Potassium Phosphate, Tribasic → 6-(1H-Indol-4-yl)-1-(phenylsulfonyl)-1H-indazole-4-carbonitrile

HRID 520508Notes

Reaction equation

HRID 520508 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:20]#[N:21])[C:5]2[CH:6]=[N:7][N:8]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:30]2[CH:38]=[CH:37][CH:36]=[C:35]3[C:31]=2[CH:32]=[CH:33][NH:34]3)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Pd](Cl)Cl.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]>[NH:34]1[C:35]2[C:31](=[C:30]([C:2]3[CH:3]=[C:4]([C:20]#[N:21])[C:5]4[CH:6]=[N:7][N:8]([S:11]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=5)(=[O:13])=[O:12])[C:9]=4[CH:10]=3)[CH:38]=[CH:37][CH:36]=2)[CH:32]=[CH:33]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 666921566-Bromo-1-(phenylsulfonyl)-1H-indazole-4-carbonitrile

Product 1

HCID 666940066-(1H-Indol-4-yl)-1-(phenylsulfonyl)-1H-indazole-4-carbonitrileYield 16.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 6-bromo-1-(phenylsulfonyl)-1H-indazole-4-carbonitrile (5 g, 13.80 mmol) in 1,4-dioxane (50 ml) and water (20 ml) was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (4.03 g, 16.57 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (1.010 g, 1.380 mmol) and potassium phosphate tribasic (8.79 g, 41.4 mmol). The mixture was heated at 60° C. for 1 h, cooled and evaporated in vacuo. The residue was partitioned between water (50 ml) and dichloromethane (100 ml). The suspended solid was collected and the organics were separated by hydrophobic frit and concentrated to approx 50 ml. The precipitated solid was collected as a beige solid (1.93 g) and the filtrate purified by silica (300 g) cartridge using a gradient of ethyl acetate and cyclohexane, to give the title compound as a pale yellow solid (0.91 g). The solid collected during partitioning was purified by pre-absorbing onto florisil and purification by silica (100 g) cartridge on Flashmaster 11 using a gradient of dichloromethane and ethyl acetate to give a further quantity of the title compound as a pale yellow solid (0.45 g).

Workup

  1. temperaturecooled
  2. customevaporated in vacuo
  3. customThe residue was partitioned between water (50 ml) and dichloromethane (100 ml)
  4. customThe suspended solid was collected
  5. customthe organics were separated by hydrophobic frit
  6. concentrationconcentrated to approx 50 ml
  7. customThe precipitated solid was collected as a beige solid (1.93 g)
  8. customthe filtrate purified by silica (300 g) cartridge

Sources & evidence

ORD record
ord-67a778b2edcc46df8efba49d1a683237
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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