Triethylamine → HCID 58827343, compound

HRID 448427Notes

Reaction equation

HRID 448427 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([N:9]=[C:10]=[O:11])[CH:5]=[CH:6][C:7]=1[CH3:8].Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].C(N(CC)CC)C>C1COCC1>[CH3:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH:13][CH2:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[C:17](=[O:33])[N:18]([CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:19]3=[O:24])=[O:11])[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 43896633,4-Dimethylphenyl isocyanateHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827343HCID 58827343, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

3,4-Dimethylphenyl isocyanate (0.4 g, 3.0 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.8 g, 2.3 mmol) and triethylamine (0.3 g, 3.2 mmol) in THF (40 mL) at 5° C. After stirring for 10 minutes at 5° C., the mixture was warmed to room temperature and stirred overnight. The mixture was concentrated, and the residue was stirred with 1N HCl (30 mL) for 30 minutes. The solid was collected and slurried with acetone (20 mL) to give 1-(3,4-dimethyl-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.8 g, 82%) as a white solid: mp 222-224° C.; 1H NMR (DMSO-d6) δ 2.05-2.08 (m, 1H), 2.12 (s, 3H), 2.14 (s, 3H), 2.50-2.65 (m, 2H), 2.84-2.97 (m, 1H), 4.70 (d, J=5.8 Hz, 2H), 5.13-5.20 (dd, J=5.3 and 12.6 Hz, 1H), 6.69 (t, J=5.9 Hz, 1H), 6.97 (d, J=8.2 Hz, 1H), 7.08 (d, J=8.2 Hz, 1H), 7.17 (s, 1H), 7.75-7.88 (m, 3H), 8.57 (s, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 18.60, 19.61, 21.99, 30.94, 38.72, 48.86, 115.33, 119.13, 121.84, 127.18, 128.75, 129.51, 131.60, 133.68, 134.71, 136.11, 137.96, 140.40, 155.29, 167.03, 167.61, 169.84, 172.78; Anal. calcd. for C23H22N4O5: C, 63.59; H, 5.10; N, 12.90. Found: C, 63.21; H, 5.09; N, 12.74.

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred overnight
  3. concentrationThe mixture was concentrated
  4. stirringthe residue was stirred with 1N HCl (30 mL) for 30 minutes
  5. customThe solid was collected

Sources & evidence

ORD record
ord-4c3a906544384f12a46b8857257b088a
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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