Synthesis method of minocycline hydrochloride

A technology of minocycline hydrochloride and a synthesis method, applied in the field of drug synthesis, can solve the problems of complicated process operation, difficult purification operation, low purity and the like

Inactive Publication Date: 2021-06-15
台州达辰药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Although the synthetic methods of minocycline hydrochloride have been reported in the prior art, they have one or more disadvantages, such as using expensive reagents and catalysts, complex process operations, difficult purification operations, low yield and low purity, isotropic structure exceeds the standard, etc., thereby restricting the industrialized production of minocycline hydrochloride

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  • Synthesis method of minocycline hydrochloride
  • Synthesis method of minocycline hydrochloride
  • Synthesis method of minocycline hydrochloride

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preparation example Construction

[0160] The invention provides a method for synthesizing 7-amino-6-demethyltetracycline. The 7-amino-6-demethyltetracycline prepared by the method has the advantages of high purity and high yield.

[0161] In a preferred example of the present invention, the synthetic method of described 7-amino-6-desmethyltetracycline comprises:

[0162] (1) In the first organic solvent, in the presence of a palladium metal complex, demethylaureomycin reacts with an aminating reagent to obtain 7-amino-6-demethyltetracycline;

[0163]

[0164] Preferably, the desmethylautetracycline is free desmethylautetracycline or a desmethylautetetracycline salt.

[0165] Preferably, the desmethylautetracycline salt is desmethylautetracycline hydrochloride.

[0166] Preferably, in the step (1), the first organic solvent includes (but not limited to): triethylamine, DMF (N,N-dimethylformamide), DMA (N,N-dimethyl Acetamide), NMP (N-methylpyrrolidone), or a combination thereof.

[0167] Preferably, in th...

Embodiment 1

[0319] The synthesis of embodiment 1 minocycline hydrochloride

[0320] (1) Synthesis of 7-amino-6-desmethyltetracycline

[0321]

[0322] In a 500ml autoclave, put 50g of demethylaureomycin hydrochloride, 300ml of DMF (N,N-dimethylformamide), 2.5g of bis(triphenylphosphine)palladium dichloride, 15g of 27% ammonia water, and replace with nitrogen After three times in the autoclave, evacuate the nitrogen, then replace it with hydrogen and fill it with hydrogen until the pressure of the hydrogen gas in the autoclave is 3MPa, react at 45°C for 8h to obtain the reaction solution; pour the reaction solution into 500ml of isopropanol, stir The solid was precipitated, then cooled to -5°C to crystallize, crystallized for 2.5h, filtered, and the filter cake was dried under reduced pressure at 40°C to obtain 42.4g of 7-amino-6-desmethyltetracycline with a yield of 95.4%, HPLC Measure purity 99.7%, the HPLC collection of illustrative plates of the prepared 7-amino-6-demethyltetracycl...

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Abstract

The invention relates to a synthesis method of minocycline hydrochloride, which comprises the following steps of: (1) reacting demeclocycline with an amination reagent in a first organic solvent in the presence of a palladium metal complex to obtain 7-amino-6-demethyltetracycline; (2) carrying out a dehydroxylation reaction on the 7-amino-6-demethyltetracycline in a second organic solvent in the presence of a first acid reagent and a first catalyst, so as to obtain 7-amino-6-demethyl-6-deoxytetracycline; and (3) in a third organic solvent, in the presence of a second acid reagent and a second catalyst, carrying out alkylation reaction on the 7-amino-6-demethyl-6-deoxytetracycline and an alkylation reagent to obtain minocycline hydrochloride. The minocycline hydrochloride prepared by the method disclosed by the invention has the advantages of simple synthesis process, high yield, high purity and easiness in large-scale production.

Description

technical field [0001] The invention relates to the field of medicine synthesis, in particular, the invention relates to a synthesis method of minocycline hydrochloride. Background technique [0002] Minocycline hydrochloride, also known as minocycline or minocycline, is a broad-spectrum antibacterial tetracycline antibiotic. It can combine with t-RNA to achieve antibacterial effect. Minocycline has a broader antibacterial spectrum than similar drugs and has antibacterial activity. The antibacterial spectrum is similar to that of tetracycline, and it has a strong effect on Gram-positive bacteria including tetracycline-resistant Staphylococcus aureus, Streptococcus and Neisseria gonorrhoeae in Gram-negative bacteria; it also has a strong effect on Chlamydia trachomatis and Mycoplasma urealyticum Good inhibitory effect. [0003] Minocycline hydrochloride, Minocycline hydrochloride, CAS: 13614-98-7, light yellow-orange amorphous solid, soluble in water, slightly soluble in e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/12C07C237/26
CPCC07C231/12C07C2603/46
Inventor 曹俊爽周魏魏谢彪张盛荣
Owner 台州达辰药业有限公司
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