Triethylamine → 2-[(4-[[4-Nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]-1-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]ethan-1-one

Participants

Reaction Steps

To a solution of 2-[(4-[4-nitro-3-(trifluoromethyl)phenyl]aminocyclohexyl)oxy]acetic acid (100 mg, 0.28 mmol) in dichloromethane (20 ml) was added 2-(piperazin-1-yl)-6-(trifluoromethyl)quinoline (93.1 mg, 0.33 mmol, 1.2 eq), EDAC.HCl (79 mg, 0.41 mmol, 1.5 eq), HOBt (56 mg, 0.41 mmol, 1.5 eq), Et3N (84 mg, 0.83 mmol, 3 eq). The resulting solution was stirred overnight at room temperature and then quenched by the addition of water (50 ml), extracted with of dichloromethane (3×30 ml) and the organic layers were combined and dried over anhydrous sodium sulfate. The organic solution was filtered and then concentrated under vacuum. The crude material was purified by Pre-TLC using 4% methanol in dichloromethane to elute. Concentration of the product-containing fractions afforded 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]-1-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]ethan-1-one as a yellow solid (77 mg, 45%). (ES, m/z): [M+H]+ 626.40. 1H NMR (300 MHz, CD3OD): δ 8.13 (d, J=9.0 Hz, 1H), 8.02-8.05 (t, J=4.5 Hz, 2H), 7.42-7.79 (m, 2H), 7.29 (d, J=9.3 Hz, 1H), 6.99 (d, J=2.4 Hz, 1H), 6.78-6.81 (dd, J=2.4, 9.2 Hz, 1H), 4.34 (s, 2H), 3.88-3.94 (m, 4H), 3.72-3.78 (m, 4H), 3.45-3.50 (m, 2H), 2.10-2.20 (m, 4H), 1.34-1.54 (m, 4H).

Provenance & Evidence