Category: 608141-42-0

Landge, Shashikant B.; Dahale, Sunil B.; Jadhav, Sanjay A.; Solanki, Pavankumar V.; Bembalkar, Saroj R.; Mathad, Vijayavitthal T. published the artcile< Development and validation of stability indicating rapid RP-LC method for determination of process and degradation related impurities of apremilast, an anti-inflammatory drug>, COA of Formula: C12H19NO4S, the main research area is RPLC degradation apremilast antiinflammatory drug.

A new, specific, rapid and stability indicating reversed phase liquid chromatog. (RP-LC) method for the determination of process related and degradation related impurities of Apremilast has been developed and validated. The degradation study performed in acid, base, oxidative, photolytic, and thermal stressed conditions. Eight process related impurities (Imp-1 to Imp-8) in test sample of Apremilast have been detected by developed RP-LC method. The good chromatog. resolution between the peaks of process related impurities, degradation impurities and Apremilast has been achieved on a Synergi Max-RP 80 A (150 × 4.6 mm ID), 4μ column. The process and degradation related impurities were characterized by mass spectrometry, 1 H NMR and FT-IR spectral data. The method was validated as per ICH guideline and found to be specific, rapid, and stability indicating. The proposed RP-PLC method was successfully applied to the anal. of drug substance samples of Apremilast.

American Journal of Analytical Chemistry published new progress about Anti-inflammatory agents. 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, COA of Formula: C12H19NO4S.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Ruchelman, Alexander L.; Connolly, Terrence J. published the artcile< Enantioselective synthesis of the apremilast aminosulfone using catalytic asymmetric hydrogenation>, COA of Formula: C12H19NO4S, the main research area is enantioselective apremilast aminosulfone catalytic asym hydrogenation.

Celgene’s Otezla (apremilast) is the first and only PDE4 inhibitor approved by the US FDA for the treatment of plaque psoriasis and psoriatic arthritis. Apremilast has been historically prepared via resolution to obtain the enantioenriched aminosulfone intermediate. Herein we have investigated the use of catalytic asym. hydrogenation for the enantioselective synthesis of the key aminosulfone intermediate in order to identify a higher yielding and greener synthesis route. Asym. reduction of the enamine 3-EtO-4-MeOC6H3C(NH2):CHSO2Me and the ketone 3-EtO-4-MeOC6H3COCH2SO2Me both proceeded with high selectivities, generating their resp. products with >95% ee.

Tetrahedron: Asymmetry published new progress about Enantioselective synthesis. 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, COA of Formula: C12H19NO4S.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Wang, Bofei; Zhong, Fangrui published the artcile< Practical and Asymmetric Synthesis of Apremilast Using Ellman's Sulfinamide as a Chiral Auxiliary>, Recommanded Product: (S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine, the main research area is apremilast preparation enantioselective imidation.

A new protocol for the asym. synthesis of apremilast using tert-butanesulfinamide as a chiral auxiliary was described. This synthetic route consisted of four steps starting from the com. available 3-hydroxy-4-methoxybenzaldehyde and apremilast was accordingly obtained in an overall 56% yield and with 95.5% ee.

Molbank published new progress about Enantioselective synthesis. 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, Recommanded Product: (S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Man, Hon-Wah; Schafer, Peter; Wong, Lu Min; Patterson, Rebecca T.; Corral, Laura G.; Raymon, Heather; Blease, Kate; Leisten, Jim; Shirley, Michael A.; Tang, Yang; Babusis, Darius M.; Chen, Roger; Stirling, Dave; Muller, George W. published the artcile< Discovery of (S)-N-{2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide (Apremilast), a Potent and Orally Active Phosphodiesterase 4 and Tumor Necrosis Factor-α Inhibitor>, HPLC of Formula: 608141-42-0, the main research area is apremilast acetylamino analog preparation PDE4 TNF inhibitor structure antiinflammatory.

In this communication, we report the discovery of 1S (apremilast), a novel potent and orally active phosphodiesterase 4 (PDE4) and tumor necrosis factor-α inhibitor. The optimization of previously reported 3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogs. Evaluation of the structure-activity relationship of substitutions on the phthalimide group led to the discovery of an acetylamino analog 1S, which is currently in clin. trials.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, HPLC of Formula: 608141-42-0.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Jagannadham, Y.; Ramadevi, B.; Prasanna, B. published the artcile< An improved economical process for preparation of apremilast and identified their impurities>, Related Products of 608141-42-0, the main research area is acetamidophthalic acid ethoxy methoxyphenyl methylsulfonyl ethylamine cyclocondensation; apremilast preparation.

