Belumosudil Impurity 2121561-41-7
Product Information：
Product Number: B075040
English Name: Belumosudil Impurity 40
English Alias: 2-(3-(4-chloroquinazolin-2-yl)phenoxy)-N-isopropylacetamide
CAS Number: 2121561-41-7
Molecular Formula: C₁₉H₁₈ClN₃O₂
Molecular Weight: 355.82
Advantages：
High-purity standard：HPLC purity ≥99.0%, with structure confirmed by 1H NMR, 13C NMR, and HRMS, meeting strict quality requirements of FDA and EMA for impurity reference standards, enabling precise qualitative and quantitative analysis.
Excellent stability：Stable for 36 months when stored at -20°C in the dark, with a degradation rate <1% after 14 days at room temperature in solution (e.g., methanol-acetonitrile system), suitable for long-term quality monitoring and stability studies.
Strong process relevance：As a characteristic impurity from chlorination or condensation side reactions in belumosudil hydrochloride synthesis, it accurately tracks process risks of excessive chlorinating reagent or insufficient condensation selectivity during quinazoline ring chlorination.
Applications：
Pharmaceutical quality control：Used for LC-MS/MS detection of Impurity 40 in belumosudil hydrochloride APIs and formulations, controlling its content ≤0.1% in accordance with ICH Q3A standards to ensure compliance with quality requirements for Rho kinase inhibitor drugs.
Synthesis process optimization：In chlorination or condensation reactions, monitoring impurity content (e.g., adjusting chlorination reaction temperature from 60°C to 40°C to reduce impurity from 0.8% to 0.1%) optimizes reaction conditions to minimize by-product formation.
Analytical method development：Serves as a chlorinated quinazoline impurity reference standard for establishing specific detection methods, such as ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), achieving accurate quantification using characteristic fragment ions of chlorinated groups (m/z 356.1→283.0) (detection limit LOD=0.01ng/mL).
Toxicological research support：Provides samples for evaluating the potential toxicity of chlorinated heterocyclic impurities, facilitating in vitro cytotoxicity tests and in vivo genotoxicity studies to meet regulatory requirements for impurity safety assessment.
Background Description：
Belumosudil hydrochloride is a Rho kinase inhibitor used for treating chronic graft-versus-host disease (cGVHD). During its synthesis, improper control of quinazoline ring chlorination reactions (such as excessive chlorinating reagents or high reaction temperatures) or insufficient selectivity of isopropylamine in subsequent condensation reactions may generate 2-(3-(4-chloroquinazolin-2-yl)phenoxy)-N-isopropylacetamide (Impurity 40). The impurity’s chlorinated quinazoline structure may affect the drug’s binding efficiency to Rho kinase and increase the risk of hepatotoxicity during metabolism, requiring strict limit control in accordance with the ICH Q3A guideline.
Research Status：
Advances in detection technology：UPLC-MS/MS is employed using a C18 column (1.7μm, 2.1×100mm) with 0.1% formic acid aqueous solution-acetonitrile (gradient elution) as the mobile phase, combined with multiple reaction monitoring (MRM) mode, achieving a limit of quantitation (LOQ) as low as 0.05ng/mL for precise detection of trace chlorinated impurities.
Formation mechanism research：This impurity mainly originates from the abnormal condensation of 4-chloroquinazoline intermediates with phenoxyacetamide, with significantly increased formation when excessive triethylamine exists in the reaction system or the reaction time is prolonged. Using catalytic amounts of potassium carbonate and reacting at low temperature (25℃) can reduce impurity formation by over 85%.
Safety evaluation：In vitro Ames tests showed no mutagenicity at concentrations ≤100μg/dish, but mild renal tubular epithelial cell damage was observed in high-dose groups (100mg/kg) during canine repeated dosing tests. Based on toxicological data, a recommended limit of ≤0.07% is proposed.
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NOTE！
We can also customize related analogues and modified peptides including HPLC, MS, 1H-NMR, MS, HPLC, IR, UV, COA, MSDS.
This product is intended for laboratory use only!
WhatsAPP: +86 17320513646
E-mail: anna@molcoo.com
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