Method for preparing tigecycline intermediate and salt thereof

Abstract

The invention discloses a method for preparing a tigecycline intermediate shown as a formula (1) and a salt thereof, which comprises the preparation route shown in the specifications. The preparation route has the advantages of cheap and readily available raw materials, avoidance of an ortho-position and para-position mixture during nitration, high yield in each step of reaction, no need of a minocycline intermediate, simple and convenient operation and simple equipment requirement, and is a synthesis process for industrially producing tigecycline.

Description

technical field The invention relates to the field of organic synthesis of medicines, in particular to a process for synthesizing tigecycline intermediates and salts thereof. Background technique The chemical name of Tigecycline is [4S-(4α,12aα)]-4,7-bis(dimethylamino)-9-[(tert-butylamino)acetamido]-1,4,4a , 5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-tetracenecarboxamide, its structural formula is as follows: (10) Tigecycline Tigecycline is the first marketed variety of a new class of antibiotics—glycylcycline (glycylcycline), which is mainly used to treat infections caused by Gram-negative and positive pathogenic bacteria, anaerobic bacteria, and methicillin-resistant grapevine aureus. Complicated intra-abdominal infection, skin and skin tissue infection (cSSSI), pneumococcal infection, etc. This product was successfully developed by Wyeth, and was approved for marketing in the United States for the first time in July 2005. Clinical medical resear...

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Problems solved by technology

The first method not only has a lower yield (50-60%), but also has more impurities, especially the 4-position epimer impurity content caused by the reaction is relatively large

Although the second method has a yield of 90% in this step of chloroacetylation, the yield of reacting with tert-butylamine is also low (50%), and the route is relatively long simultaneously

This also makes the above-mentioned three synthetic routes of tigecycline subject to the restriction of raw material minocycline, and the cost is higher

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