Triethylamine → ethyl 7-[3-(N-acetyl-N-methylamino)-1-pyrrolidinyl]-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

HRID 851097Notes

Reaction equation

HRID 851097 reaction equation
C(S([C:6]1[N:15]=[C:14]2[C:9]([C:10](=[O:24])[C:11]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:12][N:13]2[CH2:16][CH2:17][F:18])=[CH:8][C:7]=1[F:25])(=O)=O)C.[C:26]([N:29]([CH:31]1[CH2:35][CH2:34][NH:33][CH2:32]1)[CH3:30])(=[O:28])[CH3:27].C(N(CC)CC)C>C(O)C>[C:26]([N:29]([CH:31]1[CH2:35][CH2:34][N:33]([C:6]2[N:15]=[C:14]3[C:9]([C:10](=[O:24])[C:11]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:12][N:13]3[CH2:16][CH2:17][F:18])=[CH:8][C:7]=2[F:25])[CH2:32]1)[CH3:30])(=[O:28])[CH3:27]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 130411303-(N-Acetyl-N-methylamino)pyrrolidineHCID 13135049Ethyl 7-ethylsulfonyl-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

Product 1

HCID 13401978ethyl 7-[3-(N-acetyl-N-methylamino)-1-pyrrolidinyl]-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylateYield 82.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethyl 7-ethylsulfonyl-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate (26.7 g) obtained according to the Reference Example 2, 3-(N-acetyl-N-methylamino)pyrrolidine (15.5 g), triethylamine (10.0 ml), and ethanol (300 ml) was heated under reflux for one hour. The reaction mixture was concentrated to a half volume under reduced pressure. To the mixture was added water (200 ml), and the resulting crystals were collected by filtration, and recrystallized from chloroform-ethanol to give 24.8 g of ethyl 7-[3-(N-acetyl-N-methylamino)-1-pyrrolidinyl]-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate melting at 227°-229° C. A solution of the above ester (20.0 g) in 20% hydrochloric acid (120 ml) was heated under reflux for 3 hours. After the reaction was completed, water (60 ml) and ethanol (120 ml) were added to the reaction mixture, and the resulting crystals were collected by filtration. The crystals were dissolved in hot water (800 ml) and the solution was treated with charcoal. The filtrate was adjusted to pH 8.5-9.0 by addition of 27% aqueous ammonia. The crystals were collected by filtration, washed with water, and dried to give 11.0 g of the compound 4, m.p. 243°-245° C.

Workup

  1. customobtained
  2. temperaturewas heated
  3. temperatureunder reflux for one hour
  4. concentrationThe reaction mixture was concentrated to a half volume under reduced pressure
  5. additionTo the mixture was added water (200 ml)
  6. filtrationthe resulting crystals were collected by filtration
  7. customrecrystallized from chloroform-ethanol

Sources & evidence

ORD record
ord-cf99fd4e9ed8429e939694f8fd2482a6
Source dataset
uspto-grants-1983_05
Patent number
US04382937

Reaction notes

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