A kind of preparation method of hydroxychloroquine

Abstract

The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a preparation method of hydroxychloroquine. The method is to condense quinoline intermediate 7-chloro-4-hydroxyquinoline sulfonate and hydroxychloroquine side chain in a deep eutectic solvent reaction to obtain the target product; the preparation method of the quinoline intermediate 7-chloro-4-hydroxyquinoline sulfonate: (1) taking 4-chloro-2-nitrobenzoic acid as raw material, through chlorination reaction , to obtain acid chloride, then condensed with McFarlandic acid, and hydrolyzed to obtain 4-chloro-2-nitroacetophenone; Condensation reaction of amide formal, reduction cyclization of nitro group, protection reaction of hydroxyl group to obtain quinoline intermediate 7-chloro-4-hydroxyquinoline sulfonate. The invention has easy-to-obtain raw materials, mild reaction conditions, is not prone to side reactions, avoids high-temperature production conditions, reduces risks, has good intermediate stability, and obtains hydroxychloroquine with high yield and good purity, which is beneficial to large-scale production.

Description

A kind of preparation method of hydroxychloroquine technical field The invention belongs to the technical field of medicine and chemical industry, be specifically related to the preparation method of hydroxychloroquine. Background technique Hydroxychloroquine is a kind of 4-aminoquinoline derivatives, and what is in clinical application is its sulfate, that is, hydroxychloroquine sulfate Quine. Hydroxychloroquine sulfate (Hydroxychloroquine Sulfate) chemical name is 2-[[4-[(7-chloro-4-quinolinyl) Amino] pentyl] ethylamino]-ethanol sulfate, CAS number is 747-36-4, and the chemical structural formula is as follows: [0004] Hydroxychloroquine sulfate was successfully developed by Winthrop company, first listed in the United States in 1956, later in France, Dan Mai, Japan, Germany, Finland and other countries and regions listed. FDA approved hydroxychloroquine thiosulfate on May 29, 1998 Tablets are used to treat lupus erythematosus and rheumatoid arthritis. Compa...

AI Technical Summary

Problems solved by technology

The existence of this impurity will undoubtedly cause great pressure on the production process of hydroxychloroquine, and will also affect the final quality of the product

Although the product can be further purified by some purification means (CN109928925A, CN103626699A), it is also difficult to ensure the high quality of the intermediate 4,7-dichloroquinoline required for the preparation of hydroxychloroquine chloride

[0034] The organic solvents used in large quantities in the chemical and chemical production process not only cause environmental pollution, but also are expensive and difficult to recycle, which is not conducive to industrial applications. Therefore, the development of non-toxic and cheap green solvents is a very important issue for the chemical industry

Images