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

HRID 9957

Reaction equation

HRID 9957 reaction equation
N12CCCN=C1CCCCC2.CO[C:14](=[O:37])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][NH:22][C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[C:16]=1[C:33]([O:35]C)=O.Cl.[NH2:39][CH:40]1[CH2:46][CH2:45][C:44](=[O:47])[NH:43][C:41]1=[O:42].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:33](=[O:35])[N:39]([CH:40]1[CH2:46][CH2:45][C:44](=[O:47])[NH:43][C:41]1=[O:42])[C:14]2=[O:37])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 21988567Methyl-3-[(benzyloxycarbonylamino)methyl]-2-(methoxycarbonyl)benzoate

Product 1

HCID 10202353[2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamic acid benzyl esterYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

1,8-diazabicyclo[5,4,0]undec-7-ene (0.88 g, 6 mmol) was added to a stirred suspension of methyl-3-[(benzyloxycarbonylamino)methyl]-2-(methoxycarbonyl)benzoate (2.07 g, 6 mmol) and aminoglutarimide hydrochloride (0.95 g, 6 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 combined ethyl acetate extracts were washed with water (2×30 ml), brine (30 ml) and dried. Solvent was removed in vacuo and the residue was purified by chromatography (dichloromethane/ethyl acetate 8 to 2) to give 0.58 g (24%) of the product as a white solid: mp 166–168° C.; 1H NMR (DMSO-d6) δ 11.15 (s, 1H), 7.99–7.71 (m, 4H), 7.37 (m, 5H), 5.19–5.12 (dd, J=5.1 and 17.4 Hz, 1H), 5.07 (s, 2H), 4.70 (d, J=5.7 Hz, 2H), 2.97–2.83 (m, 1H), 2.64–2.51 (m, 2H), 2.08–2.04 (m, 1H); 13C NMR (DMSO-d6) δ 172.55, 169.89, 167.51, 167.01, 156.55, 139.46, 137.02, 134.87, 132.89, 131.57, 128.44, 127.92, 127.83, 127.06, 121.99, 65.69, 48.89, 30.97, 22.02; Anal. Calcd. For C22H19N3O6: C, 62.70; H, 4.54; N, 9.97. Found: C, 62.53; H, 4.57; N, 9.89.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×30 ml)
  3. washthe combined ethyl acetate extracts were washed with water (2×30 ml), brine (30 ml)
  4. customdried
  5. customSolvent was removed in vacuo
  6. customthe residue was purified by chromatography (dichloromethane/ethyl acetate 8 to 2)

Sources & evidence

ORD record
ord-6e7757d056d64b50a575967eea16aa46
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Linked notes

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