5845-66-9

Basic information

• Product Name: 3-[(4-hydroxyphenyl)methyl]piperazine-2,5-dione
• Synonyms: 3-(S)-(4-Hydroxybenzyl)piperazine-2,5-dione;Cyclic(glycyl-L-tyrosyl);Cyclo(L-tyrosylglycine);3-(4-hydroxybenzyl)piperazine-2,5-dione;(S)-3-(4-hydroxybenzyl)piperazine-2,5-dione;3-[(4-hydroxyphenyl)methyl]piperazine-2,5-dione;Cyclo(-Gln-Tyr);Levothyroxine Related Compound 1 (N-Acetyl-3,5-Diiodo-L-Tyrosine)
• CAS NO: 5845-66-9
• Molecular Formula: C11H12N2O3
• Molecular Weight: 220.23
• Mol File: 5845-66-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: 240℃
• Boiling Point: 623.1 °C at 760 mmHg
• Flash Point: 330.7 °C
• Appearance: /
• Density: 1.308
• Vapor Pressure: 4.04E-16mmHg at 25°C
• Refractive Index: 1.585
• PKA: 9.90±0.15(Predicted)
• CAS DataBase Reference: 3-[(4-hydroxyphenyl)methyl]piperazine-2,5-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 3-[(4-hydroxyphenyl)methyl]piperazine-2,5-dione(5845-66-9)
• EPA Substance Registry System: 3-[(4-hydroxyphenyl)methyl]piperazine-2,5-dione(5845-66-9)

Safety Data

• Hazardous Substances Data: 5845-66-9(Hazardous Substances Data)

Usage

InChI:InChI=1/C11H12N2O3/c14-8-3-1-7(2-4-8)5-9-11(16)12-6-10(15)13-9/h1-4,9,14H,5-6H2,(H,12,16)(H,13,15)

Synthetic route

cyclo(L-tyrosine(OBn)-glycine) (1628630-12-5) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃;	92%

CF3CO2H*H-L-Tyr-Gly-OMe → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
With 4-methyl-morpholine; acetic acid In iso-butanol at 120℃; for 3h;	43%

N-Gly-Tyr (658-79-7) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Boc-Tyr-Gly-OEt (67208-98-4) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
With 4-methyl-morpholine; hydrogenchloride; acetic acid 1.) dioxane, r.t., 30 min; 2.) 2-butanol, reflux, 3 h; Yield given. Multistep reaction;

Boc-Tyr-OH (3978-80-1) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / N,N'-dicyclohexylcarbodiimide, 1-hydroxybenztriazole 2: 1.) 4N HCl; 2.) N-methylmorpholine / 2.) 0.1M AcOH / 1.) dioxane, r.t., 30 min; 2.) 2-butanol, reflux, 3 h View Scheme
Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; 4-methyl-morpholine / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2: dichloromethane / 1 h / 20 °C / Inert atmosphere 3: acetic acid; 4-methyl-morpholine / iso-butanol / 3 h / 120 °C View Scheme

FLQLYGLPETGY-isoacyl-Hse(Bz)-NH2 (1594922-38-9) + GGGGAEW-NH2 (1594873-76-3) → C22H26N4O6 (1594962-96-5) + C11H14N2O3 (1195407-21-6) + 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
With recombinant sortase A In aq. buffer at 21℃; pH=8;

BOC-Tyr(OBzl)-Gly-OEt (40356-35-2) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: water; methanol / 0.17 h / 170 °C / Microwave irradiation 2: hydrogen; palladium 10% on activated carbon / methanol / 20 °C View Scheme

O-benzyl-N-tert-butoxycarbonyl-L-tyrosine (2130-96-3) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 2: water; methanol / 0.17 h / 170 °C / Microwave irradiation 3: hydrogen; palladium 10% on activated carbon / methanol / 20 °C View Scheme

Boc-L-Tyr-Gly-OMe (7733-20-2) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: dichloromethane / 1 h / 20 °C / Inert atmosphere 2: acetic acid; 4-methyl-morpholine / iso-butanol / 3 h / 120 °C View Scheme

L-tyrosine ethyl ester (949-67-7) + chloroacetyl chloride (79-04-9) → 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9)

