3-Fluoroaniline → Ethyl 6-((3-fluorophenyl)amino)-4-(propylamino)nicotinate

HRID 2284810Notes

Reaction equation

HRID 2284810 reaction equation
Cl[C:2]1[CH:12]=[C:11]([NH:13][CH2:14][CH2:15][CH3:16])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1.[F:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])O.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[F:17][C:18]1[CH:19]=[C:20]([NH:21][C:2]2[CH:12]=[C:11]([NH:13][CH2:14][CH2:15][CH3:16])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=2)[CH:22]=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 97423-FluoroanilineHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 90051800Ethyl 6-chloro-4-(propylamino)nicotinate

Product 1

HCID 90051842Ethyl 6-((3-fluorophenyl)amino)-4-(propylamino)nicotinateYield 90%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of tris(dibenzylideneacetone)dipalladium(0) (80 mg) and 4,5′-bis(diphenylphosphino)-9,9′-dimethylxanthene (100 mg) in 1,4-dioxane (5 mL), ethyl 6-chloro-4-(propylamino)nicotinate (S14, 210 mg), 3-fluoroaniline (193 mg) and cesium carbonate (565 mg) were added at room temperature, and the mixture was stirred at 80 to 90° C. for 5 hours. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate and ethyl acetate were added to the reaction mixture. The insoluble matter was removed by filtration through Florisil. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 90 to 60% hexane in ethyl acetate) to obtain ethyl 6-((3-fluorophenyl)amino)-4-(propylamino)nicotinate (S15, 247 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe insoluble matter was removed by filtration through Florisil
  3. customThe organic layer was separated
  4. washwashed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluent, 90 to 60% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-e8168e84ff6d4205b5228df51d33246a
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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