WO2004087732A2 - Procede de preparation de (1s, 4s)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtylamine - Google Patents

Procede de preparation de (1s, 4s)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtylamine Download PDF

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Publication number
WO2004087732A2
WO2004087732A2 PCT/IN2004/000055 IN2004000055W WO2004087732A2 WO 2004087732 A2 WO2004087732 A2 WO 2004087732A2 IN 2004000055 W IN2004000055 W IN 2004000055W WO 2004087732 A2 WO2004087732 A2 WO 2004087732A2
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WIPO (PCT)
Prior art keywords
formula
compound
dichlorophenyl
poly
dihydro
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Ceased
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PCT/IN2004/000055
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English (en)
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WO2004087732A3 (fr
Inventor
Kanaksinh Jesingbhai Jadav
Trinadha Rao Chitturi
Rajamannar Thennati
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Sun Pharmaceutical Industries Ltd
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Sun Pharmaceutical Industries Ltd
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Publication of WO2004087732A2 publication Critical patent/WO2004087732A2/fr
Publication of WO2004087732A3 publication Critical patent/WO2004087732A3/fr
Anticipated expiration legal-status Critical
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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
    • C07C209/24—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Definitions

  • the present invention relates to a process for the preparation of (lS,4S)-4-(3,4- dichlorophenyl)-l,2,3,4-tetrahydro-N-methyl-l-naphthylamine, compound of formula 1.
  • ( 1 S ,4S)-4-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-N-methyl- 1 -naphthylamine, commonly known as sertraline (INN name) is useful in the treatment of depression, obsessive-compulsive disorder and panic disorder.
  • This patent discloses the preparation of N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l(2H)- napthalenylidenejmethanamine, compound of formula 3, by reaction of 4-(3,4- dichloro ⁇ henyl)-3,4-dihydro-l(2H)-naphthalenone, compound of formula 2, with methylamine in tetrahydrofuran in the presence of a lewis acid viz. TiCl 4 .
  • This invention uses TiCl 4 as a catalyst and a dehydrating agent. It is very reactive with water and forms dense white fumes with slightest exposure to atmosphere making its handling and usage very inconvenient.
  • the process of the present invention prepares compound of formula 1 starting with preparation of compound of formula 3 without a dehydrating agent in an acyclic or cyclic polyether solvent.
  • United States Patent No. 4855500 assigned to Pfizer, Inc. discloses preparation of compound of formula 3 by contacting the compound of formula 2 with methylamine in a reaction inert aprotic organic solvent in the presence of molecular sieves acting as dehydrating agent.
  • This invention uses molecular sieves which need to be regenerated involving an additional step.
  • the process of the present invention prepares compound of formula 1 starting with preparation of compound of formula 3 without the requirement of a dehydrating agent making it economical.
  • United States Patent No. 6232500 assigned to Pfizer, Inc., claims a process for preparing N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l(2H)-naphthalenylidene]methanamine, compound of formula 3, comprising reaction of the compound of formula 2 with monomethylamine in an alcohol solvent having a boiling point that is greater than about 55° C in 92% yield.
  • the process of the present invention prepares compound of formula 1 starting with preparation of compound of formula 3 in a non-alcoholic solvent in almost quantitative yields.
  • PCT publication 9957095 assigned to Egis Gyogyszergyar RT., provides a process for the preparation of N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l(2H)- naphthalenylidenejmethanamine, compound of formula 3, by reacting the compound of formula 2 with methylamine in the absence of a dehydrating agent in a lower alkanol to yield 90-95% of compound of formula 1.
  • the process of the present invention prepares compound of formula 1 starting with preparation of compound of formula 3 in a nonalcoholic solvent in almost quantitative yields.
  • PCT publication 0136378, assigend to Ciba Speciality Chemicals Holding Inc., provides a process for the preparation of compound of formula 3 by reacting compound of formula 2 with methylamine in the presence of
