2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(4-methyl-2-pyridinyl)quinoline

Participants

Reaction Steps

Prepared according to procedure Y by heating 4-chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (70 mg, 0.244 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (57.0 mg, 0.244 mmol), XPhos (23.3 mg, 0.049 mmol), Pd2dba3 (22.4 mg, 0.024 mmol) and sodium tert butoxide (46.9 mg, 0.488 mmol) in toluene (2.0 mL) at 110° C. in a microwave reactor for 2 h. After this time the reaction was partitioned between EtOAc (70 mL) and water (30 mL). The separated aqueous layer was extracted with EtOAc (30 mL) and the combined organic layers were dried over MgSO4, filtered and evaporated in vacuo. Reverse phase HPLC (10 to 60% acetonitrile in water) gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(4-methyl-2-pyridinyl)quinoline. 1H NMR (500 MHz, chloroform-d) δ ppm 8.59 (1H, d, J=4.9 Hz), 7.84 (1H, dd, J=10.0, 2.7 Hz), 7.79 (1H, dd, J=9.3, 6.1 Hz), 7.66-7.70 (1H, m), 7.59 (1H, d, J=2.2 Hz), 7.27-7.32 (1H, m), 7.22 (1H, dd, J=5.0, 1.8 Hz), 5.81 (1H, d, J=2.4 Hz), 3.79-3.83 (2H, m), 3.72-3.78 (4H, m), 2.92-3.05 (4H, m), 2.47-2.52 (3H, m), 2.36 (3H, s), 1.57 (3H, s), 1.52 (3H, s). Mass Spectrum (ESI) m/e=484.2 (M+1).

Provenance & Evidence