Sodium Carbonate → 6-(1H-indol-4-yl)-1H-indazol-4-amine

HRID 520566Notes

Reaction equation

HRID 520566 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:11])[C:5]2[CH:6]=[N:7][NH:8][C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:20]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:21]=2[CH:22]=[CH:23][NH:24]3)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH:24]1[C:25]2[C:21](=[C:20]([C:2]3[CH:3]=[C:4]([NH2:11])[C:5]4[CH:6]=[N:7][NH:8][C:9]=4[CH:10]=3)[CH:28]=[CH:27][CH:26]=2)[CH:22]=[CH:23]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 247280636-Bromo-1H-indazol-4-amine

Product 1

HCID 582680196-(1H-indol-4-yl)-1H-indazol-4-amine

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

6-Bromo-1H-indazol-4-amine (10 g) (available from Sinova Inc.) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (16.05 g) (available from Frontier Scientific, Europe Ltd) were dissolved in 1,4-dioxane (60 ml) and water (60 ml). 2 M sodium carbonate (70.7 ml) and Pd(dppf)Cl2-DCM adduct (1.93 g) were added and the mixture was heated at 115° C. for 18 h. The reaction mixture was diluted with DCM (200 ml) and the organic and aq layers were separated using a hydrophobic frit. The aq layer was extracted with further quantities of DCM (2×200 ml), using a hydrophobic frit to separate the layers. The organic layers were combined and silica (80 g) was added. The solvent was removed in vacuo to give a crude material that was purified by chromatography on silica gel (750 g cartridge, Flashmaster II) eluting with 0-100% ethyl acetate in cyclohexane over 60 min. The oil was dried in vacuo on a drying rack overnight. The yellow foam was dissolved in DCM (3×400 ml), removing the solvent in vacuo after each dissolution. ethyl acetate (50 ml) was then added and the solvent was removed in vacuo.

Workup

  1. customthe organic and aq layers were separated
  2. extractionThe aq layer was extracted with further quantities of DCM (2×200 ml)
  3. customto separate the layers
  4. additionsilica (80 g) was added
  5. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-4749762abec443ecb313bc75db9a9336
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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