反应详情

温度

-78 °C

A RBF was charged with isoxazol-3-amine (0.016 g, 0.191 mmol) and THF (1.6 mL), and the vessel was cooled to −78° C. for 15 minutes. Lithium bis(trimethylsilyl)amide (1.0 M in THF) (0.208 ml, 0.208 mmol) was then added dropwise over 1 minute. The reaction was stirred for 10 minutes, and then a solution of 1-(2,3′-difluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonyl chloride (0.080 g, 0.173 mmol) in THF (1.6 mL) was added dropwise. The bath was removed, and the resulting mixture was stirred for 45 minutes. The reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via MPLC (ISCO, 40 g), eluting with 0 to 100% ethyl acetate in heptanes. The solid was dried under reduced pressure to provide 1-(2,3′-difluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.012 g, 0.024 mmol, 13.60% yield) as a mixture of atropisomers. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.27 (d, J=1.76 Hz, 1 H) 8.15 (d, J=2.05 Hz, 1 H) 7.97 (br. s., 1 H) 7.74-7.84 (m, 2 H) 7.43-7.53 (m, 1 H) 7.37-7.42 (m, 1 H) 7.33 (d, J=9.98 Hz, 1 H) 7.11-7.18 (m, 2 H) 7.09 (d, J=9.49 Hz, 1 H) 6.86 (dd, J=14.67, 9.29 Hz, 2 H) 6.61 (d, J=1.76 Hz, 1 H) 3.72-3.81 (m, 3 H). m/z (ESI) 510.0 (M+H)+.

1. customThe bath was removed
2. stirringthe resulting mixture was stirred for 45 minutes
3. additionThe reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL)
4. washwas washed with ethyl acetate (20 mL×3)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting material was purified via MPLC (ISCO, 40 g)
9. washeluting with 0 to 100% ethyl acetate in heptanes
10. customThe solid was dried under reduced pressure