1,4-Dioxane → 1,1-Dimethylethyl 4-[4-cyano-1-(phenylsulfonyl)-1H-indazol-6-yl]-1H-indole-1-carboxylate

HRID 520532Notes

Reaction equation

HRID 520532 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][N:34]3[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[C:20]([C:4]1[CH:3]=[C:2]([C:30]2[CH:38]=[CH:37][CH:36]=[C:35]3[C:31]=2[CH:32]=[CH:33][N:34]3[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][N:8]2[S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:13])=[O:12])#[N:21]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 60204498Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylateHCID 666921566-Bromo-1-(phenylsulfonyl)-1H-indazole-4-carbonitrile

Product 1

HCID 667768451,1-Dimethylethyl 4-[4-cyano-1-(phenylsulfonyl)-1H-indazol-6-yl]-1H-indole-1-carboxylateYield 44.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a round bottomed flask was charged 6-bromo-1-(phenylsulfonyl)-1H-indazole-4-carbonitrile (10 g, 27.6 mmol), 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (14.21 g, 41.4 mmol) and potassium phosphate tribasic (17.58 g, 83 mmol). The resulting mixture was treated with 1,4-dioxane (120 ml) and water (12 ml) that had previously been purged with nitrogen. The mixture was then treated with 1′-bis(diphenylphosphino)ferrocene palladium dichloride (1.547 g, 2.76 mmol) and heated to reflux, under nitrogen for 2 h. Additional 1′-bis(diphenylphosphino)ferrocene palladium dichloride (1.547 g, 2.76 mmol) was added and the mixture heated at reflux for a further 1 h. The hot reaction mixture was filtered through Celite, washed well with chloroform and the filtrate concentrated in vacuo. The residue was dissolved in DCM/cyclohexane (1:1, 50 ml) and purified by column chromatography on silica (750 g cartridge), eluting with 0-40% ethyl acetate/cyclohexane. The pure fractions were combined and concentrated to give the title compound as a yellow solid (6.16 g).

Workup

  1. customhad previously been purged with nitrogen
  2. temperatureheated
  3. temperatureto reflux, under nitrogen for 2 h
  4. temperaturethe mixture heated
  5. temperatureat reflux for a further 1 h
  6. filtrationThe hot reaction mixture was filtered through Celite
  7. washwashed well with chloroform
  8. concentrationthe filtrate concentrated in vacuo
  9. dissolutionThe residue was dissolved in DCM/cyclohexane (1:1, 50 ml)
  10. custompurified by column chromatography on silica (750 g cartridge)
  11. washeluting with 0-40% ethyl acetate/cyclohexane
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4ab1224befaa4a44a050552ab17d1763
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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