimethylsilylacetylene (0.45 mL) and the mixture sealed in a thick-walled tube. This was heated to 95° C. on an oil bath for 10 hours, then cooled to room temperature and diluted with diethyl ether. This was washed successively with water and brine and the combined organics dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane, 30:70; then 40:60) gave a mixture of the title compound and the corresponding trimethylsilyl derivative (155 mg). This material was converted to the title compound by treatment with 4.4 mg of potassium carbonate in 2 mL methanol. After 1 hour, the mixture was diluted with methylene chloride, washed with half-saturated sodium chloride, then brine and dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane, 30:70; then 40:60) gave the title compound (127 mg).

Provenance & Evidence