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WO2002036540A2 - PROCEDE DE PREPARATION D'UN DERIVE DE β-PHENETHYLAMINE - Google Patents

PROCEDE DE PREPARATION D'UN DERIVE DE β-PHENETHYLAMINE

Info

Publication number
WO2002036540A2
WO2002036540A2 PCT/IB2001/001996 IB0101996W WO0236540A2 WO 2002036540 A2 WO2002036540 A2 WO 2002036540A2 IB 0101996 W IB0101996 W IB 0101996W WO 0236540 A2 WO0236540 A2 WO 0236540A2
Authority
WO
WIPO (PCT)
Prior art keywords
formula
vii
sibutramine
amine
cyclobutyl
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.)
Ceased
Application number
PCT/IB2001/001996
Other languages
English (en)
Other versions
WO2002036540A3 (fr
Inventor
Sharad Kumar Vyas
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.)
Torrent Pharmaceuticals Ltd
Original Assignee
Torrent Pharmaceuticals Ltd
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 Torrent Pharmaceuticals Ltd filed Critical Torrent Pharmaceuticals Ltd
Priority to AU2002210816A priority Critical patent/AU2002210816A1/en
Publication of WO2002036540A2 publication Critical patent/WO2002036540A2/fr
Publication of WO2002036540A3 publication Critical patent/WO2002036540A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/29—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
    • 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
    • C07C209/28—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 by reduction with other reducing agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring

Definitions

  • Sibutramine is also useful in the treatment of depression, Parkinson's disease, Non Insulin Dependent Diabetes Mellitus
  • NIDDM NIRDM
  • epilepsy Barker et al, WO 97/20810
  • step (f) Eschweiler - Clarke methylation of the primary amine (VII) to yield the target compound Sibutramine.
  • the Reaction-2 above in step (b) gives an optimum yield of 80% for the magnesium complex (IV) when the ethereal solvent used initially for the preparation of Grignard reagent is removed by distillation and the reaction is carried out in an inert solvent like toluene or xylene, preferably toluene, and the
  • the first object of the present invention is to provide a simple, cost effective
  • Another object of the invention is to provide for a simple, cost effective and
  • Yet another object of the invention is to provide a process for formation of the intermediate magnesium complex (IV) wherein the reaction time is reduced with corresponding reduction in reactor occupancy and the requirement of the utilities
  • the present invention provides a process for the production of
  • the ratio of Grignard reagent to nitrile (III) used is preferably 3
  • the magnesium complex (TV) was cleaved under basic conditions, by
  • ammonium hydroxide and ammonium chloride at 0 to 10°C in a time period of 2
  • the imine was immediately reduced by using a metal hydride such as sodium
  • the target compound sibutramine can be prepared from l-[l-(4-chlorophen yl)cyclobutyl]-3-methyl butylamine (VII) first by converting it to its hydrochloride
  • the total time period involved for the conversion of the magnesium complex IV to the key intermediate, the amine (VII), by the process of the instant invention is around 22 hours. This is much lower than the time period involved in the prior
  • Leuckart reaction alone was 20 to 24 hours.
  • the present invention gave a significantly higher yield of 66%. Hence, the present invention provides a reliable reproducible, high yield and economical process for the synthesis of Sibutramine.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Un procédé de production de Sibutramine, c'est-à-dire de N-1-[1-(4-chlorophényl) cyclobutyl]-3-méthylbutyl-N, N-diméthylamine de formule (I) comprend les étapes suivantes: (a) on fait réagir un nitrile, du 1-(4-chlorophényl) cyclobutyl carbonitrile de formule (III) avec un réactif Grignard, plus exactement du bromure de magnésium isobutyle pour produire le complexe de magnésium de formule (IV); (b) on sépare le complexe de magnésium de formule (IV) dans des conditions basiques pour former une imine de formule (VIII); (c) on réduit l'imine de formule (VIII) à l'aide d'un hydrure métallique pour obtenir une amine de formula (VII), et (d) on convertit l'amine (VII) d'abord sous forme de son chlorhydrate puis en Sibutramine de formule (I) au moyen d'une méthylation de Eschweiler-Clarke. Formules (I), (III), (IV), (VIII), (VII)
PCT/IB2001/001996 2000-11-02 2001-10-25 PROCEDE DE PREPARATION D'UN DERIVE DE β-PHENETHYLAMINE Ceased WO2002036540A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002210816A AU2002210816A1 (en) 2000-11-02 2001-10-25 Process for preparation of beta-phenethylamine derivative

