D-Proline, 4-hydroxy-, methyl ester, hydrochloride (1:1), (4R)-

Product NameD-Proline, 4-hydroxy-, methyl ester, hydrochloride (1:1), (4R)-
CAS114676-59-4
MFC6H11NO3.ClH
MW181.618
EINECS
MOL File114676-59-4.mol

Chemical Properties

Melting point	121-123℃
storage temp.	under inert gas (nitrogen or Argon) at 2-8°C
form	solid
color	White
optical activity	10.30(C=1.00g/100ml MEOH)

Safety Information

HS Code

2933998090

Usage And Synthesis

Uses

D-Proline, 4-hydroxy-, methyl ester hydrochloride is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). D-Proline, 4-hydroxy-, methyl ester hydrochloride is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[2

Synthesis

67-56-1

2584-71-6

D-Proline, 4-hydroxy-, methyl ester, hydrochloride (1:1), (4R)-

114676-59-4

To a stirred solution of cis-4-hydroxy-D-proline (10.0 g, 76.3 mmol, 1 eq.) in methanol (300 mL) was slowly added thionyl chloride (10.0 mL, excess) over 1.5 min at 0 °C. The reaction mixture was gradually warmed to 23 °C and stirred continuously for 16 hours. Upon completion of the reaction, the mixture was concentrated under reduced pressure to afford (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid methyl ester hydrochloride as a white solid (15.9 g, 100% yield).

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

Preparation Products And Raw materials

Raw materials

Methanol cis-4-Hydroxy-D-proline cis-4-Hydroxy-D-proline hydrochloride Thionyl chloride

Preparation Products

1-Pyrrolidinecarboxylicacid,4-amino-2-methyl-,1,1-dimethylethylester,(2S-trans)-(9CI)N-Cbz-cis-4-hydroxy-D-proline methyl ester Methyl (R)-1-Boc-4,4-difluoropyrrolidine-2-carboxylate (3R,5S)-tert-butyl 3-aMino-5-fluoropiperidine-1-carboxylate D-Proline, 4-hydroxy-1-(phenylmethyl)-, methyl ester, (4R)-