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Tetrakis(triphenylphosphine)palladium (146 mg, 126 μmol), phenylboronic acid (461 mg, 3.78 mmol), 2 M sodium carbonate (2520 μl, 5.04 mmol), and 1-chloro-4-(trans-2,5-dimethylpiperazine-1-yl)pyrido[3,4-d]pyridazine 43 (700 mg, 2.52 mmol) were added to a round bottom flask. The reaction vessel was purged with nitrogen and toluene (25 mL) was added. The reaction was heated to 100° C. overnight. After cooling to RT, the reaction was diluted with 250 mL of ethyl acetate and washed with 1×50 mL of sat. NaHCO3 and 1×50 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 racemic 4-(trans-2,5-dimethylpiperazine-1-yl)-1-phenylpyrido[3,4-d]pyridazine 44 (750 mg, 93% yield). 1H-NMR (400 MHz, CDCl3): δ 9.76 (d, J=1.2 Hz, 1H), 8.94 (d, J=5.5 Hz, 1H), 7.84 (dd, J=5.9, 1.2 Hz, 1H), 7.78 (m, 2H), 7.57 (m, 2H), 3.83 (dqd, J=10.2, 5.9, 3.1 Hz, 1H), 3.47 (dd, J=12.1, 2.7 Hz, 1H), 3.30 (dqd, J=9.8, 6.3, 2.7 Hz, 1H), 3.25 (dd, J=12.5, 3.1 Hz, 1H), 2.94 (dq J=12.1, 10.2 Hz, 1H), 2.73 (dd, J=12.1, 9.8 Hz, 1H), 1.17 (d, J=6.3 Hz, 1H), 1.11 (d, J=6.6 Hz, 1H). MS 319.2 (calc'd) 320.2 (M+H, found).
