Pyrrolidine → Ethyl 9-fluoro-4-methyl-1-oxo-8-pyrrolidinyl-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylate

HRID 413063Notes

Reaction equation

HRID 413063 reaction equation
F[C:2]1[C:22]([F:23])=[CH:21][C:5]2[C:6]3[C:7](=[O:20])[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][N:10]([CH3:14])[C:11]=3[CH:12]=[N:13][C:4]=2[CH:3]=1.[NH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1>CN(C)C=O>[F:23][C:22]1[C:2]([N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:3][C:4]2[N:13]=[CH:12][C:11]3[N:10]([CH3:14])[CH:9]=[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:7](=[O:20])[C:6]=3[C:5]=2[CH:21]=1

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 18523355Ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate

Product 1

HCID 18523362Ethyl 9-fluoro-4-methyl-1-oxo-8-pyrrolidinyl-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylateYield 36.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 2 g of ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate and 1.1 g of pyrrolidine in 40 cm3 of dimethylformamide was heated, with stirring, at a temperature of 70° C. for 8 hours. After cooling to 20° C., the mixture was poured into 150 cm3 of ice-cold water. The insoluble material was dewatered, washed 3 times with 30 cm3 of water, and dissolved in 300 cm3 of dichloromethane; the residual water was decanted off. The organic extracts were dried over sodium sulphate; after filtration and concentration under reduced pressure (5.2 kPa), the compound obtained was purified by chromatography on 180 g of silica gel (0.06-0.20 mm). Elution was carried out with 3.6 liters of a dichloromethane-ethanol mixture (97-3 by volume) and with 6 liters of a dichloromethane-ethanol mixture (94-6 by volume), 150 cm3 fractions were collected. The fractions obtained from the latter mixture were concentrated to dryness under reduced pressure. 0.85 g of ethyl 9-fluoro-4-methyl-1-oxo-8-pyrrolidinyl-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate was obtained in the form of a yellow compound, which melted at 270° C.

Workup

  1. temperaturewas heated
  2. temperatureAfter cooling to 20° C.
  3. washwashed 3 times with 30 cm3 of water
  4. dissolutiondissolved in 300 cm3 of dichloromethane
  5. customthe residual water was decanted off
  6. dry with materialThe organic extracts were dried over sodium sulphate
  7. filtrationafter filtration and concentration under reduced pressure (5.2 kPa)
  8. customthe compound obtained
  9. customwas purified by chromatography on 180 g of silica gel (0.06-0.20 mm)
  10. washElution
  11. customwere collected
  12. customThe fractions obtained from the latter mixture
  13. concentrationwere concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-bf9704303b2a47eb855147b0c312177c
Source dataset
uspto-grants-2003_05
Patent number
US06566362B2

Reaction notes

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