反应详情

A suspension of methyl 3-(bromomethyl)-7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.732 g, 3.09 mmol) and 4-(4-piperidinyl)morpholine (0.684 g, 4.02 mmol) in acetonitrile (30 mL) was stirred for 3 h. The solvent was removed under reduced pressure, and the residue was purified via HPLC (Biotage RP, 0-50% MeCN/H2O with 0.1% TFA). The fractions containing the product were neutralized with saturated aqueous NaHCO3, and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated to afford methyl 7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.6 g, 80% yield). 1H NMR (400 MHz, DMSO-d6) δ8.40 (s, 1H), 7.98 (s, 1H), 7.87-7.93 (m, 2H), 7.75-7.83 (m, 2H), 5.11 (dt, J=6.02, 12.05 Hz, 1H), 4.00 (s, 3H), 3.61 (s, 2H), 3.51-3.56 (m, 4H), 3.41 (s, 3H), 2.62 (d, J=11.29 Hz, 2H), 2.38 (br. s., 4H), 1.95-2.05 (m, 1H), 1.81 (t, J=10.92 Hz, 2H), 1.62 (d, J=12.55 Hz, 2H), 1.43 (s, 3H), 1.41 (s, 3H), 1.20-1.29 (m, 2H); MS (m/z) 650.2 (M+H+).

1. customThe solvent was removed under reduced pressure
2. customthe residue was purified via HPLC (Biotage RP, 0-50% MeCN/H2O with 0.1% TFA)
3. additionThe fractions containing the product
4. extractionextracted with methylene chloride (three times)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated