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WO2010022690A3 - A method of preparation of highly pure vildagliptin - Google Patents

A method of preparation of highly pure vildagliptin Download PDF

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Publication number
WO2010022690A3
WO2010022690A3 PCT/CZ2009/000105 CZ2009000105W WO2010022690A3 WO 2010022690 A3 WO2010022690 A3 WO 2010022690A3 CZ 2009000105 W CZ2009000105 W CZ 2009000105W WO 2010022690 A3 WO2010022690 A3 WO 2010022690A3
Authority
WO
WIPO (PCT)
Prior art keywords
preparation
vildagliptin
highly pure
stands
chlorine
Prior art date
Application number
PCT/CZ2009/000105
Other languages
French (fr)
Other versions
WO2010022690A2 (en
Inventor
Ales Halama
Bozena Kafkova
Tomas Chvojka
Original Assignee
Zentiva, K.S.
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 Zentiva, K.S. filed Critical Zentiva, K.S.
Publication of WO2010022690A2 publication Critical patent/WO2010022690A2/en
Publication of WO2010022690A3 publication Critical patent/WO2010022690A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

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

Abstract

The present invention deals with a new method of preparation of chemically highly pure and pharmaceutically usable vildagliptin (I), including analytic control of the production process and quality of the target substance. The newly found process is based on the preparation and isolation of a mixture of l-haloacetyl-2-(S)-pyrrolidine carboxamide of chemical formula (VI), where X stands for a chlorine or bromine atom, with trialkylamine hydrohalides of chemical formula R1R2R3N*HX, where R1, R2 and R3 independently stand for a linear or branched alkyl with 1 to 6 carbon atoms, substituents R1 and R2 can be connected with a bridge and form a cycle with 2 to 6 carbon atoms, or can be connected with an ether bond, X stands for a chlorine or bromine atom. The invention also deals with analytical standards and analytical methods used for the control of the production process and final quality of vildagliptin.
PCT/CZ2009/000105 2008-08-26 2009-08-25 A method of preparation of highly pure vildagliptin WO2010022690A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZ20080512A CZ2008512A3 (en) 2008-08-26 2008-08-26 Process for preparing extremely pure vildagliptin
CZPV2008-512 2008-08-26

Publications (2)

Publication Number Publication Date
WO2010022690A2 WO2010022690A2 (en) 2010-03-04
WO2010022690A3 true WO2010022690A3 (en) 2010-11-11

Family

ID=41721993

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CZ2009/000105 WO2010022690A2 (en) 2008-08-26 2009-08-25 A method of preparation of highly pure vildagliptin

Country Status (2)

Country Link
CZ (1) CZ2008512A3 (en)
WO (1) WO2010022690A2 (en)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1400714B1 (en) 2010-07-06 2013-06-28 Chemelectiva S R L PROCESS AND INTERMEDIATE FOR THE PREPARATION OF AN ACTIVE PRINCIPLE.
HU231050B1 (en) 2010-08-19 2020-02-28 Egis Gyógyszergyár Nyrt. Process for the preparation of a pharmaceutical active ingredient
ITMI20112224A1 (en) 2011-12-06 2013-06-07 Chemelectiva S R L NEW PROCESS AND INTERMEDIATE FOR THE SYNTHESIS OF VILDAGLIPTIN
CN102617434B (en) * 2012-03-29 2014-07-23 中国科学院上海有机化学研究所 Process for preparing Vildagliptin by one-pot method
IN2012MU01383A (en) 2012-05-04 2014-02-28
CN103787944A (en) * 2012-11-01 2014-05-14 天津药物研究院 Preparation method of 1-(2-chloroacetyl)-2-(S)-nitrile pyrrolidine
CN103351320A (en) * 2013-06-17 2013-10-16 张家港威胜生物医药有限公司 Preparation method of (S)-1-(2-chloroacetyl)-pyrrolidine-2-formamide
EP3082801A4 (en) * 2013-12-18 2017-07-26 Harman Finochem Limited An advanced and cost-effective process for preparing highly pure vildagliptin
CN103804267B (en) * 2014-02-21 2016-06-08 张家港威胜生物医药有限公司 A kind of synthesis technique of vildagliptin
WO2015145467A1 (en) * 2014-03-28 2015-10-01 Laurus Labs Private Limited An improved process for preparing vildagliptin
CN105884669B (en) * 2014-09-15 2020-05-15 深圳翰宇药业股份有限公司 Process for the preparation of substituted (S) -pyrrolidine-2-carbonitriles and vildagliptin
CN104744334A (en) * 2015-03-25 2015-07-01 合肥创新医药技术有限公司 Preparation method for vildagliptin
CN104945299B (en) * 2015-05-28 2017-03-15 烟台万润药业有限公司 A kind of high-efficiency synthesis method of vildagliptin
CN105153165B (en) * 2015-07-30 2017-08-29 上海医药集团青岛国风药业股份有限公司 A kind of preparation method of vildagliptin impurity
CN105085360A (en) * 2015-09-10 2015-11-25 南京理工大学 Preparation method of high-purity vildagliptin
CN107219307A (en) * 2016-03-22 2017-09-29 中美华世通生物医药科技（武汉）有限公司 The method that enantiomter impurity in song Ge Lieting bulk drugs and its preparation is determined using HPLC
CN106338564B (en) * 2016-09-27 2018-10-12 海口南陆医药科技股份有限公司 A method of for detecting enantiomter in vildagliptin intermediate
CN107311907A (en) * 2017-07-29 2017-11-03 合肥创新医药技术有限公司 A kind of preparation method of vildagliptin isomer impurities
CN109827984B (en) * 2019-02-27 2022-05-17 南京江北新区生物医药公共服务平台有限公司 Method for determining content of impurities or structural analogue reference substances in L-prolinamide synthesis process
WO2021116897A1 (en) * 2019-12-10 2021-06-17 Optimus Drugs (P) Ltd Process for the preparation of vildagliptin
CN110940759B (en) * 2019-12-23 2022-05-03 河北科技大学 A kind of HPLC detection method of vildagliptin intermediate-5
WO2022003405A1 (en) 2020-07-03 2022-01-06 Savoi Guilherme One-pot process to obtain a pyrrolidine-2-carbonitrile intermediate compound and industrial scale telescopic process to prepare (2s)-1-[n-(3-hydroxyadamantan-1-yl)glycyl]-2-pyrrolidinecarbonitrile (vildagliptin) using same
CN112394127B (en) * 2020-12-08 2022-05-10 海南通用三洋药业有限公司 Method for determining content of 3-amino-1-adamantanol and L-prolinamide in vildagliptin
CN112557582B (en) * 2020-12-17 2022-11-01 南通恒华粘合材料科技有限公司 Method for measuring hydroxyl value of polyester polyol
CN112939837B (en) * 2021-02-03 2022-07-19 海南通用三洋药业有限公司 Method for preparing vildagliptin through multiphase compound continuous production
CN114814050B (en) * 2022-03-29 2024-08-16 浙江美诺华药物化学有限公司 Impurity detection method for 3-amino-1-adamantanol

