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

HRID 2103497Notes

Reaction equation

HRID 2103497 reaction equation
[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]

Participants

5

Reactant 3

HCID 7362FurfuralHCID 216326LenalidomideHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 98810293-{4-[(2-Furylmethyl)amino]-1-oxoisoindolin-2-yl}piperidine-2,6-dioneYield 29.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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=11.2 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); 3C 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.

Workup

  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

Sources & evidence

ORD record
ord-b4487e5fad244883a73319cd52a481bf
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Reaction notes

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