P7C3-A20

1260172-05-1

1235481-90-9

To a vial containing N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-N-(3-methoxyphenyl)-4-nitrobenzenesulfonamide (21.0 mg, 0.030 mmol) were added lithium hydroxide (3.2 mg, 0.134 mmol), N,N-dimethylformamide (0.5 mL, 0.06 M), and mercaptoacetic acid ( 4.2 μL, 0.060 mmol). The reaction mixture was stirred for 1 h at room temperature, then diluted with ethyl acetate and washed sequentially with water, saturated sodium bicarbonate solution, water (3 times) and brine. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography (eluent: 30% ethyl acetate/hexane containing 0.2% triethylamine) to give 13.6 mg of the target compound in 88% yield. Another synthetic method: DAST (diethylamino sulfur trifluoride, 0.12 mL, 0.916 mmol) was added dropwise to a solution of 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)propan-2-ol (0.102 g, 0.203 mmol) in anhydrous dichloromethane (6.0 mL), and the reaction was carried out at -78 °C. The reaction mixture was stirred at -78 °C for 1 h, then slowly warmed to 0 °C and kept for 5 h. The reaction was carried out at -78 °C. The reaction was quenched by addition of phosphate buffer (pH=8) and extracted with dichloromethane. The aqueous phase was extracted twice with dichloromethane (10 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel fast column chromatography (eluent: 20% ethyl acetate/hexane containing 0.2% triethylamine) and the fraction containing the desired fluorinated product was further purified with 40% ethyl acetate/hexane containing 0.1% triethylamine to give 5.7 mg of the target compound. Analytical data for 3,6-dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine: 1H NMR (CDCl3, 500 MHz) δ 8.16 (2H, J = 2.0 Hz), 7.56 (dd, 2H, J = 1.9, 8.7 Hz), 7.31 (d, 2H, J = 8.6 Hz), 7.11 (t, 1H, J = 8.1 Hz), 6.36 (dd, 1H, J = 2.2, 8.1 Hz), 6.23 (dd , 1H, J = 2.0, 8.0 Hz), 6.15 (t, 1H, J = 2.3 Hz), 5.11 (ddd, 1H, J = 4.6, 5.8, 10.4, 47.7 Hz), 4.60 (m, 2H), 4.39 (dm, 2H), 3.95 (t, 1H, J = 6.3 Hz), 3.75 (s, 3H). MS (ESI), m/z: 504.9 (M + 1)+. ([M + 1]+ for C22H19Br2FN2O calculated: 505.0).