4-Morpholinopiperidine → Methyl 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Participants

Reaction Steps

A suspension of methyl 3-(bromomethyl)-7-(ethyloxy)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.705 g, 3.12 mmol) and -(4-piperidinyl)morpholine (0.691 g, 4.06 mmol) in acetonitrile (30 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 were 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 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.54 g, 78% yield). 1H NMR (400 MHz, DMSO-d6) δ8.40 (s, 1H), 7.98 (s, 1H), 7.87-7.94 (m, 2H), 7.76-7.81 (m, 2H), 4.40 (q, J=6.94 Hz, 2H), 4.01 (s, 3H), 3.61 (s, 2H), 3.53 (br. s., 4H), 3.42 (s, 3H), 2.62 (d, J=11.29 Hz, 2H), 2.38 (br. s., 4H), 1.93-2.05 (m, 1H), 1.81 (t, J=11.04 Hz, 2H), 1.62 (d, J=12.05 Hz, 2H), 1.47 (t, J=6.90 Hz, 3H), 1.18-1.30 (m, 2H); MS (m/z) 636.2 (M+H+).

Provenance & Evidence