WO2015110886A1 - A process for preparation of (2s, 5r)-7-oxo-n-[(3s)-pyrrolidin-3-yloxy]-6-(sulfooxy)-1,6-diazabicyclo [3.2.1]octane-2-carboxamide - Google Patents
A process for preparation of (2s, 5r)-7-oxo-n-[(3s)-pyrrolidin-3-yloxy]-6-(sulfooxy)-1,6-diazabicyclo [3.2.1]octane-2-carboxamide Download PDFInfo
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- WO2015110886A1 WO2015110886A1 PCT/IB2014/067382 IB2014067382W WO2015110886A1 WO 2015110886 A1 WO2015110886 A1 WO 2015110886A1 IB 2014067382 W IB2014067382 W IB 2014067382W WO 2015110886 A1 WO2015110886 A1 WO 2015110886A1
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- 0 *N([C@@]1CC[C@](C(NO[C@@]2CNCC2)=O)N2C1)C2=O Chemical compound *N([C@@]1CC[C@](C(NO[C@@]2CNCC2)=O)N2C1)C2=O 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Definitions
- the invention relates to a process for preparation of (25, 5R)-7-oxo- pyrrolidin-3-yloxy]-6-(sulfooxy)-l ,6-diazabicyclo[3.2.1]octane-2-carboxamide.
- a compound of Formula (I), chemically known as (25, 5i?)-7-oxo-N-[(35)- pyrrolidin-3-yloxy]-6-(sulfooxy)-l ,6-diazabicyclo[3.2.1]octane-2-carboxamide has antibacterial properties and is disclosed in PCT International Patent Application No. PCT/IB2013/053092.
- OBn refers to benzyloxy.
- EDC refers to l-ethyl-3-(3-dimethylamino propyl)carbodiimide.
- HOBt refers to 1 -hydro xybenzotriazole.
- TBAA tetrabutylammonium acetate
- (Boc ⁇ O) refers to di-teri-butyldicarbonate.
- pharmaceutically acceptable derivative refers to and includes any pharmaceutically acceptable salt, pro-drugs, metabolites, esters, ethers, hydrates, polymorphs, solvates, complexes or adducts of a compound described herein which, upon administration to a subject, is capable of providing (directly or indirectly) the parent compound.
- antibacterial or a pharmaceutically acceptable derivative thereof includes all derivatives of the antibacterial agent (such as salt, prodrugs, metabolites, esters, ethers, hydrates, polymorphs, solvates, complexes or adducts) which, upon administration to a subject, is capable of providing (directly or indirectly) the antibacterial compound.
- the compound of Formula (IV) is obtained by reacting a compound of Formula (II) with a compound of Formula (III) in presence of suitable coupling agent and in presence of suitable solvent.
- suitable coupling agents include EDC hydrochloride, dicyclohexylcarbodiimide, diisopropylcarbodiimide (DIC), carbonyldiimidazole (CDI), pivalyl chloride, HOBt and the like.
- compound of Formula (IV) is obtained by reacting a compound of Formula (II) with a compound of Formula (III) in presence of 1 -hydroxybenzotriazole (HOBt) and l-ethyl-3- (3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HC1) at temperature of about 25°C for about 16 hour. In some embodiments, this reaction is carried out in presence of mixture of water and dimethylformamide (DMF) as reaction solvent.
- HOBt 1 -hydroxybenzotriazole
- EDC.HC1 l-ethyl-3- (3-dimethylaminopropyl)carbodiimide hydrochloride
- the compound of Formula (V) is obtained by hydrogeno lysis of a compound of a compound of Formula (IV).
- the hydrogenolysis reaction can be carried out using a suitable hydrogenolysis agent.
- hydrogenolysis of a compound of Formula (IV) to obtain a compound of Formula (V) is carried out in presence of a transition metal catalyst and a hydrogen source.
- the transition metal catalyst is palladium on carbon
- hydrogen source is hydrogen gas.
- the hydrogenolysis reaction is carried out in presence of a suitable solvent such as dichlorome thane.
- the hydrogenolysis of a compound of Formula (IV) is carried in presence 10% palladium on carbon and about 50 psi hydrogen atmosphere at a temperature of about 25°C for about 4 hour to obtain a compound of Formula (V).
- the compound of Formula (VI) is obtained by sulfonating a compound of Formula (V), followed by treatment with tetrabutylammonium acetate.
