Triethylamine → 1-(6-Fluoro-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-[[4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl]oxy]ethan-1-one

Participants

Reaction Steps

To a solution of 2-[[4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl]oxy]acetic acid (144 mg, 0.40 mmol) in dichloromethane (15 ml) was added EDAC.HCl (114 mg, 0.59 mmol), HOBt (80 mg, 0.59 mmol) and triethylamine (120 mg, 1.19 mmol) with stirring for 30 minutes. Then 6-fluoro-1,2,3,4-tetrahydroisoquinoline (60 mg, 0.40 mmol) was added to the reaction mixture and the contents were stirred overnight at room temperature. The reaction mixture was diluted with water (100 ml) and extracted with dichloromethane (3×80 ml). The organic fractions were combined, dried over anhydrous sodium sulfate, filtered, and evaporated to give a residue, which was purified by silica gel column chromatography using 5% ethyl acetate in dichloromethane to afford 1-(6-fluoro-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-[[4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl]oxy]ethan-1-one as a yellow solid (93.8 mg, 48%); (ES, m/z): [M+H]+ 496.00; 1H NMR (300 MHz, CDCl3): δ 8.01 (d, J=9.0 Hz, 1H), 7.09 (m, 1H), 6.95-6.82 (m, 3H), 6.65 (d, J=9.0 Hz, 1H), 4.69 (m, 2H), 4.28 (s, 2H), 3.84-3.70 (m, 2H), 3.48-3.33 (m, 2H), 2.93-2.83 (m, 2H), 2.16-2.13 (m, 4H), 1.52-1.40 (m, 2H), 1.34-1.16 (m, 2H).

Provenance & Evidence