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

Info

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
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
vii
oxo
propyl
Prior art date
Application number
PCT/IB2014/067330
Other languages
French (fr)
Inventor
Sanjay RAIKAR
Laxmikant PAVASE
Ravindra Dattatraya Yeole
Mahesh Vithalbhai Patel
Original Assignee
Wockhardt 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 Wockhardt Limited filed Critical Wockhardt Limited
Publication of WO2015150890A1 publication Critical patent/WO2015150890A1/en

Links

Classifications

    • 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.

Abstract

A process for preparation of compound of Formula (I) is disclosed.

Description

A PROCESS FOR PREPARATION OF ΤΤΐΑΛΉ-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
RELATED PATENT APPLICATIONS
This application claims priority to Indian Patent Application No. 1196 MUM/2014 filed on March 29, 2014, the disclosures of which are incorporated herein by reference in its entirety as if fully rewritten herein.
FIELD OF THE INVENTION
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.
BACKGROUND OF INVENTION
Several l,6-diazabicyclo[3.2.1]octan-7-one derivatives have been described as antibacterial agents in PCT International Patent Application No. PCT/IB2012/054296. A compound of Formula (I), chemically known as 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 has antibacterial properties and is also disclosed in PCT International Patent Application No.
PCT/US2013/034562.
Figure imgf000002_0001
Formula (I) SUMMARY OF THE INVENTION
In one general aspect, there is provided a process for preparation of a compound of Formula (I), comprising:
Figure imgf000003_0001
Formula (I)
(a) reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV);
Figure imgf000003_0002
Formula (II) (Formula III)
Figure imgf000003_0003
cyclizing a compound of Formula (IV) to obtain a compound of Formula
(V);
Figure imgf000003_0004
Formula (V) (c) hydrogenolysis of a compound of Formula (V) to obtain a compound of Formula (VI);
Figure imgf000004_0001
Formula (VI)
(d) sulfonating a compound of Formula (VI), followed by the treatment with tetrabutylammonium hydrogen sulfate to obtain a compound of Formula (VII); and
Figure imgf000004_0002
Formula (VII)
(e) reacting a compound of Formula (VII) with trifluoro acetic acid to obtain a compound of Formula (I).
The details of one or more embodiments of the inventions are set forth in the description below. Other features, objects and advantages of the inventions will be apparent from the following description including claims.
DETAILED DESCRIPTION OF THE INVENTION
Reference will now be made to the exemplary embodiments, and specific language will be used herein to describe the same. It should nevertheless be understood that no limitation of the scope of the invention is thereby intended. Alterations and further modifications of the inventive features illustrated herein, which would occur to one skilled in the relevant art and having possession of this disclosure, are to be considered within the scope of the invention. It must be noted that, as used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the content clearly dictates otherwise. All references including patents, patent applications, and literature cited in the specification are expressly incorporated herein by reference in their entirety.
The term "EDC" as used herein refers to l-ethyl-3-(3-dimethylamino propyl)carbodiimide.
The term "HOBt" as used herein refers to 1 -hydro xybenzotriazole.
In one general aspect, there is provided a process for preparation of a compound of Formula (I), comprising:
Figure imgf000005_0001
Formula (I)
(a) reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV);
Figure imgf000005_0002
cyclizing a compound of Formula (IV) to obtain a compound of Formula
Figure imgf000006_0001
Formula (V)
(c) hydrogenolysis of a compound of Formula (V) to obtain a compound of Formula (VI);
Figure imgf000006_0002
Formula (VI)
(d) sulfonating a compound of Formula (VI), followed by the treatment with tetrabutylammomum hydrogen sulfate to obtain a compound of Formula (VII); and
