反应详情

温度

100 °C

To a round bottomed flask was added (S)-1-chloro-4-(3-methylpiperazin-1-yl)pyrido[3,4-d]pyridazine 4 (155 mg, 588 μmol), 4-trifluoromethylphenylboronic acid (167 mg, 882 μmol), tetrakis(triphenylphosphine)palladium (34 mg, 29 μmol), and 2 M aqueous sodium carbonate (588 μl, 1.18 mmol). Toluene (5.9 mL) was added and the reaction was heated to 100° C. After 16 h, the reaction was cooled to RT and diluted with ethyl acetate (70 mL). The organic layer was washed with 1×10 mL of sat. NaHCO3, 1×10 mL of brine. The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography (10:0.5:0.1) (CH2Cl2:MeOH:Et3N) afforded (S)-4-(3-methylpiperazin-1-yl)-1-(4-(trifluoromethyl)phenyl)pyrido[3,4-d]pyridazine 47 (154 mg, 70% yield). 1H-NMR (400 MHz, CDCl3): δ 9.55 (d, J=0.8 Hz, 1H), 8.90 (d, J=5.5 Hz, 1H), 7.86 (m, 4H), 7.73 (dd, J=5.5, 0.8 Hz, 1H), 4.09 (m, 2H), 3.37 (ddd, J=12.5, 11.0, 3.5 Hz, 1H), 2.23 (m, 3H), 2.99 (dd, J=12.5, 10.2 Hz, 1H), 2.85 (br s, 1H), 1.17 (d, J=6.3 Hz, 1H). MS 373.1 (calc'd) 374.0 (M+H, found).

1. temperaturethe reaction was cooled to RT
2. washThe organic layer was washed with 1×10 mL of sat. NaHCO3, 1×10 mL of brine
3. dry with materialThe organic layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by column chromatography (10:0.5:0.1) (CH2Cl2:MeOH:Et3N)