Lithium Hydroxide → isopropyl 4-(1-(3-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methylcarbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 250 mL round bottom flask was charged with a magnetic stir bar, (R or S)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(piperidin-4-yl)ethyl)-1H-indole-3-carboxamide hydrochloride (0.467 g, 0.987 mmol) (Compound 326), DMF (2.468 ml, 0.987 mmol), THF (2.468 ml, 0.987 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.638 g, 4.94 mmol). The reaction was cooled to 0° C. and isopropyl carbonochloridate (0.160 ml, 1.086 mmol) was added drop wise via syringe. The reaction was allowed to stir for 2 h to rt and was then treated with 5 N LiOH for 1 h to remove any acylated pyridone. This material was extracted with ethyl acetate, washed with brine, dried with MgSO4 and filtered and conc. in vacuo. The resulting material was purified via silica gel chromatography (50 g) using ethyl acetate/MeOH (5:1) as eluent to afford pure title compound as a pale yellow solid (0.300 g, 0.545 mmol, 55.2% yield). LCMS 523 (M+1)+; 1H NMR (DMSO-d6, 400 MHz) δ 11.59 (br. s., 1 H), 7.74 (d, J=7.8 Hz, 1 H), 7.69 (t, J=4.9 Hz, 1 H), 7.62 (d, J=7.8 Hz, 1 H), 7.13-7.01 (m, 2 H), 6.15 (s, 1 H), 4.78-4.67 (m, 1 H), 4.32 (d, J=4.9 Hz, 2 H), 4.23-4.12 (m, 1 H), 4.12-4.02 (m, 1 H), 3.84 (s, 3 H), 3.82-3.74 (m, 1 H), 2.79-2.66 (m, 1 H), 2.58 (s, 3 H), 2.46-2.34 (m, 2 H), 2.20 (s, 3 H), 1.96-1.88 (m, 1 H), 1.58-1.46 (m, 4 H), 1.15 (d, J=6.0 Hz, 6 H), 0.95-0.89 (m, 1 H), 0.74-0.65 (m, 1 H).

Provenance & Evidence