Triethylamine → HCID 58827317, compound

HRID 448421Notes

Reaction equation

HRID 448421 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]=[C:10]=[O:11].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>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:10]([NH:9][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])=[O:11])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 69695Benzene, 1-isocyanato-2-methoxy-HCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827317HCID 58827317, compoundYield 80.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

2-Methoxyphenyl isocyanate (0.4 g, 2.6 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol) and triethylamine (0.3 g, 2.8 mmol) in THF (30 mL) at 5-10° 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 hot methanol (15 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-(2-methoxy-phenyl)-urea (0.7 g, 80%) as a white solid: mp 214-216° C.; 1H NMR (DMSO-d6) δ 2.05-2.10 (m, 1H), 2.50-2.65 (m, 2H), 2.84-2.97 (m, 1H), 3.83 (s, 3H, OCH3), 4.73 (d, J=5.7 Hz, 2H, CH2), 5.13-5.20 (dd, J=5.3 and 12.5 Hz, 1H, CH), 6.79-6.98 (m, 3H, Ar), 7.49 (t, H=5.7 Hz, 1H, NH), 7.77-7.89 (m, 3H, Ar), 8.04-8.08 (dd, J=1.4 and 7.3 Hz, 1H, Ar), 8.19 (s, 1H, NH), 11.15 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.99, 30.93, 48.86, 55.64, 110.59, 118.07, 120.42, 121.22, 121.88, 127.16, 129.20, 131.61, 133.65, 134.77, 140.112, 147.40, 155.24, 167.00, 167.50, 169.83, 172.76; Anal. calcd. for C22H20N4O6+0.66H2O: C, 58.94; H, 4.79; N, 12.50. Found: C, 59.24; H, 4.86; 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-d8b8375ffe374d778e8b0ce2b747f642
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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