DESC:RELATED PATENT APPLICATIONS

This application claims the priority to and benefit of Indian Provisional Patent Application No. 201721015503 filed on May 02, 2017; 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 oxyimino compounds, their preparation and use in treatment and/or prevention of bacterial infections.

BACKGROUND OF THE INVENTION

The emergence of bacterial resistance to known antibacterial agents is becoming a major challenge in treating bacterial infections. One way forward to treat bacterial infections, and especially those caused by resistant bacteria, is to develop new antibacterial agents that can overcome the bacterial resistance. Coates et al. (Br. J. Pharmacol. 2007; 152(8), 1147–1154) have reviewed approaches to developing new antibiotics. However, the development of new antibacterial agents is a challenging task. For example, Gwynn et al. (Annals of the New York Academy of Sciences, 2010, 1213: 5–19) have reviewed the challenges in the discovery of antibacterial agents. Several antibacterial agents have been described in the prior art. However, there remains a need for potent antibacterial agents for use in treatment and/or prevention of bacterial infections, including those caused by bacteria that have acquired resistance to one or more of the known antibacterial agents. The inventors have surprisingly discovered certain oxyimino compounds having antibacterial properties.

SUMMARY OF THE INVENTION

Accordingly, there are provided oxyimino compounds, methods for preparation of these compounds, pharmaceutical compositions comprising these compounds, and methods for treating and/or preventing bacterial infection in a subject using these compounds.

In one general aspect, there is provided a compound of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:
Q is heteroaryl or CONH;
X is O, NHCO, or C1-C6 alkyl;
Y is C1-C6 alkyl, or cycloalkyl;
R and R1 are each independently selected from:
(a) hydrogen;
(b) C1-C6 alkyl, optionally substituted with one or more substituents independently selected from NR2R3, aryl, aryl optionally substituted with OR2 or CH2NR2R3, heteroaryl, or heterocycloalkyl;
(c) NR2R3;
(d) aryl;
(e) heteroaryl; and
(f) heterocycloalkyl, optionally substituted with (C1-C6) alkyl;
R2 and R3 are each independently selected from:
(a) hydrogen; and
(b) C1-C6 alkyl, optionally substituted with NH2;
n is 0 or 1; and
M is hydrogen or a cation.

In another general aspect, there are provided pharmaceutical compositions comprising a compound of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof.

In another general aspect, there is provided a method for treating or preventing a bacterial infection in a subject, said method comprising administering to said subject a compound of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof.

In yet another general aspect, there is provided a method for treating or preventing a bacterial infection in a subject, said method comprising administering to said subject a pharmaceutical composition comprising a compound of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof.

The details of one or more embodiments of the invention are set forth in the description below. Other features, objects and advantages of the invention 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, and additional applications of the principles of the invention as illustrated herein, which would occur to one of ordinary skills 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 inventors have surprisingly discovered certain oxyimino compounds having antibacterial properties.

The term “stereoisomers” as used herein refers to and includes compounds that have identical chemical constitution, but differ with regard to the arrangement of their atoms or groups in space. The compounds of Formula (I) contain asymmetric or chiral centres, and therefore, may exist in different stereoisomeric forms. It is intended, unless specified otherwise, that all stereoisomeric forms of the compounds of Formula (I) as well as mixtures thereof, including racemic mixtures, form part of the present invention. In addition, all geometric and positional isomers (including cis and trans-forms) as well as mixtures thereof, are also embraced within the scope of the invention. In general, a reference to a compound is intended to cover its stereoisomers and a mixture of various stereoisomers.

The term “pharmaceutically acceptable salt” as used herein refers to one or more salts of a given compound which possesses the desired pharmacological activity of the free compound and which are neither biologically nor otherwise undesirable. In general, the “pharmaceutically acceptable salts” refer to and include those salts that are suitable for use in contact with the tissues of human and animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge, et al. (J. Pharmaceutical Sciences, 66: 1-19 (1977)), incorporated herein by reference in its entirety, describes various pharmaceutically acceptable salts in details.

In general, the compounds according to the invention contain basic (e.g. nitrogen atoms) as well as acid moieties (e.g SO3H group). A person of skills in the art would appreciate that such compounds, therefore, can form acidic salts (formed with inorganic and/or organic acids), as well as basic salts (formed with inorganic and/or organic bases). Such salts can be prepared using procedures described in the art. For example, the basic moiety can be converted to its salt by treating a compound with a suitable amount of acid. Typical, non-limiting examples of such suitable acids include hydrochloric acid, trifluoroacetic acid, methanesulphonic acid, and the like. Alternatively, the acid moiety may be converted into its salt by treating with a suitable base. Typical non-limiting examples of such bases include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or the like. In case of compounds containing more than one functional group capable of being converted into salt, each such functional group may be converted to a salt independently. For example, in case of compounds containing two basic nitrogen atoms, one of the basic nitrogen can form salt with one acid while the other basic nitrogen can form salt with another acid. The compounds according to the invention contain both, acidic as well as basic moieties, and thus can form inner salts or corresponding zwitterions. In general, all pharmaceutically acceptable salt forms of compounds of Formula (I) according to invention including acid addition salts, base addition salts, zwitterions or the like are contemplated to be within the scope of the present invention and are generically referred to as the pharmaceutically acceptable salts.

The term “infection” or “bacterial infection” as used herein refers to and includes presence of bacteria, in or on a subject, which, if its growth were inhibited, would result in a benefit to the subject. As such, the term “infection” in addition to referring to the presence of bacteria also refers to normal flora, which is not desirable. The term “infection” includes infection caused by bacteria.

The term “treat”, “treating” or “treatment” as used herein refers to administering a medicament, including a pharmaceutical composition, or one or more pharmaceutically active ingredients, for prophylactic and/or therapeutic purposes. The term “prophylactic treatment” refers to treating a subject who is not yet infected, but who is susceptible to, or otherwise at a risk of infection (preventing the bacterial infection). The term “therapeutic treatment” refers to administering treatment to a subject already suffering from infection. The terms “treat”, “treating” or “treatment” as used herein also refer to administering compositions or one or more of pharmaceutically active ingredients discussed herein, with or without additional pharmaceutically active or inert ingredients, in order to: (i) reduce or eliminate either a bacterial infection or one or more symptoms of the bacterial infection, or (ii) retard the progression of a bacterial infection or of one or more symptoms of the bacterial infection, or (iii) reduce the severity of a bacterial infection or of one or more symptoms of the bacterial infection, or (iv) suppress the clinical manifestation of a bacterial infection, or (v) suppress the manifestation of adverse symptoms of the bacterial infection.

The term “pharmaceutically effective amount” or “therapeutically effective amount” or “effective amount” as used herein refers to an amount, which has a therapeutic effect or is the amount required to produce a therapeutic effect in a subject. For example, a therapeutically or pharmaceutically effective amount of an antibacterial agent or a pharmaceutical composition is the amount of the antibacterial agent or the pharmaceutical composition required to produce a desired therapeutic effect as may be judged by clinical trial results, model animal infection studies, and/or in vitro studies (e.g. in agar or broth media). The pharmaceutically effective amount depends on several factors, including but not limited to, the microorganism (e.g. bacteria) involved, characteristics of the subject (for example height, weight, sex, age and medical history), severity of infection and the particular type of the antibacterial agent used. For prophylactic treatments, a therapeutically or prophylactically effective amount is that amount which would be effective in preventing a microbial (e.g. bacterial) infection. The compounds and/or pharmaceutical compositions according to the invention are used in amounts that are effective in providing the desired therapeutic effect or result.

The term “administration” or “administering” refers to and includes delivery of a composition or one or more pharmaceutically active ingredients to a subject, including for example, by any appropriate methods, which serves to deliver the composition or its active ingredients or other pharmaceutically active ingredients to the site of the infection. The method of administration may vary depending on various factors, such as for example, the components of the pharmaceutical composition or the nature of the pharmaceutically active or inert ingredients, the site of the potential or actual infection, the microorganism involved, severity of the infection, age and physical condition of the subject and a like. Some non-limiting examples of ways to administer a composition or a pharmaceutically active ingredient to a subject according to this invention includes oral, intravenous, topical, intra-respiratory, intra-peritoneal, intra-muscular, parenteral, sublingual, transdermal, intranasal, aerosol, intra-ocular, intra-tracheal, intra-rectal, vaginal, gene gun, dermal patch, eye drop, ear drop or mouthwash. In case of a pharmaceutical composition comprising more than one ingredient (active or inert), one of way of administering such composition is by admixing the ingredients (e.g. in the form of a suitable unit dosage form such as tablet, capsule, solution, powder and a like) and then administering the dosage form. Alternatively, the ingredients may also be administered separately (simultaneously or one after the other) as long as these ingredients reach beneficial therapeutic levels such that the composition as a whole provides a synergistic and/or the desired effect.

The term “growth” as used herein refers to a growth of one or more microorganisms and includes reproduction or population expansion of the microorganism (e.g. bacteria). The term “growth” also includes maintenance of on-going metabolic processes of a microorganism (e.g. bacteria), including processes that keep the microorganism alive.

The term “synergistic” or “synergy” as used herein refers to the interaction of two or more agents so that their combined effect is greater than their individual effects.

The term “antibacterial agent” as used herein refers to any substance, compound or a combination of substances or a combination compounds capable of: (i) inhibiting, reducing or preventing growth of bacteria; (ii) inhibiting or reducing ability of a bacteria to produce infection in a subject; or (iii) inhibiting or reducing ability of bacteria to multiply or remain infective in the environment. The term “antibacterial agent” also refers to compounds capable of decreasing infectivity or virulence of bacteria.

The term “pharmaceutically inert ingredient” or “carrier” or “excipient” refers to a compound or material used to facilitate administration of a compound, including for example, to increase the solubility of the compound. Typical, non-limiting examples of solid carriers include, starch, lactose, dicalcium phosphate, sucrose, and kaolin and so on. Typical, non-limiting examples of liquid carriers include sterile water, saline, buffers, non-ionic surfactants, and edible oils such as oil, peanut and sesame oils and so on. In addition, various adjuvants commonly used in the art may be included. These and other such compounds are described in the literature, for example, in the Merck Index (Merck & Company, Rahway, N.J.). Considerations for inclusion of various components in pharmaceutical compositions are described, for example, in Gilman et al. (Eds.) (1990); Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 8th Ed., Pergamon Press., which is incorporated herein by reference in its entirety.

The term “subject” as used herein refers to a vertebrate or invertebrate, including a mammal. The term “subject” includes human, animal, a bird, a fish, or an amphibian. Typical, non-limiting examples of a “subject” includes humans, cats, dogs, horses, sheep, bovine cows, pigs, lambs, rats, mice and guinea pigs.

The term “C1-C6 alkyl” as used herein refers to branched or unbranched acyclic hydrocarbon radical with 1 to 6 carbon atoms. Typical, non-limiting examples of “C1-C6 alkyl” include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, n-hexyl and the like. The “C1-C6 alkyl” may be unsubstituted, or substituted with one or more substituents.

The term “cycloalkyl” as used herein refers to three to seven member cyclic hydrocarbon radicals. The cycloalkyl group optionally incorporates one or more double or triple bonds, or a combination of double bonds and triple bonds, but which is not aromatic. Typical, non-limiting examples of cycloalkyl groups include cyclopropane, cyclobutane, cyclopentane, cyclohexane, and cycloheptane. The cycloalkyl may be unsubstituted, or substituted with one or more substituents.