Figure imgf000006_0003
Formula (VII)
(e) reacting a compound of Formula (VII) with trifluoroacetic acid to obtain a compound of Formula (I).
In some embodiments, compound of Formula (I) is prepared by using a general procedure described in Scheme 1. Typically, 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). The 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 coupling agent and suitable solvent such as N,N dimethylformamide, N,N dimethylacetamide, or 1,4 dioxane; at a temperature ranging from about - 15°C to about 60°C for about 1 hour to about 24 hour to provide an intermediate compound of Formula
(IV) . 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)-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'-tetramethyluronium hexafluorophosphate (HCTU), 0-(3,4-dihydro-4- oxo- 1 ,2,3-benzotriazine-3-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate(TDBTU), 3-(diethylphosphoryloxy)- 1 ,2,3-benzotriazin-4(3H)-one (DEPBT), carbonyldiimidazole (CDI), pivalyl chloride, HOBt and the like. In some embodiments, 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
(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; 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). In some embodiments, 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. In some embodiments, 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. Typical non- limiting examples of sulfonating reagent include sulfur trioxide pyridine complex, sulfur trioxide trimethylamine complex, sulfur trioxide triethylamine complex, sulfur trioxide Ν,Ν-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. In some embodiments, 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. In some embodiments, 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).
In some embodiments, the compound of Formula (I) is prepared using a process described in Scheme I.
In some embodiments, there is provided a process for preparation of a compound of Formula (I), comprising:
Figure imgf000009_0001
(a) reacting a compound of Formula (II) with a compound of Formula (III) in presence of 1-hydroxybenzotriazole and l-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride to obtain a compound of Formula (IV);
Figure imgf000009_0002
(b) cyclizing a compound of Formula (IV) in presence of j?-toluenesulfonyl chloride to obtain a compound of Formula (V);
Figure imgf000010_0001
Formula (V)
(c) hydrogenolysis of a compound of Formula (V) in presence of transition metal catalyst and a hydrogen source to obtain a compound of Formula (VI);
Figure imgf000010_0002
Formula (VI)
(d) sulfonating a compound of Formula (VI) in presence of sulfur trioxide pyridine complex, followed by the treatment with tetrabutylammonium hydrogen sulfate to obtain a compound of Formula (VII); and
Figure imgf000010_0003
Formula (VII)
(e) reacting a compound of Formula (VII) with trifluoroacetic acid to obtain a compound of Formula (I). In some embodiments, there is provided a compound of Formula (I) having a purity of at least about 90% as determined by HPLC.
In some embodiments, there is provided a pharmaceutical composition comprising a compound of Formula (I) having a purity of at least about 90% as determined by HPLC. In some embodiments, the said pharmaceutical composition may further comprise one or more pharmaceutically acceptable excipients.
Figure imgf000011_0001
Scheme 1
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. For example, those skilled in the art will recognize that the invention may be practiced using a variety of different compounds within the described generic descriptions.
EXAMPLES
The following examples illustrate the embodiments of the invention that are presently best known. However, it is to be understood that the following are only exemplary or illustrative of the application of the principles of the present invention. Numerous modifications and alternative compositions, methods, and systems may be devised by those skilled in the art without departing from the spirit and scope of the present invention. The appended claims are intended to cover such modifications and arrangements. Thus, while the present invention has been described above with particularity, the following examples provide further detail in connection with what are presently deemed to be the most practical and preferred embodiments of the invention.
