Pentapotassium Triphosphate → 2-[(2,5-Dichloro-4-pyridinyl)amino]-5-fluorobenzonitrile

HRID 1472583Notes

Reaction equation

HRID 1472583 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:12]=1[C:13]#[N:14].[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([NH:10][C:11]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:12]=2[C:13]#[N:14])[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 61695Pentapotassium TriphosphateHCID 27377042-Amino-5-fluorobenzonitrileHCID 534009652,5-Dichloro-4-iodopyridine

Product 1

HCID 575169182-[(2,5-Dichloro-4-pyridinyl)amino]-5-fluorobenzonitrileYield 86%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a degassed solution of 2,5-dichloro-4-iodopyridine (8 g, 29.2 mmol), 2-amino-5-fluorobenzonitrile (3.98 g, 29.2 mmol) and potassium triphosphate (18.60 g, 88 mmol) in 1,4-dioxane (100 ml) stirred under nitrogen at the room temperature was added DPEPhos (1.258 g, 2.337 mmol) and palladium acetate (0.262 g, 1.168 mmol). The reaction mixture was stirred at the reflux for 18 hr. The reaction mixture was filtered. The solvent was evaporated. Ether (50 ml) was added and the solid was filtered. 2-[(2,5-Dichloro-4-pyridinyl)amino]-5-fluorobenzonitrile (7.09 g, 25.1 mmol, 86% yield) was isolated as an orange solid. 1H NMR (400 MHz, METHANOL-d4) ppm 6.44 (s, 1 H) 7.46-7.58 (m, 2 H) 7.66 (dd, J=8.08, 2.78 Hz, 1 H) 8.08 (s, 1 H); HPLC Rt=3.23 min, MS (ESI): 382.0, 384.19 [M+H]+.

Workup

  1. temperaturereflux for 18 hr
  2. filtrationThe reaction mixture was filtered
  3. customThe solvent was evaporated
  4. additionEther (50 ml) was added
  5. filtrationthe solid was filtered

Sources & evidence

ORD record
ord-91a5217b8c3d490292d23e1769693f98
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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