Hexamethylphosphoramide → 1-Cyclopropyl-7-(2,6-dimethylpyridinyl)-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

HRID 1461385Notes

Reaction equation

HRID 1461385 reaction equation
Br[C:2]1[C:11]([F:12])=[C:10]2[C:5]([C:6](=[O:21])[C:7]([C:16]([O:18]CC)=[O:17])=[CH:8][N:9]2[CH:13]2[CH2:15][CH2:14]2)=[C:4]([F:22])[C:3]=1[F:23].[CH3:24][C:25]1[CH:30]=[C:29]([Sn](C)(C)C)[CH:28]=[C:27]([CH3:35])[N:26]=1.CN(C)P(N(C)C)(N(C)C)=O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH:13]1([N:9]2[C:10]3[C:5](=[C:4]([F:22])[C:3]([F:23])=[C:2]([C:30]4[C:25]([CH3:24])=[N:26][C:27]([CH3:35])=[CH:28][CH:29]=4)[C:11]=3[F:12])[C:6](=[O:21])[C:7]([C:16]([OH:18])=[O:17])=[CH:8]2)[CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 12679HexamethylphosphoramideHCID 11741084Ethyl 7-bromo-1-cyclopropyl-5,6,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylateHCID 129132682,6-Dimethyl-4-(trimethyl-stannyl)pyridine

Product 1

HCID 542083601-Cyclopropyl-7-(2,6-dimethylpyridinyl)-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acidYield 57.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2.8 g ethyl 7-bromo-1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, 2.2 g 2,6-dimethyl-4-(trimethylstannyl)pyridine (Example 1, part g), 2 ml hexamethylphosphoramide, 320 mg dichlorobis(triphenylphosphine)palladium and 50 ml dioxane was stirred and heated under reflux in an argon atmosphere for 24 hours. The reaction mixture was concentrated to dryness and the residue was treated with 100 ml of 1N hydrochloric acid and heated at reflux for 2 hours. The latter mixture was filtered and the filtrate concentrated to dryness. The residue was dissolved in 50 ml 5% aqueous potassium carbonate, decolorized with charcoal and filtered. The filtrate was acidified with concentrated hydrochloric acid, sodium acetate added, and the resulting precipitate was collected, dried and recrystallized from ethanol to give 1.6 g 1-cyclopropyl-7-(2,6-dimethylpyridinyl)-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid as a cream-colored solid, m.p. 264°-266° C.

Workup

  1. temperatureheated
  2. temperatureunder reflux in an argon atmosphere for 24 hours
  3. concentrationThe reaction mixture was concentrated to dryness
  4. additionthe residue was treated with 100 ml of 1N hydrochloric acid
  5. temperatureheated
  6. temperatureat reflux for 2 hours
  7. filtrationThe latter mixture was filtered
  8. concentrationthe filtrate concentrated to dryness
  9. dissolutionThe residue was dissolved in 50 ml 5% aqueous potassium carbonate
  10. filtrationfiltered
  11. additionadded
  12. customthe resulting precipitate was collected
  13. customdried
  14. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-ce640f32c47945a5811c226a590ca415
Source dataset
uspto-grants-1991_12
Patent number
US05075319

Reaction notes

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