Reaction Steps
Pd2dba3 (8.67 mg, 9.46 μmol, Strem Chemicals, MA), K3PO4 (161 mg, 0.757 mmol), XPhos (9.02 mg, 0.019 mmol, Strem Chemicals, MA), and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (248 mg, 0.946 mmol, 609) was sealed in a 5 mL conical microwave tube and evacuated and backfilled with nitrogen 3×. 8-Bromo-2-(isopropylamino)-3-(pyridin-2-yl)quinazolin-4(3H)-one (68 mg, 0.189 mmol, 415d) was added as a solution in 1,4-dioxane (0.7 mL). Water (0.2 mL) was added, and the mixture was stirred at 80° C. for 2 h. The material was cooled to RT and concentrated under reduced pressure. It was taken up in DMSO, filtered, and purified by reverse-phase preparative HPLC using an Xbridge column, 0.1% TFA in CH3CN/H2O, gradient 5% to 50% over 12 min. The product fractions were dried in a Genevac EZ-2 evaporator at 55° C. The material was solublized in 1:1 MeOH:DCM, and the free base was generated using a Si-carbonate cartridge (Silicycle, pre-washed with MeOH). The filtrate was concentrated under reduced pressure to give 2-((1-methylethyl)amino)-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-(2-pyridinyl)-4(3H)-quinazolinone as a pale yellow solid (6 mg, 7%). 1H NMR (DMSO-d6) δ ppm 12.11 (1H, br. s.), 8.70 (1H, d, J=4.5 Hz), 8.06-8.12 (1H, m), 8.04 (1H, d, J=8.2 Hz), 7.78 (1H, d, J=7.0 Hz), 7.59-7.65 (2H, m), 7.18 (1H, t, J=7.7 Hz), 7.08 (1H, s), 6.97 (1H, br. s.), 5.84 (1H, d, J=7.4 Hz), 4.18-4.29 (1H, m), 4.11 (1H, br. s.), 3.14-3.19 (2H, m), 2.86 (2H, t, J=6.9 Hz), 1.18-1.25 (6H, m). m/z (ESI, +ve) 415.0 (M+H)+.
