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WO2018104953A1 - Procédé amélioré pour la préparation de 7-{4-[4-(2,3-dichlorophényl)-pipérazin-1-yl]butoxy}-2oxo-3,4-dihydro-2h-quinolin-1-yl)méthyl dodécanoate - Google Patents

Procédé amélioré pour la préparation de 7-{4-[4-(2,3-dichlorophényl)-pipérazin-1-yl]butoxy}-2oxo-3,4-dihydro-2h-quinolin-1-yl)méthyl dodécanoate Download PDF

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WO2018104953A1
WO2018104953A1 PCT/IN2017/000138 IN2017000138W WO2018104953A1 WO 2018104953 A1 WO2018104953 A1 WO 2018104953A1 IN 2017000138 W IN2017000138 W IN 2017000138W WO 2018104953 A1 WO2018104953 A1 WO 2018104953A1
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compound
formula
reaction mixture
solvents
filtering
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Inventor
Srinivasan Thirumalai Rajan
Sajja Eswaraiah
Jakku MALLESWARA REDDY
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MSN Laboratories Pvt Ltd
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MSN Laboratories Pvt Ltd
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    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms

Definitions

  • the present invention relates to an improved and novel process for the preparation of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-I.-yl]butoxy ⁇ -2-0X0-3 ,4-dihydro-2H-quinolin- 1- yl)methyl dodecanoate compound of formula- 1 , which is represented by the following structural formula:
  • the first aspect of the present invention is to provide an improved process for the preparation of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l -yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H- quinolin-l -yl) methyl dodecanoate compound of formula- 1.
  • the second aspect of the present invention is to provide an alternative process for the preparation of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l -yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H- quinolin- l -yl)methyl dodecanoate compound of formula- 1 .
  • the third aspect of the present invention is to provide an alternative process for the preparation of the compound of formula-1.
  • the fourth aspect of the present invention is to provide novel process for the preparation of the compound of formula- 1.
  • the fifth aspect of the present invention is to provide a process for the preparation of the compound of general formula-10.
  • the sixth aspect of the present invention is to provide an alternative process for the preparation of the compound of general formula-10.
  • the seventh aspect of the present invention is to provide novel process for the preparation of the compound of formula-7.
  • the eighth aspect of the present invention is to provide the purification of lauric acid compound of formula-3.
  • Figure-1 Illustrates the powder X-ray diffraction of the compound of formula-7 obtained according to the present invention.
  • Figure-2 Illustrates the powder X-ray diffraction of the compound of formula- 1 obtained according to the present invention.
  • Figure-3 Illustrates the DSC thermogram of the compound of formula- 1 obtained according to the present invention. Detailed description of the Invention:
  • the present invention provides process for the preparation of 7- ⁇ 4-[4-(2,3-dichloro phenyl)-piperazin-l -yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H-quinolin- l -yl)methyi dodecanoate compound of formula- 1 .
