Dimethyl Sulfoxide → 1-(7-fluoro-3-methyl-2-pyridin-2-ylquinolin-4-yl)-6-morpholin-4-ylspiro[2H-indole-3,4'-oxane]

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-bromo-1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (100 mg, 0.198 mmol), morpholine and DMSO (2.5 mL) was degassed with argon for 15 min in a Schlenck tube. To the mixture was added copper (I) iodide (8 mg, 40 μmol), 1-(−)-proline (9 mg, 79 mmol) and potassium carbonate (82 mg, 595 μmol) and the mixture was heated at 120° C. overnight. After this time the reaction was cooled to rt and diluted with DCM (100 mL) and water (40 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography (hexane:EtOAc, 1:0 to 0:1) gave the desired product as a yellow oil. The product was further purified by reverse phase HPLC to give 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]. 1H NMR (400 MHz, chloroform-d) δ ppm 8.76 (1H, dd, J=3.7, 1.0 Hz), 7.75-8.00 (4H, m), 7.41 (1H, ddd, J=7.1, 5.0, 1.6 Hz), 7.21-7.27 (1H, m), 7.13 (1H, d, J=8.2 Hz), 6.35 (1H, dd, J=8.2, 2.3 Hz), 5.61 (1H, d, J=2.3 Hz), 3.96-4.09 (3H, m), 3.89-3.96 (1H, m), 3.70-3.79 (4H, m), 3.49-3.60 (2H, m, J=12.2, 12.2, 2.9, 2.7 Hz), 2.91-3.04 (4H, m), 2.38 (3H, s), 2.09-2.22 (2H, m), 1.76-1.93 (2H, m). Mass Spectrum (ESI) m/e=511 (M+1).

Provenance & Evidence