Furfural → 2-(2,6-Dioxo(3-piperidyl))-4-[(2-furylmethyl)amino]isoindoline-1,3-dione

HRID 2103482

Reaction equation

HRID 2103482 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:20])[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:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[CH:26]=O.[BH4-].[Na+]>C(O)(=O)C>[O:19]=[C:13]1[CH:12]([N:5]2[C:4](=[O:20])[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][CH2:26][C:22]3[O:21][CH:25]=[CH:24][CH:23]=3)[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

Participants

5

Reactant 3

HCID 7362FurfuralHCID 134780PomalidomideHCID 4311764Sodium borohydride

Product 1

HCID 99246762-(2,6-Dioxo(3-piperidyl))-4-[(2-furylmethyl)amino]isoindoline-1,3-dioneYield 35.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a suspension of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (0.55 g, 2 mmol) in acetic acid (20 ml) was added furan-2-carbaldehyde (0.20 g, 2.05 mmol). The mixture was heated to reflux for 5 hours and allowed to cool at room temperature. Sodium borohydride (80 mg, 2 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. The solvent was evaporated and the residue was purified by chromatography (ethyl acetate/hexane, 1:1) to give 0.25 g (35%) of product as a yellow solid: mp 171-173° C.; 1H NMR (DMSO-d6) δ 11.10 (s, 1H), 7.58 (t, J=7.1 Hz, 2H), 7.18 (d, J=8.6 Hz, 1H), 7.08-6.97 (m, 2H), 6.39-6.36 (m, 2H), 5.06 (dd, J=5.2 and 12.4 Hz, 1H), 4.57 (d, J=6.0 Hz, 2H), 2.96-2.82 (m, 1H), 2.63-2.46 (m, 2H), 2.06-2.02 (m, 1H; 13C NMR (DMSO-d6) δ 172.76, 170.01, 168.75, 167.21, 151.97, 145.81, 142.42, 136.05, 132.09, 117.60, 111.04, 110.42, 109.73, 107.38, 48.57, 30.95, 22.10; Anal. Calcd. For C18H15N3O5: C, 61.19; H, 4.28; N, 11.89. Found: C, 61.02; H, 4.24; N, 11.81.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 5 hours
  3. customThe solvent was evaporated in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
  5. washwashed with H2O (3×100 ml), saturated aqueous NaHCO3 (2×100 ml), brine (1×100 ml)
  6. customdried
  7. customThe solvent was evaporated
  8. customthe residue was purified by chromatography (ethyl acetate/hexane, 1:1)

Sources & evidence

ORD record
ord-225d1b3aee8f4c009e5455cf232c3181
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Linked notes

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