Furfural → 3-{4-[(2-Furylmethyl)amino]-1-oxoisoindolin-2-yl}piperidine-2,6-dione

HRID 9990

Reaktionsgleichung

Reaktionsgleichung von HRID 9990
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[O:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[CH:25]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[O:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[CH2:25][NH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11]

Komponenten

5

Edukt 3

HCID 7362FurfuralHCID 216326LenalidomideHCID 5049666Sodium triacetoxyborohydride

Produkt 1

HCID 98810293-{4-[(2-Furylmethyl)amino]-1-oxoisoindolin-2-yl}piperidine-2,6-dioneAusbeute 29,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

To a stirred suspension of 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.52 g, 2.0 mmol) in methanol (50 ml) was added furan-2-carbaldehyde (0.200 g, 2.05 mmol). The mixture was heated to reflux for 4 hours. The solvent was evaporated in vacuo and the residue was dissolved in acetic acid (20 ml). Sodium triacetoxyborohydride (0.450 g, 2.05 mmol) was added to the reaction mixture. The reaction mixture was stirred for 24 hours. The solvent was evaporated in vacuo and the residue was dissolved in ethyl acetate (100 ml), washed with H2O (3×100 ml), saturated aqueous NaHCO3 (2×100 ml), brine (1×100 ml), and dried over MgSO4. The solvent was evaporated in vacuo and the residue was partially purified by chromatography (100% ethyl acetate) to give an off-white solid which was recrystallized from ethanol to give 0.20 g of product as a white solid: mp 248–250° C.; 1H NMR (DMSO-d6) δ 11.02 (s, 1H), 7.57 (s, 1H), 7.27 (t, J=7.6 Hz, 1H), 6.96 (d, J=7.3 Hz, 1H), 6.85 (d, J=8.0 Hz, 1H), 6.36 (d, J=1.2 Hz, 2H), 6.22 (t, J=5.4 Hz, 1H), 5.12 (dd, J=4.9 and 13.1 Hz, 1H), 4.37 (d, J=5.5 Hz, 2H), 4.27 (d, J=17.2 Hz, 1H), 4.14 (d, J=17.2 Hz, 1H) 3.00–2.86 (m, 1H), 2.65–2.59 (m, 1H), 2.37–2.23 (m, 1H), 2.08–1.99 (m, 1H); 13C NMR (DMSO-d6) δ 172.83, 171.16, 168.70, 152.82, 143.06, 142.00, 132.09, 129.02, 126.76, 112.35, 110.63, 110.33, 107.08, 51.50, 45.73, 31.20, 22.75; Anal. Calcd. For C18H17N3O4: C, 63.71; H, 5.05; N, 12.38. Found: C, 63.41; H, 5.03; N, 11.98.

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 hours
  3. customThe solvent was evaporated in vacuo
  4. dissolutionthe residue was dissolved in acetic acid (20 ml)
  5. customThe solvent was evaporated in vacuo
  6. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
  7. washwashed with H2O (3×100 ml), saturated aqueous NaHCO3 (2×100 ml), brine (1×100 ml)
  8. dry with materialdried over MgSO4
  9. customThe solvent was evaporated in vacuo
  10. customthe residue was partially purified by chromatography (100% ethyl acetate)
  11. customto give an off-white solid which
  12. customwas recrystallized from ethanol

Quellen und Nachweise

ORD-Eintrag
ord-c63de44fa6154cee858aafdb79d6b6e4
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091353B2

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