Ethanol → 1,8-Naphthyridine-3-carboxylic acid, 1,4-dihydro-7-(3-amino-1-pyrrolidinyl)-7-fluoro-1-(2-fluoroethyl)-4-oxo-

HRID 851096Notes

Reaction equation

HRID 851096 reaction equation
C([NH:4][CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:19]=[C:18]3[C:13]([C:14](=[O:28])[C:15]([C:23]([O:25]CC)=[O:24])=[CH:16][N:17]3[CH2:20][CH2:21][F:22])=[CH:12][C:11]=2[F:29])[CH2:6]1)(=O)C.C(O)C>Cl>[NH2:4][CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:19]=[C:18]3[C:13]([C:14](=[O:28])[C:15]([C:23]([OH:25])=[O:24])=[CH:16][N:17]3[CH2:20][CH2:21][F:22])=[CH:12][C:11]=2[F:29])[CH2:6]1

Participants

4

Reactant 2

HCID 702EthanolHCID 13135053Ethyl 7-(3-acetylamino-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

Product 1

HCID 30692171,8-Naphthyridine-3-carboxylic acid, 1,4-dihydro-7-(3-amino-1-pyrrolidinyl)-7-fluoro-1-(2-fluoroethyl)-4-oxo-Yield 74.8%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A mixture of ethyl 7-ethylsulfonyl-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate (19.8 g) obtained according to the Reference Example 2, 3-acetylaminopyrrolidine (10.2 g), triethylamine (7.4 ml), and ethanol (400 ml) was heated under reflux for 2 hours. After cooling, the resulting crystals were collected by filtration, and recrystallized from chloroform-ethanol to give 16.8 g of ethyl 7-(3-acetylamino-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate melting at 269°-270° C. A solution of the above ester (15.0 g) in 20% hydrochloric acid (100 ml) was heated under reflux for 4 hours. After cooling, ethanol (100 ml) was added to the mixture and the resulting crystals were collected by filtration. The crystals were dissolved in hot water (100 ml) and treated with charcoal. The filtrate was adjusted to pH 8.5-9.0 by addition of aqueous 27% ammonia, and the resulting crystals were collected by filtration, washed with water, and dried to give 9.3 g of the compound 3, m.p. 251°-255° C.

Workup

  1. temperatureunder reflux for 4 hours
  2. temperatureAfter cooling
  3. filtrationthe resulting crystals were collected by filtration
  4. dissolutionThe crystals were dissolved in hot water (100 ml)
  5. additiontreated with charcoal
  6. additionThe filtrate was adjusted to pH 8.5-9.0 by addition of aqueous 27% ammonia
  7. filtrationthe resulting crystals were collected by filtration
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-6fcf00171df94fda91a1ded91f1f1280
Source dataset
uspto-grants-1983_05
Patent number
US04382937

Reaction notes

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