WO2015173665A1 - Procédé de préparation d'acide trans-sulfurique mono- {2-[5-(3-azétidinylamino)-méthyl- [1,3,4]-oxadiazol-2-yl]-7-oxo -1,6-diazabicyclo[3.2.1] oct-6-yl} trifluoroacétate d'ester - Google Patents

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

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Publication number
WO2015173665A1
WO2015173665A1 PCT/IB2015/052191 IB2015052191W WO2015173665A1 WO 2015173665 A1 WO2015173665 A1 WO 2015173665A1 IB 2015052191 W IB2015052191 W IB 2015052191W WO 2015173665 A1 WO2015173665 A1 WO 2015173665A1
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WIPO (PCT)
Prior art keywords
formula
compound
sulfur trioxide
complex
process according
Prior art date
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PCT/IB2015/052191
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English (en)
Inventor
Sunil Bhaginath JADHAV
Satish Bhavsar
Prasad Keshav Deshpande
Ravindra Dattatraya Yeole
Mahesh Vithalbhai Patel
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Wockhardt Limited
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Publication of WO2015173665A1 publication Critical patent/WO2015173665A1/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

Definitions

  • the invention relates to a process for preparation of irans-sulfuric acid mono- ⁇ 2- [5-(3-azetidinylamino)-methyl-[l,3,4]-oxadiazol-2-yl]-7-oxo-l,6-diazabicyclo[3.2.1]oct- 6-yl ⁇ ester trifluoroacetate.
  • a compound of Formula (I), chemically known as irans-sulfuric acid mono- ⁇ 2-[5-(3- azetidinylamino)-methyl-[l,3,4]-oxadiazol-2-yl]-7-oxo-l,6-diazabicyclo[3.2.1]oct-6-yl ⁇ ester trifluoroacetate has antibacterial properties and is also disclosed in PCT International Patent Application No. PCT/US2013/034562.
  • the present invention discloses a process for preparation of a compound of Formula (I).
  • EDC l-ethyl-3-(3-dimethylamino propyl)carbodiimide
  • HOBt refers to 1 -hydro xybenzotriazole.
  • TFA trifluoro acetic acid
  • 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).
  • coupling agent examples include EDC hydrochloride, dicyclohexylcarbodiimide, diisopropylcarbodiimide (DIC), (benzotriazol-l-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), O- (benzotriazol- 1 -yl)-N,N,N' , ⁇ ' -tetramethyluroniumhexafluorophosphate (HBTU), O- (benzotriazol-l-yl)- ⁇ , ⁇ , ⁇ ', ⁇ '-tetramethyluroniumtetrafluoroborate (TBTU), 0-(7- azabenzotriazol-l-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), O- (6-ahlorobenzotriazol-l-yl)-N,N,N',N'--tris(di
  • compound of Formula (II) is reacted with a compound of Formula (III) in presence of EDC hydrochloride and HOBt at a temperature of about 25°C to about 35°C for about 15 hours to provide an intermediate compound of Formula (IV).
  • a compound of Formula (II) is reacted with a compound of Formula (III) in presence of suitable solvent such as dimethylformamide, water or a mixture thereof.
  • 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 p-toluene sulfonyl chloride, p-nitrobenzene sulfonyl chloride, methane sulfonyl chloride or triphenylphosphine in a suitable solvent such as toluene, chloroform, dichloromethane, or N,N-dimethyl formamide at a temperature ranging from about -10° C to about 70°C for about 15 minutes to about 4 hours to provide 1,3,4-oxadiazole intermediate compound of Formula (V).
  • a compound of Formula (V) is cyclized to provide a compound of Formula (V).
  • a reagent such as p-toluene sulfonyl chloride, p-nitrobenzene sulfonyl chloride, methane
  • compound of Formula (IV) is cyclized in presence of triphenylphosphine, iodine and triethylamine, at a temperature of about -10°C to about 0°C for about 30 minutes to provide a compound of Formula (V).
  • compound of Formula (IV) is cyclized to a compound of Formula (V) in presence of dichloromethane as solvent.
  • the compound of Formula (V) is subjected for hydrogenolysis by using hydrogen source in presence of transition metal catalyst in a suitable solvent such as methanol, ethanol, dichloromethane mixture, NN-dimethylformamide or a mixture thereof at a temperature ranging from 25 °C to 60°C for about 1 hour to about 15 hours to provide a compound of Formula (VI).
  • a suitable solvent such as methanol, ethanol, dichloromethane mixture, NN-dimethylformamide or a mixture thereof at a temperature ranging from 25 °C to 60°C for about 1 hour to about 15 hours 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 - tert-butanol, triethyl silyl hydride and the like.
  • transition metal catalyst examples 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 50 psi pressure and at temperature of about 25°C to about 35°C for about 15 hours to provide a compound of Formula (VI).
  • a compound of Formula (V) is converted to a compound of Formula (VI) in presence of methanol as solvent.
  • the compound of Formula (VI) is sulfonated by reacting with a suitable sulfonating reagent in presence of a suitable solvent such as pyridine, dichloromethane or NN-dimethylformamide at a temperature ranging from 25 °C to 80°C for about 1 hour to 24 hours.
  • a suitable solvent such as pyridine, dichloromethane 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, sulfur trioxide-NN-dimethylformamide complex and the like.
  • a compound of Formula (VI) is reacted with sulfur trioxide-pyridine complex in presence of dichloromethane as solvent at a temperature of about 25°C to about 35°C for about 2 hours to provide pyridine salt of sulfonic acid compound.
  • the obtained pyridine salt of sulfonic acid compound is treated with tetrabutylammonium hydrogen sulfate to provide a tetrabutylammonium salt of sulfonic acid compound of Formula (VII).
  • the compound according to the invention is finally isolated as trifluoroacetate salt, by removing the protecting groups of a compound of Formula (VII).
  • the compound of Formula (VII) is reacted with suitable deprotecting agent such as trifluoro acetic acid in presence of a suitable solvent such as dichloromethane, chloroform or acetonitrile, at a temperature ranging from -15°C to 40°C for about 0.5 hour to about 14 hours.
  • a compound of Formula (VII) is treated with trifluoroacetic acid in presence of dichloromethane at about 0°C for about 3 hours 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 90% as determined by HPLC there is provided a process for preparation of a compound of Formula (I) having a purity of at least about 90% as determined by HPLC.
  • a pharmaceutical composition comprising a compound of Formula (I) having a purity of at least about 90 % as determined by HPLC.
  • the said pharmaceutical composition may further comprise one or more pharmaceutically acceptable excipients.
  • Step 2 Preparation of tr «s- ⁇ 2-[5-(6-benzyloxy-7-oxo-l,6-diaza-bicyclo[3.2.1]oct-2- yl)-[l,3,4]oxadiazol-2-yl]-2-oxo-ethyl ⁇ -tert-butoxycarbonyl-amino)-azetidine-l- carboxylic acid tert-butyl ester (V):
  • Triethyl amine (3.6 ml, 0.026 mol) was added to a cooled (0 °C) solution of iodine (1.62 gm, 0.0063 mol) and triphenylphosphine (1.67 g, 0.0063 mol) in dichloromethane (64 ml).
  • Step 3 Preparation of tr «s- ⁇ 2-[5-(6-hydroxy-7-oxo-l,6-diaza-bicyclo[3.2.1]oct-2- yl)-[l,3,4]-oxadiazole-2-yl]-methyl ⁇ -tert-butoxycarbonyl-amino)-azetidine-l- carboxylic acid tert-butyl ester (VI):
  • Step-4 Preparation of traras-tetrabutyl ammonium salt-methyl- ⁇ 2-[5-(7-oxo-6- sulphooxy-l,6-diaza-bicyclo[3.2.1]oct-2-yl)-[l,3,4]oxadiazol-2-yl]-methyl ⁇ -tert- butoxycarbonyl-amino )-azetidine-l-carboxylic acid fert-butyl ester (VII):
  • Step 5 Preparation of traras-sulfuric acid mono- ⁇ 2-[5-(3-azetidinylamino)-methyl- [l,3,4]-oxadiazol-2-yl]-7-oxo-l,6-diazabicyclo[3.2.1]oct-6-yl]ester trifluoroacetate (I) irans-Tetrabutyl ammonium salt-methyl- ⁇ 2-[5-(7-oxo-6-sulphooxy- 1 ,6-diaza- bicyclo[3.2.1]oct-2-yl)-[l,3,4]oxadiazol-2-yl]-methyl ⁇ -ieri-butoxycarbonyl-amino)- azetidine- 1 -carboxylic acid tert-butyl ester (VII) (2.1 g, 0.003 mol) was cooled to 0°C and to this was added trifluoro acetic acid cooled at 0°
  • reaction mixture was concentrated under high vacuum. Diethyl ether (20 ml) was added and solid precipitated was stirred and diethyl ether was decanted. This treatment was repeated twice. Solid separated was dried and dichloromethane (20 ml) was added and stirred; solid was allowed to settle and dichloromethane was decanted.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de préparation d'un composé de formule (I).
PCT/IB2015/052191 2014-05-14 2015-03-25 Procédé de préparation d'acide trans-sulfurique mono- {2-[5-(3-azétidinylamino)-méthyl- [1,3,4]-oxadiazol-2-yl]-7-oxo -1,6-diazabicyclo[3.2.1] oct-6-yl} trifluoroacétate d'ester WO2015173665A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1635/MUM/2014 2014-05-14
IN1635MU2014 2014-05-14

