WO2013164729A1 - Traitement amélioré et évolutif de préparation de dérivés de prostaglandine et de leurs intermédiaires - Google Patents

Traitement amélioré et évolutif de préparation de dérivés de prostaglandine et de leurs intermédiaires Download PDF

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Publication number
WO2013164729A1
WO2013164729A1 PCT/IB2013/053173 IB2013053173W WO2013164729A1 WO 2013164729 A1 WO2013164729 A1 WO 2013164729A1 IB 2013053173 W IB2013053173 W IB 2013053173W WO 2013164729 A1 WO2013164729 A1 WO 2013164729A1
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formula
compound
tert
group
methyl
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PCT/IB2013/053173
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English (en)
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Venkata Rambabu Kammili
Anurag Anil SMART
Rajinder Singh Siyan
Nandu Baban Bhise
Girij Pal Singh
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Lupin Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
    • C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
    • C07D307/937—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins

Definitions

  • the present invention is related to an improved and scalable process for the preparation of prostaglandin derivatives and intermediates thereof, in high yield and purity.
  • Prostaglandins are a family of biologically active compounds that are found in virtually all tissues and organs. These naturally occurring prostaglandins have extremely complex biological functions (e.g. stimulation of smooth muscles, dilation of smaller arteries and bronchi, lowering blood pressure etc.). Structurally, prostaglandins are formed of a ring and two side chains, said ring and chains being replaceable (usually hydroxyl or keto group) and optionally being partly unsaturated.
  • the compounds Bimatoprost, Travoprost and Latanoprost are analogues of prostaglandin F 2a and used in therapy in the treatment of glaucoma, in particular to reduce high endo- ocular pressure.
  • PCT Application WO2011055377 ('377) disclosed a method for preparation of prostaglandin derivatives like Travoprostcomprising; (i) Wittig reactionusing NaH, (ii) reduction using methyl oxazaborolidine (Me-CBS) and borane ⁇ , ⁇ ' -diethylaniline complex (DEANB),
  • PCT Application WO2010104344 ('344) disclosed a method for deprotection of hydroxy protecting groups using PPTS in suitable solvent.
  • the prior art process for preparation of prostaglandin derivatives has following disadvantages and drawbacks:
  • the present invention provides an improved process for the preparation of compound of formula A;
  • ⁇ represents a double bond or a single bond
  • R4 is alkoxy or alkyl amino group
  • W is a residue from group consisting of substituted and unsubstituted Ci-C 6 alkyl, C 7 - Ciearalkyl wherein the aralkyl group is optionally substituted with one to three substituents selected from the group consisting of Ci-Ceaikyl, halo and CF 3 , and (CH 2 ) n OR a , wherein n is from 1-3 and R a represents a Ce-Cio aryl group which is optionally substituted with one to three substituents selected from the group consisting of Ci-C 6 alkyl, halo and CF 3 ;
  • the present invention provides a process for the preparation of compound of formula A;
  • ⁇ represents a double bond or a single bond
  • R x and R 2 are hydroxyl protecting groups
  • R 4 is alkoxyor alkyl amino group
  • W is as defined above.
  • P is p-phenylbenzoyl (PPB), p-methoxy benzyl (PMB) or THP group and W is as defined above.
  • the present invention provides a process for preparation of compound of formula (V),
  • the present invention provides a process for isolating compound of formula (V).
  • the present invention provides a process for producinghigh purity prostaglandin and prostaglandin derivatives.
  • R4 is alkoxy or alkyl amino group;
  • W is a residue from group consisting of substituted and unsubstituted Ci-Ce alkyl, C7-Ci 6 aralkyl wherein the aralkyl group is optionally substituted with one to three substituents selected from the group consisting of Ci-Ce alkyl, halo and CF 3 , and (CH 2 )nOR a , wherein n is from 1-3 and R a represents a Ce-Cio aryl group which is optionally substituted with one to three substituents selected from the group consisting of Ci-Ce alkyl, halo and CF 3 ;
  • the oxidizing agentused in step (i) is selected fromSwern oxidation (DMSO, oxalyl chloride and TEA),Dess-Martin reagent, manganese-, chromium-, or selenium reagents, tertiary amine oxides or via radical oxidation producers using catalytic amount of TEMPO in combination with co-oxidants such as NaOCl; preferably, the oxidizing agent selected from Swern oxidation (DMSO, oxalyl chloride and TEA),Dess- Martin reagent;and more preferablythe oxidizing agent is Dess-Martin reagent.
  • step (i) is carried out in solvent or mixture of solvents selected from DCM, acetone, THF or mixtures thereof; and more preferably the reaction solvent isDCM.
  • step (i) is carried out at a temperature of-20° C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 60°C for about 30 minutes to about 8 hours, and preferably at a temperature of about 10°C to about 50°C for about 1 hour to about 6 hours.
  • the base usedin reaction step (ii) isorganic or inorganic base.
  • Specific organic bases are triethylamine, trimethylamine, dimethyl amine and tert- butyl amine.
  • the base is an inorganic base.
  • exemplary inorganic bases include, but are not limited to, hydroxides, alkoxides, bicarbonates and carbonates of alkali or alkaline earth metals; and ammonia.
  • Specific inorganic bases are ammonia solution, sodium hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium tert-butoxide, sodium isopropoxide and potassium tert-butoxide, and preferably sodium tert-butoxide, sodium isopropoxide and potassium tert-butoxide, sodium carbonate and potassium carbonate.
  • the organicsolvent used in step (ii) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane, cyclohexane, toluen