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN612CA2000 2000-11-02
IN612/CAL/2000 2000-11-02

Publications (2)

Publication Number Publication Date
WO2002036540A2 true WO2002036540A2 (fr) 2002-05-10
WO2002036540A3 WO2002036540A3 (fr) 2002-07-18

Family

ID=11096985

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2001/001996 Ceased WO2002036540A2 (fr) 2000-11-02 2001-10-25 PROCEDE DE PREPARATION D'UN DERIVE DE β-PHENETHYLAMINE

Country Status (2)

Country Link
AU (1) AU2002210816A1 (fr)
WO (1) WO2002036540A2 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004030663A1 (fr) * 2002-10-05 2004-04-15 Hanmi Pharm. Co., Ltd. Composition pharmaceutique comprenant de l'hemihydrate de methanesulfonate de sibutramine cristallin
CN100342851C (zh) * 2002-10-05 2007-10-17 韩美药品株式会社 包含西布曲明甲磺酸盐半水合物晶体的药物组合物
US7989500B2 (en) 2006-09-15 2011-08-02 Reviva Pharmaceuticals, Inc. Synthesis, methods of using, and compositions of cycloalkylmethylamines
WO2013102195A1 (fr) 2011-12-30 2013-07-04 Reviva Pharmaceuticals, Inc. Compositions, synthèses et procédés d'utilisation de dérivés de phénylcycloalkylméthylamine
US8604244B2 (en) 2010-07-02 2013-12-10 Reviva Pharmaceuticals, Inc. Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives
CN106565007A (zh) * 2016-11-09 2017-04-19 烟台史密得机电设备制造有限公司 一种三元复合驱采出水的除油剂及其制备方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IE52768B1 (en) * 1981-04-06 1988-02-17 Boots Co Ltd 1-arylcyclobutylalkylamine compounds useful as therapeutic agents
GB8501192D0 (en) * 1985-01-17 1985-02-20 Boots Co Plc Therapeutic agents
US6331571B1 (en) * 1998-08-24 2001-12-18 Sepracor, Inc. Methods of treating and preventing attention deficit disorders

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004030663A1 (fr) * 2002-10-05 2004-04-15 Hanmi Pharm. Co., Ltd. Composition pharmaceutique comprenant de l'hemihydrate de methanesulfonate de sibutramine cristallin
CN100342851C (zh) * 2002-10-05 2007-10-17 韩美药品株式会社 包含西布曲明甲磺酸盐半水合物晶体的药物组合物
US7989500B2 (en) 2006-09-15 2011-08-02 Reviva Pharmaceuticals, Inc. Synthesis, methods of using, and compositions of cycloalkylmethylamines
US8338632B2 (en) 2006-09-15 2012-12-25 Reviva Pharmaceuticals, Inc. Cycloalkylmethylamines
US8372883B2 (en) 2006-09-15 2013-02-12 Reviva Pharmaceuticals, Inc. Methods of using cycloalkylmethylamines
US8445714B2 (en) 2006-09-15 2013-05-21 Reviva Pharmaceuticals, Inc. Cycloalkylmethylamines
US9296681B2 (en) 2006-09-15 2016-03-29 Reviva Pharmaceuticals, Inc. Cycloalkylmethylamines
US9302981B2 (en) 2006-09-15 2016-04-05 Reviva Pharmaceuticals, Inc. Synthesis, methods of using, and compositions of cycloalkylmethylamines
US8604244B2 (en) 2010-07-02 2013-12-10 Reviva Pharmaceuticals, Inc. Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives
US9096515B2 (en) 2010-07-02 2015-08-04 Reviva Pharmaceuticals, Inc. Methods of using cycloalkylmethylamine derivatives
WO2013102195A1 (fr) 2011-12-30 2013-07-04 Reviva Pharmaceuticals, Inc. Compositions, synthèses et procédés d'utilisation de dérivés de phénylcycloalkylméthylamine
CN106565007A (zh) * 2016-11-09 2017-04-19 烟台史密得机电设备制造有限公司 一种三元复合驱采出水的除油剂及其制备方法

Also Published As

Publication number Publication date
WO2002036540A3 (fr) 2002-07-18
AU2002210816A1 (en) 2002-05-15

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