CAS: 934660-93-2; (S)-(3,4-Difluoro-2-((2-Fluoro-4-Iodophenyl)Amino)Phenyl)(3-Hydroxy-3-(Piperidin-2-yl)Azetidin-1-yl)Methanone

该化合物是主要用于癌症治疗,特别是治疗黑素瘤的小型分子抑制剂,它作为单体活性蛋白质动脉(MAPK)路径的选择性抑制剂,具体针对MEK1和MEK2酶,它们对于细胞扩散和存活具有关键作用.C16H15ClF2N3O2是Cbimetinib的化学配方,其分子重量约为359.76克/摩尔.Cobimetinib通常口服,并经常与其他疗法(如Vemurafenib)结合使用,以提高治疗效力.其行动机制包括阻断信号路径,促进肿瘤生长,从而抑制癌症细胞扩散.该物质的特点在于其中度溶性在有机溶剂中,水溶性相对较低.副作用可能包括胃肠扰动,皮肤反应和肝酶升高,因此在治疗期间需要仔细监测.Comelitinib以品牌Cotelic为品牌,并被批准用于特定患者的基因标记.

结构式图片

上下游产品

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid 1,1-dimethylethyl (2S)-2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylate 1,1-dimethylethyl (2S)-2-(3-hydroxyazetidin-3-yl)piperidine-1-carboxylate 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride

合成工艺路线路线简述

  • 2114329-15-4 + 934660-67-0 = 934660-93-2
    反应条件:1.1 Reagents: Ammonium Chloride Catalysts: Zinc Solvents: Tetrahydrofuran,Water; Rt; 9 H,Rt
    标题:Preparation Method Of Cobimetinib Via Oxidative Coupling Cyclization,Acylation And Addition Reaction
    参考文献:China]

    2114329-14-3 + 934660-67-0 = 934660-93-2
    反应条件:1.1 Reagents: Ammonium Chloride Catalysts: Zinc Solvents: Tetrahydrofuran,Water; Rt; 7.2 H,Rt
    标题:Process For Preparation Of Cobimetinib
    参考文献:China]

    2065147-70-6 + 29632-74-4 = 934660-93-2
    反应条件:1.1 Reagents: Lithium Bis(Trimethylsilyl)Amide Solvents: Tetrahydrofuran; 88 Min,20 - 30 °C; 2 H,20 - 30 °C1.2 Reagents: Sulfuric Acid Solvents: Water; 25 Min,20 - 30 °C; 1 H,20 - 30 °C
    标题:Preparation Of Crystalline Fumarate Salt Of (S)-[3,4-Difluoro-2-(2-Fluoro-4-Iodophenylamino)Phenyl] [3-Hydroxy-3-(Piperidin-2-Yl)Azetidin-1-Yl]-Methanone
    参考文献:World Intellectual Property Organization]

    29632-74-4 + 1597407-59-4 = 934660-93-2
    反应条件:1.1 Reagents: Lithium Bis(Trimethylsilyl)Amide Solvents: Tetrahydrofuran; 88 Min,20 °C -> 30 °C; 2 H,30 °C1.2 Reagents: Sulfuric Acid Solvents: Water; 25 Min,Rt; 1 H,Rt
    标题:Preparation Of Phenylaminophenylhydroxypiperidinylazetidinylmethanone Derivatives For Use As Mek Inhibitors
    参考文献:World Intellectual Property Organization]

    934664-19-4 + 934666-39-4 = 934660-93-2
    反应条件:1.1 Reagents: Diisopropylethylamine Solvents: Tetrahydrofuran; Overnight,Rt1.2 Reagents: Hydrochloric Acid Solvents: Methanol,1,4-Dioxane; 2 H,55 °C
    标题:Novel Carboxamide-Based Allosteric Mek Inhibitors: Discovery And Optimization Efforts Toward Xl518 (Gdc-0973)
    作者:Rice,Kenneth D.; Aay,Naing; Anand,Neel K.; Blazey,Charles M.; Bowles,Owen J.; Et Al
    参考文献:Acs Medicinal Chemistry Letters 日期:2012 卷标:3(5) 页码:416-421]

