[go: up one dir, main page]

WO2017208105A1 - Nouvelle forme cristalline de dolutégravir sodique - Google Patents

Nouvelle forme cristalline de dolutégravir sodique Download PDF

Info

Publication number
WO2017208105A1
WO2017208105A1 PCT/IB2017/052926 IB2017052926W WO2017208105A1 WO 2017208105 A1 WO2017208105 A1 WO 2017208105A1 IB 2017052926 W IB2017052926 W IB 2017052926W WO 2017208105 A1 WO2017208105 A1 WO 2017208105A1
Authority
WO
WIPO (PCT)
Prior art keywords
cmr
solvent
process according
dol
utegravi
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/IB2017/052926
Other languages
English (en)
Inventor
Lalitkumar Dilipsing RAJPUT
Palash Sanphui
Harishchandra Sambhaji Jadhav
Radhakrishna Bhikaji SHIVDAVKAR
Dhananjai Shrivastava
Girij Pal Singh
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.)
Lupin Ltd
Original Assignee
Lupin Ltd
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 Lupin Ltd filed Critical Lupin Ltd
Publication of WO2017208105A1 publication Critical patent/WO2017208105A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14—Ortho-condensed systems

Definitions

  • the present invention provides novel crystalline form A of Dolutegravir sodium and process for preparation thereof.
  • Dolutegravir is an integrase inhibitor. It is used against HIV infections as a single drug or fixed-dose combination with abacavir sulphate and lamivudine under the trade names Tivicay ⁇ andTriumeq ⁇ respectively.
  • Dolutegravir sodium is disclosed in the patent US 8129385 and the patent US 9242986 mentions crystal form of a sodium salt of dolutegravir and crystal form of a hydrate of sodi um salt of dol utegravi r.
  • Another patent US 9206197 mentions amorphous form of dolutegravir sodium and process for its preparation.
  • the applications WO 2015118460 and WO 2015139591 provide various crystalline forms of dolutegravir sodium
  • the applications WO 2015138933 and WO 2015092752 provide various crystalline forms of dolutegravir sodium solvates and WO 2016016279 mentions hydrates of dolutegravir sodium.
  • the present invention provides novel crystalline form of dol utegravi r sodi urn designated as Form A and process for preparation thereof. DESCRIPTION OF DRAWING
  • Figure 1 X-ray powder diffraction pattern of crystalline Form A of dol utegravi r sodium.
  • Figure2 Infrared absorption spectrum of crystalline FormA of dol utegravi r sodium.
  • Figure 3- DSC thermogram of crystalline FormA of dol utegravi r sodium
  • the present invention provides novel crystalline form A of dol utegravi r sodium with characteristic diffraction peaks at 633 ⁇ 4 7.83 ⁇ 4 9.33 ⁇ 4 ⁇ Ae, 12.43 ⁇ 4 13.53 ⁇ 4 12.7e ⁇ 15.13 ⁇ 4 15.8e ⁇ 18.33 ⁇ 4 19.0 ⁇ 19.6 ⁇ 20.7e ⁇ 22.8e ⁇ 23.13 ⁇ 4 24.3e and 25.8e e 0.2 degree two theta in an X-ray diffraction pattern.
  • the present invention further provides process for preparation of crystalline form A of dol utegravi r sodium
  • the present invention relates to novel crystalline form A of dol utegravi r sodium and processes for its preparation.
  • the present invention provides crystalline form A of dol utegravi r sodium.
  • the crystalline form A of dolutegravir sodium is characterized by infrared absorption spectrum as depicted i n Figure 2.
  • the crystalline form A of dolutegravir sodium is characterized by Differential Scanning Calorimetry (DSC) thermogram as depicted in Figure 3.
  • the present invention provides a process for the preparation of crystal I i ne form A of dol utegravi r sodi um comprisi ng the steps of: a) dissolving dol utegravir sodium in a first solvent;
  • step (b) addi ng the sol uti on of step (a) to a pre cool ed sol uti on of second solvent; and c) i sol ati ng form A of dol utegravi r sodi um
  • the first solvent and second solvent can be selected from polar solvent non-polar solvents or mixtures thereof.
  • Polar solvent can be selected from alcohols like methanol, ethanol, butanol, propanol; nitriles l ike acetonitrile, propionitrile, butyronitrile; ethers like tetrahydrofuran, dioxane, di methoxyethane; esters like ethyl acetate, ethyl acetoacetate, butyl acetate, propyl acetate; ketones like acetone, methyl ethyl ketone, methyl isobutyl ketone; other polar solvents li ke dimethylformamide, dimethyl sulfoxide, water and mixtures thereof.
  • Non-polar solvents can be selected from hydrocarbon like hexane, cyclohexane, n-heptane, pentane, cyclopentane, toluene; chlori nated hydrocarbon solvent like methylene chloride, ethylene chloride, chloroform, carbon tetrachloride and mixtures thereof.
  • the first solvent is preferably dimethyl sulfoxide and second solvent is preferably methanol.
  • step (b) the second solvent can be pre cooled to a temperature of less than 30eC, preferably less than 20eC, more preferably less than 10eC.
  • step (c) form A of dolutegravir sodium can be isolated by techniques known in art like filtration, concentration, evaporation of solvents etc.
  • the form A of dolutegravir sodium of the present invention was found to be stable at 40eC/ 75% RH; 25eC/ 60% RH and 5eC.
  • the total impurity content in form A of dolutegravir sodium was found to be not more than 0.1% by H PLC, in stabil ity.
  • Dolutegravir sodium which is used for preparation of form A of dol utegravir sodium can be prepared by methods as described in application WO 2010068253 or by preparations known in the literature.
  • the infrared absorption spectrum was obtained using a Perkin Elmer Precisely Spectrum 400 i nstrument usi ng K B r pel I et method.
  • E xampl e 1 Preparati on of crystal I i ne form A of dol utegravi r sodi um: A mixture of dolutegravir sodium (1 g) and dimethyl sulfoxide (250 ml) was heated at 130eC. The solution was cooled to 25-30eC. This solution was added dropwise to methanol (75 ml) at -10eC. Methanol (25 ml) was added to this mixture at -10eC and stirred for 6-7 hours. The mixture was then stirred for 15 minutes at 25eC. The solid filtered and dried under vacuum Y ield 0.8 g.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une nouvelle forme cristalline A de dolutégravir sodique ayant des pics de diffraction caractéristiques à 6,3, 7,8, 9,3, 11,4, 12,4, 13,5, 12,7, 15,1, 15,8, 18,3, 19,0, 19,6, 20,7, 22,8, 23,1, 24,3 et 25,8 ± 0,2 degré deux thêta selon un diagramme de diffraction des rayons X. La présente invention concerne en outre un procédé de préparation d'une forme cristalline A de dolutégravir sodique.
PCT/IB2017/052926 2016-05-30 2017-05-18 Nouvelle forme cristalline de dolutégravir sodique Ceased WO2017208105A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201621018583 2016-05-30
IN201621018583 2016-05-30

