CN105683209B - 2’-脱氧-2’,2’-二氟四氢尿苷的合成途径 - Google Patents

2’-脱氧-2’,2’-二氟四氢尿苷的合成途径 Download PDF

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CN105683209B
CN105683209B CN201480059455.9A CN201480059455A CN105683209B CN 105683209 B CN105683209 B CN 105683209B CN 201480059455 A CN201480059455 A CN 201480059455A CN 105683209 B CN105683209 B CN 105683209B
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compound
salt
catalyst
acid
dbu
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CN105683209A (zh
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H.崔
S.马蒂厄
F.方
B.M.路易斯
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Taiho Pharmaceutical Co Ltd
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Otsuka Pharmaceutical Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06Pyrimidine radicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0201Oxygen-containing compounds
    • B01J31/0209Esters of carboxylic or carbonic acids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235Nitrogen containing compounds
    • B01J31/0237Amines
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235Nitrogen containing compounds
    • B01J31/0244Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B57/00Separation of optically-active compounds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives
    • C07H1/06Separation; Purification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07Optical isomers
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/02Heterocyclic radicals containing only nitrogen as ring hetero atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials Engineering (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Saccharide Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201480059455.9A 2013-10-29 2014-10-29 2’-脱氧-2’,2’-二氟四氢尿苷的合成途径 Active CN105683209B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361896703P 2013-10-29 2013-10-29
US61/896703 2013-10-29
PCT/US2014/062874 WO2015066162A1 (en) 2013-10-29 2014-10-29 Synthetic route to 2'-deoxy-2',2'-difluorotetrahydrouridines

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CN105683209A CN105683209A (zh) 2016-06-15
CN105683209B true CN105683209B (zh) 2019-03-08

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US (3) US9834576B2 (enExample)
EP (1) EP3063164B1 (enExample)
JP (1) JP6427567B2 (enExample)
KR (1) KR102272773B1 (enExample)
CN (1) CN105683209B (enExample)
AU (1) AU2014342402B2 (enExample)
BR (1) BR112016008855B1 (enExample)
CA (1) CA2926734C (enExample)
ES (1) ES2712877T3 (enExample)
IL (1) IL244849B (enExample)
MX (1) MX363205B (enExample)
MY (1) MY176465A (enExample)
NZ (1) NZ718607A (enExample)
PH (1) PH12016500683B1 (enExample)
RU (1) RU2681939C2 (enExample)
SA (1) SA516371019B1 (enExample)
SG (1) SG11201602614XA (enExample)
WO (1) WO2015066162A1 (enExample)
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Families Citing this family (9)

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Publication number Priority date Publication date Assignee Title
CA2926734C (en) 2013-10-29 2022-03-15 Otsuka Pharmaceutical Co., Ltd. Synthetic route to 2'-deoxy-2',2'-difluorotetrahydrouridines
US11224610B2 (en) 2018-09-19 2022-01-18 Otsuka Pharmaceutical Co., Ltd. Low dose combination CDA substrate drug/cedazuridine with extended administration
EP4041743A4 (en) * 2019-10-08 2024-03-13 Otsuka Pharmaceutical Co., Ltd. HIGH PURITY 2'-DEOXY-2',2'-DIFLUORTETRAHYDROURIDINE AND METHOD FOR THE PRODUCTION THEREOF
PT4069254T (pt) 2020-02-25 2024-10-10 Otsuka Pharma Co Ltd Formas sólidas de dosagem oral compreendendo decitabina e cedazuridina
KR20230043904A (ko) 2020-07-24 2023-03-31 엘랑코 유에스 인코포레이티드 이속사졸린 화합물 및 이의 중간체의 제조 공정
CN113402573B (zh) * 2020-07-31 2023-06-20 集美大学 一种鞣质类化合物及其提取方法和应用
US20240279266A1 (en) * 2021-05-29 2024-08-22 Msn Laboratories Private Limited, R&D Center An improved process for the preparation of (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl) oxolan-2-yl]-4-hydroxy-1,3-diazinan-2one and its intermediate compounds
TWI821074B (zh) * 2021-12-25 2023-11-01 台灣神隆股份有限公司 製備希達路里定(cedazuridine)的方法
US20230271996A1 (en) * 2021-12-25 2023-08-31 Scinopharm Taiwan, Ltd. Process for preparing cedazuridine

