Sodium Iodide → 2-azido-N-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-yl)acetamide

HRID 2103496Notes

Reaction equation

HRID 2103496 reaction equation
[O:1]=[C:2]1[CH:7]([N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[NH:17][C:18](=[O:21])[CH2:19]Cl)[C:9]2=[O:22])[CH2:6][CH2:5][C:4](=[O:23])[NH:3]1.[N-:24]=[N+:25]=[N-:26].[Na+].[Na+].[I-]>CC(C)=O.ClCCl.O>[N:24]([CH2:19][C:18]([NH:17][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[CH2:16][N:8]([CH:7]1[CH2:6][CH2:5][C:4](=[O:23])[NH:3][C:2]1=[O:1])[C:9]2=[O:22])=[O:21])=[N+:25]=[N-:26]

Participants

7

Reactant 3

HCID 5238Sodium IodideHCID 33557Sodium Azide2×HCID 98808592-chloro-N-[2-(2,6-dioxo-3-piperidyl)-1-oxo-isoindolin-4-yl]acetamide

Product 1

HCID 102689262-azido-N-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-yl)acetamideYield 93%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of N-[2-(2,6-dioxo(3-piperidyl))-1-oxoisoindolin-4-yl]-2-chloroacetamide (4.64 g, 13.8 mmol) in acetone (60 ml) was added sodium azide (1.35 g, 20.7 mmol). The mixture was heated to reflux for 18 hours. After 18 hours, to the reaction mixture was added NaI (2.05 g, 13.8 mmol) and additional sodium azide (0.90 g, 13.8 mmol). The mixture was heated at reflux for an additional 18 hours. The solvent was evaporated in vacuo to give an off-white solid which was slurried in a mixture of dichloromethane (50 ml) and H2O (50 ml). This slurry was filtered to give 4.39 g (93%) of product: 1H NMR (DMSO-d6) δ 11.50-9.52 (bs, 2H), 7.87-7.84 (m, 1H), 7.59-7.50 (m, 2H), 5.17 (dd, J=5.0 and 13.1 Hz, 1H), 4.44 (d, J=17.6 Hz, 1H), 4.34 (d, J=17.6 Hz, 1H), 4.13 (s, 2H), 3.00-2.86 (m, 1H), 2.65-2.59 (m, 1H), 2.44-2.29 (m, 1H), 2.07-2.02 (m, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 hours
  3. temperatureThe mixture was heated
  4. temperatureat reflux for an additional 18 hours
  5. customThe solvent was evaporated in vacuo
  6. customto give an off-white solid which
  7. filtrationThis slurry was filtered

Sources & evidence

ORD record
ord-e7289d63a3eb47cdb95a82025909d534
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Reaction notes

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