WO2007027564A3 - Process for preparing gemcitabine and associated intermediates - Google Patents

Process for preparing gemcitabine and associated intermediates Download PDF

Info

Publication number
WO2007027564A3
WO2007027564A3 PCT/US2006/033431 US2006033431W WO2007027564A3 WO 2007027564 A3 WO2007027564 A3 WO 2007027564A3 US 2006033431 W US2006033431 W US 2006033431W WO 2007027564 A3 WO2007027564 A3 WO 2007027564A3
Authority
WO
WIPO (PCT)
Prior art keywords
ester
intermediates
methylbenzylcarbonyl
deoxy
difluoro
Prior art date
Application number
PCT/US2006/033431
Other languages
French (fr)
Other versions
WO2007027564A2 (en
Inventor
Jingshan Shen
Yafei Li
Joseph Kaspi
Original Assignee
Chemagis Ltd
Perrigo Company
Jingshan Shen
Yafei Li
Joseph Kaspi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chemagis Ltd, Perrigo Company, Jingshan Shen, Yafei Li, Joseph Kaspi filed Critical Chemagis Ltd
Priority to EP06802423A priority Critical patent/EP1931693A2/en
Priority to JP2008529146A priority patent/JP2009506118A/en
Publication of WO2007027564A2 publication Critical patent/WO2007027564A2/en
Publication of WO2007027564A3 publication Critical patent/WO2007027564A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C07H19/19—Purine radicals with arabinosyl as the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Provided is a process for preparing gemcitabine or a salt thereof, which preferably includes removing at least a substantial portion of the α anomer of a N-1-protected-2'-deoxy-2',2'-difluoro-cytidine-3',5'-diester from an anomeric mixture thereof; removing the 3'-ester, the 5'-ester and the N-protecting group; and optionally forming a salt. The 3'-ester and 5'-ester can be the same or different and at least one of the esters preferably is cinnamoyl, benzoyl, 1-naphthoyl, 1-naphthylmethylcarbonyl, 2-methylbenzylcarbonyl, 4-methylbenzylcarbonyl or 9-fluorenylmethyloxycarbonyl ester. Also provided are novel intermediates, including but not limited to 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-diesters, and methods of producing such intermediates.
PCT/US2006/033431 2005-08-29 2006-08-28 Process for preparing gemcitabine and associated intermediates WO2007027564A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP06802423A EP1931693A2 (en) 2005-08-29 2006-08-28 Process for preparing gemcitabine and associated intermediates
JP2008529146A JP2009506118A (en) 2005-08-29 2006-08-28 Method for producing gemcitabine and related intermediates

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US71221705P 2005-08-29 2005-08-29
US60/712,217 2005-08-29

Publications (2)

Publication Number Publication Date
WO2007027564A2 WO2007027564A2 (en) 2007-03-08
WO2007027564A3 true WO2007027564A3 (en) 2007-06-07

Family

ID=37809396

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/033431 WO2007027564A2 (en) 2005-08-29 2006-08-28 Process for preparing gemcitabine and associated intermediates

Country Status (5)

Country Link
EP (1) EP1931693A2 (en)
JP (1) JP2009506118A (en)
KR (1) KR20080039502A (en)
CN (1) CN101296934A (en)
WO (1) WO2007027564A2 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100741310B1 (en) * 2006-08-01 2007-08-01 (주) 유일팜테크 Naphthalene 2-carboxylate derivative useful for synthesizing gemcitabine and a method for preparing the same
EP2139884B1 (en) * 2007-03-23 2013-12-04 Dongwoo Syntech Co., Ltd. Process for preparing of 2'-deoxy-2'2'-difluorocytidine
KR100957756B1 (en) * 2007-12-12 2010-05-12 동우신테크 주식회사 Process for preparing of 2'-deoxy-2'2'-difluorocytidine
US20080262215A1 (en) * 2007-04-23 2008-10-23 Chemagis Ltd. Gemcitabine production process
CN100475832C (en) * 2007-05-31 2009-04-08 南京卡文迪许生物工程技术有限公司 Novel highly-solid selectively synthesizing gemcitabine process and intermediate
CN101492482B (en) * 2008-12-17 2010-09-29 美中能特医药化学科技（荆州）有限公司 Synthesis process of the industrial production of gemcitabine hydrochloride
CN101899079B (en) * 2009-05-30 2012-09-12 鲁南制药集团股份有限公司 Preparation, separation and purification method of Decitabine
CN109796506A (en) * 2019-01-28 2019-05-24 江苏八巨药业有限公司 A kind of preparation method of gemcitabine key intermediate

