A concise synthesis of Fingolimod: an orally available drug for treating multiple sclerosis

Yan, Ning; Chen, Kai; Bai, Xinfa; Bi, Lei; Yao, Lei

doi:10.1186/s13065-015-0081-8

Cited by 2 publications

(2 citation statements)

References 15 publications

(8 reference statements)

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“…The developed procedure showed that TES could reduce only the carbonyl group without cleaving the halogen. Subsequent contributions reported the selectivities of TES/TFA 30 and TES/B(C 6 F 5 ) 3 systems 27 (see Scheme 16) for similar ketones bearing nitroalkyl and alkoxy substituents (51b), respectively. It is worth mentioning that a TES/Pd(OAc) 2 /TfOSiR 3 catalytic system was employed for the safe conversion of C=S bonds in the syntheses of imidazolinium salts, which are potent ligands and catalysts.…”

Section: Scheme 13 Tes/tfa-mediated Reduction Of Ketones To Alcoholsmentioning

confidence: 99%

Recent Advances in the Applications of Triethylsilane in Organic Synthesis

Ručilová

Soural

2018

Synthesis

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The synthesis of pharmacologically relevant scaffolds is an important goal in modern organic chemistry. For this reason, the use of methodologies involving operationally simple procedures and easily handled reagents to chemoselectively and stereoselectively convert different functionalities has gained considerable attention. In this review, we summarize the latest trends in reductive reactions using triethylsilane as the key reagent that provide synthetically interesting intermediates, coupling products and structures with control of the 3D architecture.1 Introduction2 Scenario A: Reduction of C–C Multiple Bonds3 Scenario B: Reduction of Functional Groups4 Scenario C: Reductive Coupling5 Scenario D: Reductive Cyclization6 Conclusion

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Section: Scheme 13 Tes/tfa-mediated Reduction Of Ketones To Alcoholsmentioning

confidence: 99%

Recent Advances in the Applications of Triethylsilane in Organic Synthesis

Ručilová

Soural

2018

Synthesis

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“…Different synthetic pathways could be used to manufacture fingolimod, which may add other potential process‐related impurities depending on the manufacturing process, starting materials and intermediates used (Adachi et al, 1995; Kiuchi et al, 2000; Durand et al, 2000; Kalita et al, 2001; Seidel et al, 2004; Sugiyama et al, 2005; Kim et al, 2006; Matsumoto et al, 2008; Calzavara & McNulty, 2011; Feng et al, 2012; Kandagatla et al, 2013; Shaikh et al, 2015; Yan et al, 2015; Balaev et al, 2017; Maruthi Raju et al, 2017a, 2017b; Lin et al, 2018; Vinigari et al, 2019). To the prove the absence of additional impurities and ensure drug substance quality according to International Conference on Harmonization (ICH) guideline Q3A, potential process‐related impurities should be evaluated and pharmacopoeia methods should be validated by the addition of these impurities, or in‐house methods should be developed and validated including all pharmacopoeia and in‐house impurities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and control of eight process‐related and two genotoxic fingolimod impurities by a validated RP‐UPLC method

Atici¹,

Yazar²,

Rıdvanoğlu³

2022

Biomedical Chromatography

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An HPLC method has been described in the European Pharmacopoeia and United States Pharmacopeia for the determination of nine organic impurities (imp A-I) in fingolimod hydrochloride, a synthetic sphingosine-1-phosphate receptor modulator. The manufacturing process of fingolimod hydrochloride consists of multistep chemical synthesis wherein controls of precursors, intermediates and process steps should be performed to assure the final quality of the drug substance. We synthesized and isolated eight process-related impurities (FINI imp A-H) of fingolimod, which were different from the pharmacopoeial impurities. One unknown processrelated impurity was found as a key intermediate (FINI) and was identified by LC-MS. Characterization of all of the impurities were done using spectroscopic techniques ( 1 H and 13 C NMR, FTIR, MS), and the mechanistic pathways to the formation of these impurities were also discussed. Two of these impurities were evaluated as potential genotoxic impurities owing to their alerting structures and alkylating properties (alkyl sulfonates and alkyl halides, class 3, ICH M7). We also developed and validated an RP-UPLC method in line with ICH Q2 guidelines for control these impurities (FINI imp A-H) and to assure the pharmacopoeial quality drug substance.

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A concise synthesis of Fingolimod: an orally available drug for treating multiple sclerosis

Cited by 2 publications

References 15 publications

Recent Advances in the Applications of Triethylsilane in Organic Synthesis

Recent Advances in the Applications of Triethylsilane in Organic Synthesis

Synthesis, characterization and control of eight process‐related and two genotoxic fingolimod impurities by a validated RP‐UPLC method

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