Cesium carbonate → 9-Fluoro-6-phenanthridinamine

HRID 2176357Notes

Reaction equation

HRID 2176357 reaction equation
Cl[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1B1OC(C)(C)C(C)(C)O1.C1C2CC3(N)CC(C2)CC1C3.Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)Cl.O.O1CCOCC1>[F:10][C:8]1[CH:7]=[CH:6][C:3]2[C:2]([CH:9]=1)=[C:13]1[C:12]([CH:17]=[CH:16][CH:15]=[CH:14]1)=[N:11][C:4]=2[NH2:5]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 64150Amantadine HydrochlorideHCID 1090002-Chloro-4-fluorobenzonitrileHCID 27346522-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 112528289-Fluoro-6-phenanthridinamineYield 3,082.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-chloro-4-fluorobenzonitrile (1.0 g, 6.42 mmol), 2-aminophenylboronic acid pinacol ester (1.6 g, 7.1 mmol), palladium(II) acetate (0.07 g, 0.32 mmol), amantadine hydrochloride (0.24 g, 1.3 mmol) and cesium carbonate (4.6 g, 14.1 mmol) were added to dioxane previously deaerated with nitrogen and heated to reflux for 17 hours. After cooling, both distilled water and methylene chloride (50 mL) were added to the reaction mixture. The solvent layer was separated and concentrated to give a crude oil that was purified by column chromatography by first using 1:1 ethyl acetate and hexanes ratio followed by 4:1 ethyl acetate/hexanes as the eluants. The pure product was collected to give 9-fluoro-6-phenanthridinamine (42 g, 32% Yield) whose NMR spectrum is consistent with the proposed structure.

Workup

  1. temperatureheated
  2. temperatureto reflux for 17 hours
  3. temperatureAfter cooling
  4. customThe solvent layer was separated
  5. concentrationconcentrated
  6. customto give a crude oil that
  7. customwas purified by column chromatography
  8. customThe pure product was collected

Sources & evidence

ORD record
ord-c955874be25241a3a0db54ecf6a217e1
Source dataset
uspto-grants-2015_06
Patent number
US09065063B2

Reaction notes

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