+

WO2008150953A1 - Procédé de préparation de rameltéon et substances apparentées - Google Patents

Procédé de préparation de rameltéon et substances apparentées Download PDF

Info

Publication number
WO2008150953A1
WO2008150953A1 PCT/US2008/065211 US2008065211W WO2008150953A1 WO 2008150953 A1 WO2008150953 A1 WO 2008150953A1 US 2008065211 W US2008065211 W US 2008065211W WO 2008150953 A1 WO2008150953 A1 WO 2008150953A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
acid
reaction
amine
Prior art date
Application number
PCT/US2008/065211
Other languages
English (en)
Inventor
Pratap Reddy Padi
Srinivas Polavarapu
P. Sailaja
Praveen Cherukupally
Original Assignee
Dr. Reddy's Laboratories Ltd.
Dr. Reddy's Laboratories, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dr. Reddy's Laboratories Ltd., Dr. Reddy's Laboratories, Inc. filed Critical Dr. Reddy's Laboratories Ltd.
Publication of WO2008150953A1 publication Critical patent/WO2008150953A1/fr

Links

Classifications

    • 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

Definitions

  • R 1 represents an optionally substituted hydrocarbon group, an optionally substituted amino group or an optionally substituted heterocyclic group
  • R 2 represents a hydrogen atom or an optionally substituted hydrocarbon group
  • R 3 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group
  • X represents CHR 4 , NR 4 , O or S in which R 4 represents a hydrogen atom or an optionally substituted hydrocarbon group
  • Y represents C, CH or N, provided that when X is CH 2 , Y is C or CH; " ⁇ represents a single bond or a double bond
  • ring A represents an optionally substituted, 5- to 7-membered oxygen-containing heterocyclic ring
  • ring B represents an optionally substituted benzene ring
  • m represents an integer of 1 to 4, or a salt thereof.
  • Ramelteon is approved for the treatment of insomnia characterized by difficulty with sleep onset and is marketed as ROZEREM TM in US. Ramelteon, the S-enantiomer has 500-fold greater potency for binding of the MT1 receptor than its R- enantiomer.
  • U.S. Patent No. 6,034,239 describes compounds of Formula I, process for its preparation and methods of its use related to sleep disorders.
  • International Publication No. WO 2006/030739A1 and Drugs of the Future, Vol. 28, No.10, 2003 describes the processes for the preparation of compound of Formula I, which are incorporated herein as reference. There is a continuing need to develop an improved process for producing compounds of Formula I in safer and less expensive ways suitable for commercial manufacturing and use.
  • Optical purity also referred to herein as stereogenic purity, both meaning a single absolute confirmation at all chiral atoms, can be of importance in the field of pharmaceuticals and the enantiomers / diastereomers of a drug substance may sometimes exhibit vastly different properties such as solubility, potency and toxicity. Therefore, for chiral drug substances (substances including at least one chiral atom), it is required by many regulatory authorities that products be as pure (in terms of stereogenic or optical isomers) as possible. Therefore, there is a need to obtain the desired enantiomer of compounds of Formula I with high enantiomeric purity.
  • X is the chiral resolving agent, which is, preferably, a chiral acid suitable for resolving the amine of the Formula (IV);
  • the invention includes a process for the preparation of compound of Formula I, comprising: reacting isocyanate of Formula Il
  • ⁇ 11 ⁇ represents a single bond or a double bond
  • R represents ethyl, vinyl or ethynyl
  • X is a halogen.
  • the process may, in addition or instead comprise the step of converting a compound of Formula MIA
  • X is the chiral resolving agent for resolving the amine of the Formula (IV).
  • the process may, in addition or instead comprise the steps of treating an amine compound of Formula IV
  • the compound of Formula I wherein R is unsaturated and/or " ⁇ represents a double bond may be further reduced to obtain the corresponding saturated compound.
  • the process relates to a purification process of the compound of Formula I, which process includes the step of recrystallizing or slurrying the compounds of Formula I from a suitable solvent(s) to afford the desired pure compound of Formula I.
  • Purity may also include essentially pure, substantially pure and/or pure in terms of impurities other than of the stereogenic or optical isomers.
  • the compound of Formula I is both optically or stereogenically pure and pure with regard to other contaminants, reactants, reaction byproducts and the like.
  • the purity, in terms of stereogenic or optical purity and freedom from other contaminants may be different.
