120014-07-5

Usage

Uses

Used in Pharmaceutical Industry:
1-Benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylindenemethyl)piperidine is used as an impurity in the synthesis of Donepezil (D531750), a drug commonly prescribed for the treatment of Alzheimer's disease. Its presence as an impurity is crucial for the development and manufacturing process of Donepezil, ensuring the quality and efficacy of the final product.
Additionally, 1-Benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylindenemethyl)piperidine serves as an intermediate in the development of anti-Alzheimer's agents. Its unique chemical structure allows for further modification and optimization to create more effective drugs targeting the cognitive decline associated with Alzheimer's disease.

Synthesis

A solution of 5,6-dimethoxy-indanone (19 g, 0.10 mol) in methanol (8 mL) is stirred under inert atmosphere at room temperature. Slowly add NaOH flakes (12.8 g, 0.32 mol) followed by N-benzyl-piperidine-4-carboxaldehyde (20.2 g, 0.10 mol) to the reaction mixture. The mixture was stirred at room temperature for 3 h and progress of the reaction was monitored by TLC (hexane:ethyl acetate; 1:1). Once the reaction is complete, the solid formed was filtered, washed with 5 % acetic acid and then with methanol and dried. The obtained solid (34 g) was taken into a round bottom flask and refluxed with DMF (50 mL). Gradually cooled to room temperature and stirred for 2 h, filtered the solid formed, wash with chilled methanol to afford a pale yellow crystalline solid 1-Benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylindenemethyl)piperidine (32.0 g, 84 %); m.p.: 175-177 °C.

InChI:InChI=1/C24H27NO3/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18/h3-7,12,14-15,17H,8-11,13,16H2,1-2H3/b20-12+

Upstream product

• 22065-85-6 N-benzyl-4-formylpiperidine 
• 4693-38-3 3-chloro-1-(3,4-dimethoxyphenyl)propan-1-one 
• 197010-20-1 2-((1-benzyl-piperidin-4-yl)-hydroxymethyl)-5,6-dimethoxyindan-1-one 
• 67686-01-5 1-benzyl-4-piperidinemethanol 
• 24228-40-8 N-benzyl isonipecotic acid ethyl ester 
• 100-44-7 benzyl chloride 
• 1126-09-6 4-carbethoxypiperidine 
• 2107-69-9 5,6-dimethoxy-1-indanone 

Downstream Products

• 142057-77-0 donepezil hydrochloride 
• 120012-04-6 1-benzyl-4-[(5,6-dimethoxy-1-indanol)-2-yl]methylpiperidine 
• 120014-06-4 donepezil 
• 120014-30-4 debenzyldonepezil 

Relevant academic research and scientific papers

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.

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

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)

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.

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

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.

INDANONE INHIBITORS OF ACETYLCHOLINESTERASE

The present invention relates to new indanone inhibitors of acetylcholinesterase, pharmaceutical compositions thereof, and methods of use thereof.

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

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

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.