  • Compound of formula 3 prepared by this published invention could contain traces of sulfur compounds (due to sulfonic acid), which would be detrimental for subsequent hydrogenation since these can poison the hydrogenation catalyst.
  • the process of the present invention prepares compound of formula 1 starting with preparation of substantially pure compound of formula 3 in a non-alcoholic solvent in the absence of a catalyst.
  • the process of the present invention prepares compound of formula 3 in almost quantitative yields in an acyclic or cyclic polyether solvent which is hitherto not reported.
  • the object of the present invention is to prepare, (IS, 4S)-4-(3,4-dichlorophenyl)-l,2,3,4- tetrahydro-N-methyl-1-naphthylamine, compound of formula 1, starting with the preparation of compound of formula 3 in an environmentally friendly, non-hazardous reaction inert solvent without the use of dehydrating agent or catalyst.
  • the present invention describes a method for the preparation of compound of formula 1 by reacting compound of formula 3 with methylamine to yield compound of formula 3 in an acyclic or cyclic polyether solvent and then converting compound of formula 3 to a mixture of ( 1 S,4 S)-4-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-N-methyl- 1 -naphthyiamine, compound of formula 1, and its steroisomers followed by isolation of (lS,4S)-4-(3,4- dichlorophenyl)-l, 2,3, 4-tetrahydro-N-methyl-l -naphthyiamine, compound of formula 1.
  • the stereoisomers of ( 1 S,4S)-4-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-N-methyl- 1 - naphthyiamine are examples of ( 1 S,4S)-4-(3
  • step (a) i.e. reaction of compound of formula 3 with methylamine is carried out in an acyclic or cyclic polyether in the absence of an additional catalyst or a dehydrating agent.
  • the acyclic or cyclic polyether used in the present invention may be selected from the group comprising 1 ,2-dimethoxyethane, 1 ,4-dimethoxybutane, poly(alkylene glycol)s such as poly(ethylene glycol)s (PEGs), diglyme, 1,4-dioxane, crown ethers, mono alkylated or dialkylated poly(alkylene glycol)s wherein the alkyl group is selected from C ⁇ to C 6 linear or branched alkyl, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, triethylene glycol diethyl ether, tetraethylene glycol dimethyl ether (tetraglyme) & the like and mixtures thereof.
  • poly(alkylene glycol)s such as poly(ethylene glycol)s (PEGs), diglyme, 1,4-dioxane, crown ethers, mono alkylated or dialkylated poly(alkylene glycol)s
  • poly(alkylene glycol)s and monoalkylated or dialkylated poly(alkylene glycol)s being a mixtures are defined by an average molecular weight and do not have a specific boiling point, for e.g. PEG 200, poly(ethylene glycol) dimethyl ether 250 and the like.
  • the preferred polyether being an acyclic polyether, which includes polyether such as mixtures of poly(alkylene glycol)s like poly(ethylene glycol) 200 (PEG 200) having an average molecular weight of about 200, or poly(ethylene glycol) dimethyl ether with an average molecular weight of about 250.
  • polyether such as mixtures of poly(alkylene glycol)s like poly(ethylene glycol) 200 (PEG 200) having an average molecular weight of about 200, or poly(ethylene glycol) dimethyl ether with an average molecular weight of about 250.
  • step (a) is optionally carried out in the presence of catalytic amount of acid addition salt of an organic amine or an acid selected from mineral or an organic acid which can generate the acid addition salt insitu.
  • the organic a ine may be selected from Ci to C 4 alkyl mono, di or tri substituted amines such as triethylamine, diethylamine, monoethylamine, trimethylamine, dimethylamine, monomethylamine and the like.
  • the organic acid may be selected from acetic acid, citric acid, succinic acid, maleic acid, flimaric acid, oxalic acid, benzoic acid, pamoic acid, xinafoic acid, ascorbic acid and the like; alkylsulfonic acids such as methanesulfonic acid, ethanesulfonic acid and the like; halomethanesulfonic acids such as trifluoromethane sulfonic acid, fluoromethanesulfonic acid, chloromethanesulfonic acid, dichloromethanesulfonic acid, trichloromethane sulfonic acid and the like; substituted and unsubstituted aqueous arylsulfonic acids such as benzenesulfonic acid, para- toluenesulfonic acid, 4-chlorobenzenesulfonic acid and the like.
  • Mineral acid may be selected from halogen acids, sulfuric, phosphoric and
  • step (a) is carried out at temperature ranging from about -20 to 100°C, preferred being about 0 to 80°C.
  • step (a) reaction is carried out under pressure ranging from atmospheric to about 10 bars, preferably about 0.5 to 5 bars.
  • reaction of compound of formula 2 with methylamine to yield compound of formula 3 is carried out for about 5 to 25 hours, preferably for about 15 to 25 hours.