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WO2015173665A1 true WO2015173665A1 (fr) 2015-11-19

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PCT/IB2015/052191 WO2015173665A1 (fr) 2014-05-14 2015-03-25 Procédé de préparation d'acide trans-sulfurique mono- {2-[5-(3-azétidinylamino)-méthyl- [1,3,4]-oxadiazol-2-yl]-7-oxo -1,6-diazabicyclo[3.2.1] oct-6-yl} trifluoroacétate d'ester

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019144912A1 (fr) 2018-01-25 2019-08-01 苏州信诺维医药科技有限公司 INHIBITEUR DE β-LACTAMASE ET SON UTILISATION
WO2023088375A1 (fr) 2021-11-17 2023-05-25 苏州信诺维医药科技股份有限公司 INTERMÉDIAIRE D'INHIBITEUR DE β-LACTAMASE ET SON PROCÉDÉ DE PRÉPARATION

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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 (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019144912A1 (fr) 2018-01-25 2019-08-01 苏州信诺维医药科技有限公司 INHIBITEUR DE β-LACTAMASE ET SON UTILISATION
WO2023088375A1 (fr) 2021-11-17 2023-05-25 苏州信诺维医药科技股份有限公司 INTERMÉDIAIRE D'INHIBITEUR DE β-LACTAMASE ET SON PROCÉDÉ DE PRÉPARATION

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