反应详情

A suspension of methyl 3-(bromomethyl)-6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.025 g, 1.83 mmol) and 4-(4-piperidinyl)morpholine (0.405 g, 2.379 mmol) in acetonitrile (10 mL) was stirred for 3 h. The solvent was removed under reduced pressure, and the residue was dissolved in DMSO and 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 (two times), dried over Na2SO4, filtered, and concentrated in vacuo to afford methyl 6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (0.77 g, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ8.37 (s, 1H), 7.98 (s, 1H), 7.87-7.94 (m, 2H), 7.81 (s, 1H), 7.79 (d, J=7.78 Hz, 1H), 4.09 (s, 3H), 4.01 (s, 3H), 3.83 (quin, J=6.78 Hz, 1H), 3.61 (s, 2H), 3.53 (br. s., 4H), 2.59-2.69 (m, 2H), 2.38 (br. s., 4H), 2.00 (t, J=10.54 Hz, 1H), 1.77-1.86 (m, 2H), 1.62 (d, J=11.04 Hz, 2H), 1.24-1.30 (m, 2H), 1.22 (s, 3H), 1.21 (s, 3H); MS (m/z) 650.2 (M+H+).

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