  • suitable solvent refers to "hydrocarbon solvents” such as n-hexane, n-heptane, cyclohexane, pet ether, toluene, pentane, cycloheptane, methyl cyclohexane, m-, o-, or p-xylene and the like; "ether solvents” such as dimethoxymethane, tetrahydrofuran, 1 ,3-dioxane, 1 ,4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, 1 ,2-dimethoxy ethane and the like; "ester solvents” such as methyl acetate,
  • suitable base refers to inorganic bases selected from “alkali metal carbonates” such as sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate and the like; “alkali metal bicarbonates” such as sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, cesium bicarbonate and the l ike; “alkali metal hydroxides” such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like; “alkyl metals” such as n-butyl lithium and like; “metal hydrides” such as lithium hydride, sodium hydride, potassium hydride and the like; “alkali metal phosphates” such as disodium hydrogen phosphate, dipotassiumhydrogen phosphate; and “organic bases” selected from but not limited to methyl amine, ethyl amine, diisopropyl amine, diisopropylethyl amine (DIPEA), diisobutylamine, trie
  • alkali metal carbonates such
  • the term "acid” used in the present invention refers to inorganic acids selected from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid etc; organic acids such as acetic acid, maleic acid, malic acid, tartaric acid, oxalic acid, trifluoroacetic acid, methane sulfonic acid, p-toluene sulfonic acid; chiral acids such as S-(+) mandelic acid, R-(-) mandelic acid, L-(+)tartaric acid, D-(-)tartaric acid, L-malic acid, D-malic acid, D- maleic acid, (-)-naproxen, (+)-naproxen, (lR)-(-)-camphor sulfonic acid, (IS)- (+)-camphor sulfonic acid, (lR)-(+)-bromocamphor- 10-sulfonic acid, (IS)-(-)-
  • condensing agent or coupling agent used in the present invention is selected form ⁇ , ⁇ '-dicyclohexylcarbodiimide (DCC), ⁇ , ⁇ '-diisopropylcarbodiimide (DIC), carbonyldiimidazole (CDI), l -ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCI), 0-(7-aza-benzotriazole- l -yl)-N,N,N',N'-tetramethyl uronium hexafluoro phosphate (HATU), alkyl or aryl chloroformates such as ethyl chloro formate, benzylchloroformate, diphenylphosphoroazidate (DPPA), thionyl chloride, pivalyl chloride, oxalyl chloride, phosphorous oxychloride, phosphorous pent
  • phase transfer catalyst used in the present invention is selected from but are not limited to quaternary ammonium salts, quaternary phosphonium salts, crown ethers, cryptands.
  • the suitable " N-protecting agent is selected such that it is capable of protecting the nitrogen atom with any of N-protecting groups known to the person skilled in the art.
  • the suitable hydroxy protecting agent is selected such that it is capable of protecting the oxygen atom with any of hydroxy protecting groups known to the person skilled in the art.
  • deprotecting agent used in the present invention is selected based on the protecting group employed.
  • the deprotecting agent is selected from but not limited to acids; bases; hydrogenating agents such as Pd/C, Pd(OH) 2 /C (Pearlman's catalyst), palladium acetate, platinum oxide, platinum black, sodium borohydride, Na-liquid ammonia, Raney-Ni, tri(C 1 -C 6 )alkylsilanes, tri(C 1 -C 6 )alkylsilyl halides and the like.
  • the first aspect of the present invention provides an improved process for the preparation of the compound of formula- 1 , comprising of;
  • the suitable solvent is selected from alcohol solvents, hydrocarbon solvents, ether solvents, ester solvent, chloro solvents, polar aprotic solvents, ketone solvents, polar solvents or mixtures thereof;
  • the suitable base is selected from inorganic or organic bases;
  • the suitable catalyst is selected from alkali metal iodides such as sodium iodide, potassium iodide, lithium iodide; phase transfer catalyst.
  • step-a) to d) the suitable solvent is same as defined in the first aspect of the present invention; in step-a) and c) the suitable base is same as defined in the first aspect of the present invention; in step-a) the suitable catalyst is same as defined in the first aspect of the present invention.
  • the third aspect of the. present invention provides an alternative process for the preparation of compound of formula-1 comprising of:
  • step-a) to c) the suitable solvent is same as defined in the first aspect of the present invention; in step-a) the suitable base is same as defined in the first aspect of the present invention; in step-b) the suitable coupling agent is same as defined above.
  • Preferred embodiment of the present invention provides an alternative process for the preparation of compound of formula- 1 comprising:
  • Further aspect of the present invention provides a process for the preparation of 7- ⁇ 4- [4-(2,3-dichlorophenyl)-piperazin-l -yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H-quinolin- 1 -y!methyl dodecanoate compound of formula- 1 having specific surface area less than 0.5 m 2 /g comprising the following step:
  • step-a) reacting the acid chloride obtained in step-a) in-situ with paraformaldehyde or formaldehyde in presence of with or without a catalyst and a base provide the compound of formula-4a,
  • the chlorinating agent (or) coupling agent is selected from thionyl chloride, oxalyl chloride, sulfuryl chloride, phosphorous oxychloride, carbon tetra chloride, phosphorous trichloride, phosphorous pentachloride, N-chlorosuccinamide (NCS);
  • the suitable catalyst is lewis acid, preferably Zinc chloride and base is selected from organic or inorganic bases;
  • step d) the suitable base is selected from organic or inorganic bases
  • the suitable solvent is selected from alcohol solvents, hydrocarbon solvents, ether solvents, ester solvent, chloro solvents, polar aprotic solvents, ketone solvents, polar solvents or mixtures thereof.
