反应详情

温度

90 °C

A suspension of 2 g of ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate and 2.6 g of 1,3,3-trimethyl-6-azabicyclo[3.2.1]octane in 50 cm3 of dimethyl sulphoxide was heated, with stirring, at a temperature of 90° C. for 12 days. After cooling to 20° C., the mixture was poured into 200 cm3 of ice-cold water. The medium was extracted 3 times with 200 cm3 of dichloromethane, and the organic extracts were washed 3 times with 100 cm3 of water, and dried over sodium sulphate. After filtration and concentration under reduced pressure (5.2 kPa), the compound obtained was purified by chromatography on 160 g of silica gel (0.06-0.20 mm). Elution was carried out with 3 liters of a dichloromethane-ethanol mixture (97-3 by volume), collecting 200 cm3 fractions. The fractions between 1.65 and 3 liters were concentrated to dryness under reduced pressure (5.2 kPa). 0.9 g of ethyl 8-fluoro-4-methyl-1-oxo-9-(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate was obtained in the form of yellow crystals, which melted at 187° C.

1. temperaturewas heated
2. temperatureAfter cooling to 20° C.
3. extractionThe medium was extracted 3 times with 200 cm3 of dichloromethane
4. washthe organic extracts were washed 3 times with 100 cm3 of water
5. dry with materialdried over sodium sulphate
6. filtrationAfter filtration and concentration under reduced pressure (5.2 kPa)
7. customthe compound obtained
8. customwas purified by chromatography on 160 g of silica gel (0.06-0.20 mm)
9. washElution
10. customcollecting 200 cm3 fractions
11. concentrationThe fractions between 1.65 and 3 liters were concentrated to dryness under reduced pressure (5.2 kPa)