1-(BENZYLOXYCARBONYL) AZETIDINE-3-CARBOXYLIC ACID Chemical Properties

Boiling point:

421.2±45.0 °C(Predicted)

Density 

1.362

storage temp. 

2-8°C

pka

4.19±0.20(Predicted)

form 

Solid

color 

White to off-white

Safety Information

HazardClass 

IRRITANT

HS Code 

2933998090

1-(BENZYLOXYCARBONYL) AZETIDINE-3-CARBOXYLIC ACID Usage And Synthesis

Uses

1-Cbz-azetidine-3-carboxylic acid is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). 1-Cbz-azetidine-3-carboxylic acid is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1]

Synthesis

General procedure for the synthesis of 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid from 3-acridinecarboxylic acid and benzyl chloroformate: 3-acridinecarboxylic acid (4.0 g, 39.6 mmol) was dissolved in a 1 N sodium hydroxide solution (40 mL) and the solution was cooled to 0 °C. Under stirring, benzyl chloroformate (5.9 mL, 41 mmol) was slowly added, followed by dropwise addition of additional 1 N sodium hydroxide solution (41 mL). The reaction mixture was stirred vigorously at 0 °C for 16 hours. Upon completion of the reaction, the mixture was acidified to a pH of about 2-3 with 2 N hydrochloric acid.The acidified suspension was extracted with dichloromethane (2 x 100 mL) and the organic layers were combined and dried with anhydrous magnesium sulfate. After filtration, the organic phase was concentrated under reduced pressure to afford the white solid product 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid (9.3 g, 39.6 mmol, 100% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.37-7.29 (5H, m, Ar-H), 5.10 (2H, s, CH2Ph), 4.21 (4H, d, J = 7.5 Hz, NCH2), 3.43 (1H, quintuple peak, J = 7.5 Hz, CH).

IC 50

Non-cleavable Linker

References

[1] Beck A, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315-337. DOI:10.1038/nrd.2016.268
[2] Nalawansha DA, et al. PROTACs: An Emerging Therapeutic Modality in Precision Medicine. Cell Chem Biol. 2020;27(8):998-985. DOI:10.7554/eLife.57277

1-(BENZYLOXYCARBONYL) AZETIDINE-3-CARBOXYLIC ACID(97628-92-7)Related Product Information

• Cbz-S-3-Aminoisobutyric acid
• BENZYL 3-(HYDROXYMETHYL)AZETIDINE-1-CARBOXYLATE
• 1-(BENZYLOXYCARBONYL) AZETIDINE-3-CARBOXYLIC ACID