WO2015150890A1 - A process for preparation of trans-sulfuric acid mono-{2-(5-(3-amino-propyl)-[1,3,4]oxadiazol-2-yl]-7-oxo-1,6-diazabicyclo [3.2.1] oct-6-yl}ester - Google Patents

A process for preparation of trans-sulfuric acid mono-{2-(5-(3-amino-propyl)-[1,3,4]oxadiazol-2-yl]-7-oxo-1,6-diazabicyclo [3.2.1] oct-6-yl}ester Download PDF

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Publication number
WO2015150890A1
WO2015150890A1 PCT/IB2014/067330 IB2014067330W WO2015150890A1 WO 2015150890 A1 WO2015150890 A1 WO 2015150890A1 IB 2014067330 W IB2014067330 W IB 2014067330W WO 2015150890 A1 WO2015150890 A1 WO 2015150890A1
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WIPO (PCT)
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formula
compound
vii
oxo
propyl
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PCT/IB2014/067330
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English (en)
French (fr)
Inventor
Sanjay RAIKAR
Laxmikant PAVASE
Ravindra Dattatraya Yeole
Mahesh Vithalbhai Patel
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Wockhardt Limited
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Publication of WO2015150890A1 publication Critical patent/WO2015150890A1/en

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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-(3-amino-propyl)-[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.
  • a 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- 1- yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 0-(benzotriazol- l- yl)-N,N,N',N'-tetramethyluroniumhexafluorophosphate (HBTU), 0-(benzotriazol- 1-yl)- N,N,N',N'-tetramethyluroniumtetrafluoroborate (TBTU), 0-(7-azabenzotriazol- 1-yl)- N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), 0-(6-chlorobenzotriazol- l-yl)-N,NN',N'-t
  • 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 N,N- dimethylformamide as solvent at temperature ranging from 25°C to 35°C for about 4 hour to provide a compound of Formula (IV).
  • the compound of Formula (IV) is cyclized to provide a compound of Formula
  • 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; in a suitable solvent such as toluene, chloroform, dichloromethane, or N,N- dimethyl formamide; at a temperature ranging from about 25°C to 110°C for about 1 hour to about 14 hours 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, or N,N- dimethyl formamide
  • compound of Formula (IV) is reacted with j?-toluene sulfonyl chloride in presence of NN-dimethylformamide at a temperature ranging from about 55°C to about 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 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 - 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 in presence of methanol as solvent at a 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 presence of suitable solvent such as pyridine or NN-dimethylformamide, at a temperature ranging from 25 °C to 80°C for about 1 hour to about 24 hour.
  • suitable solvent such as pyridine or NN-dimethylformamide
  • Typical non- limiting examples of sulfonating reagent include sulfur trioxide pyridine complex, sulfur trioxide trimethylamine complex, sulfur trioxide triethylamine complex, sulfur trioxide ⁇ , ⁇ -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 trifluoro acetic 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).
  • the compound of Formula (I) is prepared using a process described in Scheme I.
  • 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-1 Synthesis of trans- ⁇ 4-[iV'-(6-benzyloxy-7-oxo-l,6-diaza-bicyclo[3.2.1]octane- 2-carbonyl)-hydrazino]-4-oxo-butyl ⁇ -carbamic acid fert-butyl ester (IV):
  • the reaction mixture was stirred for 15 minute and a solution of (3-hydrazinocarbonyl-propyl)-carbamic acid tert-buty ⁇ ester (II) (2.5 g, 0.011 mol) dissolved in water (150 ml) was added.
  • the reaction mixture was stirred at temperature of about 25 °C for about 18 hour.
  • the precipitated solid was filtered, washed with water (70 ml) and dried under reduced pressure.
  • the residue was suspended in water (70 ml) and stirred at temperature of about 45 °C for about 3 hour.
  • the reaction mixture was filtered and the solid was washed with water (70 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 5.0 g of the titled compound (IV) in 92% 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-yl]-propyl ⁇ -carbamic acid tert-butyl ester (V):
  • reaction mixture was stirred at temperature of about 60°C for 12 hours.
  • the solvent was evaporated under vacuum to provide a residue.
  • the residue was purified on 100-200 mesh silica gel column chromatography to provide 3.0 g of titled compound (V) in 62% 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-yl]-propyl ⁇ -carbamic acid tert-butyl ester (VI):
  • Step-4 Syntheis 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-yl]-propyl ⁇ -carbamic acid tert-butyl ester (VII):
  • the reaction mixture was stirred for about 2 hour at temperature of about 25 °C.
  • the solvent was evaporated under vacuum below temperature of about 40°C to provide a residue which was stirred in 0.5 N aqueous potassium dihydrogen phosphate solution (50 ml) for 1 hour.
  • the resulting solution was extracted successively with ethyl acetate (25 ml) and a mixture of ethyl acetate (25 ml) and dichloromethane (12.5 ml).
  • To the aqueous layer was added tetrabutylammomum hydrogen sulfate (2.0 g, 0.006 mol) and the mixture was stirred for about 2 hour at temperature of about 25 °C.
  • the product was extracted with dichloromethane.
  • the organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure.
  • the crude residue was purified by silica gel column chromatography to provide 2.4 g of titled compound (VII) in 5
  • Step-5 Synthesis of traras-sulfuric acid mono- ⁇ 2-[5-(3-amino-propyl)- [l,3,4]oxadiazol-2-yl]-7-oxo-l,6-diaza-bicyclo[3.2.1]oct-6-yl ⁇ ester (I):
  • the reaction mixture was stirred at temperature of about -10°C for 2 hours. Solvents were evaporated under vacuum and the residue was taken in diethyl ether (36.0 ml) and stirred for 1 hour. The mixture was filtered; the solid was washed with diethyl ether (12.0 ml) and dried under reduced pressure. Acetone (36.0 ml) was added to the solid and the pH of the solution was adjusted from initial pH 3 to pH 6.5 by addition of 10% solution of sodium 2-ethyl hexanoate in acetone. The reaction mixture was filtered; the solid was washed with acetone (12.0 ml) and dried under reduced pressure.

