2-(Dimethylamino)ethanol → 4-[2-(Dimethylamino)ethoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone

HRID 21098

反応式

HRID 21098 の反応式
[OH:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:34].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:54][N:55]([CH3:59])[CH2:56][CH2:57]O.CCOC(/N=N/C(OCC)=O)=O.C1(C)C=CC=CC=1>C1COCC1.O>[CH3:54][N:55]([CH3:59])[CH2:56][CH2:57][O:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:34]

参加物

7

反応物 4

HCID 79022-(Dimethylamino)ethanol3 回HCID 11776Triphenylphosphine3 回HCID 684932224-Hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinoneHCID 87147022ethyl (NE)-N-ethoxycarbonyliminocarbamate;toluene3 回

生成物 1

HCID 684934644-[2-(Dimethylamino)ethoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone収率 53.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

4-Hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (60.0 mg, 0.130 mmol) was dissolved in THF (3.6 mL), and the solution was added with triphenylphosphine (68 mg, 0.26 mmol), 2-dimethylaminoethanol (0.026 mL, 0.26 mmol) and 40% DEAD-toluene solution (0.118 mL) under ice-cooling, followed by stirring for 20 minutes. The reaction mixture was warmed to room temperature and stirred for 14 hours. The mixture was added with triphenylphosphine (68 mg, 0.26 mmol), 2-dimethylaminoethanol (0.026 mL, 0.26 mmol) and 40% DEAD-toluene solution (0.118 mL) and stirred for 1.7 hours. Then, the mixture was further added with triphenylphosphine (34 mg, 0.13 mmol), 2-dimethylaminoethanol (0.026 mL, 0.26 mmol) and 40% DEAD-toluene solution (0.059 mL), followed by stirring for 1.3 hours. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by preparative thin-layer chromatography (chloroform/methanol/7 mol/L ammonia-methanol solution=12/0.5/0.5, chloroform/methanol=3/1) to obtain 4-[2-(dimethylamino)ethoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (36.9 mg, yield 53%).

後処理

  1. temperaturecooling
  2. stirringstirred for 14 hours
  3. stirringstirred for 1.7 hours
  4. stirringby stirring for 1.3 hours
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by preparative thin-layer chromatography (chloroform/methanol/7 mol/L ammonia-methanol solution=12/0.5/0.5, chloroform/methanol=3/1)

出典と根拠

ORDレコード
ord-5b2c267b49ba40269cde09b4fcb6f39d
出典データセット
uspto-grants-2010_06
特許番号
US07745641B2

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