WO2005026121A1 - 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 Download PDF

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Publication number
WO2005026121A1
WO2005026121A1 PCT/IB2004/002956 IB2004002956W WO2005026121A1 WO 2005026121 A1 WO2005026121 A1 WO 2005026121A1 IB 2004002956 W IB2004002956 W IB 2004002956W WO 2005026121 A1 WO2005026121 A1 WO 2005026121A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound
azabicyclo
benzyl
carried out
Prior art date
Application number
PCT/IB2004/002956
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English (en)
Inventor
Mohammad Salman
Pakala Kumara Savithru Sarma
Sankaranarayanan Dharmarajan
Original Assignee
Ranbaxy Laboratories Limited
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 Limited filed Critical Ranbaxy Laboratories Limited
Priority to EP04769348A priority Critical patent/EP1670759A1/fr
Publication of WO2005026121A1 publication Critical patent/WO2005026121A1/fr

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    • 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%.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Steroid Compounds (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.
PCT/IB2004/002956 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 WO2005026121A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04769348A 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

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1168DE2003 2003-09-18
IN1168/DEL/2003 2003-09-18

Publications (1)

Publication Number Publication Date
WO2005026121A1 true WO2005026121A1 (fr) 2005-03-24

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
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

Country Status (2)

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

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007039884A1 (fr) 2005-10-05 2007-04-12 Ranbaxy Laboratories Limited Dérivés de 3 -azabicyclooctane en tant qu’antagonistes de récepteurs muscariniques
WO2007110782A1 (fr) 2005-12-30 2007-10-04 Ranbaxy Laboratories Limited Antagonistes des récepteurs muscariniques
US9133116B2 (en) 2010-09-28 2015-09-15 Panacea Biotec Ltd. Bicyclic compounds

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0413455A2 (fr) * 1989-08-16 1991-02-20 Pfizer Inc. Acides azabicyclo quinoline carboxyliques

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0413455A2 (fr) * 1989-08-16 1991-02-20 Pfizer Inc. Acides azabicyclo quinoline carboxyliques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Y. OGINO ET AL.: "Muscarinic M3 Receptor Antagonists with (2R)-2-[(1R)-3,3-Difluorocyclopentyl]-2-hydroxyphenylacetamide Structures. Part 2", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 2003, no. 13, 7 July 2003 (2003-07-07), OXFORD, GB, pages 2167 - 2172, XP002314639 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007039884A1 (fr) 2005-10-05 2007-04-12 Ranbaxy Laboratories Limited Dérivés de 3 -azabicyclooctane en tant qu’antagonistes de récepteurs muscariniques
WO2007110782A1 (fr) 2005-12-30 2007-10-04 Ranbaxy Laboratories Limited Antagonistes des récepteurs muscariniques
US9133116B2 (en) 2010-09-28 2015-09-15 Panacea Biotec Ltd. Bicyclic compounds

Also Published As

Publication number Publication date
EP1670759A1 (fr) 2006-06-21

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