Methoxyacetyl chloride → N-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]-2-methoxy-acetamide

HRID 2103483Notes

Reaction equation

HRID 2103483 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].[CH3:21][O:22][CH2:23][C:24](Cl)=[O:25]>C1COCC1>[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][C:24](=[O:25])[CH2:23][O:22][CH3:21])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

Participants

4

Reactant 2

HCID 96623Methoxyacetyl chlorideHCID 134780Pomalidomide

Product 1

HCID 9902738N-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]-2-methoxy-acetamideYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (0.55 g, 2.0 mmol) in THF (30 ml) was added 2-methoxyacetyl chloride (0.43 g, 4.0 mmol). The stirred mixture was heated to reflux for 18 hours. The solvent was evaporated in vacuo and the resulting solid was slurried in diethyl ether (20 ml) and filtered to give 0.69 g (100%) of product as an off-white solid: mp 246-248° C.; 1H NMR (DMSO-d6) δ 11.15 (s, 1H), 10.30 (s, 1H), 8.70 (d, J=8.4 Hz, 1H), 7.86 (t, J=7.8 Hz, 1H), 7.63 (d, J=7.3 Hz, 1H), 5.17 (dd, J=5.2 and 12.7 Hz, 1H), 4.11 (s, 2H), 3.49 (s, 3H), 2.98-2.84 (m, 1H), 2.66-2.47 (m, 2H), 2.12-2.07 (m, 1H); 13C NMR (DMSO-d6) δ 172.67, 169.66, 169.02, 168.25, 166.61, 136.48, 135.91, 131.24, 124.35, 118.31, 116.04, 71.40, 59.10, 48.96, 30.91, 21.94; Anal. Calcd. For C16H15N3O6: C, 55.65; H, 4.38; N, 12.17. Found: C, 55.58; H, 4.40; N, 12.08.

Workup

  1. temperatureThe stirred mixture was heated
  2. temperatureto reflux for 18 hours
  3. customThe solvent was evaporated in vacuo
  4. filtrationfiltered

Sources & evidence

ORD record
ord-718cf0dc53f549e4aa013fd602b334bc
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Reaction notes

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