Ethyl 6-(1-methylethyl)-4-oxo-1,4-dihydropyridine-3-carboxylate → Ethyl 4-[(3-methoxypropyl)amino]-6-(1-methylethyl)pyridine-3-carboxylate

Temperature

120 °C

Ethyl 6-(1-methylethyl)-4-oxo-1,4-dihydropyridine-3-carboxylate (209 mg) was suspended in phosphorus oxychloride (2 ml), and the mixture was stirred at 120° C. for 3 hr. Phosphorus oxychloride was evaporated under reduced pressure, and the mixture was cooled to 0° C. The mixture was neutralized with saturated aqueous sodium hydrogen carbonate and water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was dissolved in 2-propanol (5 ml), 3-methoxypropylamine (307 μl) and triethylamine (517 μl) were added, and the mixture was stirred with heating to reflux for 15 hr. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography, and the fraction eluted with acetic acid was concentrated under reduced pressure to give the object compound (263 mg).

1. customPhosphorus oxychloride was evaporated under reduced pressure
2. temperaturethe mixture was cooled to 0° C
3. extractionthe mixture was extracted with ethyl acetate
4. washThe extract was washed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe obtained residue was dissolved in 2-propanol (5 ml)
8. addition3-methoxypropylamine (307 μl) and triethylamine (517 μl) were added
9. stirringthe mixture was stirred
10. temperaturewith heating
11. temperatureto reflux for 15 hr
12. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate
13. additionwas added
14. extractionthe mixture was extracted with ethyl acetate
15. washThe extract was washed with saturated brine
16. dry with materialdried over anhydrous sodium sulfate
17. concentrationconcentrated under reduced pressure
18. washthe fraction eluted with acetic acid
19. concentrationwas concentrated under reduced pressure

ORD record

ord-5785b54c9b0b477f8b8d3f3adb32af02

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329691B2