An improved and com. viable process provided for the preparation of apremilast, which was simple, cost effective and non-hazardous. The usage of acetic anhydride and high temperature was avoided. An alternative process using protected 3-aminophthalic acid with acetyl chloride in the presence of triethanolamine as catalyst in dichloromethane solvent at 0 to 5° for 1 h. then followed by condensed with (S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine to get the final apremilast product was reported. Besides, there were two unknown impurities like 3-(amino-1,3-dioxoisoindolin-2-yl)phthalic acid and 4-aminoisobenzofuran-1,3-dione identified by HPLC. A thorough study was under taken to synthesize and characterize these unknown impurities. This improved process has a number of industrial advantages, such as economical material cost and relatively high yield. The structure of the synthesized compounds was elucidated by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses.

Asian Journal of Chemistry published new progress about Cyclocondensation reaction. 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, Related Products of 608141-42-0.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Bhole, Ritesh P.; Naksakhare, Sachin R.; Bonde, Chandrakant G. published the artcile< A stability indicating HPTLC Method for apremilast and identification of degradation products using MS/MS>, Electric Literature of 608141-42-0, the main research area is apremilast degradation product high performance liquid chromatog pharmaceutical formulation.

Aim: Apremilast is used for treatment of certain types of psoriasis, psoriatic arthritisand plaque psoriasis is a type of skin condition. An extensive literature search revealed that there exist very few methods on RP-HPLC reported and HPTLC method was not reported. This study deals with simple, precise, accurate and economical stability indicating HPTLC method development with validation as per ICH guidelines with application of developed method on in Apremilast pharmaceutical formulations and Identified and Characterization of degradation products using MS/MS. Method: Precoated Silica gels plates were used as stationary phase. Toluene: Et Acetate (4:6; volume/volume) was delivered best separation at 236 nm (Rf 0.55 ± 0.02) by densitometry anal. Degradation anal. was performed as per ICH guidelines (Q2R1). Isolation of degradation product by HPTLC method and identify by MS/MS method. Results: The linearity was 100-600 ng with R2 of 0.997 while, % RSD was in range. LOD and LOQ of Apremilast were found 0.77ng/spot and 2.35ng/spot resp. The recovery of Apremilast was found to be 99.70 ± 0.23%. The % assay of active substance was found in a range 80.62 to 100. HPTLC and MS/MS method revealed possible degradation mechanism of 11 degradant products. Conclusion: The Proposed developed and validated HPTLC method was found to be more sensitive, simple, precise, accurate, cost effective and robust. This method could be applied for anal. of bulk drug and tablet formulation, degradation study. This degradation pathway of drug will help to identify the degradation products of Apremilast.

Journal of Pharmaceutical Sciences and Research published new progress about HPLC. 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, Electric Literature of 608141-42-0.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Lu, Yuting; Shen, Xiaoyue; Hang, Taijun; Song, Min published the artcile< Identification and characterization of process-related substances and degradation products in apremilast: Process optimization and degradation pathway elucidation>, Product Details of C12H19NO4S, the main research area is apremilast degradation product analysis LC MS process optimization; Apremilast; LC–MS; Process optimization; Related substances.

This study aims at investigating the separation, identification and characterization of related substances in apremilast by LC-MS hyphenated techniques, as well as the synthesis optimization and the degradation pathways elucidation. Forced degradation studies were conducted under the ICH prescribed stress conditions. The chromatog. separation was achieved on XBridge C18 column (4.6 mm × 150 mm, 3.5 μm) using a mobile phase consisting of water adjusted to pH 3.0 with formic acid as solvent A and acetonitrile as solvent B in linear gradient elution program. Twelve related substances were detected all together in apremilast and its stress samples. Their structures were identified mainly through pos. ESI high-resolution TOF-MS anal. of the parent ions’ accurate masses and elemental compositions, and the corresponding MS/MS spectra elucidation. There were three process-related substances and nine degradation products, seven of them were first reported. Two degradation products and one process-related substance were further verified by semi-preparation and NMR determination Their origins and formation mechanisms were also discussed, based on which effective approaches for the synthesis optimization were conducted. Therefore, the related substances investigation are valuable for apremilast manufacturing process optimization and quality control.

