2-(2-Bromophenyl)pyrrolidine
[CAS# 129540-24-5]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Pyrroles
• Name: 2-(2-Bromophenyl)pyrrolidine
• Molecular Formula: C₁₀H₁₂BrN
• Molecular Weight: 226.11
• CAS Registry Number: 129540-24-5
• SMILES: C1CC(NC1)C2=CC=CC=C2Br

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 274.2±33.0 ºC 760 mmHg (Calc.)^*
• Flash point: 119.6±25.4 ºC (Calc.)^*
• Index of refraction: 1.567 (Calc.)^*

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

2-(2-Bromophenyl)pyrrolidine is an arylpyrrolidine intermediate characterized by a pyrrolidine ring substituted at the 2-position with an ortho-bromophenyl group. The combination of a secondary cyclic amine and an aryl bromide functional handle makes the molecule a versatile building block in modern medicinal-chemistry syntheses: the basic nitrogen can be derivatized or protected for downstream transformations, while the aryl–Br enables metal-mediated cross-coupling or nucleophilic aromatic substitution to install diverse aryl or heteroaryl substituents. These orthogonal reactivity elements underpin the compound’s frequent use as a modular fragment for assembling more complex heterocycles and fused scaffolds.

The discovery of 2-(2-bromophenyl)pyrrolidine per se is not typically recorded as a single historical event; rather, the compound appears in the literature and patent literature as a practical synthetic intermediate incorporated into series of drug candidates. In recent patent filings across oncology and enzyme-targeted programs, arylpyrrolidine fragments of this general type are described as intermediates or exemplified building blocks used to access 1H-pyrrolo[2,3-b]pyridine cores, fused tricyclic systems, macrocyclic sulfonamides and other drug-like frameworks. Those disclosures demonstrate the role of 2-(2-bromophenyl)pyrrolidine derivatives in enabling convergent syntheses, where late-stage introduction or modification of the aryl substituent provides rapid access to analogues for structure–activity relationship studies.

In applications, the arylpyrrolidine motif is leveraged most often as an intermediate en route to active pharmaceutical agents. Patent families directed to BCL-2/BCL-XL modulators and degraders, ABAD inhibitors, and other target classes cite use of pyrrolidine-containing intermediates to construct occupancy-driven small molecules and constrained heterocyclic cores. The ortho-bromo substituent is particularly valuable when a subsequent cross-coupling step is required to append heteroaryl rings or to form carbon–carbon bonds that deliver fused bicyclic or tricyclic architectures. After assembly of the target core, the pyrrolidine nitrogen is commonly elaborated (for example by N-alkylation, acylation or formation of tertiary amines) to tune basicity, polarity and pharmacokinetic properties of the resulting lead compounds.

From a synthetic-chemistry perspective, common preparative approaches to 2-(2-bromophenyl)pyrrolidine and related analogues include reductive cyclization of appropriately substituted 1,4-dicarbonyl precursors, ring closure from halo-substituted allylic intermediates, or reduction of substituted pyrroline precursors. The free base can be converted to stable crystalline salts (for example hydrochlorides or tartrates) to facilitate handling, purification and storage; such salt-forming strategies are frequently employed during scale-up of intermediates for discovery and preclinical development.

Chemists working with this intermediate must observe routine precautions for halogenated aromatics and amines: control of moisture and exclusion of strong nucleophiles or strong oxidants during storage; avoidance of uncontrolled heating in the presence of bases or acids that might induce decomposition; and selection of protecting-group strategies when the amine must survive multi-step sequences. In formulation or API development, conversion of intermediates into defined crystalline forms or counterion salts is a standard step to ensure reproducible performance downstream.

Overall, 2-(2-bromophenyl)pyrrolidine functions as a practical and widely used synthetic fragment in drug-discovery pipelines. Its dual reactivity handles — a nucleophilic, derivatizable pyrrolidine nitrogen and an electrophilic aryl bromide — enable flexible, modular assembly of diverse heterocyclic and fused systems that have been pursued across patent families for oncology, enzyme inhibition and other therapeutic areas.

References

Bcl-xl/bcl-2 degraders and uses thereof. WO-2023220425-A1. Priority date: 2022-05-12. Link

1H-pyrrolo[2,3-b]pyridine derivatives as BCL-2 inhibitors for the treatment of neoplastic and autoimmune diseases. WO-2022140224-A1. Priority date: 2020-12-22. Link

Compounds for the modulation of cyclophilins function. WO-2020043831-A1. Priority date: 2018-08-29. Link