24666-55-5

Basic information

• Product Name: Carbamic acid, (2,6-dioxo-3-piperidinyl)-, phenylmethyl ester (9CI)
• Synonyms: Carbamic acid, (2,6-dioxo-3-piperidinyl)-, phenylmethyl ester (9CI);3-N-Cbz-amino-2,6-dioxopiperidine;benzyl 2,6-dioxopiperidin-3-ylcarbamate;REF DUPL: 3-N-Cbz-amino-2,6-Dioxo-piperidine;Carbamic acid, (2,6-dioxo-3-piperidinyl)-, phenylmethyl ester;2-(Benzyloxycarbonylamino)glutarimide98%;3-Cbz-amino-2,6-dioxopiperidine
• CAS NO: 24666-55-5
• Molecular Formula: C₁₃H₁₄N₂O₄
• Molecular Weight: 262.26126
• Product Categories: N-CBZ
• Mol File: 24666-55-5.mol
• Article Data: 10

Chemical Properties

• Melting Point: 129-131 °C(Solv: isopropanol (67-63-0))
• Boiling Point: 520.2°C at 760 mmHg
• Flash Point: 268.4°C
• Appearance: /
• Density: 1.31g/cm³
• Vapor Pressure: 6.37E-11mmHg at 25°C
• Refractive Index: 1.58
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 10.58±0.20(Predicted)
• CAS DataBase Reference: Carbamic acid, (2,6-dioxo-3-piperidinyl)-, phenylmethyl ester (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: Carbamic acid, (2,6-dioxo-3-piperidinyl)-, phenylmethyl ester (9CI)(24666-55-5)
• EPA Substance Registry System: Carbamic acid, (2,6-dioxo-3-piperidinyl)-, phenylmethyl ester (9CI)(24666-55-5)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 24666-55-5(Hazardous Substances Data)

Usage

Chemical Properties

White powder

InChI:InChI=1/C13H14N2O4/c16-11-7-6-10(12(17)15-11)14-13(18)19-8-9-4-2-1-3-5-9/h1-5,10H,6-8H2,(H,14,18)(H,15,16,17)

Synthetic route

N-benzyloxycarbonyl-L-glutamic acid (1155-62-0) → 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5)

Conditions	Yield
With urea In dimethyl sulfoxide at 150℃; for 2h; Solvent; Temperature;	92%

Nα-benzyloxycarbonyl-glutamine (50516-14-8) → 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5)

Conditions	Yield
With dmap; 1,1'-carbonyldiimidazole In 1,4-dioxane at 20℃; for 17.1667h; Heating / reflux;	86%

Cbz-L-Gln (2650-64-8) → 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5)

Conditions	Yield
With thionyl chloride In N,N-dimethyl-formamide at -5℃; for 3h;	81%
With 1,1'-carbonyldiimidazole In ethyl acetate at 76 - 80℃;	80%
With 1,1'-carbonyldiimidazole In tetrahydrofuran Heating;

N2-benzyloxycarbonyl-L-glutamine methyl ester (13907-82-9, 2650-67-1) → 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5)

Conditions	Yield
With sodium methylate; benzyl alcohol

L-glutamic acid (56-86-0) + benzyl chloroformate (501-53-1) → 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: water / 2 h / 0 °C 2: urea / dimethyl sulfoxide / 2 h / 150 °C View Scheme

L-glutamine (56-85-9) + benzyl chloroformate (501-53-1) → 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water; toluene / 25 - 30 °C / pH 11 - 12 2: 1,1'-carbonyldiimidazole / ethyl acetate / 76 - 80 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → rac-α-aminoglutarimide hydrochloride (24666-56-6)

