反应详情

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 EDAC.HCl (79.4 mg, 0.41 mmol, 1.5 eq), HOBt (56 mg, 0.41 mmol, 1.5 eq), triethylamine (111.6 mg, 1.10 mmol, 4 eq), and N-(2-aminoethyl)-6-chloro-N-(2-chloroethyl)quinolin-2-amine (93.8 mg, 0.33 mmol, 1.2 eq). The resulting solution was stirred overnight at room temperature and then quenched by the addition of water (50 ml), extracted with dichloromethane (3×30 ml). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue. The crude material was purified by Pre-TLC using 4% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1-[4-(6-chloroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one as a yellow solid (69.8 mg, 42%). (ES, m/z): [M+H]+ 592.35; 1H NMR (300 MHz, CDCl3): δ 8.00 (d, J=9.0 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.61 (s, 2H), 7.52 (s, 1H), 7.01 (d, J=9.0 Hz, 1H), 6.91 (s, 1H), 6.84 (d, J=2.4 Hz, 1H), 6.61-6.65 (m, 1H), 4.45 (d, J=7.5 Hz, 1H), 4.26 (s, 2H), 3.75-3.78 (m, 7H), 3.37-3.50 (m, 2H), 2.14 (d, J=10.5 Hz, 4H), 1.44-1.51 (m, 2H), 1.24-1.35 (m, 2H).

1. customquenched by the addition of water (50 ml)
2. extractionextracted with dichloromethane (3×30 ml)
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under vacuum
6. customto give a residue
7. customThe crude material was purified by Pre-TLC
8. washto elute
9. concentrationconcentrated under vacuum