Hexamethylphosphoramide → Ethyl 1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate

HRID 1461378Notes

Reaction equation

HRID 1461378 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([Sn](C)(C)C)[CH:5]=[C:4]([CH3:12])[N:3]=1.Br[C:14]1[CH:23]=[C:22]2[C:17]([C:18](=[O:32])[C:19]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:20][N:21]2[CH:24]2[CH2:26][CH2:25]2)=[CH:16][C:15]=1[F:33].CN(C)P(N(C)C)(N(C)C)=O>O1CCOCC1.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>[CH:24]1([N:21]2[C:22]3[C:17](=[CH:16][C:15]([F:33])=[C:14]([C:6]4[CH:7]=[C:2]([CH3:1])[N:3]=[C:4]([CH3:12])[CH:5]=4)[CH:23]=3)[C:18](=[O:32])[C:19]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:20]2)[CH2:25][CH2:26]1

Participants

6

Reactant 3

HCID 12679HexamethylphosphoramideHCID 10405837Ethyl 7-bromo-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylateHCID 129132682,6-Dimethyl-4-(trimethyl-stannyl)pyridine

Product 1

HCID 9999813Ethyl 1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylateYield 92.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

2,6-Dimethyl-4-(trimethylstannyl)pyridine (part g) (10.1 g) and 1.52 g dichlorobis(triphenylphosphine)palladium was added to a stirred solution of 12.13 g ethyl 7-bromo-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate (part f) and 10 ml hexamethylphosphoramide (HMPA) in 240 ml dioxane under nitrogen. The reaction mixture was heated under reflux for 24 hours, then cooled and partitioned between water and methylene dichloride. The organic extract was washed with sodium chloride solution, dried (magnesium sulfate) and concentrated to give 12.0 g ethyl 1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, m.p. 198°-200° C.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 24 hours
  3. temperaturecooled
  4. custompartitioned between water and methylene dichloride
  5. extractionThe organic extract
  6. washwas washed with sodium chloride solution
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-882f4c18c02f478e9121634d23cf5fd4
Source dataset
uspto-grants-1991_12
Patent number
US05075319

Reaction notes

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