- An improved and efficient process for the production of donepezil hydrochloride: Substitution of sodium hydroxide for n-butyl lithium via phase transfer catalysis
-
A simple, efficient and highly economic process for the production of donepezil hydrochloride (1), an anti-Alzheimer drug is reported. The process relies upon improved and large-scale synthesis of a key intermediate: 1-benzylpiperidine-4-carboxaldehyde (2), and the introduction of operationally simple chemistry at the penultimate stage wherein 2 is reacted with 5,6-dimethoxy indanone (3) in the presence of sodium hydroxide and a phase transfer catalyst (PTC) in a biphasic solvent to furnish the intermediate 4, which is reduced and directly treated with hydrochloric acid to furnish highly pure donepezil hydrochloride with desired polymorphic form. The improved process provides donepezil hydrochloride at considerably lower cost and allows the omission of hazardous chemicals.
- Niphade, Navanath,Mali, Anil,Jagtap, Kunal,Ojha, Ramesh Chandra,Vankawala, Pravinchandra J.,Mathad, Vijayavitthal T.
-
-
Read Online
- Purification method of donepezil hydrochloride key intermediate compound (by machine translation)
-
The invention discloses a purification method of a donepezil hydrochloride key intermediate compound, and the crude molecular formula of the compound (I) is shown in the specification. Solid potassium fluoride (KFFFAl) on alumina2 O3 In the presence C6 -C12 In the aromatic hydrocarbon-containing organic solvent, the reaction 70 - 110 °C is stirred at 0.5 - 3h to obtain a high-purity compound (I), in C. 6 -C12 The benzene-containing aromatic hydrocarbon organic solvent is selected from benzene, toluene and xylene, is simple and convenient to operate, high in yield and good in product purity, and is suitable for industrial production. (by machine translation)
- -
-
Paragraph 0031-0037
(2020/08/17)
-
- Synthetic method of donepezil hydrochloride
-
The invention belongs to the technical field of medicines, and discloses a synthetic method of donepezil hydrochloride. The method comprises the following steps: taking 5, 6-dimethoxy-1-indanone and 4-pyridylaldehyde as initial raw materials, generating a
- -
-
Paragraph 0034-0039; 0052-0059
(2020/05/14)
-
- Industrially scalable synthesis of anti-alzheimer drug donepezil
-
This paper describes a simple, efficient and industrially scalable total synthesis of donepezil hydrochloride. The article also reported the X-ray studies of the 2-(1-benzylpiperidin-4-ylmethyliden)-5,6-dimethoxyindan-1-one, an intermediate in the synthesis of donepezil. The crystal structure analysis of 2-(1-benzylpiperidin-4-ylmethyliden)-5,6-dimethoxyindan-1-one shows that it crystallizes in monoclinic class under the space group P121/c1 with cell parameters, a = 17.2992(7) ?, b = 10.1999(4) ?, c = 11.9539(5) ?, β = 103.450(2)°, V = 2051.42(15) ?3 and Z = 4.
- Gaonkar, Santosh L.,Nadaf,Bilehal, Dinesh,Shetty, Nitinkumar S.
-
p. 1999 - 2004
(2017/07/27)
-
- Preparation method of donepezil hydrochloride
-
The invention discloses a preparation method of donepezil hydrochloride. The preparation method comprises the steps that 3-chlorine-1-(3, 4-dimethoxy phenyl) propane-1-ketone (II) is made to react with N-benzyl-4-formyl-piperidine (III) under the conditio
- -
-
Paragraph 0039; 0042; 0043
(2016/10/17)
-
- A PROCESS FOR THE PREPARATION OF DONEPEZIL HYDROCHLORIDE
-
The present invention is directed to an improved industrially viable, cost effective process for manufacturing 1 -benzyl-4-(5,6,-dimethoxyindanone-2-yl)methylpiperidine hydrochloride commonly known as donepezil hydrochloride in a substantially pure form with a purity level of greater than 99.9% and a novel crystalline form of 1- benzyl-4-(5,6,-dimethoxyindanone-2-yI)methylpiperidine in a substantially pure form.
