Preparation method of Draxxin

A telamectin and reagent technology, which is applied in the field of preparation of telamectin, can solve the problems of safety and cost, many reaction by-products, and low conversion rate in industrialization, and achieve ultra-low temperature reaction avoidance, good purity, and increased yield. rate effect

Active Publication Date: 2018-01-09
BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] CN102786569 takes azithromycin A as raw material, protects the 2'-position hydroxyl and 6'-position amino in azithromycin A with di-tert-butyl dicarbonate, then carries out Swern oxidation, and reacts with trimethylsulfonium bromide to obtain 4 "-position ring Oxygen compounds; finally, use n-propylamine to carry out nucleophilic addition to the 4″-position epoxy compound to obtain the target compound telamectin. The Swern reaction needs to be carried out at ultra-low temperature, and there are safety and cost problems in industrialization
The price of di-tert-butyl dicarbonate is higher
There are many reaction by-products in this synthetic route, which are not easy to purify and separate. The phase transfer catalyst affects the stability of the product and the conversion rate is low.
[0021] The route of CN104876983 is as follows, in the route, dichromate is used as oxidant, and zinc amalgam is used as reducing agent, both of which are heavily polluting reagents, and the yield is not high

Method used

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  • Preparation method of Draxxin

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Embodiment 1

[0045]The content of the invention will be further explained and illustrated below in conjunction with specific examples, but they are not intended to limit or limit the scope of the present invention. The following reagents and preparation materials are commercially available unless otherwise specified. Example 1 (comparative example, refer to patent 200510082063.7)

[0046] Put 29Kg TA04 and 160Kg dichloromethane into a 500L reactor, stir for 20-30min, put 5Kg anhydrous sodium sulfate into it, stir and dry, 1-2h, filter the whole mixture with suction, and concentrate until there is almost no fraction. Transfer the concentrated system to a 1000L reaction kettle, add 660Kg of dichloromethane at the same time, start stirring, and at the same time cool the system to -5~5°C under nitrogen protection, add 16Kg / 33Kg of benzyl chloroformate and dichloroformate dropwise to the system A solution of methyl chloride. A total of 1.5h was added dropwise, and the dropwise addition was com...

Embodiment 2

[0058] Embodiment 2 (process of the present invention)

[0059] Put 40kgTA04 and 100kg toluene into a 1000L reactor, stir for 20-30min, and concentrate at 55°C until there is no distillate. Cool down to about 25°C under the protection of nitrogen, vacuum pump 900Kg of dichloromethane, start stirring, cool down the system to -5~5°C under the protection of nitrogen, add dropwise a solution of 22kg of benzyl chloroformate and 66Kg of methylene chloride into the system . A total of about 1.5h was added dropwise, and the dropwise addition was completed. Keep warm at 0-5°C for 2-3 hours, and the conversion of raw materials is completed. (HPLC monitors the conversion of raw materials) Control the temperature T≤35°C, concentrate the reaction mixture until it becomes dry and oily, and store it at a low temperature of 0-10°C.

[0060] Add the above-mentioned TA05 and 260kgDMSO into the 500L reactor, start stirring, and after dissolving, add 18KgIBX in batches, react at 20-30°C for 2-...

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Abstract

The invention discloses a preparation method of Draxxin. The method comprises the following steps: enabling a reaction between an intermediate TA04 and benzyl chloroformate, so as to obtain TA05; oxidizing the TA05 with DMSO and IBX at the temperature of 20-30 DEG C, so as to obtain TA06; dissociating and performing aftertreatment after the TA06 becomes oxalate TA06-OX, so as to obtain purified TA06; oxidizing the TA06 with trimethylsulfonium bromide and potassium tert-butoxide, so as to obtain TA07; hydrogenating the TA07 to remove a protection group, so as to obtain TA08; enabling a reactionbetween the TA08 and n-propylamine, so as to obtain TA; dissociating and performing aftertreatment after the TA becomes oxalate TA-OX, so as to obtain purified end-product Draxxin. The total yield ofthe Draxxin prepared with the method is increased by above 20%.

Description

technical field [0001] The invention belongs to the field of pharmaceutical production and relates to a preparation method of telamectin. Background technique [0002] Respiratory tract infection is one of the most difficult diseases to control in animal husbandry, which has serious harm to animal husbandry production. At present, macrolide antibiotics are a class of commonly used drugs for the treatment of respiratory tract infections in pigs and cattle, among which tylosin and tilmicosin are widely used in my country. Although the use of these two drugs has achieved good results, with the prolongation of use time, drug resistance has appeared to varying degrees in many areas, and these two drugs are usually administered by mixing or drinking water. It takes repeated doses to be effective. Therefore, there is an urgent need in the market for novel antibacterial drugs that are highly effective, safe, broad-spectrum, and low-residue for respiratory infections. Tyramectin h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/00C07H1/00
Inventor 袁建栋符新亮丛启雷郁海徐倜
Owner BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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