Dimethylformamide → HCID 58495553, compound

HRID 1191019Notes

Reaction equation

HRID 1191019 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])=[CH:4][CH:3]=1.[CH3:22][N:23](C=O)C>O.CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.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:22]([C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])=[CH:4][CH:3]=1)#[N:23]

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 58495448HCID 58495448, compound

Product 1

HCID 58495553HCID 58495553, compoundYield 93%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

Under a nitrogen atmosphere add 6-chloro-3-[N-(cyclohexyl)-N-(2,2,2-trifluoroacetyl)-aminomethyl]-pyridine (3.7 g, 11.5 mmol), zinc cyanide (2.02 g, 17.3 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.48 g, 0.57 mmol) and DPPF (0.63 g, 1.15 mmol) to DMF (40 mL). Heat the mixture at 95° C. for 2 h. Cool the mixture to room temperature and dilute with water and EtOAc. Separate the layers and extract the aqueous layer with EtOAc. Wash the combined organic extracts with water and brine. Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (400 g) eluting with hexane/EtOAc (1:0 to 3:2 gradient) to obtain the desired intermediate (3.33 g, 93%). MS (APCI+) m/z: 312 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. customSeparate the layers
  3. extractionextract the aqueous layer with EtOAc
  4. washWash the combined organic extracts with water and brine
  5. dry with materialDry the organic phase over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel (400 g)
  9. washeluting with hexane/EtOAc (1:0 to 3:2 gradient)

Sources & evidence

ORD record
ord-18f135c3ba924db4804524a5a7f76b58
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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