2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl → 1-(7-Fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2-dihydrospiro[indole-3,3'-thietane]1',1'-dioxide

Participants

Reaction Conditions

Reaction Steps

To a microwave vial was added sodium tert-butoxide (0.017 g, 0.177 mmol), ruphos (4.12 mg, 8.83 μmol), 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)-quinoline (0.025 g, 0.093 mmol), 6-(4-morpholinyl)-1,2-dihydrospiro[indole-3,3′-thietane]1′,1′-dioxide (0.026 g, 0.088 mmol), and XPhos pre-catalyst (6.5 mg, 8.8 mmol) in toluene (0.6 mL). The suspension was deoxygenated with argon for 5 min then stirred at 100° C. for 1 h under microwave irradiation. Purification by column chromatography (eluting with a gradient of 0-10% MeOH in DCM) gave a yellow solid that was repurified by reverse phase HPLC (10-60% acetonitrile in water) to give 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2-dihydrospiro[indole-3,3′-thietane]1′,1′-dioxide as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.71 (1H, d, J=4.89 Hz), 7.99-8.05 (1H, m), 7.83-7.94 (3H, m), 7.50-7.56 (2H, m), 7.49 (1H, d, J=8.31 Hz, 6.40 (1H, dd, J=8.44, 2.08 Hz), 5.58 (1H, d, J=1.96 Hz), 4.72 (1H, dd, J=13.57, 2.32 Hz), 4.55-4.63 (3H, m), 4.35 (1H, d, J=10.03 Hz), 4.25 (1H, d, J=10.03 Hz), 3.58 (4H, t, J=4.89 Hz), 2.82-2.93 (4H, m), 2.24 (3H, s). Mass Spectrum (ESI) m/e=531.2 (M+1).

Provenance & Evidence