  • Preferred embodiment of the present invention provides a process for the preparation of 7- ⁇ 4-[4-(2,3-dichlorophenyI)-piperazin- l -yI]butoxy ⁇ -2-oxo-3,4-dihydro-2H-quinolin-l - yl)methyi dodecanoate compound of formula- 1 having specific surface area less than 0.5 m 2 /g comprising the following step:
  • the fourth aspect of the present invention provides novel process for the preparation of the compound of formula-1 , comprising of;
  • step-a) to c) the suitable solvent is same as defined in the first aspect of the present invention; in step-a) and b) the suitable base is same as defined in the first aspect of the present invention.
  • the Fifth aspect of the present invention provides a process for the preparation of the compound of formula- 10, comprising of;
  • step-a) to c) the suitable solvent is same as defined in the first aspect of the present invention; in step-a) the suitable base is same as defined in the first aspect of the present invention; in step-b) the suitable coupling agent is same as defined above.
  • the sixth aspect of the present invention provides an alternative process for the preparation of the compound of general formula- 10, comprising of;
  • step-a) to c) optionally purifying the compound of general formula- 10 using the suitable solvent.
  • the suitable solvent is same as defined in the first aspect of the present invention; in step-a) and b) the suitable base is same as defined in the first aspect of the present invention; in step-a) the suitable catalyst is same as defined in the first aspect of the present invention.
  • the seventh aspect of the present invention provides a novel process for the preparation of the compound of formula-7, comprising of;
  • step-a) to c) ' the suitable solvent is same as defined in the first aspect of the present invention; in step-a) & b) the suitable base is same as defined in the first aspect of the present invention.
  • the seventh aspect of the present invention is schematically represented as follows:
  • the eighth aspect of the present invention provides the purification of lauric acid compound of formula-3, comprising of;
  • the solvent is same as defined in the first aspect of the present invention; the suitable temperature is 30°C to reflux of the solvent used;
  • step-b) precipitating the compound optionally by adding an anti-solvent to the reaction mixture;
  • the suitable temperature is about -5°C to 30°C.
  • Preferred embodiment of the present invention provides the purification of lauric acid compound of formula-3, comprising;
  • Lauric acid compound of formula-3 prepared according to the present invention is most useful in the preparation of highly pure 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin- l - yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H-quinolin- l-yl)methyl dodecanoate compound of formula- 1.
  • novel intermediate compounds obtained according to the present invention are useful in the preparation of the compound of formula- 1.
  • Further aspect of the present invention provides novel process for the preparation of the compound of formula-1 as represented by the following schemes: Further aspect of the present invention provides a process for preparation of pure 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin- l -yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H-quinolin- l - yl)methyl dodecanoate compound of formula- 1 , comprising:
  • the suitable solvent is selected from alcohol solvents, ether solvents, ester solvent, chloro solvents, polar aprotic solvents, ketone solvents or mixtures thereof; preferably alcohol solvents, ketone solvents; the suitable temperature is 25°C to reflux temperature of the solvent used;
  • step-c) cooling the reaction mixture refers to the temperature range about - 10°C to 30°C
  • Preferred embodiment of the present invention provides a process for the preparation of pure 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin- l -yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H- quin0lin- l -yl)methyl dodecanoate compound of formula-1 , comprising:
  • Another preferred embodiment of the present invention provides a process for the preparation of pure 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin- l -y!]butoxy ⁇ -2-oxo-3,4-dihydro- 2H-quinolin-l -yl)methy! dodecanoate compound of formula- 1 , comprising:
  • step f) optionally repeating the process from steps-a) to e) to get the compound of formula- 1 , g) recrystallizing the compound obtained in step-e) or step-f) using a second solvent to provide pure compound of formula- 1 .
