Preparation method of intermediate of medicine Nirmatrevir for treating novel coronavirus

Abstract

The invention discloses a preparation method of an intermediate of a medicine Nirmatrevir for treating a novel coronavirus, which comprises the following steps: by taking 3, 3-dimethyl-4-pentenoic acid as a raw material, carrying out halogen lactonization reaction, amination, intramolecular amine ester exchange, halogenation or sulfonyl substitution, intramolecular nucleophilic substitution for closing a three-membered ring, lactam reduction and deprotection to obtain 6, 7-dihydroxy-3, 7-dimethyl-4-pentenoic acid. According to the preparation method, starting materials are cheap and easy to obtain, the preparation method is simple and convenient to operate, and compared with a caronic anhydride process, only lactam needs to be reduced, so that the dosage of a reducing agent is greatly reduced, the cost is reduced, and the preparation method is suitable for industrial production. After debenzylation, a high-purity and high-yield target product can be obtained through simple and convenient filtration and concentration post-treatment, the problem that the target product is difficult to purify in a traditional preparation method is solved, and the method is more suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a method for preparing an intermediate of Nirmatrelvir, a drug for treating novel coronavirus. Background technique [0002] 6,6-Dimethyl-3-azabicyclo[3.1.0]hexane (compound represented by formula VIII) is an important intermediate of the new crown oral drug Nirmatrelvir (PF-07321332) and HCV protease inhibitor Boceprevir, and also Widely used in other organic synthesis fields. Nirmatrelvir (PF-07321332) is the main antiviral component of the new crown oral drug Paxlovid. Nirmatrelvir blocks the activity of the new coronavirus 3CL protease, making the subsequent RNA replication process of the virus impossible. Boceprevir is the first approved anti-HCV drug that directly acts on NS3 serine protease. It has dual functions of directly inhibiting virus replication and repairing interferon activity. The structural formulas of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane, Nirmatrelv...

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Problems solved by technology

The starting material permethrin of this route has high cost, lengthy route and harsh conditions, and is not suitable for industrial production

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