Example 1
Synthesis of trans -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 (I)
Figure imgf000012_0001
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):
Figure imgf000012_0002
To a clear solution of sodium salt of ira7?s-6-benzyloxy-7-oxo-l,6-diaza-bicyclo [3.2.1]octane-2-carboxylic acid (III) (3.43 g, 0.011 mol) in water (70 ml) was added EDC hydrochloride (3.37 g, 0.017 mol), followed by HOBt (1.55 g, 0.011 mol) at temperature of about 25 °C, under stirring. 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.
Analysis:
Mass: 476.3 (M+l); for Molecular Weight: 475.6 and Molecular Formula:
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):
Figure imgf000013_0001
To a single neck round bottom flask equipped with magnetic stirrer was charged a solution of ir ns-{4-[N'-(6-Benzyloxy-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)- hydrazino]-4-oxo-butyl}-carbamic acid tert-butyl ester (IV) (5.0 g, 0.01 mmol) in chloroform (50 ml), followed by diisopropyl ethylamine (5.57 ml, 0.032 mmol) and p- toluene sulfonylchloride (2.99 g, 0.015 mmol) under stirring at about 25 °C. The 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.
Analysis:
Mass: 458.3 (M+l); for Molecular Weight: 457.5 and Molecular Formula: CMHSINSOS; and
1H NMR (DMSO-dg): δ 7.34-7.46 (m, 5 H), 6.86 (s, 1 H), 4.91-4.98 (d, 2 H), 4.59 (d, 1 H), 3.70 (s, 1 H), 2.97-3.27 (m, 2 H), 2.80-2.97 (m, 3 H), 2.70-2.73 (d, 1 H), 1.77- 2.14 (m, 6 H), 1.35 (s, 9 H).
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):
Figure imgf000014_0001
To a clear solution of ir ns-{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) (3.0 g, 0.007 mol) in methanol (30 ml) 10% palladium on carbon (0.5 g) was added at about 25 °C. The reaction mixture was stirred under hydrogen balloon pressure at about 25 °C for about 2 hour. The catalyst was filtered under suction over a celite bed. The bed was washed with methanol (15 ml). The combined filtrate was evaporated under vacuum below temperature of about 35°C to provide a 2.4 g of titled compound (VI) in 99% yield. It was used as such for further reaction.
Analysis:
Mass: 368.2 (M+l); for Molecular Weight: 367.4 and Molecular Formula: 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):
Figure imgf000015_0001
To a 1 L single neck round bottom flask equipped with magnetic stirrer was charged a solution of ir ns-{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) (2.4 g, 0.006 mol) in dichloromethane (25 ml), followed by triethylamine (2.76 ml, 0.02 mol) and sulfur trioxide pyridine complex (2.09 g, 0.013 mol) under stirring. 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 53% yield.
Analysis:
Mass: 446.3 (M-l) as a free sulfonic acid; for Molecular Weight: 690.5 and Molecular Formula:
Figure imgf000015_0002
N(C4H9)4.
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):
Figure imgf000016_0001
To a 250 ml round bottom flask equipped with magnetic stirrer was charged a solution of tetrabutyl ammonium salt of of irans-{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-buty\ ester (VII) (2.4 g, 0.003 mol) in dichloromethane (6.0 ml). The solution was cooled to about - 10°C under stirring and to it was added trifluoroacetic acid (6.0 ml) drop wise. 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. The solid (1.3 g) was dissolved in water (1.3 ml) and 2-propanal (9.1 ml) was added under stirring. The reaction mixture was stirred for 18 hours, filtered and the solid was washed with a mixture of water (0.065 ml) and 2-propanol (4.5 ml). The solid was dried under reduced pressure to yield the 0.6 g of compound of invention (I) in 51% yield.
Analysis:
Mass: 346.2 (M-l); for Molecular Weight: 347.4 and Molecular Formula: CnHnNsOeS;
1H NMR (DMSO-d6): δ 7.70 (s, 2 H), 4.60 (d, 1 H), 4.03-4.11 (m, 1 H), 3.81- 3.92 (m, 1 H), 3.32-3.40 (m, 1 H), 3.10-3.21 (m, 1 H), 2.89-2.99 (m, 4 H), 2.72 (d, 1 H), 2.13-2.16 (m, 1 H), 1.97-2.00 (m, 3 H), 1.81-1.88 (m, 1 H); and
Purity as determined by HPLC: 90.06%.

