1,8-Diazabicyclo(5.4.0)undec-7-ene → N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin4-yl]methyl}-2-methoxyacetamide

HRID 9974

Reaktionsgleichung

Reaktionsgleichung von HRID 9974
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[CH3:34][O:35][CH2:36][C:37](Cl)=[O:38]>CC#N>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:37](=[O:38])[CH2:36][O:35][CH3:34])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Komponenten

5

Edukt 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 96623Methoxyacetyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Produkt 1

HCID 10291934N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin4-yl]methyl}-2-methoxyacetamideAusbeute 66,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.62 g, 4.07 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.600 g, 1.85 mmol) in CH3CN (50 ml). After stirring for 20 min, methoxyacetyl chloride (0.22 g, 2.03 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (70 ml). The CH2Cl2 solution was washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 100:2.5) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin4-yl]methyl}-2-methoxyacetamide (0.44 g, 66%) as a white solid: mp 196–198° C.; 1H NMR (DMSO-d6) δ d 11.14 (s, 1H), 8.49 (t, J=6.1 Hz, 1H), 7.86–7.79 (m, 2H), 7.68–7.65 (m, 1H), 5.19–5.12 (dd, J=5.3 and 12.5 Hz, 1H), 4.77 (d, J=6.1 Hz, 2H), 3.92 (s, 2H), 3.36 (s, 3H), 2.96–2.83 (m, 1H), 2.64–2.49 (m, 2H), 2.09–2.04 (m, 1H); 13C NMR (DMSO-d6) δ d 172.71, 169.78, 169.58, 167.52, 166.94, 139.09, 134.70, 133.00, 131.51, 127.08, 121.82, 71.46, 58.70, 48.86, 37.47, 30.91, 21.95; Anal. Calcd. For C17H17N3O6: C, 56.82; H, 4.77; N, 11.69. Found: C, 57.02; H, 4.87; N, 11.36.

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature for 17 hours
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in CH2Cl2 (70 ml)
  4. washThe CH2Cl2 solution was washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed in vacuo
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 100:2.5)

Quellen und Nachweise

ORD-Eintrag
ord-82f4ae654ea541028155a1215bf5ab5f
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091353B2

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