  • reaction of compound of formula 2 with methylamine may be carried out in an open or closed reaction system, preferred being closed reaction system such as an autoclave.
  • reaction mass may be worked up using standard techniques known to those skilled in the art such as solvent extraction, precipitation or solvent recovery.
  • additional polyether or an antisolvent may be added to precipitate the product and the precipitated product filtered out, or the polyether distilled out along with excess of methylamine, and a solvent added to the residue to precipitate or crystallize the product.
  • the compound of formula 3 may be optionally dried using standard techniques known to those skilled in the art such as in an air oven at elevated temperatures, fluid bed drying, tray drying, rotatory drying techniques with or without application of vacuum and / or under inert conditions.
  • the compound of formula 3 may be optionally further purified by methods known to those skilled in the art.
  • Compound of formula 3 may be converted to a mixture of compound of formula 1 and its stereoisomers using any process known to a person skilled in the art, preferably as disclosed in our Indian Patent IN 187170. The same is incorporated herein by reference.
  • Compound of formula 1 may be isolated from the mixture of compound of formula 1 and its stereoisomers by any process known to a person skilled in the art, preferably as disclosed in our Indian Patent IN 187170. The same is incorporated herein by reference.
  • a mixture of poly(ethylene glycol)-200 (125 ml), 4-(3,4-dichlorophenyl)-3,4-dihydro- l(2H)-naphthalenone (25g, 0.086 mol.) and methylamine (47.62g, 1.53 mol) is stirred at 48-50°C for 20 hrs in an autoclave. Thereafter, water (100 ml) is added under stirring, the product filtered, and washed with water (100ml). The product is suck dried, and further dried in air oven at 55-60°C.
  • a mixture of poly(ethylene glycol)-200 (125 ml), 4-(3,4-dichlorophenyl)-3,4-dihydro- l(2H)-naphthalenone (25g, 0.086 mol.) and methylamine (26.4g, 0.85 mol) is stirred at 50-55°C for 20 hrs in an autoclave. Thereafter, water (100 ml) is added under stirring, the product filtered, washed with water (100ml). The product is suck dried, and further dried in air oven at 55-60°C.
  • Weight of dry N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l(2H)- napthalenylidene]methanamine is 25.9g (99.2%).
  • Reaction is carried out in a similar manner as in example 1 using 1,2-dimethoxyethane (175ml) as solvent, instead of poly(ethylene glycol)-200.
  • solvent (alongwith excess methylamine) was distilled out under reduced pressure at 50-60° C until a thick slurry resulted.
  • Water (100ml) was added and the product recovered as in example 1.
  • Reaction is carried out using 4-(3,4-dichlorophenyl)-3,4-dihydro-l(2H)-naphthalenone (5g, 0.017 mol.) in a similar manner as in example 2 using 1,2-dimethoxyethane (30ml) as solvent in -a closed reaction flask, at ambient temperature for 20 hrs. Reaction is worked-up in manner similar to example 2 to get N-[4-(3,4-dichlorophenyl)-3,4-dihydro- l (2H)-napthalenylidene]methanamine.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention a trait à un procédé de préparation d'un composé de (1S, 4S)-4-(3,4-dichlorophényl)-1,2,3,4-tétrahydro-N-méthyl-1-naphtylamine, représenté par la formule (I). Ledit procédé consiste : (a) à faire réagir un composé de (3,4-dichlorophényl)-3,4-dihydro-1(2H)-napthalénone, représenté par la formule (II), avec de la méthylamine dans un polyéther acyclique ou cyclique, afin de produire un composé de N-[4-(3,4-dichlorophényl)-3,4-dihydro-1(2H)- naphtalénylidène]méthanamine, représenté par la formule (III) ; (b) à convertir le composé représenté par la formule (III) en un mélange du composé représenté par la formule (I) et de ses stéréoisomères ; et (c) à isoler le composé représenté par la formule (I).
PCT/IN2004/000055 2003-03-11 2004-03-08 Procede de preparation de (1s, 4s)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtylamine Ceased WO2004087732A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN267MU2003 2003-03-11
IN267/MUM/2003 2003-03-11

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WO2004087732A2 true WO2004087732A2 (fr) 2004-10-14
WO2004087732A3 WO2004087732A3 (fr) 2005-04-14

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PCT/IN2004/000055 Ceased WO2004087732A2 (fr) 2003-03-11 2004-03-08 Procede de preparation de (1s, 4s)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtylamine

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Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4536518A (en) * 1979-11-01 1985-08-20 Pfizer Inc. Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine

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