tert-butyl (S)-3-((S)-1-(tert-butoxy)-3-(3-(((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzyl)amino)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate
[CAS# 2565657-87-4]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: tert-butyl (S)-3-((S)-1-(tert-butoxy)-3-(3-(((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzyl)amino)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate
• Synonyms: a,a'-[iminobis(methylene-3,1-phenylenemethylene)]bis[1-[(1,1-dimethylethoxy)carbonyl]-3-Pyrrolidineacetic acid (aS,a'S,3R,3'R)-3,3'-bis(1,1-dimethylethyl) ester
• Molecular Formula: C₄₆H₆₉N₃O₈
• Molecular Weight: 792.06
• CAS Registry Number: 2565657-87-4
• SMILES: C1=CC(=CC(=C1)CNCC2=CC=CC(=C2)C[C@H](C(OC(C)(C)C)=O)[C@H]3CCN(C3)C(=O)OC(C)(C)C)CC(C(=O)OC(C)(C)C)[C@H]4CCN(C4)C(OC(C)(C)C)=O

Properties

• Density: 1.113±0.06 g/mL (20 ºC, 760 Torr) (Calc.)
• Melting point: 783.5±55.0 ºC (Calc.)

Discovory and Applicatios

tert-butyl (S)-3-((S)-1-(tert-butoxy)-3-(3-(((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzyl)amino)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate is a heavily protected, stereodefined small-molecule intermediate commonly encountered in modern medicinal-chemistry and peptide-like synthetic sequences. It combines multiple tert-butyl (tBu and Boc) protecting groups on carboxylate and hydroxy functionalities with pyrrolidine and pyrrolidine-derived backbones bearing defined S and R stereochemistry, and an appended benzylamine motif. The compound is typically supplied as a single stereochemical diastereomer or a defined enantiomer and is used as a modular building block for convergent assembly of more complex drug-like molecules.

Such materials arise from iterative protecting-group strategies used to prevent side reactions during multistep syntheses. The tert-butyl and tert-butoxycarbonyl (Boc) groups protect carboxyl and amine functionalities, respectively, allowing selective deprotection at later stages (for example by acidolysis with trifluoroacetic acid) without perturbing base-sensitive or hydrogenation-sensitive motifs. The presence of a benzylic amino methyl linkage and an activated 3-oxopropyl unit indicates that this intermediate is primed for downstream amide couplings, reductive aminations, or intramolecular cyclizations under controlled conditions. Supplier and catalogue descriptions for closely related tert-butyl-protected pyrrolidine derivatives show this design pattern is routinely employed to enable orthogonal transformations and to preserve stereochemical integrity through peptide-type couplings.

Typical synthetic workflows that produce such intermediates employ well-established peptide/amide coupling chemistry and protecting-group manipulations. Carbodiimide or uronium-based coupling reagents (for example HATU, HBTU, EDC/HOBt) are used to form amide bonds with minimal racemization; orthogonal Boc/tBu protection allows selective deprotection sequences to unmask amines or acids in the desired order. Where stereochemical control is required, enantiomerically pure starting materials (chiral pyrrolidines or chiral amino-esters) and mild coupling conditions are selected to avoid epimerization. These practical approaches are standard in medicinal-chemistry discovery labs and are reflected in both supplier synthetic descriptions and methodology overviews used for multistep drug synthesis.

The primary application of this class of intermediate is as a convergent fragment in lead-optimization campaigns. The heavily protected scaffold serves to introduce constrained stereochemistry and steric bulk that may improve binding affinity, metabolic stability or pharmacokinetic properties when incorporated into final scaffolds. It is also useful as a masked synthon enabling later installation of polar functionality (after deprotection) or for connection into macrocycles or peptidomimetics via macrocyclization or cross-coupling steps. Recent patent literature and discovery programmes exploiting complex protected amino-alkyl fragments demonstrate how such intermediates are scaffolds for rapid exploration of structure–activity relationships in target classes such as KRAS binders and other challenging protein surfaces.

Handling, storage and quality control considerations reflect the compound’s role as an intermediate. It is generally supplied as a dry, sealed solid at specified purity (often ≥95%), and should be stored under inert atmosphere or desiccated at low temperature to avoid tBu-ester cleavage or hydrolysis. Analytical characterisation typically includes 1H and 13C NMR, HRMS, and chiral HPLC to confirm stereochemistry and enantiomeric excess. In multigram preparations the choice of reagents and conditions is tuned to minimise by-product formation and to facilitate purification (silica chromatography, crystallisation or preparative HPLC).

In summary, the named tert-butyl-protected (S)/(R) pyrrolidine derivative is a classic example of a protected, stereodefined synthetic building block used to enable convergent medicinal-chemistry syntheses. It is not typically a final therapeutic candidate itself but is an essential enabling reagent that allows chemists to assemble, diversify and tune advanced lead molecules in discovery projects.

References

World Intellectual Property Organization / Google Patents (2024) WO2024020159A1: Macrocyclic peptides targeting KRAS — example patent family illustrating use of heavily protected, stereodefined fragments in modern drug discovery.
([Google Patents][3]).