120-43-4

Basic information

• Product Name: Ethyl N-piperazinecarboxylate
• Synonyms: Ethyl 1-piperazinocarboxylate;Ethylcarbonyl piperazine;Ethyl N-pipperazinecarboxylate;1-PiperazinecarboxylicAcidEthylEtser99%(Gc);Ethyl 1-piperazinecarboxylate 98%;1-Piperazinecarboxylicacid,ethylester(6CI,7CI,8CI,9CI);N-CARBOETHYOXY PIPERAZINE aka ETHYL 1-PIPREAZINECA;ETHYL 1-PIPERAZINECARTOXYLATE
• CAS NO: 120-43-4
• Molecular Formula: C₇H₁₄N₂O₂
• Molecular Weight: 158.2
• EINECS: 204-395-2
• Product Categories: PIPERIDINE;Piperidines, Piperidones, Piperazines
• Mol File: 120-43-4.mol
• Article Data: 20

Chemical Properties

• Melting Point: 120 °C
• Boiling Point: 273 °C(lit.)
• Flash Point: >230 °F
• Appearance: Clear light yellow/Oily Liquid
• Density: 1.08 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0459mmHg at 25°C
• Refractive Index: n20/D 1.477(lit.)
• Storage Temp.: Store below +30°C.
• PKA: 8.50±0.10(Predicted)
• Water Solubility: soluble
• BRN: 125780
• CAS DataBase Reference: Ethyl N-piperazinecarboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl N-piperazinecarboxylate(120-43-4)
• EPA Substance Registry System: Ethyl N-piperazinecarboxylate(120-43-4)

Safety Data

• Hazard Codes: Xn,T
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 23-24/25-37/39-26-36
• RIDADR: UN 2810 6.1/PG 3
• WGK Germany: 3
• RTECS: TL1378000
• TSCA: Yes
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 120-43-4(Hazardous Substances Data)

Usage

Chemical Properties

clear light yellow oily liquid

Uses

Intermediate.

InChI:InChI=1/C7H14N2O2/c1-2-11-7(10)9-5-3-8-4-6-9/h8H,2-6H2,1H3/p+1

Synthetic route

piperazine (110-85-0) + Diethyl carbonate (105-58-8) → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
at 80℃; for 3h;	98.5%

1-(ethylcarboxy)-4-benzylpiperazine (59325-12-1) → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol under 2206.5 Torr; for 4h;	78%

piperazine-1,4-dicarboxylic acid ethyl ester methyl ester → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
With L-Selectride In tetrahydrofuran at 20℃; for 48h;	69%

piperazine (110-85-0) + chloroformic acid ethyl ester (541-41-3) → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
In methanol; water at 0 - 25℃; for 4h;	33.7%
In methanol; water at 0 - 25℃; for 4h;	33.7%
bei pH 2.8-4.6;

bis-cyanomethyl-carbamic acid ethyl ester (86366-60-1) → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
With ethanol; nickel Hydrogenation;

O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (205432-12-8) → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
With GLUTATHIONE; glutathione S-transferase P1-1 at 37℃; pH=7.4; Kinetics; Reagent/catalyst; Enzymatic reaction;

pentaerythritol tetraglycidylether (PETGE) + pentaerythritol tetraglycidyl ether (3126-63-4) → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
In methanol

piperazine (110-85-0) + ethyl 1-imidazolecarboxylate (19213-72-0) + piperazine dihydrochloride (142-64-3) → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
Stage #1: piperazine; piperazine dihydrochloride In water for 0.0833333h; Stage #2: ethyl 1-imidazolecarboxylate With sodium chloride In water for 0.5h; Stage #3: With sodium hydroxide In water chemoselective reaction;

tert-butyl 4-ethoxycarbonylpiperazine-1-carboxylate → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
With hydrogenchloride; water In dichloromethane at 20℃;
Stage #1: tert-butyl 4-ethoxycarbonylpiperazine-1-carboxylate With trifluoroacetic acid In dichloromethane at 0 - 20℃; Inert atmosphere; Stage #2: With ammonia In dichloromethane; water Inert atmosphere; Cooling;

O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (205432-12-8) → 4-ethoxycarbonylpiperazine (120-43-4) + S-(2,4-dinitrophenyl)glutathione (26289-39-4)

Conditions	Yield
With glutathione-S-transferase; glutathion; d(TTTTTTTTAGGATCATGGTGATGCTCTACGTGCCGTAGCCTTTTTTTTT); calcium chloride; magnesium chloride for 0.166667h; pH=7.4; Enzymatic reaction;

methyl 4-benzylpiperazine-1-carboxylate → 4-ethoxycarbonylpiperazine (120-43-4)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 40℃; for 48h;