Publications (1)

Publication Number Publication Date
WO2017208105A1 true WO2017208105A1 (fr) 2017-12-07

Family

ID=59101521

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2017/052926 Ceased WO2017208105A1 (fr) 2016-05-30 2017-05-18 Nouvelle forme cristalline de dolutégravir sodique

Country Status (1)

Country Link
WO (1) WO2017208105A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116284047A (zh) * 2023-03-24 2023-06-23 天津大学 一种多替拉韦-间羟基苯甲酸共晶及其制备方法和应用
CN116496297A (zh) * 2023-03-24 2023-07-28 天津大学 一种多替拉韦草酸共晶及其制备方法和应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010068253A1 (fr) 2008-12-11 2010-06-17 Shionogi & Co., Ltd. Synthèse d'inhibiteurs carbamoylpyridone de l'intégrase du vih et intermédiaires
US8129385B2 (en) 2005-04-28 2012-03-06 Shionogi & Co., Ltd. Substituted 5-hydroxy-3,4,6,9,9a, 10-hexanhydro-2h-1-oxa04a,8a-diaza-anthracene-6,10-dioness
WO2015092752A1 (fr) 2013-12-20 2015-06-25 Mylan Laboratories Ltd. Nouvelle forme cristalline de dolutegravir sodium
WO2015118460A1 (fr) 2014-02-07 2015-08-13 Mylan Laboratories Ltd. Formes cristallines de sodium de dolutegravir
WO2015138933A1 (fr) 2014-03-13 2015-09-17 Assia Chemical Industries Ltd. Formes à l'état solide de dolutegravir sodium
WO2015139591A1 (fr) 2014-03-19 2015-09-24 杭州普晒医药科技有限公司 Forme cristalline du sel de sodium du dolutégravir et procédé pour sa préparation
US9206197B2 (en) 2011-09-14 2015-12-08 Mapi Pharma Ltd. Amorphous form of dolutegravir
WO2016016279A1 (fr) 2014-07-29 2016-02-04 Lek Pharmaceuticals D.D. Nouveaux hydrates de sodium de dolutegravir

