Reaction Steps
To a yellow-green suspension of 8-bromo-6-methoxy-4-(2-trimethylsilanyl-ethoxymethoxy)-quinoline-2-carboxylic acid (Reference Example 27c) (4-morpholin-4-yl-phenyl)-amide (1.155 g, 1.96 mmol), N-methyl homopiperazine (0.39 mL, 3.14 mmol), and 4 Å sieves in 30 mL anhydrous toluene was added Pd2(dba)2 (90.0 mg, 0.098 mmol) and BINAP (0.358 g, 0.58 mmol). The resulting reddish brown mixture became lighter in color upon treatment with cesium carbonate (2.544 g, 7.81 mmol). The reaction mixture was heated at reflux under nitrogen for 17 hours. The clear brown solution was cooled to room temperature, concentrated, and then purified by flash chromatography on silica gel using a slow gradient of 95:5 to 50:50 methylene chloride:methanol to afford the desired product (0.989 g, 81%). 1H NMR (300 MHz, DMSO, d6) δ 9.88 (s, 1H, NH), 7.73 (s, 1H, ArH3), 7.68 (d, 2H, Jo=8.9 Hz, ArH2′ & H6′), 7.00 (d, 2H, Jo=8.9 Hz, ArH3′ & H5′), 6.94 (d, 1H, Jm=2.7 Hz, ArH5), 6.66 (d, 1H, Jm=2.7 Hz, ArH7), 5.62 (s, 2H, OCH2O), 3.87 (s, 3H, OCH3), 3.80 (t, 2H, J=8.0 Hz, OCH2CH2Si), 3.73 (t, 4H, J=4.7 Hz, OCH2CH2N), 3.63 (t, 2H, J=5.9 Hz, ArNCH2CH2CH2NCH3), 3.33 (bs, 2H, ArNCH2CH2NCH3), 3.09 (t, 4H, J=4.7 Hz, OCH2CH2N), 2.97 (bs, 2H, ArNCH2CH2NCH3), 2.69 (bs, 2H, ArNCH2CH2CH2CH3), 2.35 (s, 3H, NCH3), 2.09 (bs, 2H, ArNCH2CH2CH2NCH3), 0.94 (t, 2H, J=8.0 Hz, OCH2CH2Si), −0.03 (s, 9H, Si(CH3)3; Mass Spec.: calc. for [C33H47N5O5Si+H]+ Theor. m/z=622; Obs.=622.
