AU2020272973B2 - Novel synthetic options towards the manufacture of (6R,10S)-10- {4-[5-chloro-2-(4-chloro-1H-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6H)- pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15 -(metheno)pyrazolo [4,3-b] [1,7] diazacyclotetradecin-5(6H)-one - Google Patents

Novel synthetic options towards the manufacture of (6R,10S)-10- {4-[5-chloro-2-(4-chloro-1H-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6H)- pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15 -(metheno)pyrazolo [4,3-b] [1,7] diazacyclotetradecin-5(6H)-one

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Publication number
AU2020272973B2
AU2020272973B2 AU2020272973A AU2020272973A AU2020272973B2 AU 2020272973 B2 AU2020272973 B2 AU 2020272973B2 AU 2020272973 A AU2020272973 A AU 2020272973A AU 2020272973 A AU2020272973 A AU 2020272973A AU 2020272973 B2 AU2020272973 B2 AU 2020272973B2
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compound
alkyl
acid
yield
sep
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AU2020272973A1 (en
Inventor
Cyril BEN ΗΑΪΜ
Diego Fernando Domenico BROGGINI
Duy Chi Trung CAO
Kostiantyn CHERNICHENKO
Nicolas Cuniere
Yu Fan
Sergei KOLOTUCHIN
Sébastien François Emmanuel LEMAIRE
Subha MUKHERJEE
Eric M. SIMMONS
Amarjit Singh
Simon Albert WAGSCHAL
Carolyn S. WEI
Yi Xiao
Changxia YUAN
Bin Zheng
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Janssen Pharmaceutica NV
Bristol Myers Squibb Co
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Janssen Pharmaceutica NV
Bristol Myers Squibb Co
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Priority to AU2026201396A priority Critical patent/AU2026201396A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
AU2020272973A 2019-04-11 2020-04-10 Novel synthetic options towards the manufacture of (6R,10S)-10- {4-[5-chloro-2-(4-chloro-1H-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6H)- pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15 -(metheno)pyrazolo [4,3-b] [1,7] diazacyclotetradecin-5(6H)-one Active AU2020272973B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2026201396A AU2026201396A1 (en) 2019-04-11 2026-02-25 Novel synthetic options towards the manufacture of (6r,10s)-10-{4-[5-chloro-2-(4-chloro-1h-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6h)-pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15-(metheno)pyrazolo[4,3-b][1,7]diazacyclotetradecin-5(6h)-one

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962832614P 2019-04-11 2019-04-11
US62/832,614 2019-04-11
PCT/US2020/027655 WO2020210613A1 (en) 2019-04-11 2020-04-10 Novel synthetic options towards the manufacture of (6r,10s)-10- {4-[5-chloro-2-(4-chloro-1h-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6h)- pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15 -(metheno)pyrazolo [4,3-b] [1,7] diazacyclotetradecin-5(6h)-one

Related Child Applications (1)

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AU2026201396A Division AU2026201396A1 (en) 2019-04-11 2026-02-25 Novel synthetic options towards the manufacture of (6r,10s)-10-{4-[5-chloro-2-(4-chloro-1h-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6h)-pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15-(metheno)pyrazolo[4,3-b][1,7]diazacyclotetradecin-5(6h)-one

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AU2020272973A1 AU2020272973A1 (en) 2021-12-02
AU2020272973B2 true AU2020272973B2 (en) 2025-11-27

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AU2020272973A Active AU2020272973B2 (en) 2019-04-11 2020-04-10 Novel synthetic options towards the manufacture of (6R,10S)-10- {4-[5-chloro-2-(4-chloro-1H-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6H)- pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15 -(metheno)pyrazolo [4,3-b] [1,7] diazacyclotetradecin-5(6H)-one
AU2026201396A Pending AU2026201396A1 (en) 2019-04-11 2026-02-25 Novel synthetic options towards the manufacture of (6r,10s)-10-{4-[5-chloro-2-(4-chloro-1h-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6h)-pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15-(metheno)pyrazolo[4,3-b][1,7]diazacyclotetradecin-5(6h)-one

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AU2026201396A Pending AU2026201396A1 (en) 2019-04-11 2026-02-25 Novel synthetic options towards the manufacture of (6r,10s)-10-{4-[5-chloro-2-(4-chloro-1h-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6h)-pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15-(metheno)pyrazolo[4,3-b][1,7]diazacyclotetradecin-5(6h)-one

