CAS 35249-62-8 Ivabradine Precursor Synthesis & Specs
Physicochemical Characterization and Structural Verification of CAS 35249-62-8
3-(2-Bromo-4,5-dimethoxyphenyl)propanenitrile functions as a specialized aromatic nitrile utilized extensively in cardiovascular pharmaceutical development. The molecular structure consists of a phenylpropane backbone substituted with a bromine atom at the ortho position and methoxy groups at the 4 and 5 positions. This specific arrangement, often referred to in technical documentation as 2-Bromo-4-5-Dimethoxybenzenepropanenitrile, dictates the compound's reactivity profile during downstream coupling reactions. Accurate structural verification is critical for R&D teams to ensure batch consistency before initiating multi-step synthesis pathways.
Physical constants serve as the primary indicators of identity and bulk purity. The compound typically presents as a white to off-white crystalline powder or solid. Based on standard analytical data, the molecular weight is established at 270.12 g/mol (C₁₁H₁₂BrNO₂), correcting common typographical errors found in legacy databases. The density is recorded at approximately 1.375 g/cm³, with a boiling point reaching 379.4°C at 760 mmHg. Flash point data indicates 183.3°C, necessitating specific storage conditions to maintain stability. At NINGBO INNO PHARMCHEM CO.,LTD., every batch undergoes rigorous structural confirmation using NMR and IR spectroscopy to validate the positioning of the bromine and methoxy functional groups, ensuring the material matches the required chemical building block specifications for sensitive medicinal chemistry applications.
Advanced Protocols for CAS 35249-62-8 Ivabradine Precursor Synthesis
The manufacturing process for this Ivabradine precursor requires precise control over halogenation and nitrile introduction steps. Historical synthesis routes have explored reacting acrylonitrile derivatives with acidic catalysts, but modern industrial protocols prioritize regioselectivity to minimize isomeric impurities. The bromination step is particularly critical; uncontrolled radical substitution can lead to poly-brominated byproducts that are difficult to separate during purification. Advanced protocols utilize controlled temperature gradients and specific solvent systems to favor mono-bromination at the 2-position relative to the propanenitrile chain.
Scalability is a key consideration for commercial drug production. The synthesis must transition smoothly from kilogram-scale R&D batches to multi-ton manufacturing without significant yield loss or purity degradation. Process chemists focus on optimizing the conversion of the dimethoxyphenyl substrate, ensuring that the nitrile group remains intact during the harsh conditions often required for aromatic substitution. The resulting 3-(2-bromo-4-5-dimethoxy-phenyl)-propionitrile must be isolated with minimal residual solvent content. Drying protocols are adjusted based on the thermal stability of the nitrile group to prevent hydrolysis or decomposition, ensuring the intermediate remains stable during transport and storage prior to its use in the benzazepine ring closure steps.
Impurity Profiling and Quality Control of 3-(2-Bromo-4,5-dimethoxyphenyl)propanenitrile
Quality control for pharmaceutical intermediates extends beyond simple purity percentages. Comprehensive impurity profiling identifies specific organic byproducts that could interfere with downstream catalytic steps. Common impurities include unreacted starting materials, regioisomers where bromination occurred at the 6-position, and hydrolyzed acid derivatives resulting from nitrile degradation. High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are employed to quantify these trace components. The goal is to maintain an industrial purity level that supports high-yield coupling reactions without requiring extensive purification later in the synthesis tree.
The following table outlines the critical quality parameters typically assessed during the release of this intermediate, comparing standard specifications against premium R&D grades:
| Parameter | Standard Industrial Specification | Premium R&D Specification | Test Method |
|---|---|---|---|
| Assay (Purity) | ≥ 98.0% | ≥ 99.5% | HPLC Area Normalization |
| Related Substances | ≤ 2.0% | ≤ 0.5% | GC-MS |
| Moisture Content | ≤ 0.5% | ≤ 0.1% | Karl Fischer Titration |
| Residual Solvents | Compliant to ICH Q3C | Compliant to ICH Q3C (Class 3) | Headspace GC |
| Heavy Metals | ≤ 10 ppm | ≤ 5 ppm | ICP-MS |
Adherence to these specifications ensures that the 2-bromo-4-5-dimethoxydihydrocinnamonitrile derivative performs predictably in subsequent reactions. Batch-specific Certificates of Analysis (COA) provide the empirical data required for regulatory filings and process validation.
Downstream Reaction Performance and Yield Optimization in Ivabradine Manufacturing
The primary application of CAS 35249-62-8 lies in the construction of the benzazepine core found in Ivabradine. The bromine atom serves as a handle for palladium-catalyzed coupling or nucleophilic substitution, while the nitrile group is subsequently transformed into the lactam functionality. Reaction performance is heavily dependent on the quality of the starting intermediate. Impurities such as poly-brominated species can poison catalysts or lead to complex mixture formation, drastically reducing overall yield. Optimization strategies often involve tuning the stoichiometry of the coupling partner and selecting ligands that accommodate the steric bulk of the dimethoxy groups.
For procurement teams evaluating suppliers, consistency in downstream yield is a more valuable metric than initial purchase price. Variations in the intermediate's physical form, such as particle size or polymorphic state, can influence dissolution rates during reaction setup. To ensure access to materials validated for these critical steps, researchers can review the 3-(2-Bromo-4,5-dimethoxyphenyl)propanenitrile high purity pharma intermediate specifications. Maintaining a steady supply of this key component prevents bottlenecks in the production of the final active pharmaceutical ingredient (API), supporting both clinical trial material generation and commercial manufacturing scales.
GMP Compliance and Supply Chain Reliability for Pharmaceutical R&D
Reliable sourcing of critical intermediates requires a supply chain built on transparency and documented quality systems. While regulatory registrations vary by region, the focus for R&D procurement should remain on tangible quality metrics such as COA data, stability reports, and packaging integrity. Manufacturers must demonstrate the ability to track batches from raw material intake through final synthesis and packaging. Documentation packages should include Safety Data Sheets (SDS) that accurately reflect the hazard profile of the brominated nitrile structure, ensuring safe handling in laboratory and plant environments.
NINGBO INNO PHARMCHEM CO.,LTD. maintains robust inventory management systems to support global R&D efforts, ensuring that lead times are minimized without compromising on quality verification. Packaging options typically range from small gram-scale quantities for method development to kilogram drums for pilot plant operations. Transportation protocols adhere to international hazardous material guidelines, protecting the chemical integrity of the cargo during transit. By prioritizing supply chain reliability, pharmaceutical companies can mitigate the risk of production delays caused by material shortages or quality disputes, ensuring continuous progress in drug development pipelines.
The integration of high-quality intermediates into the synthesis workflow is fundamental to achieving consistent API production. Technical alignment between the supplier and the manufacturing team ensures that specifications meet the exacting demands of modern medicinal chemistry.
To request a batch-specific COA, SDS, or secure a bulk pricing quote, please contact our technical sales team.