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0 °C

A mixture of 6-(methylsulfonyl)-3-[(4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.977 g, 1.929 mmol), [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.449 g, 2.12 mmol), N,N-diisopropylethylamine (0.404 mL, 2.315 mmol), and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide (1.705 mL of a 50% solution in ethyl acetate, 2.89 mmol) in dichloromethane (19.29 mL) was stirred at 0° C. for 2 h, warmed to room temperature, and stirred at room temperature overnight. The mixture was diluted with 10% Na2CO3, and extracted with methylene chloride (four times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via column chromatography (ISCO, 40 g silica, 5-100% ethyl acetate hexanes) to afford 6-(methylsulfonyl)-3-[(4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.570 g, 31% yield). MS (m/z) 664.1 (M+H+).

1. temperaturewarmed to room temperature
2. stirringstirred at room temperature overnight
3. extractionextracted with methylene chloride (four times)
4. washThe combined organic extracts were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified via column chromatography (ISCO, 40 g silica, 5-100% ethyl acetate hexanes)