Ethyl isocyanate → N-{[2-(2,6-dioxo(3-piperidyl))-1-oxoisoindolin-4-yl]methyl}(ethylamino)carboxamide

HRID 10066

Reaction equation

HRID 10066 reaction equation
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][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].[CH2:33]([N:35]=[C:36]=[O:37])[CH3:34]>C(#N)C>[O:32]=[C:26]1[CH:25]([N:18]2[CH2:17][C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:36]([NH:35][CH2:33][CH3:34])=[O:37])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

5

Reactant 3

HCID 8022Ethyl isocyanateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 21988546N-{[2-(2,6-dioxo(3-piperidyl))-1-oxoisoindolin-4-yl]methyl}(ethylamino)carboxamideYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.44 g, 2.91 mmol) was added to a stirred suspension of 3-[4-(aminomethyl)-1-oxoisoindolin-2-yl]piperidine-2,6-dione hydrochloride (0.6 g, 1.94 mmol) in acetonitrile (50 mL). After stirring for 30 min, ethyl isocyanate (0.21 g, 2.91 mmol) was added. The mixture was stirred at room temperature for 17 hours. Solvent was removed and the residue was stirred with methylene chloride (70 mL) to give N-{[2-(2,6-dioxo(3-piperidyl))-1-oxoisoindolin-4-yl]methyl}(ethylamino)carboxamide (0.28 g, 42%) as a white solid: mp 341–343° C.; 1H NMR (DMSO-d6) δ 11.02 (s, 1H), 7.62–7.47 (m, 3H), 6.40 (t, J=5.9 Hz, 1H), 5.95 (t, J=5.6 Hz, 1H), 5.18–5.10 (dd, J=5.3 and 13.3 Hz, 1H), 4.52–4.30 (dd, J=17.3 and 37.7 Hz, 2H), 4.28 (d, J=5.9 Hz, 2H), 3.04 (q, J=7.2 Hz, 2H), 3.01–2.86 (m, 1H), 2.65–2.34 (m, 2H0, 2.04–1.99 (m, 1H), 0.98 (t, J=7.2 Ha, 3H); 13C NMR (DMSO-6) δ 172.82, 170.97, 168.10, 157.86, 139.78, 136.24, 131.55, 130.25, 128.16, 121.32, 51.51, 46.13, 34.14, 31.16, 22.59, 15.67; Anal. Calcd for C17H20N4O4: C, 59.29; H, 5.85; N, 16.27. Found: C, 58.98; H, 5.85; N, 16.89.

Workup

  1. stirringThe mixture was stirred at room temperature for 17 hours
  2. customSolvent was removed
  3. stirringthe residue was stirred with methylene chloride (70 mL)

Sources & evidence

ORD record
ord-265838542203460ba52244619f8d3caf
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Linked notes

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