Dimethylacetamide → HCID 67199950, compound

HRID 509990Notes

Reaction equation

HRID 509990 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][C:12]3[CH:13]=[CH:14][C:15]([NH:19][CH2:20][C:21]4[CH:22]=[N:23][C:24]([O:28][CH3:29])=[C:25]([F:27])[CH:26]=4)=[N:16][C:17]=3[F:18])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:30][N:31](C)C(=O)C>[Zn].[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]>[F:18][C:17]1[C:12]([CH2:11][C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:30]#[N:31])[CH:3]=3)[NH:8][CH:9]=2)=[CH:13][CH:14]=[C:15]([NH:19][CH2:20][C:21]2[CH:22]=[N:23][C:24]([O:28][CH3:29])=[C:25]([F:27])[CH:26]=2)[N:16]=1

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 52934254HCID 52934254, compound

Product 1

HCID 67199950HCID 67199950, compoundYield 88.8%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

To 5-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-6-fluoro-N-[(5-fluoro-6-methoxy-3-pyridyl)methyl]pyridin-2-amine (125 mg, 0.27 mmol) was added 2 mL of N,N-dimethylacetamide. The mixture suspension was degassed by bubbling with argon. To this suspension was added Zinc (5 mg, 0.08 mmol), 11,1′-Bis(diphenylphosphino)ferrocene (6 mg, 0.01 mmol), Zinc Cyanide (0.01 ml, 0.19 mmol), and Tris(dibenzylideneacetone)dipalladium (0) (7 mg, 0.01 mmol) at room temperature under argon. The mixture was heated to 120° C. for 2 hrs and cooled to room temperature. The reaction mixture was extracted with ethyl acetate and water (+saturated sodium chloride). The organic layer was washed with water and brine, dried by MgSO4. The volatiles were removed under vacuum. The residue was suspended in acetonitrile and sonicated for 45 mins. The precipitate was collected by filtration and washed with acetonitrile. A tan solid was obtained (98 mg, 88.8% yield). LC-MS showed one major peak with 98.6% purity. The structure of the product is confirmed by H1-NMR (DMSO-d6). MS (ESI) [M+H]+=406.9.

Workup

  1. customThe mixture suspension was degassed
  2. customby bubbling with argon
  3. temperaturecooled to room temperature
  4. extractionThe reaction mixture was extracted with ethyl acetate and water (+saturated sodium chloride)
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried by MgSO4
  7. customThe volatiles were removed under vacuum
  8. customsonicated for 45 mins
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with acetonitrile
  11. customA tan solid was obtained (98 mg, 88.8% yield)

Sources & evidence

ORD record
ord-b70e663013e646a680c82f67a59c88af
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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