WO2015150891A1 - Procédé de préparation de mono-[2-(5-azétidin-3-ylméthyl-[1,3,4]oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]ester d'acide sulfurique trans - Google Patents

Procédé de préparation de mono-[2-(5-azétidin-3-ylméthyl-[1,3,4]oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]ester d'acide sulfurique trans Download PDF

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Publication number
WO2015150891A1
WO2015150891A1 PCT/IB2014/067331 IB2014067331W WO2015150891A1 WO 2015150891 A1 WO2015150891 A1 WO 2015150891A1 IB 2014067331 W IB2014067331 W IB 2014067331W WO 2015150891 A1 WO2015150891 A1 WO 2015150891A1
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WIPO (PCT)
Prior art keywords
formula
compound
vii
oxo
reacting
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PCT/IB2014/067331
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English (en)
Inventor
Sanjay RAIKAR
Sanjay Kisan DABHADE
Ravindra Dattatraya Yeole
Mahesh Vithalbhai Patel
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Wockhardt Limited
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Publication of WO2015150891A1 publication Critical patent/WO2015150891A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the invention relates to a process for preparation of irans-sulfuric acid mono-[2- (5-azetidin-3-ylmethyl-[l,3,4]oxadiazol-2-yl)-7-oxo-l,6-diazabicyclo [3.2.1]oct-6-yl] ester.
  • EDC l-ethyl-3-(3-dimethylamino propyl)carbodiimide
  • HOBt refers to 1 -hydro xybenzotriazole.
  • compound of Formula (I) is prepared by using a general procedure described in Scheme 1.
  • compound of Formula (I) is prepared from sodium salt of 6-benzyloxy-7-oxo-l,6-diazabicyclo[3.2.1]octane-2-carboxylic acid (III).
  • Typical, non-limiting examples of coupling agent include EDC hydrochloride, dicyclohexylcarbodiimide, diisopropylcarbodiimide (DIC), (benzotriazol-1- yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 0-(benzotriazol-l- yl)-NN,N',N'-tetramethyluroniumhexafluorophosphate (HBTU), 0-(benzotriazol- 1-yl)- N,N,N',N'-tetramethyluroniumtetrafluoroborate (TBTU), 0-(7-bzabenzotriazol- 1-yl)- N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), 0-(6-chlorobenzotriazol- l-yl)-N,NN',N'-tetramethyluronium
  • sodium salt of 6- benzyloxy-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2-carboxylic acid (III) is reacted with (3-hydrazinocarbonyl-propyl)-carbamic acid tert-buty ⁇ ester (II) in presence of EDC hydrochloride and HOBt; and in presence NN-dimethylformamide at a temperature ranging from 25 °C to 35°C for about 4 hour to provide an intermediate compound of Formula (IV).
  • the compound of Formula (IV) is cyclized to provide a compound of Formula (V).
  • the cyclization of a compound of Formula (IV) is effected by treating with a reagent such as j?-toluenesulfonyl chloride, j?-nitrobenzenesulfonyl chloride, or methanesulfonyl chloride; and in presence of a suitable solvent such as toluene, chloroform, dichloromethane, or NN-dimethylformamide; at a temperature ranging from 25°C to 110 °C for about 1 hour to about 14 hour to provide 1,3,4-oxadiazole intermediate compound of Formula (V).
  • a reagent such as j?-toluenesulfonyl chloride, j?-nitrobenzenesulfonyl chloride, or methanesulfonyl chloride
  • a suitable solvent such as toluene, chloroform, dichloromethane
  • compound of Formula (IV) is reacted with p- toluenesulfonyl chloride in presence of NN-dimethylformamide as solvent, at a temperature ranging from 55°C to 100°C for about 24 hour to provide a compound of Formula (V).
  • the compound of Formula (V) is subjected for hydrogenolysis by using hydrogen source in presence of transition metal catalyst and in presence of suitable solvent such as methanol, ethanol, methanol dichloromethane mixture, or NN-dimethylformamide dichloromethane mixture; at a temperature ranging from 25 °C to 60 °C for about 1 hour to about 14 hour to provide a compound of Formula (VI).
  • Typical, non-limiting examples of hydrogen source include hydrogen gas, ammonium formate, cyclohexene, lithium - liquid ammonia, ammonia - teri-butanol, sodium - liquid ammonia - teri-butanol, triethylsilyl hydride and the like.
  • Typical, non-limiting examples of transition metal catalyst include 5% palladium on carbon, 10% palladium on carbon, 20% palladium hydroxide on carbon, Raney-Nickel and the like.
  • compound of Formula (V) is treated with 10% palladium on carbon in presence of hydrogen gas at 1 atmospheric pressure and methanol as solvent, at temperature ranging from 25°C to 35 °C for about 2 hour to provide a compound of Formula (VI).
  • the compound of Formula (VI) is sulfonated by reacting with suitable sulfonating reagent in a suitable solvent such as pyridine or NN-dimethylformamide, at a temperature ranging from 25°C to 80°C for about 1 hour to 24 hour.
  • suitable solvent such as pyridine or NN-dimethylformamide
  • sulfonating reagent include sulfur trioxide pyridine complex, sulfur trioxide trimethylamine complex, sulfur trioxide triethylamine complex, sulfur trioxide NN-dimethylaniline complex, sulfur trioxide 2-methylpyridine complex, sulfur trioxide dioxane complex, sulfur trioxide thioxane complex, sulfur trioxide dimethyl sulfide complex, sulfur trioxide dimethylsulfoxide complex, or sulfur trioxide N,N- dimethylformamide complex.
  • compound of Formula (VI) is reacted with sulfur trioxide pyridine complex in presence of pyridine as solvent, at a temperature ranging from 25 °C to 35°C for about 6 hour to provide pyridine salt of sulfonic acid compound.
  • the obtained pyridine salt of sulfonic acid compound is treated with tetrabutylammonium hydrogen sulfate to provide tetrabutylammonium salt of sulfonic acid compound of Formula (VII).
  • the compound according to the invention is finally isolated as zwitterions, by treating intermediate compound of Formula (VII) with trifluoroacetic acid in a suitable solvent such as dichloromethane, chloroform or acetonitrile; at a temperature ranging from -15°C to 40°C for about 0.5 to about 14 hour.
  • compound of Formula (VII) is treated with trifluoroacetic acid in presence of dichloromethane at a temperature ranging from -15°C to -5°C for about 1 hour to provide a compound of Formula (I).
  • a compound of Formula (I) is prepared using a process described in Scheme I.
  • a compound of Formula (I) having a purity of at least about 88% as determined by HPLC.
  • a pharmaceutical composition comprising a compound of Formula (I) having a purity of at least about 88% as determined by HPLC.
  • the said pharmaceutical composition may further comprise one or more pharmaceutically acceptable excipients.
  • Step-1 Synthesis of tr «s-3- ⁇ 2-[N'-(6-benzyloxy-7-oxo-l,6-diaza-bicyclo[3.2.1] octane-2-carbonyl)-hydrazino]-2-oxo-ethyl ⁇ -azetidine-l-carboxylic acid tert-butyl ester (IV):
  • the reaction mixture was stirred at about 25 °C for 18 hour.
  • the precipitated solid was filtered, washed with water (100 ml) and dried under reduced pressure.
  • the residue was suspended in water (100 ml) and stirred at about 45°C for 3 hour.
  • the reaction mixture was filtered and the solid was washed with water (100 ml).
  • the solid was dried under reduced pressure and dissolved in dichloromethane (250 ml).
  • the organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to give 10.0 g of the titled compound (IV) in 80% yield.
  • Step-2 Synthesis of tr «s-3-[5-(6-benzyloxy-7-oxo-l,6-diaza-bicyclo[3.2.1]oct-2-yl)- [l,3,4]oxadiazol-2-ylmethyl]-azetidine-l-carboxylic acid tert-butyl ester (V):
  • the reaction mixture was stirred at temperature of about 60°C for 12 hour.
  • the solvent was evaporated under vacuum to provide a residue.
  • the residue was purified on 100-200 mesh silica gel column chromatography to provide 3.3 g of titled compound (V) in 86% yield.
  • Step-3 Synthesis of tr «s-3-[5-(6-hydroxy-7-oxo-l,6-diaza-bicyclo[3.2.1]oct-2-yl)- [l,3,4]oxadiazol-2-ylmethyl]-azetidine-l-carboxylic acid tert-butyl ester (VI):
  • Step-4 Synthesis of tetrabutyl ammonium salt of tr «s-3-[5-(7-Oxo-6-sulfooxy-l,6- diaza-bicyclo[3.2.1]oct-2-yl)-[l,3,4]oxadiazol-2-ylmethyl]-azetidine-l-carboxylic acid fert-butyl ester (VII):
  • Step-5 Synthesis of trans -sulfuric acid mono-[2-(5-azetidin-3-ylmethyl- [l,3,4]oxadiazol-2-yl)-7-oxo-l,6-diaza-bicyclo[3.2.1]oct-6-yl] ester (I):