Conditions	Yield
With ammonia Multistep reaction;

prenyl bromide (870-63-3) + 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9) → cyclo-(glycyl-t-tyrosyl) 4,4-dimethylallyl ether (112900-76-2)

Conditions	Yield
With caesium carbonate; tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 20℃; for 12h;	73%
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	46%
With sodium hydride In dimethyl sulfoxide 0 deg C, then room t., 20 h;	23 mg

dimethyl sulfate (77-78-1) + 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9) → 3-<(4-methoxyphenyl)methyl>-1,4-dimethylpiperazine-2,5-dione (128520-01-4)

Conditions	Yield
With sodium hydride DMSO-THF; Multistep reaction;

3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9) + methyl iodide (74-88-4) → 3-<(4-methoxyphenyl)methyl>-1,4-dimethylpiperazine-2,5-dione (128520-01-4)

Conditions	Yield
With sodium hydride In dimethyl sulfoxide for 18h; Ambient temperature;

N-(2,4-dinitro-5-fluorophenyl)-L-alaninamide + 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione (5845-66-9) → Gly-L-FDAA + DAA-L-Tyr-OH

Conditions	Yield
Stage #1: 3-(S)-(4-hydroxy-benzyl)-piperazine-2,5-dione With hydrogenchloride In water at 125℃; for 24h; Stage #2: N-(2,4-dinitro-5-fluorophenyl)-L-alaninamide With sodium hydrogencarbonate In water; acetone at 40℃; for 1h;

Upstream product

• 40356-35-2 BOC-Tyr(OBzl)-Gly-OEt 
• 2130-96-3 O-benzyl-N-tert-butoxycarbonyl-L-tyrosine 
• 7733-20-2 Boc-L-Tyr-Gly-OMe 
• 949-67-7 L-tyrosine ethyl ester 
• 79-04-9 chloroacetyl chloride 
• 1080-06-4 L-Tyr-OMe 
• 65160-62-5 N^α-t-butyloxycarbonyl-glycyl-L-tyrosine methyl ester 
• 658-79-7 N-Gly-Tyr 
• 67208-98-4 Boc-Tyr-Gly-OEt 
• 3978-80-1 Boc-Tyr-OH 
• 1594922-38-9 FLQLYGLPETGY-isoacyl-Hse(Bz)-NH₂ 
• 1594873-76-3 GGGGAEW-NH₂ 
• 1628630-12-5 cyclo(L-tyrosine(OBn)-glycine) 
• 96935-86-3 H-Gly-Tyr-OMe 

Downstream Products

• 112900-76-2 cyclo-(glycyl-t-tyrosyl) 4,4-dimethylallyl ether 
• 128520-01-4 3-<(4-methoxyphenyl)methyl>-1,4-dimethylpiperazine-2,5-dione 

Relevant articles and documents

Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation

Alzheime?s disease (AD) is the most prominent neurodegenerative disorder with high medical need. Protein-protein-interactions (PPI) interactions have a critical role in AD where β-amyloid structures (Aβ) build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to an H3R pharmacophore. Most of them showed low nanomolar affinities at H3R and some with promising affinity to Aβ-monomers. The structure–activity relationships (SAR) described offer new possibilities for MTDL with an optimized profile combining symptomatic and potential causal therapeutic approaches in AD.

Synthesis and conformational characterization of diketopiperazines bearing a benzyl moiety

Diketopiperazines bearing a benzyl moiety with different para-substituents were synthesized and analyzed by 1HNMR spectroscopy. All of these diketopiperazines were found to adopt a folded conformation according to the upfield chemical shift of the cis-proton (cis to the benzyl moiety) due to a shielding effect in the 1HNMR spectra. An intramolecular CH-π interaction appears to be an important factor for the folded conformation due to the effects of para-substituents on the benzyl group.

THREE PIPERAZINEDIONES AND A DRIMANE DITERPENOID FROM PENICILLIUM BREVI-COMPACTUM

Three new piperazinedione metabolites isolated from cultures of Penicillium brevi-compactum are described.A drimane derivative similar to macrophorin A was isolated and characterized.