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

HRID 906733

Reaction equation

HRID 906733 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-a3e4e39b7bb24f59a38a67aa27a07ee5
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Linked notes

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