Dimethylacetamide → 2,4-Bis(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921608Notes

Reaction equation

HRID 921608 reaction equation
Br[C:2]1[N:10]2[C:5]([C:6]([S:13][CH3:14])=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[N:4][CH:3]=1.C[C:16]([N:18](C)C)=O>[C-]#N.[Zn+2].[C-]#N.[Zn].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:12][S:11][C:8]1[N:7]=[C:6]([S:13][CH3:14])[C:5]2=[N:4][CH:3]=[C:2]([C:16]#[N:18])[N:10]2[N:9]=1

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 574576447-Bromo-2,4-bis(methylthio)imidazo[2,1-f][1,2,4]triazine

Product 1

HCID 710653752,4-Bis(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

(I2A): A mixture of 7-bromo-2,4-bis(methylthio)imidazo[2,1-f][1,2,4]triazine (6 g, 20.61 mmol), zinc cyanide (1.694 g, 14.42 mmol) and zinc powder (0.270 g, 4.12 mmol) in DMA (150 mL) in a 350 mL round bottom pressure flask was degassed by evacuating with vacuum and back filling with nitrogen three times. bis(tri-t-butylphosphine)palladium (0) (1.053 g, 2.061 mmol) was added and the above process was repeated three times. The reaction mixture was heated at 100° C. for 4 hours. LCMS showed completion of reaction with small amount of de-bromination byproduct and mostly product. The reaction mixture was filtered through a plug of Celite and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (330 g column, eluting with 0-10% ethyl acetate/dichloromethane). 2,4-bis(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (3.35 g) was obtained as a light yellow solid.

Workup

  1. customwas degassed
  2. customby evacuating with vacuum
  3. customcompletion of reaction with small amount of de-bromination byproduct and mostly product
  4. filtrationThe reaction mixture was filtered through a plug of Celite
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel using
  7. washan automated ISCO system (330 g column, eluting with 0-10% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-189ab31ce7a6416fa752f5b7dc851158
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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