Dimethylformamide → HCID 66886666, compound

HRID 1895496Notes

Reaction equation

HRID 1895496 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:21]([NH:22][C:23]2[CH:28]=[CH:27][C:26](I)=[CH:25][C:24]=2[CH3:30])=[C:20]([F:31])[C:8]2[N:9]=[C:10]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[NH:11][C:7]=2[CH:6]=1)=[O:4].[CH3:32][N:33](C=O)C>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].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].[C-]#N.[C-]#N.[Zn+2]>[CH3:1][O:2][C:3]([C:5]1[C:21]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([C:32]#[N:33])=[CH:25][C:24]=2[CH3:30])=[C:20]([F:31])[C:8]2[N:9]=[C:10]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[NH:11][C:7]=2[CH:6]=1)=[O:4]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 68818776HCID 68818776, compound

Product 1

HCID 66886666HCID 66886666, compoundYield 77%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

To a stirred solution of a 1:1 mixture of N1:N3 isomers of 7-fluoro-6-(4-iodo-2-methyl-phenylamino)-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester 10jj (0.060 g, 0.108 mmol) in 1 mL DMF at room temperature under N2 is added dppf (2 mg, 0.004 mmol) followed by Pd2dba3 (2 mg, 0.002 mmol) and Zn(CN)2 (8 mg, 0.065 mmol) (Tetrahedron Lett. 1999, 40, 8193-8195). The reaction mixture is heated to 120° C. for 45 minutes. The reaction mixture is cooled to room temperature and quenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl:conc NH4OH:water. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are washed with water (3×), brine, and dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography eluted with 1:1 hexanes:ethyl acetate provides 38 mg (77%) of desired product as a 1:1 mixture of N1 and N3 isomers: APCI MS (+) m/z 455 (M+1) detected.

Workup

  1. additionTo a stirred solution of a 1:1 mixture of N1
  2. temperatureThe reaction mixture is cooled to room temperature
  3. customquenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl
  4. extractionThe aqueous layer is extracted with ethyl acetate
  5. washThe combined organic extracts are washed with water (3×), brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography
  9. washeluted with 1:1 hexanes

Sources & evidence

ORD record
ord-36805a9ce55f45cbb8d8b43a1d7c39ba
Source dataset
uspto-grants-2013_08
Patent number
US08513293B2

Reaction notes

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