Reaction Steps
A mixture of 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (24.5 mg, 0.051 mmol), Pd2dba3 (23.6 mg, 0.026 mmol), sodium tert-butoxide (49.5 mg, 0.52 mmol), 6-morpholino-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (47.1 mg, 0.17 mmol) (described herein), and 4-chloro-7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)quinoline (60 mg, 0.17 mmol) (described herein) in toluene (1.7 mL) was stirred at 100° C. for 60 min, 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, then the organic layer dried (MgSO4) and concentrated. Column chromatography afforded 1-(7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran] as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.24 (1H, d, J=2.0 Hz), 8.07 (1H, d), 7.96 (1H, d), 7.76 (3H, m), 7.31 (1H, m), 7.15 (1H, d, J=8.2 Hz), 6.36 (1H, d), 5.59 (1H, s), 4.01-4.10 (2H, m), 3.91-4.01 (2H, m), 3.69-3.82 (4H, m), 3.51-3.63 (2H, m), 3.11-3.19 (3H, m), 2.97 (4H, d, J=4.7 Hz), 2.25-2.33 (3H, m), 2.10-2.24 (2H, m), 1.89 (1H, d), 1.80 (1H, d). Mass Spectrum (ESI) m/e=588 (M+1).
