Sodium t-butoxide → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-5,7-difluoro-3-methyl-2-(1-piperidinyl)quinoline

Participants

Reaction Conditions

Reaction Steps

The 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (9.85 mg, 0.021 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(piperidin-1-yl)quinoline (38.3 mg, 0.129 mmol), 4-(3,3-dimethylindolin-6-yl)morpholine (30.0 mg, 0.129 mmol), sodium tert-butoxide (31.0 mg, 0.323 mmol) and Pd2(dba)3 (4.73 mg, 5.17 μmol) were slurried in toluene (1.00 mL) in a sealed tube and heated to 110° C. for 45 minutes. The reaction was cooled to rt and diluted with water (˜20 mL). This mixture was extracted with EtOAc (1×50 mL) and DCM (1×50 mL). The combined organic layers were dried over magnesium sulfate and the crude product was purified by medium pressure chromatography (silica, 0 to 100% EtOAc:hexane) to give 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-5,7-difluoro-3-methyl-2-(1-piperidinyl)quinoline. 1H NMR (CDCl3) δ ppm 7.31 (1H, br. s.), 7.02 (1H, d, J=8.1 Hz), 6.68 (1H, ddd, J=11.7, 9.1, 2.4 Hz), 6.26 (1H, d, J=7.3 Hz), 5.46 (1H, br. s.), 3.67-3.80 (5H, m), 3.59 (1H, d, J=8.8 Hz), 3.32 (4H, br. s.), 2.94 (4H, d, J=3.7 Hz), 2.24 (3H, s), 1.65-1.86 (6H, m), 1.45 (3H, s), 1.42 (3H, s). Mass Spectrum (ESI) m/e=493.3 (M+1).

Provenance & Evidence