Propargyl bromide → 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methyl-2-prop-2-ynyloxy-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

Participants

Reaction Steps

Sodium hydride (55% in dispersion in oil) (0.097 g) was added portionwise to a solution of 2-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide (0.4 g) from Example 12b, Stage 3 described above in dry THF (20 ml) at 0° C. The reaction mixture was stirred at room temperature for 0.5 h. Propargyl bromide (0.166 ml) was added dropwise at 0° C. and the resulting mixture was stirred at room temperature for 23 hrs. The reaction mixture was diluted with ethyl acetate and water was added dropwise. The two phases were separated and the aqueous layer was extracted thrice with ethyl acetate. The organic layers were combined, washed once with brine dried over sodium sulphate, filtered and evaporated to give a dark orange oil which was purified by column chromatography (hexane/ethyl acetate 4:2, 1:1) to yield 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methyl-2-prop-2-ynyloxy-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide as a white solid (m.p.: 95-100° C.). 1H NMR (CDCl3) δ ppm: 8.84 (1H, d); 8.22 (1H, d); 8.04 (1H, d); 7.49 (1H, dd); 7.21 (1H, d); 6.98 (1H, s br); 5.61 (1H, s); 4.19-4.16 (4H, m); 3.82-3.61 (2H, dd); 3.73 (2H, s); 3.29 (1H, s); 2.47-2.43 (2H, m); 2.21 (3H, s); 1.46 (3H, s).

Provenance & Evidence