Dimethylacetamide → 6-Chloro-1H-indazole-3-carbonitrile

HRID 2203334Notes

Reaction equation

HRID 2203334 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](I)=[N:7][NH:8]2)=[CH:4][CH:3]=1.C[C:13]([N:15](C)C)=O>[Zn].[C-]#N.[Zn+2].[C-]#N.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].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]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:13]#[N:15])=[N:7][NH:8]2)=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 178477877HCID 178477877, compound

Product 1

HCID 534084026-Chloro-1H-indazole-3-carbonitrile

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 DMA (48 mL) solution containing the intermediate from Step B (4.0 g, 14.36 mmol), zinc powder (113 mg, 1.72 mmol), zinc cyanide (1.01 g, 8.86 mmol), 1,1′-bis(diphenylphosphino)ferrocene (318 mg, 0.58 mmol) and tris(dibenzylideneacetone)dipalladium (263 mg, 0.29 mmol) was heated at 120° C. for 45 minutes. The solution was cooled to room temperature and partitioned between EtOAc and 0.5M HCl aq. The organic phase was washed twice with 0.5M HCl aq and brine. The organic phase was then dried over MgSO4, filtered and concentrated. The crude material was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated product. 1H NMR (400 MHz, CH3 CN-d3): δ 7.83 (d, J=8.7 Hz, 1H); 7.77 (d, J=1.7 Hz, 1H); 7.36 (dd, J=8.7, 1.7 Hz, 1H). m/z=178.1 (M+H).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. custompartitioned between EtOAc and 0.5M HCl aq. The organic phase
  3. washwas washed twice with 0.5M HCl aq and brine
  4. dry with materialThe organic phase was then dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography
  8. customto give the indicated product

Sources & evidence

ORD record
ord-9e46c4a5dd684fca8f17ae094d9e4aca
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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