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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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/22Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01Sulfonic acids
    • C07C309/02Sulfonic acids having sulfo groups bound to acyclic carbon atoms
    • C07C309/03Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C309/04Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing only one sulfo group
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04Heterocyclic 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
    • C07D307/18Heterocyclic 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
    • C07D307/20Oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D407/00Heterocyclic 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
    • C07D407/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04Ortho-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 (h)
EP (1) EP2831082B1 (h)
JP (1) JP6531911B2 (h)
CN (1) CN104334562A (h)
AU (1) AU2013239290B2 (h)
CA (1) CA2868627C (h)
IN (1) IN2014MN02106A (h)
WO (1) WO2013142999A1 (h)

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USRE46965E1 (en) 2004-06-03 2018-07-24 Eisai R&D Management Co., Ltd. Intermediates for the preparation of analogs of Halichondrin B
SG10201811715YA (en) 2007-10-03 2019-02-27 Eisai R&D Man Co Ltd Intermediates and methods for the synthesis of halichondrin b analogs
RU2579511C2 (ru) 2010-01-26 2016-04-10 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Производные фуро[3,2-в]пирана, применимые в синтезе аналогов
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
US9062020B2 (en) 2011-12-29 2015-06-23 Alphora Research Inc. 2-((2S,3S,4R,5R)-5-((S)-3-amino-2-hydroxyprop-1-yl)-4-methoxy-3-(phenylsulfonylmethyl)tetrahydrofuran-2-yl)acetaldehyde derivatives and process for their preparation
US9850254B2 (en) * 2013-07-03 2017-12-26 Sandoz Ag 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
US9783549B2 (en) 2013-11-04 2017-10-10 Eisai R&D Management Co., Ltd. Macrocyclization reactions and intermediates useful in the synthesis of analogs of halichondrin B
EP3505520A1 (en) 2013-12-06 2019-07-03 Eisai R&D Management Co., Ltd. Methods useful in the synthesis of halichondrin b analogs
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
WO2016003975A1 (en) 2014-06-30 2016-01-07 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
KR20250012090A (ko) * 2015-05-07 2025-01-23 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 마크롤라이드의 합성에 유용한 마크로고리화 반응 및 중간체 및 기타 단편
CN108601760A (zh) 2016-02-12 2018-09-28 卫材R&D管理有限公司 艾日布林的合成中的中间体及相关的合成方法
PE20231050A1 (es) 2016-03-02 2023-07-11 Eisai Randd Man Co Ltd Conjugados de anticuerpo y farmaco basados en eribulina y metodos para su uso
US11059799B2 (en) 2016-05-26 2021-07-13 Dr. Reddy's Laboratories Limited. Process for preparation of eribulin and intermediates thereof
CN114805322B (zh) 2016-06-30 2025-05-30 卫材R&D管理有限公司 可用于合成软海绵素大环内酯类及其类似物的普林斯反应和中间体
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
WO2018096478A2 (en) 2016-11-23 2018-05-31 Dr. Reddy’S Laboratories Limited Process for preparation of eribulin and intermediates thereof
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
LT3606928T (lt) 2017-04-05 2022-12-12 President And Fellows Of Harvard College Makrociklinis junginys ir jo panaudojimo būdai
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
ES2940688T3 (es) * 2017-07-06 2023-05-10 Harvard College Síntesis de halicondrinas
EP3710454B1 (en) 2017-11-15 2024-01-03 President And Fellows Of Harvard College Macrocyclic compounds and uses thereof
JP7469226B2 (ja) 2018-01-03 2024-04-16 エーザイ・アール・アンド・ディー・マネジメント株式会社 ハリコンドリンマクロライドとそのアナログの合成に有用なプリンス反応及び化合物
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
IL322106A (en) * 2023-01-17 2025-09-01 Systimmune Inc Eribulin drug conjugate

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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
US5436238A (en) 1992-03-12 1995-07-25 President And Fellows Of Harvard College Halichondrins and related compounds
DE69433220T2 (de) 1993-07-09 2004-08-19 Laboratoire Theramex Neue strukturelle Vitamin D Derivate
EP2272839B1 (en) 1998-06-17 2012-08-22 Eisai R&D Management Co., Ltd. Intermediate compounds for the preparation of halichondrin analogs
US7001982B2 (en) 2003-03-31 2006-02-21 Council Of Scientific And Industrial Research Non-natural C-linked carbo-β-peptides with robust secondary structures
USRE46965E1 (en) 2004-06-03 2018-07-24 Eisai R&D Management Co., Ltd. Intermediates for the preparation of analogs of Halichondrin B
US20060045846A1 (en) * 2004-08-30 2006-03-02 Horstmann Thomas E Reagents and methods for labeling terminal olefins
MX2010010902A (es) * 2008-04-04 2010-12-21 Eisai R&D Man Co Ltd Analogos de halicondrina b.
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
US9062020B2 (en) 2011-12-29 2015-06-23 Alphora Research Inc. 2-((2S,3S,4R,5R)-5-((S)-3-amino-2-hydroxyprop-1-yl)-4-methoxy-3-(phenylsulfonylmethyl)tetrahydrofuran-2-yl)acetaldehyde derivatives and process for their preparation
CA2909209A1 (en) 2013-05-15 2014-11-20 Alphora Research Inc. 3-((2s,5s)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol derivatives, their preparation and intermediates useful thereof

Also Published As

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

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