142057-79-2

Usage

Uses

Used in Pharmaceutical Research:
(RS)-2-[(1-BENZYL-4-PIPERIDYL)METHYL]-5,6-DIMETHOXYINDAN-1-ONE is used as a research chemical for investigating its potential psychoactive effects and interactions with the central nervous system. (RS)-2-[(1-BENZYL-4-PIPERIDYL)METHYL]-5,6-DIMETHOXYINDAN-1-ONE's structure, featuring a piperidine group and a benzyl group, indicates possible interactions with dopamine receptors, making it a valuable tool for studying the mechanisms of action and potential therapeutic applications in the field of neuroscience.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, (RS)-2-[(1-BENZYL-4-PIPERIDYL)METHYL]-5,6-DIMETHOXYINDAN-1-ONE serves as a novel chemical structure that may be further developed and optimized for specific therapeutic applications. Its potential interactions with dopamine receptors could be harnessed to design new drugs targeting neurological and psychiatric disorders, pending further research and understanding of its pharmacological properties.
Used in Drug Design and Development:
(RS)-2-[(1-BENZYL-4-PIPERIDYL)METHYL]-5,6-DIMETHOXYINDAN-1-ONE is used as a starting point for drug design and development, particularly in the search for new compounds with potential applications in treating neurological and psychiatric conditions. Its unique structure and potential receptor interactions make it an interesting candidate for further exploration and modification to enhance its therapeutic potential and selectivity.
Used in Toxicology and Safety Assessment:
As a synthetic compound with potential psychoactive effects, (RS)-2-[(1-BENZYL-4-PIPERIDYL)METHYL]-5,6-DIMETHOXYINDAN-1-ONE is also used in toxicology and safety assessment studies. These studies aim to evaluate the compound's safety profile, potential side effects, and risks associated with its use, ensuring that any future therapeutic applications are developed with a comprehensive understanding of its safety and potential hazards.

Upstream product

• 100-39-0 benzyl bromide 
• 120014-30-4 debenzyldonepezil 
• 145546-80-1 (E)-2-((1-benzylpiperidine-4-yl)methylene)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one 
• 142057-77-0 donepezil hydrochloride 
• 100-44-7 benzyl chloride 
• 100-52-7 benzaldehyde 
• 120013-38-9 2-((1-benzoylpiperidin-4-yl)methyl)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one 
• 120012-04-6 1-benzyl-4-[(5,6-dimethoxy-1-indanol)-2-yl]methylpiperidine 
• 61203-48-3 2-iodo-4,5-dimethoxybenzoic acid 
• 173043-61-3 2-iodo-4,5-dimethoxybenzoic acid methyl ester 
• 100-51-6 benzyl alcohol 
• 2107-69-9 5,6-dimethoxy-1-indanone 
• 67686-01-5 1-benzyl-4-piperidinemethanol 
• 24228-40-8 N-benzyl isonipecotic acid ethyl ester 

Downstream Products

• 142057-77-0 L-donepezil hydrochloric acid 
• 142057-77-0 D-donepezil hydrochloric acid 

Relevant academic research and scientific papers

Steady-state plasma concentration of donepezil enantiomers and its stereoselective metabolism and transport in vitro

The aim of the present study was to elucidate the differences in the plasma concentration of two enantiomers of donepezil in Chinese patients with Alzheimer's disease (AD) and investigate in vitro stereoselective metabolism and transport. Donepezil enantiomers were separated and determined by LC-MS/MS using D5-donepezil as an internal standard on a Sepax Chiralomix SB-5 column. In vitro stereoselective metabolism and transport of donepezil were investigated in human liver microsomes and MDCKII-MDR1 cell monolayer. Pre-dose (Css-min) plasma concentrations were determined in 52 patients. The mean plasma level of (R)-donepezil was 14.94 ng/ml and that of (S)-donepezil was 23.37 ng/ml. One patient's plasma concentration of (R)-donepezil was higher than (S)-donepezil and the ratio is 1.51. The mean plasma levels of (S)-donepezil were found to be higher than those of (R)-donepezil in 51 patients and the ratio of plasma (R)- to (S)-donepezil varies from 0.34 to 0.85. In the in vitro microsomal system, (R)-donepezil degraded faster than (S)-donepezil. Vmax of (R)-donepezil was significantly higher than (S)-donepezil. The P-gp inhibition experiment shown that the Papp of the two enantiomers was higher than 200 and the efflux ratios were 1.11 and 0.99. The results of the P-gp inhibition identification experiment showed IC50 values of 35.5 and 20.4 μM, respectively, for the two enantiomers. The results indicate that donepezil exhibits stereoselective hepatic metabolism that may explain the differences in the steady-state plasma concentrations observed. Neither (R)- nor (S)-donepezil was a P-gp substance and the two enantiomers are highly permeable through the blood-brain barrier. 2013 Wiley Periodicals, Inc.

Bisulfite Addition Compounds as Substrates for Reductive Aminations in Water

Highly valued products resulting from reductive aminations utilizing shelf-stable bisulfite addition compounds of aldehydes can be made under aqueous micellar catalysis conditions. Readily available α-picolineborane serves as the stoichiometric hydride source. Recycling of the aqueous reaction medium is easily accomplished, and several applications to targets in the pharmaceutical industry are documented.

A metal-free method for the facile synthesis of indanonesviathe intramolecular hydroacylation of 2-vinylbenzaldehyde

A facile method for the synthesis of indanones was developed under metal- and additive-free conditions, whereinl-proline served as an efficient and environmentally benign catalyst. Compared with previously synthesized indanones, synthesis by the transition-metal-catalyzed intramolecular hydroacylation of 2-vinylbenzaldehyde provided a more green synthetic pathway to indanone scaffolds with good to excellent yields. More importantly, it could be used to synthsize the anti-AD drug donepezil.

