GB2557867A8 - New synthetic path to vortioxetine salts - Google Patents

New synthetic path to vortioxetine salts

Info

Publication number
GB2557867A8
GB2557867A8 GB1520332.6A GB201520332A GB2557867A8 GB 2557867 A8 GB2557867 A8 GB 2557867A8 GB 201520332 A GB201520332 A GB 201520332A GB 2557867 A8 GB2557867 A8 GB 2557867A8
Authority
GB
United Kingdom
Prior art keywords
vortioxetine
give
piperazin
theta
preparation
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.)
Withdrawn
Application number
GB1520332.6A
Other versions
GB2557867A (en
GB201520332D0 (en
Inventor
Haferkamp Sven
Manfred Frech Christian
Aebersold Christine
Grieco Gabriele
Kieliger Nicole
Geber Aeschbacher Roman
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.)
Azad Pharma AG
Original Assignee
Azad Pharmaceutical Ingredients AG
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 Azad Pharmaceutical Ingredients AG filed Critical Azad Pharmaceutical Ingredients AG
Priority to GB1520332.6A priority Critical patent/GB2557867A/en
Publication of GB201520332D0 publication Critical patent/GB201520332D0/en
Publication of GB2557867A publication Critical patent/GB2557867A/en
Publication of GB2557867A8 publication Critical patent/GB2557867A8/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines

Abstract

The preparation of vortioxetine free base 4 and pharmaceutically acceptable vortioxetine salts, is achieved by one of: oxidation of a 1-{2-[(2,4-dimethylphenyl)sulfanyl]cyclohexyl}piperazine derivative of formula 21 (where the cyclohexyl moiety is mono- or di-unsaturated); activation of 1-phenylpiperazine by oxidisation to give compound (10) and reacting (10) with 2,4-dimethylbenzensulfenyl chloride, before reduction to vortioxetine 4; or reaction of (2-(piperazin-1-yl)aniline) 2 with tert-butyl nitrite and tetrafluoroboric acid to give (2-piperazin-1-yl)benzenediazonium tetrafluoroborate salt 3 and then reacting compound 3 in the presence of alkali 2,4-dimethylbenzenethiolate and a metal catalyst to give vortioxetine 4. A process for the preparation of a particular polymorphic form of vortioxetine hydrobromide with an X-ray powder diffraction pattern with peaks at 2 theta (±0.2º 2-theta): 7.9, 14.8, 17.8 and 26.8 is also disclosed comprising cooling crystallisation using chloroform (CHCl3) as a solvent over various cooling cycles. The invention also relates to pharmaceutical compositions comprising the polymorph of vortioxetine hydrobromide for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD).
GB1520332.6A 2015-11-18 2015-11-18 New synthetic path to vortioxetine salts Withdrawn GB2557867A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB1520332.6A GB2557867A (en) 2015-11-18 2015-11-18 New synthetic path to vortioxetine salts

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB1520332.6A GB2557867A (en) 2015-11-18 2015-11-18 New synthetic path to vortioxetine salts

Publications (3)

Publication Number Publication Date
GB201520332D0 GB201520332D0 (en) 2015-12-30
GB2557867A GB2557867A (en) 2018-07-04
GB2557867A8 true GB2557867A8 (en) 2018-08-01

Family

ID=55132970

Family Applications (1)

Application Number Title Priority Date Filing Date
GB1520332.6A Withdrawn GB2557867A (en) 2015-11-18 2015-11-18 New synthetic path to vortioxetine salts

Country Status (1)

Country Link
GB (1) GB2557867A (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111032635B (en) * 2017-09-20 2023-02-28 浙江华海药业股份有限公司 N-formyl vortioxetine, preparation method thereof and vortioxetine solid preparation
CN112250642A (en) * 2020-10-28 2021-01-22 合肥亿帆生物制药有限公司 Preparation method of hydrobromic acid vortioxetine impurity standard substance

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI2044043T2 (en) * 2006-06-16 2021-04-30 H. Lundbeck A/S 1- yš- (2, 4-dimethylphenylsulfanyl) -phenylćpiperazine as a compound with combined serotonin reuptake, 5-ht3 and 5-ht1a activity for the treatment of cognitive impairment
US9499504B2 (en) * 2012-09-19 2016-11-22 Sandoz Ag Crystalline form of vortioxetine hydrobromide
EP2878596A1 (en) * 2013-11-29 2015-06-03 LEK Pharmaceuticals d.d. Synthesis of vortioxetine via (2-(piperazine-1-yl)phenyl)lithium intermediates
CN104829558B (en) * 2014-02-10 2020-03-03 江苏豪森药业集团有限公司 Preparation method of diaryl thioether amine compound
US9687484B2 (en) * 2014-07-18 2017-06-27 Dipharma Francis S.R.L. Crystalline forms of an antidepressant compound
CN104447622B (en) * 2014-11-28 2017-01-04 郑州大明药物科技有限公司 Hydrobromic acid irrigates the preparation method for western spit of fland beta crystal
CN105367515B (en) * 2015-05-08 2017-10-27 北京北陆药业股份有限公司 A kind of preparation method of hydrobromic acid Vortioxetine alpha-crystal form

Also Published As

Publication number Publication date
GB2557867A (en) 2018-07-04
GB201520332D0 (en) 2015-12-30

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Legal Events

Date Code Title Description
AT Applications terminated before publication under section 16(1)
S20A Reinstatement of application (sect. 20a/patents act 1977)

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Effective date: 20170803

S20A Reinstatement of application (sect. 20a/patents act 1977)

Free format text: REQUEST FOR REINSTATEMENT ALLOWED

Effective date: 20170907

WAP Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1)