Method for synthesizing Ranolazine

A synthetic method, the technology of ranolazine, which is applied in a new synthetic field, can solve the problems of short reaction steps, long reaction steps, difficulties in the synthesis of ranolazine, etc.

Inactive Publication Date: 2009-06-03
TIANJIN HANKANG PHARMA BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The first synthetic route has short reaction steps and easy-to-obtain raw materials. Although piperazine is used in a large amount, it is cheap and easy to obtain; the difference between the second route and the first route is that after the reaction between o-methoxyphenol and epichlorohydrin Condensate with piperazine and then react with N-(2,6-dimethylphenyl)-2-chloroacetamide to prepare ranolazine; the third synthetic route has long reaction steps
[0010] The yields of the above synthetic methods are not high. Although the first synthetic route has great application value, there are still many steps and conditions that need to be improved to increase the yield. The present invention is based on this, and after screening and research, it has found Better process conditions solve the difficult problem of ranolazine synthesis

Method used

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  • Method for synthesizing Ranolazine
  • Method for synthesizing Ranolazine
  • Method for synthesizing Ranolazine

Examples

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Embodiment 1

[0031] 1. Preparation (yield: 80%) of 3-(2-methoxyphenoxy)-1,2-epoxypropane (intermediate I) feed ratio: o-methoxyphenol: epichlorohydrin di Hexane: water: NaOH=1:1.68:2.7:1.2:0.36(w / v / v / w)

[0032] Add 150g of o-methoxyphenol, 378ml of dioxane, 168ml of water and 50g of NaOH into a 2L three-necked reaction flask, add 252ml of epichlorohydrin under stirring at room temperature, and react under reflux for 2 hours. Cool to room temperature, add ethyl acetate, filter, separate the organic layer, extract the aqueous layer twice with ethyl acetate, combine the organic layers, dry with anhydrous sodium sulfate, distill under reduced pressure, collect 121-124 ° C / 2KPa fractions to obtain 163g product.

[0033] 2. Preparation of 2-chloro-N-(2,6xylyl)acetamide (yield: 84.3%)

[0034] Feed ratio: 2,6-dimethylaniline: chloroacetyl chloride: triethylamine: toluene = 1:0.94:1.0:10 (w / w / w / v)

[0035] Add 165g of 2,6-dimethylaniline, 165g of triethylamine, and 1,650ml of toluene into a ...

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Abstract

This invention relates to a method for synthesizing ranolazine drug for treating stenocardia. The method comprises: performing amidation and N-monoalkylation on 2, 6-dimethylaniline to obtain N-(2, 6-xylyl)-2-(1-piperazine) acetamide, and then reacting with 2-(2-methoxyphenoxy) epoxyethane generated from o-methoxyphenol and epoxy chloropropane to obtain anolazine. The reactions include the refinery of 2-chloro-N-(2,6-xylyl)acetamide by cyclohexane and the recrystallization of ranolazine by ethanol / ethyl acetate (2:1), thus can raise the yield.

Description

Technical field: [0001] The invention relates to a new synthesis method of ranolazine, an antiangina drug. Background technique: [0002] Ranolazine (ranolazine) is a new type of metabolic regulator and cardioselective anti-anginal drug developed by Syntex Corporation of the United States. Its chemical name is (±)N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)-propyl]-1-piperazine amides. It can be used to treat myocardial infarction, congestive heart disease, angina pectoris, arrhythmia and other diseases. Its mechanism of action is to inhibit the oxidation of some fatty acids and change the oxidative metabolism of fatty acids in the heart to glucose oxidative metabolism, thereby reducing the oxygen consumption of the heart and not causing heart rate. and changes in blood pressure. Patent documents US4567264, EP0483932, and the Chinese journal "West China Pharmaceutical Journal" 2004, 19(3): 191-192 report several synthetic methods of ranolazine: [0003] 1) N-...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D295/15
Inventor 严洁
Owner TIANJIN HANKANG PHARMA BIOTECH
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