Nitrogen → 2-[(2,5-Dichloro-4-pyridinyl)amino]benzonitrile

HRID 1472537Notes

Reaction equation

HRID 1472537 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][CH:16]=[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+].N#N.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>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([NH:10][C:11]2[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=2[C:13]#[N:14])[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 61695Pentapotassium TriphosphateHCID 729132-AminobenzonitrileHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 534009652,5-Dichloro-4-iodopyridine

Product 1

HCID 575168982-[(2,5-Dichloro-4-pyridinyl)amino]benzonitrileYield 79%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

The solution of 2,5-dichloro-4-iodopyridine (100 g, 365 mmol), 2-aminobenzonitrile (43.1 g, 365 mmol) and potassium triphosphate (233 g, 1095 mmol) in 1,4-dioxane (2.5 L) was degassed by N2 stream. To this solution was added DPEPhos (15.73 g, 29.2 mmol) and palladium acetate (3.28 g, 14.60 mmol). The reaction mixture was stirred at reflux for 18 hour. The solution was filtered through 0.5 in. celite and 0.2 inch of silica. The solution was evaporated. Solid was suspended in the diethyl ether and filtered. Diethyl ether was concentrated, and the resulting solid was filtered. 2-[(2,5-Dichloro-4-pyridinyl)amino]benzonitrile (80 g, 288 mmol, 79% yield) was isolated as an orange solid. 1H NMR (400 MHz, DMSO-d6) ppm 6.49 (s, 1 H) 7.50 (td, J=7.58, 1.01 Hz, 1 H) 7.56 (d, J=7.58 Hz, 1 H) 7.80 (td, J=7.83, 1.77 Hz, 1 H) 7.95 (dd, J=7.83, 1.52 Hz, 1 H) 8.26 (s, 1 H) 9.05 (brs, 1 H); HPLC Rt=2.88 min, MS (ESI): 263.9, 265.9 [M+H]+.

Workup

  1. temperatureat reflux for 18 hour
  2. filtrationThe solution was filtered through 0.5 in
  3. customThe solution was evaporated
  4. filtrationfiltered
  5. concentrationDiethyl ether was concentrated
  6. filtrationthe resulting solid was filtered

Sources & evidence

ORD record
ord-51a2292cd2634a38a768aa6f91786b7c
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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