- the sulfonation reaction can be carried out in presence of suitable sulfonating agents such as sulfur trioxide pyridine complex, sulfur trioxide dimethylformamide complex and the like.
- suitable sulfonating agents such as sulfur trioxide pyridine complex, sulfur trioxide dimethylformamide complex and the like.
- the sulfonation of a compound of Formula (V) is carried out by action of sulfur trioxide-dimethylformamide complex (SO 3 -DMF) and in presence of dimethylformamide as solvent at temperature of about 10°C.
- SO 3 -DMF sulfur trioxide-dimethylformamide complex
- the sulfonation reaction is followed by treatment with tetrabutylammonium acetate to obtain a compound of Formula (VI).
- the compound of Formula (VI) is converted to a compound of Formula (I) in presence of a suitable deprotecting reagent.
- compound of Formula (VI) is converted to a compound of Formula (I) by reacting a compound of Formula (VI) with trifluoro acetic acid in presence of suitable solvent such as dichloromethane at temperature of about -10°C for about 1 hour.
- compound of Formula (I) is prepared using a process described in Scheme 1.
- compound of Formula (I) is further converted to its pharmaceutically acceptable derivative. In some embodiments, compound of Formula (I) is converted to its corresponding sodium salt.
- a compound of Formula (I) in amorphous form there is provided a pharmaceutical composition comprising a compound of Formula (I) in amorphous form.
- a compound of Formula (I) in crystalline form there is provided a pharmaceutical composition comprising a compound of Formula (I) in crystalline form.
- a process for preparation of compound of Formula (I) in crystalline form comprising: (a) dissolving a compound of Formula (I) in water to obtain a homogeneous mixture; (b) adding isopropyl alcohol to the homogeneous mixture obtained in step (a); and (c) isolating a compound of Formula (I) in crystalline form.
- a compound of Formula (I) having a purity of more than about 95% as determined by HPLC there is provided a pharmaceutical composition comprising a compound of Formula (I) having purity of more than about 95% as determined by HPLC.
- L-hydroxyproline (VII) is decarboxylated by heating at higher temperature in presence of suitable catalyst such as 2-cyclohexen-l-one and in presence of suitable solvent such as cyclohexanol.
- the decarboxylated product is isolated as hydrochloride salt of (3-(i?)-hydroxypyrrolidine hydrochloride) (VIII).
- the compound of Formula (VIII) is reacted with di-feri-butyl dicarbonate [(Boc) 2 0] in presence of base such as triethylamine and in presence of catalyst such as 4-dimethylaminopyridine (DMAP) to obtain (3i?)-l-(ieri-butoxycarbonyl)-3-hydroxypyrrolidine (IX).
- DMAP 4-dimethylaminopyridine
- the compound of Formula (IX) is first reacted with the solution of diisopropyl azodicarboxylate and triphenylphosphine in suitable solvent under stirring, followed by reaction with N-hydroxyphthalamide to obtain (5)-3-[(l,3-dihydro-l,3-dioxo-isoindol-2- yl)oxy] -pyrrolidine- 1-carboxylic acid tert-buty ⁇ ester (X).
- the compound of Formula (X) is reacted with hydrazine hydrate in suitable solvent such as dichloromethane to obtain feri-butyl-(35)-2-[(aminooxy) pyrrolidine- 1 -carboxylate of Formula (III).
- a schematic for synthesis of a compound of Formula (III) is given in Scheme-2.
- Step 2 Preparation of (3R)-l-(tert-butoxycarbonyl)-3-hydroxypyrrolidine (IX): To a stirred suspension of 3-(i?)-hydroxypyrrolidine hydrochloride (VIII) (110 g, 0.9 mol) in dichloromethane (1100 ml), triethylamine (273 g, 2.7 mol) was added at 0- 5°C. After 5 minute of stirring di-feri-butyldicarbonate [(Boc) 2 0] (245 g, 1.125 mol) was added to the reaction mixture in small portions, followed by 4-dimethylaminopyridine (10.99 g, 0.09 mol).
- Step 3 Preparation of (5)-3-[(l,3-dihydro-l,3-dioxo-isoindol-2-yl)oxy]pyrrolidine-l- carbox lic acid tert- butyl ester (X):
- N- hydroxy phthalimide (52.4 g, 0.3204mol) was added in one portion to the reaction mass.
- the reaction mixture was allowed to warm to room temperature and stirred for 16 hour.
- the completion of the reaction was monitored by thin layer chromatography.
