Propargyl bromide → 2-(3-Ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-methoxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3-ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methoxymethyl-1-methyl-ethyl)-2-methylsulfanyl-acetamide (120 mg) in dry THF (10 ml) NaH (27 mg, 60% in oil) was added at room temperature under a nitrogen atmosphere. After 30 minute propargyl bromide (115 mg) was added to the reaction mixture. After stirring during 5 h one equivalent of NaH and one equivalent of propargyl bromide were added. The mixture was stirred during 4 h at 55° C., then quenched with water and diluted with ethyl acetate. The water phase was extracted twice with ethyl acetate and the combined organic phases dried over sodium sulfate, filtered and evaporated. The crude residue was purified by column chromatography (cyclohexane/ethyl acetate, 3:2) to give 2-(3-Ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-methoxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide (66 mg) as a light brown oil as a mixture of diastereoisomers.

Provenance & Evidence