Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of minocycline

A technology of minocycline and sancycline, which is applied in the field of preparation of minocycline, can solve problems such as difficult purification, and achieve the effect of simple purification and simple operation

Pending Publication Date: 2020-11-06
卡博金艾美斯医药(上海)有限公司
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] 4. Azo addition reduction method: under strong acidic conditions (concentrated sulfuric acid, methanesulfonic acid or trifluoroacetic acid), sancycline and dibenzyl azodicarboxylate at C-7 are addition products, the intermediate The product is obtained after catalytic hydrogenation or disulfide reduction; this method is difficult to apply to industry due to the safety and cost issues of dibenzyl azodicarboxylate and the difficulty of later purification

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of minocycline
  • Preparation method of minocycline
  • Preparation method of minocycline

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Embodiment 1 Sancycline 6-protection of ethoxycarbonyl

[0036] The structural formula is as follows:

[0037]

[0038] Sancycline (2 mmol), dichloromethane (5 mL) and triethylamine (3 mmol) were added in a 50 mL flask. The mixture was cooled to 0°C, and ethyl chloroformate (2.2 mmol) was slowly added dropwise, keeping the temperature not exceeding 5°C. The reaction was monitored by TLC, and the conversion was complete within 1 hour. Add 10 ml of water and separate the layers. The organic phase was concentrated to dryness and used directly in the next reaction without purification. ESI-MS m / z: 487.2 (M+H+).

Embodiment 2

[0039] Embodiment 2 Sancycline 6-protection of acetyl group

[0040] The structural formula is as follows:

[0041]

[0042] Shancycline (2 mmol), acetic anhydride (6 mmol) and pyridine (6 mmol) were added to 50 ml of dichloromethane and refluxed for not less than 5 hours. After the reaction is complete, cool down to room temperature, adjust to neutrality with saturated aqueous sodium bicarbonate solution, wash the organic phase with 12% brine, dry over anhydrous sodium sulfate, filter, concentrate to dryness, and directly use in the next reaction without purification . ESI-MS m / z: 457.3 (M+H+).

Embodiment 3

[0043] Embodiment 3 Sancycline 6-protection of benzoyl

[0044] The structural formula is as follows:

[0045]

[0046] Sancycline (2mmol), sodium carbonate (5g) and benzoyl chloride (2.5mmol) were added to 50ml of methanol and stirred at 25-35°C for 4 hours. TLC showed that the reaction was complete, 100 ml of purified water was added, adjusted to neutrality with saturated aqueous sodium bicarbonate solution, the organic phase was washed with 12% brine, dried over anhydrous sodium sulfate, filtered, concentrated to dryness, and used directly for Next reaction. ESI-MS m / z: 518.9 (M+H+).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of minocycline. The minocycline is (4S,4aS,5aR,12aS)-4,7-dimethylamino-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-tetraphenyl-2-formamide. According to the method, sancyline is subjected to protection of a phenolic hydroxyl group via an acyl group, and then selective dimethylamination is conducted on position 6. After a protection strategy is adopted in the process route of the method, generation of 9-position dimethylamination by-products is avoided, and purification is simple. Usage of precious metal is avoided in a reaction, a production unit is simple to operate, safe and environment-friendly, and the method is very suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of minocycline, which belongs to the technical field of medicine synthesis. Background technique [0002] The chemical name of minocycline is: (4S,4aS,5aR,12aS)-4,7-bisdimethylamino-3,10,12,12a-tetrahydroxy-1,11-dioxo-1, 4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide, the structural formula is as follows: [0003] [0004] 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- Naphthalene carboxamide; Minocycline; 7-Dimethylamino-6-desmethyl-6-deoxytetracycline, CAS: 10118-90-8. [0005] Minocycline, also known as minocycline or minocycline, is a broad-spectrum antibacterial tetracycline antibiotic. Can combine with tRNA 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 ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07C231/12C07C237/26
CPCC07C231/12C07C2603/46C07B2200/07C07C237/26Y02P20/55
Inventor 顾开春王希林
Owner 卡博金艾美斯医药(上海)有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com