253128-41-5Relevant articles and documents
PROCESS FOR THE PREPARATION OF ERIBULIN MESYLATE INTERMEDIATE
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Paragraph 0025, (2021/02/12)
The present application provides improved processes for the synthesis of eribulin intermediate, which generally comprise the steps of: a) De-protecting the eribulin-enone (compound 1) in tetrahydrofuran by using TBAF solution, buffered with imidazole HCl in the presence of molecular sieve and sodium sulphate to get an insitu mixture of eribulin-dione diastereomer at C12 carbon (compound 2). Then ketalization may be performed of eribulin-dione insitu intermediate containing mixture of diastereomer at C12 carbon (compound 2) with PPTS in dichloromethane to yield eribulin-diol (compound 3).
PROCESS FOR THE PREPARATION OF HIGH PURE ERIBULIN AND ITS MESYLATE SALT
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Page/Page column 9, (2020/06/19)
The present invention relates to a process for the preparation of high pure Eribulin and Eribulin Mesylate. The present invention involves preparation of high pure Eribulin and its mesylate salt involving chiral acid addition salts of Eribulin.
PROCESS FOR PREPARATION OF ERIBULIN AND INTERMEDIATES THEREOF
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, (2020/05/19)
The present application relate to crystalline azide compound of formula (II) which is used as an intermediate for the preparation of halichondrin B analogues such as eribulin or pharmaceutically acceptable salts thereof. The present application also covers purification process of azide compound of formula (II) and its further conversion to eribulin or a pharmaceutically acceptable salts thereof.
PURIFICATION PROCESS FOR PREPARATION OF ERIBULIN AND INTERMEDIATES THEREOF
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Page/Page column 22, (2020/02/14)
The present application relate to a purification process for preparation of halichondrin B analogues such as eribulin or pharmaceutically acceptable salts thereof having less than 0.15% or substantially free or free from one or more impurities. The present application also provide acid addition salts of eribulin and process for preparation thereof.
Intermediate for preparing Eribulin and preparation method thereof
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Paragraph 0217; 0218; 0220; 0221; 0239, (2019/05/11)
The invention relates to an intermediate for preparing Eribulin and a preparation method of the intermediate. Specifically, the method comprises the following steps: selectively removing 1,2-hydroxylprotecting groups, so that the 1,2-hydroxyl structure is selectively converted; the whole process steps are simple, the operation is simple and convenient, and the method is suitable for industrial mass production requirements.
SYNTHETIC PROCESS FOR PREPARATION OF MACROCYCLIC C1-KETO ANALOGS OF HALICHONDRIN B AND INTERMEDIATES USEFUL THEREIN INCLUDING INTERMEDIATES CONTAINING -SO2-(P-TOLYL) GROUPS
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Paragraph 0059; 00117; 00118, (2015/01/16)
Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, R7, R7', R8, R9, R10, R11, R12 and R13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed.
MACROCYCLIZATION REACTIONS AND INTERMEDIATES USEFUL IN THE SYNTHESIS OF ANALOGS OF HALICHONDRIN B
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Page/Page column 124, (2015/05/19)
The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.
METHODS USEFUL IN THE SYNTHESIS OF HALICHONDRIN B ANALOGS
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Paragraph 0082; 0083, (2015/06/17)
In general, the present invention features improved methods useful for the synthesis of analogs of halichondrin B, such as eribulin and pharmaceutically acceptable salts thereof (e.g., eribulin mesylate).
Commercial manufacture of halaven: Chemoselective transformations en route to structurally complex macrocyclic ketones
Austad, Brian C.,Calkins, Trevor L.,Chase, Charles E.,Fang, Francis G.,Horstmann, Thomas E.,Hu, Yongbo,Lewis, Bryan M.,Niu, Xiang,Noland, Thomas A.,Orr, John D.,Schnaderbeck, Matthew J.,Zhang, Huiming,Asakawa, Naoki,Asai, Naoki,Chiba, Hiroyuki,Hasebe, Takashi,Hoshino, Yorihisa,Ishizuka, Hiroyuki,Kajima, Takashi,Kayano, Akio,Komatsu, Yuki,Kubota, Manabu,Kuroda, Hirofumi,Miyazawa, Mamoru,Tagami, Katsuya,Watanabe, Tomohiro
, p. 333 - 337 (2013/04/23)
The evolution of the synthesis of Halaven (E7389, INN eribulin mesylate) from a medicinal chemistry process to the execution of the final process on pilot scale is described. The completion of the synthesis of Halaven from C1-C13 ester and C14-C35 sulfone alcohol involves a series of chemo-, regio-, and stereoselective transformations. Furthermore, a high-dilution macrocyclization presented a number of challenges for industrial-scale manufacture (throughput, processing time, and side reactions). This paper describes studies at Eisai leading to an understanding, optimization, and control of the chemistry that realized the reproducible commercial production of Halaven.
Macrocyclic ketone analogues of halichondrin B
Zheng, Wanjun,Seletsky, Boris M.,Palme, Monica H.,Lydon, Paul J.,Singer, Lori A.,Chase, Charles E.,Lemelin, Charles A.,Shen, Yongchun,Davis, Heather,Tremblay, Lynda,Towle, Murray J.,Salvato, Kathleen A.,Wels, Bruce F.,Aalfs, Kimberley K.,Kishi, Yoshito,Littlefield, Bruce A.,Yu, Melvin J.
, p. 5551 - 5554 (2007/10/03)
Synthesis and SAR studies of structurally simplified analogues of marine natural product halichondrin B resulted in the discovery of E7389, a new potential antitumor agent currently undergoing Phase I clinical trials. Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.