Water → 2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-N-(1-prop-2-ynyloxymethyl-cyclobutyl)-acet-amide

Participants

Reaction Steps

NaH (172 mg, 60% in oil) was added to a solution of 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-cyclobutyl)-2-methylsulfanyl-acetamide (850 mg) in THF (50 ml), at room temperature, under nitrogen atmosphere. The mixture was stirred until gas evolution ceased (30 min). Propargyl bromide (638 mg, 80% toluene solution) was added and the mixture was stirred at 40° C. during 3 hours, and then after cooling to room temperature poured into water and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over sodium sulphate anhydrous, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate/CH2Cl2, 1/1/1) to give 2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-N-(1-prop-2-ynyloxymethyl-cyclobutyl)-acet-amide (146 mg) as slightly brown oil. 1H NMR (CDCl3) δ ppm: 8.82 (1H, d); 8.18 (1H, d); 8.03 (1H, d); 7.44 (1H, dd); 7.21 (1H, d); 6.88 (1H, br s); 5.62 (1H, s); 4.14 (2H, s); 3.84-3.74 (2H, dd, AB system); 3.28 (1H, s); 2.49-2.13 (4H, m); 2.42 (1H, s); 2.19 (3H, s); 2.01-1.79 (2H, m).

Provenance & Evidence