METHOD FOR PRODUCING DONEPEZIL BY FLOW REACTION USING IMMOBILIZED CATALYST

PROBLEM TO BE SOLVED: To provide a method for producing donepezil in which, as the required amount can be produced when required while precisely controlling the reaction time and temperature, and the post-reaction neutralization, separation operation, intermediate isolation and purification steps can be omitted, the labor force and operation time can be significantly reduced. SOLUTION: Provided is a method for producing donepezil, including a step of Aldol condensation for yielding 1-benzyl-4-[(5,6-dimethoxy-1-indanone)-2-yliden] methylpiperidine by Aldol condensation reacting 5,6-dimethoxy-1-indanone and 1-benzyl-4-formylpiperidin, and a step of hydrogenation for yielding donepezil by hydrogenation reacting 1-benzyl-4-[(5,6-dimethoxy-1-indanone)-2-yliden] methylpiperidine, and in which at least one of the aldol condensation step and the hydrogenation step is continuously carried out by a flow method using a reactor in which the catalyst is immobilized. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPO&INPIT

Method for synthesizing donepezil in water

The invention discloses a method for synthesizing donepezil. The method comprises the following steps: adding 5,6-dimethoxyindanone, (1-benzyl-4-piperidyl)methanol, a metal iridium catalyst and potassium hydroxide into a reaction vessel, carrying out heating for a reaction for several hours, the carrying out cooling to room temperature, spin-drying a solvent, and carrying out column separation toobtain the target compound. According to the method, under the catalytic action of the metal iridium catalyst, 5,6-dimethoxyindanone reacts with (1-benzyl-4-piperidyl)methanol to directly synthesize donepezil; a commercialized reagent is used as a raw material for the reaction, and alcohol is an environment-friendly and low-toxicity chemical reagent; a by-product of the reaction water, so environmental pollution is avoided; the atom economy of the reaction is high; and reaction is conducted in water. Therefore, the reaction meets the requirements of green chemistry and has a wide development prospect.

Can Heteroarenes/Arenes Be Hydrogenated Over Catalytic Pd/C Under Ambient Conditions?

Hydrogenation of over a dozen aromatic compounds, including both heteroarenes and arenes, over palladium on carbon (Pd/C, 1–100 molpercent) with H2-balloon pressure at room temperature is reported. Analyses using pyridine as a model substrate revealed that acetic acid was the best solvent, as using only 1 molpercent Pd/C provided piperidine quantitatively. Substrate scope analysis and density functional theory calculations indicated that reaction rates are highly dependent on frontier molecular orbital characteristics and the steric bulkiness of substituents. Moreover, the established method was used for the concise synthesis of the anti-Alzheimer drug donepezil (Aricept?).

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.

The α-alkylation of ketones with alcohols in pure water catalyzed by a water-soluble Cp?Ir complex bearing a functional ligand

A water-soluble dinuclear Cp?Ir complex bearing 4,4′,6,6′-tetrahydroxy-2,2′-bipyrimidine as a bridging ligand was found to be a highly effective catalyst for the α-alkylation of ketones with alcohols in pure water. In the presence of catalyst (0.5 mol%), a series of desirable products were obtained with high reaction economy under environmentally benign conditions. The importance of the hydroxy group in the ligand for catalytic hydrogen transfer was confirmed by mechanism experiments. Furthermore, the application of this catalytic system for the synthesis of a biologically active molecule donepezil in pure water has been accomplished. Notably, this research would facilitate the progress of C-C bond-forming reactions in water catalyzed by water-soluble metal-ligand bifunctional catalysts.

Iron-Catalyzed Ligand Free α-Alkylation of Methylene Ketones and β-Alkylation of Secondary Alcohols Using Primary Alcohols

Herein, we demonstrate a general and broadly applicable catalytic cross coupling of methylene ketones and secondary alcohols with a series of primary alcohols to disubstituted branched ketones. A simple and nonprecious Fe2(CO)9 catalyst enables one-pot oxidations of both primary and secondary alcohols to a range of branched gem-bis(alkyl) ketones. A number of bond activations and formations selectively occurred in one pot to provide the ketone products. Coupling reactions can be performed in gram scale and successfully applied in the synthesis of an Alzehimer's drug. Alkylation of a steroid hormone can be achieved. A single catalyst enables sequential one-pot double alkylation to bis-hetero aryl ketones using two different alcohols. Preliminary mechanistic studies using an IR probe, deuterium labeling, and kinetic experiments established the participation of a borrowing-hydrogen process using Fe catalyst, and the reaction produces H2 and H2O as byproducts.

Purification method for Donepezil

The invention relates to a purification method for Donepezil and belongs to the technical field of preparation of raw pharmaceutical materials. The purification method for the Donepezil or pharmaceutically acceptable salts thereof, provided by the invention, comprises the steps: firstly, adding a hydrophobic organic solvent and water into the Donepezil or pharmaceutically acceptable salts thereof,so as to obtain a mixed solution, wherein the hydrophobic organic solvent is selected from dichloromethane, ethyl acetate, toluene and mixtures thereof; adjusting an aqueous phase pH of the mixed solution to be not smaller than 9 with alkali, and separating an organic phase from an aqueous phase; and subjecting the organic phase obtained in the step (3) to depressurized concentration, thereby obtaining purified Donepezil. According to the purification method for the Donepezil or pharmaceutically acceptable salts thereof, provided by the invention, high-quality raw pharmaceutical materials areprovided for preparations.