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

HRID 338428ノート

反応式

HRID 338428 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 217120691,4-dioxane N,N-dimethylformamide溶媒2 回

実験手順

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 (2.0M 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).

後処理

  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

出典と根拠

ORDレコード
ord-0d7aeb46192d4fb3ab22f4dafa13e425
出典データセット
uspto-grants-2014_11
特許番号
US08889730B2

反応ノート

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