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

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-7-fluoro-2-(pyridin-2-yl)quinoline-3-carbonitrile (30 mg, 0.11 mmol) (described herein), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-6-yl)morpholine (30 mg, 0.13 mmol) (described herein), sodium tert-butoxide (30.5 mg, 0.32 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (15.12 mg, 0.032 mmol), Pd2dba3 (14.53 mg, 0.016 mmol), and toluene (1.0 mL) was stirred at 105° C. for 3 h, then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with saturated aqueous sodium bicarbonate solution, 1M NaOH, and brine, and the organic layer dried (MgSO4) and concentrated. Chromatography afforded 4-(3,3-dimethyl-6-morpholino-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-2-(pyridin-2-yl)quinoline-3-carbonitrile as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.83 (1H, ddd, J=4.8, 1.7, 0.9 Hz), 8.19-8.31 (1H, m), 7.82-8.01 (3H, m), 7.72-7.82 (1H, m), 7.42-7.57 (1H, m), 7.28-7.37 (1H, m), 6.05-6.21 (1H, m), 4.60-4.72 (1H, m), 3.83-3.94 (1H, m), 3.70-3.83 (4H, m), 2.90-3.11 (4H, m), 1.55-1.62 (3H, m), 1.48-1.55 (3H, m). Mass Spectrum (ESI) m/e=481 (M+1).

Provenance & Evidence