CA2868627C - Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein - Google Patents

Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein Download PDF

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Publication number
CA2868627C
CA2868627C CA2868627A CA2868627A CA2868627C CA 2868627 C CA2868627 C CA 2868627C CA 2868627 A CA2868627 A CA 2868627A CA 2868627 A CA2868627 A CA 2868627A CA 2868627 C CA2868627 C CA 2868627C
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group
protecting group
compound
formula
silyl
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French (fr)
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CA2868627A1 (en
Inventor
Fabio E.S. Souza
Alena Rudolph
Ming PAN
Boris Gorin
Teng Ko NGOOI
Jason A. BEXRUD
Ricardo Orprecio
Huzaifa RANGWALA
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Alphora Research Inc
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Alphora Research Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
    • C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C309/04—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing only one sulfo group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Furan Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Peptides Or Proteins (AREA)
CA2868627A 2012-03-30 2013-03-28 Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein Active CA2868627C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261618004P 2012-03-30 2012-03-30
US61/618,004 2012-03-30
US201261647127P 2012-05-15 2012-05-15
US61/647,127 2012-05-15
PCT/CA2013/050254 WO2013142999A1 (en) 2012-03-30 2013-03-28 Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein

Publications (2)

Publication Number Publication Date
CA2868627A1 CA2868627A1 (en) 2013-10-03
CA2868627C true CA2868627C (en) 2021-02-16

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CA2868627A Active CA2868627C (en) 2012-03-30 2013-03-28 Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein

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US (2) US9278979B2 (https=)
EP (1) EP2831082B1 (https=)
JP (1) JP6531911B2 (https=)
CN (1) CN104334562A (https=)
AU (1) AU2013239290B2 (https=)
CA (1) CA2868627C (https=)
IN (1) IN2014MN02106A (https=)
WO (1) WO2013142999A1 (https=)

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RU2489437C2 (ru) 2007-10-03 2013-08-10 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Промежуточные соединения и способы синтеза аналогов галихондрина в
WO2011094339A1 (en) 2010-01-26 2011-08-04 Eisai R&D Management Co., Ltd. Furo [3, 2 -b] pyrane derivatives useful in the synthesis of halichondrin b analogs
EP2785687B1 (en) 2011-11-30 2019-02-20 Sandoz AG Process for preparation of (3r)-2,4-di-leaving group-3-methylbut-1-ene
CN104024237B (zh) 2011-12-16 2016-02-24 阿方拉研究股份有限公司 用于制备3-((2s,5s)-4-亚甲基-5-(3-氧代丙基)四氢呋喃-2-基)丙醇衍生物的方法及其有用的中间体
CN104080793B (zh) 2011-12-29 2017-09-19 阿方拉研究股份有限公司 2‑((2s,3s,4r,5r)‑5‑((s)‑3‑氨基‑2‑羟基丙‑1‑基)‑4‑甲氧基‑3‑(苯磺酰甲基)四氢呋喃‑2‑基)乙醛衍生物以及它们的制备方法
CA2916537C (en) * 2013-07-03 2021-07-27 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein including intermediates containing -so2-(p-tolyl) groups
CN103483352A (zh) * 2013-10-18 2014-01-01 李友香 抗肿瘤的药用原料药
EP3689881B1 (en) * 2013-11-04 2022-01-12 Eisai R&D Management Co., Ltd. Macrocyclization reactions and intermediates useful in the synthesis of analogs of halichondrin b
MX384292B (es) 2013-12-06 2025-03-14 Eisai R&D Man Co Ltd Metodos utiles en la sintesis de analogos de halicondrina b.
TW201617326A (zh) * 2014-03-06 2016-05-16 Ａｌｐｈｏｒａ研發股份有限公司 （ｓ）－１－（（２ｒ，３ｒ，４ｓ，５ｓ）－５－烯丙－３－甲氧－４－（對甲苯磺醯甲基）四氫呋喃－２－基）－３－氨基丙－２－醇之結晶衍生物
US10556910B2 (en) 2014-06-30 2020-02-11 President And Fellows Of Harvard College Synthesis of halichondrin analogs and uses thereof
CN105713031B (zh) * 2014-12-05 2021-05-07 正大天晴药业集团股份有限公司 一种用于制备艾日布林的中间体及其制备方法
US10344038B2 (en) 2015-04-30 2019-07-09 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
KR102743950B1 (ko) 2015-05-07 2024-12-18 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 마크롤라이드의 합성에 유용한 마크로고리화 반응 및 중간체 및 기타 단편
EP3413887B1 (en) 2016-02-12 2021-04-07 Eisai R&D Management Co., Ltd. Intermediates in the synthesis of eribulin and related methods of synthesis
EP3423105B1 (en) 2016-03-02 2021-05-05 Eisai R&D Management Co., Ltd. Eribulin-based antibody-drug conjugates and methods of use
KR20190009326A (ko) * 2016-05-26 2019-01-28 닥터 레디스 레보러터리즈 리미티드 에리불린 및 그의 중간체의 제조방법
US11136335B2 (en) 2016-06-30 2021-10-05 Eisai R&D Management Co., Ltd. Prins reaction and intermediates useful in the synthesis of halichondrin macrolides and analogs thereof
JP6978758B2 (ja) 2016-11-11 2021-12-08 プレジデント アンド フェローズ オブ ハーバード カレッジ パラジウム媒介ケトール化
CN110167536A (zh) 2016-11-23 2019-08-23 雷迪博士实验室有限公司 艾日布林及其中间体的制备方法
CN108658956B (zh) * 2017-03-28 2021-02-02 上海时莱生物技术有限公司 艾日布林中间体及其制备方法
ES2931533T3 (es) 2017-04-05 2022-12-30 Harvard College Compuesto macrocíclico y usos del mismo
US9938288B1 (en) 2017-04-05 2018-04-10 President And Fellows Of Harvard College Macrocyclic compound and uses thereof
CN108948064B (zh) * 2017-05-17 2021-02-02 上海时莱生物技术有限公司 一种艾日布林中间体及其制备方法
WO2018217894A1 (en) * 2017-05-24 2018-11-29 Eisai R&D Management Co., Ltd. Fluorine-labelled halichondrin derivatives and related methods of synthesis
US11498892B2 (en) 2017-07-06 2022-11-15 President And Fellows Of Harvard College Fe/Cu-mediated ketone synthesis
HUE061306T2 (hu) * 2017-07-06 2023-06-28 Harvard College Halikondrinok szintézise
CN111566113B (zh) 2017-11-15 2024-01-09 哈佛大学的校长及成员们 大环化合物及其用途
SG11202005548WA (en) * 2018-01-03 2020-07-29 Eisai R&D Man Co Ltd Prins reaction and compounds useful in the synthesis of halichondrin macrolides and analogs thereof
IL279168B (en) * 2020-12-02 2022-04-01 Finetech Pharmaceutical Ltd A process for the preparation of eribulin
CN114213429B (zh) * 2021-12-22 2023-06-20 苏州正济药业有限公司 一种甲磺酸艾立布林杂质的制备方法
KR20250133788A (ko) * 2023-01-17 2025-09-08 시스트이뮨, 인코포레이티드 에리불린 약물 접합체