    934663-52-2 = 934660-93-2
    反应条件:1.1 Reagents: Trifluoroacetic Acid,Triethylsilane Solvents: Dichloromethane; 0 °C; 3 H,0 °C
    标题:Strain-Release-Driven Homologation Of Boronic Esters: Application To The Modular Synthesis Of Azetidines
    作者:Fawcett,Alexander; Murtaza,Amna; Gregson,Charlotte H. U.; Aggarwal,Varinder K.
    参考文献:Journal Of The American Chemical Society 日期:2019 卷标:141(11) 页码:4573-4578]

    2035072-28-5 + 29632-74-4 = 934660-93-2
    反应条件:1.1 Reagents: Diisopropylethylamine Solvents: Tetrahydrofuran; 8 H,50 °C
    标题:Method For Synthesizing Cobimetinib
    参考文献:China]

    934663-52-2 = 934660-93-2
    反应条件:1.1 Reagents: Hydrochloric Acid Solvents: Methanol,Water; Rt; 1 H,Rt1.2 Reagents: Potassium Carbonate Solvents: Water; Ph 8 - 9,Rt
    标题:Method For Synthesizing (S)-3-(Piperidine-2-Yl)-Azetidine-3-Ol
    参考文献:China]

    934663-52-2 = 934660-93-2
    反应条件:1.1 Reagents: Hydrochloric Acid Solvents: Methanol; Rt; 4 H,Rt1.2 Reagents: Sodium Bicarbonate Solvents: Water; Ph 8 - 9
    标题:A Preparation Method Of Derivative Of 3-(Piperidin-2-Yl)-Azetidin-3-Ol And Application Thereof
    参考文献:China]

    391211-97-5 + 934666-39-4 = 934660-93-2
    反应条件:1.1 Catalysts: Pybop Solvents: Dimethylformamide; 30 Min1.2 Reagents: Diisopropylethylamine; Rt -> 50 °C; 34 H,45 - 50 °C
    标题:Process For The Preparation Of Cobimetinib
    参考文献:World Intellectual Property Organization]

    = 934660-93-2 [标题:Reaction Conditions
    标题:Preparation Of The Prodrug Compound And Their Medical Applications
    参考文献:World Intellectual Property Organization]

    = 934660-93-2 [标题:Reaction Conditions
    标题:Process For The Production Of Cobimetinib
    参考文献:World Intellectual Property Organization
2-(2-氟-4-碘苯胺)-3,4-二氟苯甲酸置于4-二甲氨基吡啶,氯化铵,盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺,锌体系中,用 二氯甲烷,水 作为反应溶剂,化学反应 16.2H,反应生成 考比替尼
参考文献:一种卡比替尼的化学合成方法
标题:一种卡比替尼的化学合成方法
摘要:本发明属于化学合成领域,具体涉及一种卡比替尼的制备方法.该方法以2,3,4‑三氟苯甲酸苄酯为起始原料,通过取代反应,脱保护反应,酰胺化反应,催化加成反应等步骤得到卡比替尼.该方法原料价廉易得,工艺路线段,工反应过程易于操作,收率高,且环境友好,适合工业化大批量生产.

海关参考信息

专利信息


专利号:US-12391691-B2
优先权日:2018-11-16
标题:Synthesis of key intermediate of KRAS G12C inhibitor compound
发明人:PARSONS ANDREW THOMAS; COCHRAN BRIAN MCNEIL; POWAZINIK IV WILLIAM; CAPORINI MARC ANTHONY
权利人:AMGEN INC
摘要:The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure n nuseful for the synthesis of compounds that target KRAS G12C mutations, such as

专利号:US-2025206736-A1
优先权日:2019-11-14
标题 :Synthesis of kras g12c inhibitor compound
发明人:CORBETT MICHAEL THOMAS; CAILLE SEBASTIEN
权利人:AMGEN INC
摘要:The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2-isopropyl-4-methylpyridin-3-amine, useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.

