Ozone → 1,6-Naphthyridine-8-carbaldehyde

A solution of ethyl (2Z)-3-(1,6-naphthyridin-8-yl)prop-2-enoate (30 g) in dichloromethane (500 mL) and methanol (125 mL) was cooled to −78° C. and reacted with ozone until the color of the reaction mixture became light blue (˜3 h). The reaction was purged with nitrogen to remove the residual ozone. Methyl sulfide (60 mL) was then added, and the reaction was allowed to warm to room temperature and then concentrated. The resulting residue was dissolved in dichloromethane (300 mL), washed with water (100 mL) and saturated aqueous sodium bicarbonate (100 mL) and dried over sodium sulfate. The solvent was removed and product was slurried in heptane/ethyl acetate mixture (5:1). The solid was then filtered and dried under reduced pressure to provide the title compound: LCMS m/z 158.97 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 11.39 (s, 1 H), 9.09 (s, 1 H), 9.13 (m, 1 H), 9.07 (s, 1 H), 8.43 (d, J=8.3 Hz, 1 H), 7.78 (dd, J=8.7, 4.8 Hz, 1 H), 7.63 (dd, J=8.2, 4.2 Hz, 1 H), 7.34 (dd, J=8.7, 2.2 Hz, 1 H), 7.07 (m, 1 H), 3.55-3.53 (m, 1 H), 0.62-0.61 (m, 4 H).

1. customblue (˜3 h)
2. customThe reaction was purged with nitrogen
3. customto remove the residual ozone
4. additionMethyl sulfide (60 mL) was then added
5. concentrationconcentrated
6. dissolutionThe resulting residue was dissolved in dichloromethane (300 mL)
7. washwashed with water (100 mL) and saturated aqueous sodium bicarbonate (100 mL)
8. dry with materialdried over sodium sulfate
9. customThe solvent was removed
10. filtrationThe solid was then filtered
11. customdried under reduced pressure

ORD record

ord-a969f4900119449abe915c5efc47ff1c

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382226B2