4-ethoxycarbonylpiperazine (120-43-4) + propargyl bromide (106-96-7) → ethyl 4-(prop-2-yn-1-yl)piperazine-1-carboxylate (141403-43-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 0℃; for 1.5h;	100%

4-ethoxycarbonylpiperazine (120-43-4) + teroxirone (2451-62-9) → carboxylate protected tris(2,3-epoxypropyl)isocyanurate

Conditions	Yield
In methanol; 1,2-dimethoxyethane at 25℃; for 51h;	100%

4-ethoxycarbonylpiperazine (120-43-4) + 4-[{4-chloro-2-[(2-chlorophenyl)(hydroxy)methyl]-phenyl}(2,2-dimethylpropyl)amino]-4-oxobutanoic acid (1292849-66-1) → ethyl 4-{4-[{4-chloro-2-[(2-chlorophenyl)(hydroxy)-methyl]phenyl}(2,2-dimethylpropyl)amino]-4-oxobutanoyl}-piperazine-1-carboxylate (1292849-78-5)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 18h;	100%

4-ethoxycarbonylpiperazine (120-43-4) + Cbz-L-Gln (2650-64-8) → 4-((S)-2-benzyloxycarbonylamino-4-carbamoylbutyryl)piperazine-1-carboxylic acid ethyl ester (1021703-31-0)

Conditions	Yield
Stage #1: Cbz-L-Gln With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran; dichloromethane at 20℃; for 0.0833333h; Stage #2: 4-ethoxycarbonylpiperazine In tetrahydrofuran; dichloromethane at 20℃; for 24h;	100%

4-ethoxycarbonylpiperazine (120-43-4) + (2R)-2-{[(benzyloxy)carbonyl]amino}-4-tert-butoxy-4-oxobutanoic acid (71449-08-6) → 4-((R)-2-benzyloxycarbonylamino-3-tert-butoxycarbonylpropionyl)piperazine-1-carboxylic acid ethyl ester

Conditions	Yield
Stage #1: (R)-2-(((benzyloxy)carbonyl)amino)-4-(tertbutoxy)-4-oxobutanoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; dichloromethane at 20℃; for 0.25h; Stage #2: 4-ethoxycarbonylpiperazine In tetrahydrofuran; dichloromethane at 20℃; for 24h;	100%

3-chloromethyl-5-(2-fluoro-5-methyl-phenyl)-[1,2,4]oxadiazole (657424-58-3) + 4-ethoxycarbonylpiperazine (120-43-4) → 4-[5-(2-fluoro-5-methyl-phenyl)-[1,2,4]oxadiazol-3-ylmethyl]-piperazine-1-carboxylic acid ethyl ester

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	99.1%

4-ethoxycarbonylpiperazine (120-43-4) + 7-Chloro-2-methoxy-4-trifluoromethyl-[1,8]naphthyridine (210643-01-9) → 4-(7-Methoxy-5-trifluoromethyl-[1,8]naphthyridin-2-yl)-piperazine-1-carboxylic acid ethyl ester (210643-02-0)

Conditions	Yield
With triethylamine at 100℃; for 24h;	98%

2-iodo-propane (75-30-9) + 4-ethoxycarbonylpiperazine (120-43-4) → ethyl 4-(1-methylethyl)piperazine-1-carboxylate (61014-91-3)

Conditions	Yield
With potassium carbonate In acetonitrile for 24h; Heating;	98%

4-ethoxycarbonylpiperazine (120-43-4) + C54H96N6O18S2 → C96H180N18O30S2

Conditions	Yield
In methanol at 20℃; for 24h;	98%

4-ethoxycarbonylpiperazine (120-43-4) + phenyl isothiocyanate (103-72-0) → ethyl 4-(phenylthiocarbamoyl)piperazine-1-carboxylate (332033-11-1)

Conditions	Yield
In diethyl ether for 0.5h;	98%
In benzene at 45℃; for 6h; Reflux;	85%

4-ethoxycarbonylpiperazine (120-43-4) + 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid azide (1426433-94-4) → ethyl 4-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-ylcarbamoyl)piperazine-1-carboxylate

Conditions	Yield
In toluene for 1h; Curtius Rearrangement; Reflux;	98%

4-(1H-indazole-3-carboxamido)benzoic acid + 4-ethoxycarbonylpiperazine (120-43-4) → ethyl 4-[4-(1H-indazole-3-carboxamido)benzoyl]piperazine-1-carboxylate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 16h;	98%