  • the first solvent is selected from alcohol solvents, ether solvents, ester solvent, chloro solvents, polar aprotic solvents, ketone solvents or mixtures thereof; preferably alcohol solvents; in step-a) the suitable temperature is 25°C to reflux temperature of the solvent used;
  • step-c) cooling the reaction mixture refers to the temperature range about - 10°C to 30°C.
  • step-g) the second solvent is selected from ketone solvents, preferably acetone.
  • Preferred embodiment of the present invention provides a process for preparation of pure 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l -yI]butoxy ⁇ -2-oxo-3,4-dihydro-2H-quinolin- l - yl)methyl dodecanoate compound of formula- 1 , comprising:
  • step-d) filtering the solid obtained in step-d) and washing with methanol, f) repeating the steps-a) to e) to get the compound of formula- 1 ,
  • step-e) recrystallizing the compound obtained in step-e) or step-f) using acetone to provide the pure compound of formula- 1 .
  • Further aspect of the present invention provides the compound of formula- 1 obtained according to the present invention having purity by HPLC >99%, preferably >99.5% which is having ⁇ 0.1 % of Aripiprazole & ⁇ 0. 1 % of N-Hydroxymethyl impurities.
  • Further aspect of the present invention provides particle size of 7- ⁇ 4-[4-(2,3- dichlorophenyl)-piperazin-l -yl]butoxy ⁇ -2-oxo-3,4-dihydro-2H-quinolin- l -yl)methyl dodecanoate compound of formula- l obtained according to the present invention havjng D(90) ⁇ 150 ⁇ m, D(50) ⁇ 50 ⁇ m and D(10) ⁇ 15 ⁇ m..
  • the compound of formula- l obtained according to the present invention is designated as crystalline form-I and its PXRD pattern is illustrated in figure-2 and is further characterized by its powder X-Ray diffraction pattern having peaks at 6.9, 8.5, 1 1.9, 13.3, 13.9, 14.8, 15.2, 18.2, 20.1 , 20.8, 21 .6, 22.1 , 23.9 & 25.0 ⁇ 0.2 degrees of 2-theta. Further it is having the endotherm at 84oC ⁇ 3°C in its differential scanning calorimetric (DSC) thermogram as shown in figure-3.
  • DSC differential scanning calorimetric
  • the crystalline form-I of the compound of formula- ] obtained according to the present invention having purity by HPLC >99%, preferably >99.5%.
  • a gas chromatographic system is equipped with FID.
  • Chloromethyl laurate and its related substances were analyzed by GC with the following chromatographic conditions:
  • a gas chromatographic system is equipped with FID.
  • Column HP-5 Capillery column; Length: 30 mts; Injection- temperature: 280°C; Detector temperature: 260°C; Carrier gas: Helium; Carrier gas pressure: l Opsi; Hydrogen flow: 40 ml/min; Air flow: 400 ml/min; Make up (N2): 30ml/min; Injection volume: 1 ⁇ ; Diluent: Acetonitrile.
  • a liquid chromatograph is equipped with variable wavelength UV Detector.
  • Mobile phase-A Buffer (100%); Mobile phase-B: Acetonitrile:Buffer:Methanol [80: 10: 10 v/v/v]
  • PXRD analysis of compound of formula- 1 produced by the present invention was carried out using BRUKER D8 ADVANCED/AXS X-Ray diffractometer using Cu K ⁇ radiation of wavelength 1.5406 A° and continuous scan speed of 0.03°/min.
