Dimethylformamide → 2-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

Participants

Reaction Steps

1-Hydroxy-7-azabenzotriazole (0.717 g), O-(1H benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium tetrafluoroborate (1.692 g) and 2-mmino-2-methyl-3-prop-2-ynyloxy-propan-1-ol hydrochloric salt (0.947 g) were added at room temperature to a solution of triethylamine (2.14 ml) and (3-ethynyl-quinolin-6-yloxy)-methylsulfanyl-acetic acid (1.20 g) in DMF. The reaction mixture was stirred 16 hrs at room temperature and then poured onto a mixture of ethyl acetate and brine. The two layers were separated and the aqueous layer was extracted thrice with ethyl acetate. The organic layers were combined, washed with sat. sodium hydrogen carbonate, with water and brine and then dried over sodium sulphate. After filtration and concentration under reduced pressure the crude residue was purified was dissolved in 24 ml of THF/H2O (1/1) and treated with of LiOH monohydrate at room temperature for 1 h 45 min. The crude mixture was extracted (pH=11) thrice with ethyl acetate. The organic layers were combined, washed with water and brine and after separation dried over sodium sulphate. Filtration and concentration under reduced pressure provided crude 2-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide as a yellow oil that was used in the next step, Stage 4, without any further purification. 1H NMR (CDCl3) δ ppm: 8.88 (1H, d); 8.22 (1H, d); 8.07 (1H, d); 7.49 (1H, dd); 7.39 (1H, s br); 7.22 (1H, m); 5.68 (1H, s); 4.22-4.16 (2H, m); 3.90 (1H, s br); 3.81-3.60 (4H, m); 3.30 (1H, s); 2.45 (1H, dt); [{2.22 (s), 2.20 (s) 3H}, isomer A and isomer B]; [{1.40 (s), 1.34 (s) 3H}, isomer A and isomer B].

Provenance & Evidence