  • a product could be essentially pure in terms of contaminants and substantially pure in terms of other optical or stereogenic species.
  • they are both "pure" as defined herein.
  • the present patent application relates to a process for the synthesis of compound of Formula I, which process includes one or more of the following steps: a) treating racemic amine of the Formula IV
  • X is the chiral resolving agent, preferably, chiral acid suitable for resolving the amine of the Formula (IV); b) optionally generating a chiral amine compound of Formula III from compound of Formula HIA;
  • Each step is separately contemplated.
  • the process of resolution in step (a) includes preparation of a solution of racemic amine of the Formula IV followed by treatment with a chiral resolving agent in presence of a solvent to form a salt of compound of Formula MIA.
  • racemic amine of the Formula IV may be prepared by dissolving racemic amine of the Formula IV prepared using any of the processes described in the art, such as dissolving in a solvent, or such a solution may be obtained directly from a reaction in which racemic amine of the Formula IV is formed.
  • Racemic used in this context is used loosely to cover any combination of optical or stereogenic isomers with a purity (in terms of other stereogenic isomers) of less than about 90% of any one species including true racemic (50:50) mixtures.
  • the chiral resolving agents that may be utilized for this step include, but are not limited to, pyroglutamic acid, tartaric acid, mandelic acid, di-p-toluyl tartaric acid, debenzoyl tartraric acid, camphor sulfonic acid, ⁇ -methoxy- ⁇ - (trifluoromethyl)phenylacetic acid (also known as Mosher's acid), naproxen and the like.
  • Other suitable chiral acid resolving agents may be determined by testing and the use thereof in a process as described above falls within the scope of the present invention.
  • the solvents that may be utilized for this step include, but are not limited to, alcoholic solvents such as methanol, ethanol, isopropyl alcohol and n-propanol; halogenated solvents such as dichloromethane, 1 ,2-dichloroethane, chloroform and carbon tetrachloride; ketone solvents such as acetone, ethylmethyl ketone and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate and t-butyl acetate; ether solvents such as diethyl ether, dimethylether, di-isopropylether, methyltertiarybutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbon solvents such as toluene, xylene, n-heptane, cyclo
  • the temperatures may range from about 0 0 C to reflux temperature of the solvent used.
  • the reaction time may range from about 30 minutes to about 30 hours, or longer, depending on the conditions chosen.
  • the obtained salt of compound of Formula IMA (which are generally optically enriched as a single enantiomer) may be isolated by techniques, such as centrifugation, gravity filtration, or vacuum filtration or other techniques known in the art for the separation of solids.
  • the solvent from the reaction mass may be removed completely or partially by distillation techniques such as atmospheric distillation, distillation under vacuum or evaporation before isolation.
  • the salt of compound of Formula IHA thus obtained may be further purified to remove impurities, reaction byproducts, and the like by slurrying or crystallizing from a suitable solvent.
  • the solvents mentioned above may be used for this purification step.
  • (b) involves preparing a solution or slurry of the salt of the Formula (IIIA) followed by adjusting the pH of the solution to a basic value.
  • Either the wet solid or a dry solid of compound of Formula IHA may be used for preparation of the solution or slurry of the salt.
  • the solvents that may be utilized for this step include, but are not limited to, alcoholic solvents such as methanol, ethanol, isopropyl alcohol and n-propanol; halogenated solvents such as dichloromethane, 1 ,2-dichloroethane, chloroform and carbon tetrachloride; ketone solvents such as acetone, ethylmethyl ketone and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate and t-butyl acetate; ether solvents such as diethyl ether, dimethylether, di-isopropylether, methyltertiarybutyl ether, tetrahydrofuran and 1 ,4-dioxane; hydrocarbon solvents such as toluene, xylene, n-heptane,
  • Bases that are useful in this step include, but are not limited to: inorganic bases such as alkali metal or alkaline earth metal carbonates, hydrogen carbonates, hydroxides, oxides, carboxylates, and alkoxides, e.g., sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium hydroxide, calcium oxide, sodium acetate, sodium methoxide, and the like or their aqueous solutions; and organic bases such as, for example, tertiary amines, e.g., N 1 N- diethylethanamine, N-(1-methylethyl)-2-propanamine, 4-ethylmorpholine, 1,4- diazabicyclo[2.2.2]-octane, N-methyl morpholine, diisopropyl ethyl amine, pyridine, and the like.
