Dimethylformamide → HCID 21099467, compound

HRID 1351631Notes

Reaction equation

HRID 1351631 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22](Br)[CH:21]=2)(=[O:19])=[O:18])=[CH:13][N:12]=1.[CH3:27][N:28](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:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:27]#[N:28])[CH:21]=2)(=[O:19])=[O:18])=[CH:13][N:12]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 21099466HCID 21099466, compound

Product 1

HCID 21099467HCID 21099467, compoundYield 19%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

2-[(E)-2-(2,4-Difluorophenyl)vinyl]-5-[(3-bromophenyl)sulfonyl]pyridine (Example 27, 340 mg, 0.779 mmol) and zinc cyanide (110 mg, 0.93 mmol) were combined in N,N-dimethylformamide (5 mL) and degassed. Tetrakis-(triphenyl phosphine)palladium(0) (68 mg, 0.059 mmol) was added and the reaction heated at 100° C. under nitrogen for 6 hours. Further tetrakis(triphenylphosphine)palladium(0) (60 mg) was added and heating continued for 18 hours. The cooled reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers dried over MgSO4 and concentrated in vacuo. The residue was purified by mass-triggered preparative HPLC (Nebula) to give the title compound as a beige solid (56 mg, 19%). This was purified further by recrystallisation from isopropyl alcohol/dichloromethane. δH (500 MHz, d6 DMSO): 9.16 (1H, s), 8.57 (1H, s), 8.40 (1H, dd, J=2.2, 8.4 Hz), 8.33 (1H, d, J=8.2 Hz), 8.18 (1H, d, J=7.8 Hz), 7.96–7.82 (3H, m), 7.76 (1H, d, J=8.3 Hz), 7.46 (1H, d, J=16.1 Hz), 7.36–7.31 (1H, m), 7.20–7.16 (1H, m); m/z (ES+) 383 [MH+].

Workup

  1. customdegassed
  2. temperatureheating
  3. customThe cooled reaction mixture
  4. customwas partitioned between ethyl acetate and water
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined organic layers dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by mass-triggered preparative HPLC (Nebula)

Sources & evidence

ORD record
ord-98d2e9fae1c74e55930286e010c56dc0
Source dataset
uspto-grants-2007_05
Patent number
US07217740B2

Reaction notes

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