Tetrahydrofuran → (S)-2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine

Participants

Reaction Conditions

Reaction Steps

A 1.0 M solution of lithium aluminum hydride in THF (23.0 mL, 3.00 mmol) was added to a vessel containing (S)-2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one (63 mg, 0.120 mmol). The reaction flask was then capped and the pink reaction mixture was heated to 55° C. and stirred at that temperature. After 1.5 h the oil bath was removed, the reaction mixture was diluted with 6 mL of THF, and the reaction flask cooled to 0° C. Then 0.9 mL of a 9:1 THF/H2O mixture was added dropwise, followed by 3 mL of THF, and 0.3 mL of 2 N NaOH was slowly added. After stirring for 5 min, the ice bath was removed and 600 μL of H2O and 6 mL of THF were added. The mixture was stirred for 10 min, then 900 mg of magnesium sulfate were added and the mixture further stirred. The mixture was then filtered over Celite® and the filter cake washed with EtOAc. The filtrate was concentrated and the residue was purified by FCC (0-50% EtOAc/heptanes) to provide (S)-2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.14-7.19 (m, 1 H) 7.06-7.12 (m, 3 H) 6.94 (d, J=1.5 Hz, 1 H) 6.83 (dd, J=7.8, 1.5 Hz, 1 H) 6.68 (s, 1 H) 4.10-4.22 (m, 2 H) 3.28 (s, 3 H) 3.07-3.18 (m, 1 H) 2.73-3.04 (m, 6 H) 2.23 (s, 3 H) 2.00 (s, 6 H) 1.91-2.03 (m, 2 H) 1.58 (d, J=9.3 Hz, 1 H) 1.20-1.28 (m, 1 H) 1.16 (d, J=6.8 Hz, 6 H) 1.01 (d, J=10.4 Hz, 6 H); MS (ESI+) m/z 512.4 (M+H)+.

Provenance & Evidence