  • step (ii) is carried out at a temperature of-20°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 60°C for about 30 minutes to about 48 hours, and preferably at a temperature of about 10°C to about 50°C for about 1 hour to about 24 hours.
  • the compound of formula (II) optionally isolating from mother liquor.
  • the reducing agent usedin reaction step(iii) is selected fromborane-dimethylsulfide complex, (-)-DIP chloride, lithium l,l'-binaphthyl-2,2'- dioxyaluminium hydride; and more preferably the reducing agent is (-)-DIP chloride.
  • the solvent used in step (iii) selected fromthe group consisting of methanol, ethanol, n- propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane, cyclohexane, toluene
  • step (iii) is carried out at a temperature of-80° C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about -50°C to about 60°C for about 30 minutes to about 15 hours, and preferably at a temperature of about -30°C to about 5°C for about 1 hour to about 8 hours.
  • step (iv) comprising catalytic hydrogenation.
  • the 4-nitrobenzoyl halide used in step (v) is selected from 4- nitrobenzoyl chloride, 4-nitrobenzoyl bromide and the like;more preferably,4- nitrobenzoyl chloride.
  • the catalyst used in step (v) is DMAP and the like; and the base used in step (v) is organic or inorganic base, selected from triethylamine, trimethylamine, dimethyl amine and tert-butyl amine; ammonia solution, sodium hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium tert-butoxide, sodium isopropoxide and potassium tert-butoxide; and more preferably, the base istriethylamine.
  • the organicsolvent used in step (v) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane, cyclohexane, toluene
  • step (v) is carried out at a temperature of -5°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 60°C for about 30 minutes to about 10 hours, and preferably at a temperature of about 5°C to about 30° C for about 1 hour to about 6 hours.
  • the base used in step (vi) is organic or inorganic base, selected from triethylamine, trimethylamine, dimethyl amine and tert-butyl amine; ammonia solution, sodium hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium tert-butoxide, sodium isopropoxide and potassium tert-butoxide; and more preferably, the base is potassium carbonate.
  • the organicsolvent used in step (vi) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane, cyclohexane, toluene
  • step (vi) is carried out at a temperature of -5°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 60°C for about 30 minutes to about 10 hours, and preferably at a temperature of about 5°C to about 30°C for about 1 hour to about 6 hours.
  • the suitable hydroxy protecting groupof step (vii) selected fromtrimethylsilylhalide,tetrabutyl dimethyl silyl halide, 2-methoxyethoxymethyl halide, 3,4-dihydro-2H-pyran and the like; more preferably, the hydroxy protecting groupis 3,4- dihydro-2H-pyran.
  • the catalyst used in step (vii) is PPTS and the like;
  • the organicsolvent used in step (vii) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane, cyclohexane, toluene
  • step (vii) is carried out at a temperature of -5°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 60°C for about 30 minutes to about 10 hours, and preferably at a temperature of about 5°C to about 30°C for about 1 hour to about 8 hours.
  • the derivatization reaction step (X) is carried out using alkyl halide or alkyl amine.
  • alkyl halide includes, but not limited to, ethyl halide, methyl halide or isopropyl halide.
  • exemplaryalkyl amine includes, but not limited to, ethyl amine, methyl amine or isopropyl amine.
  • reaction solvent used in step (viii), (ix), (x) and (xi) selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane
  • reaction of step (viii), (ix), (x) and (xi) is carried out at a temperature of -75°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about -65°C to about 45°C for about 30 minutes to about 10 hours, and preferably at a temperature of about -65°C to about 35°C for about 1 hour to about 8 hours.
  • a temperature of -75°C to the reflux temperature of the solvent used for at least 15 minutes specifically at a temperature of about -65°C to about 45°C for about 30 minutes to about 10 hours, and preferably at a temperature of about -65°C to about 35°C for about 1 hour to about 8 hours.
  • ⁇ represents a double bond or a single bond
  • R4 is alkoxy or alkyl amino group
  • W is a residue from group consisting of substituted and unsubstituted Ci-C 6 alkyl, C7- Ciearalkyl wherein the aralkyl group is optionally substituted with one to three substituents selected from the group consisting of Ci-Cealkyl, halo and CF 3 , and (CH 2 ) n OR a , wherein n is from 1-3 and R a represents a Ce-Cio aryl group which is optionally substituted with one to three substituents selected from the group consisting of Ci-Cealkyl, halo and CF 3 ; by deprotection of compound of formula (X),
  • Ri, R 2 ,R 4 and W are as defined above; in the presence of ZrCl 4 and organic solvent.
  • the organicsolvent used in deprotection of formula (X) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane, cyclohex
  • Thedeprotection of formula (X) is carried out at a temperature of -5°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 65°C for about 30 minutes to about 10 hours, and preferably at a temperature of about 35°C to about 45°C for about 1 hour to about 8 hours.
  • P is p-phenylbenzoyl (PPB), p-methoxy benzyl (PMB) or THP group and W are as defined above ;comprisingreaction of compound of formula (II),
  • the base usedin process for the preparation of compound of formula (III) is organic or inorganic base selected fromtriethylamine, trimethylamine, dimethyl amine and tert-butyl amine, ammonia solution, sodium hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium tert-butoxide, sodium isopropoxide and potassium tert-butoxide, and preferably sodium tert-butoxide, sodium isopropoxide and potassium tert-butoxide, sodium carbonate and potassium carbonate.