Journal of Pharmaceutical and Biomedical Analysis published new progress about Chromatography. 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, Product Details of C12H19NO4S.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Jana, Anupam; Zielinski, Grzegorz Krzysztof; Czarnocka-Sniadala, Sylwia; Grudzien, Krzysztof; Podwysocka, Dominika; Szulc, Marcin; Kajetanowicz, Anna; Grela, Karol published the artcile< Synthesis of Substituted β-Functionalised Styrenes by Microwave-Assisted Olefin Cross-Metathesis and Scalable Synthesis of Apremilast>, HPLC of Formula: 608141-42-0, the main research area is Apremilast scalable synthesis; styryl sulfone diastereoselective preparation; styrene diastereoselective cross metathesis vinyl sulfone microwave irradiation; allylbenzene isomerization deuteration cross metathesis vinyl sulfone.

Preparation of diversely substituted β-functionalized styrenes R1CH:CHR2 (R1 = Ph, 4-BrC6H4, 3-EtO-4-MeOC6H3, etc.; R2 = MeSO2, Et2NSO2, CHO, EtO2C, etc.) by microwave-assisted olefin cross-metathesis of styrenes R1CH:CH2 with functionalized terminal alkenes R2CH:CH2 is described. This method can be also employed in the synthesis of β-deuterated α,β-unsaturated sulfones from inexpensive allylbenzenes though unprecedented one-pot isomerization/deuteration/cross-metathesis sequence. One of such obtained cross-metathesis products has been utilized in a new scalable synthesis of Apremilast, a potent and orally active phosphodiesterase 4 and tumor necrosis factor-α inhibitor. The same strategy was used in synthesis of ent-Apremilast.

ChemCatChem published new progress about Cross-metathesis (stereoselective). 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, HPLC of Formula: 608141-42-0.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Mhlongo, Msizi I.; Piater, Lizelle A.; Dubery, Ian A. published the artcile< Profiling of Volatile Organic Compounds from Four Plant Growth-Promoting Rhizobacteria by SPME-GC-MS: A Metabolomics Study>, Reference of 608141-42-0, the main research area is PGPR volatile organic compound metabolomics profiling SPME GCMS; metabolomics profiling; multivariate data analysis (MVDA); plant growth promoting rhizobacteria (PGPR); solid-phase micro-extraction gas chromatography mass spectrometry (SPME–GC–MS); volatile organic compounds (VOCs).

The rhizosphere microbiome is a major determinant of plant health. Plant-beneficial or plant growth-promoting rhizobacteria (PGPR) influence plant growth, plant development and adaptive responses, such as induced resistance/priming. These new eco-friendly choices have highlighted volatile organic compounds (biogenic VOCs) as a potentially inexpensive, effective and efficient substitute for the use of agrochems. Secreted bacterial VOCs are low mol. weight lipophilic compounds with a low b.p. and high vapor pressures. As such, they can act as short- or long-distance signals in the rhizosphere, affecting competing microorganisms and impacting plant health. In this study, secreted VOCs from four PGPR strains (Pseudomonas koreensis (N19), Ps. fluorescens (N04), Lysinibacillus sphaericus (T19) and Paenibacillus alvei (T22)) were profiled by solid-phase micro-extraction gas chromatog. mass spectrometry (SPME-GC-MS) combined with a multivariate data anal. Metabolomic profiling with chemometric analyses revealed novel data on the composition of the secreted VOC blends of the four PGPR strains. Of the 121 annotated metabolites, most are known as bioactives which are able to affect metabolism in plant hosts. These VOCs belong to the following classes: alcs., aldehydes, ketones, alkanes, alkenes, acids, amines, salicylic acid derivatives, pyrazines, furans, sulfides and terpenoids. The results further demonstrated the presence of species-specific and strain-specific VOCs, characterized by either the absence or presence of specific VOCs in the different strains. These mols. could be further investigated as biomarkers for the classification of an organism as a PGPR and selection for agricultural use.

Metabolites published new progress about Acids Role: ANT (Analyte), PUR (Purification or Recovery), ANST (Analytical Study), PREP (Preparation). 608141-42-0 belongs to class ethers-buliding-blocks, and the molecular formula is C12H19NO4S, Reference of 608141-42-0.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem