WO2005028457A1 - Preparation de quetiapine - Google Patents

Preparation de quetiapine Download PDF

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Publication number
WO2005028457A1
WO2005028457A1 PCT/FI2004/000559 FI2004000559W WO2005028457A1 WO 2005028457 A1 WO2005028457 A1 WO 2005028457A1 FI 2004000559 W FI2004000559 W FI 2004000559W WO 2005028457 A1 WO2005028457 A1 WO 2005028457A1
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WO
WIPO (PCT)
Prior art keywords
ethyl
ethoxy
mixture
compound
bis
Prior art date
Application number
PCT/FI2004/000559
Other languages
English (en)
Inventor
Arne Grumann
Soini Huhta
Petteri Rummakko
Original Assignee
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
Application filed by Fermion Oy filed Critical Fermion Oy
Publication of WO2005028457A1 publication Critical patent/WO2005028457A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/08—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D281/02—Seven-membered rings
    • C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D281/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
    • C07D281/16—[b, f]-condensed
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers

Definitions

  • quetiapine I Several methods for the preparation of quetiapine I are known, as disclosed in e.g. GB 8607684, GB 8705574, and WO 01/55125.
  • halo derivative e.g. iminochloride
  • dibenzo[b,fj[l,4]-thiazepin-l l(10-H)-one with l-(hydroxyethoxyethyl)piperazine
  • reacting the aforementioned halo derivative with piperazine and reacting the resulting intermediate with a haloethoxyethanol and reacting a haloethylpiperazinylthiazepine derivative with ethylene glycol.
  • the target compound I is prepared by reacting dibenzo[b,f][l,4]thiazepin-ll-ylamine with a compound of the general formula II: II wherein PG is a is a hydroxyl protecting group selected from the group consisting of acetyl, benzoyl, pivaloyl, methoxymethyl, benzyl, 4-methoxybenzyl, allyl, tetrahydropyranyl, silyl, alkyl carbonate, aryl carbonate, aralkyl carbonate, benzyl carbonate, allylsulfonyl, benzylsulfonyl, toluenesulfonyl; preferably PG is methoxymethyl, benzyl, tetrahydropyryl or acyl; LG is a suitable leaving group selected from halogen, trifluoromethyl, O-p-toluenesulfonyl and O-methyl
  • Dibenzo[b,f][l,4]thiazepin ⁇ l 1-ylamine may be prepared e.g. according to J.Heterocyclic Chem., 34, 465 (1997) from 2-aminothiophenol and 2- chlorobenzonitrile.
  • the compound of formula II is [2-(2-benzyloxy-ethoxy)-ethyl]bis-(2-chloroethyl)amine VI.
  • intermediate VII is produced:
  • the debenzylation step is carried out with a suitable Lewis acid, preferably boron trichloride, or alternatively using catalytic hydrogenation.
  • a suitable Lewis acid preferably boron trichloride, or alternatively using catalytic hydrogenation.
  • the compound according to formula II is bis(2-chloroethyl)- ⁇ 2-[2-(tetrahydropyran-2-yloxy)ethoxy]ethyl ⁇ amine TV, whereby intermediate IX above, which can be deprotected to product I, is obtained.
  • [2-(2-benzyloxy-ethoxy)-ethyl]bis-(2-chloroethyl)amine VI may be prepared starting from (2-chloro-ethoxymethylbenzene) by reacting it with triethanolamine to obtain a dihydroxy compound.
  • the reaction is carried out without a solvent at a temperature of 20 -160 °C.
  • derivatives with alternative leaving groups at the 2-site may be used, e.g. other halogens, O-p-toluenesulfonyl or O-methanesulfonyl.
  • this alternative route involves reacting [2- (2-chloro-ethoxy)-ethoxymethyl]benzene TV (obtained from bromomethylbenzene and 2-(2-chloro-ethoxy)-ethanol) with diethanolamine:
  • the resulting diol V may be converted to the dichloro derivative VI, preferably using thionyl chloride.
  • Triethanolamine 150 ml, 1 mol was charged into a reaction flask and warmed to 60 °C.
  • 60% sodium hydride (16 g, 0.4 mol) was added in small portions at 60-100 °C.
  • the mixture was stirred for 30 min. at 60-100 °C.
  • (2-chloroethoxymethyl)- benzene 60 g, 0.35 mol
  • potassium iodide 0.1 g
  • the mixture was warmed for 6 h at 140 °C.
  • the mixture was cooled to 30 °C. 10% NaCl-water (300 ml) was added, and the obtained solution was washed with a mixture of 80 ml hexane and 20 ml toluene.
  • the product was used without further purification.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

Abstract

La présente invention concerne un procédé de préparation de quétiapine, consistant à faire réagir la dibenzo[b,f][1,4]thiazépin-11-ylamine avec un composé de formule générale (II), ainsi que de nouveaux intermédiaires utiles dans la mise en oeuvre dudit procédé.
PCT/FI2004/000559 2003-09-23 2004-09-23 Preparation de quetiapine WO2005028457A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US50498303P 2003-09-23 2003-09-23
US60/504,983 2003-09-23

Publications (1)

Publication Number Publication Date
WO2005028457A1 true WO2005028457A1 (fr) 2005-03-31

Family

ID=34375550

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/FI2004/000559 WO2005028457A1 (fr) 2003-09-23 2004-09-23 Preparation de quetiapine