Conditions	Yield
With hydrogenchloride; hydrogen; 5% palladium over charcoal In methanol; water under 3102.97 Torr; for 4h;	100%
With hydrogenchloride In dimethyl sulfoxide	92%
Stage #1: 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine With palladium 10% on activated carbon; hydrogen In methanol; water at 25 - 30℃; under 2250.23 - 2625.26 Torr; Stage #2: With hydrogenchloride In methanol; water at 25 - 30℃;	90%
With hydrogenchloride; palladium 10% on activated carbon; hydrogen In methanol at 25℃; for 5h;	90.5%
With hydrogenchloride; hydrogen; palladium on activated charcoal In ethyl acetate under 2585.74 - 3102.89 Torr;

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-aminopiperidine-2,6-dione hydrobromide (90802-45-2)

Conditions	Yield
With hydrogen bromide; acetic acid at 20℃; for 2h;	97%
With hydrogen bromide In acetic anhydride at 50℃; for 0.75h;	96%
With hydrogen bromide; acetic acid at 60℃; for 1h;	95.2%
With hydrogen bromide In nitromethane	92%

o-azidobenzoyl chloride (34897-85-3) + 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → [1-(2-azidobenzoyl)-2,6-dioxo-piperidin-3-yl]carbamic acid benzyl ester

Conditions	Yield
Stage #1: 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine With methyllithium In tetrahydrofuran; diethyl ether at -78℃; for 0.5h; Stage #2: o-azidobenzoyl chloride In tetrahydrofuran at 20℃;	52%

benzaldehyde (100-52-7) + 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 2-(Benzylideneamino)glutarimide (73839-05-1)

Conditions	Yield
With hydrogen; palladium on activated charcoal 1) THF, 12h 1 at H2 2) 3h room temperature; Yield given. Multistep reaction;

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 4-(2-aminoethoxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (390367-50-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 97 percent / aq. HBr; AcOH / 2 h / 20 °C 2.1: dimethylformamide / 24 h / 60 °C 2.2: 71 percent / N,N-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / dimethylformamide / 54 h / 63 °C 3.1: tetraethylammonium fluoride / 72 h / 20 °C 4.1: 34 percent / TFA / CH2Cl2 / 0.75 h / 20 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → (R)-4-(2-aminoethoxy)-thalidomide

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 97 percent / aq. HBr; AcOH / 2 h / 20 °C 2.1: dimethylformamide / 24 h / 60 °C 2.2: 71 percent / N,N-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / dimethylformamide / 54 h / 63 °C 3.1: tetraethylammonium fluoride / 72 h / 20 °C 4.1: 34 percent / TFA / CH2Cl2 / 0.75 h / 20 °C 5.1: CH2Cl2 / HPLC on Chiracel OJ column separation View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → (S)-4-(2-aminoethoxy)-thalidomide

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 97 percent / aq. HBr; AcOH / 2 h / 20 °C 2.1: dimethylformamide / 24 h / 60 °C 2.2: 71 percent / N,N-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / dimethylformamide / 54 h / 63 °C 3.1: tetraethylammonium fluoride / 72 h / 20 °C 4.1: 34 percent / TFA / CH2Cl2 / 0.75 h / 20 °C 5.1: CH2Cl2 / HPLC on Chiracel OJ column separation View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → tert-butyl (2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)ethyl)carbamate (390367-45-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 97 percent / aq. HBr; AcOH / 2 h / 20 °C 2.1: dimethylformamide / 24 h / 60 °C 2.2: 71 percent / N,N-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / dimethylformamide / 54 h / 63 °C 3.1: tetraethylammonium fluoride / 72 h / 20 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 6-{6-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoylamino}-hexanoic acid {2-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yloxy]-ethyl}-amide