  • inorganic bases such as alkali metal or alkaline earth metal carbonates, hydrogen carbonates, hydroxides, oxides, carboxylates,
  • the pH of the reaction mass may range from about 7 to about 14.
  • the temperatures for this step may range from about 10 0 C to about 60 0 C.
  • an organic solvent which is insoluble in water may be added and stirred for sufficient time and then the organic layer containing the free base may be separated. This layer may be progressed to further processing directly or it may be concentrated to form a residue. The residue thus obtained may be further purified to remove impurities, reaction byproducts, and the like by slurrying or crystallizing from a solvent.
  • the product of Formula III obtained from this reaction may be used in the next reaction step, without isolation from the reaction mixture or in the form of a crude product.
  • reaction mixture may be isolated from the reaction mixture by ordinary methods, and it can be easily purified to remove impurities, reaction byproducts, and the like by means of separation, for example, recrystallization, distillation, chromatography and slurrying in a solvent.
  • separation for example, recrystallization, distillation, chromatography and slurrying in a solvent.
  • the solvents described above may be used for this purification step.
  • the solvent that may be used in this step include, but are not limited to, chlorinated aliphatic hydrocarbons such as methylene dichloride, chloroform, ethylene dichloride, 1 ,1 ,1 ,-trichloroethane, trichloroethylene etc. or aromatic hydrocarbon solvent such as toluene, xylene, chlorobenzene, etc. or aprotic solvents including Dimethyl formamide, dimethyl acetamide, N-methyl pyrrolidine and acetonitrile.
  • chlorinated aliphatic hydrocarbons such as methylene dichloride, chloroform, ethylene dichloride, 1 ,1 ,1 ,-trichloroethane, trichloroethylene etc.
  • aromatic hydrocarbon solvent such as toluene, xylene, chlorobenzene, etc.
  • aprotic solvents including Dimethyl formamide, dimethyl acetamide, N-methyl pyrrolidine and acetonitrile.
  • Bases that are useful in the reaction include, but are not limited to, inorganic bases such as alkali metal or alkaline earth metal carbonates, hydrogen carbonates, hydroxides, carboxylates, and alkoxides, e.g., sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium hydroxide, sodium acetate, sodium methoxide, and the like or their aqueous solutions; and organic bases such as, for example, tertiary amines, e.g., N,N-diethylethanamine, N-(1-methylethyl)-2-propanamine, 4- ethylmorpholine, 1 ,4-diazabicyclo[2.2.2]-octane, N-methyl morpholine, diisopropyl ethyl amine, pyridine, and the like.
  • inorganic bases such as alkali metal or alkaline earth metal carbonates, hydrogen carbonates, hydroxides, carboxylates, and alkoxide
  • the compound may be isolated by removal of the solvent.
  • the solvent may be removed using any suitable methods such as evaporation, atmospheric distillation, or distillation under vacuum.
  • the Grignard reagent that may be used in this step include, ethyl magnesium halide, vinyl magnesium halide or ethynyl magnesium halide.
  • Ethyl magnesium halide and vinyl magnesium halides are commercially available.
  • Ethynyl magnesium halide may be prepared according to the procedures disclosed in the Journal, Molecules, 2002, 7, 341-352 or any other methods known in the art.
  • the compound of Formula I wherein R is unsaturated and/or " ⁇ * 1 represents a double bond may be reduced to obtain the corresponding saturated compound.
  • the catalysts to be used for the reduction include, for example, platinum oxide, platinum on activated carbon, palladium on activated carbon, palladium on barium sulfate, raney-nickel, copper- chromium oxide, rhodium, cobalt, ruthenium, etc.
  • the amount of the catalyst to be used may be approximately 5 to 1000% by weight, preferably approximately 5 to 300% by weight relative to compound of Formula I.
  • the reaction is advantageously conducted in a solvent inert to the reaction. While, as the solvent, any one can be used so far as the reaction advances therein, for example, alcohols such as methanol, ethanol, propanol, etc.; ketonic solvents such as acetone, ethyl methyl ketone, and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, and t-butyl acetate; nitrile solvents such as acetonitrile, and propionitrile; halogenated solvents such as dichloromethane, ethylene dichloride, and chloroform; ethers such as dimethylether, diethylether, diisopropyl ether, methylter
