Dimethylformamide → 4-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbonitrile

HRID 475223Notes

Reaction equation

HRID 475223 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]2[N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[CH:7]=[N:8][C:4]=2[C:3]=1[Cl:17].[CH3:18][N:19](C=O)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2]>[Cl:17][C:3]1[C:4]2[N:8]=[CH:7][N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[C:5]=2[CH:15]=[CH:16][C:2]=1[C:18]#[N:19]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 712721545-bromo-4-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

Product 1

HCID 712724394-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbonitrileYield 70%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

A solution of 130 (26 g, 0.082 mol) in dry DMF (550 mL) was degassed for 10 min. To the solution was added sequentially Pd2(dba)3 (1.5 g, 0.00164 mol), dppf (1.8 g, 0.00328 mol) and Zn(CN)2 (9.19 g, 0.0657 mol). After degassing for 15 min the resulting solution was heated to 110° C. for 6 h. After the reaction was complete, the reaction mixture was filtered through a Celite® pad. The pad was washed well with EtOAc. The filtrate was washed with water and saturated brine solution. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to afford 15 g (70%) of 4-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbonitrile (132) as a pale yellow solid.

Workup

  1. customAfter degassing for 15 min the resulting solution
  2. filtrationthe reaction mixture was filtered through a Celite® pad
  3. washThe pad was washed well with EtOAc
  4. washThe filtrate was washed with water and saturated brine solution
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c3863dfa928544cc93ec0cc97ec9183e
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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