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US (2) US12378246B2 (https=)
EP (2) EP4234555A3 (https=)
JP (2) JP7631218B2 (https=)
KR (2) KR20260047658A (https=)
CN (2) CN114375290B (https=)
AR (1) AR118649A1 (https=)
AU (2) AU2020272973B2 (https=)
BR (1) BR112021020368A2 (https=)
CA (1) CA3132365A1 (https=)
EA (1) EA202192807A1 (https=)
ES (1) ES2969253T3 (https=)
IL (1) IL287102B2 (https=)
MX (2) MX2021012286A (https=)
SG (1) SG11202111132WA (https=)
TW (1) TWI880924B (https=)
WO (1) WO2020210613A1 (https=)

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EP4133064A4 (en) 2020-04-10 2024-07-24 Codexis, Inc. Engineered transaminase polypeptides
TW202229280A (zh) * 2020-10-12 2022-08-01 美商必治妥美雅史谷比公司 （６ｒ，１０ｓ）－１０－｛４－［５－氯－２－（４－氯－１ｈ－１，２，３－三唑－１－基）苯基］－６－側氧基－１（６ｈ）－嘧啶基｝－１－（二氟甲基）－６－甲基－１，４，７，８，９，１０－六氫－１１，１５－（亞甲橋基）吡唑并［４，３－ｂ］［１，７］二氮雜環十四炔－５（６ｈ）－酮之製備方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3293186A1 (en) * 2014-10-01 2018-03-14 Bristol-Myers Squibb Company Pyrimidinones as factor xia inhibitors
WO2018133793A1 (zh) * 2017-01-18 2018-07-26 广东东阳光药业有限公司 凝血因子XIa抑制剂及其用途

Family Cites Families (7)

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WO2012125797A1 (en) 2011-03-15 2012-09-20 Abbott Laboratories Nuclear hormone receptor modulators
SG10201908467RA (en) 2014-01-31 2019-10-30 Bristol Myers Squibb Co Macrocycles with hetrocyclic p2' groups as factor xia inhibitors
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
CN105294496A (zh) * 2015-09-28 2016-02-03 中山大学 一种西酞普兰中间体的制备方法
WO2020211781A1 (zh) * 2019-04-16 2020-10-22 南京明德新药研发有限公司 作为XIa因子抑制剂的大环衍生物
CN114008047B (zh) * 2019-07-23 2023-03-21 南京明德新药研发有限公司 作为XIa因子抑制剂的大环衍生物
JP7747337B2 (ja) * 2020-04-10 2025-10-01 コデクシス， インコーポレイテッド 速度論的光学分割のためのカルボキシエステラーゼポリペプチド

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3293186A1 (en) * 2014-10-01 2018-03-14 Bristol-Myers Squibb Company Pyrimidinones as factor xia inhibitors
WO2018133793A1 (zh) * 2017-01-18 2018-07-26 广东东阳光药业有限公司 凝血因子XIa抑制剂及其用途

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Publication number Publication date
EP3953334A1 (en) 2022-02-16
TWI880924B (zh) 2025-04-21
US20220144836A1 (en) 2022-05-12
IL287102A (en) 2021-12-01
AR118649A1 (es) 2021-10-20
KR20220045105A (ko) 2022-04-12
BR112021020368A2 (pt) 2021-12-07
EP4234555A2 (en) 2023-08-30
JP2022526659A (ja) 2022-05-25
TW202104188A (zh) 2021-02-01
ES2969253T3 (es) 2024-05-17
IL287102B1 (en) 2025-08-01
EP3953334B1 (en) 2023-11-22
CN119775276A (zh) 2025-04-08
CA3132365A1 (en) 2020-10-15
WO2020210613A1 (en) 2020-10-15
IL287102B2 (en) 2025-12-01
EP4234555A3 (en) 2024-01-03
KR102929951B1 (ko) 2026-02-24
SG11202111132WA (en) 2021-11-29
JP7631218B2 (ja) 2025-02-18
EA202192807A1 (ru) 2022-02-24
MX2021012286A (es) 2022-04-06
MX2025014306A (es) 2026-01-07
JP2025084766A (ja) 2025-06-03
AU2020272973A1 (en) 2021-12-02
CN114375290A (zh) 2022-04-19
KR20260047658A (ko) 2026-04-08
US12378246B2 (en) 2025-08-05
CN114375290B (zh) 2024-11-29
AU2026201396A1 (en) 2026-03-19
US20260092066A1 (en) 2026-04-02

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