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Potassium Carbonate → 4-Fluoro-N-(2-{4-[2-(1H-indol-4-yl)-pyridin-3-yl]-piperazin-1-yl}-ethyl)-N-methyl-benzenesulfonamide hydrochloride

HRID 553516
ノート
印刷プレビュー

反応式

HRID 553516 の反応式
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:27])[S:17]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:28]1[C:36]2[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[C:31]=2[CH:30]=[CH:29]1.C(=O)([O-])[O-].[K+].[K+].B(O)O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[F:26][C:23]1[CH:24]=[CH:25][C:20]([S:17]([N:16]([CH2:15][CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:7]3[C:2]([C:32]4[CH:33]=[CH:34][CH:35]=[C:36]5[C:31]=4[CH:30]=[CH:29][NH:28]5)=[N:3][CH:4]=[CH:5][CH:6]=3)[CH2:9][CH2:10]2)[CH3:27])(=[O:19])=[O:18])=[CH:21][CH:22]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 27631731H-Indole-4-boronic acidHCID 86640209N-{2-[4-(2-Chloro-pyridin-3-yl)-piperazin-1-yl]-ethyl}-4-fluoro-N-methyl-benzenesulfonamide

生成物 1

HCID 673670934-Fluoro-N-(2-{4-[2-(1H-indol-4-yl)-pyridin-3-yl]-piperazin-1-yl}-ethyl)-N-methyl-benzenesulfonamide hydrochloride収率 15.1%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

Dissolve N-{2-[4-(2-chloro-pyridin-3-yl)-piperazin-1-yl]-ethyl}-4-fluoro-N-methyl-benzenesulfonamide (0.160 g, 0.387 mmol) in DME (5 mL, previously degassed with nitrogen). Add 4-indole boronic acid (0.094 g, 0.581 mmol), 2N aqueous potassium carbonate (0.464 mL, 0.129 g, 0.930 mmol), and tetrakis(triphenylphosphine)palladium (0.022 g, 0.022 mmol). Stir the reaction mixture at 80° C. for 18 hr. Add fresh catalyst (0.015 g) and boronic acid (0.050 g). Stir an additional 8 hr. at 95° C. Cool to room temperature and concentrate to remove DME. Dilute with ethyl acetate and brine. Extract the aqueous layer with ethyl acetate. Combine the organic layers, dry over sodium sulfate, filter, and concentrate. Purify the resulting material by silica gel chromatography eluting with dichloromethane:methanol 94:6 to 90:10 to afford the title compound (0.031 g).

後処理

  1. custompreviously degassed with nitrogen)
  2. stirringStir an additional 8 hr
  3. customat 95° C
  4. temperatureCool to room temperature
  5. concentrationconcentrate
  6. customto remove DME
  7. additionDilute with ethyl acetate and brine
  8. extractionExtract the aqueous layer with ethyl acetate
  9. dry with materialdry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify the resulting material by silica gel chromatography
  13. washeluting with dichloromethane:methanol 94:6 to 90:10

出典と根拠

ORDレコード
ord-4bdadbb919334267b45f5d2714c15373
出典データセット
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08048884B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート