3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxo-3-piperidyl)-4-(pentylamino)isoindoline-1,3-dione

HRID 906742Notes

Reaction equation

HRID 906742 reaction equation
[CH2:1]([NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:9]([C:10]([OH:12])=O)[C:8]=1[C:16]([OH:18])=O)[CH2:2][CH2:3][CH2:4][CH3:5].Cl.[NH2:20][CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:22]1=[O:28]>C(O)(=O)C>[O:28]=[C:22]1[CH:21]([N:20]2[C:16](=[O:18])[C:8]3[C:9](=[CH:13][CH:14]=[CH:15][C:7]=3[NH:6][CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[C:10]2=[O:12])[CH2:26][CH2:25][C:24](=[O:27])[NH:23]1

Participants

4

Reactant 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 219885603-Pentylamino-phthalic acid

Product 1

HCID 99026612-(2,6-Dioxo-3-piperidyl)-4-(pentylamino)isoindoline-1,3-dioneYield 53%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 3-pentylamino-phthalic acid (2.51 g, 10 mmol) in acetic acid (50 ml) was added 3-amino-piperidine-2,6-dione hydrochloride (1.81 g, 11 mmol). The reaction mixture was heated to reflux overnight. The solvent was evaporated in vacuo and the residue dissolved in ethyl acetate (100 ml). The ethyl acetate mixture was washed with water (2×100 ml), saturated aqueous sodium bicarbonate (2×100 ml), brine (1×100 ml), and dried (MgSO4). The solvent was evaporated in vacuo and the solid residue was purified by chromatography (25% ethyl acetate/hexane) to give 1.82 g (53%) of product as a yellow solid: mp 141-143° C.; 1H NMR (DMSO-d6) d 11.09 (s, 1H); 7.58 (t, J=8.3 Hz, 1H), 7.08 (d, J=8.6 Hz, 1H), 7.02 (d, J=7.0 Hz, 1H), 6.519 (t, J=5.7 Hz, 1H), 5.06 (dd, J=5.3 and 12.4 Hz, 1H), 3.32-3.25 (m, 2H), 2.97-2.82 (m, 1H), 2.62-2.46 (m, 2H), 2.06-2.01 (m, 1H), 1.61-1.55 (m, 2H), 1.35-1.32 (m, 4H), 0.88 (t, J=6.7 Hz, 3H); 13C NMR (DMSO-d6) d 172.72, 170.01, 168.92, 167.25, 146.39, 136.21, 132.14, 117.08, 110.31, 108.99, 48.52, 41.77, 30.94, 28.46, 28.33, 22.12, 21.82, 13.85; Anal. Calcd. For C18H21N3O4: C, 62.96; H, 6.16; N, 12.24. Found: C, 62.92; H, 6.17; N, 12.15.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux overnight
  3. customThe solvent was evaporated in vacuo
  4. dissolutionthe residue dissolved in ethyl acetate (100 ml)
  5. washThe ethyl acetate mixture was washed with water (2×100 ml), saturated aqueous sodium bicarbonate (2×100 ml), brine (1×100 ml)
  6. dry with materialdried (MgSO4)
  7. customThe solvent was evaporated in vacuo
  8. customthe solid residue was purified by chromatography (25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d33752af971e44799a1005c7e5b78abe
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Reaction notes

Loading…