The term “heterocycloalkyl” as used herein refers to four to seven member cycloalkyl group containing one or more heteroatoms selected from nitrogen, oxygen or sulfur. The heterocycloalkyl group optionally incorporates one or more double or triple bonds, or a combination of double bonds and triple bonds, but which is not aromatic. Typical, non-limiting examples of heterocycloalkyl groups include azetidine, pyrrolidine, 2-oxo-pyrrolidine, imidazolidin-2-one, piperidine, oxazine, thiazine, piperazine, piperazin-2,3-dione, morpholine, thiamorpholine, azapane, and the like. The heterocycloalkyl may be unsubstituted, or substituted with one or more substituents.

The term “aryl” as used herein refers to a monocyclic or polycyclic aromatic hydrocarbon. Typical, non-limiting examples of aryl groups include phenyl, naphthyl, anthracenyl, fluorenyl, phenanthrenyl, and the like. The aryl group may be unsubstituted, or substituted with one or more substituents.

The term “heteroaryl” as used herein refers to a monocyclic or polycyclic aromatic hydrocarbon group wherein one or more carbon atoms have been replaced with heteroatoms selected from nitrogen, oxygen, and sulfur. If the heteroaryl group contains more than one heteroatom, the heteroatoms may be the same or different. Typical, non-limiting example of heteroaryl groups include 1,2,4-oxadiazol, 1,3,4-oxadiazol, 1,3,4-thiadiazol, 1,2,3,4-tetrazol, 1,3-oxazol, 1,3-thiazole, pyridine, pyrimidine, pyrazine, pyridazine, furan, pyrrol, thiophene, imidazole, pyrazole, benzofuran, benzothiophene, benzimidazole, benzoxazole, benzothiazole, thiazole, and the like. The heteroaryl group may be unsubstituted, or substituted with one or more substituents.
.
The term “optionally substituted” as used herein means that substitution is optional and therefore includes both unsubstituted and substituted atoms and moieties. A “substituted” atom or moiety indicates that any hydrogen on the designated atom or moiety can be replaced with a selection from the indicated substituent group, provided that the normal valence of the designated atom or moiety is not exceeded, and that the substitution results in a stable compound.

In one general aspect, there is provided a compound of Formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof;

wherein:
Q is heteroaryl or CONH;
X is O, NHCO, or C1-C6 alkyl;
Y is C1-C6 alkyl, or cycloalkyl;
R and R1 are each independently selected from:
(a) hydrogen;
(b) C1-C6 alkyl, optionally substituted with one or more substituents independently selected from NR2R3, aryl, aryl optionally substituted with OR2 or CH2NR2R3, heteroaryl, or heterocycloalkyl;
(c) NR2R3;
(d) aryl;
(e) heteroaryl; and
(f) heterocycloalkyl, optionally substituted with (C1-C6) alkyl;
R2 and R3 are each independently selected from:
(a) hydrogen; and
(b) C1-C6 alkyl, optionally substituted with NH2;
n is 0 or 1; and
M is hydrogen or a cation

Typical, non-limiting examples of compounds according to the invention include the following:

(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-2-yl)-methoxyimino-butanoyl) -hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-propyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-3-methylbutanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-(S)-pyrrolidin-2-yl-methoxyimino)-butanoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-piperidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(4-aminomethyl-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2-aminoethoxy)-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(1H-1,2,3-triazolyl)-ethoxyimino)-butanoyl) -hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-1,2,3-triazolyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-tetrazoyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(pyridin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-ethoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-propanoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((S)-pyrrolidin-2-yl-methoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-propanoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-pyrrolidin-2-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(piperazin-4-yl)-ethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-3-((R)-pyrrolidin-2-yl)-propionyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-phenyl-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-(2-amino-2-methoxyimino)-ethoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-aminoethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(4-aminomethyl-benzyloxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-imidazolyl-ethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-tetrazolyl-ethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-methoxyimino-2-phenylethoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-hydroxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-(2-aminoethoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-ethoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-propanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-propanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-2-phenyl-ethanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-3-(piperidin-1-yl)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane; or
a stereoisomer or a pharmaceutically acceptable salt thereof.

Typical, non-limiting examples of salts of the compounds according to the invention include the following:

Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino) -butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-2-yl)-methoxyimino-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoroacetic acid and sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2-aminoethoxy)-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(1H-1,2,3-triazolyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-1,2,3-triazolyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-tetrazoyl)-ethoxyimino) -butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(pyridin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-pyrrolidin-2-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Di -(trifluoro acetic acid) salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(piperazin-4-yl)-ethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-imidazolyl-ethoxyimino) -propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-tetrazolyl-ethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-methoxyimino-2-phenylethoxy) -carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-hydroxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-2-phenyl-ethanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-3-(piperidin-1-yl)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoroacetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[(5-(E/Z)-(2-(2-aminoethoxy-benzyloxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-propyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-3-methyl butanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-(S)-pyrrolidin-2-yl-methoxyimino)-butanoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-piperidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(4-aminomethyl-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-ethoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-propanoxyimino) -pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((S)-pyrrolidin-2-yl-methoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-propanoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-3-((R)-pyrrolidin-2-yl)-propionyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-phenyl-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-(2-amino-2-methoxyimino)-ethoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-aminoethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(4-aminomethyl-benzyloxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-(2-aminoethoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-ethoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-propanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-propanoxyimino) -butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-Oxo-6-sulfooxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane; or
a stereoisomer thereof.

The compounds of the invention can be prepared according to the general procedure given in Schemes 1 to 4. Individual stereoisomers can be prepared using appropriate starting materials and reagents. A person of skills in the art would appreciate that the described methods can be varied and/or optimized further to provide the desired and related compounds.

A. Preparation of compounds of Formula (I) wherein Q is CONH and X is NHCO:

Scheme 1

Typically, a compound of Formula (VIIa) is reacted with a compound of Formula (VIIIa) to obtain a compound of Formula (IIa). The compound of Formula (IIa) is reacted with a sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diaza-bicyclo [3.2.1] octane-2-carboxylic acid (III) to obtain a compound of Formula (IVa). The compound of Formula (IVa) is then converted into a compound of Formula (Va) in presence of a suitable debenzylating agent. Typical, not-limiting example of a suitable debenzylating agent includes hydrogen gas in presence of a transition metal catalyst such as palladium on carbon. The compound of Formula (Va) is converted into a compound of Formula (VIa) in presence of a suitable sulfonating agent. Typical, not-limiting example of a suitable sulfonating agent includes sulfurtrioxide pyridine complex. The sulfonation reaction is followed by treatment with tetrabutylammonium hydrogen sulphate to obtain a compound of Formula (VIa).

B. Preparation of compounds of formula (I) wherein Q is CONH and X is O:

Scheme 2

Typically, a compound of Formula (VIIb) is reacted with a compound of Formula (VIIIb) to obtain a compound of Formula (IIb). The compound of Formula (IIb) is reacted with a sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diaza-bicyclo [3.2.1] octane-2-carboxylic acid (III) to obtain a compound of Formula (IVb). The compound of Formula (IVb) is then converted into a compound of Formula (Vb) in presence of a suitable debenzylating agent. Typical, not-limiting example of a suitable debenzylating agent includes hydrogen gas in presence of a transition metal catalyst such as palladium on carbon. The compound of Formula (Vb) is converted into a compound of Formula (VIb) in presence of a suitable sulfonating agent. Typical, not-limiting example of a suitable sulfonating agent includes sulfurtrioxide pyridine complex. The sulfonation reaction is followed by treatment with tetrabutylammonium hydrogen sulphate to obtain a compound of Formula (VIb).

C. Preparation of compounds of formula (I) wherein Q is CONH and X is C1-C6 alkyl;

Scheme 3

Typically, a compound of Formula (VIIc) is reacted with a compound of Formula (VIIIc) to obtain a compound of Formula (IIc). The compound of Formula (IIc) is reacted with a sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diaza-bicyclo [3.2.1] octane-2-carboxylic acid (III) to obtain a compound of Formula (IVc). The compound of Formula (IVc) is then converted into a compound of Formula (Vc) in presence of a suitable debenzylating agent. Typical, not-limiting example of a suitable debenzylating agent includes hydrogen gas in presence of a transition metal catalyst such as palladium on carbon. The compound of Formula (Vc) is converted into a compound of Formula (VIc) in presence of a suitable sulfonating agent. Typical, not-limiting example of a suitable sulfonating agent includes sulfurtrioxide pyridine complex. The sulfonation reaction is followed by treatment with tetrabutylammonium hydrogen sulphate to obtain a compound of Formula (VIc).

D. Preparation of compounds of formula (I) wherein Q is heteroaryl and X is C1-C6 alkyl;

Scheme 4

Typically, a compound of Formula (IVa) is cyclised to a compound of Formula (IVd) in presence of a suitable reagent. Typical, non-limiting examples of a suitable reagent that can be used for cyclising compound of Formula (IVa) to a compound of Formula (IVd) include p-toluenesulfonyl chloride. The compound of Formula (IVd) is then converted into a compound of Formula (Vd) in presence of a suitable debenzylating agent. Typical, not-limiting example of a suitable debenzylating agent includes hydrogen gas in presence of a transition metal catalyst such as palladium on carbon. The compound of Formula (Vd) is converted into a compound of Formula (VId) in presence of a suitable sulfonating agent. Typical, not-limiting example of a suitable sulfonating agent includes sulfurtrioxide pyridine complex. The sulfonation reaction is followed by treatment with tetrabutylammonium hydrogen sulphate to obtain a compound of Formula (VId).

The compounds according to invention can be isolated as zwitterions or as corresponding salts. A wide variety of other reagents which can bring about these functional group transformations can be used.

In another general aspect, there are provided pharmaceutical compositions comprising a compound of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof. The pharmaceutical compositions according to the invention may include one or more pharmaceutically acceptable carriers or excipients or a like. Typical, non-limiting examples of such carriers or excipients include mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, sodium crosscarmellose, glucose, gelatin, sucrose, magnesium carbonate, wetting agents, emulsifying agents, solubilizing agents, pH buffering agents, lubricants, stabilizing agents, binding agents and a like.

The pharmaceutical composition or the active ingredients according to the present invention may be formulated into a variety of dosage forms. Typical, non-limiting examples of dosage forms include solid, semi-solid, liquid and aerosol dosage forms; such as tablets, capsules, powders, solutions, suspensions, suppositories, aerosols, granules, emulsions, syrups, elixirs and a like. In some embodiments, the pharmaceutical composition is in the form of a powder or a solution. In some other embodiments, the pharmaceutical compositions according to the invention are in the form of a powder that can be reconstituted by addition of a compatible reconstitution diluent prior to parenteral administration. Non-limiting example of such a compatible reconstitution diluent includes water. In some other embodiments, the pharmaceutical compositions according to the invention are in the form of a frozen composition that can be diluted with a compatible diluent prior to parenteral administration. In some other embodiments, the pharmaceutical compositions according to the invention are in the form ready to use for parenteral administration.

In the methods according to the invention, the pharmaceutical composition and/or other pharmaceutically active ingredients disclosed herein may be administered by any appropriate method, which serves to deliver the composition or its constituents or the active ingredients to the desired site. The method of administration can vary depending on various factors, such as for example, the components of the pharmaceutical composition and nature of the active ingredients, the site of the potential or actual infection, the microorganism (e.g. bacteria) involved, severity of infection, age and physical condition of the subject. Some non-limiting examples of administering the composition to a subject according to this invention include oral, intravenous, topical, intra-respiratory, intra-peritoneal, intra-muscular, parenteral, sublingual, transdermal, intranasal, aerosol, intraocular, intra-tracheal, intra-rectal, vaginal, gene gun, dermal patch, eye drop, ear drop or mouthwash.