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 97 percent / aq. HBr; AcOH / 2 h / 20 °C 2.1: dimethylformamide / 24 h / 60 °C 2.2: 71 percent / N,N-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / dimethylformamide / 54 h / 63 °C 3.1: tetraethylammonium fluoride / 72 h / 20 °C 4.1: 34 percent / TFA / CH2Cl2 / 0.75 h / 20 °C 5.1: 70 percent / dimethylformamide / 3 h / 20 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 4-Hydroxythalidomide (5054-59-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 97 percent / aq. HBr; AcOH / 2 h / 20 °C 2.1: dimethylformamide / 24 h / 60 °C 2.2: 71 percent / N,N-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / dimethylformamide / 54 h / 63 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 2-amino-N-(2,6-dioxo-piperidin-3-yl)benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 96 percent / aq. HBr / acetic anhydride / 0.75 h / 50 °C 2: 39 percent / triethylamine / acetonitrile / 3 h / 60 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 2-azido-N-(2,6-dioxo-piperidin-3-yl)benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 96 percent / aq. HBr / acetic anhydride / 0.75 h / 50 °C 2.1: thionyl chloride / 2 h / 80 °C 2.2: 78 percent / triethylamine / dioxane / 40 - 50 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 2-benzyloxycarbonylamino-4-(4-oxo-3,4-dihydroquinazolin-2-yl)butyric acid

Conditions	Yield
Multi-step reaction with 2 steps 1.1: methyllithium / diethyl ether; tetrahydrofuran / 0.5 h / -78 °C 1.2: 52 percent / tetrahydrofuran / 20 °C 2.1: 38 percent / triethyl phosphite / toluene / 6 h / Heating View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 2-(2,6-dioxo-3-piperidinyl)-5-nitro-1H-isoindole-1,3(2H)-dione (55003-81-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: AcOH / Heating View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 4-NT (19171-18-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: AcOH / Heating View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-(7-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C 3: H2 / 10 percent Pd/C / methanol View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → Lenalidomide (879126-98-4, 879126-99-5, 191732-72-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C 3: H2 / 10 percent Pd/C / methanol View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride / dimethyl sulfoxide 2: triethylamine / acetonitrile / 3 h / Reflux 3: 5%-palladium/activated carbon; hydrogen / ethanol / 1 h / 3040.2 Torr View Scheme
Multi-step reaction with 3 steps 1: hydrogen bromide; acetic acid / 1 h / 60 °C 2: triethylamine / acetonitrile / 10 h / 20 - 80 °C 3: tin(ll) chloride / ethanol / 2 h / 15 - 80 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-(6-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C 3: H2 / 10 percent Pd/C / methanol View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-(5-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C 3: H2 / 10 percent Pd/C / methanol View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-(5-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (827026-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen bromide; acetic acid / 1 h / 60 °C 2: triethylamine / acetonitrile / 10 h / 20 - 80 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-(6-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (1063995-49-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 2-(2,6-dioxo-3-piperidinyl)-5-amino-1H-isoindole-1,3(2H)-dione (191732-76-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: AcOH / Heating 3: H2 / 10 percent Pd/C / acetone / 2585.74 - 3102.89 Torr View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → 3-(4-nitro-3-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione (1063995-54-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: Et3N / dimethylformamide / 80 °C View Scheme

3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine (24666-55-5) → pomalidomide (19171-19-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2, aq. HCl / 10 percent Pd/C / ethyl acetate / 2585.74 - 3102.89 Torr 2: AcOH / Heating 3: H2 / 10 percent Pd/C / acetone / 2585.74 - 3102.89 Torr View Scheme

Upstream product

• 13907-82-9 N²-benzyloxycarbonyl-L-glutamine methyl ester 
• 56-85-9 L-glutamine 
• 501-53-1 benzyl chloroformate 
• 1155-62-0 N-benzyloxycarbonyl-L-glutamic acid 
• 56-86-0 L-glutamic acid 
• 50516-14-8 Nα-benzyloxycarbonyl-glutamine 
• 2650-64-8 Cbz-L-Gln 

