WO2002102761A1 - A novel process for the preparation of (is-cis) -4-(3, 4-dichlorophenyl) -1, 2, 3, 4 - tetrahydro-n-methyl-1-naphthalenamine - Google Patents
A novel process for the preparation of (is-cis) -4-(3, 4-dichlorophenyl) -1, 2, 3, 4 - tetrahydro-n-methyl-1-naphthalenamine Download PDFInfo
- 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
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cis
- dichlorophenyl
- tetrahydro
- naphthalenamine
- methyl
- Prior art date
Links
Classifications
-
- 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
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002448499A CA2448499A1 (en) | 2001-06-15 | 2002-06-14 | A novel process for the preparation of (is-cis) -4-(3, 4-dichlorophenyl) -1, 2, 3, 4 - tetrahydro-n-methyl-1-naphthalenamine |
EP02743288A EP1401800A1 (en) | 2001-06-15 | 2002-06-14 | A novel process for the preparation of (is-cis) -4-(3, 4-dichlorophenyl) -1, 2, 3, 4 - tetrahydro-n-methyl-1-naphthalenamine |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US29808801P | 2001-06-15 | 2001-06-15 | |
FI20011271A FI20011271A0 (en) | 2001-06-15 | 2001-06-15 | Production Process |
FI20011271 | 2001-06-15 | ||
US60/298,088 | 2001-06-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002102761A1 true WO2002102761A1 (en) | 2002-12-27 |
Family
ID=26161186
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FI2002/000518 WO2002102761A1 (en) | 2001-06-15 | 2002-06-14 | A novel process for the preparation of (is-cis) -4-(3, 4-dichlorophenyl) -1, 2, 3, 4 - tetrahydro-n-methyl-1-naphthalenamine |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1401800A1 (en) |
CA (1) | CA2448499A1 (en) |
WO (1) | WO2002102761A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004092110A2 (en) * | 2003-04-14 | 2004-10-28 | Teva Pharmaceutical Industries Ltd. | Hydrogenation of imine intermediates of sertraline with catalysts |
WO2005121074A2 (en) * | 2004-06-09 | 2005-12-22 | Ranbaxy Laboratories Limited | Processes for the preparation of sertraline hydrochloride |
WO2007071421A1 (en) * | 2005-12-23 | 2007-06-28 | Sandoz Ag | An improved process for the preparation of sertraline |
WO2007124920A1 (en) * | 2006-04-28 | 2007-11-08 | Sandoz Ag | Process for the preparation of [4(s,r)-(3,4-dichlorophenyl)-3,4-dihydro-1(2h)-naphthalen-1-ylidene]methylamine |
CN111632400A (en) * | 2020-06-21 | 2020-09-08 | 赤峰制药股份有限公司 | Recrystallization purification method of enamine salt |
Citations (6)
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 (en) * | 1987-05-28 | 1988-11-30 | RIMAR CHIMICA S.p.A. | Process for the catalytic reduction of aromatic nitro-halo-derivatives |
WO1999057093A1 (en) * | 1998-05-05 | 1999-11-11 | EGIS Gyógyszergyár Rt. | Process for the preparation of sertraline and its 1,r-stereoisomer |
WO2001068566A1 (en) * | 2000-03-14 | 2001-09-20 | Teva Pharmaceutical Industries Ltd. | Novel process for preparing (+)-cis-sertraline |
-
2002
- 2002-06-14 WO PCT/FI2002/000518 patent/WO2002102761A1/en not_active Application Discontinuation
- 2002-06-14 CA CA002448499A patent/CA2448499A1/en not_active Abandoned
- 2002-06-14 EP EP02743288A patent/EP1401800A1/en not_active Withdrawn
Patent Citations (6)
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 (en) * | 1987-05-28 | 1988-11-30 | RIMAR CHIMICA S.p.A. | Process for the catalytic reduction of aromatic nitro-halo-derivatives |
WO1999057093A1 (en) * | 1998-05-05 | 1999-11-11 | EGIS Gyógyszergyár Rt. | Process for the preparation of sertraline and its 1,r-stereoisomer |
WO2001068566A1 (en) * | 2000-03-14 | 2001-09-20 | Teva Pharmaceutical Industries Ltd. | Novel process for preparing (+)-cis-sertraline |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004092110A2 (en) * | 2003-04-14 | 2004-10-28 | Teva Pharmaceutical Industries Ltd. | Hydrogenation of imine intermediates of sertraline with catalysts |
WO2004092110A3 (en) * | 2003-04-14 | 2005-06-09 | Teva Pharma | Hydrogenation of imine intermediates of sertraline with catalysts |
US7276629B2 (en) | 2003-04-14 | 2007-10-02 | Teva Pharmaceutical Industries Ltd. | Hydrogenation of imine intermediates of sertraline with catalysts |
WO2005121074A2 (en) * | 2004-06-09 | 2005-12-22 | Ranbaxy Laboratories Limited | Processes for the preparation of sertraline hydrochloride |
WO2005121074A3 (en) * | 2004-06-09 | 2006-05-18 | Ranbaxy Lab Ltd | Processes for the preparation of sertraline hydrochloride |
WO2007071421A1 (en) * | 2005-12-23 | 2007-06-28 | Sandoz Ag | An improved process for the preparation of sertraline |
WO2007124920A1 (en) * | 2006-04-28 | 2007-11-08 | Sandoz Ag | Process for the preparation of [4(s,r)-(3,4-dichlorophenyl)-3,4-dihydro-1(2h)-naphthalen-1-ylidene]methylamine |
CN111632400A (en) * | 2020-06-21 | 2020-09-08 | 赤峰制药股份有限公司 | Recrystallization purification method of enamine salt |
Also Published As
Publication number | Publication date |
---|---|
EP1401800A1 (en) | 2004-03-31 |
CA2448499A1 (en) | 2002-12-27 |
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