WO2004103977A3 - Process for the preparation of pyrimidine derivatives - Google Patents

Process for the preparation of pyrimidine derivatives Download PDF

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Publication number
WO2004103977A3
WO2004103977A3 PCT/EP2004/050762 EP2004050762W WO2004103977A3 WO 2004103977 A3 WO2004103977 A3 WO 2004103977A3 EP 2004050762 W EP2004050762 W EP 2004050762W WO 2004103977 A3 WO2004103977 A3 WO 2004103977A3
Authority
WO
WIPO (PCT)
Prior art keywords
preparation
hydrogen
pyrimidine derivatives
unsubstituted
compounds
Prior art date
Application number
PCT/EP2004/050762
Other languages
French (fr)
Other versions
WO2004103977A2 (en
Inventor
Nicole End
Yvonne Richter
Original Assignee
Ciba Sc Holding Ag
Nicole End
Yvonne Richter
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 Ciba Sc Holding Ag, Nicole End, Yvonne Richter filed Critical Ciba Sc Holding Ag
Publication of WO2004103977A2 publication Critical patent/WO2004103977A2/en
Publication of WO2004103977A3 publication Critical patent/WO2004103977A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/38—One sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Obesity (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

There is described a process for the preparation of compounds of formula (1) starting from the reaction of the compounds of formulae (24), (25) and (26) to form the compound of formula (23), wherein in each case R1, R2 and R3 are each independently of the others an unsubstituted or substituted organic radical; R4 is hydrogen, unsubstituted or substituted C1-C8alkyl, C1-C8alkoxy, phenoxy or benzyloxy, or halogen; Y1 and Y2 are each independently of the other hydrogen or a protecting group, or Y1 and Y2 together are a protecting bridge; and X1 is hydrogen, an organic radical or a cation; and also novel intermediates.
PCT/EP2004/050762 2003-05-21 2004-05-12 Process for the preparation of pyrimidine derivatives WO2004103977A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP03405355.3 2003-05-21
EP03405355 2003-05-21

Publications (2)

Publication Number Publication Date
WO2004103977A2 WO2004103977A2 (en) 2004-12-02
WO2004103977A3 true WO2004103977A3 (en) 2005-01-06

Family

ID=33462271

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2004/050762 WO2004103977A2 (en) 2003-05-21 2004-05-12 Process for the preparation of pyrimidine derivatives

Country Status (2)

Country Link
AR (1) AR044400A1 (en)
WO (1) WO2004103977A2 (en)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL1015744C2 (en) 2000-07-19 2002-01-22 Dsm Nv Process for the preparation of 2- (6-substituted-1,3-dioxan-4-yl) acetic acid derivatives.
ATE349431T1 (en) 2001-07-13 2007-01-15 Astrazeneca Uk Ltd PREPARATION OF AMINOPYRIMIDINE COMPOUNDS
GB0218781D0 (en) 2002-08-13 2002-09-18 Astrazeneca Ab Chemical process
WO2004054986A2 (en) 2002-12-16 2004-07-01 Astrazeneca Uk Limited Process for the preparation of pyrimidine compounds
GB0312896D0 (en) 2003-06-05 2003-07-09 Astrazeneca Ab Chemical process
GB0324791D0 (en) 2003-10-24 2003-11-26 Astrazeneca Ab Chemical process
WO2005054207A1 (en) * 2003-12-04 2005-06-16 Glenmark Pharmaceuticals Limited Process for the preparation of pyrimidine derivatives
GB0428328D0 (en) 2004-12-24 2005-02-02 Astrazeneca Uk Ltd Chemical process
CN100351240C (en) * 2005-01-19 2007-11-28 安徽省庆云医药化工有限公司 Rosuvastatin calcium synthesis method
KR100945763B1 (en) * 2005-02-22 2010-03-08 테바 파마슈티컬 인더스트리즈 리미티드 Preparation of rosuvastatin
EP1817293A1 (en) * 2005-10-03 2007-08-15 Teva Pharmaceutical Industries Ltd. Diastereomeric purification of rosuvastatin
WO2007099561A1 (en) * 2006-02-27 2007-09-07 Cadila Healthcare Limited Process for preparing rosuvastatin calcium
WO2009157014A2 (en) * 2008-01-30 2009-12-30 Cadila Healthcare Limited A process for preparing hmg-coa reductase inhibitors and intermediates
CA2725052C (en) 2008-05-27 2014-09-16 Changzhou Pharmaceutical Factory Co., Ltd. Preparation method of rosuvastatin calcium and its intermediates
CN101955463B (en) * 2010-08-04 2012-01-04 重庆博腾制药科技股份有限公司 Method for preparing rosuvastatin calcium intermediate
HU230987B1 (en) * 2010-11-29 2019-08-28 Egis Gyógyszergyár Nyrt. Process for the preparation of pharmaceutical intermediates with high purity
CN102617481A (en) * 2012-03-16 2012-08-01 湖南欧亚生物有限公司 Preparation method of rosuvastatin calcium
CN102633727A (en) * 2012-04-01 2012-08-15 浙江工业大学 Synthetic method of 2-methylthio-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-methyl carbonate
CN103113356A (en) * 2013-03-07 2013-05-22 上海现代制药股份有限公司 Method for preparing rosuvastatin calcium intermediate
US9850213B2 (en) * 2013-11-25 2017-12-26 Jiangxi Boya Seehot Pharmaceutical Co., Ltd. Method for preparing rosuvastatin sodium
CN103804414B (en) * 2014-03-07 2016-04-13 凯莱英医药集团（天津）股份有限公司 For the preparation of rosuvastain calcium midbody compound and prepared the method for rosuvastain calcium by it
JP6240346B2 (en) * 2014-03-07 2017-11-29 ▲凱▼菜英医▲薬▼集▲団▼（天津）股▲フン▼有限公司 Intermediate compound for producing rosuvastatin calcium and method for producing rosuvastatin calcium using the same
CN104059024B (en) * 2014-06-16 2016-04-06 浙江大学 The preparation method of Rosuvastatin intermediate and midbody compound
CN105175345B (en) * 2015-09-22 2018-05-22 上海应用技术学院 A kind of method for preparing Rosuvastatin intermediate
CN106397335A (en) * 2016-08-31 2017-02-15 湖北祥云(集团)化工股份有限公司 Preparation method of rosuvastatin intermediate
CN108191772A (en) * 2017-12-28 2018-06-22 江苏悦兴医药技术有限公司 The synthetic method of rosuvastain calcium intermediate impurities
CN115819408A (en) * 2022-10-21 2023-03-21 宿迁阿尔法科技有限公司 Method for highly selectively synthesizing rosuvastatin key intermediate