  • N-dimethylacetamide water or mixtures thereof.
  • solvent from the solution may be removed completed or partially using techniques such as atmospheric distillation, distillation under vacuum, evaporation etc.
  • Other solvent(s) or the same solvent may be added to the remaining reaction mass before its isolation.
  • the solvents listed above may be used for this step.
  • the reaction mass may be cooled before the isolation of the product. Crystal formation from the solution may be promoted by cooling the solution.
  • a seeding sample may be added to isolate the desired polymorphic form during the recrystallization step.
  • Isolation of the product thus obtained includes collection of the material with or without cooling below the operating temperature by any techniques such as filtration by gravity or suction, centrifugation, and the like and optional washing with the solvent.
  • the solid material obtained by any of the techniques described above may be further dried. Drying may be suitably carried out by any known methods such as tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like. The drying may be carried out under reduced pressures and at temperatures. The temperature may range from about ambient temperature to about 100 0 C for a time period that produces the desired result.
  • the compound of Formula I may also be prepared with the process described in the present patent application with high stereogenic purity such as at least 99.0 wt%, or at least 99.5 wt %, or at least 99.9 wt %.
  • the level of isomeric impurity may be less than about 1 wt %, 0.5 wt %, or 0.1 wt % as determined by chiral high performance liquid chromatography (CHPLC).
  • CHPLC chiral high performance liquid chromatography
  • the present application provides substantially pure compounds of Formula I.
  • pure refers to chemical purity.
  • compound of Formula I of the present application may also contain less than about 0.5% of total impurities, or more preferably less than about 0.1 % of total impurities. These impurities can be characterized by high performance liquid chromatography ("HPLC").
  • HPLC high performance liquid chromatography
  • the present invention also includes compounds II, III, HIA and IV individually, preferably in isolated and at least essentially pure form.
  • compound of Formula I obtained by the process of the present invention has a average particle size of about 250 microns, often less than about 200 microns as measured by sieve analysis by weight. The desired particle size may be obtained directly from the process or may be obtained by using the techniques known to the person skilled in the art such as milling, grinding, spray drying etc.
  • the starting material amine of Formula IV may be prepared by any known process or by the following process.
  • the temperature for addition of phosphorous oxychloride in step (i) may range from about 0 0 C to about 50°C or from about 25 0 C to about 30 0 C.
  • the solvents which may be used in step (a) include but are not limited to; aprotic polar solvents such as N,N-dimethylformamide (DMF), Dimethylsulfoxide (DMSO), N 1 N- dimethylacetamide (DMA) and the like; or mixtures thereof in various proportions.
  • the base includes, for example, inorganic bases such as sodium hydroxide, potassium hydroxide, etc.; basic salts such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogencarbonate, etc.; aromatic amines such as pyridine, lutidine, etc.; tertiary amines such as triethylamine, tripropylamine, tributylamine, cyclohexyldimethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, piperidine, N-methylpiperidine, N-methylpyrrolidine, N-methylmorpholine, etc.
  • inorganic bases such as sodium hydroxide, potassium hydroxide, etc.
  • basic salts such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogencarbonate, etc.
  • aromatic amines such as pyridine, lutidine, etc.
  • tertiary amines such as triethylamine, tripropylamine,
  • the hydrolysis step may also be carried out in presence of inorganic basic compound such as calcium carbonate, sodium carbonate, sodium hydroxide, sodium hydrogen carbonate and the like may be used for this step.
  • inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and the like may also be used for this hydrolysis step. Any other methods that accomplish the hydrolysis without affecting the product molecule may also be used.
  • the reaction may be carried out from about room temperature to about the reflux temperature of the solvent used.
