AR098504A1 - PROCEDURE FOR THE PREPARATION OF DONEPEZYL CHLORHYDRATE FORMS I AND III; AND OF AN INTERMEDIARY COMPOUND OF THE SAME - Google Patents

PROCEDURE FOR THE PREPARATION OF DONEPEZYL CHLORHYDRATE FORMS I AND III; AND OF AN INTERMEDIARY COMPOUND OF THE SAME

Info

Publication number
AR098504A1
AR098504A1 ARP140104381A ARP140104381A AR098504A1 AR 098504 A1 AR098504 A1 AR 098504A1 AR P140104381 A ARP140104381 A AR P140104381A AR P140104381 A ARP140104381 A AR P140104381A AR 098504 A1 AR098504 A1 AR 098504A1
Authority
AR
Argentina
Prior art keywords
formula
donepezil hydrochloride
preparation
temperature
iii
Prior art date
Application number
ARP140104381A
Other languages
Spanish (es)
Inventor
Lzaro Llanes Garca Ariel
De Castro Pacheco Ogari
Original Assignee
Cristália Produtos Químicos Farmacêuticos Ltda
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 Cristália Produtos Químicos Farmacêuticos Ltda filed Critical Cristália Produtos Químicos Farmacêuticos Ltda
Publication of AR098504A1 publication Critical patent/AR098504A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

La presente solicitud se refiere a un procedimiento eficiente e industrialmente viable para la preparación de clorhidrato de donepezilo en las formas cristalinas comerciales, Formas I y III, con alta pureza y de manera selectiva. La presente solicitud se refiere también a un procedimiento para la preparación de un compuesto intermediario útil en la preparación de clorhidrato de donepezilo. Reivindicación 1: Procedimiento para la preparación del clorhidrato de donepezilo monohidratado, Forma I, representado por la fórmula (1) caracterizado por comprender las etapas de: (a) reacciones concomitantes de reducción del doble enlace a,b-carbonilo exocíclico y desbencilación del compuesto 1-bencil-4-[(5,6-dimetoxi-1-indanon-2-ilideno)metil]piperidina de fórmula (2); en presencia del catalizador metálico de paladio 10% sobre carbono y de un agente de transferencia de hidrógeno, en un disolvente orgánico, o mezcla de un disolvente orgánico con agua, a una temperatura de 53 - 63ºC; seguido por el tratamiento del medio de reacción con ácido clorhídrico concentrado para obtener el compuesto intermediario clorhidrato de 5,6-dimetoxi-2-[(piperidin-4-il)metil]indan-1-ona, representado por la fórmula (3); b) reacción de bencilación del intermediario de fórmula (3) con un derivado de bencilo representado por la fórmula (4) en la que X representa un grupo saliente seleccionado del grupo que consiste de cloruro, bromuro, ioduro, tosilato y mesilato; en presencia de una base y de un catalizador de transferencia de fases, en una mezcla heterogénea de disolventes constituida por agua y un dialquil éter, en una proporción de 1:1 a 1:10, a una temperatura de 30ºC a 80ºC, obteniéndose donepezilo en forma de base libre, el cual se disuelve en acetato de etilo o de isopropilo, seguido por tratamiento de la solución con ácido clorhídrico concentrado para la obtención de clorhidrato de donepezilo, Forma III, representado por la fórmula (5); c) conversión del clorhidrato de donepezilo anhidro, Forma III, en clorhidrato de donepezilo monohidratado, Forma I, mediante la disolución del clorhidrato de donepezilo en 3 - 6 partes de metanol que contiene de 2% a 20% de agua, a una temperatura entre 40ºC y 65ºC, seguido por enfriamiento de la solución hidroalcohólica a temperatura ambiente, y la adición lenta de la solución sobre 15 - 25 partes del antidisolvente etil terc-butil éter, agitado a una temperatura de 0ºC a 12ºC.The present application refers to an efficient and industrially viable process for the preparation of donepezil hydrochloride in commercial crystalline forms, Forms I and III, with high purity and selectively. The present application also relates to a process for the preparation of an intermediate compound useful in the preparation of donepezil hydrochloride. Claim 1: Process for the preparation of donepezil hydrochloride monohydrate, Form I, represented by the formula (1) characterized by comprising the steps of: (a) concomitant reactions of reduction of the double bond a, exocyclic b-carbonyl and debenzylation of the compound 1-Benzyl-4 - [(5,6-dimethoxy-1-indanon-2-ylidene) methyl] piperidine of formula (2); in the presence of the 10% palladium metal catalyst on carbon and a hydrogen transfer agent, in an organic solvent, or mixture of an organic solvent with water, at a temperature of 53-63 ° C; followed by treatment of the reaction medium with concentrated hydrochloric acid to obtain the intermediate compound 5,6-dimethoxy-2 - [(piperidin-4-yl) methyl] indan-1-one hydrochloride, represented by the formula (3) ; b) benzylation reaction of the intermediate of formula (3) with a benzyl derivative represented by formula (4) in which X represents a leaving group selected from the group consisting of chloride, bromide, iodide, tosylate and mesylate; in the presence of a base and a phase transfer catalyst, in a heterogeneous mixture of solvents consisting of water and a dialkyl ether, in a ratio of 1: 1 to 1:10, at a temperature of 30 ° C to 80 ° C, obtaining donepezil in the form of a free base, which is dissolved in ethyl acetate or isopropyl, followed by treatment of the solution with concentrated hydrochloric acid to obtain donepezil hydrochloride, Form III, represented by the formula (5); c) conversion of anhydrous donepezil hydrochloride, Form III, to donepezil hydrochloride monohydrate, Form I, by dissolving donepezil hydrochloride in 3-6 parts of methanol containing 2% to 20% water, at a temperature between 40 ° C and 65 ° C, followed by cooling the hydroalcoholic solution to room temperature, and the slow addition of the solution over 15-25 parts of the ethyl tert-butyl ether antisolvent, stirred at a temperature of 0 ° C to 12 ° C.