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0521474A1 (en) * 1991-07-03 1993-01-07 MITSUI TOATSU CHEMICALS, Inc. Colour-developing composition for pressure-sensitive copying paper

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0521474A1 (en) * 1991-07-03 1993-01-07 MITSUI TOATSU CHEMICALS, Inc. Colour-developing composition for pressure-sensitive copying paper

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
DANDIA A ET AL: "Synthesis of fluorinated ethyl 4-aryl-6-methyl-1,2,3,4-tetrahydropyri midin-2-one/thione-5-carboxylates under microwave irradiation", JOURNAL OF FLUORINE CHEMISTRY, ELSEVIER SEQUOIA. LAUSANNE, CH, vol. 90, no. 1, 26 June 1998 (1998-06-26), pages 17 - 21, XP004123688, ISSN: 0022-1139 *
FOROUGHIFAR N ET AL: "SYNTHESIS, CHARACTERIZATION AND MICROBIAL ACTIVITY STUDIES OF SOME-4-ARYL-6-METHYL-2-THIOXO (OR OXO) 1,2,3,4-TETRAHYDROPYRIMIDINE-5 CARBOXYLIC ACID DERIVATIVES", SCIENTIST OF PHYSICAL SCIENCES, ANSARI, BHOPAL, IN, vol. 12, no. 3, 2000, pages 277 - 280, XP009013701, ISSN: 0970-9150 *
FU N-Y ET AL: "Indium(III) bromide-catalyzed preparation of dihydropyrimidinones: improved protocol conditions for the Biginelli reaction", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 58, no. 24, 10 June 2002 (2002-06-10), pages 4801 - 4807, XP004366397, ISSN: 0040-4020 *
LU J ET AL: "One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using lanthanum chloride as a catalyst", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 41, no. 47, 18 November 2000 (2000-11-18), pages 9075 - 9078, XP004236191, ISSN: 0040-4039 *
MAITI G ET AL: "One-pot synthesis of dihydropyrimidinones catalysed by lithium bromide: an improved procedure for the Biginelli reaction", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 44, no. 13, 24 March 2003 (2003-03-24), pages 2757 - 2758, XP004413298, ISSN: 0040-4039 *
REDDY C V ET AL: "Zirconium(IV) chloride catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 43, no. 14, 1 April 2002 (2002-04-01), pages 2657 - 2659, XP004343976, ISSN: 0040-4039 *
SABITHA G ET AL: "Vanadium(III) chloride catalyzed Biginelli condensation: solution phase library generation of dihydropyrimidin-(2H)-ones", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 44, no. 34, 18 August 2003 (2003-08-18), pages 6497 - 6499, XP004442784, ISSN: 0040-4039 *
SALEHI P ET AL: "Silica sulfuric acid: an efficient and reusable catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 44, no. 14, 31 March 2003 (2003-03-31), pages 2889 - 2891, XP004414428, ISSN: 0040-4039 *
SALOUTIN V I ET AL: "Biginelli condensations of fluorinated 3-oxo esters and 1,3-diketones [1]", JOURNAL OF FLUORINE CHEMISTRY, ELSEVIER SEQUOIA, LAUSANNE, CH, vol. 103, no. 1, April 2000 (2000-04-01), pages 17 - 23, XP004191148, ISSN: 0022-1139 *
SHAABANI A ET AL: "Ammonium chloride-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones under solvent-free conditions", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 44, no. 4, 20 January 2003 (2003-01-20), pages 857 - 859, XP004405152, ISSN: 0040-4039 *
SINGH K ET AL: "An Expedient Protocol of The Biginelli Dihydropyrimidine Synthesis Using Carbonyl Equivalents", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 55, no. 44, 29 October 1999 (1999-10-29), pages 12873 - 12880, XP004180378, ISSN: 0040-4020 *
STADLER A ET AL: "AUTOMATED LIBRARY GENERATION USING SEQUENTIAL MICROWAVE-ASSISTED CHEMISTRY. APPLICATION TOWARD THE BIGINELLI MULTICOMPONENT CONDENSATION", JOURNAL OF COMBINATORIAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US, vol. 3, no. 6, 10 April 2001 (2001-04-10), pages 624 - 630, XP001184142, ISSN: 1520-4766 *

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Publication number Publication date
AR044400A1 (en) 2005-09-14
WO2004103977A2 (en) 2004-12-02

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