Nitrogen was bubbled into a mixture of 7-(3-dimethylaminomethylcyclobutyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (891.5 mg, 2.401 mmol), 2-phenyl-7-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-quinoline (795 mg, 2.40 mmol), Na2CO3 (634 mg, 5.98 mmol), and Pd(PPh3)4 (171 mg, 0.148 mmol; 6 mol %) in DMF (40 mL)/water (8 mL) for 5 min at ambient temperature, then the mixture was heated to 80° C. (bath temp.) for 4.5 h. The solvents were evaporated, water was added, the mixture was extracted with CH2Cl2 (4×30 mL), and the combined extracts were washed with brine and dried over MgSO4. The crude material (yellow oil) was chromatographed on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with CH2Cl2 (1-28)→5% MeOH in CH2Cl2 (29-56)→10% MeOH in CH2Cl2 (57-80)→10% MeOH in CH2Cl2 with 0.07M NH3 (81-130)]. Mixed fractions were chromatographed again [5 g/25 mL cartridge, eluting with CH2Cl2 (1-5)→5% MeOH in CH2Cl2 (6-24)→10% MeOH in CH2Cl2 with 0.07M NH3 (25-40)]. One obtained the target compound as beige solid. 1H NMR (CDCl3, 400 MHz): δ=2.10-2.23 (mc, 2H), 2.27 (s, 6H), 2.35-2.46 (m, 1H), 2.49 (d, J=6.8 Hz, 2H), 2.77-2.86 (mc, 2H), 5.17 (brs, 2H), 5.20-5.30 (m, 1H), 7.31 (s, 1H), 7.46-7.52 (m, 1H), 7.52-7.58 (m, 2H), 7.70 (dd, J=1.6, 8.4 Hz, 1H), 7.92 (d, J=8.7 Hz, 1H), 7.94 (d, J=8.1 Hz, 1H), 8.17-8.22 (m, 2H), 8.27 (d, J=8.5 Hz, 1H), 8.30 (brs, 1H), 8.36 (s, 1H). 13C NMR (CDCl3, 100.6 MHz, DEPT135): δ=27.13 (+), 36.50 (2C, −), 45.26 (+), 45.73 (2C, +), 66.10 (−), 101.20 (Cquart), 116.07 (Cquart), 119.00 (+), 120.74 (+), 125.98 (Cquart), 127.38 (+), 127.55 (2C, +), 128.28 (+), 128.47 (+), 128.86 (2C, +), 129.52 (+), 136.45 (Cquart), 136.55 (+), 139.41 (Cquart), 148.51 (Cquart), 150.92 (Cquart), 152.04 (+), 156.99 (Cquart), 158.13 (Cquart). MS (ES+): m/z 449.2 (23) [MH+], 404.1 (4) [MH+-HN(CH3)2], 338.2 (4) [MH+-C4H5CH2N(CH3)2]. HPLC: tR=2.0 min (OpenLynx, polar—5 min).
