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Phthalide → 2-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2,3-dihydro-1H-isoindol-1-one

HRID 15839
ノート
印刷プレビュー

反応式

HRID 15839 の反応式
C[Al](C)C.[CH3:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]3[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=3)[NH2:27])[CH2:18][CH2:17]2)[N:7]=1.[C:31]1([C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34]O1)=[O:32].C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O>ClCCl>[CH3:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[N:16]2[CH2:17][CH2:18][N:19]([CH2:22][CH2:23][C:24]3[CH:25]=[C:26]([N:27]4[CH2:34][C:35]5[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=5)[C:31]4=[O:32])[CH:28]=[CH:29][CH:30]=3)[CH2:20][CH2:21]2)[N:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 6885PhthalideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 16682925TrimethylaluminumHCID 498521053-(2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}aniline

生成物 1

HCID 574783532-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2,3-dihydro-1H-isoindol-1-one
収率 45%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of trimethylaluminium (2.0 M in hexane, 1 eq) was added slowly to a stirred solution of 3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}aniline (D6, 1 eq) in dichloromethane (0.1 M) at 0° C. The reaction mixture was stirred for 15 min then a solution of phthalide (1 eq) in dichloromethane was added dropwise. The solution was stirred for 2 h at 0° C. then partitioned between saturated aqueous ammonium chloride solution and ethyl acetate. The organic phase was dried over sodium sulfate and the solution was concentrated under reduced pressure. The crude 2-(hydroxymethyl)-N-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)benzamide was dissolved in dichloromethane then N,N-diisopropylethylamine (1 eq.) and methanesulfonyl chloride (1 eq.) were added successively. The reaction mixture was stirred for 2 hours at room temperature then partitioned between saturated aqueous ammonium chloride solution and dichloromethane. The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography (SPE cartridge, Silica) eluting with a gradient from dichloromethane-methanol (100:2) to (98:2) affording the title compound (yield 45%).

後処理

  1. stirringThe solution was stirred for 2 h at 0° C.
  2. customthen partitioned between saturated aqueous ammonium chloride solution and ethyl acetate
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationthe solution was concentrated under reduced pressure
  5. dissolutionThe crude 2-(hydroxymethyl)-N-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)benzamide was dissolved in dichloromethane
  6. stirringThe reaction mixture was stirred for 2 hours at room temperature
  7. customthen partitioned between saturated aqueous ammonium chloride solution and dichloromethane
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography (SPE cartridge, Silica)
  11. washeluting with a gradient from dichloromethane-methanol (100:2) to (98:2)

出典と根拠

ORDレコード
ord-e0248e3693dd4609b3e5f8baf161748f
出典データセット
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07732600B2

反応ノート

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