Dimethylacetamide → HCID 67777609, compound

HRID 1026310Notes

Reaction equation

HRID 1026310 reaction equation
Br[C:2]1[C:10]2[C:6](=[CH:7][N:8]([C:11]3[CH:24]=[CH:23][C:14]([O:15][CH2:16][C@@H:17]([NH:19][C:20](=[O:22])[CH3:21])[CH3:18])=[CH:13][CH:12]=3)[N:9]=2)[CH:5]=[CH:4][C:3]=1[O:25][CH2:26][CH:27]1[CH2:29][CH2:28]1.[CH3:30][N:31](C)C(=O)C>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].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.[Zn]>[C:30]([C:2]1[C:10]2[C:6](=[CH:7][N:8]([C:11]3[CH:24]=[CH:23][C:14]([O:15][CH2:16][C@@H:17]([NH:19][C:20](=[O:22])[CH3:21])[CH3:18])=[CH:13][CH:12]=3)[N:9]=2)[CH:5]=[CH:4][C:3]=1[O:25][CH2:26][CH:27]1[CH2:29][CH2:28]1)#[N:31]

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 67778665HCID 67778665, compound

Product 1

HCID 67777609HCID 67777609, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
120 °C

Procedure

A mixture of N-[(1S)-2-{4-[7-bromo-6-(cyclopropylmethoxy)-2H-indazol-2-yl]phenoxy}-1-methylethyl]acetamide (150 mg), tris(dibenzylideneacetone)dipalladium(0) (45 mg), 1,1′-bis(diphenylphosphino)ferrocene (54.4 mg), zinc cyanide (57.7 mg), zinc powder (10.7 mg) and N,N-dimethylacetamide (3 mL) was stirred at 120° C. for 1.5 hr under an argon atmosphere. The reaction mixture was filtered through silica gel, and the filtrate was concentrated under reduced pressure. To the residue was added water, and the mixture was extracted with ethyl acetate. The combined organic layer was washed three times with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as colorless crystals (54.5 mg).

Workup

  1. filtrationThe reaction mixture was filtered through silica gel
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionTo the residue was added water
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe combined organic layer was washed three times with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-640264467cb24e03803387dfb383a40d
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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