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

HRID 1772150Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1772150
[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]

Komponenten

7

Edukt 4

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

Produkt 1

HCID 666102972-Bromo-6-(5-(dimethylamino)-1-oxoisoindolin-2-yl)benzyl AcetateAusbeute 320,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 83717Copper iodideKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-05fc149eecaf47d4bf0274905c4dccc0
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09249123B2

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