Tetrahydrofuran → 2-(2,6-Dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine

Participants

Reaction Steps

A 1.0 M solution of lithium aluminum hydride in THF (405 μL, 0.405 mmol) was added to a vessel containing 2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-methoxy-7,8-dihydro-1,6-naphthyridin-5(6H)-one (42 mg, 0.101 mmol). The reaction mixture, which bubbled and turned clear orange, was stirred at room temperature. After 1 h, the reaction mixture was diluted with 1 mL of THF and cooled to 0° C. with an ice bath. 150 μL of a 9:1 THF/H2O mixture was added dropwise, followed by the slow addition of 100 μL of 1 N aqueous NaOH. After stirring for 5 min, the ice bath was removed and 100 μL of H2O and 1 mL of THF were added in sequence. The mixture was stirred for 10 min, then 150 mg of magnesium sulfate were added and the flask was stirred and shaken gently. The mixture was then filtered over Celite® and the filter cake washed with EtOAc. The filtrate was concentrated and the residue purified by FCC (0-20% EtOAc/heptane) to provide 2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.19 (dd, J=8.4, 6.8 Hz, 1 H) 7.09-7.14 (m, 3 H) 7.03 (d, J=1.5 Hz, 1 H) 6.89 (dd, J=7.7, 1.6 Hz, 1 H) 6.81 (s, 1 H) 4.00-4.03 (m, 2 H) 3.86 (s, 3 H) 3.22 (t, J=5.7 Hz, 2 H) 2.97 (t, J=5.6 Hz, 2 H) 2.86 (spt, J=6.8 Hz, 1 H) 2.25 (s, 3 H) 2.03 (s, 6 H) 1.19 (d, J=7.1 Hz, 6 H); MS (ESI+) m/z 401.3 (M+H)+.

Provenance & Evidence