Methanol → 2-Benzyloxy-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-acetamide

HRID 9994

Reaction equation

HRID 9994 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].[CH2:21]([O:28][CH2:29][C:30](Cl)=[O:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CO>C1COCC1>[CH2:21]([O:28][CH2:29][C:30]([NH: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:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 134780PomalidomideHCID 177085Benzyloxyacetyl chloride

Product 1

HCID 102239522-Benzyloxy-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-acetamideYield 80.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (1.10 g, 4 mmol) in THF (30 ml) was added benzyloxyacetyl chloride (1.26 ml, 8 mmol). The mixture was heated to reflux for 18 hours. The reaction was cooled to room temperature, methanol (2 ml) was added, and the mixture stirred for 1 hour. The solvent was evaporated in vacuo and the residue was slurried in diethyl ether (30 ml), filtered, recrystallized from a minimal amount of acetic acid, slurried in ethyl acetate (15 ml), and filtered to give 1.35 g (80%) of product: mp 204–206° C.; 1H NMR (DMSO-d6) d 11.20 (s, 1H), 10.40 (s, 1H), 8.71 (d, J=8.4 Hz, 1H), 7.86 (t, J=7.9 Hz, 1H), 7.64 (d, J=7.2 Hz, 1H), 7.50–7.28 (m, 5H), 5.17 (dd, J=5.0 and 12.5 Hz, 1H), 4.72 (s, 2H), 4.21 (s, 2H), 2.99–2.85 (m, 1H), 2.67–2.51 (m, 2H), 2.12–2.08 (m, 1H); 13C NMR (DMSO-d6) d 172.78, 169.78, 169.01, 168.27, 166.67, 137.04, 136.52, 135.93, 131.29, 128.36, 127.82, 124.40, 118.38, 116.08, 72.78, 69.23, 48.97, 30.92, 21.98; Anal. Calcd. For C22H19N3O6: C, 62.70; H, 4.54; N, 9.97. Found: C, 62.77; H, 4.54; N, 9.82.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 hours
  3. customThe solvent was evaporated in vacuo
  4. filtrationfiltered
  5. customrecrystallized from a minimal amount of acetic acid
  6. filtrationfiltered

Sources & evidence

ORD record
ord-92144a870eff4e91b4fc3206bd4fc14e
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Linked notes

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