3-Aminopiperidine-2,6-dione hydrochloride → [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea

HRID 448434Notes

Reaction equation

HRID 448434 reaction equation
[NH:1]([CH2:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:8]([C:9]([OH:11])=O)[C:7]=1[C:15]([OH:17])=O)[C:2]([NH2:4])=[O:3].Cl.[NH2:19][CH:20]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:21]1=[O:22]>N1C=CC=CC=1>[O:22]=[C:21]1[CH:20]([N:19]2[C:15](=[O:17])[C:7]3[C:8](=[CH:12][CH:13]=[CH:14][C:6]=3[CH2:5][NH:1][C:2]([NH2:4])=[O:3])[C:9]2=[O:11])[CH2:26][CH2:25][C:24](=[O:27])[NH:23]1

Participants

4

Reactant 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 672298293-Ureidomethyl-phthalic acid

Product 1

HCID 44132357[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-ureaYield 36%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 3-ureidomethyl-phthalic acid (1.5 g, 6.1 mmol) and α-amino-glutarimide hydrochloride (1.0 g, 6.1 mmol) in pyridine (15 mL) was refluxed for 5 hours. The mixture was concentrated and the residue was stirred with water (20 mL). The solid was slurried with hot methanol to give [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.7 g, 36%): mp 292-294° C.; 1H NMR (DMSO-d6) δ 2.04-2.08 (m, 1H), 2.50-2.63 (m, 2H), 2.83-2.98 (m, 1H), 4.61 (d, J=6.1 Hz, 2H, CH2), 5.11-5.18 (m, dd, J=5.3 and 12.5 Hz, 1H, CH), 5.71 (s, 2H, NH2), 6.57 (t, J=6.0 Hz, 1H, NH), 7.70-7.87 (m, 3H, Ar), 11.15 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.98, 30.92, 38.66, 48.82, 121.63, 126.95, 131.50, 133.32, 134.61, 141.06, 158.65, 167.04, 167.57, 169.82, 172.76; Anal. calcd. for C15H14N4O5: C, 54.44; H, 4.27; N, 16.96. Found: C, 54.47; H, 4.17; N, 16.76.

Workup

  1. temperaturewas refluxed for 5 hours
  2. concentrationThe mixture was concentrated

Sources & evidence

ORD record
ord-5a45bc4e78d04e18953838ba2edf4bc9
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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