Similarly, in the methods according to the invention, the active ingredients disclosed herein may be administered to a subject in several ways depending on the requirements. In some embodiments, the active ingredients are admixed in appropriate amounts and then the admixture is administered to a subject. In some other embodiments, the active ingredients are administered separately. Since the invention contemplates that the active ingredients agents may be administered separately, the invention further provides for combining separate pharmaceutical compositions in kit form. The kit may comprise one or more separate pharmaceutical compositions, each comprising one or more active ingredients. Each of such separate compositions may be present in a separate container such as a bottle, vial, syringes, boxes, bags, and the like. Typically, the kit comprises directions for the administration of the separate components. The kit form is particularly advantageous when the separate components are preferably administered in different dosage forms (e.g., oral and parenteral) ore are administered at different dosage intervals. When the active ingredients are administered separately, they may be administered simultaneously or sequentially.

In some other embodiments, there are provided methods for treating or preventing bacterial infection in a subject, said method comprising administering to said subject a compound of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof.

In some embodiments, there are provided methods for treating or preventing bacterial infection in a subject, said method comprising administering to said subject a pharmaceutical composition comprising a compound of Formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof.

In general, the compounds, pharmaceutical compositions and method disclosed herein are useful in treating and/or preventing bacterial infections. Advantageously, the compounds, compositions and methods disclosed herein are also effective in treating or preventing infections caused by bacteria that are considered be less or not susceptible to one or more of known antibacterial agents or their known compositions. Some non-limiting examples of such bacteria known to have developed resistance to various antibacterial agents include Acinetobacter, E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterobacter, Klebsiella, Citrobacter and a like. Other non-limiting examples of infections that may be treated or prevented using the compounds, compositions and/or methods according to the invention include: skin and soft tissue infections, febrile neutropenia, urinary tract infection, intraabdominal infections, respiratory tract infections, pneumonia (nosocomial), bacteremia meningitis, surgical infections etc.

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

(2S,5R)-7-Oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane

Step-1: Preparation of 3-[(E/Z)-(R)-2-(tert-butoxycarbonyl)amino-propanoxyimino]-butanoic acid hydrazide (1a):

To a clear solution of O-(R)-2-(tert-butoxycarbonyl)amino-propanyl hydroxylamine (7 gm, 33 mmol) and ethyl-acetoacetate (4.22 ml, 33 mmol) in toluene (70 ml), was added sodium acetate (14 gm, 165 mmol) at 30°C under stirring to obtain a suspension. The suspension was stirred at the same temperature for 5 hours, and then filtered. The filtrate was washed with 10% aqueous KHSO4 solution. Organic layer was separated and evaporated to obtain a crude mass, which was purified using silica gel column chromatography (60-120 mesh, 15% ethyl acetate in hexane) to obtain 8.4 gm of ethyl-3-[(E/Z)-(R)-2-(tert-butoxycarbonyl)amino-propanoxyimino]-butanoate as a colourless syrup (84% yield).

Analysis:
Mass (M+1): ES 302.2 for C14H26N2O5;
1H NMR (400 MHz, CDCl3): d 4.78 (br s, NH), 4.16-4.21 (m, 2H), 3.91-4.08 (m, 2H), 3.33 (s, 1H), 3.20 (s, 1H), 1.98-1.94 (d, 3H), 1.44 (s, 9H), 1.26 (t, 3H), 1.14-1.65 (m, 3H).

A mixture of ethyl-3-[(E/Z)-(R)-2-(tert-butoxycarbonyl)amino-propanoxyimino]-butanoate (5 gm, 16.5 mmol) and hydrazine hydrate (99%, 2 ml, 33 mmol) in ethanol (50 ml) was stirred at 30°C for 6 hours. The reaction mixture was concentrated under vacuum to obtain a residue, which was dissolved in chloroform (50 ml). The organic layer was washed with water (5 ml ? 2) and dried over sodium sulphate. Solvent was evaporated under vacuum to provide 4.9 gm of 3-[(E/Z)-(R)-2-(tert-butoxycarbonyl)amino-propanoxyimino]-butanoic acid hydrazide (compound 1a).

Analysis:
Mass (M+1): ES 289.5 for C12H24N4O4;
1H NMR (400 MHz, CDCl3): d 8.17 (br s, NH), 4.52 (d, NH), 4.10 (dd, 2H), 3.91-4.02 (m, 2H), 3.73-3.75 (m, 1H), 3.24 (d, 1H), 3.10 (d, 1H), 1.85-1.88 (m, 3H), 1.44 (s, 9H), 1.11-1.17 (m, 3H).

Step-2: Preparation of (2S,5R)-7-oxo-6-benzyloxy-2-[N’-((E/Z)-3-((R)-2-(tert-butoxycarbonyl) amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane (1b):

To a stirred solution of compound (1a) (4.9 gm, 17.2 mmol) and sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylic acid (compound (III), 5 gm , 17.2 mmol) in dimethylformamide (50 ml) was added N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC.HCl, 4.9 gm, 25.8 mmol), 1-hydroxybenzotriazole (HOBt, 2.32 gm, 17.2 mmol) and diisopropyl ethyl amine (DIPEA, 9.13 ml. 51.6 mmol) and the contents were stirred at 30°C for 6 hours. After completion of reaction, solvent from the reaction mixture was evaporated under vacuum, and water (100 ml) was added to the residue. The suspension was extracted with ethyl acetate (100 ml). Organic layer was washed with saturated sodium bicarbonate aqueous solution followed by saturated ammonium chloride aqueous solution. Organic layer was dried over sodium sulphate and was evaporated under vacuum to obtain a residue, which was purified using silica gel column chromatography (60-120 mesh, 30% acetone in hexane as an eluent) to obtain 5.7 gm of compound (1b) as a solid.

Analysis:
Mass (M+1): ES 547.5 for C26H38N6O7;
1H NMR (400 MHz, CDCl3): d 8.91 (br s, 1H), 8.32 (br s, 1H), 8.26 (s, 1H), 7.37-7.45 (m, 5H), 5.06 (d, 1H), 4.92 (d, 1H), 4.10-4.17 (m, 2H), 4.02 (d, 1H), 3.73-3.76 (m, 1H), 3.29 (br s, 2H), 3.06-3.25 (m, 2H), 2.32-2.35 (m, 1H), 1.93-2.01 (m, 1H), 1.90 (s, 3H), 1.42 (s, 3H), 1.27 (d, 9H), 1.11-1.15 (m, 3H).

Step-3: Preparation of (2S,5R)-7-oxo-6-hydroxy-2-[N’-((E/Z)-3-((R)-2-(tert-butoxycarbonyl) amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane (1c):

To a solution of compound (1b) (5.7 gm, 10.4 mmol) in methanol (60 ml), was added palladium on carbon catalyst (10%, 0.6 gm) and the resulting black suspension was stirred under 1 atm. hydrogen pressure at 30°C for 2 hours. After completion of reaction, the suspension was filtered under suction over celite bed and the filtrate was concentrated under vacuum to provide 3.5 gm of compound (1c) as a white solid (73% yield).

Analysis:
Mass (M+1): ES 457.3 for C19H32N6O7.

Step-4: Preparation of tetrabutylammonium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-(tert-butoxycarbonyl)amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane (1d):

To a solution of compound (1c) (3.5 gm, 7.6 mmol) in dichloromethane (50 ml) was added triethyl amine (3.19 ml, 22.8 mmol) followed by sulfurtrioxide pyridine complex (2.45 gm, 15.3 mmol) and the reaction mixture was stirred for 2 hours at 30°C. After completion of the reaction, tetrabutylammonium hydrogen sulphate (2.58 gm, 7.6 mmol) was added to the reaction contents and the stirring was continued for another 1 hour. To the reaction mixture was added 0.5 N potassium dihydrogen phosphate (KH2PO4) aqueous solution (50 ml) and layers were separated. The organic layer was dried over sodium sulphate and evaporated under vacuum to obtain a reation mass, which was purified using silica gel column chromatography (60-120 mesh, using 4% methanol in chloroform) to obtain 5.4 gm of compound (1d) as a colourless solid (96% yield).

Analysis:
Mass (M-1): ES 535.2 as a free acid for C19H32N6O10S.C16H36N.

Step-5:(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-(tert-butoxycarbonyl)amino-propanoxyimino) -butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane (1):

A solution of compound (1d) (5.4 gm, 10 mmol) in dichloromethane (15 ml) was cooled to about -5°C and to this solution was added trifluoroacetic acid (15 ml) at -5°C under stirring. The reaction contents were stirred for 1 hour. After completion of reaction the solvent was removed under vacuum below 30°C and the residue obtained was washed with diethyl ether, acetonitrile and dichloromethane to obtain 2.7 gm of compound (1) as a white solid (62% yield).

Analysis:
Mass (M-1): ES 435.3 for C14H24N6O8S;
1H NMR (400 MHz, DMSO-d6): ? 10.03 (d, 1H), 9.96 (d, 1H), 7.73 (br d, 3H), 3.92-5.75 (m, 3H), 3.84 (t, 1H), 3.38 (d, 1H), 3.14-3.28 (m, 2H), 3.08 (s, 1H), 3.02-3.04 (m, 1H), 2.00-2.05 (m, 1H), 1.84-1.92 (m, 4H), 1.70-1.74 (m, 1H), 1.56-1.64 (m, 1H), 1.18 (d, 3H).

Following examples (Table 1, Example 2-29) were prepared using procedure described in Example-1 and Scheme-1 by reacting appropriate hydrazides (IIa) with sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylic acid (III).

