Process method suitable for amplification preparation of 4-(6-aminopyridin-3-yl) substituted piperidine

A technology of base piperidone and piperidine, which is applied in the field of amplifying the preparation of 4-substituted piperidines, can solve the problems of difficult purification and removal of impurities, low synthesis process yield, poor economic benefits and the like, and achieves short route steps and optimized preparation. Craftsmanship, universal effect
CN110540535AActive Publication Date: 2019-12-06SHANGHAI ZAIQI BIO TECH
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
SHANGHAI ZAIQI BIO TECH
Publication Date
2019-12-06

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Abstract

The invention discloses a process method suitable for amplification preparation of 4-(6-aminopyridin-3-yl) substituted piperidine, and belongs to the synthesis field of a medicine intermediate. N-substituted piperidone, aryl sulfohydrazide and 2-amino-5-bromopyridine are subjected to a coupling reaction under a palladium catalyst, and then are subjected to a hydrogenation to obtain 4-(6-aminopyridin-3-yl) substituted piperidine. According to the process, the raw materials in pyridine do not need to be protected; the condensation and the coupling are carried out in the same reaction kettle, sothat the operation cost is reduced, the steps of performing protection at first and then performing protection removal as in documents can be avoided, and production cost of the existing biological, medicine and chemical intermediates is greatly reduced; and the process is subjected to amplification verification in kilogram-scale, and the verification proves that the yield and the product purity are basically equal to those of gram-scale, so that the method can be used as a process for industrial scale production.
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Description

technical field

[0001] The invention belongs to the field of synthesis of pharmaceutical intermediates, and in particular relates to a process suitable for the scale-up preparation of 4-(6-aminopyridin-3-yl)-substituted piperidines. Background technique

[0002] In recent years, major pharmaceutical companies in the world have developed a variety of selective CDK4 / CDK6 inhibitors, such as palbociclib developed by Pfizer / Onyx, abemaciclib developed by Eli Lilly, ribociclib developed by Novartis, for the treatment of cancer, cardiovascular Disorders and inflammatory diseases.

[0003] WO2014183520 discloses a selective CDK4 / CDK6 inhibitor with a new structure, and found that the compound with this structure exhibits excellent effects and effects, especially excellent pharmacokinetic absorption activity, and has the following structure: In this inhibitor, 4-(6-aminopyridin-3-yl) substituted piperidine is an important structural fragment, for example: tert-butyl 4-(6-aminopyri...

Claims

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