Hydrochloric Acid → 1-((1S,3S)-3-(3-fluorophenyl)cyclopentyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide

Participants

Reaction Steps

A 10-mL RBF was charged with perfluorophenyl 1-(3-(3-fluorophenyl)cyclopentyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (110 mg, 0.199 mmol) then purged with nitrogen for 10 min. Tetrahydrofuran (732 μL) and 3-aminoisoxazole (19.09 μl, 0.258 mmol) were sequentially introduced and the resultant solution cooled to 0° C. A solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 M, 457 μL, 0.457 mmol) was added dropwise via syringe to the stirred reaction mixture over 3 min. After 15 min, 1.0 N HCl (5 mL) was introduced and the resultant reaction mixture was allowed to warm to ambient temperature. The mixture was diluted with and EtOAc (10 mL) and the layers were separated, and the aqueous layer was further extracted with EtOAc (3×10 mL). The combined organic layers were then washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by flash column chromatography (25-g Biotage Snap Ultra Column, eluent: gradient, 0 to 100% EtOAc in hexanes with CH2Cl2 as a 10% additive) to afford 1-01R,3R)-3-(3-fluorophenypcyclopentyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide, 1-((1R,3S)-3-(3-fluorophenyl)cyclopentyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide, 1-((1S,3R)-3-(3-fluorophenyl)cyclopentyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide, 1-((1S,3S)-3-(3-fluorophenyl)cyclopentyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide (50 mg, 0.110 mmol, 55.5% yield)—one unassigned disastereomer was isolated, mixture of enantiomers (since unassigned stereochemistry—listing all the possible products). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.65 (s, 1 H) 8.73 (d, J=1.76 Hz, 1 H) 8.32 (dd, J=6.22, 1.35 Hz, 1 H) 8.08 (d, J=9.54 Hz; 1 H) 8.01 (m, J=1.60 Hz, 2 H) 7.31-7.42 (m, 1 H) 7.14-7.24 (m, 2 H) 6.97-7.08 (m, 1 H) 6.71 (d, J=9.43 Hz, 1 H) 6.47 (d, J=1.76 Hz, 1 H) 5.88 (d, J=1.76 Hz, 1 H) 5.51-5.71 (m, 1 H) 3.70-3.91 (m, 1 H) 3.16-3.29 (m, 1 H) 2.01-2.47 (m, 5 H) 1.70-1.87 (m, 1 H). m/z (ESI) 454.0 (M+H)+.

Provenance & Evidence