- -
-
Page/Page column 9-10
(2011/05/11)
-
- INDANONE INHIBITORS OF ACETYLCHOLINESTERASE
-
The present invention relates to new indanone inhibitors of acetylcholinesterase, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 15
(2010/06/19)
-
- Synthesis and Preparations of Intermediates and New Polymorphs Thereof Useful For The Preparation Of Donepezil Hydrochlcoride
-
The invention relates to an improved process for preparing 2-(1-benzylpiperidin-4-ylmethyliden)-5,6-dimethoxyin-dan-1-one (a key intermediate in the synthesis of donepezil hydrochloride), crystalline polymorph forms of this key intermediate and their use
- -
-
Page/Page column 3
(2009/10/18)
-
- PROCESS FOR PRODUCING 1-BENZYL-4-[(5,6-DIMETHOXY-1-INDANONE)-2-YLIDENE]METHYLPIPERIDINE
-
It is intended to provide a process for producing 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-ylidene]methylpiperidine represented by the structural formula (I): (I) which is useful as an intermediate material for a pharmaceutical or a solvate thereof in whic
- -
-
Page/Page column 11-12
(2008/06/13)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF DONEPEZIL
-
An improved, novel and simple industrial process for the preparation of Donepezil of formula (I) and its pharmaceutically acceptable salts manufactured by the condensation of 5,6-dimethoxy indanone of formula (III) with 1-benzyl-4-piperidine carboxaldehyde of formula (IV) to give 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-ylidenyl] methyl piperidine in the presence of base in organic solvents or an aqueous solvent or mixture thereof followed by the reduction carried out using at least one metal borohydride in the presence of catalytic amount of cobalt salts and suitable solvent or mixture thereof.
- -
-
Page/Page column 17
(2008/06/13)
-
- PROCESS AND INTERMEDIATE FOR PREPARATION OF DONEPEZIL
-
The invention relates to new compounds of formula (III): wherein R is a C1-C4 linear or branched alkyl group. The invention also relates to new compounds of formula (IV) wherein M is a metal. The invention also relates to methods of making compounds of formulas (III) and (IV) and to methods of making donepezil and pharmaceutically acceptable salts thereof, such as donepezil hydrochloride, using the compounds.
- -
-
Page/Page column 8; 10
(2008/06/13)
-
- PROCESS FOR THE PREPARATION OF HIGHLY PURE DONEPEZIL
-
The present invention relates to the preparation of highly pure donepezil of formula I or salt thereof, by hydrogenating indanonylidenyl compound of formula II, using platinum catalysts.
- -
-
Page/Page column 12-13
(2008/06/13)
-
- Process for the preparation of donepezil hydrochloride
-
The present invention relates to an improved process for the preparation of 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride of Formula I.
- -
-
Page/Page column 3
(2008/06/13)
-
- NERVE REVENERATION PROMOTER
-
A nerve regeneration stimulator comprising a compound having a cholinesterase inhibitory activity, a pharmacologically acceptable salt thereof or a solvate thereof.
- -
-
Page/Page column 31-32
(2010/11/27)
-
- Therapeutic agent for overactive bladder resulting from cerebral infarction
-
An agent for treating overactive bladder resulting from cerebral infarction, comprising administrating a compound having a cholinesterase inhibitory activity or a pharmacologically acceptable salt thereof.
- -
-
Page/Page column 1.b
(2008/06/13)
-
- Therapeutic agent for overactive bladder involved in aging
-
A method for treating overactive bladder involved in aging, comprising administrating a compound having a cholinesterase inhibitory activity, a pharmacologically acceptable salt or a solvate thereof to a patient with the overactive bladder involved in aging.
- -
-
Page/Page column 18
(2010/11/08)
-
- Synthesis and structure-activity relationships of acetylcholinesterase inhibitors: 1-Benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine hydrochloride and related compounds
-
Following the discovery of a new series of anti-acetylcholinesterase (anti-AChE) inhibitors such as 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine (1), we reported that its rigid analogue, 1-benzyl-4-(2-isoindolin-2- ylethyl)piperidine (5), had more potent activity. We have extended the structure-activity relationship (SAR) study for the rigid analogue and found that the 2-isoindoline moiety in compound 5 can be replaced with a indanone moiety (8) without a major loss in potency. Among the indanone derivatives, 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (13e) (E2020) (IC50 = 5.7 nM) was found to be one of the most potent anti-AChE inhibitors. Compound 13e showed a selective affinity 1250 times greater for AChE than for butyrylcholinesterase. In vivo studies demonstrated that 13e has a longer duration of action than physostigmine at a dose of 5 mg/kg (po) and produced a marked and significant increase in acetylcholine content in rat cerebral cortex. We report the synthesis, SAR, and a proposed hypothetical binding site of 13e (E2020).
- Sugimoto,Iimura,Yamanishi,Yamatsu
-
p. 4821 - 4829
(2007/10/03)
-