Water → 6-(1H-Indol-4-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbonitrile

HRID 520530Notes

Reaction equation

HRID 520530 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:21]#[N:22])[C:5]2[CH:6]=[N:7][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:31]2[CH:39]=[CH:38][CH:37]=[C:36]3[C:32]=2[CH:33]=[CH:34][NH:35]3)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.[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:35]1[C:36]2[C:32](=[C:31]([C:2]3[CH:3]=[C:4]([C:21]#[N:22])[C:5]4[CH:6]=[N:7][N:8]([S:11]([C:14]5[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=5)(=[O:12])=[O:13])[C:9]=4[CH:10]=3)[CH:39]=[CH:38][CH:37]=2)[CH:33]=[CH:34]1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 666914596-bromo-1-(4-methylbenzenesulfonyl)-1H-indazole-4-carbonitrile

Product 1

HCID 667767806-(1H-Indol-4-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbonitrile

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a suspension of 6-bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbonitrile in 1,4-dioxane (100 ml) was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (4.79 g, 10.72 mmol, available from Frontier Scientific Europe), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (2.061 g, 2.82 mmol) and potassium phosphate tribasic (8.97 g, 42.3 mmol). Water (20 ml) was added and the reaction mixture heated to 80° C. for 1 h. The solvent was removed and the residue partitioned between water (50 ml) and ethyl acetate (100 ml). The layers were filtered and the filtrate partitioned and concentrated, then purified by column chromatography, on a silica cartridge (300 g), eluting with a gradient of cyclohexane and ethyl acetate to give the title compound as a pale yellow solid (2.5 g).

Workup

  1. customThe solvent was removed
  2. customthe residue partitioned between water (50 ml) and ethyl acetate (100 ml)
  3. filtrationThe layers were filtered
  4. customthe filtrate partitioned
  5. concentrationconcentrated
  6. custompurified by column chromatography, on a silica cartridge (300 g)
  7. washeluting with a gradient of cyclohexane and ethyl acetate

Sources & evidence

ORD record
ord-e63a9cf7728f4d2793548f0248cf2a83
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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