EP1670759A1 - Procede de preparation de (1$g(a), 5$g(a), 6$g(a))-6-aminomethyl-3-benzyl-3-azabicyclo 3.1.0|hexane - Google Patents

Procede de preparation de (1$g(a), 5$g(a), 6$g(a))-6-aminomethyl-3-benzyl-3-azabicyclo 3.1.0|hexane

Info

Publication number
EP1670759A1
EP1670759A1 EP04769348A EP04769348A EP1670759A1 EP 1670759 A1 EP1670759 A1 EP 1670759A1 EP 04769348 A EP04769348 A EP 04769348A EP 04769348 A EP04769348 A EP 04769348A EP 1670759 A1 EP1670759 A1 EP 1670759A1
Authority
EP
European Patent Office
Prior art keywords
formula
compound
azabicyclo
benzyl
carried out
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.)
Withdrawn
Application number
EP04769348A
Other languages
German (de)
English (en)
Inventor
Mohammad Salman
Pakala Kumara Savithru Sarma
Sankaranarayanan Dharmarajan
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.)
Ranbaxy Laboratories Ltd
Original Assignee
Ranbaxy Laboratories 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 Ranbaxy Laboratories Ltd filed Critical Ranbaxy Laboratories Ltd
Publication of EP1670759A1 publication Critical patent/EP1670759A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered

