Water → 4-(4-Amino-2-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 2240249Notes

Reaction equation

HRID 2240249 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18]C(=O)C(F)(F)F)=[CH:14][C:13]=2[F:25])[N:4](S(C2C=CC(C)=CC=2)(=O)=O)[CH:3]=1.[CH3:36][N:37](C=O)C.O.[OH-].[Li+]>C([O-])(=O)C.[Zn+2].C([O-])(=O)C.[Zn].[C-]#N.[Zn+2].[C-]#N.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)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].C1COCC1>[NH2:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][C:9]2[CH:8]=[CH:7][N:6]=[C:5]3[NH:4][CH:3]=[C:2]([C:36]#[N:37])[C:10]=23)=[C:13]([F:25])[CH:14]=1

Participants

11

Reactant 4

HCID 962Water2×HCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 59304989N-[4-({3-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}methyl)-3-fluorophenyl]-2,2,2-trifluoroacetamide

Product 1

HCID 593049784-(4-Amino-2-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Reagents, catalysts & solvents 6

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11192Zinc AcetateCatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

1.70 g (2.98 mmol) of N-[4-({3-bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-methyl)-3-fluorophenyl]-2,2,2-trifluoroacetamide, 219 mg (1.19 mmol) of zinc acetate, 78 mg (1.19 mmol) of zinc dust, 189 mg (1.61 mmol) of zinc cyanide, 50.0 mg (0.09 mmol) of bis(diphenylphosphino)ferrocene and 27.3 mg (0.03 mmol) of tris(dibenzylideneacetone)dipalladium are initially charged. Under argon, a degassed mixture of 17 ml of DMF and 0.17 ml of water is added, and the mixture is heated at 100° C. for 20 hours. 10 ml of water, 8 ml of THF and 1.21 g (50.3 mmol) of lithium hydroxide are added to the crude mixture, which is then stirred at RT for 20 h. The mixture is concentrated a little and extracted with ethyl acetate. The organic phase is dried over sodium sulfate and concentrated under reduced pressure. The product is purified by chromatography on silica gel (mobile phase: dichloromethane:methanol 25:1).

Workup

  1. additionis added
  2. concentrationThe mixture is concentrated a little and
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe product is purified by chromatography on silica gel (mobile phase: dichloromethane:methanol 25:1)

Sources & evidence

ORD record
ord-d08bfc67665f4cc98d8f379cb6ef4955
Source dataset
uspto-grants-2010_05
Patent number
US07723347B2

Reaction notes

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