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne un procédé de préparation d'un composé de formule (I). (I)
PCT/IB2014/067331 2014-03-29 2014-12-25 Procédé de préparation de mono-[2-(5-azétidin-3-ylméthyl-[1,3,4]oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]ester d'acide sulfurique trans WO2015150891A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1195/MUM/2014 2014-03-29
IN1195MU2014 IN2014MU01195A (fr) 2014-03-29 2014-12-25

Publications (1)

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WO2015150891A1 true WO2015150891A1 (fr) 2015-10-08

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PCT/IB2014/067331 WO2015150891A1 (fr) 2014-03-29 2014-12-25 Procédé de préparation de mono-[2-(5-azétidin-3-ylméthyl-[1,3,4]oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]ester d'acide sulfurique trans

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IN (1) IN2014MU01195A (fr)
WO (1) WO2015150891A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009091856A2 (fr) * 2008-01-18 2009-07-23 Merck & Co., Inc. Inhibiteurs de bêta-lactamase
WO2013030735A1 (fr) * 2011-08-30 2013-03-07 Wockhardt Limited Dérivés 1,6-diazabicyclo[3,2,1]octane-7-one et leur utilisation dans le traitent d'infections bactériennes
WO2013149121A1 (fr) * 2012-03-30 2013-10-03 Cubist Pharmaceuticals, Inc. Inhibiteurs de la 1,3,4-oxadiazole et de la 1,3,4-thiadiazole bêta-lactamase

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009091856A2 (fr) * 2008-01-18 2009-07-23 Merck & Co., Inc. Inhibiteurs de bêta-lactamase
WO2013030735A1 (fr) * 2011-08-30 2013-03-07 Wockhardt Limited Dérivés 1,6-diazabicyclo[3,2,1]octane-7-one et leur utilisation dans le traitent d'infections bactériennes
WO2013149121A1 (fr) * 2012-03-30 2013-10-03 Cubist Pharmaceuticals, Inc. Inhibiteurs de la 1,3,4-oxadiazole et de la 1,3,4-thiadiazole bêta-lactamase

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