Country Status (1)

Country Link
WO (1) WO2005028457A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009095529A1 (fr) * 2008-01-31 2009-08-06 Fermion Oy Procédé de préparation de quétiapine
US7687622B2 (en) 2005-04-14 2010-03-30 Teva Pharmaceutical Industries, Ltd Process for preparing quetiapine fumarate
WO2010100623A1 (fr) 2009-03-04 2010-09-10 Ranbaxy Laboratories Limited Procede de preparation de fumarate de quetiapine
DE202009018024U1 (de) 2008-08-01 2010-12-09 Krka Tovarna Zdravil, D.D., Novo Mesto Quetiapin-Zusammensetzung
US8101597B2 (en) 2007-05-07 2012-01-24 Actavis Group Ptc Ehf Quetiapine salts and their polymorphs
CN103304515A (zh) * 2012-03-07 2013-09-18 华东师范大学 11-氨基二苯并［b,f］［1,4］硫氮杂卓的制备方法
CN111492046A (zh) * 2017-12-20 2020-08-04 亨斯迈石油化学有限责任公司 基于芳族的聚醚胺烷氧基化物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2891063A (en) * 1959-06-16 Piperazine derivatives and process of
US3539573A (en) * 1967-03-22 1970-11-10 Jean Schmutz 11-basic substituted dibenzodiazepines and dibenzothiazepines
EP0711763A1 (fr) * 1993-07-28 1996-05-15 Santen Pharmaceutical Co., Ltd. Nouveau derive de 1,4-di(phenylalkyl)piperazine

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2891063A (en) * 1959-06-16 Piperazine derivatives and process of
US3539573A (en) * 1967-03-22 1970-11-10 Jean Schmutz 11-basic substituted dibenzodiazepines and dibenzothiazepines
EP0711763A1 (fr) * 1993-07-28 1996-05-15 Santen Pharmaceutical Co., Ltd. Nouveau derive de 1,4-di(phenylalkyl)piperazine

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DOUMAUX A R ET AL: "Hydroxide Tetrakis(2-hydroxyethyl)ammonium", JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 38, no. 20, 1973, pages 3630 - 3632, XP002316540, ISSN: 0022-3263 *
RYCKMANS THOMAS ET AL: "Dual NK(1) antagonists--serotonin reuptake inhibitors as potential antidepressants. Part 2: SAR and activity of benzyloxyphenethyl piperazine derivatives.", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 4 NOV 2002, vol. 12, no. 21, 4 November 2002 (2002-11-04), pages 3195 - 3198, XP002317322, ISSN: 0960-894X *
SUZUKI R ET AL: "Synthesis of azacrown ethers modified with side-chains containing germanium", JOURNAL OF ORGANOMETALLIC CHEMISTRY, ELSEVIER-SEQUOIA S.A. LAUSANNE, CH, vol. 636, no. 1-2, 25 November 2001 (2001-11-25), pages 108 - 123, XP004311765, ISSN: 0022-328X *
WILSON E ET AL: "NITROGEN MUSTARDS", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, vol. 73, August 1951 (1951-08-01), pages 3635 - 3636, XP001061588, ISSN: 0002-7863 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7687622B2 (en) 2005-04-14 2010-03-30 Teva Pharmaceutical Industries, Ltd Process for preparing quetiapine fumarate
US8101597B2 (en) 2007-05-07 2012-01-24 Actavis Group Ptc Ehf Quetiapine salts and their polymorphs
WO2009095529A1 (fr) * 2008-01-31 2009-08-06 Fermion Oy Procédé de préparation de quétiapine
US8420807B2 (en) 2008-01-31 2013-04-16 Fermion Oy Process for the preparation of quetiapine
DE202009018024U1 (de) 2008-08-01 2010-12-09 Krka Tovarna Zdravil, D.D., Novo Mesto Quetiapin-Zusammensetzung
WO2010100623A1 (fr) 2009-03-04 2010-09-10 Ranbaxy Laboratories Limited Procede de preparation de fumarate de quetiapine
CN103304515A (zh) * 2012-03-07 2013-09-18 华东师范大学 11-氨基二苯并［b,f］［1,4］硫氮杂卓的制备方法
CN111492046A (zh) * 2017-12-20 2020-08-04 亨斯迈石油化学有限责任公司 基于芳族的聚醚胺烷氧基化物
JP2021507076A (ja) * 2017-12-20 2021-02-22 ハンツマン ペトロケミカル エルエルシーＨｕｎｔｓｍａｎ Ｐｅｔｒｏｃｈｅｍｉｃａｌ ＬＬＣ 芳香族系ポリエーテルアミンアルコキシレート
EP3728541A4 (fr) * 2017-12-20 2021-09-15 Huntsman Petrochemical LLC Alcoxylates de polyétheramine à base aromatique
CN111492046B (zh) * 2017-12-20 2022-09-09 亨斯迈石油化学有限责任公司 基于芳族的聚醚胺烷氧基化物
US11603436B2 (en) 2017-12-20 2023-03-14 Huntsman Petrochemical Llc Aromatic-based polyetheramine alkoxylates
JP7372921B2 (ja) 2017-12-20 2023-11-01 ハンツマン ペトロケミカル エルエルシー 芳香族系ポリエーテルアミンアルコキシレート

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