Methyl 4-(benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate

Methyl 4-(benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate is the core pyrrolidine scaffold for Atrasentan (ABT-627 / A-147627), a potent and selective endothelin-A (ETA) receptor antagonist originally developed by Abbott Laboratories for the treatment of diabetic nephropathy and other cardiovascular conditions. The stereochemical arrangement of Methyl 4-(benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate (with (2R,3R,4S) relative configuration) pre-organizes the key pharmacophore elements for optimal ETA receptor recognition, and subsequent elaboration of the pyrrolidine nitrogen yields the clinical candidate with sub-nanomolar receptor affinity . Early exploratory work demonstrated that the benzodioxole unit contributes substantially to potency, while the 4-methoxyphenyl substituent further modulates receptor subtype selectivity against the ETB receptor. Today, Methyl 4-(benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate is supplied primarily as a chemical intermediate and reference standard for quality control, analytical method validation, and process-related impurity profiling of Atrasentan drug substance, especially in the context of generic ANDA filings and commercial manufacturing of the finished pharmaceutical product.

Product Parameters

Product Advantages

1.Stereochemically Defined Scaffold

The (2R,3R,4S) trisubstituted pyrrolidine core is established using a validated diastereoselective 6-endo-trig cyclization and ring contraction, ensuring reproducible stereochemistry batch after batch. For Atrasentan synthesis, this stereochemical integrity is non-negotiable — and Cosperpharm delivers it consistently [8†L26-L29].

2.Atrasentan Core Scaffold

This pyrrolidine is the central framework of Atrasentan (ABT-627), a drug candidate that progressed to clinical development for diabetic nephropathy. As the key intermediate leading to the pyrrolidine-3-carboxylic acid scaffold of the drug, it provides the ideal starting point for research or manufacturing programs targeting this endothelin antagonist class.

3.Fully Functionalized, Ready for Final Steps

With the two aryl groups already installed on the pyrrolidine ring and a methyl ester at the 3-position that can be hydrolyzed to the free acid, this scaffold is primed for late-stage transformations. The available NH on the pyrrolidine offers a site for introducing the final N-acyl substitution to reach the Atrasentan structure.

4.Scales from Research to Production

Available from 1g R&D samples to 1kg+ batches, with industrial grade (99%) purity specifications also available upon request to meet your development stage.

5.Quality Control and Regulatory Support

Beyond synthesis, this compound serves as an impurity reference standard for Atrasentan API release testing and stability monitoring. Cosperpharm supports these applications with full method validation documentation and storage stability data tailored to regulatory expectations.

Storage Conditions

Methyl 4-(benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate should be stored in a tightly sealed container placed in a dry, cool, dark environment, protected from moisture and direct sunlight. For long-term storage exceeding six months, refrigeration at 2–8°C under an inert atmosphere (nitrogen or argon) is recommended to preserve optimal stability. Opened containers should be resealed immediately after use to minimize exposure to ambient humidity.

Accelerated (40°C / 75% RH) and long-term stability data are available upon request to support your regulatory filing.

Product Quality Assurance

Cosperpharm maintains a rigorous quality management system for Methyl 4-(benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate that meets the demanding standards of pharmaceutical reference materials and intermediates:

1.Full batch characterization

Each production batch undergoes HPLC purity analysis (≥98%, with higher specifications available), chiral HPLC verification of (2R,3R,4S) stereochemistry, ¹H NMR and ¹³C NMR structure confirmation, residual solvent analysis, and water content determination (Karl Fischer). Appearance and other physical properties are verified against established acceptance criteria.

2.Comprehensive documentation

Every shipment includes a Certificate of Analysis (COA) with batch-specific purity and impurity data. DMF-ready documentation packages, accelerated and long-term stability summaries, and method validation reports are available upon request to support your regulatory filings.

3.Full traceability

From raw material sourcing through synthesis, purification, drying, and final packaging, every step is documented and fully traceable. Each batch receives a unique lot number with complete retention samples.

4.Stability monitoring

Ongoing stability studies under ICH-recommended conditions (long-term storage and accelerated testing) are conducted. Stability data packages are available to support customer regulatory submissions.

5.Customer-initiated quality audits

Qualified customers are welcome to audit our manufacturing and quality control facilities. Please contact our regulatory team to schedule an audit.

Contact us

Need a reliable supply of Methyl 4-(benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate for your Atrasentan project? Whether you are at the discovery stage, process development, or commercial manufacturing, we are ready to support you.