专利号:US-2022233673-A1
优先权日:2019-06-04
标 题:METHODS OF PRODUCING SHIGA TOXIN B-SUBUNIT (STxB) MONOMERS AND OLIGOMERS, AND USES THEREOF
发明人:BILLET ANNE; SCHMIDT FRÉDÉRIC; JOHANNES LUDGER; SERVENT DENIS; MOURIER GILLES; TARTOUR ÉRIC; KAY MICHAEL; FULCHER JAMES M
权利人:INST CURIE; CENTRE NAT RECH SCIENT; INST NAT SANTE RECH MED; COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES CEA; APHP ASSIST PUBLIQUE HOPITAUX DE PARIS; UNIV PARIS; UNIV OF UTAH RESEARCH FOUDATION; UNIV UTAH RES FOUND
摘要:A method of producing a monomer of a Shiga toxin B-subunit (STxB) protein or of a variant thereof by peptide chemical synthesis, as well as to a method of producing a pentamer of the STxB protein or of the variant thereof. The methods are particularly advantageous as they overcome major issues typically observed in peptide chemical synthesis, including solubility and purity issues.

专利号:US-11612610-B2
优先权日:2018-12-14
标题:Mito-magnolol compounds and methods of synthesis and use thereof
发明人:KALYANARAMAN BALARAMAN; ZIELONKA JACEK MICHAL; CHENG GANG; HARDY MICAEL JOËL; OUARI OLIVIER
权利人:MEDICAL COLLEGE WISCONSIN INC; AIX MARSEILLE UNIV; MEDICAL COLLEGE OF WISCONSIN INC
摘要:The present invention provides mito-magnolol compounds, pharmaceutical compositions thereof, and methods of using the mito-magnolol compounds in the treatment of cancer, especially anti-cancer therapy or kinase resistant cancers.

专利号:US-2022118094-A1
优先权日:2019-02-21
标题:Synthesis of biomimetic cell wall structure
发明人:WANG YONG; SHI PENG
权利人:PENN STATE RES FOUND
摘要:The present invention relates generally to methods of generating a biomimetic cell wall (BCW) on a target surface, compositions comprising the BCW, and methods of use of the compositions, including biomedical applications of the BCW coated compositions.

专利号:US-2025289827-A1
优先权日:2022-12-02
标 题:Morphic forms of a mutant braf degrader and methods of manufacture thereof
发明人:YU ROBERT T; HE MINSHENG; SCHNADERBECK MATTHEW J; KREGER BRIDGET; POLLOCK ROY MACFARLANE; JIANG SIYI; LI MEIQI; CHEN BOLU; LU JIANNAN
权利人:C4 THERAPEUTICS INC
摘要:Advantageous isolated morphic forms of (3R)-3-[6-[2-cyano-3-[[ethyl(methyl)sulfamoyl]amino]-6-fluorophenoxy]-4-oxoquinazolin-3-yl]-8-[2-[1-[3-(2,4-dioxo-1,3-diazinan-1-yl)-5-fluoro-1-methylindazol-6-yl]-4-hydroxypiperidin-4-yl]acetyl]-1-oxa-8-azaspiro[4.5]decane (Compound 1), which is a mutant BRAF degrader, and methods to prepare Compound 1 morphic forms for therapeutic applications are provided in the invention. The invention also provides improved methods for the synthesis of Compound 1, new pharmaceutical compositions comprising Compound 1, and new uses of Compound 1.
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✅ COA系统入驻 | 共享模式

主要参考文献


1: Krens S, van der Meulen E, Jansman FGA, Burger DM, van Erp NP. Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC-MS/MS. Biomed Chromatogr. 2019 Nov
22:e4758. doi: 10.1002/bmc.4758. [Epub ahead of print] doi: 10.4103/ijo.IJO_2025_18. Available from http://www.ncbi.nlm.nih.gov/books/NBK548657/ doi: 10.1002/ccr3.2297. eCollection 2019 Oct.
8: Sorich MJ, Rowland A, Hopkins AM. Validation of dabrafenib-trametinib prognostic groups in patients treated with vemurafenib and cobimetinib for advanced BRAF-mutated melanoma. Melanoma Res. 2019 Aug 14. doi: 10.1097/CMR.0000000000000634. [Epub ahead of print] doi: 10.1038/s41416-019-0546-y. Epub 2019 Aug 16. doi: 10.1111/exd.14010. Epub 2019 Aug 19. doi: 10.1177/2050313X19847358. eCollection 2019.

合成参考文献


摘要:S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (2021) DOI:10.1021/acsenvironau.1c00008. List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355
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