8-Hydroxyquinoline → tert-Butyl 9-methyl-2-(2-oxo-4-(4-(trifluoromethyl)phenyl)pyridin-1(2H)-yl)-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 2-bromo-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (0.15 g, 0.41 mmol), 4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (98 mg, 0.41 mmol), and Cs2CO3 (0.15 g, 0.45 mmol) were suspended in DMSO (2.4 mL), and the air was removed under vacuum for 15 min. The system was flushed with Ar, and 8-hydroxyquinoline (18 mg, 0.12 mmol) and copper iodide (94 mg, 0.49 mmol) were added to the suspension. The evacuation/Ar flushing process was repeated twice more, and the reaction mixture was heated at 130° C. for 18 h under N2. The mixture was cooled, diluted with 5.0:3.5:1.5 NH4Cl(aq.)/NH4OH/H2O (70 mL), and the resulting solution was stirred at ambient temperature for 30 min, extracted with CH2Cl2 (3×20 mL), and washed with 5.0:3.5:1.5 NH4Cl(aq.)/NH4OH/H2O (4×20 mL). The resulting organic solution was dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 48 mL, increased to 50:50 over 240 mL and held for 48 mL; increased to 0:100 over 120 mL) gave the title compound (0.14 g, 63%) as a yellow powder: 1H NMR (300 MHz, DMSO-d6) δ 8.09-8.80 (m, 4H), 7.88 (d, J=8.1 Hz, 2H), 7.39 (d, J=8.1 Hz, 1H), 6.90 (d, J=1.8 Hz, 1H), 6.77 (dd, J=7.5, 2.1 Hz, 1H), 4.59 (s, 2H), 3.77 (t, J=6.0 Hz, 2H), 3.70 (s, 3H), 2.90 (t, J=4.8 Hz, 2H), 1.45 (s, 9H); ESI MS m/z 525 [M+H]+.

Provenance & Evidence