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4097665A (en) * 1974-11-22 1978-06-27 Asahi Kasei Kogyo Kabushiki Kaisha Diacylnucleosides and process for preparing the same
US4751221A (en) * 1985-10-18 1988-06-14 Sloan-Kettering Institute For Cancer Research 2-fluoro-arabinofuranosyl purine nucleosides
US4965374A (en) * 1987-08-28 1990-10-23 Eli Lilly And Company Process for and intermediates of 2',2'-difluoronucleosides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4097665A (en) * 1974-11-22 1978-06-27 Asahi Kasei Kogyo Kabushiki Kaisha Diacylnucleosides and process for preparing the same
US4751221A (en) * 1985-10-18 1988-06-14 Sloan-Kettering Institute For Cancer Research 2-fluoro-arabinofuranosyl purine nucleosides
US4965374A (en) * 1987-08-28 1990-10-23 Eli Lilly And Company Process for and intermediates of 2',2'-difluoronucleosides

Also Published As

Publication number Publication date
JP2009506118A (en) 2009-02-12
WO2007027564A2 (en) 2007-03-08
CN101296934A (en) 2008-10-29
EP1931693A2 (en) 2008-06-18
KR20080039502A (en) 2008-05-07

Similar Documents

Publication Publication Date Title
WO2007027564A3 (en) Process for preparing gemcitabine and associated intermediates
WO2019152459A8 (en) Stereoselective synthesis and process for the manufacturing of 2'-deoxynucleosides
EP1838864A2 (en) Antifungal properties of various forms of sophorolipids
WO2005086670A3 (en) Production of chemicals from lignocellulose, biomass or sugars
WO2005108411A3 (en) Substituted pixyl protecting groups for oligonucleotide synthesis
WO2004043407A3 (en) Methods and products for treating staphylococcal infections
EP1130042A3 (en) Polyhydroxyalkanoate containing 3-hydroxybenzoylalkanoic acid as monomer unit, and method for producing the same
JPH02211889A (en) Method of selective acylation of sugar
MY150408A (en) P-TOLUENE SULFONIC ACID SALT OF 5-AMINO-3-(2'-O-ACETYL-3'-DEOXY-ß-D-RIBOFURANOSYL)-3H-THIAZOLE[4,5-D]PYRIMIDINE-2-ONE AND METHODS FOR PREPARATION
WO2007030165A3 (en) Zirconium strip meterial and process for making same
Wu et al. Strategies for desymmetrising trehalose to synthesise trehalose glycolipids
Murakami et al. Medicinal foodstuffs. XXIV. Chemical constituents of the processed leaves of Apocynum venetum L.: Absolute stereostructures of apocynosides I and II
EP1813622A4 (en) Sucrose fatty acid ester with low degree of substitution and process for producing the same
Dasgupta et al. Oligosaccharides through reactivity tuning: convergent synthesis of the trisaccharides of the steroid glycoside Sokodoside B isolated from marine sponge Erylus placenta
Takigawa et al. Identification and characterization of component organic and glycosidic acids of crude resin glycoside fraction from Calystegia soldanella
EP1170370A3 (en) Method for producing nucleotide by fermentation
PT711349E (en) GENES THAT ENCODE FOR THE COMPLEX DEIDROGENASE OF ALPHA-CETONIC ACID FROM BRANCHED CHAIN FROM STREPTOMYCES AVERMITILIS
WO2010086667A3 (en) Compositions comprising sugar ester of mycolic acid derivatives and process the preparation thereof
WO2008105593A1 (en) METHOD FOR STEREOSELECTIVE PREPARATION AND SEPARATION OF TRI-O-ACETYL-5-DEOXY-ß-D-RIBOFURANOSE
WO2001058920A3 (en) Process for selectively producing 1-phosphorylated sugar derivative anomer and process for producing nucleoside
IL189852A0 (en) Selective o-acylation of nucleosides
Chauvin et al. Synthesis of an apiose-containing disaccharide fragment of rhamnogalacturonan-II and some analogues
TW200718705A (en) Processes for the preparation of docetaxel
Cui et al. Stereoselective synthesis of α-glycosyl azides by ring-opening of 1, 6-anhydrosugars with trimethylsilyl azide
WO1999064430A3 (en) Morphine-6-glucuronide synthesis

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200680039700.5

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application
DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 845/KOLNP/2008

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2008529146

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: KR

WWE Wipo information: entry into national phase

Ref document number: 2006802423

Country of ref document: EP