Table 1
Example Compound of Formula (IIa) Compound of Formula (Ia) Analysis
2


1H NMR (400 MHz, DMSO-d6): d 9.92 (s, 2H), 4.00 (s, 1H), 3.82 (d, 1H), 3.37-3.73 (m, 3H), 3.19-3.23 (m, 2H), 2.98-3.04 (m, 2H), 1.99-2.03 (m, 1H), 1.82-1.86 (m, 3H), 1.62-1.75 (m, 3H).
Mass: (M-1): ES: 392.3 as a free acid for C12H18N5O8S.Na
3


1H NMR (400 MHz, DMSO-d6): d 10.00 (d, 1H), 9.96 (d, 1H), 7.71 (br d, 3H), 4.12-4.16 (m, 2H), 3.86 (s, 1H), 3.84 (t, 1H), 3.30-3.37 (m, 1H), 3.16-3.21 (m, 1H), 3.08 (s, 3H), 3.02-3.05 (m, 2H), 2.01-2.05 (m, 1H), 1.89-1.91 (m, 3H), 1.72-1.73 (m, 1H), 1.59-1.62 (m, 1H).
Mass: (M-1): ES 421.2 for C13H22N6O8S
4


1H NMR (400 MHz, DMSO-d6): d 9.95 (s, 1H), 9.93 (s, 1H), 7.64 (br s, 3H), 4.02-4.07 (m, 2H), 3.80-3.85 (m, 4H), 3.18-3.25 (m, 2H), 3.01-3.06 (m, 2H), 2.86-2.91 (m, 2H), 2.02-2.05 (m, 1H), 1.86 (d, 3H), 1.69-1.83 (m, 2H), 1,61-1.67 (m, 1H).
Mass: (M-1): ES 435.4 for C14H24N6O8S
5


1H NMR (400 MHz, DMSO-d6): d 10.03 (d, 1H), 9.96 (d, 1H), 7.74 (br d, 3H), 3.93-4.10 (m, 3H), 3.85 (t, 1H), 3.46 (br s, 1H), 3.03-3.27 (m, 4H), 2.02-2.08 (m, 1H), 1.91 (d, 4H), 1.61-1.85 (m, 2H), 1.17-1.19 (m, 3H).
Mass: (M-1): ES 435.3 for C14H24N6O8S
6


1H NMR (400 MHz, DMSO-d6): d 10.02 (br s, 1H), 9.95 (br s, 1H), 7.80 (br s, 3H), 4.16-4.22 (m, 1H), 4.03-4.10 (m, 2H), 3.85 (t, 1H), 3.38-3.43 (m, 1H), 3.17-3.28 (m, 2H), 3.00-3.09 (m, 2H), 2.00-2.06 (m, 1H), 1.85-1.96 (m, 5H), 1,71-1.75 (m, 1H), 1.61-1.64 (m, 1H), 0.95-0.98 (m, 6H).
Mass: (M-1): ES 463.4 for C16H28N6O8S
7


1H NMR (400 MHz, DMSO-d6): d 9.98 (t, 2H), 8.89 (br s, 1H), 8.37 (br s, 1H), 4.19-4.24 (m, 1H), 4.10-4.15 (m, 1H), 4.03 (s, 1H), 3.85 (t, 1H), 3.77 (br s, 1H), 3.38 (t, 1H), 3.31 (d, 1H), 3.18-3.26 (m, 3H), 3.11 (s, 1H), 3.02 (d, 1H), 2.02-2.08 (m, 3H), 1.91 (s, 3H), 1.84-1.89 (m, 2H), 1.71-1.75 (m, 1H), 1.61-1.68 (m, 1H).
Mass: (M-1): ES: 461.4 for C16H26N6O8S.
8


1H NMR (400 MHz, DMSO-d6): d 9.97 (d, 1H), 9.95 (d, 1H), 8.87 (br d, 1H), 8.38 (br d, 1H), 4.18-4-23 (m, 1H), 4.06-4.14 (m, 1H), 4.02 (s, 1H), 3.85 (t, 1H), 3.76-3.77 (m, 1H), 3.30 (s, 1H), 3.14-3.21 (m, 3H), 3.10 (s, 1H), 3.01 (d, 1H), 2.00-2.08 (m, 2H), 1.83-1.95 (m, 6H), 1.69-1.75 (m, 1H), 1.58-1.67 (m, 2H).
Mass: (M-1): ES: 461.2 for C16H26N6O8S
9


1H NMR (400 MHz, DMSO-d6): d 9.93 (t, 2H), 8.60 (br s, 2H), 3.98-4.06 (m, 2H), 3.90-3.95 (m, 1H), 3.83 (d, 1H), 3.14-3.29 (m, 5H), 3.02-3.06 (m, 2H), 2.93 (br s, 1H), 2.56-2.62 (m, 1H), 1.88-2.03 (m, 2H), 1.80 (d, 3H), 1.57-1.71 (m, 4H).
Mass: (M-1): ES 461.3 for C16H26N6O8S
10


1H NMR (400 MHz, DMSO-d6): d 9.96 (d, 1H), 9.92 (d, 1H), 8.47 (br s, 1H), 8.25 (br s, 1H), 4.02 (s, 1H), 3.83-3.94 (m, 3H), 3.17-3.37 (m, 4H), 3.00-3.06 (m, 2H), 2.67-2.78 (m, 2H), 2.02-2.05 (m, 2H), 1.86 (d, 3H), 1.58-1.81 (m, 5H), 1.21-1.24 (m, 2H).
Mass: (M-1): ES: 475.4 for C17H28N6O8S
11


1H NMR (400 MHz, DMSO-d6): d 9.94 (d, 1H), 9.92(d, 1H), 8.82 (br s, 1H), 8.11 (br s, 1H), 4.02 (s, 1H), 3.87 (d, 1H), 3.83 (d, 2H), 3.19-3.24 (m, 4H), 2.99-3.05 (m, 2H), 2.86-2.89 (m, 2H), 1.57-2.04 (m, 10H), 1.33-1.39 (m, 2H).
Mass: (M-1): ES 475.4 for C17H28N6O8S
12

1H NMR (400 MHz, DMSO-d6): d 9.94 (t, 2H), 8.09 (br s, 3H), 7.40-7.45 (m, 4H), 5.02 (d, 2H), 4.02 (br s, 3H), 3.81 (t, 1H), 2.99-3.39 (m, 4H), 1.88-2.00 (m, 1H), 1.83 (d, 3H), 1.59-1.63 (m, 3H).
Mass: (M-1): ES 497.4 for C19H26N6O8S
13


1H NMR (400 MHz, DMSO-d6): d 9.99 (br s, 2H), 7.90 (br s, 3H), 7.27-7.35 (m, 2H), 6.99-7.03 (m, 2H), 5.17 (d, 2H), 4.17 (d, 2H), 4.02 (s, 1H), 3.83 (d, 1H), 3.19-3.26 (m, 3H), 3.07 (s, 2H), 3.01 (d, 1H), 2.00-2.04 (m, 1H), 1.83-1.92 (m, 4H), 1.63-1.77 (m, 2H).
Mass: (M-1): ES 527.4 for free acid and base C20H28N6O9SNa.C2F3O2
14


1H NMR (400 MHz, DMSO-d6): d 9.94 (br s, 2H), 8.06 (d, 1H), 7.71 (d, 1H), 4.62-4.66 (m, 2H), 4.29-4.35 (m, 2H), 4.01 (s, 1H), 3.82 (d, 1H), 3.20 (d, 2H), 3.06 (s, 1H), 3.00 (d, 1H), 2.00-2.05 (m, 1H), 1.83-1.88 (m, 2H), 1.77 (s, 3H), 1.60-1.74 (m, 1H).
Mass: (M-1): ES: 473.4 as free acid for C15H21N8O8S.Na
15


1H NMR (400 MHz, DMSO-d6): d 9.90 (br s, 2H), 8.77 (s, 2H), 4.42-4.67 (m, 2H), 4.36-4.41 (m, 2H), 4.00 (s, 1H), 3.81 (d, 1H), 3.18 (d, 1H), 3.14 (d, 1H), 3.01 (t, 2H), 2.00-2.05 (m, 1H), 1.83-1.86 (m, 2H), 1.73 (s, 3H), 1.62-1.72 (m, 1H).
Mass: (M-1): ES: 473.4 as free acid for C15H21N8O8S.Na
16


1H NMR (400 MHz, DMSO-d6): d 9.90 (br s,2H), 8.97 (s, 1H), 4.94-4.95 (m, 2H), 4.43-4.48 (m, 2H), 4.00 (s, 1H), 3.81 (d, 1H), 3.19 (d, 1H), 3.11 (s, 1H), 3.02 (s, 2H), 1.99-2.03 (m, 1H), 1.83-1.87 (m, 2H), 1.68 (s, 3H), 1.60-1.64 (m, 1H).
Mass: (M-1): ES 474.4 as a free acid for C14H20N9O8S.Na
17


1H NMR (400 MHz, DMSO-d6): d 9.94 (br s, 2H), 8.51-8.56 (m, 2H), 7.77 (d, 1H), 7.40 (d, 1H), 5.07 (d, 2H), 4.00 (s, 1H), 3.81 (d, 1H), 3.19-3.23 (m, 1H), 3.05 (s, 2H), 3.00 (d, 1H), 1.99-2.03 (m, 1H), 1.87 (d, 3H), 1.65-1.72 (m, 3H).
Mass: (M-1): ES: 469.3 as a free acid for C17H21N6O8S.Na
18


1H NMR (400 MHz, DMSO-d6): d 9.90 (s, 1H), 9.70 (s, 1H), 7.70 (br s, 3H), 4.11-4.13 (m, 2H), 4.03 (s, 1H), 3.83 (d, 1H), 3.19-3.23 (m, 1H), 3.04-3.10 (m, 3H), 2.41 (d, 1H), 2.35-2.37 (m, 3H), 2.00-2.07 (m, 1H), 1.82-1.90 (m, 4H), 1.70-1.78 (m, 1H), 1.60-1.65 (m, 1H).
Mass: (M-1): ES 435.3 for C14H24N6O8S
19


1H NMR (400 MHz, DMSO-d6): d 9.86 (s, 1H), 9.78 (s, 1H), 7.71 (br s, 3H), 4.03-4.06 (m, 2H), 3.93-3.98 (m, 1H), 3.84 (d, 1H), 3.45-3.50 (m, 2H), 3.18-3.23 (m, 1H), 3.02 (d, 1H), 2.41 (d, 1H), 2.33-2.38 (m, 2H), 1.85-2.04 (m, 1H), 1.83-1.84 (m, 4H), 1.70-1.73 (m, 1H), 1.61-1.67 (m, 1H), 1.12-1.16 (m, 3H).
Mass: (M-1): ES 449.4 for C15H26N6O8S
20


1H NMR (400 MHz, DMSO-d6): d 9.88 (s, 1H), 9.80 (s, 1H), 8.84 (br s, 1H), 8.37 (br s, 1H), 4.16-4.21 (m, 1H), 4.02-4.10 (m, 2H), 3.71-3.83 (m, 2H), 3.60(br s, 2H), 3.18-3.24 (m, 3H), 3.01 (d, 1H), 2.32-2.39 (m, 3H), 2.00-2.08 (m, 2H), 1.86-1.91 (m, 4H), 1.57-1.79 (m, 4H).
Mass: (M-1): ES 475.4 for C17H28N6O8S
21


1H NMR (400 MHz, DMSO-d6): d 10.02 (d, 1H), 9.97 (d, 1H), 7.66 (br s, 3H), 4.02 (s, 1H), 3.75-3.84 (m, 4H), 3.30-3.48 (m, 2H), 3.16-3.26 (m, 1H), 2.59-3.03 (m, 3H), 2.57 (t, 2H), 1.99-2.04 (m, 1H), 1.82-1.86 (m, 1H), 1,69-1.76 (m, 1H), 1.59-1.64 (m, 1H).
Mass: (M-1): ES 421.2 for C13H22N6O8S
22


1H NMR (400 MHz, DMSO-d6): d 9.96 (br s, 2H), 7.66 (br s, 3H), 4.02 (s, 1H), 3.94 (t, 2H), 3.83 (d, 1H), 3.27-3.37 (m, 1H), 3.14-3.21 (m, 2H), 2.97-3.05 (m, 3H), 2.57 (t, 2H), 1.99-2.04 (m, 1H), 1.83- 1.89 (m, 1H), 1.68-1.75 (m, 1H), 1.56-1.64 (m, 3H), 0.88 (t, 3H).
Mass: (M-1): ES 449.3 for C15H26N6O8S
23