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WO2001096295A2 (en) * 2000-06-13 2001-12-20 Novartis Ag 2-cyanopyrrolidine derivatives and their use as medicaments
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EP1595866A1 (en) * 2003-01-31 2005-11-16 Sanwa Kagaku Kenkyusho Co., Ltd. Compound inhibiting dipeptidyl peptidase iv
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EP1137635B1 (en) * 1998-12-10 2005-10-19 Novartis AG N-substituted 2-cyanopyrrolidines
WO2001096295A2 (en) * 2000-06-13 2001-12-20 Novartis Ag 2-cyanopyrrolidine derivatives and their use as medicaments
WO2003051848A2 (en) * 2001-12-14 2003-06-26 Ferring Bv Imidazolidineacetic acid derivatives
EP1595866A1 (en) * 2003-01-31 2005-11-16 Sanwa Kagaku Kenkyusho Co., Ltd. Compound inhibiting dipeptidyl peptidase iv
WO2004092127A1 (en) * 2003-04-16 2004-10-28 Novartis Ag Process for the preparation of n-substituted 2-cyanopyrrolidines
WO2006100181A2 (en) * 2005-03-22 2006-09-28 F. Hoffmann-La Roche Ag New salt and polymorphs of a dpp-iv inhibitor
WO2008084383A2 (en) * 2007-01-10 2008-07-17 Medichem, S.A. Process for preparing vildagliptin
WO2009058531A1 (en) * 2007-10-31 2009-05-07 Exxonmobil Chemical Patents Inc. Oxidation of hydrocarbons

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MCINTYRE J A ET AL: "Vildagliptin. Agent for type 2 diabetes, dipeptidyl-peptidase IV inhibitor", DRUGS OF THE FUTURE, PROUS SCIENCE, ES LNKD- DOI:10.1358/DOF.2004.029.09.841366, vol. 29, no. 9, 1 September 2004 (2004-09-01), pages 887 - 891, XP002483135, ISSN: 0377-8282 *
VILLHAUER E B ET AL: "1-Ä2-Ä(5-CYANOPYRIDIN-2-YL)AMINOÜ-ETHYLAMINOÜACETYL-2-(S)-PYRROLIDINE CARBONITRILE: A POTENT, SELECTIVE, AND ORALLY BIOAVAILABLE DIPEPTIDYL PEPTIDASE IV INHIBITOR WITH ANTIHYPERGLYCEMIC PROPERTIES", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US LNKD- DOI:10.1021/JM025522Z, vol. 45, no. 12, 6 June 2002 (2002-06-06), pages 2362 - 2365, XP001165748, ISSN: 0022-2623 *
VILLHAUER E B ET AL: "1-ÄÄ(3-HYDROXY-1-ADAMANTYL)AMINOÜACETYLÜ-2-CYANO-(S)-PYRROLIDINE: A POTENT, SELECTIVE, AND ORALLY BIOAVAILABLE DIPEPTIDYL PEPTIDASE IV INHIBITOR WITH ANTIHYPERGLYCEMIC PROPERTIES", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US LNKD- DOI:10.1021/JM030091L, vol. 46, no. 13, 1 January 2003 (2003-01-01), pages 2774 - 2789, XP001165747, ISSN: 0022-2623 *

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WO2010022690A2 (en) 2010-03-04
CZ2008512A3 (en) 2010-03-10

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