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

Participants

Reaction Conditions

Reaction Steps

A screw cap vial was charged with 2-benzyl-4-chloro-5,7-difluoro-3-methylquinoline (37 mg, 0.122 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (36.9 mg, 0.158 mmol), Pd2dba3 (16.7 mg, 0.018 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (17.4 mg, 0.037 mmol), sodium tert-butoxide (35.1 mg, 0.365 mmol), and toluene (1.22 mL). The mixture was heated to 95° C. under N2 for 18 h. The reaction was concentrated and diluted with EtOAc, then washed with saturated aqueous sodium bicarbonate solution, water, brine, and 1M NaOH. The organic layer was dried (MgSO4) and concentrated. The crude product was purified by preparative HPLC (10-70% acetonitrile in water) to give 2-benzyl-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methylquinoline as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.60-7.68 (1H, m), 7.50 (1H, d, J=2.3 Hz), 7.27-7.31 (2H, m), 7.22-7.25 (3H, m), 6.96 (1H, ddd, J=11.9, 9.0, 2.5 Hz), 5.52 (1H, d, J=2.3 Hz), 4.42 (2H, s), 3.79-3.85 (1H, m), 3.68-3.77 (4H, m), 3.56 (1H, d, J=9.0 Hz), 2.89-2.96 (4H, m), 2.19 (3H, s), 1.51 (3H, s), 1.45 (3H, s). Mass Spectrum (ESI) m/e=512.0 (M+1).

Provenance & Evidence