  • the reaction time is generally 30 minutes to 12 hours, preferably 30 minutes to 6 hours.
  • the reaction temperature is generally -20 to 200 0 C, preferably -5 to 12O 0 C.
  • the product (VII) produced by the above-mentioned cyclization can be used in the next reaction step, while it is in the reaction mixture or in the form of a crude product. If desired, however, it may be isolated from the reaction mixture by ordinary methods, and it can be easily purified in terms of impurities, byproducts, contaminants, and the like by means of separation, for example, recrystallization, distillation and chromatography.
  • Compound of formula (Vl) as in step (vii) may be produced by catalytically reducing compound (VII) in a hydrogen atmosphere in the presence of various catalysts.
  • any one can be used so far as the reaction advances therein, for example, alcohols such as methanol, ethanol, propanol, etc.; ketonic solvents such as acetone, ethyl methyl ketone, and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, and t-butyl acetate; nitrile solvents such as acetonitrile, and propionitrile; halogenated solvents such as dichloromethane, ethylene dichloride, and chloroform; ethers such as dimethylether, diethylether, diisopropyl ether, methyltertiarybutyl ether, tetrahydrofuran, and1 ,4-dioxane; hydrocarbons solvents such as toluene, xylene, n-hex
  • the reaction time varies, depending on the activity of the catalyst and the amount thereof used. In general, it is 30 minutes to 24 hours, preferably 30 minutes to 6 hours.
  • the reaction temperature is generally 0 to 12O 0 C, preferably 20 to 8O 0 C.
  • the pressure for the reaction is generally 1 to 100 atmospheres. Additives (promoters) that enhance the activity of the catalyst used can be added to the reaction system.
  • Modified release compositions may include hydrophilic or hydrophobic, or combinations of hydrophilic and hydrophobic, release rate controlling substances to form matrix or reservoir systems or combinations of matrix and reservoir systems.
  • the compositions may be prepared by direct blending, dry granulation or wet granulation or by extrusion and spheronization.
  • the compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated or modified release coated.
  • the compositions of the present patent application may further comprise one or more pharmaceutically acceptable excipients.
  • compositions that find use in the present patent application include, but are not limited to: diluents for example starch, pregelatinized starch, lactose, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar and the like; binders for example acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, pregelatinized starch and the like; disintegrants for example starch, sodium starch glycolate, pregelatinized starch, crospovidone, croscarmellose sodium, colloidal silicon dioxide and the like; lubricants for example stearic acid, magnesium stearate, zinc stearate and the like; glidants for example colloidal silicon dioxide and the like; solubility or wetting enhancers such as anionic or cationic or neutral surfactants
  • EXAMPLE 11 Preparation of racemic 2-(1 , 6,7,8,- tetrahydro-2H-indeno[5,4-b] furan-8-yl) ethyl amine (FORMULA IV, wherein " 8 ⁇ represents a single bond) 27gm of 2-(1 ,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-ylidene)acetonitrile of Formula V (wherein ⁇ represents a single bond), Aqueous Ammonia (373.6 ml) and 27 g of raney nickel and ethanol (1188 ml) were charged into an autoclave and the resultant reaction mixture was maintained at about 5.0 kg/cm 2 hydrogen pressures at about 30-38 0 C for about 5- 6 hours.
  • the reaction mass was heated to about 7O 0 C to get complete dissolution.
  • the reaction mass was cooled to 26 0 C and stirred for about 4-5 hours for solid separation.
  • the separated solid was filtered and washed with ethanol.
  • the obtained solid was dried at 7O 0 C to a constant weight to afford 4.5 g of the title compound.
  • the obtained crude was charged in to a clean and dry 4 necks round bottom flask containing 100 ml of toluene followed by stirring given.
  • the reaction solution was cooled to about O 0 C.
  • 70 ml of ethyl magnesium bromide was slowly added through a dropper at about O 0 C followed by stirring the stirring the reaction mass at the same temperature for the completion of the reaction.
  • the resultant reaction mass was quenched by addition of 20% acetic acid solution followed by stirring for about 15-20 minutes and organic and aqueous layers were separated.
  • the obtained aqueous layer was extracted with ethyl acetate and separated the organic and aqueous layer. The separated organic layers were combined and washed with water.

