| Identification | Back Directory | [Name]
2,4-Piperadinedione | [CAS]
50607-30-2 | [Synonyms]
2,4-PIPERADINEDIONE
2,4-Piperidinedione
PIPERIDIN-2,4-DIONE
2,4-Dioxopiperidine
Piperidine-2,4-dione
2,4-PiperadinedioneE
2,4-Diketopiperidine
2,4-Piperidinedione>
Piperidine-2,4-dione 97%
2,4-Piperidinedione, 95+%
dihydropyridine-4,6-dione
piperidine-2,4-dione, dihydropyridine-4,6-dione, 2,4-dioxopiperidine, 2,4-piperidinedione, piperidin-2,4-dione, 2,4-diketopiperidine, Piperidine-2,4-dione | [EINECS(EC#)]
803-771-9 | [Molecular Formula]
C5H7NO2 | [MDL Number]
MFCD08704814 | [MOL File]
50607-30-2.mol | [Molecular Weight]
113.11 |
| Chemical Properties | Back Directory | [Melting point ]
98.0 to 102.0 °C | [Boiling point ]
362.1±35.0 °C(Predicted) | [density ]
1.184±0.06 g/cm3(Predicted) | [storage temp. ]
Inert atmosphere,2-8°C | [form ]
powder to crystal | [pka]
12.00±0.70(Predicted) | [color ]
White to Orange to Green | [InChI]
InChI=1S/C5H7NO2/c7-4-1-2-6-5(8)3-4/h1-3H2,(H,6,8) | [InChIKey]
RDNZDMDLRIQQAX-UHFFFAOYSA-N | [SMILES]
N1CCC(=O)CC1=O |
| Hazard Information | Back Directory | [Description]
2,4-Piperidinedione is an important piperidine ring-containing intermediate, and its 2,4-piperidinedione, as a characteristic fragment, is widely used as an intermediate in the synthesis of ibrutinib and paliperidone drugs. | [Chemical Properties]
White to light yellow solid | [Uses]
2,4-Piperidinedione is a reactant in the synthesis of 1,4-dihydropyridines as TGFβ/Smad inhibitors. | [Preparation]
The synthesis of 2,4-Piperidinedione involved dissolving 400 mg (2.34 mmol, 1.00 eq.) of Methyl 2,4-dioxo-piperidine-3-carboxylate in a mixture of acetonitrile (20 mL) and water (0.2 mL). The solution was then heated to approximately 86° C. and maintained at this temperature for around 4 hours. After completion of the reaction, the solvent was removed under vacuum, leaving behind a residue of 2,4-Piperidinedione. This residue was further purified using silica gel column chromatography with a mobile phase consisting of dichloromethane and methanol in a ratio of 100:1. The target product, 2,4-Piperidinedione, was obtained as a white solid, with a yield of 27%, corresponding to 70 mg. | [Synthesis]
The general procedure for the synthesis of 2,4-piperidinediones from tert-butyl 2,4-dipiperidone-1-carboxylate was as follows: at 0 °C and under nitrogen protection, Boc-β-alanine (25 g, 132 mmol), Meldrum acid (20.9 g, 145 mmol), and 4-dimethylaminopyridine (DMAP, 24.2 g, 198 mmol) were dissolved in 700 mL of anhydrous dichloromethane (DCM). To this solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 30.4 g, 158 mmol). The reaction mixture was slowly warmed to room temperature and stirred overnight. After completion of the reaction, the reaction mixture was washed with 5% KHSO4 aqueous solution (0.5 L x 4). The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product [tert-butyl [3-(2,2-dimethyl-4,6-dioxo-[1,3]dioxol-5-yl)-3-oxo-propyl]-carbamate. The crude product was dissolved in 600 mL of ethyl acetate and refluxed for 4 hours. It was concentrated under reduced pressure to a volume of about 150 mL and subsequently crystallized at 4°C overnight. The solid was collected by filtration and washed with cold ethyl acetate to afford 18.4 g (65% yield) of 2,4-piperidinedione.1H NMR (400 MHz, DMSO-D6) δppm: 1.44 (s, 9H), 2.44 (m, 2H), 3.71 (m, 2H), 4.95 (s, 1H), 11.2 (bs, 1H). The resulting product was converted quantitatively to piperidine-2,4-dione by dissolving in dichloromethane and treating with trifluoroacetic acid for 3 h at room temperature. | [References]
[1] Patent: WO2008/104475, 2008, A1. Location in patent: Page/Page column 22
[2] Patent: WO2012/35078, 2012, A1. Location in patent: Page/Page column 144
[3] Patent: US2014/45872, 2014, A1. Location in patent: Paragraph 0911
[4] Journal of Medicinal Chemistry, 2008, vol. 51, # 3, p. 487 - 501
[5] Angewandte Chemie - International Edition, 2014, vol. 53, # 14, p. 3594 - 3598 |
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