1H NMR (400 MHz, DMSO-d6): d 10.2 (br s, 2H), 8.04 (br s, 5H), 4.19 (d, 2H), 4.03 (s, 1H), 3.86 (d, 1H), 3.33-3.39 (m, 2H), 3.10-3.20 (m, 2H), 3.03-3.07 (m, 2H), 2.51-2.70 (m, 2H), 2.08 (s, 3H), 2.02-2.04 (m, 1H), 1.85-1.88 (m, 1H), 1.71-1.76 (m, 1H), 1.61-1.65 (m, 1H).
Mass: (M-1): ES 450.3 as a free base for C14H26N7O8S.C2F3O2.
24

1H NMR (400 MHz, DMSO-d6): d 8.20 (br s, 5H), 3.98-4.14 (m, 2H), 3.86 (d, 1H), 3.48-3.53 (m, 2H), 3.32-3.46 (m, 5H), 3.15-3.20 (m, 2H), 3.03 (t, 2H), 2.67-2.72 (m, 1H), 2.58 (t, 1H), 2.01-2.07 (m, 1H), 1.87-1.91 (m, 1H), 1.71-1.76 (m, 1H), 1.61-1.65 (m, 1H), 1.88 (d, 3H).
Mass: (M-1): ES 464.4 as a free base for C15H28N7O8S.C2F3O2
25


1H NMR (400 MHz, DMSO-d6): d 10.03 (br s, 1H), 8.10 (br s, 6H), 4.10-4.24 (m, 2H), 4.02 (s, 1H), 3.85 (d, 1H), 3.75-3.78 (m, 1H), 3.30-3.61 (m, 4H), 3.14-3.20 (m, 4H), 3.00-3.05 (m, 3H), 2.66-.268 (m, 1H), 2.58 (t, 1H), 1.85-2.04 (m, 2H), 1,60-1.75 (m, 3H).
Mass: (M-1): ES: 490.4 as free base for C17H30N7O8S.C2F3O2
26


1H NMR (400 MHz, DMSO-d6): d 10.02 (br s, 1H), 8.22 ( br s, 5H), 4.03 (br s, 1H), 3.84-3.88 (m, 3H), 3.18-3.32 (m, 4H), 2.96-3.04 (m, 3H), 2.82-2.87 (m, 2H), 2.55-2.58 (m, 3H), 1.61-2.04 (m, 7H), 1.27-1.35 (m, 2H).
Mass: (M-1): ES 504.5 as a free base for C18H31N7O8S.C2F3O2
27


1H NMR (400 MHz, DMSO-d6): d 10.01 (d, 1H), 9.96 (d, 1H), 8.70 (br s, 2H), 7.70 (br s, 2H), 4.20 (br s, 2H), 4.02 (br s, 2H), 3.84 (d, 1H), 3.75 (d, 1H), 3.25-3.35 (m, 2H), 3.13-3.16 (m, 4H), 2.95-3.03 (m, 6H), 2.49-2.58 (m, 4H), 1.99-2.02 (m, 1H), 1.74-1.78 (m, 1H), 1.68-1.73 (m, 1H), 1.59-1.62 (m, 1H).
Mass: (M-1): ES 419.4 for C18H32N8O8S.C4F6O4
28


1H NMR (400 MHz, DMSO-d6): d 10.00 (s, 2H), 9.20 (br s, 2H), 4.29-4.32 (m, 1H), 4.02 (s, 1H), 3.83-3.87 (m, 3H), 3.45-3.51 (m, 1H), 3.32-3.37 (m, 1H), 3.17-3.27 (m, 3H), 3.01 (d, 1H), 2.22-2.25 (m, 1H), 1.80-2.03 (m, 6H), 1.59-1.75 (m, 2H).
Mass: (M-1): ES: 447.2 for C15H24N6O8S
29


1H NMR (400 MHz, DMSO-d6): d 9.94 (br s, 2H), 7.31-7.46 (m, 5H), 4.80 (s, 1H), 4.22 (d, 1H), 3.95 (d, 3H), 3.85 (s, 1H), 3.68 (s, 1H), 3.38 (s, 2H), 3.24 (d, 1H), 3.20 (s, 1H), 2.22-2.26 (m, 1H), 2.10-2.14 (m, 1H), 1.95-2.00 (m, 1H), 1.82-1.88 (m, 1H).
Mass: (M-1): ES: 468.4 as free acid for C18H22N5O8S.Na

Example-30
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane.

Step-1: Preparation of (2E/Z)-1-(aminooxy)-N-methoxypropan-2-imine (30a):

To a stirred solution of (2E/Z)-1-chloro-N-methoxypropan-2-imine (1.5 gm, 12 mmol) in dimethylformamide (30 ml) was added N-hydroxypthalamide (1.63 gm, 10 mmol) and potassium carbonate (2.0 gm, 15 mmol) at 30°C. The reaction mixture was stirred at 30°C for overnight. After completion of the reaction the suspension was filtered and solid was washed with ethyl acetate (10 ml). To the filtrate was added water (200 ml) and the mixture was extracted with ethyl acetate (50 ml ? 2). Combined organic layer was washed by saturated aqueous ammonium chloride solution followed by saturated brine solution. Layers were separated and organic layer was dried over sodium sulphate. Evaporation of solvent under vacuum provided 1.8 gm of 2-{[(2E/Z)-2-(methoxyimino)propyl]oxy}-1H-isoindole-1,3(2H)-dione as a solid (72.5% yield).

Analysis:
Mass (M+1): ES 249.2 for C12H12N2O4;
1H NMR (400 MHz, CDCl3): d 7.82-7.84 (m, 2H), 7.73-7.75 (m, 2H), 4.63 (s, 2H), 3.76 (s, 3H), 2.11 (s, 3H).

To a solution of 2-{[(2E/Z)-2-(methoxyimino)propyl]oxy}-1H-isoindole-1,3(2H)-dione (4.0 gm, 16 mmol) in dichloromethane (80 ml) was added hydrazine hydrate (1.6 gm, 32 mmol) and the reaction mixture was stirred at 30°C for 2 hours to provide a suspension. The suspension obtained was filtered and washed with dichloromethane (20 ml). The filtrate was added water (30 ml) and layers were separated. Organic layer was dried over sodium sulphate and solvent was evaporated under vacuum at below 25°C to provide 1.8 gm compound (30a) as brownish oil (94% yield).

Analysis:
1H NMR (400 MHz, CDCl3): d 5.47 (br s, 2H, NH2), 4.17 (s, 2H), 3.88 (s, 3H), 1.88 (s, 3H).

Step-2: Preparation of (2S,5R)-7-oxo-6-benzyloxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (30b):

To a suspension of sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylic acid (compound (III), 5 gm, 17.2 mmol), N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC.HCl, 5.22 gm, 27 mmol) and 1-hydroxybenzotriazole (HOBt, 2.4 gm, 18.3 mmol) in dimethylformamide (30 ml) was added compound (30a) (1.8 gm, 15 mmol) at 30°C under stirring. The reaction mixture was stirred at 30°C for 16 hours. After completion of the reaction, water (250 ml) was added and the mixture was extracted with ethyl acetate (50 ml ? 2). Combined organic layer was washed with saturated aqueous ammonium chloride solution followed by saturated brine solution. Layers were separated and the organic layer was evaporated under vacuum to provide crude mass. The crude mass was purified using silica gel column chromatography (60-120 mesh 20-35% acetone in hexane) to provide 1.7 gm of compound (30b) as a foam (35% yield).

Analysis:
Mass (M+1): ES 377.3 for C18H24N4O5;
1H NMR (400 MHz, CDCl3): d 9.08 ( br s, 1H) 7.37-7.44 (m, 5H), 5.05 (d, 1H), 4.90 (d, 1H), 4.34-4.42 (dd, 2H), 3.94 (d, 1H), 3.80 (s, 3H), 2.98 (s, 1H), 2.99 (d, 1H), 2.78 (d, 1H), 2.17-2.35 (m, 1H), 1.97-1.99 (m, 1H), 1.93 (s, 3H), 1.61-1.66 (m, 2H).

Step-3: Preparation of (2S,5R)-7-oxo-6-hydroxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (30c):

To a solution of compound (30b) (1.7 gm, 4 mmol) in methanol (20 ml) was added palladium on carbon (10%, 0.5 gm) to provide black suspension. The suspension was stirred under 1 atm. pressure of hydrogen at 30°C for 2 hours. After completion of the reaction, the suspension was filtered through celite bed and washed with methanol. Filtrate was evaporated under vacuum to provide 1.25 gm of compound (30c) as solid (96% yield), which was used immediately for the next reaction.

Analysis:
Mass (M+1): ES 287.3 for C11H18N4O5

Step-4: Preparation of tetrabutylammonium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (30d):

To a solution of compound (30c) in dichloromethane was added triethylamine followed by sulfurtrioxide pyridine complex at 30°C and the solution was stirred at 30°C for 2 hours. After completion of the reaction tetrabutyl ammonium hydrogen sulphate was added and the stirring was continued for 2 hours. To the reaction mixture was added 10% aqueous solution of potassium dihydrogen phosphate (KH2PO4) and stirred for 5 minutes. Layers were separated and aqueous layer was extracted with dichloromethane. Combined organic layer was dried over sodium sulphate and the solvent was evaporated under vacuum to afford crude mass which was purified using silica gel column chromatography (60-120 mesh, 2-5% methanol in chloroform), to provide 2.0 gm of compound (30d) as a foam (78% yield).

Analysis:
Mass (M-1): ES 365.2 for C11H17N4O8S. C16H36N;
1H NMR (400 MHz, DMSO-d6): ? 11.46 (s, 1H) 4.25-4.27 (dd, 2H), 4.00 (s, 1H), 3.71 (s, 3H), 3.68-3.69 (m, 1H), 3.14-3.18 (m, 8H), 2.98-3.01 (m, 2H), 2.00 (d,1H), 1.88 (s, 3H), 1.64-1.66 (m, 2H), 1.52-1.56 (m, 9H), 1.26-1.31 (m, 8H), 0.91-0.95 (m, 12H).

Step-5: Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (30):

A solution of compound (30d) (2.0 gm, 3.3 mmol) in 10% THF in water was passed through a column containing Amberlite IR120 sodium resin and eluted with 10% THF in water. Pure fractions were evaporated under vacuum below 35°C to remove approximately 10% volume and remaining aqueous layer was washed with dichloromethane. Layers were separated and aqueous layer was evaporated under vacuum below 35°C to provide 0.8 gm of compound (30) as a colourless solid (52% yield).
Analysis:
Mass (M-1): ES 465.2 as a free acid for C11H17N4O8SNa;
1H NMR (400 MHz, DMSO-d6): ? 11.44 (br s, 1H), 4.23 (d, 2H), 3.98 (s, 1H), 3.75 (s, 3H), 3.65 (d, 1H), 3.02 (d, 1H), 2.93 (d, 1H), 1.95 (d, 1H), 1.86-1.88 (m, 4H), 1.62-1.67 (m, 2H).

Following examples (Table 2, Example 31-35) were prepared using procedure described in Example-30 and Scheme-2 by reacting appropriate hydroxyl amine (IIb) with sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylic acid (III).

