Potassium Carbonate → 6-chloro-5-{4-[1-(methylsulfonyl)pyrrolidin-2-yl]phenyl}-1H-indole-3-carbaldehyde

HRID 1054771Notes

Reaction equation

HRID 1054771 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=[O:22])([O-])[O-].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:36][CH2:35][CH2:34][N:33]2[S:37]([CH3:40])(=[O:39])=[O:38])=[CH:28][CH:27]=1>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].O1CCOCC1.CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:22])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:27]=[CH:28][C:29]([CH:32]2[CH2:36][CH2:35][CH2:34][N:33]2[S:37]([CH3:40])(=[O:38])=[O:39])=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 473202792-(4-Bromophenyl)-1-(methylsulfonyl)pyrrolidineHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Product 1

HCID 866987616-chloro-5-{4-[1-(methylsulfonyl)pyrrolidin-2-yl]phenyl}-1H-indole-3-carbaldehydeYield 24%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 217120691,4-dioxane N,N-dimethylformamideSolvent2×

Procedure

To a suspension of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (210 mg, 0.80 mmol) in a solvent mixture of 1,4-dioxane/N,N-dimethylformamide=5:1 (3 mL) was added Vilsmer-salt (232 mg, 4.80 mmol) under nitrogen and the mixture was stirred at room temperature for 30 minutes. Potassium carbonate (2.0 M in water, 2.0 mL) was added to the above suspension followed by the addition of 2-(4-bromophenyl)-1-(methylsulfonyl)pyrrolidine (240 mg, 0.79 mmol) in a solvent mixture of 1,4-dioxane/N,N-dimethylformamide=5:1 (3 mL) added under nitrogen. The mixture was degassed with nitrogen for 10 minutes. The mixture was treated with Pd(dppf)Cl2 (87 mg, 0.12 mmol) and stirred at 90° C. under nitrogen for 30 minutes. The mixture was filtered through a celite pad and the filtrate was partitioned between ethyl acetate (10 mL) and water (20 mL). The aqueous phase was extracted three additional times with ethyl acetate (10 mL) and the combined the organic phases were washed with brine (15 mL), dried over sodium sulfate, filtered and concentrated to afford crude which was purified by silica-gel chromatography to give the title compound (76.7 mg, 24.0% yield).

Workup

  1. additionadded under nitrogen
  2. customThe mixture was degassed with nitrogen for 10 minutes
  3. stirringstirred at 90° C. under nitrogen for 30 minutes
  4. filtrationThe mixture was filtered through a celite pad
  5. customthe filtrate was partitioned between ethyl acetate (10 mL) and water (20 mL)
  6. extractionThe aqueous phase was extracted three additional times with ethyl acetate (10 mL)
  7. washwere washed with brine (15 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford crude which
  12. customwas purified by silica-gel chromatography

Sources & evidence

ORD record
ord-254f126a0ad44fc595590165e6a70c34
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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