Preparation method of tulathromycin

A technology of telamycin and methyl azithromycin, which is applied to the preparation of sugar derivatives, chemical instruments and methods, sugar derivatives, etc., can solve the problems of epoxidation with many impurities, low yield of double-protected intermediates, and difficulty in purification, etc. problem, to achieve high yield, easy to protect, and beneficial to industrial production

Active Publication Date: 2017-07-11
AMICOGEN CHINA BIOPHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The yield of the double-protected intermediate is low, and the deprotection is carried out be...

Method used

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  • Preparation method of tulathromycin
  • Preparation method of tulathromycin

Examples

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Embodiment 1

[0057] (1) Preparation of Intermediate A

[0058] Add 140mL dichloromethane and 17g (23.1mmol) demethylazithromycin to the reaction flask, control the temperature at -5~0°C, add 6.0g (27.6mmol) p-nitrobenzyl chloroformate, add dropwise 3.0g (23.1mmol) ) diisopropylethylamine, reacted for 3h to obtain a dichloromethane solution of intermediate A, and directly carried out the next step reaction.

[0059] (2) Preparation of Intermediate B

[0060] Add 32 g (409.5 mol) of dimethyl sulfoxide to the obtained solution of intermediate A, lower the temperature to -80~-70° C., add 16.2 g (77.0 mmol) of trifluoroacetic anhydride dropwise, and react for 1 hour after dropping. Add 17.2 g (170.0 mmol) of triethylamine and react for 1 hour. After the reaction is complete, add 100 mL of water to the system for extraction three times, distill the organic phase under reduced pressure until the solvent is viscous, add 200 mL of isopropanol to dissolve, and adjust Crystallization temperature 15...

Embodiment 2

[0067] (1) Preparation of Intermediate A

[0068] Add 170mL dichloromethane and 17g (23.1mmol) demethylazithromycin to the reaction flask, control the temperature at -5~0°C, add 6.0g (27.6mmol) p-nitrobenzyl chloroformate, add dropwise 6.5g (34.7mmol) ) tributylamine, reacted for 3h, prepared the dichloromethane solution of intermediate A, and directly carried out the next step reaction.

[0069] (2) Preparation of Intermediate B

[0070] Add 32 g (409.5 mol) of dimethyl sulfoxide to the obtained solution of intermediate A, lower the temperature to -80~-70° C., add 16.2 g (77.0 mmol) of trifluoroacetic anhydride dropwise, and react for 1 hour after dropping. Add 31.4g (170.0mmol) of tributylamine, and react for 1 hour. After the reaction is completed, add 100mL water to the system for extraction three times each time. The organic phase is distilled under reduced pressure until the solvent is viscous. After adding 200mL isopropanol to dissolve, adjust The crystallization temp...

Embodiment 3

[0077] (1) Preparation of Intermediate A

[0078] Add 200mL of dichloromethane and 17g (23.1mmol) of demethylazithromycin to the reaction flask, control the temperature at -5~0°C, add 6.0g (27.6mmol) of p-nitrobenzyl chloroformate, add 3g (34.7mmol) dropwise Triethylamine was reacted for 3 hours to obtain a dichloromethane solution of Intermediate A, which was directly carried out to the next step.

[0079] (2) Preparation of Intermediate B

[0080] Add 32 g (409.5 mol) of dimethyl sulfoxide to the obtained solution of intermediate A, lower the temperature to -80~-70° C., add 16.2 g (77.0 mmol) of trifluoroacetic anhydride dropwise, and react for 1 hour after dropping. Add 17.2 g (170.0 mmol) of triethylamine and react for 1 hour. After the reaction is complete, add 100 mL of water to the system for extraction three times. The organic phase is distilled under reduced pressure until it becomes viscous. After adding 200 mL of ethanol to dissolve, adjust the crystallization temp...

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Abstract

The invention relates to the field of chemical synthesis and particularly relates to a preparation method of tulathromycin. The method comprises protecting a 2-hydroxyl group of demethyl azithromycin through 4-nitrobenzyl chloroformate, carrying out oxidation and epoxidation on a 4"-hydroxyl group, and carrying out deprotection and 4"-epoxy nucleophilic addition through n-propylamine to obtain tulathromycin. Comprised with the prior art, the preparation method has simple processes, mild conditions and a high yield, is free of palladium-carbon hydrodeprotection and is conducive to industrial production.

Description

technical field [0001] The invention relates to the field of chemical synthesis, in particular to a preparation method of telamycin. Background technique [0002] Respiratory tract infection is one of the difficult-to-control heat transfer diseases in animal husbandry, which seriously harms animal husbandry production. Because respiratory tract infections are generally multiple infections, with many pathogenic factors and complicated conditions, there are currently no very effective preventive measures. For the respiratory infection of animals, drug treatment is still the main method at present while seeking biological treatment and environmental blocking. Seeking effective, safe, broad-spectrum, high-efficiency, and low-residue new antibacterial drugs for respiratory infections is an important direction for veterinary drug research and development. [0003] Tulathromycin (Tulathromycin), also known as tulamycin, tolamycin, trade name "Draxxin", Chinese name "Rui Kexin". ...

Claims

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Application Information

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IPC IPC(8): C07H17/00C07H1/00
CPCC07H1/00C07H17/00
Inventor 金永东陈强王晶李秀秀杨申永王玲李建国
Owner AMICOGEN CHINA BIOPHARM CO LTD
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