Dimethylformamide → N-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]-2-ethoxy-acetamide

HRID 2103524

Reaktionsgleichung

Reaktionsgleichung von HRID 2103524
[CH2:1]([O:3][CH2:4][C:5]([OH:7])=O)[CH3:2].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:19][C:20]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:21]=1[C:22](=[O:38])[N:23]([CH:30]1[CH2:35][CH2:34][C:33](=[O:36])[NH:32][C:31]1=[O:37])[C:24]2=[O:29]>CCOCC.CO.C1COCC1>[O:37]=[C:31]1[CH:30]([N:23]2[C:22](=[O:38])[C:21]3[C:25](=[CH:26][CH:27]=[CH:28][C:20]=3[NH:19][C:5](=[O:7])[CH2:4][O:3][CH2:1][CH3:2])[C:24]2=[O:29])[CH2:35][CH2:34][C:33](=[O:36])[NH:32]1

Komponenten

8

Edukt 4

HCID 6228DimethylformamideHCID 12301Ethoxyacetic acidHCID 65578Oxalyl chlorideHCID 134780Pomalidomide

Produkt 1

HCID 21988552N-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]-2-ethoxy-acetamideAusbeute 90,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of ethoxyacetic acid (0.8 mL, 8.5 mmol) and oxalyl chloride (0.7 mL, 8.0 mmol) in ether (5 mL) was added DMF (0.03 mL) at room temperature. After 3 h, 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (1.1 g, 4.0 mmol) and THF (40 mL) was added to the mixture. Then the mixture was heated to reflux for 15 h. To the mixture was added methanol (10 mL) to give a suspension. The suspension was filtered and washed with methanol (10 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-2-ethoxy-acetamide as a white solid (1.3 g, 87% yield): mp, 253-255° C.; 1H NMR (DMSO-d6) δ 1.27 (t, J=7.0 Hz, 3H, CH3), 2.06-2.10 (m, 1H, CHH), 2.46-2.64 (m, 2H, CH2), 2.84-2.98 (m, 1H, CHH), 3.66 (q, J=7.0 Hz, 2H, CH2), 4.14 (s, 2H, CH2), 5.17 (dd, J=5.2, 12.7 Hz, 1H, NCH), 7.62 (d, J=7.2 Hz, 1H, Ar), 7.87 (t, J=8.2 Hz, 1H, Ar), 8.75 (d, J=8.4 Hz, 1H, Ar), 10.39 (s, 1H, NH), 1.16 (s, 1H, NH); 13C NMR (DMSO-d6) δ 14.88, 21.93, 30.92, 48.98, 66.89, 69.49, 116.00, 118.28, 124.25, 131.31, 135.99, 136.53, 166.69, 168.31, 169.49, 169.73, 174.71; Anal Calcd for C17H17N3O6: C, 56.82; H, 4.77; N, 11.69. Found C, 56.82; H, 4.71; N, 11.60.

Aufarbeitung

  1. temperatureThen the mixture was heated
  2. temperatureto reflux for 15 h
  3. customto give a suspension
  4. filtrationThe suspension was filtered
  5. washwashed with methanol (10 mL)

Quellen und Nachweise

ORD-Eintrag
ord-f742cc25b5dc4de69b9d49b4be235992
Quelldatensatz
uspto-grants-2009_08
Patentnummer
US07576104B2

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