(2,6-Dioxopiperidin-4-yl)acetic acid → HCID 66751033, compound

HRID 534880Notes

Reaction equation

HRID 534880 reaction equation
Cl.Cl.[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([CH3:6])([CH3:5])[CH3:4].[O:19]=[C:20]1[CH2:25][CH:24]([CH2:26][C:27](O)=[O:28])[CH2:23][C:22](=[O:30])[NH:21]1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>O.CN(C)C=O.C(N(CC)CC)C>[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][N:16]([C:27](=[O:28])[CH2:26][CH:24]2[CH2:23][C:22](=[O:30])[NH:21][C:20](=[O:19])[CH2:25]2)[CH2:15][CH2:14]1)([CH3:6])([CH3:4])[CH3:5]

Participants

8

Reactant 4

HCID 234331(2,6-Dioxopiperidin-4-yl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667511491-(2-Tert-butylphenyl)piperazine dihydrochloride

Product 1

HCID 66751033HCID 66751033, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (500 mg), (2,6-dioxopiperidin-4-yl)acetic acid (311 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (403 mg), 1-hydroxy-1H-benzotriazole monohydrate (322 mg), triethylamine (0.627 mL), and N,N-dimethylformamide (5 mL) was stirred at room temperature for over-night. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to purification by high performance liquid chromatography [Column: Gilson, Ltd. High throughput purification system, YMC Combiprep ODS-A, S-5 μm, 50 mm×20 mm; Gradient cycle: H2O (contains 0.1% CF3COOH)-acetonitrile (contains 0.1% CF3COOH), 90:10 (0 min)-90:10 (1 min)-10:90 (4.2 min)-10:90 (5.4 min)-90:10 (5.5 min)-90:10 (5.6 min); Flow rate: 25 mL/min; detection wavelength: UV 220 nm] to give the title compound (47 mg, 13%) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was subjected to purification by high performance liquid chromatography [Column: Gilson, Ltd. High throughput purification system, YMC Combiprep ODS-A, S-5 μm, 50 mm×20 mm; Gradient cycle: H2O (contains 0.1% CF3COOH)-acetonitrile (contains 0.1% CF3COOH), 90:10 (0 min)-90:10 (1 min)-10:90 (4.2 min)-10:90 (5.4 min)-90:10 (5.5 min)-90:10 (5.6 min); Flow rate: 25 mL/min; detection wavelength: UV 220 nm]

Sources & evidence

ORD record
ord-eed810b46456444bb0dbff994f8cff3d
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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