Dimethylformamide → 5-[3-(2,4-Difluorophenyl)-[1,2,4]triazin-5-yl]-2-fluorobenzonitrile

HRID 1064279Notes

Reaction equation

HRID 1064279 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].[CH3:23][N:24](C)C=O>[C-]#N.[Zn+2].[C-]#N.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:22][C:16]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=1[C:11]1[N:12]=[N:13][CH:14]=[C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([CH:3]=2)[C:23]#[N:24])[N:10]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 103842555-(3-Bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazine

Product 1

HCID 99727745-[3-(2,4-Difluorophenyl)-[1,2,4]triazin-5-yl]-2-fluorobenzonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
150 °C

Procedure

A mixture of 5-(3-bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazine (0.1 g, 0.27 mmol), zinc cyanide (0.032 g, 0.27 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.016 g, 0.01 mmol) in N,N-dimethylformamide (4 ml) was heated to 150° C. Fog 600 s in a Smith Synthesiser microwave reactor (Personal Chemistry, Uppsala, Sweden). The reaction was partitioned between ethyl acetate (80 ml) and water (40 ml). The organic layer was washed with water (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 50% ethyl acetate in isohexane, to give 5-[3-(2,4-difluorophenyl)-[1,2,4]triazin-5-yl]-2-fluorobenzonitrile as a yellow solid (0.054 g): δH (400 MHz, CDCl3) 7.02-7.14 (2H, m), 7.48 (1H, t, J 8.6 Hz), 8.33-8.39 (1H, m), 8.49-8.53 (1H, m), 8.62 (1H, dd, J 2.2, 6.1 Hz), 9.65 (1H, s); m/z(ES+) 313.

Workup

  1. customFog 600 s
  2. customThe reaction was partitioned between ethyl acetate (80 ml) and water (40 ml)
  3. washThe organic layer was washed with water (40 ml)
  4. dry with materialthe combined organics dried over Mg2SO4
  5. filtrationfiltered
  6. customthe solvent removed at reduced pressure
  7. customThe crude product was chromatographed on silica gel, eluent 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-6301ba235f3342028f393f4d3d68d8bf
Source dataset
uspto-grants-2005_11
Patent number
US06969716B2

Reaction notes

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