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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)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cephalosporin Compounds (AREA)
PCT/IB2014/067330 2014-03-29 2014-12-25 A process for preparation of trans-sulfuric acid mono-{2-(5-(3-amino-propyl)-[1,3,4]oxadiazol-2-yl]-7-oxo-1,6-diazabicyclo [3.2.1] oct-6-yl}ester WO2015150890A1 (en)

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IN1196/MUM/2014 2014-03-29
IN1196MU2014 IN2014MU01196A (enrdf_load_stackoverflow) 2014-03-29 2014-12-25

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019144912A1 (zh) 2018-01-25 2019-08-01 苏州信诺维医药科技有限公司 β-内酰胺酶抑制剂及其用途
WO2023088375A1 (zh) 2021-11-17 2023-05-25 苏州信诺维医药科技股份有限公司 β-内酰胺酶抑制剂中间体及制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009091856A2 (en) * 2008-01-18 2009-07-23 Merck & Co., Inc. Beta-lactamase inhibitors
WO2013030735A1 (en) * 2011-08-30 2013-03-07 Wockhardt Limited 1,6- diazabicyclo [3,2,1] octan- 7 - one derivatives and their use in the treatment of bacterial infections
WO2013149121A1 (en) * 2012-03-30 2013-10-03 Cubist Pharmaceuticals, Inc. 1,3,4-oxadiazole and 1,3,4-thiadiazole beta-lactamase inhibitors

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009091856A2 (en) * 2008-01-18 2009-07-23 Merck & Co., Inc. Beta-lactamase inhibitors
WO2013030735A1 (en) * 2011-08-30 2013-03-07 Wockhardt Limited 1,6- diazabicyclo [3,2,1] octan- 7 - one derivatives and their use in the treatment of bacterial infections
WO2013149121A1 (en) * 2012-03-30 2013-10-03 Cubist Pharmaceuticals, Inc. 1,3,4-oxadiazole and 1,3,4-thiadiazole beta-lactamase inhibitors

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019144912A1 (zh) 2018-01-25 2019-08-01 苏州信诺维医药科技有限公司 β-内酰胺酶抑制剂及其用途
CN111670187A (zh) * 2018-01-25 2020-09-15 苏州信诺维医药科技有限公司 β-内酰胺酶抑制剂及其用途
CN111670187B (zh) * 2018-01-25 2021-04-16 苏州信诺维医药科技有限公司 β-内酰胺酶抑制剂及其用途
US11078202B2 (en) 2018-01-25 2021-08-03 Suzhou Sinovent Pharmaceuticals Co., Ltd. β-lactamase inhibitor and use thereof
WO2023088375A1 (zh) 2021-11-17 2023-05-25 苏州信诺维医药科技股份有限公司 β-内酰胺酶抑制剂中间体及制备方法

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