- the solvent was evaporated under reduced pressure.
- the residue thus obtained was stirred with di-isopropyl ether (600 ml).
- the precipitate formed was filtered under suction.
- the filtrate was concentrated under reduced pressure and the residual mass was purified by silica gel (60-120 mesh) column chromatography using 1-5 % mixtures of acetone: hexane as an eluent.
- Step 1 Preparation of fert-butyl-(35)-3-[( ⁇ [25, 5R)-6-(benzyloxy)-7-oxo-l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl ⁇ amino)oxy]pyrrolidine-l-carboxylate (IV):
- Step 3 Preparation of tert-butyl-(35)-3-[( ⁇ [25,5R)-6-(sulfooxy)-7-oxo-l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl ⁇ amino)oxy]pyrrolidine-l-carboxylate, tetrabutyl ammonium salt (VI):
- Step 4 Preparation of (25,5R)-7-oxo-iV-[(35)-pyrrolidin-2-yl-oxy]-6-(sulfooxy)-l,6- diazabicyclo [3.2.1]octane-2-carboxamide (I):
- Typical X-ray analysis was performed as follows. Pass the test substance through sieve #100 BSS or gently grind it with a mortar and pestle. Place the test substance uniformly on a sample holder having cavity surface on one side, press the sample and cut into thin uniform film using a glass slide in such a way that the surface of the sample should be smooth and even. Record the X-ray diffractogram using the following instrument parameters.
- Anti- scattering slit (Diffracted beam) 5.5 mm
- Scan range 3 to 40°
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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IN194MU2014 IN2014MU00194A (zh) | 2014-01-21 | 2014-12-29 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111095082A (zh) * | 2018-03-01 | 2020-05-01 | 依视路国际公司 | 镜片元件 |
CN112209865A (zh) * | 2019-07-09 | 2021-01-12 | 中山澳达特罗生物科技有限公司 | 一种(R)-(-)-N-Boc-3-吡咯烷醇的生产方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5233053A (en) | 1989-03-17 | 1993-08-03 | Pfizer Inc. | Pyrrolidine derivatives |
WO2014033560A1 (en) * | 2012-08-25 | 2014-03-06 | Wockhardt Limited | 1,6- diazabicyclo [3,2,1] octan- 7- one derivatives and their use in the treatment of bacterial infections |
WO2014091268A1 (en) * | 2012-12-11 | 2014-06-19 | Naeja Pharmaceutical Inc. | NEW BICYCLIC COMPOUNDS AND THEIR USE AS ANTIBACTERIAL AGENTS AND β-LACTAMASE INHIBITORS |
-
2014
- 2014-12-29 WO PCT/IB2014/067382 patent/WO2015110886A1/en active Application Filing
- 2014-12-29 IN IN194MU2014 patent/IN2014MU00194A/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5233053A (en) | 1989-03-17 | 1993-08-03 | Pfizer Inc. | Pyrrolidine derivatives |
WO2014033560A1 (en) * | 2012-08-25 | 2014-03-06 | Wockhardt Limited | 1,6- diazabicyclo [3,2,1] octan- 7- one derivatives and their use in the treatment of bacterial infections |
WO2014091268A1 (en) * | 2012-12-11 | 2014-06-19 | Naeja Pharmaceutical Inc. | NEW BICYCLIC COMPOUNDS AND THEIR USE AS ANTIBACTERIAL AGENTS AND β-LACTAMASE INHIBITORS |
Non-Patent Citations (2)
Title |
---|
CAIRA: "Crystalline Polymorphism of Organic Compounds", TOPICS IN CURRENT CHEMISTRY, SPRINGER, BERLIN, DE, vol. 198, 1 January 1998 (1998-01-01), pages 163 - 208, XP008166276, ISSN: 0340-1022 * |
CHEMISTRY LETTERS, 1986, pages 893 - 896 |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN111095082A (zh) * | 2018-03-01 | 2020-05-01 | 依视路国际公司 | 镜片元件 |
US11067832B2 (en) | 2018-03-01 | 2021-07-20 | Essilor International | Lens element |
CN111095082B (zh) * | 2018-03-01 | 2021-11-30 | 依视路国际公司 | 镜片元件 |
CN112209865A (zh) * | 2019-07-09 | 2021-01-12 | 中山澳达特罗生物科技有限公司 | 一种(R)-(-)-N-Boc-3-吡咯烷醇的生产方法 |
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