Downstream Products

• 73839-05-1 2-(Benzylideneamino)glutarimide 
• 827026-45-9 3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione 
• 2353-44-8 (+/-)-α-aminoglutarimide 
• 73839-06-2 3-amino-3-methyl-piperidine-2,6-dione hydrochloride 
• 903890-66-4 3-[benzylideneamino]-3-methylpiperidine-2,6-dione 
• 19171-19-8 pomalidomide 
• 191732-76-0 2-(2,6-dioxo-3-piperidinyl)-5-amino-1H-isoindole-1,3(2H)-dione 
• 879126-98-4 Lenalidomide 
• 19171-18-7 4-NT 
• 55003-81-1 2-(2,6-dioxo-3-piperidinyl)-5-nitro-1H-isoindole-1,3(2H)-dione 
• 537696-00-7 2-amino-N-(2,6-dioxo-piperidin-3-yl)benzamide 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 90802-45-2 DL-3-amino-2,6-piperidinone hydrobromide 

Relevant articles and documents

Preparation method of lenadomide

The invention discloses a preparation method of lenalidomide, and belongs to the field of organic synthesis. 2-methyl-3-methyl nitrobenzoate and 3-N-benzyloxy-carbonyl-L-glutamine serve as starting materials, and an important intermediate 2-brooethyl-3-methyl nitrobenzoate is obtained through a bromination reaction of 2-methyl-3-methyl nitrobenzoate. 3-N-benzyloxy-carbonyl-L-glutamine is cyclizedunder catalysis to produce 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine, an amino group is subjected to deprotection to produce 3-amino-2,6-piperidone halide, 3-(4-nitro-1-oxo-1,3-o-xylylenimine-2-yl)piperidine-2,6-diketone is obtained through an aminolysis reaction of 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine and 2-brooethyl-3-methyl nitrobenzoate, and then lenalidomide is prepared through reduction. The method has the advantages that the cost of raw materials are low, aftertreatment is simple, and the yield is high, and the production cost of the lenalidomide as a bulk drug is greatly reduced. The method is a convenient and efficient lenalidomide synthesis method suitable for industrial production.

A method for the preparation of amine to that (by machine translation)

The invention discloses a method for the preparation of amine to that, the specific step includes: to 2 - methyl - 3 - nitro benzoic acid as the raw material, to obtain 2 - bromomethyl - 3 - nitro-benzoic acid methyl ester; L - glutamic acid as the raw material to make the N - CBZ - L - glutamic acid; to N - CBZ - L - glutamic acid as the raw material to make the 3 - amino - 2, 6 - piperidine dione hydrochloride; to 2 - methyl - 3 - nitro-benzoic acid methyl ester with 3 - amino - 2, 6 - piperidine dione hydrochloride as the raw material to make the 3 - (4 - nitro - 1, 3 dihydro - 1 - oxo - 2 hydrogen - isoindol - 2 - yl) piperidine - 2, 6 - dione; to 3 - (4 - nitro - 1, 3 dihydro - 1 - oxo - 2 hydrogen - isoindol - 2 - yl) piperidine - 2, 6 - dione as raw materials to that amine. The method of the invention has simple technological process, raw material economic, few by-products, and purification is simple, high yield, environment-friendly and the like, after treatment is simple, has better practicability and application value, has great industrial prospects. (by machine translation)

PYRROLINE-2-ONE DERIVATIVES AGAINST CELL RELEASING TUMOR NECROSIS FACTOR, PREPARATION METHODS AND USES THEREOF

Compounds represented by Formula (I) or Formula (II), their pharmaceutically acceptable salts or hydrates wherein A, B and E independently represent CH2 or CO; D represents S, NH, or NC1-6 alkylhydrocarbyl; R represents H or R3, R1 represents H, or 1-2 same or different occurrences of radical(s) selected from the group consisting of F, Cl, Br, C1-4 alkylhydrocarbyl, OH, OC1-4 alkylhydrocarbyl, NO2, NHC(O)C1-4 alkylhydrocarbyl, NH2, NH(C1-4 alkylhydrocarbyl), N(C1-4 alkylhydrocarbyl)2; and R2 represents F, CF3, H or C1-4 alkylhydrocarbyl; are active inhibitors of TNFα. Provided are also preparation methods and uses thereof.