Methanol → N-[2-(3-Methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-propionamide

HRID 906786Notes

Reaction equation

HRID 906786 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:21])[N:5]([C:12]1([CH3:20])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[C:22](Cl)(=[O:25])[CH2:23][CH3:24].CO>C1COCC1>[CH3:20][C:12]1([N:5]2[C:4](=[O:21])[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:22](=[O:25])[CH2:23][CH3:24])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19]

Participants

5

Reactant 3

HCID 887MethanolHCID 62324Propionyl chlorideHCID 115220774-Amino-2-(3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Product 1

HCID 21988564N-[2-(3-Methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-propionamideYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-amino-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione (0.10 g, 0.35 mmol) in THF (15 ml) was added propionyl chloride (0.07 g, 0.70 mmol). The mixture was heated to reflux for 18 h. The reaction mixture was allowed to cool and to the solution was added methanol (2 ml). The reaction mixture was stirred for an additional 15 minutes followed by solvent evaporation in vacuo. The resulting solid was slurried in diethyl ether (20 ml) and filtered to give 0.07 g (63%) of product as an off-white solid: mp 222-224° C.; 1H NMR (DMSO-d6) 11.03 (s, 1H), 9.63 (s, 1H), 8.51 (d, J=8.3 Hz, 1H), 7.79 (t, J=7.6 Hz, 1H), 7.51 (d, J=7.3 Hz, 1H), 2.76-2.45 (m, 5H), 2.10-2.03 (m, 1H), 1.90 (s, 3H), 1.12 (t, J=7.5 Hz, 3H); 13C NMR (DMSO-d6) 172.70, 172.14, 172.03, 168.80, 167.37, 136.48, 135.94, 131.20, 125.59, 117.67, 116.21, 58.81, 29.71, 29.07, 28.53, 20.97, 14.74, 9.18; Anal. Calcd. For C17H17N3O5: C, 59.47; H, 4.99; N, 12.24 Found: C, 59.24; H, 5.06; N, 11.97.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 h
  3. temperatureto cool and to the solution
  4. customfollowed by solvent evaporation in vacuo
  5. filtrationfiltered

Sources & evidence

ORD record
ord-c130b4a2229648b4a66716ddf9452ee2
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Reaction notes

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