反应详情

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)+.

1. customThe reaction mixture, which bubbled
2. additionthe reaction mixture was diluted with 1 mL of THF
3. temperaturecooled to 0° C. with an ice bath
4. addition150 μL of a 9:1 THF/H2O mixture was added dropwise
5. additionfollowed by the slow addition of 100 μL of 1 N aqueous NaOH
6. stirringAfter stirring for 5 min
7. customthe ice bath was removed
8. addition100 μL of H2O and 1 mL of THF were added in sequence
9. stirringThe mixture was stirred for 10 min
10. addition150 mg of magnesium sulfate were added
11. stirringthe flask was stirred
12. stirringshaken gently
13. filtrationThe mixture was then filtered over Celite®
14. washthe filter cake washed with EtOAc
15. concentrationThe filtrate was concentrated
16. customthe residue purified by FCC (0-20% EtOAc/heptane)