Acetic Acid → 6-[(1-methylethyl)sulfonyl]-3-{[3-methyl-4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide

Participants

Reaction Steps

Acetic acid (9.73 μL, 0.170 mmol), morpholine (0.030 g, 0.340 mmol), and sodium triacetoxyborohydride (0.048 g, 0.227 mmol) were added to a suspension of 6-[(1-methylethyl)sulfonyl]-3-[(3-methyl-4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.080 g, 0.113 mmol) in dichloromethane (1.5 mL). The mixture was stirred at room temperature for 3 d. The solution was diluted with water (3 mL) and methylene chloride (5 mL) and poured into a hydrophobic frit to separate the phases. The organic phase was concentrated and the residue was purified via HPLC (Waters, Sunfire C18, 30×100 mm, 35-69% CH3CN/H2O with 0.1% TFA) to afford 6-[(1-methylethyl)sulfonyl]-3-{[3-methyl-4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.040 g, 45% yield) as a mixture of diastereomers. 1H NMR (400 MHz, DMSO-d6) δ10.1250=4 Hz, 0.5H), 10.045 (br d, J=4 Hz, 0.5H), 8.38 (m, 2H), 8.14 (m, 2H), 7.97 (m, 2 H), 7.84 (d, J=8 Hz, 1H), 7.73 (m, 1H), 7.63 (m, 2H), 7.45 (br s, 2H), 6.24 (apparent q, J=6.8 Hz, 1H), 3.50 (m, 4H), 3.17 (m, 1H), 2.40-2.05 (m, 5H), 1.95-0.75 (m, 14H), 0.410 (d, J=6 Hz, 1.7H), 0.295 (br d, J=4 Hz, 1.3H). MS (m/z) 777.3 (M+H+).

Provenance & Evidence