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

Participants

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 (0.19 g, 0.52 mmol), 4-(5-(trifluoromethyl)pyridin-2-yl)pyridin-2(1H)-one (0.14 g, 0.57 mmol), and K3PO4 (0.22 g, 1.0 mmol) were suspended in 1,4-dioxane (15 mL), and N2 was bubbled through the suspension for 45 min. To the suspension was added (1S,2S) N,N′-bismethyl-1,2-cyclohexane-diamine (20 μL, 0.14 mmol) and copper iodide (50 mg, 0.26 mmol). The reaction mixture was heated at reflux for 20 h under N2. The mixture was cooled, passed through a silica gel plug eluting with 80:18:2 CH2Cl2/MeOH/NH4OH, 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 4 column volumes, increased to 50:50 over 20 column volumes and held for 4 column volumes; increased to 0:100 over 10 column volumes and held for 4 column volumes) followed by additional flash chromatography (24 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 4 column volumes, increased to 50:50 over 16 column volumes and held for 4 column volumes; increased to 0:100 over 10 column volumes) gave the title compound (82 mg, 30%) as a yellow film: 1H NMR (500 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.43-8.34 (m, 2H), 8.07 (d, J=8.0 Hz, 2H), 7.41 (d, J=8.0 Hz, 1H), 7.31 (d, J=1.5 Hz, 1H), 7.12 (dd, J=7.5, 2.0 Hz, 1H), 4.59 (s, 2H), 3.77 (t, J=5.5 Hz, 2H), 3.70 (s, 3H), 2.90 (t, J=5.5 Hz, 2H), 1.45 (s, 9H).

Provenance & Evidence