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101827856A (zh) * 2007-10-16 2010-09-08 卫才公司 作为胞嘧啶核苷脱氨酶抑制剂的2′-氟-2′-脱氧四氢尿苷

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US4526988A (en) 1983-03-10 1985-07-02 Eli Lilly And Company Difluoro antivirals and intermediate therefor
US4965374A (en) 1987-08-28 1990-10-23 Eli Lilly And Company Process for and intermediates of 2',2'-difluoronucleosides
US5223608A (en) 1987-08-28 1993-06-29 Eli Lilly And Company Process for and intermediates of 2',2'-difluoronucleosides
FR2682112B1 (fr) 1991-10-08 1993-12-10 Commissariat A Energie Atomique Procede de synthese d'acide ribonucleique (arn) utilisant un nouveau reactif de deprotection.
US5371210A (en) 1992-06-22 1994-12-06 Eli Lilly And Company Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides
US5521294A (en) 1995-01-18 1996-05-28 Eli Lilly And Company 2,2-difluoro-3-carbamoyl ribose sulfonate compounds and process for the preparation of beta nucleosides
US6001994A (en) 1995-12-13 1999-12-14 Eli Lilly And Company Process for making gemcitabine hydrochloride
EP0876149A4 (en) 1995-12-22 2001-09-26 Univ East Carolina METHOD FOR TREATING DISORDERS CHARACTERIZED BY A CYTIDINE DEAMINASE OR DESOXYCYTIDINE DEAMINASE
US5760208A (en) 1996-08-14 1998-06-02 The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations Process to prepare pyrimidine nucleosides
CN102241720B (zh) 2000-11-29 2014-01-29 三井化学株式会社 L-核酸衍生物及其合成方法
FI112640B (fi) 2000-12-22 2003-12-31 Kone Corp Hissin turvalaite
KR101108407B1 (ko) * 2006-06-21 2012-01-30 일라이 릴리 앤드 캄파니 젬시타빈 아미드 전구약물의 결정 형태, 그의 조성물 및 용도
CA2926734C (en) 2013-10-29 2022-03-15 Otsuka Pharmaceutical Co., Ltd. Synthetic route to 2'-deoxy-2',2'-difluorotetrahydrouridines

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101827856A (zh) * 2007-10-16 2010-09-08 卫才公司 作为胞嘧啶核苷脱氨酶抑制剂的2′-氟-2′-脱氧四氢尿苷

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Publication number Publication date
PH12016500683A1 (en) 2016-05-30
US10526362B2 (en) 2020-01-07
EP3063164A1 (en) 2016-09-07
RU2681939C2 (ru) 2019-03-14
BR112016008855A2 (enExample) 2017-08-01
US11028119B2 (en) 2021-06-08
AU2014342402B2 (en) 2018-11-01
CA2926734C (en) 2022-03-15
AU2014342402A1 (en) 2016-04-21
KR20160083021A (ko) 2016-07-11
US20160237107A1 (en) 2016-08-18
EP3063164B1 (en) 2018-12-05
ZA201602315B (en) 2019-07-31
RU2016115523A3 (enExample) 2018-06-05
JP6427567B2 (ja) 2018-11-21
JP2017500281A (ja) 2017-01-05
ES2712877T3 (es) 2019-05-16
US20200123189A1 (en) 2020-04-23
IL244849B (en) 2019-10-31
KR102272773B1 (ko) 2021-07-02
CN105683209A (zh) 2016-06-15
US20180072768A1 (en) 2018-03-15
HK1223627A1 (en) 2017-08-04
SA516371019B1 (ar) 2018-01-23
MX2016005596A (es) 2016-12-09
WO2015066162A1 (en) 2015-05-07
US9834576B2 (en) 2017-12-05
NZ718607A (en) 2019-10-25
RU2016115523A (ru) 2017-12-04
BR112016008855B1 (pt) 2023-01-17
PH12016500683B1 (en) 2020-02-14
MY176465A (en) 2020-08-11
CA2926734A1 (en) 2015-05-07
IL244849A0 (en) 2016-05-31
SG11201602614XA (en) 2016-05-30
MX363205B (es) 2019-03-13

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