  • DSC Differential scanning calorimetric
  • Example-1 Preparation of 7-(4-(4-(2,3-Dichlorophenyl)piperazin-l-yl)butoxy)-l- (hydroxymethyl)-3,4-dihydroquinolin-2(lH)-one compound of formula-7:
  • Aripiprazole 100 gm was added to the solution of chloromethyl laureate (416.1 1 gm) in 2500 ml of dichloromethane at 25-30°C and stirred the reaction mixture for 10 minutes.
  • Dimethylamino pyridine 13.4 gm
  • triethyl amine 93.2 ml was slowly added to the reaction mixture at 25-30°C and stirred for 22 hours at the same temperature.
  • Water was added to the reaction mixture at 25-30°C and stirred for 10 minutes. Separated the both aqueous and organic layers and the organic layer was washed with aqueous sodium chloride solution. Distilled off the solvent from the organic layer under reduced pressure and co- distilled with methanol. Recrystallized the obtained compound from methanol to get the title compound. Yield: 73 gm.
  • Example-11 Preparation of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l-yl] butoxy ⁇ -2-oxo- 3,4-dihydro-2H-quinolin-l-yl)methyl dodecanoate:
  • Potassium tertiary butoxide (37.5 gm) was added to the mixture of Aripiprazole ( 100 gm) and tetrahydrofuran ( 1000 ml) at -5 to 0°C.
  • Chloromethyl laurate ( 138.7 gm) was slowly added to the reaction mixture at -5 to 0°C and stirred for 3 hours at the same temperature.
  • Water and ethyl acetate were added to the reaction mixture. Raised the temperature of reaction mixture to 25-30°C and stirred for 30 minutes at the same temperature. Filtered the reaction mixture through hyflow bed and the obtained filtrate was stirred for 10 minutes at 25-30° C.
  • the other impurities i.e., Diamide Impurity, Tridecano Impurity, Tetradecano Impurity, Decano Impurity & Undecano Impurity are well below 0.05%.
  • Example-13 Purification of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l-yl]butoxy ⁇ -2-oxo- 3,4-dihydro-2H-quinolin-l-yl)methyl dodecanoate compound of formula-1 using acetone:
  • Example-14 Purification of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l-yl] butoxy ⁇ -2-oxo- 3,4-dihydro-2H-quinolin-l-yl)methyl dodecanoate using methanol :
  • Example-15 Purification of 7- ⁇ 4-[4-(2,3-dichlorophenyI)-piperazin-l-yl]butoxy ⁇ -2-oxo- 3,4-dihydro-2H-quinolin-l-yl)methyl dodecanoate using ethyl acetate:
  • Example-16 Purification of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l-yl]butoxy ⁇ -2-oxo- 3,4-dihydro-2H-quinolin-l-yl)methyl dodecanoate using isopropanol:
  • Example-17 Purification of 7- ⁇ 4-[4-(2,3-dichlorophenyl)-piperazin-l-yl]butoxy ⁇ -2-oxo- 3,4-dihydro-2H-quinoIin-l-yl)methyl dodecanoate using acetonitrile:

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Abstract

La présente invention concerne un procédé amélioré pour la préparation d'un composé de 7-{4-[4- (2,3-dichlorophényl)-pipérazin-1-yl]butoxy }-2 oxo-3,4-dihydro-2H-quinolin-1-yl)méthyl dodécanoate de formule -1, qui est représenté par la formule structurale suivante :
PCT/IN2017/000138 2016-12-07 2017-12-06 Procédé amélioré pour la préparation de 7-{4-[4-(2,3-dichlorophényl)-pipérazin-1-yl]butoxy}-2oxo-3,4-dihydro-2h-quinolin-1-yl)méthyl dodécanoate Ceased WO2018104953A1 (fr)

