The action environment of “3-(4-Nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione” would be influenced by various factors. For instance, the compound should be stored under an inert atmosphere at 2-8°C . This suggests that temperature and atmospheric conditions could influence the compound’s action, efficacy, and stability.

準備方法

The synthesis of 3-(4-Nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione involves several steps. One common method includes the reaction of methyl 2-(bromomethyl)-3-nitrobenzoate with 3-aminopiperidine-2,6-dione hydrochloride in the presence of triethylamine and dimethyl sulfoxide . The reaction mixture is heated to 50-55°C, and the product is purified to obtain the desired compound .

Industrial production methods often involve solvent recrystallization, desolvation, vapor diffusion, and rapid precipitation techniques to obtain polymorphs of the compound .

化学反応の分析

3-(4-Nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione undergoes various chemical reactions, including:

Oxidation: The nitro group can be reduced to an amino group under specific conditions.

Reduction: The compound can be reduced to form 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

Substitution: The compound can undergo nucleophilic substitution reactions, where the nitro group is replaced by other functional groups.

Common reagents used in these reactions include reducing agents like hydrogen gas and catalysts such as palladium on carbon . The major products formed from these reactions include 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione and other substituted derivatives .

類似化合物との比較

3-(4-Nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione is similar to other compounds such as:

Lenalidomide: Both compounds share a similar structure and mechanism of action.

Thalidomide: Another analog with immunomodulatory and anti-cancer properties.

Pomalidomide: A derivative with enhanced anti-cancer activity.

The uniqueness of 3-(4-Nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione lies in its specific structural modifications, which confer distinct pharmacological properties and potential therapeutic applications .

特性

IUPAC Name	3-(7-nitro-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

InChI	InChI=1S/C13H11N3O5/c17-11-5-4-10(12(18)14-11)15-6-8-7(13(15)19)2-1-3-9(8)16(20)21/h1-3,10H,4-6H2,(H,14,17,18)	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

InChI Key	JKPJLYIGKKDZDT-UHFFFAOYSA-N	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Canonical SMILES	C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3[N+](=O)[O-]	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Molecular Formula	C13H11N3O5	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

DSSTOX Substance ID	DTXSID40467017	Source
Record name	3-(4-Nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione
Source	EPA DSSTox
URL	https://comptox.epa.gov/dashboard/DTXSID40467017
Description	DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.

Molecular Weight	289.24 g/mol	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

CAS No.	827026-45-9	Source
Record name	4-Nitro lenalidomide
Source	ChemIDplus
URL	https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0827026459
Description	ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system.

Record name	3-(4-Nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione
Source	EPA DSSTox
URL	https://comptox.epa.gov/dashboard/DTXSID40467017
Description	DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.

Record name	4-NITRO LENALIDOMIDE
Source	FDA Global Substance Registration System (GSRS)
URL	https://gsrs.ncats.nih.gov/ginas/app/beta/substances/5CBC4TCM54
Description	The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions.
Explanation	Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.

Synthesis routes and methods I

Procedure details

By catalytic hydrogenation of 3-(4-nitro-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione in solvents such as dimethylformamide, methanol, ethanol, isopropyl alcohol or mixture of these solvents at temperature 50-100.0° C. under pressure or bubbling of hydrogen gas at atmospheric pressure, then filteration of the catalyst followed by distillation under high vacuum Lenalidomide polymorphic form-I is obtained. The polymorphic form-I of Lenalidomide can also be obtained by transfer hydrogenation of 3-(4-nitro-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione using solvents dimethylformamide, methanol, ethanol, isopropyl alcohol or mixture of these solvents at temperature 50-100.0° C. using ammonium formate or formic acid as source of hydrogen. The precious metal catalysts used in the hydrogenation are Raney Nickel, palladium etc., followed by filteration of catalyst and distillation of the solvent under high vacuum.

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isopropyl alcohol

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ethanol

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methanol

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3-(4-nitro-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione

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dimethylformamide

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isopropyl alcohol

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ethanol

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methanol

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Lenalidomide

Name

3-(4-nitro-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione

Details

Synthesis routes and methods II

Procedure details

To a mixture of 3-(4-nitro-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-isoglutamine (9 g) in N,N-dimethylformamide (80 ml), was added thionyl chloride (6.6 g) by droplet below 0° C. for stirred reaction in heat preservation for 2˜3 hours. The resulting solution was added by droplet into mixture of ice and water and pH value was adjusted to 7˜8 with sodium carbonate. The mixture was stirred for 30 minutes and filtered to get light yellow crude. Refining with methanol gave 6.6 g of target yield as a light yellow solid. yield: 78%.

Name

3-(4-nitro-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-isoglutamine

Quantity

9 g

Type

reactant

Reaction Step One

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N,N-dimethylformamide

Quantity

80 mL

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solvent

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thionyl chloride

Quantity

6.6 g

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reactant

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water

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sodium carbonate

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methanol

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3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2,6-dioxopiperidine

Yield

78%

Details

Synthesis routes and methods III

Procedure details

Triethylamine (140.8 g, 2.29 mol) was added at 25-30° C. to a solution of 3-amino-piperidine-2,6-dione hydrochloride (100 g, 0.61 mol) in N,N-dimethylformamide (800 ml). A solution of methyl 2-bromomethyl-3-nitro-benzoate (186.0 g, 1.13 mol) in acetonitrile (200 ml) was then added under stirring and a nitrogen atmosphere and the reaction mixture was heated to 50-55° C. for 8-10 hours. After completion of the reaction approximately 60% solvent was removed by distillation at 50-60° C. under reduced pressure (100 mbar). Water (1000 ml) was added to the residual mixture at 50-55° C. and stirred for 1 hour at this temperature. The resultant solid product was cooled to 25-30° C. and filtered. The solid was washed with water (500 ml) at 50-55° C., cooled at ambient temperature and filtered again. Finally the solid was washed with methanol (500 ml) at 50-55° C., cooled at 25-30° C. and filtered. The filtered solid product was dried at 50-55° C. under low pressure (200 mmHg) for 4 hours to give 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione as a purple to ash coloured solid.

Name

Triethylamine

Quantity

140.8 g

Type

reactant

Reaction Step One

Name

3-amino-piperidine-2,6-dione hydrochloride

Quantity

100 g

Type

reactant

Reaction Step One

Name

N,N-dimethylformamide

Quantity

800 mL

Type

solvent

Reaction Step One

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methyl 2-bromomethyl-3-nitro-benzoate

Quantity

186 g

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reactant

Reaction Step Two

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acetonitrile

Quantity

200 mL

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solvent

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[Compound]

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solvent

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0 (± 1) mol

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reactant

Reaction Step Three

Name

3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione

Details

Retrosynthesis Analysis

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