2-[2-(2-Azidoethoxy)ethoxy]ethanamine Chemical Properties

storage temp. 

-20°C, protect from light

solubility 

Soluble in Water, DMSO, DMF, DCM

form 

Liquid

color 

Colorless to light yellow

Appearance

colorlessoryellowish oil

InChI

InChI=1S/C6H14N4O2/c7-1-3-11-5-6-12-4-2-9-10-8/h1-7H2

InChIKey

ZHWGWSYNZIZTFL-UHFFFAOYSA-N

SMILES

NCCOCCOCCN=[N+]=[N-]

CAS DataBase Reference

166388-57-4

Safety Information

HS Code 

2929900090

2-[2-(2-Azidoethoxy)ethoxy]ethanamine Usage And Synthesis

Description

Azido-PEG2-amine is a bifunctional crosslinker containing an amino and an azide group. The amino group is reactive with carboxylic acids, activated NHS esters,. The azide(N3) group can react with alkyne, BCN, DBCO via Click Chemistry to yield a stable triazole linkage.

Uses

Azido-PEG2-C2-amine (N3-PEG2-CH2CH2NH2) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. Azido-PEG2-C2-amine is also a non-cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2]. Azido-PEG2-C2-amine is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

Synthesis

2-[2-(2-Hydroxyethoxy)ethoxy]ethyl chloride (15 g, 88.9 mmol), NaI(4.06 g, 27.1 mmol), and NaN₃ (45.3 mg, 697 mmol) were dissolved in distilled water (90 mL), and the solution was stirred for 48 h at 50 °C. The reaction mixture extracted with ethyl acetate for three times. The organic layer was dried over Na₂SO₄ , and evaporated to collect 2-[2-(2-azidoethoxy)ethoxy]ethanol (14.0 g, 90.1%) as a yellow oil.To the solution 2-[2-(2-azidoethoxy)ethoxy]ethanol (8 g, 45.7 mmol) in THF (22.4 mL), 6 M NaOH(20.8 mL) and TsCl (13.1 g, 68.6 mmol) were added at 0 °C. The reaction mixture was stirred for 1 h at room temperature under nitrogen atmosphere. The solution was then extracted with diethyl ether four times, and the organic layer was washed with 1 M NaOH. After evaporation of the organic layer,2-[2-(2-azidoethoxy)ethoxy]ethyl tosylate (16.8 g, 98.6%) was obtained as a yellow oil.Finally, ammonia solution (28%, 14.8 mL, 365 mol) was added to the 2-[2-(2-azidoethoxy)ethoxy]-ethyl tosylate (8 g, 24.3 mmol) dissolved in THF (95.9 mL), and reaction mixture was stirred for 96 h at 40 °C. After the reaction, distilled water (50 mL) was added to the solution. The mixture was washed with diethyl ether and then extracted with dichloromethane. The organic layer was dried over NaSO₄ and evaporated to obtain 2-[2-(2-azidoethoxy)ethoxy]ethanamine (2.49 g, 58.8%) as a yellow oil.

IC 50

PEGs; Non-cleavable Linker

References

[1] Su S, et al. Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders. J Med Chem. 2019 Aug 22;62(16):7575-7582. DOI:10.1021/acs.jmedchem.9b00871
[2] Tominari, Yusuk , et al. Heterocyclic compound. WO2020027225A1.

2-[2-(2-Azidoethoxy)ethoxy]ethanamine(166388-57-4)Related Product Information

• 2-(2-Azidoethoxy)ethanol
• Biotin-PEG3-propionic acid
• HS-PEG4-tBu
• 5,8,11,14-Tetraoxa-2-azahexadecanoic acid,16-amino-,1,1-dimethyl ester
• 3,6,9,12-tetraoxatridecylamine
• PENTAETHYLENE GLYCOL
• H2N-PEG4-tBu
• 1H-Thieno[3,4-d]imidazole-4-pentanamide,N-(14-amino-3,6,9,12-tetraoxatetradec-1-yl)hexahydro-2-oxo-,(3aS,4S,6aR)-
• Decaethylene glycol
• O-(2-AMINOETHYL)-O-(2-(BOC-AMINO)ETHYL)OCTAETHYLENE GLYCOL
• 6-Maleimidocaproic acid
• 2-[2-(2-methoxyethoxy)ethoxy]-ethanethiol
• 2,5,8,11,14,17,20,23-Octaoxapentacosane-25-thiol
• HEPTAETHYLENE GLYCOL
• FMOC-15-AMINO-4,7,10,13-TETRAOXAPENTADECANOIC ACID
• MPEG7-CH2CH2COOH
• (R)-N-(3,6,9,12-Tetraoxatridecyl)-alpha-lipoamide
• Z-15-aMino-4,7,10,13-tetraoxapentadecacanoic acid