ARP140104381A 2013-11-29 2014-11-21 PROCEDURE FOR THE PREPARATION OF DONEPEZYL CHLORHYDRATE FORMS I AND III; AND OF AN INTERMEDIARY COMPOUND OF THE SAME AR098504A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
BR102013030928A BR102013030928A2 (en) 2013-11-29 2013-11-29 process for the preparation of donepezil hydrochloride forms i and iii; and an intermediate compound thereof

Publications (1)

Publication Number Publication Date
AR098504A1 true AR098504A1 (en) 2016-06-01

Family

ID=53680522

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP140104381A AR098504A1 (en) 2013-11-29 2014-11-21 PROCEDURE FOR THE PREPARATION OF DONEPEZYL CHLORHYDRATE FORMS I AND III; AND OF AN INTERMEDIARY COMPOUND OF THE SAME

Country Status (3)

Country Link
AR (1) AR098504A1 (en)
BR (1) BR102013030928A2 (en)
WO (1) WO2015109377A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110183374A (en) * 2018-12-31 2019-08-30 山东诚汇双达药业有限公司 A kind of preparation method of Doneppezil Hydrochloride intermediate
CN110540520B (en) * 2019-09-12 2022-02-08 迪嘉药业集团有限公司 Method for purifying donepezil

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006015338A2 (en) * 2004-07-30 2006-02-09 Dr. Reddy's Laboratories Ltd. Crystalline form of donepezil hydrochloride
HU227474B1 (en) * 2005-12-20 2011-07-28 Richter Gedeon Nyrt Process for industrial scale production of high purity donepezil hydrochloride polymorph i.
BRPI0720211A2 (en) * 2006-12-11 2013-12-24 Reviva Pharmaceuticals Inc INDANONE DERIVATIVE, COMPOSITION, AND, USE OF A COMPOSITION

Also Published As

Publication number Publication date
WO2015109377A1 (en) 2015-07-30
BR102013030928A2 (en) 2015-09-22

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