  • the organicsolvent used in preparation of compound of formula (III) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n- hexane, n- heptane, cyclohexane,
  • the process for the preparation of compound of formula (III) is carried out at a temperature of-20°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 60°C for about 30 minutes to about 48 hours, and preferably at a temperature of about 10°C to about 50°C for about 1 hour to about 24 hours.
  • an improved process for the preparation of compound of formula (V) is provided.
  • P p-phenylbenzoyl
  • PMB p-methoxy benzyl
  • R 3 p-nitrobenzoyl
  • the 4-nitrobenzoyl halide used in the preparation of compound of formula (V) is selected from 4-nitrobenzoyl chloride, 4-nitrobenzoyl bromide and the like;more preferably,4-nitrobenzoyl chloride.
  • the catalyst used in the preparation of compound of formula (V) is DMAP and the like; and the base used in process for the preparation of compound of formula (V) is organic or inorganic base, selected from triethylamine, trimethylamine, dimethyl amine and tert- butyl amine; ammonia solution, sodium hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium tert- butoxide, sodium isopropoxide and potassium tert-butoxide; and more preferably, the base is triethylamine.
  • the organicsolvent used in the preparation of compound of formula (V) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n- hexane, n- heptane, cyclohexane
  • the process for the preparation of compound of formula (V) is carried out at a temperature of -5°C to the reflux temperature of the solvent used for at least 15 minutes, specifically at a temperature of about 0°C to about 60°C for about 30 minutes to about 10 hours, and preferably at a temperature of about 5°C to about 30°C for about 1 hour to about 6 hours.
  • the organicsolvent used in step (i) selected fromthe group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, amyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone, acetonitrile, ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, n-pentane, n-hexane, n- heptane, cyclohexane, tol
  • Suitable methods such as prep HPLC, crystallization, gravity column chromatography using suitable organic solvents.
  • suitable organic solvents includeethers such as ethyl acetate, methyl acetate and the like; cyclic hydrocarbons such as n-hexane, n- heptan, cyclohexane and the like; ketones such as acetone, ethyl methyl ketone, and the like; and their mixtures thereof. Most preferably 30% cyclohexane and acetone is used.
  • the highly pure prostaglandins and prostaglandin analogsobtained by the above process may be further dried in, for example, a Vacuum Tray Dryer, a Rotocon Vacuum Dryer, a Vacuum Paddle Dryer or a pilot plant Rota vapor, to further lower residual solvents. Drying can be carried out under reduced pressure until the residual solvent content reduces to the desired amount such as an amount that is within the limits given by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (“ICH”) guidelines.
  • ICH International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use
  • the drying is carried out at atmospheric pressure or a reduced pressure, such as below about 200 mm Hg, or below about 50 mm Hg, at temperatures such as about 35°C to about 70°C.
  • the drying can be carried out for any desired time period that achieves the desired result, such as times about 1 to 20 hours. Drying may also be carried out for shorter or longer periods of time depending on the product specifications. Temperatures and pressures will be chosen based on the volatility of the solvent being used and the foregoing should be considered as only a general guidance. Drying can be suitably carried out in a tray dryer, vacuum oven, air oven, or using a fluidized bed drier, spin flash dryer, flash dryer, and the like. Drying equipment selection is well within the ordinary skill in the art.
  • THF refers to tetrahydrofuran
  • DCM refers to dichloromethane
  • DMSO N,N-dimethylsulfoxide
  • DMF refers to N,N-dimethylformamide
  • IPA refers to isopropyl alcohol
  • DIBAL-H refers to diisobutylaluminium hydride
  • DMAP refers to 4-dimethylaminopyridine
  • DBU refers to l ,8-diazabicyclo[5.4.0]undec-7-ene
  • (-)-DIP chloride refers to (-)-B-chlorodiisopinocamphenylborane
  • PPTS refers to pyridinium p-toluene sulfonate
  • THP refers to tetrahydropyran
  • ZnCl 2 refers to zinc chloride
  • ZrCLi refers to zirconium chloride
  • NH 4 C1 refers to ammonium chloride
  • NaCl refers to sodium chloride
  • K 2 CO 3 refers to potassium carbonate
  • NaHMDS refers to sodium hexamethyldisilazide
  • NaHCC>3 refers to sodium hydrogen carbonate
  • NaOCl refers to sodium hypochlorite
  • KO'Bu refers to potassium tertbutoxide
  • TEMPO refers to 2,2,6,6-Tetramethylpiperidinyloxy
  • DM water refers to demineralised water
  • gm refers to gram
  • hr/ hrs refers to hours
  • RT refers to room temperature
  • reaction mixture was neutralized using acetic acid (30 ml) and washed with water several times. Organic layer was separated and concentrated under vacuum. Methanol (400 ml) was added to the reaction mass and the mixture was stirred for 1-2 hrs. Solid obtained was filtered and washed with methanol, dried under vacuum at 55°C to 60°C for 20-24 hrs to afford compound (III).
  • the oily mass was purified by column chromatograph using7% acetone: cyclohexane as eluting solvent system to afford pure colourless oil.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé amélioré, économiquement viable et industriellement avantageux de préparation de dérivés de prostaglandine et de leurs intermédiaires, avec un haut rendement et une grande pureté.
PCT/IB2013/053173 2012-05-03 2013-04-22 Traitement amélioré et évolutif de préparation de dérivés de prostaglandine et de leurs intermédiaires WO2013164729A1 (fr)

