Cesium carbonate → 2-Fluoro-4-[(3-nitropyridin-2-yl)amino]benzonitrile

HRID 2272707Notes

Reaction equation

HRID 2272707 reaction equation
[N+:1]([C:4]1[C:5]([NH2:10])=[N:6][CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Br[C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[F:20][C:14]1[CH:13]=[C:12]([NH:10][C:5]2[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=[CH:7][N:6]=2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 778873-Nitropyridin-2-ylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7360294-Bromo-2-fluorobenzonitrile

Product 1

HCID 867300692-Fluoro-4-[(3-nitropyridin-2-yl)amino]benzonitrile

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 3-nitropyridin-2-amine (3.44 g, 24.7 mmol), 4-bromo-2-fluorobenzonitrile (4.95 g, 24.7 mmol), tris(dibenzylideneacetone)dipalladium(0) (226 mg, 0.247 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos, 286 mg, 0.494 mmol) and cesium carbonate (32.3 g, 99.0 mmol) in 1,4-dioxane (124 mL) was degassed, placed under nitrogen and stirred at 100° C. for 30 minutes. The reaction mixture was filtered through a pad of Celite using tetrahydrofuran, and the filtrate was concentrated in vacuo. A 1:1 mixture of heptane and ethyl acetate was added to the residue, and the mixture was cooled in an ice/water bath. The solid was collected via filtration and washed with cold 1:1 heptane/ethyl acetate to afford the product as a gray solid. Yield: 6.2 g, 24 mmol, 97%. LCMS m/z 259.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 10.46 (br s, 1H), 8.60-8.63 (m, 2H), 8.16 (dd, J=11.8, 2.1 Hz, 1H), 7.59 (dd, J=8.5, 7.2 Hz, 1H), 7.40 (br dd, J=8.6, 2 Hz, 1H), 7.05-7.09 (m, 1H).

Workup

  1. customwas degassed
  2. filtrationThe reaction mixture was filtered through a pad of Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionA 1:1 mixture of heptane and ethyl acetate
  5. additionwas added to the residue
  6. temperaturethe mixture was cooled in an ice/water bath
  7. filtrationThe solid was collected via filtration
  8. washwashed with cold 1:1 heptane/ethyl acetate

Sources & evidence

ORD record
ord-99f15a37edae40c0848ae389beb0f3de
Source dataset
uspto-grants-2015_09
Patent number
US09120788B2

Reaction notes

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