Methanol → N-[2-(3-methyl-2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]pentanamide

HRID 906783Notes

Reaction equation

HRID 906783 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:21])[N:5]([C:12]1([CH3:20])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[C:22](Cl)(=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26].CO>C1COCC1>[CH3:20][C:12]1([N:5]2[C:4](=[O:21])[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:22](=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19]

Participants

5

Reactant 3

HCID 887MethanolHCID 61186Valeryl chlorideHCID 115220774-Amino-2-(3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Product 1

HCID 21040150N-[2-(3-methyl-2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]pentanamideYield 84.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-amino-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione (0.10 g, 0.35 mmol) in THF (15 ml) was added valeryl chloride (0.08 g, 0.70 mmol). The mixture was heated to reflux for 18 h. The reaction mixture was allowed to cool and to the solution was added methanol (2 ml). The reaction mixture was stirred for an additional 15 minutes followed by solvent evaporation in vacuo. The resulting solid was slurried in diethyl ether (20 ml) and filtered to give 0.11 g (81%) of product as an off-white solid: mp 190-192° C.; 1H NMR (DMSO-d6) 11.04 (s, 1H), 9.65 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.79 (t, J=7.8 Hz, 1H), 7.52 (d, J=7.2 Hz, 1H), 2.74-2.44 (m, 5H), 2.10-2.03 (m, 1H), 1.90 (s, 3H), 1.66-1.54 (m, 2H), 1.42-1.27 (m, 2H), 0.91 (t, J=7.3 Hz, 3H); 13C NMR (DMSO-d6) 172.13, 172.03, 168.75, 167.36, 136.42, 135.91, 131.20, 125.68, 117.71, 116.29, 58.81, 36.25, 29.07, 28.54, 26.83, 21.65, 20.98, 13.64; Anal. Calcd. For C19H21N3O5: C, 61.39; H, 5.70; N, 11.30. Found: C, 61.03; H, 5.51; N, 11.13+0.02H2O.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 h
  3. temperatureto cool and to the solution
  4. customfollowed by solvent evaporation in vacuo
  5. filtrationfiltered

Sources & evidence

ORD record
ord-0f67c6a30609450faaa22175e3b1faee
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Reaction notes

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