Claims

1. A process for preparation of a compound of Formula (I), comprising:
Figure imgf000017_0001
Formula (I)
(a) reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV);
Figure imgf000017_0002
ormu a
(b) cyclizing a compound of Formula (IV) to obtain a compound of Formula
(V);
Figure imgf000018_0001
Formula (V)
(c) hydrogenolysis of a compound of Formula (V) to obtain a compound of Formula (VI);
Figure imgf000018_0002
Formula (VI)
(d) sulfonating a compound of Formula (VI), followed by the treatment with tetrabutylammomum hydrogen sulfate to obtain a compound of Formula (VII); and
Figure imgf000018_0003
Formula (VII)
(e) reacting a compound of Formula (VII) with trifluoroacetic acid to obtain a compound of Formula (I).
2. A process according to Claim 1, wherein a compound of Formula (IV) is obtained by reacting a compound of Formula (II) with a compound of Formula (III) in presence of 1-hydroxybenzotriazole and l-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride.
3. A process according to Claim 1, wherein cyclization of a compound of Formula (IV) is carried in presence of j?-toluenesulfonyl chloride.
4. A process according to Claim 1, wherein the hydrogenolysis of a compound of Formula (V) is carried out in presence of transition metal catalyst and a hydrogen source.
5. A process according to Claim 4, wherein the transition metal catalyst is palladium on carbon.
6. A process according to Claim 4, wherein the hydrogen source is hydrogen gas.
7. A process according to Claim 1, wherein sulfonation of a compound of Formula (VI) is carried in presence of sulfur trioxide pyridine complex.
8. A process for preparation of a compound of Formula (I), comprising:
Figure imgf000019_0001
Formula (I)
(a) reacting a compound of Formula (II) with a compound of Formula (III) in presence of 1-hydroxybenzotriazole and l-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride to obtain a compound of Formula (IV);
Figure imgf000020_0001
Formula (IV)
(b) cyclizing a compound of Formula (IV) in presence of j?-toluenesulfonyl chloride to obtain a compound of Formula (V);
Figure imgf000020_0002
Formula (V)
(c) hydrogenolysis of a compound of Formula (V) in presence of transition metal catalyst and a hydrogen source to obtain a compound of Formula (VI);
Figure imgf000020_0003
Formula (VI) (d) sulfonating a compound of Formula (VI) in presence of sulfur trioxide pyridine complex, followed by the treatment with tetrabutylammonium hydrogen sulfate to obtain a compound of Formula (VII); and
Figure imgf000021_0001
Formula (VII)
(e) reacting a compound of Formula (VII) with trifluoroacetic acid to obtain a compound of Formula (I).
9. A compound of Formula (I) having purity of at least about 90% as determined by HPLC.
10. A pharmaceutical composition comprising a compound of Formula (I) according to Claim 9.
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)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1196/MUM/2014 2014-03-29
IN1196MU2014 IN2014MU01196A (en) 2014-03-29 2014-12-25

Publications (1)

Publication Number Publication Date
WO2015150890A1 true WO2015150890A1 (en) 2015-10-08

Family

ID=54239456

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2014/067330 WO2015150890A1 (en) 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

Country Status (2)

Country Link
IN (1) IN2014MU01196A (en)
WO (1) WO2015150890A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019144912A1 (en) 2018-01-25 2019-08-01 苏州信诺维医药科技有限公司 β-LACTAMASE INHIBITOR AND USE THEREOF
WO2023088375A1 (en) * 2021-11-17 2023-05-25 苏州信诺维医药科技股份有限公司 β-LACTAMASE INHIBITOR INTERMEDIATE AND PREPARATION METHOD THEREFOR

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 (en) 2018-01-25 2019-08-01 苏州信诺维医药科技有限公司 β-LACTAMASE INHIBITOR AND USE THEREOF
CN111670187A (en) * 2018-01-25 2020-09-15 苏州信诺维医药科技有限公司 Beta-lactamase inhibitor and use thereof
CN111670187B (en) * 2018-01-25 2021-04-16 苏州信诺维医药科技有限公司 Beta-lactamase inhibitor and use thereof
US11078202B2 (en) 2018-01-25 2021-08-03 Suzhou Sinovent Pharmaceuticals Co., Ltd. β-lactamase inhibitor and use thereof
WO2023088375A1 (en) * 2021-11-17 2023-05-25 苏州信诺维医药科技股份有限公司 β-LACTAMASE INHIBITOR INTERMEDIATE AND PREPARATION METHOD THEREFOR

