反应详情

温度

110 °C

Aniline (22.4 mg, 0.24 mmol), cesium carbonate (91 mg, 0.28 mmol), palladium (II) acetate (2.25 mg, 0.01 mmol) and (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (9.34 mg, 0.015 mmol) were added to a dry microwave vial. The vial was capped and purged with nitrogen. A degassed solution of EXAMPLE 70A (74.5 mg, 0.2 mmol) in toluene (1 mL) was added to the microwave vial and the reaction was stirred at 110° C. for 3 hours. The reaction mixture was concentrated and purified on silica gel with 2-25% methanol in dichloromethane to afford 3-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5-phenylamino-pyridine-2-carbonitrile. A solution of this (20 mg, 0.052 mmol) in dimethylsulfoxide was treated with potassium carbonate (36 mg, 0.26 mmol) and 30% hydrogen peroxide (1 mL) while keeping temperature below 0° C. The reaction mixture was stirred at 0° C. for 1 hour and then at room temperature for 18 hours. The reaction was quenched by the addition water, filtered, washed with water and dried to provide the title compound. 1H NMR (DMSO-d6) δ ppm 10.15 (s, 1H), 8.64 (s, 1H), 7.83-7.78 (m, 1H), 7.65 (d, J=2.3, 1H), 7.26 (t, J=7.7, 2H), 7.21 (d, J=3.4, 1H), 7.11-7.04 (m, 4H), 6.96-6.88 (m, 4H), 3.12-3.04 (m, 4H), 2.42-2.32 (m, 4H), 2.20 (s, 3H); MS (ESI) m/z 402 (M+H)+.

1. customThe vial was capped
2. custompurged with nitrogen
3. concentrationThe reaction mixture was concentrated
4. custompurified on silica gel with 2-25% methanol in dichloromethane