Table 2
Example Compound of Formula (IIb) Compound of Formula (Ib) Analysis
31

1H NMR (400 MHz, DMSO-d6): d 11.45 (s, 1H), 7.77 (br s, 3H), 4.26-4.33 (m, 2H), 4.16 (s, 2H), 4.02 (s, 1H), 3.70 (d, 1H), 3.38 (d, 1H), 3.07 (d, 1H), 3.00 (s, 2H), 1.96 (s, 3H), 1.80-1.87 (m, 1H), 1.65-1.67 (m, 3H).
Mass: (M-1): ES 394.3 for C12H21N5O8S
32


1H NMR (400 MHz, DMSO-d6): d 11.45 (br s, 1H), 7.80 (br s, 3H), 4.26-4.33 (m, 2H), 4.00-4.09 (m, 3H), 3.70 (d, 1H), 3.36-3.47 (m, 2H), 2.99 (s, 1H), 1.97 (s, 3H), 1.89-1.94 (m, 1H), 1.83-1.87 (m, 1H), 1.65-1.69 (m, 2H), 1.17 (d, 3H).
Mass: (M-1): ES 408.2 for C13H23N5O8S
33


1H NMR (400 MHz, DMSO-d6): d 11.44 (br s, 1H), 7.79 (br s, 3H), 4.26-4.33 (m, 2H), 4.00-4.08 (m, 3H), 3.70 (d, 1H), 3.44-3.47 (m, 2H), 2.99 (s, 1H), 1.97 (s, 3H), 1.87-1.94 (m, 1H), 1.85-1.86 (m, 1H), 1.65-1.69 (m, 2H), 1.15 (d, 3H).
Mass: (M-1): ES 408.3 for C13H23N5O8S
34


1H NMR (400 MHz, DMSO-d6): d 11.44 (s, 1H), 8.91 (br s, 1H), 8.48 (br s, 1H), 4.31 (s, 1H), 4.11-4.27 (m, 2H), 4.02 (s, 1H), 3.70-3.74 (m, 2H), 3.37-3.41 (m, 1H), 3.17-3.19 (m, 2H), 3.00 (s, 2H), 1.86-2.07 (m, 8H), 1.58-1.67 (m, 3H).
Mass: (M-1): ES 434.4 for C15H25N5O8S

35

1H NMR (400 MHz, DMSO-d6): d 11.40 (s, 1H), 8.10 (br s, 3H), 7.42 (d, 2H), 7.37 (d, 2H), 5.07 (s, 2H), 4.27 (s, 2H), 4.04 (s, 2H), 3.89 (s, 1H), 3.61 (d, 1H), 1.83 (d, 1H), 2.70 (d, 1H), 1.95 (s, 3H), 1.80-1.90 (m, 1H), 1.56-1.62 (m, 2H).
Mass: (M-1): ES: 470.2 as free acid for C18H25N5O8S.

Example-36
(2S,5R)-7-Oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane.

Step-1: Preparation of tert-butyl [(2R)-1-({[(2E/Z)-4-aminobutan-2-ylidene]amino}oxy)-3-methylbutan-2-yl]carbamate (36a):

To a solution of tert-butyl [(2R)-1-(aminooxy)-3-methylbutan-2-yl]carbamate (5.0 gm, 23.04 mmol) in pyridine (50 ml) was added N-(3-oxo-butyl)-pthalamide (5.0 gm, 23.04 mmol) under stirring at 30°C. The reaction mixture was stirred at 30°C for 12 hours. After completion of the reaction, solvent was evaporated under vacuum and the residue obtained was dissolved in ethyl acetate (200 ml). The ethyl acetate layer was washed with saturated aqueous ammonium chloride solution, water and brine solution. Layers were separated and organic layer was dried over sodium sulphate. Evaporation of solvent provided crude mass, which was purified by triturating with diethyl ether to provide 6.1 gm of 2-[(3E/Z)-3-({[(2R)-2-(tert-butoxycarbonyl)amino-3-methylbutyl]oxy}imino)butyl]-1H-isoindole-1,3(2H)-dione as a colourless oil (63% yield).

Analysis:
Mass (M+1): ES: 418.3 for C22H31N3O5;
1H NMR (400 MHz, CDCl3): d 7.83-7.88 (m, 2H), 7.70-7.73 (m, 2H), 4.67-4.70 (br s, 1H), 3.84-3.98 (m, 2H), 2.65-2.89 (m, 2H), 2.53 (ddd, 1H), 1.91 (d, 3H), 1.70-1.77 (m, 1H), 1.43 (s, 9H), 0.84-0.90 (m, 6H).

To a stirred solution of 2-[(3E/Z)-3-({[(2R)-2-(tert-butoxycarbonyl)amino-3-methylbutyl]oxy}imino)butyl]-1H-isoindole-1,3(2H)-dione (6.0 gm, 14.39 mmol) in methanol (100 ml) was added hydrazine hydrate (99%, 1.5 gm, 28.77 mmol) at 30°C and the solution was stirred for 5 hours at the reflux temperature, to obtain a turbid suspension. The reaction mixture was cooled and filtered. Solid so obtained was washed with dichloromethane (100 ml) and the filtrate was evaporated to dryness to provide a solid residue. The solid residue obtained was dissolved in dichloromethane (200 ml) and washed with water (200 ml), followed by brine solution. Layers were separated and organic layer was dried over sodium sulphate. Organic layer was evaporated to dryness under vacuum to provide 3.3 gm of compound (36a) as a yellow oil tert-butyl [(2R)-1-({[(2E/Z)-4-aminobutan-2-ylidene]amino}oxy)-3-methylbutan-2-yl]carbamate (80% yield).

Analysis:
Mass (M+1): ES: 288.4 for C14H29N3O3;
1H NMR (400 MHz, CDCl3): d 4.70-4.77 (m, 1H), 4.07-4.13 (m, 1H), 4.00-4.06 (m, 1H), 2.85-2.92 (m, 2H), 2.47 (t, 1H), 2.30 (t, 2H), 1.83 (s, 3H), 1.76-1.80 (m, 1H), 1.45 (s, 9H), 0.90-0.96 (m, 6H).

Step-2: Preparation of (2S,5R)-7-oxo-6-benzyloxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (36b):

To a stirred suspension of sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylic acid (compound (III) , 3 gm, 10.06 mmol) in dimethylformamide (30 ml) was added diisopropyl ethyl amine (DIPEA, 5.4 ml, 30.27 mmol), N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC.HCl, 2.9 gm, 15.09 mmol), 1-hydroxybenzotriazole (HOBt, 1.4 gm, 10.06 mmol) and added a solution of compound (36a) ( 3.1 gm, 11.07 mmol) in dimethylformamide (30 ml) in one lot under stirring at 30°C. The reaction mixture was stirred at 30°C for 14 hours. After completion of the reaction, the reaction mixture was poured on crushed ice (200 gm). The solid obtained was filtered and washed with cold water (200 ml), air dried and dissolved in diethyl ether (200 ml). The diethyl ether solution was dried over sodium sulphate and evaporated under vacuum to provide 3.1 gm of compound (36b) as a sticky solid (58% yield).

Analysis:
Mass (M+1): ES: 546.6 for C28H43N5O6;
1H NMR (400 MHz, CDCl3): d 7.36-7.41 (m, 5H), 7.13 (br s, 1H), 4.86 (d, 2H), 4.82 (d, 1H), 3.85-4.11 (m, 3H), 3.64 (br s, 1H), 3.50 (s, 1H), 3.32 (s, 1H), 2.96 (t, 2H), 2.72 (d, 1H), 2.35 (s, 2H), 1.76-2.00 (m, 7H), 1.60-1.71 (m, 1H), 1.42 (s, 9H), 0.90-0.95 (m, 6H).

Step-3: Preparation of (2S,5R)-7-oxo-6-hydroxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (36c):

To a solution of compound (36b) (3 gm, 5.50 mmol) in methanol (60 ml) was added palladium on carbon (20%, 0.6 gm) and the suspension was stirred at 30°C under 1 atm. hydrogen pressure for 2 hours. After completion of the reaction, the suspension was filtered over a celite bed and the bed was washed with methanol (30 ml). The filtrate was evaporated under vacuum below 30°C to provide 2.5 gm of compound (36c) as solid. This intermediate was used immediately for the next reaction

Analysis:
Mass (M+1): ES: 456.5 for C21H37N5O6.

Step-4: Preparation of tetrabutylammonium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (36d):

To a stirred solution of compound (36c) (2.5 gm, 5.50 mmol) in dichloromethane (40 ml) was added triethylamine (2.3 ml, 16.48 mmol), sulfurtrioxide pyridine complex (1.8 gm, 11 mmol) at 30°C and the reaction mixture was stirred for 2 hours at 30°C. After completion of the reaction, tetrabutylammonium hydrogen sulphate (1.9 gm, 5.50 mmol) was added and the contents were stirred for 14 hours. The reaction mixture was diluted with 0.1 M aqueous potassium dihydrogen phosphate (KH2PO4) solution and the layers were separated. Organic layer was washed with water, brine solution and solvent was evaporated under vacuum below 30°C to provide a crude mass, which was purified using silica gel column chromatography (60-120 mesh, 6-8% methanol in chloroform) to provide 3.1 gm of compound (36d) as a foam (70% yield).

Analysis:
Mass (M-1): ES: 534.4 for C21H36N5O9S.C4H36N;
1H NMR (400 MHz, CDCl3): d 7.80 (br s, 1H), 4,76 (d, 1H), 4.33 (s, 1H), 3.92-4.11 (m, 2H), 3.87 (d, 1H), 3.43-3.73 (m, 4H), 3.28-3.32 (m, 8H), 2.78 (d, 1H), 2.30-2.37 (m, 2H), 1.83-1.88 (m, 7H), 1.63-1.70 (m, 9H), 1.40-1.50 (s, 17H), 0.94-1.02 (m, 12H), 0.86-0.92 (m, 6H).

Step-5: (2S,5R)-7-oxo-6-benzyloxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane (36):

To a solution of compound (36d) (3.0 gm, 5.6 mmol) in dichloromethane (10 ml) was cooled to -5°C and to this solution was added trifluoroacetic acid (10 ml) at -5°C under stirring. The reaction contents were stirred at -5°C for 30 minutes. After completion of the reaction, solvent was removed under vacuum below 30°C to provide a residue. The residue obtained was suspended in diethyl ether (50 ml ? 2) followed by acetonitrile (50 ml ? 2) and dichloromethane (50 ml ? 2). The suspension was filtered to provide 1.4 gm of compound (36) as a colourless solid (83% yield).

Analysis:
Mass (M-1): ES: 434.4 for C16H29N5O7S;
1H NMR (400 MHz, DMSO-d6): d 8.10 (t, 1H), 7.80 (br s, 3H), 3.98-4.11 (m, 3H), 3.66 (t, 1H), 3.33-3.54 (m, 2H), 3.14-3.24 (m, 2H), 2.97 (d, 1H), 2.81-2.86 (m, 1H), 2.26-2.30 (m, 2H), 2.03-2.07 (m, 1H), 1.88-1.93 (m, 1H), 1.82 (d, 3H), 1.55-1.66 (m, 2H), 0.92 (d, 6H).

Following examples ( Table 3, Example 37-46) were prepared using procedure described as above in Example- 36 and Scheme-3 by reacting appropriate amines (IIc) with sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylic acid (III).