Also Published As

Publication number Publication date
IN2014MU01196A (en) 2015-10-02

Similar Documents

Publication Publication Date Title
US6388070B1 (en) Thioester derivatives of thiazolyl acetic acid and their use in the preparation of cephalosporin compounds
AU2018236290B2 (en) MK2 inhibitors, synthesis thereof, and intermediates thereto
EP3152191B1 (en) Improved process for making duocarmycin prodrugs
WO2018137679A1 (en) Process for the Preparation of (10R) -7- (2-aminoacetyl) amino-12-fluoro-2, 10, 16-trimethyl-15-oxo-10, 15, 16, 17-tetrahydro-2H-8, 4- (metheno) pyrazolo [4, 3-h] [2, 5, 11] -benzoxadiazacyclotetradecine-3-carbonitrile
JP7112963B2 (en) Secoma macrolide compound
WO2015150890A1 (en) 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
US9688677B1 (en) Process for preparation of sodium (2S, 5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate
CN110139857B (en) Sulfoximine, sulfoximinamide, sulfodiimine, and diimine sulfonamide compounds as indoleamine 2,3-dioxygenase inhibitors
JP2018528928A5 (en)
WO2016120752A1 (en) A process for preparation of (2s, 5r)-n-(2-amino ethoxy)-6-(sulfooxy)-7-oxo-1,6- diazabicyclo [3.2.1] octane-2-carboxamide
US8354426B2 (en) Naphthyridine derivative monohydrate and method for producing the same
EP2763971A1 (en) Preparation of micafungin intermediates
WO2015173665A1 (en) A process for preparation of trans-sulfuric acid mono-{2-[5-(3-azetidinylamino)-methyl-[1,3,4]- oxadiazol-2-yl]-7-oxo-1,6-diazabicyclo[3.2.1] oct-6-yl} ester trifluoroacetate
WO2015150891A1 (en) A process for preparation of trans-sulfuric acid mono-[2-(5-azetidin-3-ylmethyl-[1,3,4]oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo [3.2.1]oct-6-yl]ester
US7205384B2 (en) Process for preparing peptidyl heterocyclic ketone derivatives
WO2015173663A1 (en) A process for preparation of trans-sulfuric acid mono-{2-[5-(2-methylamino-ethyl)-[1,3,4]-oxadiazol-2-yl]-7-oxo-1,6-diaza-bicyclo [3.2.1]oct-6-yl} ester
AU2010212232A1 (en) Derivatives of 6-(6-O-substituted-triazolopyridazine-sulfanyl) benzothiazoles and benzimidazoles, preparation thereof, use thereof as drugs, and use thereof as MET inhibitors
WO2015110886A1 (en) A process for preparation of (2s, 5r)-7-oxo-n-[(3s)-pyrrolidin-3-yloxy]-6-(sulfooxy)-1,6-diazabicyclo [3.2.1]octane-2-carboxamide
KR930005174B1 (en) Process for preparing antibiotic derivatives
KR970005893B1 (en) Process for preparing cephalosporin compounds
CA3224971A1 (en) Process for preparing aficamten
WO2016157057A1 (en) A process for preparation of sodium salt of (2s, 5r) sulfuric acid mono-(2-[1,3,4]oxadiazol-2-yl-7-oxo-1,6-diazabicyclo[3.2.1 ]oct-6-yl)ester
CN111655670A (en) Process for preparing 2-chloro-4-nitroimidazole derivatives
KR100361829B1 (en) The process for preparing a ceftriaxone from reactive organic acid derivatives
KR930001405B1 (en) Process for preparing 2-(4-substituted amino-3-oxo-isoxazolydin-5-oxo)-tetra hydrofuran carboxyl acid derivatives

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14837074

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase
122 Ep: pct application non-entry in european phase

Ref document number: 14837074

Country of ref document: EP

Kind code of ref document: A1