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8129385B2 (en) 2005-04-28 2012-03-06 Shionogi & Co., Ltd. Substituted 5-hydroxy-3,4,6,9,9a, 10-hexanhydro-2h-1-oxa04a,8a-diaza-anthracene-6,10-dioness
WO2010068253A1 (fr) 2008-12-11 2010-06-17 Shionogi & Co., Ltd. Synthèse d'inhibiteurs carbamoylpyridone de l'intégrase du vih et intermédiaires
US9242986B2 (en) 2008-12-11 2016-01-26 Shionogi & Co., Ltd. Synthesis of carbamoylpyridone HIV integrase inhibitors and intermediates
US9206197B2 (en) 2011-09-14 2015-12-08 Mapi Pharma Ltd. Amorphous form of dolutegravir
WO2015092752A1 (fr) 2013-12-20 2015-06-25 Mylan Laboratories Ltd. Nouvelle forme cristalline de dolutegravir sodium
WO2015118460A1 (fr) 2014-02-07 2015-08-13 Mylan Laboratories Ltd. Formes cristallines de sodium de dolutegravir
WO2015138933A1 (fr) 2014-03-13 2015-09-17 Assia Chemical Industries Ltd. Formes à l'état solide de dolutegravir sodium
WO2015139591A1 (fr) 2014-03-19 2015-09-24 杭州普晒医药科技有限公司 Forme cristalline du sel de sodium du dolutégravir et procédé pour sa préparation
WO2016016279A1 (fr) 2014-07-29 2016-02-04 Lek Pharmaceuticals D.D. Nouveaux hydrates de sodium de dolutegravir

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116284047A (zh) * 2023-03-24 2023-06-23 天津大学 一种多替拉韦-间羟基苯甲酸共晶及其制备方法和应用
CN116496297A (zh) * 2023-03-24 2023-07-28 天津大学 一种多替拉韦草酸共晶及其制备方法和应用
CN116284047B (zh) * 2023-03-24 2024-05-24 天津大学 一种多替拉韦-间羟基苯甲酸共晶及其制备方法和应用

Similar Documents

Publication Publication Date Title
WO2017208105A1 (fr) Nouvelle forme cristalline de dolutégravir sodique
TWI491356B (zh) Synthesis of 2-ethyl-3,7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) quinolin-4-ylmethyl carbonate and a method for producing the same Crystallization of the pesticide composition
SE453195B (sv) Cefuroximaxetil i amorf form, forfarande for framstellning derav och komposition innehallande denna
JP6170146B2 (ja) チロシンキナーゼ阻害剤二マレイン酸塩のｉ型結晶およびその製造法
CN111295372A (zh) 硝羟喹啉前药及其用途
RU2009104959A (ru) Кристаллические противогрибковые соединения
MXPA06012220A (es) Procesos para preparar sodio de montelukast.
EP0882047A1 (fr) Quinolones et leur utilisation therapeutique
JP2019527724A5 (fr)
AU2016276426A1 (en) Polymorphic forms of Afatinib free base and Afatinib dimaleate
EP3083568A1 (fr) Procédé et intermédiaires pour la préparation d'enzalutamide
CN114746412A (zh) Kd-025的新晶型及其制备方法
RU2607083C2 (ru) Кристалл циклопептида высокой чистоты, а также способ его получения и его применение
CN103755723B (zh) 一种利福平i晶型的制备方法
WO2018167652A1 (fr) Procédé de préparation d'une forme amorphe du vénétoclax
WO2013034087A1 (fr) Cristaux d'hydrate de doripénème et leur procédé de préparation
CN103965185B (zh) 含有噻唑基和酯基的1,5-苯并二氮杂卓化合物及其应用
CN102464669A (zh) 无定形依维莫司及其制备方法
EP2231613A1 (fr) Sels de pipérazine de benzhydryle de montélukast et leur procédé de préparation
CN108675963B (zh) 嘧菌酯1，4二氧六环溶剂化物及制备方法
US20170354644A1 (en) Polymorphic Forms of Methyl((1S)-1-(((2S)-2-(5-(4'-(2-((2S)-1-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-5-yl)-4-biphenylyl)-1H-imidazol-2-yl)-1-pyrrolidinyl) carbonyl)-2-methylpropyl)carbamate and Salts Thereof
JPWO2020099923A5 (fr)
CN106749222B (zh) 艾沙康唑的晶型a及其制备方法、药物组合物和用途
WO2016107331A1 (fr) Nouvelle forme cristalline d'un composé cefathiamidine et son procédé de préparation
WO2014189308A1 (fr) Nouvelle forme cristalline du cefditoren pivoxil, et son procédé de préparation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17732219

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17732219

Country of ref document: EP

Kind code of ref document: A1