Table 3
Example Compound of Formula (IIc) Compound of Formula (Ic) Analysis
37


1H NMR (400 MHz, DMSO-d6): d 10.55 (br s, 1H), 8.18 (t, 1H), 3.98 (s, 1H), 3.86 (dd, 1H), 3.76 (dd, 2H), 2.94-3.02 (m, 2H), 2.05-2.12 (m, 1H), 1.84-1.86(m, 1H), 1.70 (s, 3H), 1.62-1.69 (m, 2H).
Mass: (M-1): ES: 335.3 for C10H15N4O7SNa
38


1H NMR (400 MHz, DMSO-d6): d 8.20 (t, 1H), 3.97 (s, 1H), 3.85-3.87 (m, 1H), 3.72 (s, 3H), 3.69-3.71 (m, 2H), 2.98 (s, 2H), 2.00-2.05 (m, 1H), 1.81-1.83 (m, 1H), 1.69 (d, 3H), 1.61-1.68 (m, 2H).
Mass: (M-1): ES: 349.2 for C11H17N4O7SNa
39


1H NMR (400 MHz, DMSO-d6): d 8.21 (t, 1H), 7.73 (br s, 3H), 4.11 (t, 2H), 3.91-4.04 (m, 2H), 3.72-3.81 (m, 2H), 3.34-3.39 (m, 2H), 2.93-2.96 (m, 2H), 2.84 (d, 1H), 2.00-2.10 (m, 1H), 1.78(s, 3H), 1.57-1.69 (m, 2H).
Mass: (M-1): ES: 378.3 for C12H21N5O7S
40


1H NMR (400 MHz, DMSO-d6): d 8.01 (t, 1H), 7.74 (br s, 3H), 4.09 (br s, 2H), 4.00 (s, 1H), 3.68 (d, 1H), 3.21-3.29 (m, 1H), 2.98-3.07 (m, 4H), 2.87 (d, 1H), 2.32 (t, 2H), 2.07-2.09 (m, 2H), 1.84 (d, 3H), 1.57-1.69 (m, 2H).
Mass: (M-1): ES 392.3 for C13H23N5O7S
41


1H NMR (400 MHz, DMSO-d6): d 8.02 (t, 1H), 7.77 (br s, 3H), 3.92-4.03 (m, 3H), 3.68 (d, 1H), 3.32-3.44 (m, 4H), 3.23-3.30 (m, 1H), 2.99 (d, 1H), 2.86 (d, 1H), 2.29-2.33 (m, 1H), 2.06-2.11 (m, 1H), 1.84 (d, 3H), 1.57-1.70 (m, 2H), 1.16 (d, 3H).
Mass: (M-1): ES: 406.4 for C14H25N5O7S
42


1H NMR (400 MHz, DMSO-d6): d 8.00 (t, 1H), 7.77 (br s, 3H), 3.94-4.02 (m, 3H), 3.68 (d, 1H), 3.37-3.47 (m, 3H), 3.23-3.27 (m, 1H), 2.98-3.00 (m, 1H), 2.85-2.88 (m, 1H), 2.32 (t, 1H), 2.06-2.10 (m, 1H), 1.84 (d, 3H), 1.62-1.67 (m, 3H), 1.18 (d, 3H).
Mass: (M-1): ES: 406.3 for C14H25N5O7S
43


1H NMR (400 MHz, DMSO-d6): d 8.01 (t, 1H), 7.80 (br s, 3H), 4.12 (d, 1H), 4.00-4.10 (m, 2H), 3.68 (t, 1H), 3.26-3.39 (m, 2H), 3.17 (br s, 1H), 2.98 (d, 1H), 2.87 (d, 1H), 2.32 (br s, 1H), 2.07 (br s, 2H), 1.84-1.96 (m, 5H), 1.62-1.68 (m, 2H), 0.95 (d, 6H).
Mass: (M-1): ES: 434.4 for C16H29N5O7S
44


1H NMR (400 MHz, DMSO-d6): d 8.91 (br s, 1H), 8.45 (br s, 1H), 8.05 (br s, 1H), 4.00-4.18 (m, 3H), 3.68-3.81 (m, 2H), 3.35-3.42 (m, 2H), 3.19-3.28 (m, 3H), 2.98 (d, 1H), 2.85-2.88 (m, 1H), 2.33 (t, 1H), 2.02-2.09 (m, 2H), 1.85-1.90 (m, 6H), 1.55-1.69 (m, 3H).
Mass: (M-1): ES: 432.4 for C16H27N5O7S
45


1H NMR (400 MHz, DMSO-d6): d 8.25 (t, 1H), 7.50-7.52 (m, 2H), 7.36-7.38 (m, 3H), 4.51 (dd, 1H), 4.23 (dd, 1H), 3.90 (s, 3H), 3.78 (s, 1H), 3.56 (d, 1H), 2.57 (d, 1H), 2.16 (d, 1H), 1.91 (dd, 1H), 1.68-1.72 (m, 1H), 1.51-1.57 (m, 1H), 1.37-1.42 (m, 1H).
Mass: (M-1): ES: 411.3 as free acid for C16H19N4O7SNa
46


1H NMR (400 MHz, DMSO-d6): d 8.50 (t, 1H), 4.07-4.08 (m, 2H), 3.97 (s, 1H), 3.77 (s, 3H), 3.72-3.74 (m, 1H), 3.33-3.37 (m, 3H), 2.99-3.02 (m, 3H), 2.87-2.90 (m, 1H), 2.26-2.30 (m, 3H), 2.09-2.13 (m, 1H), 1.81-1.85 (m, 1H), 1.56-1.67 (m, 2H), 1.48 (br s, 2H), 1.34 (br s, 2H).
Mass: (M-1): ES: 432.4 for C16H26N5O7SNa

Example-47
(2S,5R)-7-Oxo-6-sulfooxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane.

Step-1: Preparation of (2S,5R)-7-oxo-6-benzyloxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane (47a):

To a solution of (2S,5R)-7-oxo-6-benzyloxy-2-[N’-((E/Z)-3-((R)-2-(tert-butoxycarbonyl) amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane (1b) (6.5 gm, 11.9 mmol) in chloroform (100 ml) was added p-toluenesulfonyl chloride (3.39 gm, 17.8 mmol), diisopropyl ethyl amine (7 ml, 35.7 mmol) and the reaction mixture was stirred at 60°C for 8 hours. After completion of the reaction, reaction mixture was cooled to room temperature and water was added. Layers were separated and organic layer was washed with 10% aqueous potassium hydrogen sulphate (KHSO4) solution. Organic layer was dried over sodium sulphate and evaporated under vacuum to dryness to provide crude compound, which was further purified using silica gel column chromatography (60-120 mesh, 20% acetone in hexane) to provide 3.2 gm of compound (47a) as brownish solid (50% yield).

Analysis:
Mass (M+1): ES: 529.5.3 for C26H36N6O6;
1H NMR (400 MHz, DMSO-d6): ? 7.36-7.47 (m, 5H), 6.68 (d, 1H), 4.92-4.99 (m, 2H), 4.64 (d, 1H), 3.96 (d, 1H), 3.83-3.87 (m, 3H), 3.67-3.76 (m, 3H), 2.86 (d, 1H), 2.69 (d, 1H), 1.98-2.17 (m, 3H), 1.86 (d, 3H), 1.36 (s, 9H), 0.95-0.99 (m, 3H).

Step-2: Preparation of (2S,5R)-7-oxo-6-hydroxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane (47b):

To a solution of compound (47a) (3.2 gm, 5.0 mmol) obtained as above in methanol (40 ml) was added palladium on carbon (10%, 0.5 gm) and the suspension was stirred under 1 atm. hydrogen pressure at 30°C for 2 hours. After completion of the reaction, the suspension was filtered over celite bed and the bed was washed with methanol (15 ml). Filtrate was evaporated under vacuum below 30°C to provide 2.0 gm of compound (47b) as a solid (91% yield). This intermediate was immediately used for the next reaction.

Step-3: Preparation of tetrabutylammonium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane (47c):

To a solution of compound (47b) (2 gm, 45 mmol) in dichloromethane (20 ml) was added triethylamine (2 ml, 135 mmol), sulfurtrioxide pyridine complex (1.45 gm, 91 mmol) at 30°C and the reaction mixture was stirred at 30°C for 3 hours. After completion of the reaction, tetrabutylammonium hydrogen sulphate (1.5 g, 45 mmol) was added and the mixture was stirred for 1 hour. To the reaction mixture was added 0.5 N aqueous potassium dihydrogen phosphate (KH2PO4) solution (50 ml) and layers were separated. Organic layer was dried over sodium sulphate and evaporated below 40°C to afford crude mass, which was purified using silica gel column chromatography (60-120 mesh, 4% methanol in chloroform) to provide 3 gm of compound (47c) (87% yield).

Analysis:
Mass (M-1): ES: 517.2 as free acid for C19H32N6O9S. C12H36N.

Step-4: (2S,5R)-7-oxo-6-sulfooxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane (47):

A solution of compound (47c) (3 g, 39 mmol) in dichloromethane (7.5 ml) was cooled to -5°C and to this solution was added trifluoroacetic acid (7.5 ml) dropwise at -5°C under nitrogen. The reaction mixture was stirred at -5°C for 1 hour. Volatiles were distilled out under vacuum to provide a residue and the residue was triturated with diethyl ether (50 ml ? 2) to effect solidification. Solid was dried under vacuum and was suspended in dichloromethane (50 ml). The suspension was stirred for 1 hour, filtered and dried to provide 1.3g of compound (47) as a colourless solid (79% yield).

Analysis:
Mass (M+1): ES: 419.3 for C14H22N6O7S;
1H NMR (400 MHz, DMSO-d6): ? 7.78 (br s, 3H), 4.62 (t, 1H), 3.95-4.09 (m, 4H), 3.41-3.44 (m, 2H), 2.96 (d, 1H), 2.69 (t, 1H), 2.16-2.20 (m, 1H), 1.96-2.04 (m, 2H), 1.90 (d, 3H), 1.83-1.87 (m, 1H), 1.13-1.15 (m, 3H).

Example 48
Trifluoroacetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[(5-(E/Z)-(2-(2-aminoethoxy-benzyloxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane

This compound was prepared as per the procedure according to Example 47, wherein (2S,5R)-7-oxo-6-benzyloxy-2-[N'-{(E/Z)-[-3-{2-(tert-butoxycarbonylaminoethoxy)} benzyloxyimino]-butanoyl}-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane was used in place of (2S,5R)-7-oxo-6-benzyloxy-2-[N’-((E/Z)-3-((R)-2-(tert-butoxycarbonyl) amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane (1b) in step-1.

Analysis:
Mass (M-1): ES: 509.4 as free acid for C20H26N6O8S.C2F3O2;
1H NMR (400 MHz, DMSO-d6): ? 7.81 (br s, 3H), 7.27 (d, 2H), 7.00 (d, 2H), 5.16 (br s, 2H), 4.63 (d, 1H), 4.16 (s, 2H), 4.02-4.05 (m, 1H), 3.90 (s, 1H), 3.24-3.32 (m, 3H), 2.93 (d, 1H), 2.64 (d, 1H), 2.16-2.33 (m, 2H), 1.82-1.99 (m, 5H).

Biological Activity

The biological activity of representative compounds of the invention against various bacterial strains was investigated. In a typical study, overnight grown bacterial cultures were diluted appropriately and inoculated on the agar media containing doubling dilutions of the test compounds. Observation for growth or no growth was performed after 16 -20 hours of incubation at 35 ± 2°C in ambient air. The overall procedure was performed as per Clinical and Laboratory Standards Institute (CLSI), Performance Standard for Antimicrobial Susceptibility Testing, 20th Informational Supplement, M100-S20, Volume 30, No. 1, 2010. Antibacterial activity of representative compounds according to invention against various E. coli strains (NCTC 13351, M 50 and 7 MP) expressing ESBL (Extended Spectrum Beta Lactamases) enzymes is given in Table 4.

