5-(3-Bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazine → 6,2'-Difluoro-5'-[3-(2,4-difluorophenyl)-[1,2,4]triazin-5-yl]biphenyl-2-carbonitrile

HRID 1064274Notes

Reaction equation

HRID 1064274 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])[N:12]=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8].[F:23][C:24]1[C:25](B2OC(C)(C)C(C)(C)O2)=[C:26]([CH:29]=[CH:30][CH:31]=1)[C:27]#[N:28]>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:23][C:24]1[CH:31]=[CH:30][CH:29]=[C:26]([C:27]#[N:28])[C:25]=1[C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])[N:12]=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 2

HCID 103842555-(3-Bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazineHCID 222401043-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Product 1

HCID 99786476,2'-Difluoro-5'-[3-(2,4-difluorophenyl)-[1,2,4]triazin-5-yl]biphenyl-2-carbonitrileYield 6.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed mixture of 5-(3-bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazine (0.2 g, 0.55 mmol) and 3-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (0.270 g, 1.1 mmol) in 1,4-dioxane (6 ml) and sodium carbonate (2 ml, 2N solution) was added tetrakis(triphenylphosphine)palladium(0), and the mixture heated at 80° C. Fog 24 h. The mixture was cooled to ambient temperature and partitioned between water (30 ml) and dichloromethane (40 ml). The aqueous layer was extracted with dichloromethane (2×40 ml) and the combined organics dried over Mg2SO4, filtered and the solvent removed at reduced pressure. The crude product was chromatographed on silica gel, eluent 5% ethyl acetate in dichloromethane, to give the product as a pale yellow solid (0.014 g): δH (400 MHz, CDCl3) 6.99-7.10 (2H, m), 7.49 (4H, m), 8.30-8.44 (3H, m), 9.69 (1H, dd, J 0.8, 2.0 Hz); m/z (ES+) 407.

Workup

  1. customFog 24 h
  2. temperatureThe mixture was cooled to ambient temperature
  3. custompartitioned between water (30 ml) and dichloromethane (40 ml)
  4. extractionThe aqueous layer was extracted with dichloromethane (2×40 ml)
  5. dry with materialthe combined organics dried over Mg2SO4
  6. filtrationfiltered
  7. customthe solvent removed at reduced pressure
  8. customThe crude product was chromatographed on silica gel, eluent 5% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-d2ef4f95d4694ea6984f4878fdf38197
Source dataset
uspto-grants-2005_11
Patent number
US06969716B2

Reaction notes

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