反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 90 °C
PROCEDURE
实验过程
1-(5-Bromo-2-methoxy phenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.300 g, 0.630 mmol), (3-(trifluoromethyl)phenyl)boronic acid (0.179 g, 0.945 mmol), potassium carbonate (0.261 g, 1.890 mmol), and Pd(PPh3)4 (0.073 g, 0.063 mmol) were combined in 1,4-dioxane (2.362 ml) and water (0.787 ml). The reaction was heated to 90° C. for 3 h. The reaction was cooled to RT and quenched with NH4Cl (saturated aqueous solution), and extracted with DCM (×3) and the organics were then dried via phase separator and concentrated in vacuo. The material was purified via MPLC, eluting with 0-100% ethyl acetate in heptanes to yield N-(isoxazol-3-yl)-1-(4-methoxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.149 g, 0.275 mmol, 43.7% yield) as a light yellow solid. MS (ESL pos. ion) m/z: [M+1] 542.2 NMR (400 MHz, DMSO-d6) □ ppm 3.74 (s, 3 H) 6.44 (d, J=1.76 Hz, 1 H) 6.82 (dd, J=9.24, 3.77 Hz, 2H) 7.42 (d, J=8.80 Hz, 1 H) 7.66-7.70 (m, 2 H) 7.84 (dd, J=9.05, 2.20 Hz, 1 H) 7.89 (d, J=2.45 Hz, 1 H) 7.97-8.07 (m, 3 H) 8.23 (d, J=9.49 Hz, 1 H) 8.38 (d, J=2.35 Hz, 1 H) 8.72 (d, J=1.76 Hz, 1 H) 11.65 (s, 1 H). N-3-Isoxazolyl-1-(4-methoxy-3′-(trifluoromethyl)-3-biphenylyl)-2-oxo-1,2-dihydro-6-quinolinesulfonamide was separated by chiral SFC on a Chiralpak AD with 35% MeOH to give (P)—N-3-isoxazolyl-1-(4-methoxy-3′-(trifluoromethyl)-3-biphenylyl)-2-oxo-1,2-dihydro-6-quinolinesulfonamide as peak 1 and (M)-N-3-isoxazolyl-1-(4-methoxy-3′-(trifluoromethyl)-3-biphenylyl)-2-oxo-1,2-dihydro-6-quinolinesulfonamide as peak 2, both as white solids. Data for peak 1: NMR (400 MHz, DMSO-d6) δ ppm 3.73 (s, 3 H) 6.16-6.27 (m, 1 H) 6.66-6.72 (m, 1 H) 6.72-6.77 (m, 1 H) 7.35-7.45 (m, 1 H) 7.64-7.69 (m, 2 H) 7.73-7.79 (m, 1 H) 7.83-7.87 (m, 1 H) 7.96-8.06 (m, 3 H) 8.13-8.20 (m, 1 H) 8.20-8.24 (m, 1 H) 8.35-8.43 (m, 1 H). MS (ESI, pos. ion) m/z: [M+1] 542.2; Data for peak 2: 1H NMR (400 MHz, DMSO-d6) δ ppm 3.73 (s, 3 H) 6.08-6.18 (m, 1 H) 6.58-6.67 (m, 1 H) 6.68-6.75 (m, 1 H) 7.36-7.44 (m, 1 H) 7.61-7.74 (m, 3 H) 7.80-7.86 (m, 1 H) 7.96-8.06 (m, 3 H) 8.11-8.18 (m, 2 H) 8.20-8.25 (m, 1 H); MS (ESL pos. ion) m/z: [M+1] 542.0.
WORKUP
后处理
- temperatureThe reaction was cooled to RT
- customquenched with NH4Cl (saturated aqueous solution)
- extractionextracted with DCM (×3)
- customthe organics were then dried via phase separator
- concentrationconcentrated in vacuo
- customThe material was purified via MPLC
- washeluting with 0-100% ethyl acetate in heptanes