Definitions

  • the present invention relates to a new and indiistrially advantageous process for the preparation of (l ⁇ , 5 ⁇ , 6 ⁇ )-6-aminomethyl-3-benzyl-3-azabicyclo[3.1.0]hexane of Formula I
  • This compound is a key intermediate for the synthesis of azabicyclo quinolone derivatives, which are useful as antimicrobials, and fox the synthesis of various azabicyclo [3.1.0]hexane derivatives, which are useful as muscarinic receptor antagonists.
  • azabicyclo quinolone derivatives are disclosed in U.S. Patent Nos. 5,164,402, 5,391,763, 5,229,396, 5,266,569 and European Patent Application No. 0413455 A2.
  • the azabicyclo quinolone derivatives reportedly are useful in the treatment of bacterial infections of broad spectrum, particularly against sensitive and resistant strains of gram positive pathogens, such as methicillin resistant staphylococcus aureus (MRS A), methicillin resistant staphylococcus epidermidis (MRSE), quinolone resistant staphylococcus aureus (QRSA) and Vancomycin resistant enterococci (VRSE).
  • MRS A methicillin resistant staphylococcus aureus
  • MRSE methicillin resistant staphylococcus epidermidis
  • QRSA quinolone resistant staphylococcus aureus
  • VRSE Vancomycin resistant enterococci
  • Patent Nos. 5,164,402, 5,391,763, 5,229,396, 5,266,569 and European Patent Application No. 0413455 A2 which comprises: (1) oxidizing [l ⁇ ,5 ⁇ ,6 ⁇ ]-3-benzyl-6-hydroxymethyl-3- azabicyclo[3.1.0]hexane of Formula II
  • Such limitations include the following: (i) the process requires the use of oxalyl chloride, which is corrosive, toxic, moisture sensitive and hence difficult to handle on commercial scale; (ii) very low temperature conditions are employed (i.e., 65°C), which are very difficult to maintain at commercial scale, requiring special equipment to maintain such temperature conditions; (iii) the process requires the use of lithium aluminum hydride, which is corrosive, air sensitive, highly flammable and hygroscopic, and thus, poses a handling problem; (iv) lithium aluminum hydride is an expensive reagent that increases the overall cost of preparation of final product; and
  • the reaction of the compound of Formula II with methane sulphonyl chloride can be carried out in an organic solvent, which can be selected from, for example, dichloromethane, dichloroethane, chloroform, ethyl acetate, and a mixture thereof.
  • the reaction of the compound of Formula II with methane sulphonyl chloride can be carried out in the presence of an organic base, which can be selected from, for example, triethylamine, pyridine and a mixture thereof. In some embodiments, the organic base is triethylamine.
  • the reaction of the compound of Formula II with methane sulphonyl chloride can be carried out in the presence of a catalyst, wherein the catalyst is 4-dimethylamino pyridine.
  • the reaction of the compound of Formula II with methane sulphonyl chloride is carried out at a temperature of from about 0 °C to about 30 °C.
  • reaction of the compound of Formula V with sodium azide to give the compound of Formula VI is carried out in an organic solvent, for example, dimethylformamide, dimethylsulphoxide, and a mixture thereof.
  • reaction of the compound of Formula V with sodium azide is carried out at a temperature from about 50 °C to about 100 °C.
  • the reduction of the compound of Formula VI to give the compound of Formula I is carried out in an organic solvent, for example, tetrahydrofuran, 1,4-dioxolane, and a mixture thereof.
  • the reduction of the compound of Formula VI is carried out with a reducing agent, wherein the reducing agent is triphenyl phosphine.
  • the reaction in step i) can be carried out in an organic solvent and in the presence of a catalyst and an organic base at a temperature from about 0 °C to about 30 °C.
  • the catalyst can be N,N-dimethyl amino pyridine.
  • the organic base can be triethylamine, pyridine or a mixture thereof.
  • the organic solvent can be dichloromethane, dichloroethane, chloroform, ethyl acetate, or a mixture thereof.
  • the reaction in step ii) can be carried out in an organic solvent at a temperature ranging from about 90 to about 110°C.
  • the organic solvent can be dimethylformamide, dimethylsulphoxide, or a mixture thereof.
  • the reaction in step iii) can be carried out using a reducing agent in an organic solvent.
  • the reducing agent can be triphenyl phosphine.
  • the organic solvent can be tetrahydrofuran, dimethylsulphoxide, 1,4-dioxolane, or a mixture thereof.
  • reaction mixture was diluted with dichloromethane and washed with saturated aqueous solution of sodium bicarbonate.
  • the organic layer was separated, washed with a water and brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to yield the title compound with a yield of 74%.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne un nouveau et avantageux procédé industriel de préparation de (1α, 5α, 6α)-6-aminométhyl-3-benzyl-3-azabicyclo[3.1.0]hexane, qui constitue un produit intermédiaire clé pour la synthèse de dérivés d'azabicyclo quinolone utiles comme agents anti-microbiens et pour la synthèse de divers dérivés d'azabicyclo[3.1.0]hexane.
EP04769348A 2003-09-18 2004-09-13 Procede de preparation de (1$g(a), 5$g(a), 6$g(a))-6-aminomethyl-3-benzyl-3-azabicyclo 3.1.0|hexane Withdrawn EP1670759A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1168DE2003 2003-09-18
PCT/IB2004/002956 WO2005026121A1 (fr) 2003-09-18 2004-09-13 Procede de preparation de (1$g(a), 5$g(a), 6$g(a))-6-aminomethyl-3-benzyl-3-azabicyclo[3.1.0]hexane

Publications (1)

Publication Number Publication Date
EP1670759A1 true EP1670759A1 (fr) 2006-06-21

Family

ID=34308046

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04769348A Withdrawn EP1670759A1 (fr) 2003-09-18 2004-09-13 Procede de preparation de (1$g(a), 5$g(a), 6$g(a))-6-aminomethyl-3-benzyl-3-azabicyclo 3.1.0|hexane

Country Status (2)

Country Link
EP (1) EP1670759A1 (fr)
WO (1) WO2005026121A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090131410A1 (en) 2005-10-05 2009-05-21 Naresh Kumar 3-azabicyclooctane derivatives as muscarinic receptor antagonists
EP1968980A1 (fr) 2005-12-30 2008-09-17 Ranbaxy Laboratories, Ltd. Antagonistes des récepteurs muscariniques
WO2012042539A2 (fr) 2010-09-28 2012-04-05 Panacea Biotec Ltd Nouveaux composés bicycliques

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991002526A1 (fr) * 1989-08-16 1991-03-07 Pfizer Inc. Acides azabicyclo quinolone carboxyliques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005026121A1 *

Also Published As

Publication number Publication date
WO2005026121A1 (fr) 2005-03-24

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