2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-(3,5-dimethylphenyl)-7-fluoro-3-methylquinoline

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-chloro-2-(3,5-dimethylphenyl)-7-fluoro-3-methylquinoline (39 mg, 0.13 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (30 mg, 0.13 mmol) in toluene (1.5 mL) was added Pd2dba3 (12 mg, 0.013 mmol), XPhos (12 mg, 0.026 mmol) and sodium tert-butoxide (25 mg, 0.26 mmol) and the reaction was heated in the microwave for 1 h at 100° C. After this time the reaction was cooled to rt and treated with EtOAc (100 mL) and water (40 mL). The separated organic layer was washed with NaCl (saturated aqueous solution, 40 mL), dried over MgSO4, filtered and evaporated in vacuo. Purification by 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)-2-(3,5-dimethylphenyl)-7-fluoro-3-methylquinoline as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.84 (1H, dd, J=10.0, 2.5 Hz), 7.77 (1H, dd, J=9.3, 6.0 Hz), 7.60 (1H, d, J=2.3 Hz), 7.23-7.29 (1H, m), 7.17-7.21 (2H, m), 7.11 (1H, d, J=1.8 Hz), 5.79 (1H, d, J=2.3 Hz), 3.82 (2H, s), 3.73-3.78 (4H, m), 2.93-3.04 (4H, m), 2.39-2.44 (6H, m), 2.27 (3H, s), 1.58 (3H, s), 1.52 (3H, s). Mass Spectrum (ESI) m/e=497 (M+1).

Provenance & Evidence