Hydrochloric Acid → 1-(9-Methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

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Reaction Steps

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 (0.14 g, 0.26 mmol) was treated with 1.25 M HCl in MeOH (6.0 mL), and the resulting suspension was stirred at ambient temperature for 18 h. To the suspension was added CH2Cl2 (1.0 mL) and 1.25 M HCl in MeOH (2.0 mL), and the resulting solution was stirred at ambient temperature for 18 h. The solution was concentrated, diluted with CH2Cl2 (30 mL), washed with saturated NaHCO3 solution (2×10 mL), dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, CH2Cl2/(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 30 column volumes) followed by preparative HPLC (Phenomenex Luna C18 (2), 250.0×50.0 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA) gave the title compound (51 mg, 46%) as a yellow powder: 1H NMR (500 MHz, DMSO-d6) δ 8.06-8.00 (m, 3H), 7.93 (d, J=8.0 Hz, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.35 (d, J=8.0 Hz, 1H), 6.89 (d, J=1.5 Hz, 1H), 6.76 (dd, J=7.5, 2.0 Hz, 1H), 3.89 (s, 2H), 3.67 (s, 3H), 3.08 (t, J=5.5 Hz, 2H), 2.75 (t, J=5.5 Hz, 2H).

Provenance & Evidence