Water → [2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamic acid ethyl ester

HRID 9955

Reaction equation

HRID 9955 reaction equation
N12CCCN=C1CCCCC2.CO[C:14](=[O:32])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][NH:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:16]=1[C:28]([O:30]C)=O.Cl.[NH2:34][CH:35]1[CH2:41][CH2:40][C:39](=[O:42])[NH:38][C:36]1=[O:37].O>CN(C=O)C>[CH2:26]([O:25][C:23](=[O:24])[NH:22][CH2:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]2[C:16]=1[C:28](=[O:30])[N:34]([CH:35]1[CH2:41][CH2:40][C:39](=[O:42])[NH:38][C:36]1=[O:37])[C:14]2=[O:32])[CH3:27]

Participants

6

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 21988600Methyl-3-[(Ethoxycarbonylamino)methyl]-2-(methoxycarbonyl)benzoate

Product 1

HCID 9968775[2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamic acid ethyl esterYield 46.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.8 g, 5 mmol) was added to a stirred suspension of methyl-3-[(ethoxycarbonylamino)methyl]-2-(methoxycarbonyl)benzoate (1.54 g, 5 mmol) and aminoglutarimide hydrochloride (0.86 g, 5 mmol) in DMF (15 ml). The mixture was heated to 120° C. for 24 hours. The mixture was cooled to room temperature and poured into water (150 ml). The mixture was extracted with ethyl acetate (3×30 ml) and the ethyl acetate solution was washed with water (30 ml), brine (30 ml) and dried. Solvent was removed and the residue was purified by flash chromatography (dichloromethane/ethyl acetate 7 to 3) to give 0.84 g (45%) of the product as a white solid: mp 187–189° C.; 1H NMR (DMSO-d6) δ 11.03 (s, 1H), 7.76–7.58 (m, 4H), 5.06–4.99 (dd, J=5.4 and 12.6 Hz, 1H), 4.52 (d, J=5.9 Hz, 2H), 3.91 (q, J=7.0 Hz, 2H), 2.79–2.70 (m, 1H), 2.51–2.38 (m, 2H), 1.96–1.86 (m, 1H), 1.06 (t, J=7.0 Hz, 3H); 13C NMR (DMSO-d6) δ 172.89, 169.93, 167.55, 167.05, 156.72, 139.69, 134.91, 132.90, 131.58, 127.04, 121.97, 60.15, 48.90, 39.34, 30.98, 22.04, 14.69; Anal. Calcd. For C17H17N3O6: C, 56.82; H, 4.77; N, 11.69. Found: C, 56.94; H, 4.81; N, 11.37.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×30 ml)
  3. washthe ethyl acetate solution was washed with water (30 ml), brine (30 ml)
  4. customdried
  5. customSolvent was removed
  6. customthe residue was purified by flash chromatography (dichloromethane/ethyl acetate 7 to 3)

Sources & evidence

ORD record
ord-6ebefc0c0c2647b2b8ee5f59d2e48aa8
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Linked notes

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