145546-80-1

Usage

Uses

Used in Pharmaceutical Industry:
2-[(E)-(1-BENZYL-4-PIPERIDINYL)METHYLIDENE]-5,6-DIMETHOXY-1-INDANONE is used as a nootropic agent for enhancing cognitive function and memory. Its structure is derived from Donepezil, a known acetylcholinesterase inhibitor, which suggests that it may have similar mechanisms of action in improving cognitive performance.
Used in Research and Development:
In the field of medicinal chemistry, 2-[(E)-(1-BENZYL-4-PIPERIDINYL)METHYLIDENE]-5,6-DIMETHOXY-1-INDANONE serves as a valuable research tool for understanding the structure-activity relationships of nootropic agents and acetylcholinesterase inhibitors. It can be used to develop new drugs with improved efficacy and fewer side effects.
Used in Drug Synthesis:
As a derivative of Donepezil, 2-[(E)-(1-BENZYL-4-PIPERIDINYL)METHYLIDENE]-5,6-DIMETHOXY-1-INDANONE may be utilized in the synthesis of novel drugs with potential applications in the treatment of Alzheimer's disease and other cognitive disorders. Its unique structure could provide new insights into the design of more effective therapeutic agents.

Upstream product

• 2107-69-9 5,6-dimethoxy-1-indanone 
• 22065-85-6 N-benzyl-4-formylpiperidine 
• 1126-09-6 4-carbethoxypiperidine 
• 100-44-7 benzyl chloride 
• 24228-40-8 N-benzyl isonipecotic acid ethyl ester 
• 67686-01-5 1-benzyl-4-piperidinemethanol 
• 4693-38-3 3-chloro-1-(3,4-dimethoxyphenyl)propan-1-one 
• 2747-08-2 2-bromo-5,6-dimethoxy-1-indanone 
• 100-52-7 benzaldehyde 
• 134256-32-9 N-benzyl-2-(2-hydroxyethyl)piperidine 
• 77034-34-5 ethyl N-benzylpipecolinate 
• 1025909-53-8 (1-benzylpiperidin-2-yl)acetaldehyde 
• 2107-70-2 3,4-methoxycinnamic acid 
• 197010-20-1 2-((1-benzyl-piperidin-4-yl)-hydroxymethyl)-5,6-dimethoxyindan-1-one 

Relevant academic research and scientific papers

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)

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

Basic Anion-Exchange Resin-Catalyzed Aldol Condensation of Aromatic Ketones with Aldehydes in Continuous Flow

A general method for the aldol condensation of aromatic ketones with aldehydes was developed under continuous-flow conditions using a commercially available, strongly basic anion-exchange resin (A26) as catalyst. This procedure, in addition to exhibiting a wide substrate scope, promoted carbon-carbon bond formation under mild conditions using a quasi-stoichiometric ratio of starting reagents with good to excellent yields, thereby forming a limited amount of waste and allowing the process to be applied to sequential-flow systems. A proof of concept was developed in the first fully heterogeneously catalyzed two-step flow synthesis of donepezil, which is a blockbuster commercial anti-Alzheimer's drug.

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.

Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil

A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil. The most active analogue 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (67) afforded an in vitro IC50value of 0.03 ± 0.07 μM against acetylcholinesterase with no cytotoxicity observed (IC50of >100 μM, SH-SY5Y cell line). In comparison donepezil had an IC50of 0.05 ± 0.06 μM and an observed cytotoxicity IC50of 15.54 ± 1.12 μM. Molecular modelling showed a strong correlation between activity and in silico binding in the active site of acetylcholinesterase.

Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors

An ecofriendly synthetic pathway for the synthesis of donepezil precursors is described. Alternative energy sources were used for the total synthesis in order to improve yields, regioselectively, and rate of each synthetic step and to reduce the coproduction of waste at the same time. For all products, characterized by an improved structural rigidity respect to donepezil, the inhibitor activity on AChE, the selectivity vs BuChE, the side-activity on BACE-1, and the effect on SHSY-5Y neuroblastoma cells viability were tested. Two potential new lead compounds for a dual therapeutic strategy against Alzheimers disease were envisaged.

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

Part I: The development of the catalytic wittig reaction

We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The utilization of an organosilane was pivotal for success as it allowed for the chemoselective reduction of a phosphane oxide. Protocol optimization evaluated the phosphane oxide precatalyst structure, loading, organosilane, temperature, solvent, and base. These studies demonstrated that to maintain viable catalytic performance it was necessary to employ cyclic phosphane oxide precatalysts of type 1. Initial substrate studies utilized sodium carbonate as a base, and further experimentation identified N,N-diisopropylethylamine (DIPEA) as a soluble alternative. The use of DIPEA improved the ease of use, broadened the substrate scope, and decreased the precatalyst loading. The optimized protocols were compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl, and thienyl) aldehydes to produce both di- and trisubstituted olefins in moderate-to-high yields (60-96 %) by using a precatalyst loading of 4-10 mol %. Kinetic E/Z selectivity was generally 66:34; complete E selectivity for disubstituted α,β-unsaturated products was achieved through a phosphane-mediated isomerization event. The CWR was applied to the synthesis of 54, a known precursor to the anti-Alzheimer drug donepezil hydrochloride, on a multigram scale (12.2 g, 74 % yield). In addition, to our knowledge, the described CWR is the only transition-/heavy-metal-free catalytic olefination process, excluding proton-catalyzed elimination reactions. A point of difference: By utilizing an organosilane to chemoselectively reduce a phosphane oxide precatalyst to a phosphane (see scheme), the first catalytic (in phosphane) Wittig reaction has been developed. The methodology has been applied to the synthesis of 22 disubstituted and 24 trisubstituted olefins, including a multigram synthesis of a precursor to the anti-Alzheimer drug donepezil hydrochloride.

Method for making donepezil

The method in accordance with the present invention has: mixing E2M, an organic solvent, a weak base, sodium dithionite, and a phase transfer catalyst to obtain an E2M mixture solution; heating the E2M mixture solution and adding water to obtain a heated E2M aqueous solution having an organic layer; and extracting the organic layer from the heated E2M aqueous solution, and condensing and drying the organic layer to obtain donepezil. Employing sodium dithionite as a reducing agent improves safety over hydrogen gas used in conventional methods and lowers the cost in contrast to the conventional noble metal catalysts that are extremely expensive. Furthermore, the method of the present invention requires only 60 minutes of reaction time to synthesize donepezil with a promising yield more than 85%, which greatly raises the efficiency and economic value of the manufacture of donepezil.

Method For Making Donepezil

The method in accordance with the present invention has: mixing E2M, an organic solvent, a weak base, sodium dithionite, and a phase transfer catalyst to obtain an E2M mixture solution; heating the E2M mixture solution and adding water to obtain a heated E2M aqueous solution having an organic layer; and extracting the organic layer from the heated E2M aqueous solution, and condensing and drying the organic layer to obtain donepezil. Employing sodium dithionite as a reducing agent improves safety over hydrogen gas used in conventional methods and lowers the cost in contrast to the conventional noble metal catalysts that are extremely expensive. Furthermore, the method of the present invention requires only 60 minutes of reaction time to synthesize donepezil with a promising yield more than 85%, which greatly raises the efficiency and economic value of the manufacture of donepezil.