Dimethylacetamide → HCID 44538882, compound

HRID 1639583Notes

Reaction equation

HRID 1639583 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:28][N:29](C)C(=O)C>[Zn].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[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].O>[C:28]([C:2]1[N:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:22])=[O:23])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1)#[N:29]

Participants

8

Reactant 2

HCID 31374DimethylacetamideHCID 44538981HCID 44538981, compound

Product 1

HCID 44538882HCID 44538882, compoundYield 41.6%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

In a vial containing propane-1-sulfonic acid [3-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4-difluoro-phenyl]-amide (P-0002, 0.075 g, 0.16 mmol), N,N-dimethylacetamide (0.147 mL, 1.58 mmol) was added. The solution was degassed by bubbling with argon. Zinc powder (0.99 mg, 0.015 mmol), 1,1′-bis(diphenylphosphino)ferrocene (2.87 mg, 0.00518 mmol), zinc cyanide (11.2 mg, 0.0959 mmol), and Tris(dibenzylideneacetone)dipalladium (0) (02.7 mg, 0.0026 mmol) were added at room temperature under argon. The mixture was heated at 120° C., for 1 hour and 50 minutes and cooled to room temperature. Then, 2 mL of water was added and the reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was purified by silica gel column chromatography eluting with a gradient from 1 to 3% methanol in dichloromethane. Appropriate fractions were combined and concentrated under vacuum to give the desired compound (P-0006, 27 mg). MS (ESI)[M+H+]+=406.0.

Workup

  1. additionwas added
  2. customThe solution was degassed
  3. customby bubbling with argon
  4. temperaturecooled to room temperature
  5. extractionthe reaction mixture was extracted with ethyl acetate and water
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated under vacuum
  10. customThe residue was purified by silica gel column chromatography
  11. washeluting with a gradient from 1 to 3% methanol in dichloromethane
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-2253355042ea470fa357537f7000013d
Source dataset
uspto-grants-2012_02
Patent number
US08110576B2

Reaction notes

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