Benzimidazole → HCID 178509450, compound

HRID 2272116Notes

Reaction equation

HRID 2272116 reaction equation
FC(F)(F)S([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([N:17]3[CH2:22][CH2:21][CH2:20][C@@H:19]4[C:23]5[CH:24]=[C:25](OS(C(F)(F)F)(=O)=O)[CH:26]=[CH:27][C:28]=5[CH2:29][C@H:18]34)=[O:16])=[CH:14][C:9]=2[N:8]=[CH:7]1)(=O)=O.[N:40]1C2C=CC=CC=2N[CH:41]=1>[C-]#N.[Zn+2].[C-]#N.CN(C)C=O>[NH:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([N:17]3[CH2:22][CH2:21][CH2:20][C@@H:19]4[C:23]5[CH:24]=[C:25]([C:41]#[N:40])[CH:26]=[CH:27][C:28]=5[CH2:29][C@H:18]34)=[O:16])=[CH:14][C:9]=2[N:8]=[CH:7]1

Participants

5

Reactant 2

HCID 5798BenzimidazoleHCID 86654157HCID 86654157, compound

Product 1

HCID 178509450HCID 178509450, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A flask charged with a stir bar, zinc cyanide (0.32 g), trifluoromethanesulfonic acid cis-1-(1-trifluoromethanesulfonyl-1H-benzoimidazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-yl ester (mixture of isomers regarding sulfonyl group attachment at N-1 or N-3 of the benzimidazole, 1.08 g), and N,N-dimethylformamide (5 mL) is sparged with argon for 10 min. Tetrakis(triphenylphosphine)palladium(0) (0.31 g) is then added and the resulting mixture is heated to 100° C. and stirred at this temperature for 2 h. After cooling to room temperature, 1-hydroxybenzotriazole hydrate (0.45 g) and water (1.5 mL) are added and stirring is continued at room temperature for 3 h. Ethyl acetate, little methanol, and saturated aqueous Na2CO3 solution are added and the mixture is filtered over Celite. The aqueous phase of the filtrate is separated and neutralized with 2 M aqueous citric acid and extracted with ethyl acetate. The organic phases are combined and washed with brine and dried (Na2SO4). The solvent is evaporated and the residue is chromatographed on silica gel (dichloromethane/methanol 96:4→90:10) to give the title compound as a solid. Yield: 0.42 g (68% of theory).

Workup

  1. additionA flask charged with a stir bar
  2. customis sparged with argon for 10 min
  3. additionTetrakis(triphenylphosphine)palladium(0) (0.31 g) is then added
  4. temperatureAfter cooling to room temperature
  5. addition1-hydroxybenzotriazole hydrate (0.45 g) and water (1.5 mL) are added
  6. stirringstirring
  7. waitis continued at room temperature for 3 h
  8. additionEthyl acetate, little methanol, and saturated aqueous Na2CO3 solution are added
  9. filtrationthe mixture is filtered over Celite
  10. customThe aqueous phase of the filtrate is separated
  11. extractionextracted with ethyl acetate
  12. washwashed with brine
  13. dry with materialdried (Na2SO4)
  14. customThe solvent is evaporated
  15. customthe residue is chromatographed on silica gel (dichloromethane/methanol 96:4→90:10)

Sources & evidence

ORD record
ord-60860a1fbece473686a5b8904af6761c
Source dataset
uspto-grants-2015_09
Patent number
US09120769B2

Reaction notes

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