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Donepezil synthesis method

A synthetic method, the technology of donepezil, which is applied in the field of organic compound synthesis and application, can solve the problems of cumbersome process and low efficiency, and achieve the effects of improving reaction efficiency, easy handling, and shortening reaction time

Active Publication Date: 2018-04-13
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, there are many ways to synthesize donepezil, but the process is too cumbersome and the efficiency is not high

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] The synthetic method of donepezil of the present embodiment, steps are as follows:

[0022] In a 15 ml Schlenk tube, add 76.88 mg (0.4 mmol) 5,6-dimethoxyindanone, 90.33 mg (0.44 mmol) 1-benzyl-4-piperidinemethanol, 53.26 mg (0.5 equiv) Potassium phosphate hydrate, 0.5 ml toluene, magnetic stirring under argon atmosphere, and react at 120°C for 12 h. After TLC analysis, No Reaction.

Embodiment 2

[0024] The synthetic method of donepezil of the present embodiment, steps are as follows:

[0025] In a 15 ml Schlenk tube, add 76.88 mg (0.4 mmol) 5,6-dimethoxyindanone, 82.1 mg (0.4 mmol) 1-benzyl-4-piperidinemethanol, 1.55 mg (0.5 mol%) Pincer metal ruthenium (II) compound, 11.61 mg (0.25 equiv) sodium phenoxide, 0.5 ml toluene, magnetic stirring under argon atmosphere, react at 120°C for 12 h. According to TLC analysis, the raw materials had been completely reacted. Vacuum rotary evaporation, separation and purification by thin layer chromatography, the quality of the product donepezil was 100.71 mg, and the yield was 66%.

[0026] product by 1 H NMR, 13 Confirmed by C NMR. 1 H NMR (400 MHz, CDCl 3 ) δ 7.32-7.22 (m, 5H),7.16 (s, 1H), 6.84 (s, 1H), 3.94 (s, 3H), 3.88 (s, 3H), 3.50 (s, 2H), 3.25-3.18 (m, 1H), 2.92-2.88 (m, 2H), 2.71-2.66 (m, 2H), 2.03-1.87 (m, 3H), 1.74-1.64 (m, 2H), 1.38-1.27 (m, 4H). 13 C NMR (100 MHz, CDCl 3 ) δ 207.7, 155.5, 149.4, 148.7, 138...

Embodiment 3

[0028] The synthetic method of donepezil of the present embodiment, steps are as follows:

[0029] In a 15 ml Schlenk tube, add 76.88 mg (0.4 mmol) 5,6-dimethoxyindanone, 98.5 mg (0.48 mmol) 1-benzyl-4-piperidinemethanol, 1.55 mg (0.5 mol%) Pincer metal ruthenium (II) compound, 53.26 mg (0.5 equiv) potassium phosphate trihydrate, 0.5 ml dioxane, magnetic stirring under argon atmosphere, and react at 120°C for 12 hours. According to TLC analysis, the raw materials had been completely reacted. Vacuum rotary evaporation, using ethyl acetate and petroleum ether at a volume ratio of 1:1 for thin-layer chromatography separation and purification, the mass of the product donepezil was 114.44 mg, and the yield was 75%.

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Abstract

The invention discloses a donepezil synthesis method which comprises the following steps: sequentially putting 5,6-dimethoxy indanone, 1-benzyl-4-piperidine methanol, a catalyst, an alkali and a solvent into a reactor; in an argon atmosphere, performing a magnetic stirring reaction in an oil bath pot sufficiently, after the reaction is completed, performing vacuum rotation evaporation and spectrumseparation, and drying, thereby obtaining a target product. By adopting the method disclosed by the invention, the problem that a great amount of byproducts are generated as reagents are used in a conventional synthesis method is solved since the components are cheap, easy to preserve and environmental-friendly and are renewable petroleum base replaceable compounds. An NNN type pincerlike metal ruthenium (II) compound is adopted as a catalyst for catalyzing reactions in the method, the reactions are completed at one step, the method is simple and convenient to operate and high in reaction efficiency, and requirements of sustainable development of environmental-friendly chemicals are met.

Description

technical field [0001] The invention belongs to the technical field of synthesis and application of organic compounds, and in particular relates to a synthesis method of donepezil. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia, is one of the common diseases of the elderly, mainly manifested as memory loss and cognitive impairment. Senile dementia is a chronic mental disability and fatal disease. Therefore, researching and preventing senile dementia drugs is a major topic in the medical field. [0003] The chemical name of donepezil (donepezil) is 1-benzyl-4-[(5,6-dimethoxyindanon-2-yl)methyl]piperidine, which is mainly used for the treatment of mild and moderate Alzheimer's disease. silent disease. AD is an acquired mental retardation with memory loss as the main manifestation, accompanied by other cognitive impairments. Research in the past 30 years has shown that the progressive degeneration of AD cholinergic neurons is the cause ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/32
CPCC07D211/32
Inventor 徐琰贾赵栋曹筱妞黄恩玲朱新举郝新奇宋毛平
Owner ZHENGZHOU UNIV
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