Landscapes

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

Abstract

La présente invention concerne un procédé de préparation de composés de formule I (LA FORMULE CHIMIQUE DOIT ÊTRE INSÉRÉE ICI COMME IL APPARAÎT SUR L'EXTRAIT SOUS LA FORME PAPIER) formule I dans laquelle …. représente une simple liaison ou une double liaison. R représente un groupe éthyle, vinyle ou éthynyle.
PCT/US2008/065211 2007-05-30 2008-05-30 Procédé de préparation de rameltéon et substances apparentées WO2008150953A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN1129/CHE/2007 2007-05-30
IN1129CH2007 2007-05-30
US2951108P 2008-02-18 2008-02-18
US61/029,511 2008-02-18

Publications (1)

Publication Number Publication Date
WO2008150953A1 true WO2008150953A1 (fr) 2008-12-11

Family

ID=39727579

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/065211 WO2008150953A1 (fr) 2007-05-30 2008-05-30 Procédé de préparation de rameltéon et substances apparentées

Country Status (1)

Country Link
WO (1) WO2008150953A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009060318A2 (fr) * 2007-07-12 2009-05-14 Teva Pharmaceutical Industries Ltd. Formes polymorphes de rameltéon et leurs procédés de préparation
US8084630B2 (en) 2007-05-31 2011-12-27 Teva Pharmaceutical Industries Ltd. Process for the synthesis of ramelteon and its intermediates
CN102648192A (zh) * 2009-09-29 2012-08-22 隆萨有限公司 1,2,6,7-四氢-8h-茚并[5,4-b] 呋喃-8-酮的制备方法
CN102924410A (zh) * 2012-10-29 2013-02-13 华润赛科药业有限责任公司 一种雷美替胺的制备方法及其中间体
CN104119307A (zh) * 2013-04-24 2014-10-29 辰欣药业股份有限公司 (s)-2-(1,6,7,8-四氢-2h-茚并[5,4-b]呋喃-8-基)乙胺的制备方法
CN112500380A (zh) * 2020-11-11 2021-03-16 山东鲁药制药有限公司 一种雷美替胺的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006030739A1 (fr) * 2004-09-13 2006-03-23 Takeda Pharmaceutical Company Limited Procédé de fabrication de dérivés d’amines optiquement actifs
WO2008062468A2 (fr) * 2006-10-26 2008-05-29 Cadila Healthcare Limited Procédé de préparation de derivés d'indéno[5,4-b] furane optiquement purs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006030739A1 (fr) * 2004-09-13 2006-03-23 Takeda Pharmaceutical Company Limited Procédé de fabrication de dérivés d’amines optiquement actifs
EP1792899A1 (fr) * 2004-09-13 2007-06-06 Takeda Pharmaceutical Company Limited Procédé de fabrication de dérivés d amines optiquement actifs
WO2008062468A2 (fr) * 2006-10-26 2008-05-29 Cadila Healthcare Limited Procédé de préparation de derivés d'indéno[5,4-b] furane optiquement purs