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US5338865A (en) 1992-03-12 1994-08-16 President And Fellows Of Harvard College Synthesis of halichondrin B and norhalichondrin B
RU2153491C2 (ru) 1993-07-09 2000-07-27 Лаборатуар Терамекс С.А. Аналоги витамина d, соединения, способы их получения и фармацевтическая композиция
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US20060045846A1 (en) * 2004-08-30 2006-03-02 Horstmann Thomas E Reagents and methods for labeling terminal olefins
CN105801599A (zh) * 2008-04-04 2016-07-27 卫材R&D管理有限公司 软海绵素b类似物
EP2785687B1 (en) 2011-11-30 2019-02-20 Sandoz AG Process for preparation of (3r)-2,4-di-leaving group-3-methylbut-1-ene
CN104024237B (zh) 2011-12-16 2016-02-24 阿方拉研究股份有限公司 用于制备3-((2s,5s)-4-亚甲基-5-(3-氧代丙基)四氢呋喃-2-基)丙醇衍生物的方法及其有用的中间体
CN104080793B (zh) 2011-12-29 2017-09-19 阿方拉研究股份有限公司 2‑((2s,3s,4r,5r)‑5‑((s)‑3‑氨基‑2‑羟基丙‑1‑基)‑4‑甲氧基‑3‑(苯磺酰甲基)四氢呋喃‑2‑基)乙醛衍生物以及它们的制备方法
AR096238A1 (es) 2013-05-15 2015-12-16 Alphora Res Inc Proceso para preparar derivados de 3-((2s,5s)-4-metilen-5-(3-oxopropil)tetrahidrofuran-2-il)propanol e intermediarios útiles para el mismo

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Publication number Publication date
EP2831082A4 (en) 2016-01-06
US9695187B2 (en) 2017-07-04
CN104334562A (zh) 2015-02-04
WO2013142999A1 (en) 2013-10-03
EP2831082B1 (en) 2019-02-20
CA2868627A1 (en) 2013-10-03
US20160152631A1 (en) 2016-06-02
US9278979B2 (en) 2016-03-08
AU2013239290A1 (en) 2014-10-30
JP6531911B2 (ja) 2019-06-19
US20150065733A1 (en) 2015-03-05
JP2015512897A (ja) 2015-04-30
IN2014MN02106A (https=) 2015-09-11
EP2831082A1 (en) 2015-02-04
AU2013239290B2 (en) 2017-08-03

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