N,N'-Dimethylethylenediamine → 2-Bromo-6-(5-(dimethylamino)-1-oxoisoindolin-2-yl)benzyl Acetate

HRID 1772150ノート

反応式

HRID 1772150 の反応式
[CH3:1][N:2]([CH3:13])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH2:6]2.[Br:14][C:15]1[C:16]([CH3:36])=[C:17](NCC2C=C(C(C)(C)C)SC=2C(OC)=O)[CH:18]=[CH:19][CH:20]=1.[C:37](=[O:40])([O-])[O-:38].[Cs+].[Cs+].[CH3:43]NCCNC>[Cu](I)I.O1CCOCC1>[C:37]([O:38][CH2:36][C:16]1[C:17]([N:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[C:3]([N:2]([CH3:13])[CH3:1])[CH:4]=3)[C:8]2=[O:12])=[CH:18][CH:19]=[CH:20][C:15]=1[Br:14])(=[O:40])[CH3:43]

参加物

7

反応物 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 666103345-(Dimethylamino)isoindolin-1-oneHCID 86697931Methyl 3-((3-Bromo-2-methylphenylamino)methyl)-5-tert-butylthiophene-2-carboxylate

生成物 1

HCID 666102972-Bromo-6-(5-(dimethylamino)-1-oxoisoindolin-2-yl)benzyl Acetate収率 320.6%

試薬・触媒・溶媒 2

HCID 83717Copper iodide触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
105 °C

実験手順

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was charged with 123c (2.40 g, 13.6 mmol), 102d (8.34 g, 27.3 mmol), cesium carbonate (1.34 g, 4.10 mmol), N,N′-dimethylethylenediamine (181 mg, 2.05 mmol) and 1,4-dioxane (12 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper iodide (195 mg, 1.03 mmol) was added. A reflux condenser was attached to the flask, and the reaction mixture was heated at 105° C. for 16 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (150 mL) and water (75 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×50 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (silica, 70:30 hexanes/ethyl acetate) to afford a 48% yield (2.65 g) of 123d as a white solid: mp 93-95° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.75 (d, 1H, J=8.5 Hz), 7.62 (dd, 1H, J=7.5, 1.0 Hz), 7.27 (m, 2H), 6.81 (t, 1H, J=6.5 Hz), 6.68 (s, 1H), 5.21 (s, 2H), 4.69 (s, 2H), 3.09 (s, 6H), 2.00 (s, 3H); (ESI+) m/z 403.6 (M+H).

後処理

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
  2. customAfter bubbling nitrogen through the resulting suspension for 30 min
  3. customA reflux condenser was attached to the flask
  4. temperatureAfter this time, the mixture was cooled to room temperature
  5. filtrationfiltered
  6. additionThe filtrate was diluted with ethyl acetate (150 mL) and water (75 mL)
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  9. washthe combined organic layers were washed with brine (100 mL)
  10. dry with materialdried over sodium sulfate
  11. customThe drying agent was removed by filtration
  12. concentrationThe filtrate was concentrated under reduced pressure
  13. customthe resulting residue was purified by flash column chromatography (silica, 70:30 hexanes/ethyl acetate)

出典と根拠

ORDレコード
ord-05fc149eecaf47d4bf0274905c4dccc0
出典データセット
uspto-grants-2016_02
特許番号
US09249123B2

反応ノート

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