WO2002102761A1 - Nouveau procede pour la preparation de (is-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine - Google Patents

Nouveau procede pour la preparation de (is-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine Download PDF

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Publication number
WO2002102761A1
WO2002102761A1 PCT/FI2002/000518 FI0200518W WO02102761A1 WO 2002102761 A1 WO2002102761 A1 WO 2002102761A1 FI 0200518 W FI0200518 W FI 0200518W WO 02102761 A1 WO02102761 A1 WO 02102761A1
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WIPO (PCT)
Prior art keywords
cis
dichlorophenyl
tetrahydro
naphthalenamine
methyl
Prior art date
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Ceased
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PCT/FI2002/000518
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English (en)
Inventor
Ilpo Laitinen
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Fermion Oy
Original Assignee
Orion Yhtyma Fermion Oy
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
Priority claimed from FI20011271A external-priority patent/FI20011271A0/fi
Application filed by Orion Yhtyma Fermion Oy filed Critical Orion Yhtyma Fermion Oy
Priority to CA002448499A priority Critical patent/CA2448499A1/fr
Priority to EP02743288A priority patent/EP1401800A1/fr
Publication of WO2002102761A1 publication Critical patent/WO2002102761A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C07C209/70—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by reduction of unsaturated amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/82—Purification; Separation; Stabilisation; Use of additives
    • C07C209/86—Separation
    • C07C209/88—Separation of optical isomers

Definitions

  • the present invention relates to a novel process for the preparation of (1S- cis)-4-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-N-methyl- 1 -naphthalenamine (sertraline) comprising hydrogenation of N-[4-(3,4-dichlorophenyl)-3,4-dihydro- 5 1 (2H)-naphthalenylidene]methanamine.
  • One object of the present invention is to provide an improved preparation method for cis-sertraline or a pharmaceutically acceptable acid addition salt thereof.
  • the other object of the present invention is the pharmaceutical composition comprising cis-sertraline or a pharmaceutically acceptable acid addition salt thereof made by the process of the invention.
  • the present invention provides a process for the preparation of cis-sertraline comprising hydrogenating N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l(2H)- naphthalenylidene]methanamine in the presence of a catalyst and a dehalogenation inhibitor to achieve cis-racemate of 4-(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-N- methyl- 1 -naphthalenamine.
  • the ratio of cis:trans isomers is improved to as high as 97:3 and the formation of dehalogenation byproducts may be reduced to even less than 0.1 %. No further purification process is needed before resolution or crystallization. This is achieved by using the inhibitors of the invention in the hydrogenation process.
  • Cis-sertraline is prepared starting from 4-(3 ,4-dichlorophenyl)-3 ,4-dihy dro- 1 -
  • (2H)-naphthalenone (tetralone), which can be prepared by methods known in the art, e.g. as decsribed in US 5,019,655. Tetralone is reacted with monomethylamine to form an imine, which can be performed by methods known in the art, e.g. as described in US 4,536,518.
  • the imine obtained is further hydrogenated to cis- racemate of 4-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-N-methyl- 1 -naphthalenamine in the presence of a catalyst and a dehalogenation inhibitor of the invention. From this mixture, the cis-compound can be either resolved by e.g.
  • the hydrogenation of the imine is performed in the presence of a catalyst and an inhibitor, which is selected from the group consisting of hypophosphorous acid, esters of hypophosphorous acid, phosphorous acid, esters of phosphorous acid, phosphine and substituted phosphines.
  • Suitable inhibitors are e.g. mono-,di- and triesters of phosphorous acid, preferably trimethyl phosphite, triphenyl phosphite or tritolyl phosphite.
  • suitable phosphines are e.g. trimethylphosphine, triethylphosphine, triisopropylphosphine, tritolylphosphine and tribenzylphosphine.
  • the amount of the inhibitor used in the process is typically 0.5 - 10 mol %, preferably 3 - 5 mol %, based on the number of moles of the metal in the catalyst used.
  • the catalyst used can be any suitable catalyst known in the art, e.g. palladium on carbon, palladium on graphite, palladium on carbon paste or PtO 2 .
  • the catalyst is typically used in the amount of 0.1 - 1.0 % (w/w, calculated as the pure metal in the catalyst) based on the weight of the imine used.
  • the hydrogenation may be carried out in an organic solvent, which can be any suitable protic or aprotic solvent or mixtures thereof. Examples of solvents are e.g.
  • dimethylformamide DMF
  • esters like ethyl acetate, chlorinated hydrocarbons like methylene chloride or chloroform, or alcohols like methanol, ethanol or isopropanol.
  • alcohols like methanol, ethanol or isopropanol.
  • a lower alcohol e.g. methanol or ethanol or their mixture with DMF is used as a solvent.
  • the reaction can be carried out at a temperature of 0-100 °C, preferably at 20 - 50 °C.
  • the hydrogen pressure used is from 1 to 50 bar, preferably from 2 to 5 bar.
  • the reaction time can vary from half an hour to 24 hours depending on the catalyst used, on hydrogen pressure, on the reaction temperature and on the equipment used.
  • the hydrogenation time is about 2 to 6 hours.
  • N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l-(2H)-naphthalenylidene]-methanamine 50 g
  • methanol 300 ml
  • palladium on graphite 5 % 2.5 g
  • trimethyl phosphite 0.004 g
  • the reaction mixture is hydrogenated at 5 bar overpressure of hydrogen for 5 hours at about 40 °C.
  • the catalyst is removed by filtration and the cake is washed with methanol.
  • the cis:trans ratio is 97:3.
  • the amount of dehalogenation byproducts is ⁇ 0.1 %.
  • the reaction mixture can be used directly in the resolution step or crystallized as HC1 salt.
  • N-[4-(3,4-Dichlorophenyl)-3,4-dihydro-l(2H)-naphthalenylidene]methanamine 40 g
  • dimethylformamide 150 ml
  • methanol 150 ml
  • palladium on graphite catalyst 4 g
  • triphenyl phosphite 0.0010 g