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IN493KO2012 2012-05-03

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107973767A (zh) * 2016-10-21 2018-05-01 扬子江药业集团有限公司 他氟前列素中间体的制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050209337A1 (en) * 2000-01-27 2005-09-22 Finetech Laboratories Ltd Process for the preparation of prostaglandin derivatives
US20100010239A1 (en) 2008-07-10 2010-01-14 Sandoz Ag Process for the Production of Prostaglandins and Prostaglandin Analogs
WO2010104344A2 (fr) 2009-03-11 2010-09-16 Yonsung Fine Chemical Co., Ltd. Procédé de préparation de dérivés de prostaglandine
WO2011055377A1 (fr) 2009-11-05 2011-05-12 Biocon Limited Nouveau procédé de préparation de prostaglandines et de leurs intermédiaires

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050209337A1 (en) * 2000-01-27 2005-09-22 Finetech Laboratories Ltd Process for the preparation of prostaglandin derivatives
US20100010239A1 (en) 2008-07-10 2010-01-14 Sandoz Ag Process for the Production of Prostaglandins and Prostaglandin Analogs
WO2010104344A2 (fr) 2009-03-11 2010-09-16 Yonsung Fine Chemical Co., Ltd. Procédé de préparation de dérivés de prostaglandine
WO2011055377A1 (fr) 2009-11-05 2011-05-12 Biocon Limited Nouveau procédé de préparation de prostaglandines et de leurs intermédiaires

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107973767A (zh) * 2016-10-21 2018-05-01 扬子江药业集团有限公司 他氟前列素中间体的制备方法

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