Preparation method of galanthamine key intermediate

A technology of galantamine and intermediates, which is applied in the preparation of organic compounds, chemical instruments and methods, preparation of aminohydroxy compounds, etc., can solve the problems of low industrialized production yield of galantamine, etc., and achieves control of production costs, Simple operation and mild reaction conditions

Active Publication Date: 2017-07-25
ZHANG JIA GANG VINSCE BIO PHARM
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The invention discloses a method for preparing a key intermediate of galantamine—N-methyl-(4-hydroxyphenethyl)-2-bromo-5-hydroxy-4-methoxybenzylam

Method used

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  • Preparation method of galanthamine key intermediate

Examples

Experimental program
Comparison scheme
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Example Embodiment

[0021] Example 1

[0022] (1) Preparation of dichloromethane solution of N-methyl-(4-benzyloxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride compound

[0023] 24g p-benzyloxyphenethyl alcohol, 35g 2-bromo-5-benzyloxy-4-methoxybenzaldehyde and 10g methylamine hydrochloride were dispersed and dissolved in 300ml 1,4-dioxane, 30g cyanoborohydrogenation Sodium was dissolved in 10 ml of acetic acid, dropped into the raw material solution at room temperature, reacted at room temperature, and the reaction was monitored by HPLC until the raw material was basically reacted, and water was added to quench the reaction, and extracted with 500 ml of dichloromethane and 200 ml of water to obtain an organic phase to obtain N- Methyl-(4-benzyloxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride solution in dichloromethane, N- Methyl-(4-benzyloxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride was 95.3% pure.

[0024] (2) Preparatio...

Example Embodiment

[0028] Example 2

[0029] (1) Preparation of dichloromethane solution of N-methyl-(4-benzyloxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride compound

[0030] 24g of p-benzyloxyphenethyl alcohol, 35g of 2-bromo-5-benzyloxy-4-methoxybenzaldehyde and 10g of methylamine hydrochloride were dispersed and dissolved in 300ml of tetrahydrofuran, and 30g of sodium cyanoborohydride was dissolved in 10ml of acetic acid. Drop into the raw material solution at room temperature, react at room temperature, monitor the reaction by HPLC until the raw material is basically reacted, add water to quench the reaction, extract with 500 ml of dichloromethane and 200 ml of water, obtain the organic phase, and obtain N-methyl-(4-benzyl) Dichloromethane solution of oxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride, HPLC measured N-methyl-(4-benzyl in this solution Oxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride was 95.1% pure.

[003...

Example Embodiment

[0035] Example 3

[0036] (1) Preparation of dichloromethane solution of N-methyl-(4-benzyloxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride compound

[0037] 24g p-benzyloxyphenethyl alcohol, 35g 2-bromo-5-benzyloxy-4-methoxybenzaldehyde and 10g methylamine hydrochloride were dispersed and dissolved in 300ml tetrahydropyran, 30g sodium cyanoborohydride was dissolved in 10ml In the acetic acid, dropwise into the raw material solution at room temperature, react at room temperature, HPLC monitors the reaction until the raw material basically reacts completely, add water to quench the reaction, extract with 500 ml of dichloromethane and 200 ml of water, obtain the organic phase, and obtain N-methyl-( The dichloromethane solution of 4-benzyloxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride, the N-methyl-( 4-Benzyloxyphenethyl)-2-bromo-5-benzyloxy-4-methoxybenzylamine cyanoborohydride was 95.3% pure.

[0038] (2) Preparation of N-methyl...

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Abstract

The invention discloses a preparation method of galanthamine key intermediate -N-methyl(4-leptodactyline)-2-bromo-5-hydroxyl-4-methoxybenzylamine. The preparation method comprises the following steps: by taking 2-bromo-5-benzyloxy-4-methoxybenzaldehyde, benzyloxyphenyl ethanol and methylamine hydrochloride as raw materials, condensing, degrading and performing debenylation reaction to prepare N-methyl(4-leptodactyline)-2-bromo-5-hydroxyl-4-methoxybenzylamine. Cheap and easily available raw materials are adopted in the method, so that the production cost can be effectively controlled, the operation is simple, and the reaction conditions are mild. The intermediate is used for industrial synthesis of galanthamine, and the problem that the yield from the industrial production of galanthamine is low can be effectively solved.

Description

technical field [0001] The invention relates to a preparation method of N-methyl-(4-hydroxyphenethyl)-2-bromo-5-hydroxy-4-methoxybenzylamine, a galantamine intermediate, and belongs to the field of medicine and chemical industry. Background technique [0002] Galantamine was first researched and produced by Sopharma Pharmaceutical Company in Bulgaria, and is used for myasthenia gravis, progressive muscular dystrophy, sequelae of poliomyelitis, children with cerebral palsy, sensory or motor disorders caused by nervous system diseases, multiple neuritis etc. It is easy to pass through the blood-brain barrier, so it has a strong central action and can be used for myasthenia gravis. It is currently on the market in many countries around the world under the product name: Nivalin. Galantamine was first isolated and extracted from the bulbs of snowdrops. Because the species to be extracted is rare and the extraction of galantamine is expensive, many companies around the world hav...

Claims

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Application Information

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IPC IPC(8): C07C213/08C07C217/64
CPCC07C213/08C07F5/027C07C217/64
Inventor 张梅彭学东赵金召弓旻
Owner ZHANG JIA GANG VINSCE BIO PHARM
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