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IN201641041768 2016-12-07

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109096249A (zh) * 2018-08-13 2018-12-28 中国科学院兰州化学物理研究所 一种阿立哌唑的合成方法
WO2019020821A1 (fr) * 2017-07-28 2019-01-31 Interquim, S.A. Procédé de préparation d'aripiprazole lauroxil
CN110790704A (zh) * 2018-08-01 2020-02-14 北京万全德众医药生物技术有限公司 一种月桂酰阿立哌唑的制备方法
CN110790703A (zh) * 2018-08-01 2020-02-14 北京万全德众医药生物技术有限公司 月桂酰阿立哌唑的制备方法
WO2021009087A1 (fr) 2019-07-12 2021-01-21 Interquim, S.A. Procédé de préparation de lauroxil d'aripiprazole
CN114685367A (zh) * 2020-12-30 2022-07-01 上海现代药物制剂工程研究中心有限公司 一种月桂酰氧甲基阿立哌唑的制备方法
CN120481419A (zh) * 2025-07-15 2025-08-15 群力塑胶有限公司 一种具有低温热封性能的bopp薄膜及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4189571A (en) * 1978-02-07 1980-02-19 Fisons Limited Esters of cromoglycates
US8431576B2 (en) * 2009-06-25 2013-04-30 Alkermes Pharma Ireland Limited Heterocyclic compounds for the treatment of neurological and psychological disorders
US20160051546A1 (en) * 2014-08-25 2016-02-25 Alkermes Pharma Ireland Limited Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4189571A (en) * 1978-02-07 1980-02-19 Fisons Limited Esters of cromoglycates
US8431576B2 (en) * 2009-06-25 2013-04-30 Alkermes Pharma Ireland Limited Heterocyclic compounds for the treatment of neurological and psychological disorders
US20160051546A1 (en) * 2014-08-25 2016-02-25 Alkermes Pharma Ireland Limited Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MORTEN ROHDE ET AL.: "Biological conversion of aripiprazole lauroxil -An N-acyloxymethyl aripiprazole prodrug", PHARMA SCIENCES, vol. 4, 2014, pages 19 - 25, XP055218681 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111315722A (zh) * 2017-07-28 2020-06-19 因特奎姆私人控股公司 制备月桂酰阿立哌唑的方法
WO2019020821A1 (fr) * 2017-07-28 2019-01-31 Interquim, S.A. Procédé de préparation d'aripiprazole lauroxil
US12172979B2 (en) 2017-07-28 2024-12-24 Interquim, S.A. Process for the preparation of aripiprazole lauroxil
CN111315722B (zh) * 2017-07-28 2023-06-16 因特奎姆私人控股公司 制备月桂酰阿立哌唑的方法
CN110790703A (zh) * 2018-08-01 2020-02-14 北京万全德众医药生物技术有限公司 月桂酰阿立哌唑的制备方法
CN110790704A (zh) * 2018-08-01 2020-02-14 北京万全德众医药生物技术有限公司 一种月桂酰阿立哌唑的制备方法
CN109096249B (zh) * 2018-08-13 2021-04-09 中国科学院兰州化学物理研究所 一种阿立哌唑的合成方法
CN109096249A (zh) * 2018-08-13 2018-12-28 中国科学院兰州化学物理研究所 一种阿立哌唑的合成方法
WO2021009087A1 (fr) 2019-07-12 2021-01-21 Interquim, S.A. Procédé de préparation de lauroxil d'aripiprazole
JP2022543990A (ja) * 2019-07-12 2022-10-17 インタークイム，エス．エー． アリピプラゾールラウロキシルの調製のためのプロセス
US12312315B2 (en) 2019-07-12 2025-05-27 Interquim, S.A. Process for the preparation of aripiprazole lauroxil
JP7710435B2 (ja) 2019-07-12 2025-07-18 インタークイム，エス．エー． アリピプラゾールラウロキシルの調製のためのプロセス
CN114685367A (zh) * 2020-12-30 2022-07-01 上海现代药物制剂工程研究中心有限公司 一种月桂酰氧甲基阿立哌唑的制备方法
CN114685367B (zh) * 2020-12-30 2024-03-01 上海现代药物制剂工程研究中心有限公司 一种月桂酰氧甲基阿立哌唑的制备方法
CN120481419A (zh) * 2025-07-15 2025-08-15 群力塑胶有限公司 一种具有低温热封性能的bopp薄膜及其制备方法

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