N-[2-[(1S)-1-(3-Ethoxy-4-Methoxyphenyl)(Methylthio)Ethyl]-2,3-Dihydro-1,3-Dioxo-1H-Isoindol-4-Yl]Acetamide置于溶剂黄146,Sodium Tungstate (Vi) Dihydrate,双氧水体系中,用 乙腈 作为反应溶剂,化学反应 7.0H,以91%的收率获得产物阿普斯特 参考文献: Processes For The Preparation Of Apremilast And Intermediates Thereof[fr] Procédés De Préparation D'Aprémilast,Et Ses Intermédiaires 标题: Processes For The Preparation Of Apremilast And Intermediates Thereof[fr] Procédés De Préparation D'Aprémilast,Et Ses Intermédiaires 摘要:披露了用于制备阿普雷米拉斯特及其中间体的制备过程.
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-2025206743-A1 优先权日:2022-03-25 标 题:Tyk2 inhibitor synthesis and intermediates thereof 发明人:MASSE CRAIG E; PHADKE AVINASH S; LAWSON JON P; LEVY STUART; YANG XIAOWEI; WU GUISHENG; FAN SHUFENG 权利人:TAKEDA PHARMACEUTICALS CO 摘要:Described herein are methods of synthesis of a tyrosine-protein kinase 2 (TYK2) inhibitor and to intermediate compounds of the synthesis and methods of making the intermediates. Also provided are pharmaceutically acceptable compositions including compounds prepared by the synthetic method and methods of treating disorders using the same.
专利号:WO-2016192694-A1 优先权日:2015-06-05 标 题 :A process for preparing the key intermediate of apremilast, using enzymatic resolution of the racemic amines 发明人:DOUBSKY JAN; KLVANA ROBERT; RICHTER JINDRICH; Lehnert Petr 权利人:ZENTIVA KS 摘要:The invention relates to a preparation method of (S)-l-(3-ethoxy-4-methoxyphenyl)- 2-(methylsulfonyl)-ethyl-amine (S)-l, or its N-acyl derivatives of general formula (S)-2. The amine (S)-l is the key intermediate in the synthesis of (S)-{2-[l-(3-ethoxy-4- methoxyphenyi)-2-methyisulfonylethyl]-4-acetylaminoisoindolin-l ?3-dione, known as Apremilast. In this synthesis, the amine (S)-l, or its respective salts, are subjected to condensation with 3-acetamidophthalic anhydride 4, providing the desired product 3 (Scheme 1).
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-8242310-B2 优先权日:2008-09-10 标题:Processes for the preparation of aminosulfone compounds 发明人:SAINDANE MANOHAR T; GE CHUANSHENG 权利人:SAINDANE MANOHAR T; GE CHUANSHENG; CELGENE CORP 摘要:Processes for synthesizing aminosulfone compounds are provided. Aminosulfone compounds obtained using methods provided herein are useful in production or synthesis of isoindoline based PDE 4 modulators.
1: Nassim D, Alajmi A, Jfri A, Pehr K. Apremilast in dermatology: A review of literature. Dermatol Ther. 2020 Nov;33(6):e14261. doi: 10.1111/dth.14261. Epub 2020 Sep 27. 88(1):40-51. doi: 10.1016/j.jaad.2022.08.061. Epub 2022 Sep 14. 155(4):421-433. doi: 10.23736/S0392-0488.20.06684-5. Epub 2020 Jun 15. 77(4):459-472. doi: 10.1007/s40265-017-0709-1. 31(2):131-140. doi: 10.1080/09546634.2019.1589641. Epub 2019 Apr 2. 6: Hatemi G, Mahr A, Ishigatsubo Y, Song YW, Takeno M, Kim D, Melikoğlu M, Cheng S, McCue S, Paris M, Chen M, Yazici Y. Trial of Apremilast for Oral Ulcers in Behçet's Syndrome. N Engl J Med. 2019 Nov 14;381(20):1918-1928. doi: 10.1056/NEJMoa1816594. 86(1):77-85. doi: 10.1016/j.jaad.2021.07.040. Epub 2021 Jul 31. 155(4):386-399. doi: 10.23736/S0392-0488.20.06640-7. 73(1):37-49. doi: 10.1016/j.jaad.2015.03.049. 107(4):216-220. doi: 10.12788/cutis.0231. 158(12):1357-1366. doi: 10.1001/jamadermatol.2022.3917. 12: Chimenti MS, Gramiccia T, Saraceno R, Bianchi L, Garofalo V, Buonomo O, Perricone R, Chimenti S, Chiricozzi A. Apremilast for the treatment of psoriasis. Expert Opin Pharmacother. 2015;16(13):2083-94. doi: 10.1517/14656566.2015.1076794. Epub 2015 Aug 4. 36(2):237-246. doi: 10.1111/jdv.17769. Epub 2021 Nov 13.
合成参考文献
摘要: 摘要:DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 6, 2015: 摘要:European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP), European Public Assessment Report (EPAR): Otezla (Apremilast) p.27 (November 20, 2014). Available from, as of February 26, 2015: 摘要:European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP), European Public Assessment Report (EPAR): Otezla (Apremilast) p.35 (November 20, 2014). Available from, as of February 26, 2015: 摘要:Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829210