2-(4-Cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoic acid → 2-(2,6-Dioxopiperidin-3-yl)-1-oxoisoindoline-4-carbonitrile

HRID 906818Notes

Reaction equation

HRID 906818 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][N:6]([CH:13]([CH2:17][CH2:18][C:19](=[O:21])[NH2:20])[C:14](O)=[O:15])[C:7]2=[O:12])#[N:2]>C(#N)C>[O:15]=[C:14]1[CH:13]([N:6]2[CH2:5][C:4]3[C:3]([C:1]#[N:2])=[CH:11][CH:10]=[CH:9][C:8]=3[C:7]2=[O:12])[CH2:17][CH2:18][C:19](=[O:21])[NH:20]1

Participants

3

Reactant 1

HCID 219885622-(4-Cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoic acid

Product 1

HCID 219885472-(2,6-Dioxopiperidin-3-yl)-1-oxoisoindoline-4-carbonitrileYield 83%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-(4-cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoic acid (0.6 g, 2.09 mmol) and 1,1-carbonyldiimidazole (0.44 g, 2.72 mmol) in acetonitrile (20 mL) was heated to reflux for 2 hours. The mixture was cooled to room temperature and filtered to give 2-(2,6-dioxo(3-piperidyl))-1-oxoisoindoline-4-carbonitrile (0.44 g, 83%) as a white solid: mp 312-314° C.; 1H NMR (DMSO-d6) δ 11.04 (s, 1H), 8.16 (d, J=7.0 Hz, 1H), 8.06 (d, J=7.1 Hz, 1H), 7.74 (t, J=7.7 Hz, 1H), 5.20-5.13 (dd, J=5.2 and 13.2 Hz, 1H), 4.69 (d, J=18.1 Hz, 1H), 4.57 (d, J=18.1 Hz, 1H), 2.97-2.85 (m, 1H), 2.64-2.45 (m, 2H), 2.05-1.97 (m, 1H); 13C NMR (DMSO-d6) δ 172.81, 170.69, 166.49, 145.36, 135.37, 132.85, 129.36, 127.91, 116.01, 107.09, 51.77, 46.72, 31.14, 22.22; Anal. Calcd. For C14H, N3O3: C, 62.45; H, 4.12; N, 15.61. Found: C, 62.26; H, 4.10; N, 15.51.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 hours
  3. filtrationfiltered

Sources & evidence

ORD record
ord-3d089e9f12c34698aebbbd8aab83f80c
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Reaction notes

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