Table 4: Antibacterial activity of representative compounds according to the invention (MIC expressed in mcg/ml)

Compound according to Example No. Bacterial Strains
E. coli
NCTC 13351 E. coli
M50 E. coli
7 MP IC50
(E. coli M50)
1 0.5 0.5 1 0.160
2 1 1 4 0.0578
3 0.5 0.5 1 0.172
4 0.5 0.5 2 0.0744
5 0.5 1 2 0.0684
6 0.5 1 2 0.0469
7 0.5 0.5 2 0.0505
8 0.5 0.5 2 0.017
9 0.5 0.5 2 0.0401
10 1 1 4 0.0673
11 1 1 4 0.1017
12 8 8 16 0.0539
13 8 8 16 0.0542
14 2 2 32 0.0154
15 32 > 32 > 32 0.0184
16 16 32 > 32 0.00226
17 8 8 > 32 0.00205
18 1 1 2 0.0487
19 1 1 4 0.0583
20 2 2 4 0.0880
21 1 1 2 0.118
22 2 2 4 0.076
23 0.5 0.5 2 0.0478
24 1 1 2 0.0738
25 1 1 2 0.136
26 1 1 4 0.1449
27 2 2 8 0.0331
28 2 2 4 0.044
29 > 32 > 32 > 32 0.0097
30 > 32 > 32 > 32 0.0063
33 32 16 32 0.89
34 > 32 32 > 32 0.0274
36 > 32 > 32 > 32 0.0012
37 > 32 > 32 > 32 0.0340
38 > 32 > 32 > 32 0.018
39 8 8 > 32 0.0376
41 16 8 32 0.0417
43 > 32 > 32 > 32 0.0489
44 16 8 32 0.062
45 > 32 > 32 > 32 0.0037
46 > 32 >32 > 32 0.0056
47 > 32 > 32 > 32 0.0082
48 > 32 > 32 > 32 0.0087
Avibactam - - - 0.037
Clavulanic Acid - - - > 10
,CLAIMS:1. A compound of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:
Q is heteroaryl or CONH;
X is O, NHCO, or C1-C6 alkyl;
Y is C1-C6 alkyl, or cycloalkyl;
R and R1 are each independently selected from:
(a) hydrogen;
(b) C1-C6 alkyl, optionally substituted with one or more substituents independently selected from NR2R3, aryl, aryl optionally substituted with OR2 or CH2NR2R3, heteroaryl, or heterocycloalkyl;
(c) NR2R3;
(d) aryl;
(e) heteroaryl; and
(f) heterocycloalkyl, optionally substituted with (C1-C6) alkyl;
R2 and R3 are each independently selected from:
(a) hydrogen; and
(b) C1-C6 alkyl, optionally substituted with NH2;
n is 0 or 1; and
M is hydrogen or a cation

2. The compound as claimed in Claim 1, selected from:

(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-2-yl)-methoxyimino-butanoyl) -hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-propyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-3-methylbutanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-(S)-pyrrolidin-2-yl-methoxyimino)-butanoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-piperidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(4-aminomethyl-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2-aminoethoxy)-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(1H-1,2,3-triazolyl)-ethoxyimino)-butanoyl) -hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-1,2,3-triazolyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-tetrazoyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(pyridin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-ethoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-propanoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((S)-pyrrolidin-2-yl-methoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-propanoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-pyrrolidin-2-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(piperazin-4-yl)-ethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-3-((R)-pyrrolidin-2-yl)-propionyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-phenyl-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-(2-amino-2-methoxyimino)-ethoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-aminoethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(4-aminomethyl-benzyloxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-imidazolyl-ethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-tetrazolyl-ethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-methoxyimino-2-phenylethoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-hydroxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-(2-aminoethoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-ethoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-propanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-propanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-2-phenyl-ethanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-3-(piperidin-1-yl)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
(2S,5R)-7-oxo-6-sulfooxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane; or
a stereoisomer or a pharmaceutically acceptable salt thereof.

3. The compound as claimed in Claim 1, selected from:

Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino) -butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-2-yl)-methoxyimino-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoroacetic acid and sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2-aminoethoxy)-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(1H-1,2,3-triazolyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-1,2,3-triazolyl)-ethoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(2H-tetrazoyl)-ethoxyimino) -butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(pyridin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-aminoethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-2-amino-propanoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-pyrrolidin-2-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoro acetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Di -(trifluoro acetic acid) salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-(piperazin-4-yl)-ethoxyimino)-5-aminopetanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-imidazolyl-ethoxyimino) -propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-1H-tetrazolyl-ethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-methoxyimino-2-phenylethoxy) -carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-hydroxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-2-phenyl-ethanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-methoxyimino)-3-(piperidin-1-yl)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Trifluoroacetic acid salt of (2S,5R)-7-oxo-6-sulfooxy-2-[(5-(E/Z)-(2-(2-aminoethoxy-benzyloxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(2-amino-propanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-propyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((S)-2-amino-3-methyl butanoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-(S)-pyrrolidin-2-yl-methoxyimino)-butanoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-pyrrolidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-((R)-piperidin-3-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(piperidin-4-yl-methoxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-(4-aminomethyl-benzyloxyimino)-butanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-ethoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((R)-2-amino-propanoxyimino) -pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-4-((S)-pyrrolidin-2-yl-methoxyimino)-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-propanoxyimino-5-aminopentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-3-((R)-pyrrolidin-2-yl)-propionyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-3-methoxyimino-5-phenyl-pentanoyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-(2-amino-2-methoxyimino)-ethoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(2-aminoethoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-propanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-2-amino-3-methyl-butanoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((S)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-((R)-pyrrolidin-2-yl-methoxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-((E/Z)-2-(4-aminomethyl-benzyloxyimino)-propanoxy)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(2-(E/Z)-(2-aminoethoxyimino)-propanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-ethoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-propanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-2-amino-propanoxyimino) -butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-2-amino-3-methyl-butanoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((S)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-oxo-6-sulfooxy-2-[N’-(3-(E/Z)-((R)-pyrrolidin-2-yl-methoxyimino)-butanyl)-carbamoyl]-1,6-diaza-bicyclo[3.2.1]-octane;
Sodium salt of (2S,5R)-7-Oxo-6-sulfooxy-2-[(5-(E/Z)-((R)-2-amino-propanoxyimino)-propanyl)-1,3,4-oxadiazol-2-yl]-1,6-diaza-bicyclo[3.2.1]-octane; or
a stereoisomer thereof.

4. A pharmaceutical composition comprising a compound as claimed in any one of the Claims 1 to 3.

5. Use of a compound as claimed in any one of the Claims 1 to 3, in treating or preventing a bacterial infection.

6. Use of a pharmaceutical composition as claimed in Claim 4, in treating or preventing a bacterial infection.

7. A process for preparation of a compound of Formula (Ia),

wherein:
Y is C1-C6 alkyl, or cycloalkyl;
R and R1 are each independently selected from:
(a) hydrogen;
(b) C1-C6 alkyl, optionally substituted with one or more substituents independently selected from NR2R3, aryl, aryl optionally substituted with OR2 or CH2NR2R3, heteroaryl, or heterocycloalkyl;
(c) NR2R3;
(d) aryl;
(e) heteroaryl; and
(f) heterocycloalkyl, optionally substituted with (C1-C6) alkyl;
R2 and R3 are each independently selected from:
(a) hydrogen; and
(b) C1-C6 alkyl, optionally substituted with NH2;
n is 0 or 1; and
M is hydrogen or a cation

Comprising:
(a) reacting a compound of Formula (VIIa) with a compound of Formula (VIIIa) to obtain a compound of Formula (IIa);

(b) reacting a compound of Formula (IIa) with a compound of Formula (III) to obtain a compound of Formula (IVa);

(c) converting a compound of Formula (IVa) into a compound of Formula (Va);

(d) converting a compound of Formula (Va) into a compound of Formula (VIa); and

(e) converting a compound of Formula (VIa) into a compound of Formula (Ia).

8. A process for preparation of a compound of Formula (Ib),

wherein:
Y is C1-C6 alkyl, or cycloalkyl;
R and R1 are each independently selected from:
(a) hydrogen;
(b) C1-C6 alkyl, optionally substituted with one or more substituents independently selected from NR2R3, aryl, aryl optionally substituted with OR2 or CH2NR2R3, heteroaryl, or heterocycloalkyl;
(c) NR2R3;
(d) aryl;
(e) heteroaryl; and
(f) heterocycloalkyl, optionally substituted with (C1-C6) alkyl;
R2 and R3 are each independently selected from:
(a) hydrogen; and
(b) C1-C6 alkyl, optionally substituted with NH2;
n is 0 or 1; and
M is hydrogen or a cation

Comprising:
(a) reacting a compound of Formula (VIIb) with a compound of Formula (VIIIb) to obtain a compound of Formula (IIb);

(b) reacting a compound of Formula (IIb) with a compound of Formula (III) to obtain a compound of Formula (IVb);

(c) converting a compound of Formula (IVb) into a compound of Formula (Vb);

(d) converting a compound of Formula (Vb) into a compound of Formula (VIb); and

(e) converting a compound of Formula (VIb) into a compound of Formula (Ib).

9. A process for preparation of a compound of Formula (Ic),

wherein:
Y is C1-C6 alkyl, or cycloalkyl;
R and R1 are each independently selected from:
(a) hydrogen;
(b) C1-C6 alkyl, optionally substituted with one or more substituents independently selected from NR2R3, aryl, aryl optionally substituted with OR2 or CH2NR2R3, heteroaryl, or heterocycloalkyl;
(c) NR2R3;
(d) aryl;
(e) heteroaryl; and
(f) heterocycloalkyl, optionally substituted with (C1-C6) alkyl;
R2 and R3 are each independently selected from:
(a) hydrogen; and
(b) C1-C6 alkyl, optionally substituted with NH2;
n is 0 or 1; and
M is hydrogen or a cation

Comprising:
(a) reacting a compound of Formula (VIIc) with a compound of Formula (VIIIc) to obtain a compound of Formula (IIc);

(b) reacting a compound of Formula (IIc) with a compound of Formula (III) to obtain a compound of Formula (IVc);

(c) converting a compound of Formula (IVc) into a compound of Formula (Vc);

(d) converting a compound of Formula (Vc) into a compound of Formula (VIc); and

(e) converting a compound of Formula (VIc) into a compound of Formula (Ic).

10. A process for preparation of a compound of Formula (Id),

wherein:
Y is C1-C6 alkyl, or cycloalkyl;
R and R1 are each independently selected from:
(a) hydrogen;
(b) C1-C6 alkyl, optionally substituted with one or more substituents independently selected from NR2R3, aryl, aryl optionally substituted with OR2 or CH2NR2R3, heteroaryl, or heterocycloalkyl;
(c) NR2R3;
(d) aryl;
(e) heteroaryl; and
(f) heterocycloalkyl, optionally substituted with (C1-C6) alkyl;
R2 and R3 are each independently selected from:
(a) hydrogen; and
(b) C1-C6 alkyl, optionally substituted with NH2;
n is 0 or 1; and
M is hydrogen or a cation

Comprising:
(a) converting a compound of Formula (IVa) into a compound of Formula (IVd);

(b) converting a compound of Formula (IVd) into a compound of Formula (Vd);

(c) converting a compound of Formula (Vd) into a compound of Formula (VId); and

(d) converting a compound of Formula (VId) into a compound of Formula (Id).