Upstream product

• 110-85-0 piperazine 
• 541-41-3 chloroformic acid ethyl ester 
• 86366-60-1 bis-cyanomethyl-carbamic acid ethyl ester 
• 59325-12-1 1-(ethylcarboxy)-4-benzylpiperazine 
• 205432-12-8 O²-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate 
• 219509-82-7 tert-butyl 4-ethoxycarbonylpiperazine-1-carboxylate 
• 105-58-8 Diethyl carbonate 
• 19213-72-0 ethyl 1-imidazolecarboxylate 
• 142-64-3 piperazine dihydrochloride 
• 3126-63-4 pentaerythritol tetraglycidyl ether 

Downstream Products

• 101354-80-7 4-(toluene-4-sulfonylmethyl)-piperazine-1-carboxylic acid ethyl ester 
• 59325-11-0 ethyl 4-methyl-1-piperazinecarboxylate 
• 856843-19-1 2-(4-ethoxycarbonyl-piperazino)-propionic acid ethyl ester 
• 63207-02-3 4-decyl-piperazine-1-carboxylic acid ethyl ester 
• 100957-07-1 4-(3,4-dichloro-phenacyl)-piperazine-1-carboxylic acid ethyl ester 
• 54041-93-9 1-(p-Methoxybenzhydryl)piperazine 
• 101889-42-3 4-[(2,4,6-trimethyl-phenylcarbamoyl)-methyl]-piperazine-1-carboxylic acid ethyl ester 
• 109511-69-5 4-[2-(N-ethyl-anilino)-ethyl]-piperazine-1-carboxylic acid ethyl ester 
• 102292-48-8 4-(3,4-dichloro-benzyl)-piperazine-1-carboxylic acid ethyl ester 
• 171609-72-6 1-(3,4-dichloro-benzyl)-piperazine; dihydrochloride 
• 59325-12-1 1-(ethylcarboxy)-4-benzylpiperazine 
• 55037-88-2 4-(4-methoxy-benzyl)-piperazine-1-carboxylic acid ethyl ester 
• 100723-38-4 4-benzoyl-piperazine-1-carboxylic acid ethyl ester 
• 13349-82-1 1-[2-(2-hydroxyethoxy)ethyl]piperazine 

Relevant articles and documents

L-selectride as a convenient reagent for the selective cleavage of carbamates

L-Selectride(R) was shown to selectively cleave methyl carbamates in the presence of more sterically demanding carbamates, including the selective cleavage of a methyl carbamate in the presence of an N-Boc group.

Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs

Nitric oxide (NO) prodrugs such as O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics. Nitric oxide release from the anti-cancer lead compound, JS-K, is proposed to occur through a nucleophilic aromatic substitution by glutathione (GSH) catalyzed by glutathione S-transferase (GST) to form a diazeniumdiolate anion that spontaneously releases NO. In this study, a number of structural analogues of JS-K were synthesized and their chemical and biological properties were compared with those of JS-K. The homopiperazine analogue of JS-K showed anti-cancer activity that is comparable with that of JS-K but with a diminished reactivity towards both GSH and GSH/GST; both the aforementioned compounds displayed no cytotoxic activity towards normal renal epithelial cell line at concentrations where they significantly diminished the proliferation of a panel of renal cancer cell lines. These properties may prove advantageous in the further development of this class of nitric oxide prodrugs as cancer therapeutic agents.

Heteroaryl substituted dihydro pyrimidine compounds and their use in medicine

The invention relates to heteroaryl-substituted dihydropyrimidine compounds and application thereof in medicines, particularly application in medicines for treating and preventing hepatitis B. Particularly, the invention relates to compounds disclosed as general formula (I) or (Ia), or enantiomers, diastereoisomers, hydrates, solvates or pharmaceutically acceptable salts thereof, wherein the variables are defined in the specification. The invention also relates to application of the compounds disclosed as general formula (I) or (Ia), or enantiomers, diastereoisomers, hydrates, solvates or pharmaceutically acceptable salts thereof, especially application in medicines for treating and preventing hepatitis B.

BENZOPIPERIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES

A compound of formula I: (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from H, halo, C1-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, C1-4 alkyloxy, NH-C1-4 alkyl and cyano; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (IIa), where R7a is selected from N-linked N-containing C5-7 heterocycyl and (A); or (ii) (IIb), where X is selected from CH2, N H and O, one of R8a and R8b is selected from CI and ethoxy and the other of R8a and R8b is H.