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

On prépare de la (1S-cis)-4-(3,4-dichlorophényl)-1,2,3,4-tétrahydro-N-méthyl-1-naphtalènamine (sertraline), en hydrogénant de la N-[4-(3,4-dichlorophényl)-3,4-dihydro-1(2H)-naphtalènylidène]méthanamine en présence d'un inhibiteur de déhalogénation, par exemple à base de triphénylphosphite ou de triméthylphosphite, et d'un catalyseur.
PCT/FI2002/000518 2001-06-15 2002-06-14 Nouveau procede pour la preparation de (is-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine Ceased WO2002102761A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CA002448499A CA2448499A1 (fr) 2001-06-15 2002-06-14 Nouveau procede pour la preparation de (is-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine
EP02743288A EP1401800A1 (fr) 2001-06-15 2002-06-14 Nouveau procede pour la preparation de (is-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US29808801P 2001-06-15 2001-06-15
FI20011271 2001-06-15
FI20011271A FI20011271A0 (fi) 2001-06-15 2001-06-15 Valmistusmenetelmä
US60/298,088 2001-06-15

Publications (1)

Publication Number Publication Date
WO2002102761A1 true WO2002102761A1 (fr) 2002-12-27

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/FI2002/000518 Ceased WO2002102761A1 (fr) 2001-06-15 2002-06-14 Nouveau procede pour la preparation de (is-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine

Country Status (3)

Country Link
EP (1) EP1401800A1 (fr)
CA (1) CA2448499A1 (fr)
WO (1) WO2002102761A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004092110A3 (fr) * 2003-04-14 2005-06-09 Teva Pharma Hydrogenation d'intermediaires imine de la sertraline avec des catalyseurs
WO2005121074A3 (fr) * 2004-06-09 2006-05-18 Ranbaxy Lab Ltd Procedes pour la preparation de chlorhydrate de sertraline
WO2007071421A1 (fr) * 2005-12-23 2007-06-28 Sandoz Ag Procédé amélioré de synthèse de la sertraline
WO2007124920A1 (fr) * 2006-04-28 2007-11-08 Sandoz Ag Procédé de synthèse de la [4(s,r)-(3,4-dichlorophényl)-3,4-dihydro-1(2h)-naphtalén-1-ylidène]méthylamine
CN111632400A (zh) * 2020-06-21 2020-09-08 赤峰制药股份有限公司 一种烯胺盐重结晶纯化方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3474144A (en) * 1966-08-17 1969-10-21 Gaf Corp Catalytic reduction of chloronitro aromatic compounds
US4020107A (en) * 1975-04-07 1977-04-26 E. I. Du Pont De Nemours And Co. Catalytic reduction of halonitroaromatic compounds
US4536518A (en) * 1979-11-01 1985-08-20 Pfizer Inc. Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine
EP0292682A2 (fr) * 1987-05-28 1988-11-30 RIMAR CHIMICA S.p.A. Procédé de réduction catalytique de dérivés aromatiques nitro-halogonés
WO1999057093A1 (fr) * 1998-05-05 1999-11-11 EGIS Gyógyszergyár Rt. Procede de preparation de sertraline et de son 1,r-stereoisomere
WO2001068566A1 (fr) * 2000-03-14 2001-09-20 Teva Pharmaceutical Industries Ltd. Nouveau procede de preparation de (+)-cis-sertraline

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3474144A (en) * 1966-08-17 1969-10-21 Gaf Corp Catalytic reduction of chloronitro aromatic compounds
US4020107A (en) * 1975-04-07 1977-04-26 E. I. Du Pont De Nemours And Co. Catalytic reduction of halonitroaromatic compounds
US4536518A (en) * 1979-11-01 1985-08-20 Pfizer Inc. Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine
EP0292682A2 (fr) * 1987-05-28 1988-11-30 RIMAR CHIMICA S.p.A. Procédé de réduction catalytique de dérivés aromatiques nitro-halogonés
WO1999057093A1 (fr) * 1998-05-05 1999-11-11 EGIS Gyógyszergyár Rt. Procede de preparation de sertraline et de son 1,r-stereoisomere
WO2001068566A1 (fr) * 2000-03-14 2001-09-20 Teva Pharmaceutical Industries Ltd. Nouveau procede de preparation de (+)-cis-sertraline

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004092110A3 (fr) * 2003-04-14 2005-06-09 Teva Pharma Hydrogenation d'intermediaires imine de la sertraline avec des catalyseurs
US7276629B2 (en) 2003-04-14 2007-10-02 Teva Pharmaceutical Industries Ltd. Hydrogenation of imine intermediates of sertraline with catalysts
WO2005121074A3 (fr) * 2004-06-09 2006-05-18 Ranbaxy Lab Ltd Procedes pour la preparation de chlorhydrate de sertraline
WO2007071421A1 (fr) * 2005-12-23 2007-06-28 Sandoz Ag Procédé amélioré de synthèse de la sertraline
WO2007124920A1 (fr) * 2006-04-28 2007-11-08 Sandoz Ag Procédé de synthèse de la [4(s,r)-(3,4-dichlorophényl)-3,4-dihydro-1(2h)-naphtalén-1-ylidène]méthylamine
CN111632400A (zh) * 2020-06-21 2020-09-08 赤峰制药股份有限公司 一种烯胺盐重结晶纯化方法

Also Published As

Publication number Publication date
CA2448499A1 (fr) 2002-12-27
EP1401800A1 (fr) 2004-03-31

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