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHILMAN-BLAIR, K. ET AL: "TAK-375: treatment of insomnia treatment of circadian rhythm disorders melatonin MT1/MT2 agonist", DRUGS OF THE FUTURE , 28(10), 950-958 CODEN: DRFUD4; ISSN: 0377-8282, 2003, XP002495177 *
TARUI, NAOKI ET AL: "Kinetic resolution of an indan derivative using Bacillus sp. SUI-12: synthesis of a key intermediate of the melatonin receptor agonist TAK-375", JOURNAL OF BIOSCIENCE AND BIOENGINEERING , 93(1), 44-47 CODEN: JBBIF6; ISSN: 1389-1723, 2002, XP002495178 *
UCHIKAWA, OSAMU ET AL: "Synthesis of a Novel Series of Tricyclic Indan Derivatives as Melatonin Receptor Agonists", JOURNAL OF MEDICINAL CHEMISTRY , 45(19), 4222-4239 CODEN: JMCMAR; ISSN: 0022-2623, 2002, XP002990691 *
YAMANO, TORU ET AL: "Approach to the stereoselective synthesis of melatonin receptor agonist Ramelteon via asymmetric hydrogenation", TETRAHEDRON: ASYMMETRY , 17(2), 184-190 CODEN: TASYE3; ISSN: 0957-4166, 2006, XP005288039 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8084630B2 (en) 2007-05-31 2011-12-27 Teva Pharmaceutical Industries Ltd. Process for the synthesis of ramelteon and its intermediates
WO2009060318A2 (fr) * 2007-07-12 2009-05-14 Teva Pharmaceutical Industries Ltd. Formes polymorphes de rameltéon et leurs procédés de préparation
WO2009060318A3 (fr) * 2007-07-12 2009-12-10 Teva Pharmaceutical Industries Ltd. Formes polymorphes de rameltéon et leurs procédés de préparation
CN102648192A (zh) * 2009-09-29 2012-08-22 隆萨有限公司 1,2,6,7-四氢-8h-茚并[5,4-b] 呋喃-8-酮的制备方法
CN102648192B (zh) * 2009-09-29 2015-08-26 广州南沙龙沙有限公司 1,2,6,7-四氢-8h-茚并[5,4-b] 呋喃-8-酮的制备方法
CN102924410A (zh) * 2012-10-29 2013-02-13 华润赛科药业有限责任公司 一种雷美替胺的制备方法及其中间体
CN104119307A (zh) * 2013-04-24 2014-10-29 辰欣药业股份有限公司 (s)-2-(1,6,7,8-四氢-2h-茚并[5,4-b]呋喃-8-基)乙胺的制备方法
CN112500380A (zh) * 2020-11-11 2021-03-16 山东鲁药制药有限公司 一种雷美替胺的制备方法

Similar Documents

Publication Publication Date Title
US9233966B2 (en) Preparation of ticagrelor
CA2707790C (fr) Procedes de preparation de sitagliptine et sels pharmaceutiquement acceptables de celle-ci
US20240287072A1 (en) Solid state forms of lumateperone salts and processes for preparation of lumateperone and salts thereof
WO2008150953A1 (fr) Procédé de préparation de rameltéon et substances apparentées
WO2008011462A2 (fr) Procédé de fabrication de solifénacine et de ses sels
JP5531097B2 (ja) アンブリセンタンを調製するための改善された方法およびその新規な中間体
WO2018148361A1 (fr) Procédé de préparation de rémimazolam et formes à l'état solide de sels de rémimazolam
KR19990022096A (ko) 모노시클릭 아미노기를 갖는 인다졸 유도체
WO2011025932A2 (fr) Préparation de la sitagliptine et de ses sels
JP5160219B2 (ja) テルミサルタンの製造方法
JPH10504820A (ja) Ｎ−置換されたフェノチアジン類の使用
WO2020051014A1 (fr) Procédés pour la préparation de ténapanor et d'intermédiaires de ceux-ci
JP3257708B2 (ja) トリアザスピロデカノン−メチルクロマン類
JP4799592B2 (ja) フェニルエタノールアミンの結晶形の製造方法
US20240010632A1 (en) Solid state forms of erdafitinib salts and processes for preparation of erdafitinib
KR20160126697A (ko) 신규 결정형의 바레니클린 옥살산 염 수화물, 이의 제조방법, 및 이를 포함하는 약학 조성물
KR101576620B1 (ko) 3-아미노-9,13b-디하이드로-1H-디벤즈-[c,f]이미다조[1,5-a]-아제핀 브롬산염의 신규 제조방법
US20220153744A1 (en) Solid state forms of acalabrutinib
US20210198211A1 (en) Crystalline eltrombopag monoethanolamine salt form d
WO2015104602A2 (fr) Procédé de préparation d'anagliptine et de ses intermédiaires
US20150099753A1 (en) Form 5 polymorph of 7-(tert-butyl-d9)-3-(2,5-difluorophenyl)-6-((1-methyl-1h-1,2,4-triazol-5-yl)methoxy)-[1,2,4]triazolo[4,3-b]pyridazine
US20240239791A1 (en) Processes for the synthesis of valbenazine
US20060094764A1 (en) Cyanothiophenes, their preparation and their use in pharmaceutical compositions
US20070238721A1 (en) Highly Selective Novel Amidation Method
US20220289764A1 (en) Crystalline lorlatinib : fumaric acid and solid state form thereof

Legal Events

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

Ref document number: 08769853

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08769853

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载